CardioNerds Case Reports Archives - Cardionerds

View Details

CardioNerds join Dr. Neel Patel, Dr. Victoria Odeleye, and Dr. Jay Ramsay from the University of Tennessee, Nashville, for a deep dive into cardiovascular medicine in the vibrant city of Nashville. They discuss the following case: A 57-year-old male with a history of prior cardiac surgery, hypertension, and polysubstance use presented with syncope and chest pain. Initial workup revealed a large saccular ascending aortic aneurysm. While under conservative management, he experienced acute hemodynamic collapse, leading to the discovery of an unprecedented aorto-right ventricular fistula. This episode examines the clinical presentation, diagnostic journey, and management challenges of this rare and complex aortic pathology, highlighting the role of multimodal imaging and the interplay of multifactorial risk factors. Expert commentary is provided by Dr. Andrew Zurick III. Episode audio was edited by CardioNerds Intern student Dr. Pacey Wetstein.

We Were Thrilled to Join the American Heart Association’s Scientific Sessions 2025!AHA Scientific Sessions 2025 took place November 7–10 in New Orleans, LA — one of the premier annual gatherings in cardiovascular science and education.

It was an incredible opportunity to connect with colleagues, hear cutting-edge research, and contribute to the ongoing conversations shaping the future of cardiovascular care.

We’re grateful to everyone who joined us in New Orleans and made this year’s meeting so impactful.

“To study the phenomena of disease without books is to sail an uncharted sea, while to study books without patients is not to go to sea at all.” – Sir William Osler. CardioNerds thank the patients and their loved ones whose stories teach us the Art of Medicine and support our Mission to Democratize Cardiovascular Medicine.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.

CardioNerds Case Reports Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll

CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!

Pearls1. Saccular Aneurysm Risk: Saccular aortic aneurysms, though less common than fusiform, carry a higher inherent rupture risk due to concentrated wall shear stress, often exacerbated by prior cardiac surgery, chronic hypertension, and polysubstance use. 2. Unprecedented Rupture: The direct rupture of an aortic aneurysm into a cardiac chamber, specifically the right ventricle, is an exceedingly rare event, with no prior reported cases in the literature, highlighting the unpredictable nature of complex aortic pathology. 3. Hemodynamic Catastrophe: A large aorto-right ventricular fistula creates a massive left-to-right shunt, leading to acute right ventricular pressure and volume overload, culminating in rapid cardiogenic shock and refractory right ventricular failure. 4. Multimodal Imaging Imperative: Multimodal imaging (CT angiography for anatomy, TTE/TEE for real-time hemodynamics and fistula detection, CMR for tissue characterization) is indispensable for rapid diagnosis and comprehensive characterization of life-threatening cardiovascular emergencies. 5. High-Risk Intervention: Emergent surgical repair of a ruptured aortic aneurysm with an aorto-right ventricular fistula is a high-risk procedure associated with significant mortality, underscoring the need for prompt multidisciplinary care and realistic outcome expectations.

Notes – Notes (drafted by Dr Neel Patel):

What are the unique characteristics and rupture risk of saccular aortic aneurysms?

Saccular aortic aneurysms are less common than fusiform aneurysms.
They are generally considered more prone to rupture due to higher wall shear stress concentrated at the neck of the aneurysm, acting as a focal point of weakness.
Contributing Factors to Aneurysm Formation and Rupture in this Case:
Prior Cardiac Surgery: Aortic cannulation during the VSD/ASD repair decades ago likely created a localized structural weakness or predisposition.
Chronic, Poorly Controlled Hypertension: Imposed relentless systemic stress on the arterial walls, accelerating dilation and weakening.
Polysubstance Use: Particularly stimulants like cocaine and methamphetamines, which directly contribute to vascular damage by inducing severe, uncontrolled hypertension and direct arterial wall injury. This significantly increases the risk of aneurysm formation and rupture, especially with pre-existing conditions.
The direct rupture of an aortic aneurysm into a cardiac chamber, specifically the right ventricle, is an exceedingly rare event, with no prior reported cases in the literature, making this a “first of its kind” report.

What are the hemodynamic consequences and management challenges associated with aorto-right ventricular fistulas?

Hemodynamic Impact: A large aorto-right ventricular fistula results in a significant anatomic left-to-right shunt, where blood from the high-pressure aorta is shunted directly into the lower-pressure right ventricle.
This leads to acute right ventricular pressure and volume overload, causing rapid right ventricular dilation, increased right ventricular wall stress, and ultimately, acute right ventricular failure.
This directly explained the sudden onset of cardiogenic shock, as the right ventricle was unable to maintain forward flow, leading to systemic hypoperfusion and shock.
Management Challenges:
The patient required emergent, extremely high-risk salvage aortic aneurysm repair surgery.
Marked hemodynamic instability occurred immediately after anesthesia induction (systolic blood pressure dropped to 50 mmHg), necessitating immediate initiation of external cardiopulmonary bypass.
Intra-operatively, a large (2 cm diameter) hole in the ascending aorta communicating with the saccular aneurysm was found, along with a massive (4-5 cm) fistula into the right ventricular outflow tract (RVOT) area, just proximal to the pulmonic valve, with several smaller holes.
Surgical repair involved a 5×10 cm bovine pericardial patch for the right ventricular wall and replacement of a 5 cm segment of the ascending aorta with a 34 mm gelweave straight graft.
Post-operative Course: Severely complicated by severe coagulopathy and extensive bleeding (requiring multiple blood products and a Cabral fistula).
Continued severe right ventricular dysfunction necessitated the placement of a Right Ventricular Assist Device (RVAD).
Despite support, hemodynamic function continued to decline, with severely depressed Left Ventricular (LV) function observed.
The patient ultimately passed away due to refractory right heart failure and hemodynamic collapse, highlighting the extremely high mortality risk associated with such complex, emergent cardiac surgical interventions.

What is the role of multimodal imaging in diagnosing this complex and rare cardiovascular emergency?

CT Angiography: Crucial for initial identification and comprehensive characterization of the large saccular ascending aortic aneurysm, providing precise dimensions, revealing layered thrombus, and understanding anatomical relationships. Its high spatial resolution and wide field of view are excellent for aortic assessment.
Transthoracic and Transesophageal Echocardiography (TTE/TEE): Absolutely critical for real-time diagnosis of the fistula during acute deterioration. Bedside echocardiography, particularly TEE, allowed for visualization of the new continuous, turbulent flow from the aorta directly into the right ventricle, quantification of acute right ventricular dilation, and estimation of significantly increased RVSP. Its accessibility and real-time capabilities are unmatched for acute hemodynamic assessment and shunt detection.
Cardiac MRI (CMR): Provided additional tissue characterization of the aneurysm, confirming partial thrombosis and, importantly, showing no significant late gadolinium enhancement (LGE) in the myocardium, which was reassuring regarding the absence of significant myocardial scar related to the aneurysm itself. CMR offers superior soft tissue characterization compared to CT.
Complementary Nature: This case demonstrated the complementary nature of these modalities: CT provided the initial anatomical roadmap, echocardiography offered real-time hemodynamic assessment and immediate diagnosis of the acute rupture and shunt, and CMR contributed valuable tissue characterization. Imaging choices are guided by clinical questions, urgency, and specific information needed for critical management decisions.

What are the multi-factorial risk factors contributing to complex aortic disease, including the often-overlooked impact of polysubstance use?

Prior Cardiac Surgery: The patient’s history of open-heart surgery decades prior, involving aortic cannulation for cardiopulmonary bypass, is a recognized risk factor for the subsequent development of iatrogenic aneurysms, creating a localized structural weakness or predisposition.
Chronic, Poorly Controlled Hypertension: Imposes relentless systemic stress on the arterial walls, accelerating dilation and weakening, significantly contributing to aneurysm progression.
Polysubstance Use:
The patient’s long-standing history of polysubstance use, particularly stimulants like cocaine and methamphetamines, represents a significant contributing factor to his vascular pathology.
These substances are not merely comorbidities; they directly contribute to vascular damage.
Chronic stimulant use can induce severe, uncontrolled hypertension and direct arterial wall injury.
This significantly increases the risk of aneurysm formation and rupture, especially when combined with pre-existing conditions like essential hypertension and prior cardiac surgery.
Multi-hit Phenomenon: This case illustrates a multi-factorial pathology where various insults on vascular integrity over time converge to create a highly complex and catastrophic cardiovascular event. The presence of these factors emphasizes the critical importance of a thorough social history in cardiovascular risk assessment, moving beyond a superficial listing to understanding the profound pathophysiological impact on vascular health.

References – 1. Lavall D, Schäfers HJ, Böhm M, Laufs U. Aneurysms of the ascending aorta. Dtsch Arztebl Int. 2012 Mar;109(13):227-33. doi: 10.3238/arztebl.2012.0227. Epub 2012 Mar 30. PMID: 22532815; PMCID: PMC3334714. 2. Shang EK, Nathan DP, Boonn WW, Lys-Dobradin IA, Fairman RM, Woo EY, Wang GJ, Jackson BM. A modern experience with saccular aortic aneurysms. J Vasc Surg. 2013 Jan;57(1):84-8. doi: 10.1016/j.jvs.2012.07.002. Epub 2012 Nov 3. PMID: 23127980. 3. Brown PM, Zelt DT, Sobolev B. The risk of rupture in untreated aneurysms: the impact of size, gender, and expansion rate. J Vasc Surg. 2003 Feb;37(2):280-4. doi: 10.1067/mva.2003.119. PMID: 12563196. 4. Natsume K, Shiiya N, Takehara Y, Sugiyama M, Satoh H, Yamashita K, Washiyama N. Characterizing saccular aortic arch aneurysms from the geometry-flow dynamics relationship. J Thorac Cardiovasc Surg. 2017 Jun;153(6):1413-1420.e1. doi: 10.1016/j.jtcvs.2016.11.032. Epub 2016 Nov 22. PMID: 28027791. 5. Jeroen Walpot, Cees Klazen, Raymond Hokken, Jetze Sorgedrager, Martha Hoevenaar, Judith den Braber, Aorto-right ventricular fistula as an occasional finding, European Journal of Echocardiography, Volume 6, Issue 1, January 2005, Pages 65–66, https://doi.org/10.1016/j.euje.2004.08.009 6. De Viti D, Santoro F, Raimondo P, Brunetti ND, Memmola C. Congenital Aorto-Right Ventricular Fistula Associated with Pulmonary Hypertension in an Old Female Patient. J Cardiovasc Echogr. 2018 Apr-Jun;28(2):141-142. doi: 10.4103/jcecho.jcecho_58_17. PMID: 29911015; PMCID: PMC5989549. 7. Konda MK, Kalavakunta JK, Pratt JW, Martin D, Gupta V. Aorto-right Ventricular Fistula Following Percutaneous Transcatheter Aortic Valve Replacement: Case Report and Literature Review. Heart Views. 2017 Oct-Dec;18(4):133-136. doi: 10.4103/HEARTVIEWS.HEARTVIEWS_115_16. PMID: 29326776; PMCID: PMC5755194. 8. Vainrib AF, Ibrahim H, Hisamoto K, Staniloae CS, Jilaihawi H, Benenstein RJ, Latson L, Williams MR, Saric M. Aorto-Right Ventricular Fistula Post-Transcatheter Aortic Valve Replacement: Multimodality Imaging of Successful Percutaneous Closure. CASE (Phila). 2017 Apr 24;1(2):70-74. doi: 10.1016/j.case.2017.02.002. PMID: 30062248; PMCID: PMC6034486. 9. Walpot J, Klazen C, Hokken R, Sorgedrager J, Hoevenaar M, den Braber J. Aorto-right ventricular fistula as an occasional finding. Eur J Echocardiogr. 2005 Jan;6(1):65-6. doi: 10.1016/j.euje.2004.08.009. PMID: 15664555. 10. Ghuran A, Nolan J. The cardiac complications of recreational drug use. West J Med. 2000 Dec;173(6):412-5. doi: 10.1136/ewjm.173.6.412. PMID: 11112762; PMCID: PMC1071198. 11. Gagnon LR, Sadasivan C, Perera K, Oudit GY. Cardiac Complications of Common Drugs of Abuse: Pharmacology, Toxicology, and Management. Can J Cardiol. 2022 Sep;38(9):1331-1341. doi: 10.1016/j.cjca.2021.10.008. Epub 2021 Nov 1. PMID: 34737034. 12. Alabbady AM, Sattur S, Bauch TD, Harjai KJ. Aorto-Right Ventricular Fistula and Paravalvular Leak After Transcatheter Aortic Valve Implantation. JACC Case Rep. 2019 Dec 18;1(5):859-864. doi: 10.1016/j.jaccas.2019.11.025. PMID: 34316946; PMCID: PMC8288756. 13. Chia R, Kalutota C, Cao K, Douedi S, Chang W, Pinciotti D, Beizaeipour M, Joiner J, Ice D, Ross R, Kovach R, Chen C, Raza M. Management of Aorto-Right Ventricular Fistulas After TAVR. JACC Case Rep. 2024 Nov 6;29(21):102655. doi: 10.1016/j.jaccas.2024.102655. PMID: 39619019; PMCID: PMC11602638. 14. Samuels LE, Kaufman MS, Rodriguez-Vega J, Morris RJ, Brockman SK. Diagnosis and management of traumatic aorto-right ventricular fistulas. Ann Thorac Surg. 1998 Jan;65(1):288-92. doi: 10.1016/s0003-4975(97)01084-9. PMID: 9456147.

Case Media* * * * * * * * * *

View Details

CardioNerds guest host Dr. Colin Blumenthal joins Dr. Juma Bin Firos and Dr. Aishwarya Verma from the Trinity Health Livonia Hospital to discuss a fascinating case involving malignant ventricular arrhythmias. Expert commentary is provided by Dr. Mohammad-Ali Jazayeri. Audio editing for this episode was performed by CardioNerds Intern,Julia Marques Fernandes.

It was an incredible opportunity to connect with colleagues, hear cutting-edge research, and contribute to the ongoing conversations shaping the future of cardiovascular care.

We’re grateful to everyone who joined us in New Orleans and made this year’s meeting so impactful.

This case explores the puzzling presentation of exercise-induced ventricular tachycardia in a young, otherwise healthy male who suffered recurrent out-of-hospital cardiac arrests. With no traditional risk factors and an unremarkable ischemic workup, the challenge lay in uncovering the underlying cause of his malignant arrhythmias. Electrophysiology studies and advanced imaging played a pivotal role in systematically narrowing the differentials, revealing an unexpected arrhythmogenic substrate. This episode delves into the diagnostic dilemma, the role of EP testing, and the critical decision-making surrounding ICD placement in a patient with a concealed but life-threatening condition.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.

CardioNerds Case Reports Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll

CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!

Pearls- Malignant Ventricular ArrhythmiasThis case highlights the challenges and importance of diagnosing and managing ventricular arrhythmias in young, seemingly healthy individuals. Here are five key takeaways from the episode:

Electrophysiology (EP) studies play a crucial role in identifying arrhythmogenic substrates in patients with exercise-induced ventricular tachycardia (VT) without obvious structural heart disease. In this case, substrate mapping revealed late abnormal ventricular afterdepolarizations in the basal inferior left ventricle, providing valuable insights into the underlying mechanism.
Cardiac MRI can be a powerful tool for detecting subtle myocardial abnormalities. The subepicardial late gadolinium enhancement (LGE) in the lateral and inferior LV walls suggested an underlying myocardial process, even when other imaging modalities appeared normal.
The VT morphology can provide clues about the underlying mechanism. In this case, the right bundle branch block pattern with a northwest axis and shifting exit sites pointed towards a scar-mediated mechanism rather than a channelopathy or idiopathic VT.
Implantable cardioverter-defibrillator (ICD) placement is crucial for secondary prevention of sudden cardiac death (SCD) in patients with malignant ventricular arrhythmias, even in young individuals. The patient’s initial deferral of ICD implantation highlights the importance of shared decision-making and patient education in these complex cases.
“Scar-mediated VT introduces the risk of new arrhythmogenic substrates over time, reinforcing the need for ICD therapy even when catheter ablation is considered.” This pearl emphasizes the dynamic nature of the arrhythmogenic substrate and the importance of long-term risk mitigation strategies.

Notes – Malignant Ventricular ArrhythmiasNotes were drafted by Juma Bin Firos.

What underlying pathologies cause ventricular arrhythmias in young patients without overt structural heart disease?Myocardial fibrosis:
Detected via late gadolinium enhancement (LGE) on cardiac MRI
Present in 38% of nonischemic cardiomyopathy cases
Increases sudden cardiac death (SCD) risk 5-fold
Often localized to subepicardial regions, particularly in the inferolateral left ventricle (LV)
May precede overt systolic dysfunction by years

Subclinical cardiomyopathy:

67% of young VT patients show subtle cardiac dysfunction
Suggests VT may be the first manifestation of cardiomyopathy
Can include early-stage genetic cardiomyopathies (e.g., ARVC, LMNA mutations)
Often associated with preserved ejection fraction (EF >50%)

Arrhythmogenic substrate:

EP studies localize re-entry circuits to specific regions:
- Basal inferior LV near the mitral annulus (as in this case)
- Right ventricular outflow tract (RVOT) in idiopathic VT
- Papillary muscles or fascicular regions
Substrate can exist even with normal EF and no visible structural abnormalities on echocardiography

Channelopathies:

Long QT syndrome (LQTS): QTc >460ms in males, >470ms in females
Brugada syndrome: Coved ST elevation in V1-V3
Catecholaminergic polymorphic VT (CPVT): Normal resting ECG, bidirectional VT with exercise
Short QT syndrome: QTc <330ms

Inflammatory conditions:

Myocarditis: Can cause transient or persistent arrhythmogenic substrate
Cardiac sarcoidosis: Patchy inflammation and fibrosis, often affecting the septum

How do electrophysiology studies differentiate scar-mediated VT from channelopathies?Substrate mapping:
Identifies late abnormal potentials (LAPs) with 92% specificity for re-entry circuits
Utilizes multi-electrode catheters (e.g., Penta Ray) for high-density mapping
LAPs indicate slow conduction through fibrotic tissue, key for re-entry
Absent in purely electrical disorders like channelopathies

Inducibility:

Programmed electrical stimulation (PES) protocols:
Up to triple extra stimuli at multiple sites (RV apex, RVOT, LV)
Burst pacing at cycle lengths down to 200-250ms
Scar-mediated VT is often inducible with aggressive stimulation
Polymorphic VT/VF induction suggests a structural substrate
Channelopathies like Catecholaminergic polymorphic ventricular tachycardia CPVT) typically requires isoproterenol or exercise for induction

VT morphology analysis:

Right bundle branch block (RBBB) + northwest axis localizes to LV basal inferior wall
Left bundle branch block (LBBB) + inferior axis suggests RVOT origin
Fascicular VT: RBBB + left anterior or posterior fascicular block pattern
Papillary muscle VT: RBBB or LBBB with variable axis

Entrainment mapping:

Performed during sustained monomorphic VT
Post-pacing interval minus tachycardia cycle length (PPI-TCL) <30ms indicates critical isthmus
Not applicable to polymorphic VT or channelopathies

Electroanatomic voltage mapping:

Low voltage areas (<1.5mV bipolar) indicate scar tissue
Normal voltage throughout suggests functional (non-scar) VT mechanism

What are key management considerations for recurrent VT/VF in young patients? ICD for secondary prevention:*
- Class I indication after cardiac arrest or sustained VT without a reversible cause
- Reduces mortality from 13% (8-year untreated) to <5%, especially with LGE present
Device selection:
- Single-chamber ICD if no pacing indication
- Subcutaneous ICD (S-ICD) in young patients to avoid transvenous lead complications
- Consider cardiac resynchronization therapy defibrillator (CRT-D) if LBBB or wide QRS
LifeVest limitations:
- Bridges ≤3 months; not a long-term solution
- Recurrent arrests double mortality vs. prompt ICD implantation
- Compliance issues: must be worn consistently to be effective
Oral antiarrhythmic medications:
- Amiodarone:
  - Effective for acute VT suppression
  - Long-term use limited by side effects (thyroid, liver, pulmonary toxicity)
- Beta-blockers: First line for most VT/VF, especially exercise-induced
- Sotalol: Alternative for those with preserved LV function
- Mexiletine: Adjunct for frequent ICD shocks, especially with LQT3
Catheter ablation:
- Consider early in the course for recurrent ICD shocks
- Success rates 60-80% for scar-related VT
- May reduce ICD shocks and improve quality of life
- Limitations: deep intramural or epicardial substrates may require specialized approaches
Lifestyle modifications:
- Exercise restrictions: Avoid high-intensity activities that trigger arrhythmias
- Stress management: Consider cognitive behavioral therapy or mindfulness training
- Avoidance of QT-prolonging medications in LQTS patients
Genetic testing and family screening:
- Recommended for suspected inherited arrhythmia syndromes
- Can guide management and risk stratification for family members

Why does exercise exacerbate arrhythmia risk in these patients? Sympathetic surge:*
- Increases myocardial oxygen demand
- Enhances automaticity and triggered activity
- Can unmask concealed conduction abnormalities
Hemodynamic changes:
- Increased preload and afterload stress fibrotic regions
- Volume shifts may alter electrolyte concentrations locally
Metabolic factors:
- Lactic acid accumulation can promote ectopic beats
- Catecholamine release exacerbates ion channel dysfunction in channelopathies
Exercise-induced VT/VF correlates with 8× higher SCD risk vs. rest-onset arrhythmias:
- Warrants activity restrictions tailored to individual risk profile
- May indicate more malignant substrate or advanced disease process
Treadmill testing:
- Should guide therapy in asymptomatic patients with exercise-related VT
  - Protocols:
  - Bruce protocol for general assessment
  - Modified protocols (e.g., longer stages) for specific arrhythmia provocation
- Endpoints:
  - Induction of sustained VT/VF
  - Achieving target heart rate (85% of age-predicted maximum)
  - Development of concerning symptoms (pre-syncope, chest pain)
Cardiac rehabilitation:
Supervised exercise programs can improve outcomes
Gradual increase in intensity with continuous monitoring
Helps define safe exercise thresholds for patients

How does LGE on cardiac MRI refine risk stratification?Late gadolinium enhancement (LGE) on cardiac MRI acts like a “scar map” of the heart, revealing areas of damaged or fibrotic tissue. These scars create electrical instability, increasing the risk of dangerous heart rhythms and sudden cardiac death (SCD). Here’s how LGE refines risk assessment:

1. Predicting Sudden Cardiac Death (SCD)

Major risk multiplier:
- Patients with LGE have 4.3× higher odds of life-threatening arrhythmia, regardless of their heart’s pumping ability (ejection fraction, EF).
- For every 1% increase in scar size (as % of heart muscle), SCD risk rises by 15%.
Thresholds matter:
- In hypertrophic cardiomyopathy (HCM), LGE covering ≥5% of the heart muscle adds critical risk stratification, even in patients not initially flagged as high-risk by guidelines.
- Larger scars (≥10-15%) correlate with dramatically higher SCD risk, especially in HCM.

2. Mortality Signals

Annual death rates:
- LGE+ patients: 4.7% annual mortality (similar to ischemic heart disease).
- LGE− patients: 1.7% annual mortality.
Patterns and locations:
- Midwall scars (e.g., in dilated cardiomyopathy): 4.6× higher risk of SCD.
- Inferolateral scars (common in cardiac sarcoidosis): Linked to frequent ventricular tachycardia (VT).

3. Quantifying Scars: Methods Matter

Full Width at Half Maximum (FWHM):
- Most reproducible method for measuring scar size.
- Reduces overestimation compared to other techniques.
Standard Deviation (SD) thresholds:
- 5-SD method: Widely used but may overestimate scar size.
- 6-SD method: Best studied; 10% LGE is the optimal cutoff for predicting SCD in HCM.
Dark-blood vs. bright-blood imaging:
- Dark-blood LGE improves scar visualization in ischemic heart disease but performs similarly to bright-blood LGE in non-ischemic conditions.

4. Guideline Gaps and Solutions

Current ICD criteria fall short:
- Guidelines focus on EF ≤35%, missing high-risk patients with EF >35% but significant LGE.
- Example: A patient with EF 45% and 12% LGE has higher SCD risk than many with EF ≤35%.
Emerging recommendations:
- Use LGE to guide ICD decisions in the “grey zone” (EF 36-50%).
- The 2022 ESC HCM model now integrates LGE for better risk prediction.

5. Tracking Changes Over Time

Serial imaging:
- Repeat MRIs every 1-2 years monitor scar progression.
- Example: If LGE grows from 8% to 14%, ICD may be warranted even if EF remains normal.

6. Limitations

Not all scars are equal:
- Ischemic scars (from blocked arteries) vs. non-ischemic scars (e.g., HCM) carry different risks.
Technical challenges:
- Labs use different methods (e.g., FWHM vs. SD), causing variability in measurements.
Contraindications:
- Severe kidney disease (risk of gadolinium toxicity) or implanted devices (e.g., older pacemakers) may limit MRI use.

References – Malignant Ventricular ArrhythmiasAl-Khatib, S. M., Stevenson, W. G., Ackerman, M. J., Bryant, W. J., Callans, D. J., Curtis, A. B., … & Page, R. L. (2018). 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Journal of the American College of Cardiology, 72(14), e91-e220. https://www.ahajournals.org/doi/10.1161/CIR.0000000000000549

Di Marco, A., Anguera, I., Schmitt, M., Klem, I., Neilan, T. G., White, J. A., … & Cequier, A. (2017). Late gadolinium enhancement and the risk for ventricular arrhythmias or sudden death in dilated cardiomyopathy: systematic review and meta-analysis. JACC: Heart Failure, 5(1), 28-38. https://www.sciencedirect.com/science/article/pii/S2213177916305698?via%3Dihub

Kuruvilla, S., Adenaw, N., Katwal, A. B., Lipinski, M. J., Kramer, C. M., & Salerno, M. (2014). Late gadolinium enhancement on cardiac magnetic resonance predicts adverse cardiovascular outcomes in nonischemic cardiomyopathy: a systematic review and meta-analysis. Circulation: Cardiovascular Imaging, 7(2), 250-258.

https://pubmed.ncbi.nlm.nih.gov/24363358

Gulati, A., Jabbour, A., Ismail, T. F., Guha, K., Khwaja, J., Raza, S., … & Prasad, S. K. (2013). Association of fibrosis with mortality and sudden cardiac death in patients with nonischemic dilated cardiomyopathy. Jama, 309(9), 896-908. https://jamanetwork.com/journals/jama/fullarticle/1660382

Piers, S. R., Tao, Q., van Huls van Taxis, C. F., Schalij, M. J., van der Geest, R. J., & Zeppenfeld, K. (2013). Contrast-enhanced MRI–derived scar patterns and associated ventricular tachycardias in nonischemic cardiomyopathy: implications for the ablation strategy. Circulation: Arrhythmia and Electrophysiology, 6(5), 875-883. https://pubmed.ncbi.nlm.nih.gov/24036134/

Priori, S. G., Blomström-Lundqvist, C., Mazzanti, A., Blom, N., Borggrefe, M., Camm, J., … & Van Veldhuisen, D. J. (2015). ESC Scientific Document Group. 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC). Eur Heart J, 36(41), 2793-2867. https://pubmed.ncbi.nlm.nih.gov/26320108/

Wang, J., Yang, S., Ma, X., Zhao, K., Yang, K., Yu, S., … & Zhao, S. (2023). Assessment of late gadolinium enhancement in hypertrophic cardiomyopathy improves risk stratification based on current guidelines. European heart journal, 44(45), 4781-4792. https://pubmed.ncbi.nlm.nih.gov/37795986/

Kiaos, A., Daskalopoulos, G. N., Kamperidis, V., Ziakas, A., Efthimiadis, G., & Karamitsos, T. D. (2024). Quantitative late gadolinium enhancement cardiac magnetic resonance and sudden death in hypertrophic cardiomyopathy: a meta-analysis. Cardiovascular Imaging, 17(5), 489-497. https://pubmed.ncbi.nlm.nih.gov/37795986/

Case Media

View Details

CardioNerds (Dr. Rick Ferraro and Dr. Dan Ambinder) join Dr. Sahar Samimi and Dr. Lorraine Mascarenhas from Baylor College of Medicine, Houston, Texas, at the Houston Rodeo for some tasty Texas BBQ and a tour of the lively rodeo grounds to discuss an interesting case full of clinical pearls involving a patient with nonbacterial thrombotic endocarditis (NBTE). Expert commentary is provided by Dr. Basant Arya. Episode audio was edited by CardioNerds Intern Dr. Bhavya Shah.

(Photo by Xu Jianmei/Xinhua via Getty Images)Xinhua News Agency via Getty ImagesWe discuss a case of a 38-year-old woman with advanced endometrial cancer who presents with acute abdominal pain, found to have splenic and renal infarcts, severe aortic regurgitation, and persistently negative blood cultures, ultimately diagnosed with nonbacterial thrombotic endocarditis (NBTE). We review the definition and pathophysiology of NBTE in the context of malignancy and hypercoagulability, discuss initial evaluation and echocardiographic findings, and highlight important management considerations. Emphasis is placed on the complexities of anticoagulation choice, the role of valvular surveillance, and the need for coordinated, multidisciplinary care.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.

CardioNerds Case Reports Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll

CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!

Pearls- Nonbacterial Thrombotic Endocarditis1. Eliminate the Usual Suspects. NBTE is a diagnosis of exclusion! Always rule out infective endocarditis (IE) first with serial blood cultures and serologic tests. 2. More than Meets the Echo. Distinguishing NBTE from culture-negative endocarditis can be tricky. Look beyond the echo—focus on clinical context (underlying malignancy, autoimmune issues) and lab findings to clinch the diagnosis. 3. TEE for the Win… Mostly. While TEE is more sensitive than TTE, NBTE vegetations can be sneaky and may embolize quickly. Don’t hesitate to use advanced imaging (i.e., cardiac MRI, CTA) or repeat imaging if you still suspect NBTE. 4. Choose your champion. In cancer-associated NBTE, guideline recommendations for anticoagulation choice are lacking. Consider DOACs and LMWH as agents of choice, but ultimately use shared decision-making to guide management. 5. No obvious trigger? Go hunting for hidden malignancies or autoimmune disorders. A thorough workup is essential to uncover the driving force behind NBTE.

Check out this state-of-the-art review for a comprehensive, one-stop summary of NBTE: European Heart Journal, 46(3), 236–245. Please note that the figures and tables referenced in the following notes are adapted from this review.

notes- Nonbacterial Thrombotic EndocarditisNotes were drafted by Dr. Sahar Samimi.

What is nonbacterial thrombotic endocarditis (NBTE)?
NBTE, previously known as marantic endocarditis, is a rare condition in which sterile vegetations form on heart valves.1
It occurs most commonly in association with malignancies and autoimmune conditions (i.e, antiphospholipid antibody syndrome or systemic lupus erythematosus).1 In addition, NBTE has been reported in association with COVID-19 infection, burns, sepsis, and indwelling catheters.2
Precise mechanisms remain unclear, but an interplay of endothelial injury, hypercoagulability, hypoxia, and immune complex deposition contributes to the formation of these sterile vegetations. 1
How do we diagnose NBTE?
Physicians should have a high level of suspicion for NBTE in at-risk patients (e.g., with active malignancy) who present with recent or recurrent embolic events (i.e., stroke, splenic, renal, or mesenteric infarct, and acute coronary syndrome).1
Once vegetations are observed, the diagnosis of NBTE is focused on ruling out IE, followed by looking for the underlying etiology, if not already evident.1 A focused clinical assessment, including a thorough history, physical exam, and relevant microbiological and serological tests, should aim to rule out IE using the modified Duke criteria.3
Persistently negative blood cultures after adequate sampling increase the likelihood of NBTE but do not exclude culture-negative endocarditis. Vegetations found in patients with risk factors raise the suspicion for NBTE, whereas signs of systemic infection—such as ongoing fever, recent antibiotic exposure, or potential zoonotic sources—may point instead toward CNE.1
New diagnostic techniques, including specialized serology and metagenomic sequencing, have significantly enhanced our ability to detect elusive pathogens in CNE.1
How should imaging be approached in suspected NBTE?
In cases of suspected endocarditis, guidelines from the American College of Cardiology, the American Heart Association, and the European Society of Cardiology recommend starting the assessment with a TTE to visualize potential valvular vegetations. 4,5
TTE is less sensitive than TEE, particularly for detecting smaller vegetations < 5 mm that are often associated with NBTE. Therefore, a subsequent TEE is recommended due to its superior ability to detect subtle valvular abnormalities. 4,5
Echocardiographic features of vegetations alone do not reliably distinguish NBTE from IE; hence, clinical context, along with laboratory and microbiological findings, is crucial for accurate diagnosis. 1
Uncertainty may remain following a TEE or in cases where TEE is not feasible. In such situations, advanced imaging techniques like cardiac MRI and CT scanning are emerging tools for more detailed cardiac tissue characterization. 1
What are the management strategies for NBTE?
NBTE’s complexity necessitates a multidisciplinary treatment strategy, with each patient’s prognosis shaped by individual clinical factors. 1
Primary therapy involves anticoagulation, alongside targeted management of malignancy or autoimmune disorder driving the hypercoagulable state. 1
While the criteria for surgical intervention are similar to those used in IE, surgery generally has a more limited role in NBTE. 1
What factors into choosing the anticoagulation agent?
Anticoagulation outcomes in NBTE can vary greatly: some patients have vegetations resolve, while others experience disease progression to new valves despite therapy.1
Because NBTE-specific evidence remains sparse, the underlying clinical context primarily guides the choice of anticoagulant:
Multiple case reports describe DOAC failure with recurrent embolization in patients with cancer and NBTE. 6-8
LMWH remains a mainstay for patients with cancer or when patients experience thrombotic complications on DOACs. 1
Warfarin is the preferred anticoagulant among patients with thrombotic antiphospholipid syndrome. 9
The duration of anticoagulation should take into consideration the status of the underlying disease, the presence of valvular lesions on follow-up imaging, and an individualized assessment of risks and benefits. 1

References – Nonbacterial Thrombotic Endocarditis1. Ahmed O, King NE, Qureshi MA, et al. Non-bacterial thrombotic endocarditis: a clinical and pathophysiological reappraisal. European Heart Journal. 2025;46(3):236-49. 2. Balata D, Mellergård J, Ekqvist D, et al. Non-bacterial thrombotic endocarditis: a presentation of COVID-19. European journal of case reports in internal medicine. 2020;7(8). 3. Li JS, Sexton DJ, Mick N, et al. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis 2000;30: 633–8. 4. Otto CM, Nishimura RA, Bonow RO, et al. 2020 ACC/AHA guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol 2021;77:e25–197. 5. Vahanian A, Beyersdorf F, Praz F, et al.; ESC/EACTS Scientific Document Group. 2021 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J. 2022 Feb 12;43(7):561-632. 6. Mantovani F, Navazio A, Barbieri A, Boriani G. A first described case of cancer- associated non-bacterial thrombotic endocarditis in the era of direct oral anticoagulants. Thromb Res 2017;149:45–7. 7. Panicucci E, Bruno C, Ferrari V, Suissa L. Recurrence of ischemic stroke on direct oral anticoagulant therapy in a patient with marantic endocarditis related to lung cancer. J Cardiol Cases 2021;23:242–5. 8. Shoji MK, Kim JH, Bakshi S, et al. Nonbacterial thrombotic endocarditis due to primary gallbladder malignancy with recurrent stroke despite anticoagulation: case report and literature review. J Gen Intern Med 2019;34:1934–40. 9. Khairani CD, Bejjani A, Piazza G, et al. Direct oral anticoagulants vs vitamin K antagonists in patients with antiphospholipid syndromes: meta-analysis of randomized trials. J Am Coll Cardiol 2023;81:16–30.

Case Media* * * * TTE and TEE

View Details

CardioNerds (Dr. Claire Cambron and Dr. Rawan Amir) join Dr. Ayan Purkayastha, Dr. David Song, and Dr. Justin Wang from NewYork-Presbyterian Queens for an afternoon of hot pot in downtown Flushing. They discuss a case of congenital heart disease presenting in adulthood. Expert commentary is provided by Dr. Su Yuan, and audio editing for this episode was performed by CardioNerds Intern, Julia Marques Fernandes.

A 53-year-old woman with a past medical history of hypertension visiting from Guyana presented with 2 days of chest pain. EKG showed dominant R wave in V1 with precordial T wave inversions. Troponin levels were normal, however she was started on therapeutic heparin with plan for left heart catheterization. Her chest X-ray revealed dextrocardia and echocardiogram was suspicious for the systemic ventricle being the morphologic right ventricle with reduced systolic function and the pulmonic ventricle being the morphologic left ventricle. Patient underwent coronary CT angiography which confirmed diagnosis of congenitally corrected transposition of the great arteries (CCTGA) as well as minimal non-obstructive coronary artery disease. Her chest pain spontaneously improved and catheterization was deferred. Patient opted to follow with a congenital specialist back in her home country upon discharge.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.

CardioNerds Case Reports Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll

CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!

Pearls- A Case of Congenital Heart Disease Presenting in Adulthood1. Congenitally Corrected Transposition of the Great Arteries (CCTGA) is a rare and unique structural heart disease which presents as an isolated combination of atrioventricular and ventriculoarterial discordance resulting in physiologically corrected blood flow. 2. CCTGA occurs due to L looping of the embryologic heart tube. As a result, the morphologic right ventricle outflows into the systemic circulation, and the morphologic left ventricle outflows into the pulmonary circulation. 3. CCTGA is frequently associated with ventricular septal defects, pulmonic stenosis, tricuspid valve abnormalities and dextrocardia. 4. CCTGA is often asymptomatic in childhood and can present later in adulthood with symptoms of morphologic right ventricular failure, tricuspid regurgitation, or cardiac arrhythmias. 5. Systemic atrioventricular valve (SAVV) intervention can be a valuable option for treating right ventricular failure and degeneration of the morphologic tricuspid valve.

notes- A Case of Congenital Heart Disease Presenting in AdulthoodNotes were drafted by Ayan Purkayastha.

What is the pathogenesis of Congenitally Corrected Transposition of the Great Arteries?

Occurs due to disorders in the development of the primary cardiac tube
Bulboventricular part of the primary heart forms a left-sided loop instead of right-sided loop, leading to the normally located atria being connected to morphologically incompatible ventricles
This is accompanied by abnormal torsion of the aortopulmonary septum (transposition of the great vessels)
As a result, there is ‘physiologic correction’ of blood flow. Non-oxygenated blood flows into the right atrium and through the mitral valve into the morphologic left ventricle, which pumps blood into the pulmonary artery. Oxygenated blood from the pulmonary veins flows into the left atrium and through the tricuspid valve to the morphologic right ventricle, which pumps blood to the aorta. Compared with standard anatomy, the flow of blood is appropriate, but it is going through the incorrect ventricle on both sides.
Frequent conditions associated with CCTGA include VSD, pulmonic stenosis and dextrocardia

What is the presentation of Congenitally Corrected Transposition of the Great Arteries?

In cases without concomitant deficits CCTA is asymptomatic early in life and often for several decades. Cyanosis and dyspnea are common presenting symptoms.

Systemic right ventricular dysfunction due to high systemic pressures over time
Arrythmias, commonly AV block, due to abnormal structure of the conduction system
Tricuspid valve regurgitation resulting from dilation of the right ventricle and tricuspid valve annulus

What is Dextrocardia and how is it associated with CCTGA?

Dextrocardia is a cardiac positional anomaly where the heart is located in the right hemithorax with base to apex axis directed to the right and caudad
Dextrocardia can occur in up to 20% cases of CCTGA
Can be associated with both situs solitus (normal anatomic arrangement of chest and abdominal organs) or situs inversus (chest and abdominal organs are mirrored from their normal positions)

How is CCTGA Diagnosed?

Transthoracic echocardiography is the primary diagnostic tool in CCTGA
Assessment of the systemic RV function is crucial but can be challenging. Techniques such as speckle tracking echocardiography and global longitudinal strain can help with assessment of systemic RV function
Cardiac MRI can also provide accurate measurements of ventricular volumes as well as quantification of valvular regurgitation

What is the long-term management of CCTGA in adults?

Many patients with CCTGA and no associated lesions have long life expectancies with minimal or non-specific symptoms
Symptoms of circulatory failure occur mainly in 5th and 6th decades of life

The 2018 AHA/ACC Guidelines for the Management of Adults with Congenital Heart Disease recommends the following routine follow-up and testing intervals for CCTGA

Physiologic stage A: Outpatient ACHD follow up every 12 months with ECG(12 months), TTE(12-24 months), Holter monitor(12-60 months), CMR/CCT and exercise test(36-60 months)
Physiologic stage B: outpatient ACHD follow up every 12 months with ECG and TTE(12 months), Holter monitor(12-60 months), CMR/CCT and exercise test(36-60 months)
Physiologic stage C: outpatient ACHD follow up every 6-12 months with ECG and TTE(12 months), pulse oximetry at each visit, Holter monitor(12-36 months), CMR/CCT and exercise test(12-24 months)
Physiologic stage D: outpatient ACHD follow up every 3-6 months, ECG and TTE every 12 months, pulse oximetry at each visit, Holter monitor, CMR/CCT and exercise test every 12 months

What is the role of Systemic Atrioventricular Valve Surgery (SAVV) for treatment of CCTGA as an adult?

In CCTGA the morphologic tricuspid valve acts as the SAVV and is subject to functional deterioration from high systemic pressures
Tricuspid valve regurgitation is a key prognostic overall survival determinant in CCTGA patients
Studies have shown that 94% of patients with CCTGA suffered from intrinsic tricuspid valve abnormalities
SAV surgery remains a valuable option with low early mortality and good long-term outcomes, especially with ejection fraction > 40%.
The 2018 AHA/ACC Guidelines for the Management of Adults with Congenital Heart Disease recommends tricuspid valve replacement for symptomatic adults with CCTGA and severe TR and preserved or mildly depressed systemic ventricular function (class IB recommendation).

References – A Case of Congenital Heart Disease Presenting in Adulthood1. Baruteau AE, Abrams DJ, Ho SY, Thambo JB, McLeod CJ, Shah MJ. Cardiac Conduction System in Congenitally Corrected Transposition of the Great Arteries and Its Clinical Relevance. J Am Heart Assoc. 2017;6(12). doi:10.1161/JAHA.117.007759

Susheel Kumar TK. Congenitally corrected transposition of the great arteries. J Thorac Dis. 2020;12(3):1213-1218. doi:10.21037/jtd.2019.10.15
Osakada K, Ohya M, Waki K, Nasu H, Kadota K. Congenitally Corrected Transposition of the Great Arteries at Age 88 Years. CJC Open. 2020;2(6):726-728. doi:10.1016/j.cjco.2020.08.003
Munaf M, Farooqui S, Kazmi SK, Ul-Haque I. Congenitally Corrected Transposition of Great Arteries with Dextrocardia, Patent Ductus Arteriosus, Atrial Septal Defects and Ventricular Septal Defects in a 15-Year-Old Marfanoid Habitus Patient: A Case Study. Cureus. Published online July 1, 2020. doi:10.7759/cureus.8937
Abdelrehim AA, Stephens EH, Miranda WR, et al. Systemic Atrioventricular Valve Surgery in Patients With Congenitally Corrected Transposition of the Great Vessels. J Am Coll Cardiol. 2023;82(23):2197-2208. doi:10.1016/j.jacc.2023.09.822
Lippmann MR, Maron BA. The Right Ventricle: From Embryologic Development to RV Failure. Curr Heart Fail Rep. 2022;19(5):325-333. doi:10.1007/s11897-022-00572-z
Brida M, Diller GP, Gatzoulis MA. Systemic Right Ventricle in Adults with Congenital Heart Disease. Circulation. 2018;137(5):508-518. doi:10.1161/CIRCULATIONAHA.117.031544
Bevilacqua F, Pasqualin G, Ferrero P, et al. Overview of Long-Term Outcome in Adults with Systemic Right Ventricle and Transposition of the Great Arteries: A Review. Diagnostics. 2023;13(13). doi:10.3390/diagnostics13132205
Maldjian PD, Saric M. Approach to dextrocardia in adults: Review. American Journal of Roentgenology. 2007;188(6 SUPPL.). doi:10.2214/AJR.06.1179
Kandakure PR, Katta Y, Batra MJ, Timmanwar A, Lakka VK, Reddy B. Dextrocardia and corrected transposition of the great arteries with rheumatic tricuspid stenosis: a unique association. Indian J Thorac Cardiovasc Surg. 2019;35(2):230-232. doi:10.1007/s12055-018-0778-0
Stout KK, Daniels CJ, Aboulhosn JA, et al. 2018 AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139(14):e698-e800. doi:10.1161/CIR.0000000000000603
Zubrzycki M, Schramm R, Costard-Jäckle A, et al. Pathogenesis and Surgical Treatment of Congenitally Corrected Transposition of the Great Arteries (ccTGA): Part III. J Clin Med. 2024;13(18). doi:10.3390/jcm13185461

View Details

CardioNerds Critical Care Cardiology Council members Dr. Gurleen Kaur and Dr. Katie Vanchiere meet with Dr. Yash Patel, Dr. Akanksha, and Dr. Mohammed El Nayir from Trinity Health Ann Arbor. They discuss a case of pulmonary air embolism, RV failure, and cardiac arrest secondary to an ocular venous air embolism. Expert insights provided by Dr. Tanmay Swadia. Audio editing by CardioNerds Academy intern, Grace Qiu.

A 36-year-old man with a history of multiple ocular surgeries, including a complex retinal detachment repair, suffered a post-vitrectomy collapse at home. He was found hypoxic, tachycardic, and hypotensive, later diagnosed with a pulmonary embolism from ocular venous air embolism leading to severe right heart failure. Despite a mild embolic burden, the cardiovascular response was profound, requiring advanced hemodynamic support, including an Impella RP device (Abiomed, Inc.). Multidisciplinary management, including fluid optimization, vasopressors and mechanical support to facilitate recovery. This case underscores the need for early recognition and individualized intervention in cases of ocular venous air embolism.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.

CardioNerds Case Reports Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll

CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!

Pearls- Clear Vision, Clouded Heart: Ocular Venous Air Embolism with Pulmonary Air Embolism, RV Failure, and Cardiac Arrest 1. Hypoxia, hypotension and tachycardia in a patient following ocular instrumentation are classic findings suggestive of pulmonary embolism from possible air embolism. 2. The diagnosis of RV failure is based on clinical presentation, echocardiographic findings (such as McConnell’s sign), and invasive hemodynamic assessment via right heart catheterization. 3. Mechanical circulatory support can be considered as a temporary measure for patients with refractory RV failure.

Central Figure: Approach to Pulmonary Embolism with Acute RV FailureNotes – Clear Vision, Clouded Heart: Ocular Venous Air Embolism with Pulmonary Air Embolism, RV Failure, and Cardiac Arrest 1. What is an Ocular Venous Air Embolism (VAE), and how can it be managed in critically ill patients?

An Ocular Venous Air Embolism is defined as the entry of air into the systemic venous circulation through the ocular venous circulation, often during vitrectomy procedures. Early diagnosis is key to preventing cardiovascular collapse in cases of Ocular Venous Air Embolism (VAE).
The goal is to stop further air entry. This can be done by covering the surgical site with saline-soaked dressings and checking for air entry points.
Adjusting the operating table can help, especially with a reverse Trendelenburg position for lower-body procedures.
The moment VAE is suspected, discontinue nitrous oxide and switch to 100% oxygen. This helps with oxygenation, speeds up nitrogen elimination, and shrinks air bubbles.
Hyperbaric Oxygen Therapy can reduce bubble size and improve oxygenation, especially in cases of cerebral air embolism, when administered within 6 hours of the incident.
Though delayed hyperbaric oxygen therapy can still offer benefits, the evidence is mixed.
VAE increases right heart strain, so inotropic agents like dobutamine can help boost cardiac output, while norepinephrine supports ventricular function and systemic vascular resistance, but this may also worsen pulmonary resistance.
Aspiration of air via multi-orifice or Swan-Ganz catheters has limited success, with success rates ranging from 6% to 16%. In contrast, the Bunegin-Albin catheter has shown more promise, with a 30-60% success rate. Catheterization for acute VAE-induced hemodynamic compromise is controversial, and there’s insufficient evidence to support its widespread emergency use.
What are the key hemodynamic parameters used to assess RV function?
On echocardiogram, there are a number of parameters that can assess RV function:
- Tricuspid Annular Plane Systolic Excursion (TAPSE): Measures the lateral tricuspid annulus’ movement during systole. A TAPSE value below 1.6 cm is associated with poor prognosis.
- RV Outflow Tract (RVOT) Acceleration Time: Measured via pulsed wave Doppler, an acceleration time of <100 ms is abnormal, with values ≤60 ms indicating a worse prognosis.
- Global RV Longitudinal Strain: Assessed via speckle tracking, with a strain value of −20% being highly predictive of RV dysfunction (normal values typically range -24.5 to -28.5%).
- Tricuspid Regurgitation (TR) Jet Velocity: Helps estimate pulmonary systolic pressure and provides prognostic information.
- Inferior Vena Cava (IVC) Collapsibility: Useful in estimating right atrial pressure and guiding volume resuscitation, though it lacks prognostic significance.
- The RV:LV diameter ratio offers prognostic value, with a ratio greater than 0.9 linked to worse outcomes.
Invasive Hemodynamic Monitoring (Right heart catheterization, PA Catheter)
- The Pulmonary Artery Pulsatility Index (PAPI) is an invasive hemodynamic parameter used to assess right ventricular (RV) function, particularly in cases of RV failure and cardiogenic shock. PAPi is the pulmonary arterial pulse pressure divided by the RA pressure. A PAPi of <0.9 is a poor indicator, especially in the acute myocardial infarction population.
What are the core principles in managing a patient with RV failure?
The management to optimize RV function is centered around optimizing preload, afterload, and contractility.
- Optimizing preload – Optimizing preload is one of the most important aspects in the management of acute decompensated RV failure. The majority of us are taught that the RV is “preload dependent” and patients should be fluid resuscitated. However, many patients are actually volume overloaded and may benefit from diuresis. Overall, this is a patient-to-patient decision, depending on the clinical picture, to optimize preload; though the use of pulmonary artery (PA) catheters in this setting is not well supported.
- Reducing afterload – Avoid intubation if clinically feasible, as they may increase PVR; however, if essential, ideally, oxygen saturation (SaO₂) should be maintained above 92%, and ventilator settings should be adjusted to optimize lung volume and maintain a normal pH and PCO₂. Nitric oxide has also been beneficial in improving oxygenation and reducing PVR with its vasodilatory effects.
- Support cardiac output
  - May support with the use of inotropes as well as mechanical circulatory support.
    - Pressors: The ideal vasopressor increases systemic arterial pressure and RV contractility without raising pulmonary vascular resistance.
      - Norepinephrine: Primarily an α1 agonist, it improves systemic blood pressure with some β1 stimulation. It has shown benefits in maintaining RV-PA coupling.
      - Dobutamine: A β1 agonist that improves myocardial contractility and RV-PA coupling, though it can cause vasodilation at higher doses.
      - In general, dobutamine is considered the best for acute RVF with PH, unless hypotension is a significant concern, in which case norepinephrine might be preferred. Milrinone is another option.
    - MCS: short-term MCS should be considered in patients with cardiogenic shock as a bridge to recovery, a bridge to decision, or a bridge to bridge whilst the underlying causes for cardiogenic shock are addressed further described below
      - Options include:
        
        Venous-arterial extracorporeal membranous oxygenation (V-A ECMO)
        
        RA to PA extracorporeal pump. (surgical RVAD)
        
        Flow device with an intake in the RA and an output in the PA. (Impella RP, Protek Duo)
When should we consider mechanical circulatory support for right ventricular (RV) failure?
Short-term MCS should be considered in patients with cardiogenic shock as a bridge to recovery, a bridge to decision, or a bridge to bridge whilst the underlying causes for cardiogenic shock are addressed.
Clinical parameters that suggest acute MCS use include signs of relative hypoperfusion plus hemodynamic features suggestive of RV failure, which were present in our patient. A specific additional consideration relates to where acute left-sided MCS reveals acute RV failure. Discerning whether this is intrinsic RV failure or due to persistently elevated RV afterload from inadequate LV support is also essential, as it will define management.
The goal of percutaneous mechanical support is to bypass the right ventricle and improve hemodynamics, while allowing time for optimization of the patient and recovery of the RV.

ReferencesArrigo, Mattia, et al. “Diagnosis and Treatment of Right Ventricular Failure Secondary to Acutely Increased Right Ventricular Afterload (Acute Cor Pulmonale). A Clinical Consensus Statement of the Association for Acute CardioVascular Care (ACVC) of the ESC.” European Heart Journal. Acute Cardiovascular Care, vol. 13, no. 3, 22 Dec. 2023, pp. 304–312, https://doi.org/10.1093/ehjacc/zuad157. Accessed 17 May 2024.

Chen, Guohai, et al. “INCIDENCE of ENDOPHTHALMITIS after VITRECTOMY: A Systematic Review and Meta-Analysis.” Retina (Philadelphia, Pa.), vol. 39, no. 5, May 2019, pp. 844–852, pubmed.ncbi.nlm.nih.gov/29370034/, https://doi.org/10.1097/IAE.0000000000002055.

Fakkert, Raoul A, et al. “Early Hyperbaric Oxygen Therapy Is Associated with Favorable Outcome in Patients with Iatrogenic Cerebral Arterial Gas Embolism: Systematic Review and Individual Patient Data Meta-Analysis of Observational Studies.” Critical Care, vol. 27, no. 1, 12 July 2023, https://doi.org/10.1186/s13054-023-04563-x. Accessed 7 June 2024.

Flaxel, Christina J., et al. “Idiopathic Epiretinal Membrane and Vitreomacular Traction Preferred Practice Pattern®.” Ophthalmology, vol. 127, no. 2, Feb. 2020, pp. P145–P183, https://doi.org/10.1016/j.ophtha.2019.09.022. Accessed 16 July 2020.

Frémont, Benoît, et al. “Prognostic Value of Echocardiographic Right/Left Ventricular End-Diastolic Diameter Ratio in Patients with Acute Pulmonary Embolism.” Chest, vol. 133, no. 2, Feb. 2008, pp. 358–362, https://doi.org/10.1378/chest.07-1231.

Huang, Ryan S, et al. “Pars Plana Vitrectomy with Silicone Oil or Gas Tamponade for Uncomplicated Retinal Detachment: A Systematic Review and Meta-Analysis.” American Journal of Ophthalmology, vol. 266, Oct. 2024, pp. 144–155, pubmed.ncbi.nlm.nih.gov/38815844/, https://doi.org/10.1016/j.ajo.2024.05.008.

Kanwar, Manreet K, et al. “Epidemiology and Management of Right Ventricular-Predominant Heart Failure and Shock in the Cardiac Intensive Care Unit.” European Heart Journal. Acute Cardiovascular Care, vol. 11, no. 7, 29 June 2022, pp. 584–594, https://doi.org/10.1093/ehjacc/zuac063. Accessed 5 Mar. 2023.

Lahm, Tim, et al. “Medical and Surgical Treatment of Acute Right Ventricular Failure.” Journal of the American College of Cardiology, vol. 56, no. 18, Oct. 2010, pp. 1435–1446, www.onlinejacc.org/content/56/18/1435, https://doi.org/10.1016/j.jacc.2010.05.046. Accessed 30 Nov. 2019.

Mirski, Marek A., et al. “Diagnosis and Treatment of Vascular Air Embolism.” Anesthesiology, vol. 106, no. 1, 1 Jan. 2007, pp. 164–177, pubs.asahq.org/anesthesiology/article/106/1/164/8884/Diagnosis-and-Treatment-of-Vascular-Air-Embolism, https://doi.org/10.1097/00000542-200701000-00026. Accessed 13 Apr. 2021.

Moon, Young Eun. “Venous Air Embolism during Vitrectomy: A Rare but Potentially Fatal Complication.” Korean Journal of Anesthesiology, vol. 67, no. 5, 1 Jan. 2014, pp. 297–297, pmc.ncbi.nlm.nih.gov/articles/PMC4252339/, https://doi.org/10.4097/kjae.2014.67.5.297. Accessed 10 Mar. 2025.

“Right Ventricular Failure.” Escardio.org, 2016, www.escardio.org/Journals/E-Journal-of-Cardiology-Practice/Volume-14/Right-ventricular-failure.

Stickel, Simone, et al. “The Practical Management of Fluid Retention in Adults with Right Heart Failure due to Pulmonary Arterial Hypertension.” European Heart Journal Supplements, vol. 21, 1 Dec. 2019, pp. 46–53, academic.oup.com/eurheartjsupp/article/21/Supplement_K/K46/5678698, https://doi.org/10.1093/eurheartj/suz207.

Ventetuolo, Corey E., and James R. Klinger. “Management of Acute Right Ventricular Failure in the Intensive Care Unit.” Annals of the American Thoracic Society, vol. 11, no. 5, 1 June 2014, pp. 811–822, www.ncbi.nlm.nih.gov/pmc/articles/PMC4225807/#:~:text=Abstract, https://doi.org/10.1513/AnnalsATS.201312-446FR. Accessed 10 Aug. 2020.

What Is Vitrectomy. “What Is Vitrectomy?” American Academy of Ophthalmology, 15 May 2019, www.aao.org/eye-health/treatments/what-is-vitrectomy.

Zhao, Steven, and Oren Friedman. “Management of Right Ventricular Failure in Pulmonary Embolism.” Critical Care Clinics, vol. 36, no. 3, July 2020, pp. 505–515, https://doi.org/10.1016/j.ccc.2020.02.006. Accessed 29 Nov. 2020.

CCC: Approach to RV Predominant Cardiogenic Shock with Dr. Ryan Tedford

View Details

CardioNerds (Drs. Daniel Ambinder and Eunice Dugan) are joined by Namrita Ashokprabhu, incoming medical student, along with Drs. Yulith Roca Alvarez and Mehmet Yildiz from The Christ Hospital. Expert insights provided by Dr. Odayme Quesada. Audio editing by CardioNerds intern Christiana Dangas. This episode explores how cardiac MRI and coronary function testing revealed coronary vasospasm in a case of MINOCA.

Cardiac MRI is crucial in evaluating myocardial infarction with nonobstructive coronary arteries (MINOCA) and diagnosing myocarditis, but findings must be interpreted within clinical context. A 58-year-old man with hypertension, hyperlipidemia, diabetes, a family history of cardiovascular disease, and smoking history presented with sudden chest pain, non-ST-elevation on EKG, and elevated troponin I (0.64 µg/L). Cardiac angiography revealed nonobstructive coronary disease, including a 40% stenosis in the LAD, consistent with MINOCA. Eight weeks later, another event (troponin I 1.18 µg/L) led to cardiac MRI findings suggesting myocarditis. Further history revealed episodic chest pain and coronary vasospasm, confirmed by coronary functional angiography showing severe vasoconstriction, resolved with nitroglycerin. Management included calcium channel blockers and long-acting nitrates, reducing symptoms. Coronary vasospasm is a frequent MINOCA cause and can mimic myocarditis on CMRI. Invasive coronary functional testing, including acetylcholine provocation testing, is indicated in suspicious cases.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.

CardioNerds Case Reports Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll

CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!

Notes – Coronary Vasospasm1. What are the potential underlying causes of MINOCA (Myocardial Infarction with Non-Obstructive Coronary Arteries)? * Plaque Rupture: Plaque disruption, which includes plaque rupture, erosion, and calcified nodules, occurs as lipids accumulate in coronary arteries, leading to inflammation, necrosis, fibrosis, and calcification. Plaque rupture exposes the plaque to the lumen, causing thrombosis and thromboembolism, while plaque erosion results from thrombus formation without rupture and is more common in women and smokers. Intravascular imaging, such as IVUS and OCT, can detect plaque rupture and erosion, with studies showing plaque disruption as a frequent cause of MINOCA, particularly in women, though the true prevalence may be underestimated due to limited imaging coverage. * Coronary Vasospasm: Coronary vasospasm is characterized by nitrate-responsive chest pain, transient ischemic EKG changes, and >90% vasoconstriction during provocative testing with acetylcholine or ergonovine, due to hyper-reactivity in vascular smooth muscle. It is a common cause of MINOCA, with approximately half of MINOCA patients testing positive in provocative tests, and Asians are at a significantly higher risk than Whites. Smoking is a known risk factor for vasospasm. In contrast, traditional risk factors like sex, hypertension, and diabetes do not increase the risk, and vasospasm is associated with a 2.5–13% long-term risk of major adverse cardiovascular events (MACE). * Spontaneous Coronary Artery Dissection: Spontaneous coronary artery dissection (SCAD) involves the formation of a false lumen in epicardial coronary arteries without atherosclerosis, caused by either an inside-out tear or outside-in intramural hemorrhage. SCAD is classified into four types based on angiographic features, with coronary angiography being the primary diagnostic tool. However, in uncertain cases, advanced imaging like IVUS or OCT may be used cautiously. While the true prevalence is unclear due to missed diagnoses, SCAD is more common in women and is considered a cause of MINOCA when it results in non-obstructive lesions, with various predisposing factors including genetics, fibromuscular dysplasia, and emotional stress. * Coronary Embolism/Thrombosis: Coronary embolism, often underdiagnosed, can be classified based on thrombus origin as direct, paradoxical, or iatrogenic, with atrial fibrillation being the most common cause. A Japanese study found that only 2.9% of AMI patients were related to coronary embolism, and 73% of these cases were due to atrial fibrillation, with recurrent thromboembolic events occurring in 10% of patients during follow-up. Risk factors for coronary thromboembolism include hereditary thrombophilia, with 14% of MINOCA patients having hereditary thrombophilia, and an extensive evaluation, including a hypercoagulable workup and screening for atrial fibrillation or patent foramen ovale, is crucial to determine the underlying cause. * Coronary Microvascular Dysfunction: The role of microvascular dysfunction in MINOCA remains uncertain due to limited data, though it is characterized by impaired vasodilation, increased vasoconstriction, and abnormal microcirculation remodeling, which affects coronary flow reserve without epicardial disease. Microvascular dysfunction is often underdiagnosed because it requires invasive functional testing, and studies in patients with ischemia but no obstructive coronary disease (INOCA) show a prevalence of up to 41%. A small study of MINOCA patients found that 25% had low myocardial perfusion reserve, suggesting potential involvement, but further research is needed to establish its role as a cause of MINOCA. * MINOCA mimickers: * Myocarditis: Myocarditis, often caused by viral infections, can also result from bacterial infections, toxic substances, or autoimmune disorders, and is more common in younger patients, though it can affect all ages. Fulminant myocarditis, though rare, can lead to life-threatening cardiogenic shock, and is diagnosed through CMR showing diffuse myocardial edema on T2 and myocardial biopsy. A meta-analysis found that one-third of MINOCA patients had myocarditis, particularly younger patients and those with elevated C-reactive protein levels. * Non-ischemic Cardiomyopathy: Non-ischemic cardiomyopathy encompasses conditions like dilated, hypertrophic, restrictive, and arrhythmogenic cardiomyopathy, with dilated cardiomyopathy being the most common. A longitudinal study found that 25% of MINOCA patients had non-ischemic cardiomyopathy, which was associated with the highest mortality compared to other MINOCA mechanisms. Stress CMR has also identified underlying microvascular dysfunction in patients with dilated cardiomyopathy. * Takotsubo Cardiomyopathy: Takotsubo cardiomyopathy, or stress-induced cardiomyopathy, is characterized by reversible wall motion abnormalities without obstructive CAD. It is often triggered by emotional or physical stress and is associated with a catecholamine surge. The condition is more common in postmenopausal women and has four main anatomical variants, with apical ballooning being the most common. Diagnosis typically involves coronary angiography, ventriculography, and CMRI to rule out other causes of AMI, with risks of cardiogenic shock and death comparable to those of AMI patients with CAD. 2. What are the key diagnostic tests to evaluate MINOCA, and how are they applied in this case? * Coronary Intravascular Imaging: Coronary intravascular imaging with IVUS and OCT is essential for diagnosing plaque disruption in MINOCA and should be performed during coronary angiography of all three major epicardial arteries. IVUS identifies plaque disruption in up to 40% of MINOCA cases, while OCT detects the culprit lesion in about 50%. These imaging techniques are also valuable for evaluating SCAD in cases of diagnostic uncertainty. * Cardiac Imaging: Transthoracic echocardiography is valuable for assessing cardiac function after MINOCA, diagnosing Takotsubo and non-ischemic cardiomyopathy, and monitoring recovery of left ventricular function. Transesophageal echocardiography may be considered when coronary embolism is suspected. CMR is recommended for uncertain MINOCA diagnoses, providing accurate results in 74–87% of cases. It can differentiate between ischemic and non-ischemic MI, diagnose myocarditis, and detect coronary microvascular dysfunction through perfusion imaging. CMR’s diagnostic accuracy improves when performed closer to the event and also serves as a prognostic tool for long-term cardiovascular outcomes. * Invasive Coronary Functional Testing: Provocative spasm testing with intracoronary acetylcholine helps diagnose coronary vasospasm (epicardial or microvascular) and endothelial-dependent microvascular dysfunction, with a low complication rate (0.5%). In MINOCA patients, spasm testing is positive in about half, with epicardial spasm in 65% and microvascular spasm in 35%. CFR assessed by doppler flow velocity or thermodilution (with values <2.0) and IMR (>25) are used to assess microvascular dysfunction, though CFR is more sensitive. While coronary microvascular dysfunction is linked to worse outcomes in INOCA, its prognostic impact in MINOCA is less clear. However, low CFR has been associated with increased mortality across various patient populations. 3. How is MINOCA treated based on its underlying etiology? * Plaque Rupture: Patients with plaque disruption should be treated with aspirin and high-intensity statin therapy. Additionally, for those with plaque disruption who do not require stenting, dual antiplatelet therapy with ticagrelor for up to 1 month may be considered, given the low revascularization rates at 1 year (5.7%) and 4 years (21.1%) follow-up. * Coronary Vasospasm: Long-acting calcium channel blockers (both dihydropyridine and non-dihydropyridine) are commonly used in MINOCA patients with epicardial coronary vasospasm. They relax vascular smooth muscle by inhibiting calcium ion influx. For patients with refractory angina, nitrates may be added to calcium channel blockers to enhance smooth muscle relaxation through increased nitric oxide availability. * SCAD: Conservative management is preferred over PCI in SCAD patients, as most dissections heal without intervention and PCI carries higher complication risks. PCI is reserved for STEMI, cardiogenic shock, or persistent ischemia. The use of antithrombotic agents during acute SCAD is debated, and secondary prevention (aspirin, beta-blockers, statins, and ACE inhibitors) should be tailored to individual risk factors. * CMD: Treatment options for coronary microvascular dysfunction are limited and mainly based on data from INOCA patients. Statins and renin-angiotensin system inhibitors have been shown to improve coronary flow reserve (CFR). Antianginal therapies such as beta-blockers, calcium channel blockers, and ranolazine are commonly used for patients with chest pain. * MINOCA Mimickers: * Takotsubo Cardiomyopathy: Management of MINOCA mimickers mainly involves supportive care and guideline-directed medical therapy for heart failure, though evidence is limited. Most patients with Takotsubo cardiomyopathy recover normal cardiac function spontaneously, while those with left ventricular dysfunction are treated with beta-blockers and renin-angiotensin system inhibitors. In cases of progressive circulatory failure, mechanical circulatory support may be needed. * Myocarditis: Myocarditis typically resolves within 2–4 weeks, but patients with arrhythmias or persistent cardiac dysfunction should receive guideline-directed therapy. Physical activity should be avoided in the acute phase for up to 6 months. Ongoing trials on antiviral and immunosuppressive treatments may offer targeted therapies in the future.

References – Coronary Vasospasm1. Tamis-Holland JE, Jneid H, Reynolds HR, et al. Contemporary diagnosis and management of patients with myocardial infarction in the absence of obstructive coronary artery disease: a scientific statement from the American Heart Association. Circulation. 2019;139:e891–908. doi:10.1161/CIR.0000000000000670 2. Reynolds HR, Maehara A, Kwong RY, et al. Coronary optical coherence tomography and cardiac magnetic resonance imaging to determine underlying causes of myocardial infarction with nonobstructive coronary arteries in women. Circulation. 2021;143:624–40. doi:10.1161/CIRCULATIONAHA.120.052008 3. di Fusco SA, Rossini R, Zilio F, et al. Spontaneous coronary artery dissection: overview of pathophysiology. Trends Cardiovasc Med. 2022;32:92–100. doi:10.1016/j.tcm.2021.01.002 4. Zilio F, Muraglia S, Morat F, et al. Sex differences in clinical and angiographic characteristics in spontaneous coronary artery dissection. Future Cardiol. 2021;17:669–75. doi:10.2217/fca-2020-0124 5. Omerovic E, Citro R, Bossone E, et al. Pathophysiology of takotsubo syndrome – a joint scientific statement from the heart failure association takotsubo syndrome study group and myocardial function working group of the European society of cardiology – part 2: vascular pathophysiology, gender and sex hormones, genetics, chronic cardiovascular problems and clinical implications. Eur J Heart Fail. 2022;24:274–86. doi:10.1002/ejhf.2368 6. Agdamag AC, Patel H, Chandra S, et al. Sex differences in takotsubo syndrome: a narrative review. J Womens Health. 2020;29:1122–30. doi:10.1089/jwh.2019.7741 7. Bentzon JF, Otsuka F, Virmani R, Falk E. Mechanisms of plaque formation and rupture. Circ Res. 2014;114:1852–66. doi:10.1161/CIRCRESAHA.114.302721 8. Virmani R, Burke AP, Farb A, Kolodgie FD. Pathology of the vulnerable plaque. J Am Coll Cardiol. 2006;47:C13–8. doi:10.1016/j.jacc.2005.10.065 9. Montone RA, Niccoli G, Fracassi F, et al. Patients with acute myocardial infarction and non-obstructive coronary arteries: safety and prognostic relevance of invasive coronary provocative tests. Eur Heart J. 2017;39:91–8. doi:10.1093/eurheartj/ehx667 10. Raphael CE, Heit JA, Reeder GS, et al. Coronary embolus: an underappreciated cause of acute coronary syndromes. JACC Cardiovasc Interv. 2018;11:172–80. doi:10.1016/j.jcin.2017.08.057 11. Tschöpe C, Ammirati E, Bozkurt B, et al. Myocarditis and inflammatory cardiomyopathy: current evidence and future directions. Nat Rev Cardiol. 2021;18:169–93. doi:10.1038/s41569-020-00435-x 12. Tornvall P, Gerbaud E, Behaghel A, et al. Myocarditis or “true” infarction by cardiac magnetic resonance in patients with a clinical diagnosis of myocardial infarction without obstructive coronary disease: a meta-analysis of individual patient data. Atherosclerosis. 2015;241:87–91. doi:10.1016/j.atherosclerosis.2015.04.816 13. Lintingre P-F, Nivet H, Clément-Guinaudeau S, et al. High-resolution late gadolinium enhancement magnetic resonance for the diagnosis of myocardial infarction with nonobstructed coronary arteries. JACC Cardiovasc Imaging. 2020;13:1135–48. doi:10.1016/j.jcmg.2019.11.020 14. AlBadri A, Bairey Merz CN, Johnson BD, et al. Impact of abnormal coronary reactivity on long-term clinical outcomes in women. J Am Coll Cardiol. 2019;73:684–93. doi:10.1016/j.jacc.2018.11.040 15. Kelshiker MA, Seligman H, Howard JP, et al. Coronary flow reserve and cardiovascular outcomes: a systematic review and meta-analysis. Eur Heart J. 2022;43:1582–93. doi:10.1093/EURHEARTJ/EHAB775 16. Slavich M, Patel RS. Coronary artery spasm: current knowledge and residual uncertainties. IJC Heart Vasculat. 2016;10:47–53. doi:10.1016/j.ijcha.2016.01.003 17. Samuels B, Shah S, Widmer R, et al. Comprehensive management of ANOCA, Part 1—definition, patient population, and diagnosis: JACC state-of-the-art review. JACC. 2023;82(12):1245–63. doi:10.1016/j.jacc.2023.06.043 18. Smilowitz N, Prasad M, Widmer R, et al. Comprehensive management of ANOCA, Part 2—program development, treatment, and research initiatives: JACC state-of-the-art review. JACC. 2023;82(12):1264–79. doi:10.1016/j.jacc.2023.06.044 19. Quesada O, Ashokprabhu ND, Tapp DN, et al. Utilizing invasive coronary functional testing in a coronary microvascular and vasomotor dysfunction program: methods and considerations. Catheter Cardiovasc Interv. 2024;104(7):1327–36. doi:10.1002/ccd.31282 20. Yildiz M, Ashokprabhu N, Shewale A, et al. Myocardial infarction with non-obstructive coronary arteries (MINOCA). Front Cardiovasc Med. 2022;9:1032436. doi:10.3389/fcvm.2022.1032436

View Details

CardioNerds co-founders Dr. Daniel Ambinder and Dr. Amit Goyal are joined by Dr. Spencer Weintraub, Chief Resident of Internal Medicine at Northwell Health, Dr. Michael Albosta, third-year Internal Medicine resident at the University of Miami, and Anna Biggins, Registered Dietitian Nutritionist at the Georgia Heart Institute. Expert commentary is provided by Dr. Zahid Ahmad, Associate Professor in the Division of Endocrinology at the University of Texas Southwestern. Together, they discuss a fascinating case involving a patient with a new diagnosis of hypertriglyceridemia. Episode audio was edited by CardioNerds Intern Student Dr. Pacey Wetstein.

A woman in her 30s with type 2 diabetes, HIV, and polycystic ovarian syndrome presented with one day of sharp epigastric pain, non-bloody vomiting, and a new lower extremity rash. She was diagnosed with hypertriglyceridemia-induced pancreatitis, necessitating insulin infusion and plasmapheresis.

The CardioNerds discuss the pathophysiology of hypertriglyceridemia-induced pancreatitis, potential organic and iatrogenic causes, and the cardiovascular implications of triglyceride disorders. We explore differential diagnoses for cardiac and non-cardiac causes of epigastric pain, review acute and long-term management of hypertriglyceridemia, and discuss strategies for the management of the chylomicronemia syndrome, focusing on lifestyle changes and pharmacotherapy.

This episode is part of a case reports series developed in collaboration with the National Lipid Association and their Lipid Scholarship Program, with mentorship from Dr. Daniel Soffer and Dr. Eugenia Gianos.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.

CardioNerds Case Reports Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll

CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!

Pearls – Hypertriglyceridemia1. Cardiac sarcoidosis can present with a variety of symptoms, including arrhythmias, heart block, heart failure, or sudden cardiac death. The acute management of hypertriglyceridemia-induced pancreatitis involves prompt recognition and initiation of therapy to lower triglyceride levels using either plasmapheresis or intravenous insulin infusion +/- heparin infusion. Insulin infusion is used more commonly, while plasmapheresis is preferred in pregnancy. 2. Medications such as fibrates and omega-3 fatty acids can be used to maintain long-term triglyceride reduction to prevent the recurrence of pancreatitis, especially in patients with persistent triglyceride elevation despite lifestyle modifications. Statins can be used in patients for ASCVD reduction in patients with a 10-year ASCVD risk > 5%, age > 40 years old, and diabetes or diabetes with end-organ damage or known atherosclerosis. Consider preferential use of icosapent ethyl as an omega-3 fatty acid for triglyceride lowering if the patients fit the populations that appeared to benefit in the REDUCE IT trial. 3. Apply targeted dietary interventions within the context of an overall healthy dietary pattern, such as a Mediterranean or DASH diet. Limit full-fat dairy, fatty meats, refined starches, added sugars, and alcohol. Encourage high-fiber vegetables, whole fruits, low-fat or fat-free dairy, plant proteins, lean poultry, and fish. Pay special attention to the cooking oils to ensure the patient is not using palm oil, coconut oil, or butter when cooking. Instead, use liquid non-tropical plant oils. Initiate a very low-fat diet (< 5% of total daily calories from fat) for 1-4 weeks when TG levels are > 750 mg/dL. 4. Recommend and encourage patients to exercise regularly, with a minimum goal of 150 minutes/week of moderate-intensity aerobic activity. If weight loss is required, aim for more than >225 – 250 minutes/week. 5. Develop patient-centered and multidisciplinary strategies for preventing hypertriglyceridemia-induced pancreatitis by incorporating patient education on the importance of medication adherence, specialist follow-up, regular monitoring of triglyceride levels, and lifestyle modifications to maintain optimal lipid profiles and reduce the future risk of pancreatitis.

Notes – Hypertriglyceridemia1. Who is at risk for hypertriglyceridemia and what are the key pathophysiological mechanisms by which elevated triglycerides may lead to pancreatitis? * The exact mechanism is not clear. The proposed mechanism is that when serum triglycerides exceed 1000 mg/dL, blood flow is impaired through the capillary beds supplying the pancreas, resulting in ischemia. The ischemic injury resulting from this disruption of microcirculation disrupts the acinar structure of pancreatic cells and exposes pancreatic enzymes to triglyceride-rich particles. This results in activation of enzymatic activity with degradation of the chylomicron-triglycerides particles, which causes inflammation, subsequently leading to hemorrhage, edema, and necrosis of the pancreatic tissue. * Chylomicronemia syndrome can be multifactorial or familial. Familial chylomicronemia syndrome (FCS) is often discovered very early in life, and patients have a loss of function in one of the several genes involved in regulating triglyceride metabolism. These genes include LPL, APOC2, APOA5, LMF1, and GPIHBP1. * Multifactorial chylomicronemia syndrome is the most common cause of chylomicronemia syndrome. It is usually the result of a clustering of genetic variants, including heterozygosity of one of the five genes previously mentioned, as well as more frequent variants with small effects in more than 40 additional genes that have been implicated. Having a genetic variant plus an aggravating factor will often exacerbate the metabolic defect and lead to chylomicronemia syndrome. There are many potential aggravating factors, but some of the more common ones include a diet high in refined sugars, heavy alcohol consumption, obesity with or without metabolic syndrome, medications, renal disease, HIV, and pregnancy. 2. What are the acute treatment strategies for hypertriglyceridemia-induced pancreatitis, and how are they similar and different to treating pancreatitis from other etiologies? * All patients should be assessed for hemodynamic compromise, the severity of illness with or without scoring systems, and end-organ damage to determine the need for intensive care resources. Initially, patients usually require aggressive fluid resuscitation and pain management, which are standard across all types of acute pancreatitis. Delayed fluid resuscitation has been associated with worse outcomes. Multiple trials have been performed evaluating the best amount of fluid. Although there is not an exact answer to this, as all patients are different, all patients should be resuscitated until euvolemic. The WATERFALL trial showed that administration of 10 mL/kg bolus followed by 1.5 mL/kg maintenance until the patient reaches euvolemia was a superior approach to more aggressive fluid resuscitation. A patient’s volume status should be reassessed every 6 hours for 24 – 48 hours, and fluids should be discontinued once euvolemia has been achieved. There is no guideline consensus on the preferred analgesic management, but it is generally recommended to administer medication to mitigate symptoms of pain and nausea for all patients. * For hypertriglyceridemia-induced pancreatitis, it is key to initiate fasting to decrease chylomicron production and further increasing triglyceride levels. Although historically, this was the same approach for other causes of pancreatitis, more recent data shows that early enteral feeding reduces the risk of complications such as pancreatic necrosis. However, these studies were not performed in patients with pancreatitis from hypertriglyceridemia and should not be extrapolated to this distinct population. Currently, it is recommended that patients be kept NPO until triglycerides are below 500 mg/dL, which is the point at which LPL activity becomes saturated. When feeding is initiated, it should be with a very low-fat diet with no refined carbohydrates. * Hypertriglyceridemia differs from other causes of pancreatitis as the management is centered around the rapid reduction of triglyceride content in the blood. Generally, these patients are admitted to the intensive care unit to undergo either insulin infusion +/- heparin drip or plasmapheresis. Although there has never been a clinical trial comparing these two approaches, a recent comprehensive meta-analysis showed no significant difference in mortality or clinical outcomes. Insulin infusion had a lower number of deaths, but a higher rate of acute renal failure, hypoglycemia, and hypotension, neither of which reached statistical significance. Insulin is more commonly used and generally preferred given that it is more cost-effective, less invasive, and can have utility in treating underlying diabetes exacerbation, which is common amongst these patients. Insulin infusion works by increasing the activity of lipoprotein lipase (LPL), resulting in increased clearance of chylomicron particles. Although in some countries, insulin is combined with heparin, given heparin’s ability to increase LPL release, this is rarely done as heparin can deplete endothelial LPL, increase bleeding events, and potentially cause heparin-induced thrombocytopenia. Plasmapheresis, on the other hand, works by removing the triglycerides directly from the bloodstream, which can rapidly reduce levels. It does require central venous access, which is more invasive. Plasmapheresis is preferred in pregnancy as data in case series supports it reduces the risk of a systemic inflammatory response. 3. What are the proposed mechanisms by which high triglycerides may contribute to atherosclerosis? * There are several proposed mechanisms for the association between elevated triglyceride levels and ASCVD. First, elevated triglyceride levels correspond with high circulating triglyceride-rich lipoprotein particles, also known as remnant cholesterol. This includes VLDL, IDL, and chylomicron remnants. These particles are thought to be at least as, if not more, atherogenic than LDL-C. Remnant particles readily penetrate the arterial wall, similar to LDL, but do not require oxidative modification for macrophage uptake and can be taken up unregulated, leading to foam cells and atherosclerosis. * Second, having elevated levels of triglyceride-rich lipoproteins is pro-inflammatory. When triglyceride-rich lipoproteins are hydrolyzed by lipoprotein and endothelial lipases, the release of oxidized free fatty acids along the endothelial wall leads to the activation of pro-inflammatory signaling pathways that can increase vascular permeability and promote the migration of leukocytes and atherogenic lipoprotein particles into the arterial wall. This is mediated by cytokines and chemoattractant proteins. 4. What long-term pharmacologic management strategies should be considered in patients with hypertriglyceridemia-induced pancreatitis? * Fibrates are the first line pharmacotherapy when the goal of treatment is to prevent acute pancreatitis, especially when triglyceride levels are >1000. The ability of lipoprotein lipase to clear triglyceride-rich lipoproteins becomes saturated at TG levels of approximately 500-700 mg/dL. When the ability to clear TRL is impaired, dietary fat intake can lead to large increases in blood TG levels. Those with TG >1000 are at particularly high risk of acute pancreatitis. Fibrates stimulate PPAR alpha and primarily decrease TGs via the upregulation of LPL. The reduction of TGs from fibrates ranges from 25-50%. Some data suggests fenofibrate may be more effective at lowering TG then gemfibrozil. Gemfibrozil is the only Fibrate therapy that has shown a reduction in cardiovascular events in the VA-HIT and HHS trials. However, it is worth noting these trials were not performed on background statin therapy, which is now contraindicated in patients taking Gemfibrozil due to the increased risk of rhabdomyolysis. * Prescription Omega-3 fatty acids lower TGs, possibly via decreased activity of SREBP1c. These are less potent reducers of triglycerides with reductions between 10-50%. While Icosapent Ethyl, a purified form of EPA, does have TG-lowering effects, it is primarily used for ASCVD risk reduction in individuals >age 50 with TG >150 and a history of ASCVD or those without ASCVD but with diabetes mellitus and multiple risk factors. This is based on the aforementioned REDUCE-IT trial. Briefly, REDUCE-IT randomized patients having moderate hypertriglyceridemia and a history of ASCVD or diabetes and other risk factors on background statin therapy to receive icosapent ethyl (pure EPA) or placebo. Patients in the icosapent ethyl group experienced an 18.3% reduction in triglyceride level compared to a 2.2% increase in the placebo group, as well as a 4.8% absolute risk reduction and 25% relative risk reduction in the primary endpoint, a composite of CV death, non-fatal MI, non-fatal stroke, coronary revascularization, or unstable angina with an NNT of 21. The therapy was associated with a slight, although significant, increase in risk of atrial fibrillation, which occurred in 5.3% of patients receiving IPE compared to 3.9% in the placebo group. There was also an increased risk of bleeding, which approached statistical significance. The use of biologically active mineral oil as the placebo has led to some controversy regarding the validity of REDUCE-IT results. In this case, our patient does not exactly fit this study population investigated in that clinical trial. Other Omega-3 fatty acids include mixtures of EPA/DHA such as Omega-3-acid ethyl esters and Omega-3-carboxylic acids, which are often used to reduce the risk of pancreatitis in those with triglyceride levels >500 mg/dL. Combined EPA/DHA products have been investigated in several trials, including but not limited to STRENGTH, VITAL, ASCEND, and OMEMI. However, none of these trials have shown any significant reduction in cardiovascular endpoints. * Statins are primarily used for reducing ASCVD risk, although they do lower triglycerides primarily through increased clearance of VLDL via upregulation of the remnant receptor. The 2021 ACC Expert Consensus Decision Pathway for hypertriglyceridemia recommends initiating or intensifying statin therapy for patients aged 40-75 years, with triglycerides of 500-999 mg/dL and with either a 10-year ASCVD risk of ≥5% or diabetes mellitus. The 2018 ACC/AHA multisociety Guideline on the Management of Blood Cholesterol provides key groups that qualify for primary prevention of statin therapy, including those with ASCVD risk >7.5%, age between 40-75 with diabetes mellitus type 1 or 2, and low-density lipoprotein cholesterol (LDL-c) >190 mg/dL. These guidelines further elaborate that in adults 20 to 39 years of age with diabetes mellitus type 2, statin therapy can be considered if they have type 2 diabetes mellitus ≥10 years, albuminuria (≥30 mcg of albumin/mg creatinine), eGFR < 60 mL/min/1.73 m2, retinopathy, neuropathy, or ABI <0.9. 5. What dietary management approaches are effective in preventing recurrent episodes of hypertriglyceridemia-induced pancreatitis, and how do they impact triglyceride levels? * There are many ways to approach dietary interventions in the clinic. The National Lipid Association created a 2023 guideline called “Nutrition interventions for adults with dyslipidemia: A Clinical Perspective from the National Lipid Association,” which can be helpful in guiding clinical care. Always use a patient-centered approach and incorporate patients’ preferences, cultural backgrounds, financial resources, and food availability when applying the dietary guidelines. * Start by identifying the food sources in a patient’s diet that can dramatically raise triglycerides: foods rich in added sugars, refined starches, saturated fats, and alcohol. Identifying and minimizing or eliminating these foods upfront (depending on the severity of the hypertriglyceridemia) will lead to substantial improvements in a patient’s lipid profile. * The NLA guidelines created four categories based on the severity of hypertriglyceridemia and whether patients have FCS. These categories include patients with triglycerides >= 750 mg/dL with FCS, >= 750mg/dL with suspected MCS, >= 500 mg/dL and < 500 mg/dL. * All patients with elevated triglycerides should be advised to strive for an overall healthy dietary pattern such as a Mediterranean or DASH Diet, maximize plant sources of protein, limit or eliminate beverages and foods with added sugars, limit full-fat dairy products, maximize intake of fibrous vegetables, and are encouraged to perform at least 150 minutes/week of moderate-intensity exercise or 75 minutes/week of vigorous exercise but increasing the exercise past this threshold will continue to have added benefits as recommended by the American College of Sports Medicine. * The NLA recommends completely abstaining from alcohol for patients with triglycerides >500 mg/dL. For those below 500 mg/dL the recommendation is that men do not exceed two drinks/day and women do not exceed one drink/day. However, in general, it’s best to advise all patients to limit their alcohol as much as possible because it increases the secretion of VLDL, impairs lipolysis, and increases free fatty acid fluxes from adipose tissue to the liver. * Dietary saturated fats can also raise both triglycerides and LDL-C and should be replaced with unsaturated fatty acids. Foods rich in saturated fats include those such as butter, beef, and tropical oils such as coconut oil, palm, and palm kernel oil. A thorough review of how patients prepare their food should be performed because making simple changes, such as cooking with olive oil rather than butter or tropical oils, can improve triglycerides and LDL-C. * For those with TG levels > 750mg/dL: the goal should be initially to maintain a very low-fat diet with <5%, but after 4 weeks and improvement of triglyceride elevations, there can be liberalization of the patient’s diet. Depending on the patient’s risk profile, including whether they have FCS and current triglyceride levels, cautious relaxation of dietary restrictions can be allowed to improve quality of life and allow for more flexibility in food intake. Patients with FCS must maintain a very low-fat diet for life and should be referred to a registered dietitian specializing in lipid management.

References – Hypertriglyceridemia1. Varbo A, Benn M, Tybjærg-Hansen A, Jørgensen AB, Frikke-Schmidt R, Nordestgaard BG. Remnant cholesterol as a causal risk factor for ischemic heart disease. J Am Coll Cardiol. 2013 Jan 29;61(4):427-436. doi:10.1016/j.jacc.2012.08.1026. https://www.sciencedirect.com/science/article/pii/S0735109712055222?via%3Dihub 2. Nordestgaard BG. Triglyceride-Rich Lipoproteins and Atherosclerotic Cardiovascular Disease: New Insights From Epidemiology, Genetics, and Biology. Circ Res. 2016 Feb 19;118(4):547-563. doi:10.1161/circresaha.115.306249. https://www.ahajournals.org/doi/full/10.1161/CIRCRESAHA.115.306249 3. Toth PP. Triglyceride-rich lipoproteins as a causal factor for cardiovascular disease. Vasc Health Risk Manag. 2016;12:171-183. doi:10.2147/vhrm.S104369. https://www.dovepress.com/triglyceride-rich-lipoproteins-as-a-causal-factor-for-cardiovascular-d-peer-reviewed-fulltext-article-VHRM 4. Goldberg RB, Chait A. A Comprehensive Update on the Chylomicronemia Syndrome. Front Endocrinol (Lausanne). 2020;11:593931. doi:10.3389/fendo.2020.593931. https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2020.593931/full 5. Kaur G, Gulati M. Considerations for treatment of lipid disorders during pregnancy and breastfeeding. Prog Cardiovasc Dis. 2022 Nov-Dec;75:33-39. doi:10.1016/j.pcad.2022.11.001. https://www.sciencedirect.com/science/article/abs/pii/S003306202200113X?via%3Dihub 6. Donnelly JE, Blair SN, Jakicic JM, Manore MM, Rankin JW, Smith BK. American College of Sports Medicine Position Stand. Appropriate physical activity intervention strategies for weight loss and prevention of weight regain for adults. Med Sci Sports Exerc. 2009 Feb;41(2):459-471. doi:10.1249/MSS.0b013e3181949333. https://journals.lww.com/acsm-msse/fulltext/2001/12000/appropriate_intervention_strategies_for_weight.26.aspx 7. Piplani S, Jain A, Singh K, Gulati S, Chaturvedi S, Bejugam VR, Brown D, Asuzu C, Kolli ST, Shah U, Reet J, Mihajlovic M, Jelic V, Jelic G, Roberts RS, Damania D, Radulovic M. Efficacy and adverse effects of insulin versus plasmapheresis in patients with hypertriglyceridemia-3-induced acute pancreatitis: a systematic review and meta-analysis. Ann Gastroenterol. 2024 Jan-Feb;37(1):109-116. doi: 10.20524/aog.2023.0849. Epub 2023 Dec 20. PMID: 38223249; PMCID: PMC10785016. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10785016/#:~:text=From%20this%20study’s%20analysis%2C%20insulin,%25CI%200.25%2D1.95). 8. Atkinson FS, Brand-Miller JC, Foster-Powell K, Buyken AE, Goletzke J. International tables of glycemic index and glycemic load values 2021: a systematic review. Am J Clin Nutr. 2021 Nov 8;114(5):1625-1632. doi: 10.1093/ajcn/nqab233. PMID: 34258626. https://www.sciencedirect.com/science/article/pii/S0002916522004944?via%3Dihub 9. Gouni-Berthold I, Schwarz J, Berthold HK. Updates in Drug Treatment of Severe Hypertriglyceridemia. Curr Atheroscler Rep. 2023 Oct;25(10):701-709. doi: 10.1007/s11883-023-01140-z. PMID: 37642858; PMCID: PMC10564803. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10564803/ 10. Raal FJ, Rosenson RS, Reeskamp LF, Hovingh GK, Kastelein JJP, Rubba P, Ali S, Banerjee P, Chan KC, Gipe DA, Khilla N, Pordy R, Weinreich DM, Yancopoulos GD, Zhang Y, Gaudet D; ELIPSE HoFH Investigators. Evinacumab for Homozygous Familial Hypercholesterolemia. N Engl J Med. 2020 Aug 20;383(8):711-720. doi: 10.1056/NEJMoa2004215. PMID: 32813947. https://www.nejm.org/doi/full/10.1056/NEJMoa2004215 11. Rosenson RS, Gaudet D, Ballantyne CM, Baum SJ, Bergeron J, Kershaw EE, Moriarty PM, Rubba P, Whitcomb DC, Banerjee P, Gewitz A, Gonzaga-Jauregui C, McGinniss J, Ponda MP, Pordy R, Zhao J, Rader DJ. Evinacumab in severe hypertriglyceridemia with or without lipoprotein lipase pathway mutations: a phase 2 randomized trial. Nat Med. 2023 Mar;29(3):729-737. doi: 10.1038/s41591-023-02222-w. PMID: 36879129; PMCID: PMC10033404. https://www.nature.com/articles/s41591-023-02222-w 12. Witztum JL, Gaudet D, Arca M, Jones A, Soran H, Gouni-Berthold I, Stroes ESG, Alexander VJ, Jones R, Watts L, Xia S, Tsimikas S. Volanesorsen and triglyceride levels in familial chylomicronemia syndrome: Long-term efficacy and safety data from patients in an open-label extension trial. J Clin Lipidol. 2023 May-Jun;17(3):342-355. doi: 10.1016/j.jacl.2023.03.007. PMID: 37100699. Erratum in: J Clin Lipidol. 2023 Oct 13;: PMID: 37100699. https://www.lipidjournal.com/article/S1933-2874(23)00065-X/fulltext 13. Witztum JL, Gaudet D, Freedman SD, Alexander VJ, Digenio A, Williams KR, Yang Q, Hughes SG, Geary RS, Arca M, Stroes ESG, Bergeron J, Soran H, Civeira F, Hemphill L, Tsimikas S, Blom DJ, O’Dea L, Bruckert E. Volanesorsen and Triglyceride Levels in Familial Chylomicronemia Syndrome. N Engl J Med. 2019 Aug 8;381(6):531-542. doi: 10.1056/NEJMoa1715944. PMID: 31390500. https://www.nejm.org/doi/10.1056/NEJMoa1715944?url_ver=Z39.88-2003𝔯_id=ori:rid:crossref.org𝔯_dat=cr_pub%20%200pubmed 14. Tardif JC, Karwatowska-Prokopczuk E, Amour ES, Ballantyne CM, Shapiro MD, Moriarty PM, Baum SJ, Hurh E, Bartlett VJ, Kingsbury J, Figueroa AL, Alexander VJ, Tami J, Witztum JL, Geary RS, O’Dea LSL, Tsimikas S, Gaudet D. Apolipoprotein C-III reduction in subjects with moderate hypertriglyceridaemia and at high cardiovascular risk. Eur Heart J. 2022 Apr 6;43(14):1401-1412. doi: 10.1093/eurheartj/ehab820. PMID: 35025993; PMCID: PMC8986458. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8986458/ 15. Kirkpatrick CF, Sikand G, Petersen KS, Anderson CAM, Aspry KE, Bolick JP, Kris-Etherton PM, Maki KC. Nutrition interventions for adults with dyslipidemia: A Clinical Perspective from the National Lipid Association. J Clin Lipidol. 2023 Jul-Aug;17(4):428-451. doi: 10.1016/j.jacl.2023.05.099. PMID: 37271600. https://www.lipidjournal.com/article/S1933-2874(23)00185-X/fulltext 16. Fialkow J. Omega-3 Fatty Acid Formulations in Cardiovascular Disease: Dietary Supplements are Not Substitutes for Prescription Products. Am J Cardiovasc Drugs. 2016 Aug;16(4):229-239. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947114/ 17. Skulas-Ray AC, Wilson PWF, Harris WS, Brinton EA, Kris-Etherton PM, Richter CK, Jacobson TA, Engler MB, Miller M, Robinson JG, Blum CB, Rodriguez-Leyva D, de Ferranti SD, Welty FK., American Heart Association Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Lifestyle and Cardiometabolic Health; Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; and Council on Clinical Cardiology. Omega-3 Fatty Acids for the Management of Hypertriglyceridemia: A Science Advisory From the American Heart Association. Circulation. 2019 Sep 17;140(12) https://www.ahajournals.org/doi/full/10.1161/CIR.0000000000000709?rfr_dat=cr_pub++0pubmed&url_ver=Z39.88-2003𝔯_id=ori%3Arid%3Acrossref.org 18. Ito MK. A Comparative Overview of Prescription Omega-3 Fatty Acid Products. P T. 2015 Dec;40(12):826-857. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4671468/ 19. Laufs U, Parhofer KG, Ginsberg HN, Hegele RA. Clinical review on triglycerides. Eur Heart J. 2020 Jan 1;41(1):99-109c. doi: 10.1093/eurheartj/ehz785. PMID: 31764986; PMCID: PMC6938588. https://academic.oup.com/eurheartj/article/41/1/99/5640489 20. Virani SS, Morris PB, Agarwala A, Ballantyne CM, Birtcher KK, Kris-Etherton PM, Ladden-Stirling AB, Miller M, Orringer CE, Stone NJ. 2021 ACC Expert Consensus Decision Pathway on the Management of ASCVD Risk Reduction in Patients With Persistent Hypertriglyceridemia: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2021 Aug 31;78(9):960-993. doi: 10.1016/j.jacc.2021.06.011. PMID: 34332805. https://www.jacc.org/doi/10.1016/j.jacc.2021.06.011 21. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019 Jun 18;139(25). doi: 10.1161/CIR.0000000000000625. Epub 2018 Nov 10. Erratum in: Circulation. 2019 Jun 18;139(25). doi: 10.1161/CIR.0000000000000698. Erratum in: Circulation. 2023 Aug 15;148(7). doi: 10.1161/CIR.0000000000001172. PMID: 30586774; PMCID: PMC7403606.\ https://www.ahajournals.org/doi/10.1161/CIR.0000000000000625 22. Writing Committee; Lloyd-Jones DM, Morris PB, Ballantyne CM, Birtcher KK, Covington AM, DePalma SM, Minissian MB, Orringer CE, Smith SC Jr, Waring AA, Wilkins JT. 2022 ACC Expert Consensus Decision Pathway on the Role of Nonstatin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2022 Oct 4;80(14):1366-1418. doi: 10.1016/j.jacc.2022.07.006. Epub 2022 Aug 25. Erratum in: J Am Coll Cardiol. 2023 Jan 3;81(1):104. doi: 10.1016/j.jacc.2022.11.016. PMID: 36031461. https://www.jacc.org/doi/10.1016/j.jacc.2022.07.006

View Details

CardioNerds (Dr. Rick Ferraro and Dr. Dan Ambinder) join Dr. Sri Mandava, Dr. David Meister, and Dr. Marissa Donatelle from the Columbia University Division of Cardiology at Mount Sinai Medical Center in Miami. Expert commentary is provided by Dr. Pranav Venkataraman. They discuss the following case involving a patient with cardiac sarcoidosis presenting as STEMI.

A 57-year-old man with a history of hyperlipidemia presented with sudden onset chest pain. On admission, he was vitally stable with a normal cardiorespiratory exam but appeared in acute distress and was diffusely diaphoretic. His ECG revealed sinus rhythm, a right bundle branch block (RBBB), and ST elevation in the inferior-posterior leads. He was promptly taken for emergent cardiac catheterization, which identified a complete thrombotic occlusion of the mid-left circumflex artery (LCX) and large obtuse marginal (OM) branch, with no underlying coronary atherosclerotic disease. Aspiration thrombectomy and percutaneous coronary intervention (PCI) were performed, with one drug-eluting stent placed. An echocardiogram showed a left ventricular ejection fraction (EF) of 31%, hypokinesis of the inferior, lateral, and apical regions, and an apical left ventricular thrombus. The patient was started on triple therapy. A hypercoagulable workup was negative. A cardiac MRI was obtained to further evaluate non-ischemic cardiomyopathy. In conjunction with a subsequent CT chest, the results raised suspicion for cardiac sarcoidosis with systemic involvement. In view of a reduced EF and significant late-gadolinium enhancement, electrophysiology was consulted to evaluate for ICD candidacy. A decision was made to delay ICD implantation until a definitive diagnosis of cardiac sarcoidosis could be established by tissue biopsy. The patient was started on HF-GDMT and discharged with a LifeVest. Close outpatient follow-up with cardiology and electrophysiology was arranged.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.

CardioNerds Case Reports Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll

CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!

Pearls – Cardiac Sarcoidosis Presenting as STEMI1. Cardiac sarcoidosis can present with a variety of symptoms, including arrhythmias, heart block, heart failure, or sudden cardiac death. Symptoms can be subtle or mimic other cardiac conditions. 2. Conduction abnormalities, particularly AV block or ventricular arrhythmias, are common and may be the initial indication of cardiac involvement with sarcoidosis. 3. The additive value of Echocardiography, FDG-PET, and cardiac MR is indispensable in the diagnostic workup of suspected cardiac sarcoidosis. 4. Specific role of MRI/PET: Both cardiac MRI and FDG-PET provide a complementary role in the diagnosis of cardiac sarcoidosis. Cardiac MRI is an effective diagnostic screening tool with fairly high sensitivity but is limited by its inability to decipher inflammatory (“active” disease) versus fibrotic myocardium. FDG-PT helps to make this discrimination, refine the diagnosis, and guide clinical management. Ultimately, these studies are most useful when interpreted in the context of other clinical information. 5. Primary prevention of sudden cardiac death in cardiac sarcoidosis focuses on risk stratification, with ICD placement for high-risk patients. For patients awaiting definitive diagnosis, a LifeVest may be used as a temporary measure to protect from sudden arrhythmic events until an ICD is placed.

Notes – Cardiac Sarcoidosis Presenting as STEMI1. Is STEMI always a result of coronary artery disease?

By definition, a STEMI is an acute S-T segment elevation myocardial infarction. This occurs when there is occlusion of a major coronary artery, which results in transmural ischemia and damage, resulting in electrical changes seen on the ECG. The most common cause of coronary artery occlusion is coronary artery disease (CAD) from plaque rupture and thrombus formation; however, many other causes of coronary artery occlusion are not related to CAD. These include vasospasm (isolated and recurrent), in-situ thrombotic occlusion, spontaneous coronary artery dissection, and supply-demand mismatch, such as in the setting of severe anemia. DDx includes other causes of injury current, such as myocarditis. It is important to keep these other differentials in mind while preparing for coronary angiography, as it may help guide intra-catheterization and post-catheterization management.

2. What are the most common causes of LV thrombus?

When considering the causes of thrombus formation, think of Virchow’s triad. As with any other location, thrombus formation in the LV may be caused by injury/inflammation, systemic thrombophilia, and stasis.

Acute myocardial infarction (especially anterior MI) – damaged myocardium and impaired LV function lead to blood stasis and thrombus formation.
Heart failure with reduced ejection fraction (HFrEF) – severely impaired contractility increases the risk of thrombus development
Non-Ischemic cardiomyopathies – dilated or hypertrophic cardiomyopathies may cause abnormal blood flow, promoting thrombus formation.
Arrhythmias – although more associated with atrial thrombus, atrial fibrillation can also contribute to LVT in cases of significant LV dysfunction. Ventricular arrhythmias can also cause LV thrombus.
Hypercoagulable conditions – Conditions such as antiphospholipid antibody syndrome, inherited thrombophilias, malignancy-associated hypercoagulability, polycythemia vera, hyperhomocysteinemia, nephrotic syndrome or systemic lupus erythematous may predispose to LV thrombus formation
Inflammatory conditions – conditions like myocarditis or cardiac sarcoidosis can lead to inflammation along with focal stasis from aneurysmal changes, contributing to thrombus formation

3. What is the clinical presentation of cardiac sarcoidosis?

Chest pain: can arise from several mechanisms such as myocardial inflammation, pericarditis, coronary artery involvement, or arrhythmias.
Heart Failure: symptoms such as dyspnea, fatigue, and peripheral edema may result from left ventricular dysfunction or restrictive cardiomyopathy.
Arrhythmias: palpitations, dizziness or syncope may occur due to ventricular tachycardia or ventricular fibrillation.
Conduction abnormalities: Heart block, especially complete AV block, is a common early manifestation. Some studies have found that AV block is the presenting symptom in more than 40% of patients with cardiac sarcoidosis.
Sudden cardiac death (SCD): sudden death can occur due to ventricular arrhythmias or severe heart block.
Asymptomatic: in some cases, cardiac sarcoidosis is discovered incidentally during imaging or evaluation for systemic sarcoidosis.

4. What are the key imaging modalities used in the diagnosis of cardiac sarcoidosis?

Echocardiography, FDG-PET, and cardiac MRI are the key imaging modalities used to diagnose cardiac sarcoidosis. The echocardiogram is often normal in clinically silent disease, but several key features may be seen in clinically active disease. The most specific findings are basal interventricular thinning and LV aneurysm. Other less specific findings include increased LV wall thickness, LV/RV diastolic and/or systolic dysfunction, and wall motion abnormalities (non-coronary distribution). Strain imaging is promising for use in earlier stages of disease, but this is not well established yet. FDG-PET is crucial in the initial diagnosis of cardiac sarcoidosis, allowing active inflammatory disease to be detected. There is no pathognomonic PET finding; however, focal or focal-on-diffuse FDG uptake patterns are highly suggestive of active disease. It should be noted that FDG-PET is also useful in guiding treatment or response to immunosuppressive therapy, as it can track the degree of inflammation over time. The role of cardiac MRI is discussed below.

5. What is the specific role of cardiac MRI in the diagnosis of cardiac sarcoidosis?

This depends on the specific clinical setting. A patient with established extra-cardiac sarcoidosis but asymptomatic from a cardiac standpoint should be appropriately screened for cardiac involvement by clinical history, ECG, echocardiography, and cardiac monitoring (e.g. Holter monitor, etc). If any of the aforementioned “screening” tests are abnormal, a cardiac MRI is then indicated to assess for evidence of cardiac sarcoidosis. More specifically, cardiac MRI detects inflammation and edema at earlier stages of disease and scar tissue at later stages. The classical finding specific for cardiac sarcoidosis is patchy late gadolinium enhancement, with a predilection for the basal septum and basal inferolateral wall. The enhancement is either subepicardial or mid-wall and rarely transmural. It should be noted that once cardiac sarcoidosis is diagnosed, FDG-PET imaging should be utilized in conjunction with, or complementary to MRI, to assess for “active sarcoid” (i.e. myocardial inflammation).

On the other hand, a patient with no known extracardiac sarcoidosis but with suggestive cardiac findings should have a cardiac MRI to assess for typical features as mentioned above, in addition to assessment for non-cardiac involvement.

It should be noted that cardiac MRI can also provide significant prognostic information. The presence of LGE portends a worse prognosis due to increased CV death and ventricular arrhythmias. It should also be noted that LGE does not discriminate between active inflammation and fibrosis. Tissue characterization with T1 and T2 mapping techniques or PET imaging, as described above, can be more useful in this sense.

References1.) Cheng RK, Kittleson MM, Beavers CJ, et al. Diagnosis and management of cardiac sarcoidosis: a scientific statement from the American Heart Association. Circulation. 2024;149.

2.) Lehtonen J, Uusitalo V, Pöyhönen P, Mäyränpää MI, Kupari M. Cardiac sarcoidosis: phenotypes, diagnosis, treatment, and prognosis. European Heart Journal. 2023;44:1495–1510.

3.) Kouranos V, Sharma R. Cardiac sarcoidosis: state-of-the-art review. Heart. 2021;107:1591–1599.

4.) Birnie DH, Nery PB, Ha AC, Beanlands RSB. Cardiac sarcoidosis. Journal of the American College of Cardiology. 2016;68:411–421.

View Details

CardioNerds (Dr. Colin Blumenthal and Dr. Saahil Jumkhawala) join Dr. Rohan Ganti, Dr. Nikita Mishra, and Dr. Jorge Naranjo from the Rutgers – Robert Wood Johnson program for a college basketball game, as the buzz around campus is high. They discuss the following case involving a patient with ventricular tachycardia:

The case involves a 61-year-old man with a medical history of hypothyroidism, hypertension, hyperlipidemia, seizure disorder on anti-epileptic medications, and major depressive disorder, who presented to the ER following an out-of-hospital cardiac arrest. During hospitalization, he experienced refractory polymorphic ventricular tachycardia (VT), requiring 18 defibrillation shocks. Further evaluation revealed non-obstructive hypertrophic cardiomyopathy (HCM). We review the initial management of electrical storm, special ECG considerations, diagnostic approaches once ischemia has been excluded, medications implicated in polymorphic VT, the role of multi-modality imaging in diagnosing hypertrophic cardiomyopathy, and risk stratification for implantable cardioverter-defibrillator (ICD) placement in patients with HCM.

Expert commentary is provided by Dr. Sabahat Bokhari. Episode audio was edited by CardioNerds Intern and student Dr. Pacey Wetstein.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.

CardioNerds Case Reports Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll

CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!

Pearls – A Curious Case of Refractory Ventricular Tachycardia – Rutgers-Robert Wood Johnson1. Diagnostic Uncertainty in VT Storm: In VT storm, ischemia is a primary consideration; when coronary angiography excludes significant epicardial disease, alternative causes such as cardiomyopathies, channelopathies, myocarditis, electrolyte disturbances, or drug-induced arrhythmias must be explored. 2. ST elevations in ECG lead aVR: ST elevations in lead aVR and diffuse ST depressions can sometimes represent post-arrest oxygen demand and myocardial mismatch rather than an acute coronary syndrome. This pattern may occur in the context of polymorphic VT (PMVT), where myocardial oxygen demands outstrip supply, especially after an arrest. While these ECG changes could suggest myocardial ischemia, caution is needed, as they might not always indicate coronary pathology. However, PMVT generally should raise suspicion for underlying coronary disease and may warrant a coronary angiogram for further evaluation. 3. Medication Implications in PMVT and HCM: Certain medications, including psychotropic drugs (e.g., antidepressants, antipsychotics) and anti-epileptic drugs, can prolong the QT interval or interact with other drugs, thereby increasing the risk of polymorphic VT in patients with underlying conditions like HCM. Careful management of these medications is critical to avoid arrhythmic events in predisposed individuals. 4. Multi-Modality Imaging in HCM: Cardiac MRI with late gadolinium enhancement (LGE) is invaluable in assessing myocardial fibrosis, a key predictor of arrhythmic risk, and can guide decisions regarding ICD implantation. Echocardiography and contrast-enhanced CT can provide additional insights into structural abnormalities and risk assessment. 5. Polymorphic VT in Nonobstructive HCM: Polymorphic ventricular tachycardia (PMVT) can occur in nonobstructive hypertrophic cardiomyopathy due to myocardial fibrosis and disarray, even in the absence of significant late gadolinium enhancement and left ventricular outflow tract obstruction. 6. ICD Risk Stratification in HCM: Risk stratification for ICD placement in HCM includes assessment of clinical features such as family history of sudden cardiac death, history of unexplained syncope, presence of nonsustained VT on ambulatory monitoring, massive left ventricular hypertrophy (wall thickness ≥30 mm), and evidence of extensive myocardial fibrosis on cardiac MRI.

Notes – A Curious Case of Refractory Ventricular Tachycardia – Rutgers-Robert Wood Johnson1. Is there a benefit of starting antiarrhythmic medications for patients presenting with an out-of-hospital cardiac arrest with shock-refractory VT or VF? * There is likely no benefit. An RCT published by Kudenchuk et al in 2016 in which patients who had a non-traumatic out-of-hospital cardiac arrest with shock-refractory VF or pulseless VT were randomly assigned to receive lidocaine, amiodarone, or saline placebo, in addition to standard care, showed that neither antiarrhythmic drug had a significantly higher rate of survival or favorable neurologic outcome compared to placebo6. 2. What is the differential diagnosis and empiric management for a patient with polymorphic ventricular tachycardia? * The differential diagnosis for ventricular tachycardia includes myocardial ischemia, electrolyte derangements, medications that may cause QT prolongation, congenital long QT syndrome, Brugada syndrome, myocarditis, dilated cardiomyopathy, arrhythmic cardiomyopathies, and infiltrative or structural heart disease. * Standard BLS and ACLS measures are first-line treatment for pulseless VT. * For stable patients, the 2017 AHA/ACC/HRS0 guidelines list beta-blockers as first-line antiarrhythmic therapy because they have been shown to reduce mortality and suppress ventricular arrhythmias in structurally normal hearts3. Amiodarone is also listed, though its long-term effect on survival is unclear, with most studies showing no clear benefit over placebo 3. Lidocaine and mexiletine are also commonly used, but because they are less efficacious compared to amiodarone, they are usually used as combination therapy for refractory patients4. Multiple trials have demonstrated the efficacy of procainamide as an adjunct medication in patients with ongoing ventricular arrhythmias, despite amiodarone and lidocaine4. Quinidine has also been used for patients as a salvage therapy for patients with structural heart disease for recurrent ventricular arrhythmias despite antiarrhythmic drug treatment 4. 3. What medications can be associated with polymorphic VT? * Medications that are commonly associated with QT prolongation, therefore making patients more susceptible to developing VT, include Class I and Class III antiarrhythmics; fluoroquinolone and macrolide antibiotics, as well as antifungals; tricyclic antidepressants as well as certain SSRI’s and SNRI’s; and antipsychotics, among others5. * In this video, Dr. Nino Isakadze explains the proper way to measure the QT interval. 4. How can multimodal imaging help reach a diagnosis in patients with PMVT with a relatively normal echocardiogram and no coronary artery disease? * Multimodal imaging, specifically cardiac MRI, is useful for reaching a diagnosis in patients with PMVT due to improved myocardial tissue characterization. * Improved definition of the myocardium allows for the detection of structural abnormalities that may not be as easily visualized on TTE, such as LV non-compaction, now called excessive trabeculation of the left ventricle, and to more accurately measure left ventricular wall thickness, which is useful for diagnosing and risk stratifying patients with hypertrophic cardiomyopathy. * Improved tissue characterization by measuring T1 relaxation time, T2 relaxation time, extracellular volume, and late gadolinium enhancement (LGE) pattern is also useful for diagnosing infiltrative disease. Certain LGE patterns are associated with different cardiac conditions and play a role in determining prognosis. For example, the detection of mid-wall LGE in patients with dilated cardiomyopathy portends an increased risk of adverse events. 5. What are the risk factors for sudden cardiac death in patients with HCM? * The updated 2024 HCM guidelines have outlined several risk factors for sudden cardiac death 1 1. Family history of sudden cardiac death 2. Unexplained syncope 3. NSVT episodes on ambulatory monitoring when runs are frequent (≥ 3), longer (≥ 10 beats), and faster (≥ 200 bpm) 4. Increased LV wall thickness, with elevated risk greater than 30 mm * Other risk stratification markers include extensive LGE seen on cardiac MRI, apical aneurysm, and EF < 50% in patients without high-risk features 1 * The AHA HCM SCD Calculator can be used to risk stratify patients to assist with decision-making in ICD implantation in these patients2

References 1. Ommen SR, Ho CY, Asif IM, et al. 2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines [published correction appears in Circulation. 2024 Aug 20;150(8):e198. doi: 10.1161/CIR.0000000000001277]. Circulation. 2024;149(23):e1239-e1311. doi:10.1161/CIR.0000000000001250 2. AHA HCM SCD Calculator 3. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society [published correction appears in Circulation. 2018 Sep 25;138(13):e419-e420. doi: 10.1161/CIR.0000000000000614]. Circulation. 2018;138(13):e272-e391. doi:10.1161/CIR.0000000000000549 4. Larson J, Rich L, Deshmukh A, Judge EC, Liang JJ. Pharmacologic Management for Ventricular Arrhythmias: Overview of Anti-Arrhythmic Drugs. J Clin Med. 2022;11(11):3233. Published 2022 Jun 6. doi:10.3390/jcm11113233 5. Nachimuthu S, Assar MD, Schussler JM. Drug-induced QT interval prolongation: mechanisms and clinical management. Ther Adv Drug Saf. 2012;3(5):241-253. doi:10.1177/2042098612454283 6. Kudenchuk PJ, Brown SP, Daya M, et al. Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest. N Engl J Med. 2016;374(18):1711-1722. doi:10.1056/NEJMoa1514204

View Details

CardioNerds (Dr. Dan Ambinder and guest host, Dr. Pooja Prasad) join Dr. Donny Mattia from Phoenix Children’s pediatric cardiology fellowship, Dr. Sri Nayak from the Mayo Clinic – Arizona adult cardiology fellowship, and Dr. Harrison VanDolah from the University of Arizona College of Medicine – Phoenix Med/Peds program for a sunrise hike of Piestewa Peak, followed by some coffee at Berdena’s in Old Town Scottsdale (before the bachelorette parties arrive), then finally a stroll through the Phoenix Desert Botanical Gardens to discuss a thought-provoking case series full of clinical cardiology pearls. Expert commentary is provided by Dr. Tabitha Moe. Episode audio was edited by Dan Ambinder.

They discuss the following case: Cardiology is consulted by the OB team for a 27-year-old female G1, now P1, who has just delivered a healthy baby boy at 34 weeks gestation after going into premature labor. She is experiencing shortness of breath and is found to have a significant past cardiac history, including atrial fibrillation and preexcitation, now with a pacemaker and intracardiac defibrillator. We review the differential diagnosis for peripartum cardiomyopathy (PPCM) and then combine findings from her infant son, who is seen by our pediatric cardiology colleagues and is found to have severe hypertrophic cardiomyopathy (HCM). Genetic testing for both ultimately reveals a LAMP2 mutation consistent with Danon Disease. The case discussion focuses on the differential diagnosis for PPCM, HCM, pearls on Danon Disease and other HCM “phenocopies,” and the importance of good history.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.

CardioNerds Case Reports Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll

CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!

Case MediaPearls1. Peripartum cardiomyopathy is a diagnosis of exclusion – we must exclude other possible etiologies of heart failure! 2. Be on the lookout for features of non-sarcomeric HCM – as Dr. Michelle Kittleson said in Episode 166, “LVH plus” states. HCM with preexcitation, heart block, strong family history, or extracardiac symptoms such as peripheral neuropathy, myopathy, or cognitive impairment should be evaluated for infiltrative/inherited cardiomyopathies! 3. As an X-linked dominant disorder, Danon disease will present differently in males vs females, with males having much more severe and earlier onset disease with extracardiac features. 4. Making the diagnosis for genetic disorders such as Danon disease is important for getting the rest of family members tested as well as the opportunity for specialized treatments such as gene therapy 5. Up to 5% of Danon disease cases may be due to copy number variants, which may be missed in genetic testing that does not do targeted deletion/duplication analysis!).

NotesWhat is the differential diagnosis for peripartum cardiomyopathy? Peripartum cardiomyopathy is a diagnosis of exclusion* – we must exclude other possible etiologies of heart failure! * First, ensure that you are not missing an acute life-threatening etiology of acute decompensated heart failure – pulmonary embolism, amniotic fluid embolism, ACS, and SCAD should all be ruled out. * Second, a careful history can identify underlying heart disease or risk factors for the development of heart failure, such as substance use, high-risk behaviors that put one at risk for HIV infection, and family history that suggests an inheritable cardiomyopathy. * Lastly, a careful review of echocardiographic imaging may also identify underlying etiologies that warrant a change in management. * Diagnosis of peripartum cardiomyopathy is important to consider as within 7 days of onset, patients may be eligible for treatment with bromocriptine – consider referring the patient for enrollment in the ongoing RCT ReBIRTH. * Check out Cardionerds Episode 113 and the great article linked below for more details on heart failure in pregnancy and postpartum!

What is the differential diagnosis for hypertrophic cardiomyopathy? Though by far the most common differential diagnosis for HCM is simple LVH or athlete’s heart, as Dr. Michelle Kittleson taught us in CardioNerds Episode 166, we should “remain alert for “LVH+” states.” * It is helpful to think of them in two buckets – sarcomeric mutations (classic HCM) or non-sarcomeric causes (“phenocopies”). * If you see systemic signs like peripheral neuropathy, renal dysfunction, or skin changes – clues towards a systemic pathology (for adult colleagues, first think amyloidosis; for peds, colleagues, think genetic syndromes such as RASopathies like Noonan syndrome, glycogen, and lysosomal storage diseases like Fabry). * Additionally, certain additional cardiac findings can point towards a non-sarcomeric HCM – recall way back in CardioNerds Episode 68 when our friends at VCU presented a man in his 60s with a history of WPW/preexcitation and HCM and was found to have a PRKAG2* mutation, which is a similar lysosomal vacuolopathy to Danon disease. Another example was seen in Episode 349 when we saw a patient with HCM and heart block who was found to have Fabry disease.

What is Danon disease, and how does it present? Danon disease is a rare X-linked dominant genetic disorder due to deficiency in LAMP2, a glycoprotein involved in protecting the lysosome from its roles in endocytosis and autophagy * When deficiency of LAMP2 occurs, products build up into vacuoles and lead to cardiomyocyte dysfunction and death. * Interestingly, autophagy disruption is the suspected mechanism of cardiomyopathies from anthracyclines and hydroxychloroquine – Danon disease severity underscores the importance of this process! * Estimated prevalence of Danon disease in adult patients with HCM is 1-4%, however when both HCM and pre-excitation are present, this rises to 17%. * It is highly penetrant, meaning most patients with the mutation will show symptoms. * There are several extracardiac features such as skeletal myopathy, retinopathy, and cognitive impairment – these correlated with areas in the body where LAMP2 is expressed more! * Classic presentations – remember that X-linked inheritance results in differential expression between males and females! + Males: young onset with severe LVH/HCM and extracardiac phenotype + Females: isolated cardiomyopathy (can be either dilated or hypertrophic) with preexcitation arrhythmias with a family history suggesting X-linked dominant transmission (i.e., males more severely affected than females). * When taking a family history, note that male-to-male transmission (can’t happen since males don’t pass on an X chromosome to their male children) or female-to-offspring transmission (suggests mitochondrial disease) should prompt alternate diagnosis. However, an estimated 1/3 of Danon disease cases are de novo mutations!* * See Episode 300 for a great in-depth overview of the pathophysiology of Danon disease

How is Danon disease diagnosed? Though there are some proposed characteristic cardiac MRI findings (diffuse LGE sparing the interventricular septum), diagnosis is genetic with a loss-of-function mutation in LAMP2 paired with characteristic cardiac or extracardiac features (see below diagnostic algorithm from Hong et al. JACC 2023) * LAMP2 is now included in most hypertrophic and dilated CM panels – if found, it is crucial to ensure the patient’s family members also undergo testing and potentially cardiac evaluation! (Note: up to 5% of Danon disease cases may be due to copy number variants, which may be missed in genetic testing that does not do targeted deletion/duplication analysis!) * Differential Diagnosis + Sarcomeric HCM – the “classic” HCM, which has numerous genetic causes, all of which affect the sarcomere with age-related penetrance leading to three peaks in age at onset (infancy <1yr, teenage/early adulthood, and mid-adulthood). Progression towards massive LVH and systolic dysfunction is uncommon (<10%) and should raise suspicion of a rare genocopy such as Danon. EKG is usually mostly normal in these patients, unlike in Danon disease, which often has striking abnormalities. + Pompe disease – lysosome storage disease from mutations in acid alpha-glucosidase leading to lysosomal glycogen accumulation. Autosomal recessive. It can be an infantile form with severe LVH/HCM, and the later forms can have classic skeletal myopathy as well, but usually, these patients have less severe cardiac features. + RAS-opathies – genetic diseases due to mutations in the RAS/MAPkinase pathway. Classic examples are Noonan syndrome, LEOPARD syndrome, and Costello syndrome. All have classic extracardiac manifestations as well as oftentimes HCM, as well as congenital heart disease such as pulmonary valve stenosis. + Fabry disease – also an X-linked recessive lysosomal disorder due to alpha-galactosidase A enzyme deficiency; however, it is rarely prominent in childhood and is usually more characterized by extracardiac manifestations. HCM is a cardiac manifestation presenting in the 30s-40s. + Friedrich ataxia – autosomal recessive multisystem disease due to GAA sequence expansion in the FXN gene that encodes frataxin, a mitochondrial protein, which impairs mitochondrial oxidative phosphorylation. “HCM” is a common disease manifestation in addition to the classic severe neurologic presentation. + Mitochondrial diseases – heterogenous conditions affecting mitochondrial DNA, transmitted in matrilinear pattern, with cardiac hypertrophy being a classic disease manifestation in addition to preexcitation. These may present with severe cognitive impairment than Danon disease. + PRKAG2 mutations – cause dysregulation of adenosine monophosphate kinase, culminating in accumulation of vacuoles within glycogen stores. Early-onset cardiac hypertrophy with preexcitation can be similar to Danon disease. There are no extracardiac features and the inheritance pattern is autosomal dominant. + For a great summary, see Table 2 in Hong K et al. International Consensus on Differential Diagnosis and Management of Patients with Danon disease: JACC state-of-the-art Review. JACC 2023 Oct, 82 (16) 1628-1647. * For patients who undergo heart transplantation for a genetic/inherited cause, it is crucial to recall their index diagnosis after transplant – they may have extracardiac disease manifestations!*

References * Davis M et al. Peripartum cardiomyopathy: JACC state-of-the-art review. JACC 2020 Jan, 75 (2) 207-221. https://www.jacc.org/doi/10.1016/j.jacc.2019.11.014 * DeFilippis EM et al. Cardio-obstetrics and heart failure: JACC: Heart Failure state-of-the-art review. JACC: HF 2023 Sep, 11(9) 1165-1180. https://www.jacc.org/doi/10.1016/j.jchf.2023.07.009_ga=2.84541658.274573079.1723517623-224546423.1716483762 * Hong K et al. International consensus on differential diagnosis and management of patients with Danon disease: JACC state-of-the-art review. JACC 2023 Oct, 82 (16) 1628- 1647. https://www.jacc.org/doi/abs/10.1016/j.jacc.2023.08.014 * Miliou A et al. Danon cardiomyopathy: specific imaging signs. JACC: Case Rep 2022 Nov 6;4(22):1496-1500. https://www.sciencedirect.com/science/article/pii/S2666084922006015 * Padkins MR, Bell MR. 33-year-old woman with postpartum acute shortness of breath. Mayo Clinic Proceedings 2020;95(9):2000-2004 https://www.mayoclinicproceedings.org/article/S0025-6196(20)30713-8/fulltext * Rigolli M et al. Cardiac magnetic resonance imaging in Danon disease cardiomyopathy. JACC: Imaging 2021 Feb, 14 (2) 514-516. https://www.jacc.org/doi/10.1016/j.jcmg.2020.08.011

View Details

CardioNerds Dan Ambinder and Dr. Devesh Rai join cardiology fellows and National Lipid Association lipid scholars Dr. Oby Ibe from Temple University and Dr. Elizabeth Epstein from Scripps Clinic. They discuss a case involving a patient with elevated Lp(a). Dr. Jessica Pena provides expert commentary. Drs. Oby Ibe and Elizabeth Epstein drafted notes. CardioNerds Intern Christiana Dangas engineered episode audio. This episode is part of a case reports series developed in collaboration with the National Lipid Association and their Lipid Scholarship Program, with mentorship from Dr. Daniel Soffer and Dr. Eugenia Gianos.

This is a 63-year-old man with hypertension, hyperlipidemia, and active tobacco smoking who presented with acute dyspnea. He was tachycardic but otherwise initially hemodynamically stable. The physical exam demonstrated warm extremities with no murmurs or peripheral edema. Chest X-ray revealed diffuse pulmonary edema, and the ECG showed sinus tachycardia with T-wave inversions in the inferior leads. A bedside echocardiogram revealed a flail anterior mitral valve leaflet. The patient was taken for cardiac catheterization that revealed nonobstructive mid-RCA atheroma with a distal RCA occlusion, which was felt to reflect embolic occlusion from recanalized plaque. PCI was not performed. Right heart catheterization then demonstrated a low cardiac index as well as elevated PCWP and PA pressures. An intra-aortic balloon pump was placed at that time. A TEE was performed soon after which showed the posteromedial papillary muscle was ruptured with flail segments of the anterior mitral leaflet as well as severe posteriorly directed mitral regurgitation. The patient ultimately underwent a successful tissue mitral valve replacement and CABG.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.

CardioNerds Case Reports Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll

CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!

Pearls – Little (a), Big Deal – National Lipid Association1. You are never too young to see a preventive cardiologist! The field of preventive cardiology is shifting focus towards the identification of early upstream risk and intervention before the development of clinical ASCVD (1,5). Patients who have a strong family history of cardiovascular disease, a personal history of CVD at an early age, multiple risk factors, or genetic disorders such as familial hypercholesterolemia especially benefit from early cardiovascular risk assessment and reduction. 2. Female-specific risk factors to incorporate into a young woman’s cardiovascular risk assessment include polycystic ovarian syndrome, hormone contraceptive use, early menarche (age <10 years old), primary ovarian insufficiency, fertility therapy, hypertensive disorders of pregnancy (eclampsia, preeclampsia, gestational hypertension, preterm delivery, gestational diabetes, multi-parity >5 pregnancies), early menopause (age <45 years old), & post-menopausal hormone therapy. 3. Lp(a) testing for all! The most recent NLA scientific statement on the use of Lp(a) in clinical practice recommends measuring Lp(a) at least once in every adult for risk stratification. 4. While Lp(a) has not yet been incorporated into our risk calculators, we do know that elevated Lp(a) increases 10-year risk. The European Atherosclerosis Society published a consensus statement on Lp(a), which includes a handy table to quantify the degree to which a patient’s 10-year risk increases as Lp(a) increases. 5. Lifestyle changes are the first line and can reduce the risk of high Lp(a) by 66%. Next, we can consider the risks and benefits of LDL-lowering in a young patient and monitor closely for the development of plaque over time. Lp(a) lowering drugs such as olpasiran are on the horizon, and we can keep this patient in mind as a potential candidate for therapy in the future.

Notes – Little (a), Big Deal – National Lipid AssociationWhen should patients see a preventive cardiologist?

Strong family history of cardiovascular disease – A positive family history of CVD was defined as a self‐reported diagnosis of CVD in parents, siblings, or children that occurred at 60 years or younger. A positive family history of CVD is an independent predictor of both myocardial infarction and stroke. Among individuals with hypertension, family history of CVD has been shown to be independently associated with mortality by ischemic heart disease and family history of CVD mortality with incidence of overall CVD. Family history of CVD modifies future CVD risk depending on the number and age of affected first-degree relatives. Siblings of patients with CVD have about a 40% risk increase, while offspring of parents with premature CVD have a 60% to 75% risk increase.
Personal history of early CVD – A personal history of cardiovascular disease at an age younger than 60 years. For young and middle-aged adults, increases in heart disease between 2020 and 2021 explain more than 4% of the most recent shortening in life expectancy. In particular, hypertensive heart disease, heart failure, and endocarditis have increased in young adults, particularly among Black individuals, through 2018. Consequently, young adults make up a growing proportion of cardiovascular disease events, with the proportion of premature myocardial infarction among adults younger than 40 years increasing by 2% every year. The increasing event rates observed among younger adults can be attributed to the increasing prevalence and onset of risk factors such as obesity and hypertension at younger ages, which exacerbate cumulative exposure and cardiovascular disease risk over near- and long-term time horizons.
Multiple cardiovascular risk factors – Risk factors include hyperlipidemia, high triglycerides, elevated lp(a), diabetes mellitus, obesity, tobacco use, unhealthy diet, and lack of physical activity. Unadjusted event rates were 8-fold to 30-fold higher in persons with adverse levels of risk factor exposure during young adulthood (age 20–39 years) compared with persons with optimal levels of exposure.
Familial hypercholesterolemia – In primary prevention, patients with FH had incidences of ASCVD and coronary heart disease (CHD) of 14.9/1000 and 5.8/1000 person-years, respectively, compared to 7.1/1000 and 2.1/1000 person-years in the normolipidemic group. FH conferred a hazard ratio (HR) of 7.1 and 16.7 for ASCVD and CHD, respectively, in patients younger than 35 years. In secondary prevention, patients with FH had incidences of ASCVD and CHD of 89.7/1000 and 34.5/1000 person-years, respectively, compared to 90.9/1000 and 28.2/1000 person-years in the normolipidemic group

What are some female-specific risk factors for cardiovascular disease? (7)

PCOS – Polycystic ovarian syndrome (PCOS) is a disorder characterized by hyperandrogenism and menstrual irregularities. Women affected by PCOS have a heightened risk of developing diabetes due to associated insulin resistance, central obesity, and hypertension. This adverse cardiovascular risk profile in women with PCOS may lead to premature atherosclerosis (8,20). Women with PCOS have been shown to have an increased risk for CVD events (21).
Depression — Among 593,616 young adults (aged 18–49 years) from 2017 to 2020, depression was independently associated with CHD and suboptimal cardiovascular health (CVH), with a dose‐response relationship (CVH was determined using 7 cardiovascular risk factors: hypertension, hypercholesterolemia, overweight/obesity, current smoking, diabetes, physical inactivity, and inadequate fruit and vegetable intake) (13). Suboptimal CVH was defined as the presence of ≥2 of these 7 cardiovascular risk factors, whereas optimal CVH was 0 or 1 cardiovascular risk factor.
Early menarche – Results from the Women’s Ischemia Syndrome Evaluation (WISE) study demonstrated that in comparison to women with menarche at age 12 years, there was an approximately 4-fold adjusted increased risk for major adverse cardiac events for menarche ≤ 10 years (15).
African descent – Safford et al. found that among those at the highest CHD risk, Black women’s hyperlipidemia was the least likely to be treated or controlled. Lp(a) is significantly higher among Blacks versus Whites, and in both, increased Lp(a) correlates positively with LDL-C and negatively with triglycerides. Another study based on the MESA population demonstrated that Black participants showed a significant risk of CHD in those with Lp(a) levels ≥ 75 nmol/L as opposed to White and Hispanic participants who had a greater risk with Lp(a) levels ≥125 nmol/L.
Elevated BMI – Obesity and higher measures of central adiposity are associated with significantly higher rates of CAD, CVD mortality, sudden cardiac death, heart failure, and arrhythmias (23). High BMI accounted for 4.0 million deaths in 2015, more than two-thirds of which were caused by cardiovascular disease. Marked increases in obesity prevalence among adolescents over the past 35 years ultimately contribute to CVD risk into young adulthood.

Who should be getting an Lp(a) measured?

Per the most NLA-focused update to the 2019 scientific statement on the use of Lp(a) in clinical practice, we now have sufficient evidence to support measuring Lp(a) at least once in all adults for risk stratification.

What risk calculators would apply to a young adult?

The American Heart Association recently released the PREVENT calculator (c-statistic 0.72) for 10- and 30-year risk estimation of total CVD (composite of atherosclerotic CVD and heart failure) in primary prevention patients (10). This improves upon the prior pooled cohort equation because it is based on newer data from a larger, more diverse sample (6,612,004 US adults 30 to 79 years of age) than the existing tool. The calculator also takes into account other health conditions, such as cardiovascular-kidney-metabolic risk factors, adjusts for competing risk of non-CVD death, and incorporates an indicator of social determinants of health. Race was not included because it is a social construct, not a biological risk factor, and could, therefore, create bias. Three research teams were awarded $150,000 from AHA to further study how the risk calculator performs among people of various ages, racial and ethnic backgrounds, locations, and socioeconomic levels.
A universal calculator (c-statistic 0.747 and 0.691 for patients with and without CAD) was also recently published in JACC. This was unique because it can be used in patients both with and without CAD, doing away with the concepts of primary vs secondary prevention and placing everyone on the same spectrum of risk. The calculator incorporates ASCVD vs no ASCVD, age, diabetes, SBP, HTN treatment, TC, smoking history, CRP, NT Pro-BNP, hs Troponin T and provides a 5- and 10-year risk of MACE. The calculator was able to identify patients without CAD who had a higher risk than those with prior CAD. This calculator is not yet available online, but the authors did publish their formulae, which can be plugged into Excel to create a calculator. Unfortunately, this calculator may not apply to our patient because it was validated in a cohort of patients aged 45-64 years.
QRISK3 (c-statistic 0.75) has been validated in patients aged 25-84 years, so it can be useful in predicting cardiovascular disease in both younger and older patients. It also incorporates a wider variety of risk-enhancing factors than most other calculators, including diagnosis of HIV/AIDS, inflammatory diseases, CKD stage, type 1 and type 2 diabetes, and erectile dysfunction. However, it is important to note that this calculator was validated in a primarily European population, and the risk prediction may not be as accurate in other ethnic groups.

How does elevated Lp(a) influence a patient’s 10-year risk, and can we quantify it?

A recent observational study demonstrated that elevated Lp(a) is associated with long-term MACE in both patients with and without cardiovascular disease. Among patients with ASCVD, individuals in the 71st to 90th percentile group had a 21% increased hazard of MACE (adjusted HR: 1.21; P < 0.001), and among patients without ASCVD, individuals in the 91st to 100th Lp(a) percentile group had the highest relative risk with an adjusted HR of 1.93 (P < 0.001). In patients without ASCVD, there was a linear association between Lp(a) and CV events, whereas in patients with prior ASCVD, the association plateaued between 150-200 nmol/L.
Similarly, the 2019 consensus statement from HEART UK categorized the impact of CV risk associated with Lp(a) as minor, moderate, high, or very high based on the level of Lp(a). The table from this paper is a clinically useful tool to categorize risk from Lp(a).
The European Atherosclerosis Society has published a consensus statement on Lp(a) in the European Heart Journal which includes another useful table to adjust a patient’s 10-year risk based on the Lp(a) level(12).

How do we manage a young patient with elevated Lp(a)? Which patients might benefit from treatment with emerging Lp(a)-lowering therapies?

Given we do not yet have Lp(a) lowering therapies available for clinical use, the mainstay of management for patients with elevated Lp(a) is intensive risk factor management. Beyond the question of LDL lowering, we know that lifestyle change plays a big role in patients with elevated Lp(a) specifically. While it was previously thought that lifestyle has no impact on ASCVD risk associated with elevated Lp(a), in fact, it very much does. It doesn’t lower Lp(a) directly but following the AHA Life’s Simple 8 lowers the risk of Lp(a) by 66%.
There is some newer data suggesting that in patients with coronary artery disease, aggressive LDL lowering down to 50 can reduce the risk of Lp(a) by up to 50% (6). LDL of 50 mg/dL is a pretty aggressive treatment goal, which makes sense in very high-risk patients with existing CAD. However, we still need more data to guide LDL treatment goals in young patients(18).
Novel Lp(a)-lowering therapies such as olpasiran are currently in clinical trials (19). We await the data from these trials in order to understand which patients would benefit most from treatment.

ReferencesAllen N, Wilkins JT. The Urgent Need to Refocus Cardiovascular Disease Prevention Efforts on Young Adults. JAMA. 2023;329(11):886-887. doi:10.1001/jama.2023.2308

https://jamanetwork.com/journals/jama/fullarticle/2802264

Baber, Usman, Roxana Mehran, Samantha Sartori, Mikkel Malby Schoos, Henrik Sillesen, Pieter Muntendam, Mario J. Garcia, et al. 2015. “Prevalence, Impact, and Predictive Value of Detecting Subclinical Coronary and Carotid Atherosclerosis in Asymptomatic Adults: The BioImage Study.” Journal of the American College of Cardiology 65 (11): 1065–74.

https://pubmed.ncbi.nlm.nih.gov/25790876

Bhatia, H. S., Trainor, P., Carlisle, S., Tsai, M. Y., Criqui, M. H., DeFilippis, A., & Tsimikas, S. (2024). Aspirin and Cardiovascular Risk in Individuals With Elevated Lipoprotein (a): The Multi‐Ethnic Study of Atherosclerosis. Journal of the American Heart Association, 13(3), e033562.

https://www.ahajournals.org/doi/10.1161/JAHA.123.033562

Coll, B., Betriu, A., Feinstein, S. B., Valdivielso, J. M., Zamorano, J. L., & Fernandez, E. (2013). The role of carotid ultrasound in assessing carotid atherosclerosis in individuals at low-to-intermediate cardiovascular risk. Revista Española de Cardiología (English Edition), 66(12), 929-934.

https://pubmed.ncbi.nlm.nih.gov/24774105

Devesa, A, Ibanez, B, Malick, W. et al. Primary Prevention of Subclinical Atherosclerosis in Young Adults: JACC Review Topic of the Week. J Am Coll Cardiol. 2023 Nov, 82 (22) 2152–2162.

https://www.jacc.org/doi/10.1016/j.jacc.2023.09.817

Dykun, Iryna, Jürgen Kampf, Tienush Rassaf, and Amir A. Mahabadi. 2023. “Interaction between Elevated Lipoprotein(a) and LDL Cholesterol on Mortality Risk in Patients with Coronary Artery Disease.” European Journal of Preventive Cardiology 30 (13): e64–65.

https://academic.oup.com/eurjpc/article-abstract/30/13/e64/7065497?redirectedFrom=PDF

Elder P, Sharma G, Gulati M, Michos ED. Identification of female-specific risk enhancers throughout the lifespan of women to improve cardiovascular disease prevention. Am J Prev Cardiol. 2020;2:100028. Published 2020 Jun 6. doi:10.1016/j.ajpc.2020.100028

https://www.sciencedirect.com/science/article/pii/S2666667720300283

Glintborg D, Rubin KH, Nybo M, Abrahamsen B, Andersen M. Cardiovascular disease in a nationwide population of Danish women with polycystic ovary syndrome. Cardiovasc Diabetol. 2018;17(1):37. Published 2018 Mar 8. doi:10.1186/s12933-018-0680-5

https://pubmed.ncbi.nlm.nih.gov/29519249

Guan, W., Cao, J., Steffen, B. T., Post, W. S., Stein, J. H., Tattersall, M. C., … & Tsai, M. Y. (2015). Race is a key variable in assigning lipoprotein (a) cutoff values for coronary heart disease risk assessment: the Multi-Ethnic Study of Atherosclerosis. Arteriosclerosis, thrombosis, and vascular biology, 35(4), 996-1001.

https://pubmed.ncbi.nlm.nih.gov/25810300

Khan, S. S., Coresh, J., Pencina, M. J., Ndumele, C. E., Rangaswami, J., Chow, S. L., … & American Heart Association. (2023). Novel prediction equations for absolute risk assessment of total cardiovascular disease incorporating cardiovascular-kidney-metabolic health: a scientific statement from the American Heart Association. Circulation, 148(24), 1982-2004.

https://www.ahajournals.org/doi/10.1161/CIR.0000000000001191

Kolber MR, Scrimshaw C. Family history of cardiovascular disease. Can Fam Physician. 2014;60(11):1016.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4229162/#:~:text=Family%20history%20of%20CVD%20modifies,%25%20to%2075%25%20risk%20increase.

Kronenberg, Florian, Samia Mora, Erik S. G. Stroes, Brian A. Ference, Benoit J. Arsenault, Lars Berglund, Marc R. Dweck, et al. 2022. “Lipoprotein(a) in Atherosclerotic Cardiovascular Disease and Aortic Stenosis: A European Atherosclerosis Society Consensus Statement.” European Heart Journal 43 (39): 3925–46.

https://pubmed.ncbi.nlm.nih.gov/36036785

Kwapong YA, Boakye E, Khan SS, et al. Association of Depression and Poor Mental Health With Cardiovascular Disease and Suboptimal Cardiovascular Health Among Young Adults in the United States. J Am Heart Assoc. 2023;12(3):e028332. doi:10.1161/JAHA.122.028332

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9973664

Lau, F. D., & Giugliano, R. P. (2022). Lipoprotein (a) and its significance in cardiovascular disease: a review. Jama Cardiology.

https://pubmed.ncbi.nlm.nih.gov/35583875

Lee, J. J., Cook‐Wiens, G., Johnson, B. D., Braunstein, G. D., Berga, S. L., Stanczyk, F. Z., … & Shufelt, C. L. (2019). Age at menarche and risk of cardiovascular disease outcomes: findings from the National Heart Lung and Blood Institute‐sponsored Women’s Ischemia Syndrome Evaluation. Journal of the American Heart Association, 8(12), e012406.

https://pubmed.ncbi.nlm.nih.gov/31165670

Masana L, Zamora A, Plana N, et al. Incidence of Cardiovascular Disease in Patients with Familial Hypercholesterolemia Phenotype: Analysis of 5 Years Follow-Up of Real-World Data from More than 1.5 Million Patients. J Clin Med. 2019;8(7):1080. Published 2019 Jul 23. doi:10.3390/jcm8071080

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678686

Mendieta, Guiomar, Stuart Pocock, Virginia Mass, Andrea Moreno, Ruth Owen, Inés García-Lunar, Beatriz López-Melgar, et al. 2023. “Determinants of Progression and Regression of Subclinical Atherosclerosis Over 6 Years.” Journal of the American College of Cardiology 82 (22): 2069–83.

https://pubmed.ncbi.nlm.nih.gov/37993199

Navar, A. M., Fine, L. J., Ambrosius, W. T., Brown, A., Douglas, P. S., Johnson, K., … & Lewis, C. E. (2022). Earlier treatment in adults with high lifetime risk of cardiovascular diseases: what prevention trials are feasible and could change clinical practice? Report of a National Heart, Lung, and Blood Institute (NHLBI) workshop. American journal of preventive cardiology, 12, 100430.

https://pubmed.ncbi.nlm.nih.gov/36439649

O’Donoghue, M. L., Rosenson, R. S., Gencer, B., López, J. A. G., Lepor, N. E., Baum, S. J., … & Sabatine, M. S. (2022). Small interfering RNA to reduce lipoprotein (a) in cardiovascular disease. New England Journal of Medicine, 387(20), 1855-1864.

https://www.nejm.org/doi/full/10.1056/NEJMoa2211023

Orio Jr, F., Palomba, S., Cascella, T., De Simone, B., Di Biase, S., Russo, T., … & Colao, A. (2004). Early impairment of endothelial structure and function in young normal-weight women with polycystic ovary syndrome. The Journal of Clinical Endocrinology & Metabolism, 89(9), 4588-4593.

https://pubmed.ncbi.nlm.nih.gov/15356067

Osibogun O, Ogunmoroti O, Michos ED. Polycystic ovary syndrome and cardiometabolic risk: Opportunities for cardiovascular disease prevention. Trends Cardiovasc Med. 2020;30(7):399-404. doi:10.1016/j.tcm.2019.08.010

https://www.sciencedirect.com/science/article/pii/S1050173819301288?via%3Dihub

Pletcher MJ, Vittinghoff E, Thanataveerat A, Bibbins-Domingo K, Moran AE. Young Adult Exposure to Cardiovascular Risk Factors and Risk of Events Later in Life: The Framingham Offspring Study. PLoS One. 2016;11(5):e0154288. Published 2016 May 3. doi:10.1371/journal.pone.0154288

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4854462

Powell-Wiley, T. M., Poirier, P., Burke, L. E., Després, J. P., Gordon-Larsen, P., Lavie, C. J., … & American Heart Association Council on Lifestyle and Cardiometabolic Health; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; Council on Epidemiology and Prevention; and Stroke Council. (2021). Obesity and cardiovascular disease: a scientific statement from the American Heart Association. Circulation, 143(21), e984-e1010.

https://pubmed.ncbi.nlm.nih.gov/33882682

Safford, M. M., Gamboa, C. M., Durant, R. W., Brown, T. M., Glasser, S. P., Shikany, J. M., … & Muntner, P. (2015). Race–Sex Differences in the Management of Hyperlipidemia: The REasons for Geographic And Racial Differences in Stroke Study. American journal of preventive medicine, 48(5), 520-527.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422177

Talbott EO, Zborowski JV, Rager JR, Boudreaux MY, Edmundowicz DA, Guzick DS. Evidence for an association between metabolic cardiovascular syndrome and coronary and aortic calcification among women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2004;89(11):5454-5461. doi:10.1210/jc.2003-032237

https://academic.oup.com/jcem/article/89/11/5454/2844369?login=false

Wilson DP, Jacobson TA, Jones PH, et al. Use of Lipoprotein(a) in clinical practice: A biomarker whose time has come. A scientific statement from the National Lipid Association [published correction appears in J Clin Lipidol. 2022 Sep-Oct;16(5):e77-e95]. J Clin Lipidol. 2019;13(3):374-392. doi:10.1016/j.jacl.2019.04.010

https://www.lipidjournal.com/article/S1933-2874(22)00244-6/fulltext#seccesectitle0006

View Details

CardioNerds co-founder Dan Ambinder joins Dr. Lefan He, Dr. Sina Salehi Omran, and Dr. Neil Gupta from the University of Rochester Cardiovascular Disease Fellowship Program for a day sailing on Lake Ontario. Expert commentary is provided by Dr. Jeffrey Bruckel, and CV Fellowship Program Director Dr. Burr Hall shares insights on the University of Rochester fellowship. The episode audio was edited by CardioNerds intern Dr. Atefeh Ghorbanzadeh. They discuss the following case involving a patient with papillary muscle rupture.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.

CardioNerds Case Reports Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll

CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!

case MediaPearls – A Case of Papillary Muscle Rupture1. Most cases of papillary muscle rupture demonstrate only small areas of ischemia with preserved ventricular function, thus causing high shear force on the ischemic papillary muscle. 2. The posteromedial papillary muscle has a single blood supply from the posterior descending artery, while the anterolateral papillary muscle has a dual blood supply from the LAD and the circumflex. Therefore, the posteromedial papillary muscle is more vulnerable to ischemia and, hence, rupture. 3. A murmur may be absent in cases of papillary muscle rupture due to the rapid equalization of left atrial and left ventricular pressures caused by the acuteness of the severe MR. Papillary muscle rupture should always be on the differential for acute dyspnea when ACS is suspected. 4. While mostly associated with STEMIs, mechanical complications of acute myocardial infarctions can also occur after NSTEMIs. Always auscultate patients carefully after a myocardial infarction! 5. When evaluating patients with chest pain presenting with acute or rapidly progressive heart failure and a hypercontractile LVEF should raise suspicion for mechanical complications of MI. 6. Once a papillary muscle rupture is diagnosed, cardiac surgery should be immediately contacted. Temporizing measures prior to surgery include positive pressure ventilation, IV nitroglycerin/nitroprusside, and temporary mechanical circulatory support.

Notes – A Case of Papillary Muscle RuptureWhat is the clinical presentation of acute mitral regurgitation from papillary muscle rupture?

Patients typically present 3-5 days after a transmural infarct. Roughly half of these patients present with pulmonary edema that may quickly progress to cardiogenic shock.
Most cases are associated with STEMIs, but papillary muscle rupture is also possible with an NSTEMI.
The classic murmur is a mid-, late-, or holosystolic murmur. However, due to the rapid equalization of pressures between the LA and LV, many patients may not present with a murmur!

What is the pathophysiology of papillary muscle rupture?

The most common etiology is acute occlusion of the RCA causing infarct of the posteromedial papillary muscle, which then leads to a partial or complete tear 2-7 days later.
The posteromedial papillary muscle has a single blood supply from the posterior descending artery, while the anterolateral papillary muscle has a dual blood supply from the LAD and the circumflex. Therefore, the posteromedial papillary muscle is more vulnerable to ischemia and, hence, rupture.

What are the echocardiographic features of acute mitral regurgitation?

Typically, acute mitral regurgitation is caused by acute insult to the mitral valve or mitral valve apparatus. Examples include endocarditis with leaflet perforation, acute flail leaflet in the setting of mitral valve prolapse, and infarct-related papillary muscle rupture. Also, the LVEF can be hypercontractile.
Left ventricular and left atrial dimensions tend to be normal in acute MR as the heart has not had time to remodel. This also leads to rapid equalization of the LV-LA pressure during systole, blunting both the Doppler signal and the audible murmur which may under-appreciate acute severe mitral regurgitation.
Severe mitral regurgitation typically has a regurgitant volume of ≥60 mL or a regurgitant fraction of at least 50%. Additionally, an effective regurgitant orifice area of 0.4 cm^2 is typically indicative of severe mitral regurgitation. A complete multiparametric assessment is more important than any single parameter.
Systolic flow reversal in the pulmonary veins is pathognomonic for severe mitral regurgitation. This may not be apparent in all pulmonary veins if the MR is eccentric, as is usually the case of papillary muscle or acute leaflet flail.

How should acute mitral regurgitation due to papillary muscle rupture be managed?

Afterload reduction may help, but this may be limited by hypotension in the acute setting.
Temporary mechanical circulatory support may be necessary, often with an intra-aortic balloon pump which can be effective in improving forward flow.
The ultimate and definitive treatment is urgent cardiac surgery along with concomitant bypass grafting as appropriate. Transcatheter edge-to-edge repair may be considered sparingly when surgery is deemed very high risk.

What are the other mechanical complications of acute myocardial infarction?

Ventricular septal rupture typically occur 3-5 days after an infarct but there is a bimodal distribution. The presentation can vary from an isolated systolic murmur all the way to cardiogenic shock. Echocardiography will show a left to right shunt and right heart cath will show a step-up in oxygenation between the RA and PA as well as an elevated Qp/Qs. VSRs require urgent surgical or percutaneous repair.
Ventricular free wall rupture also occurs 3-5 days after an infarct and presents with elevated jugular venous distension, muffled heart sounds, and pulsus paradoxus. As blood irritates the pericardium, the patient’s ECG can show new ST-elevations. Management is emergent surgery.
Pseudoaneurysms present weeks to years after an infarct. These occur when a cardiac rupture is contained by pericardial adhesions and typically involve the inferior or lateral walls. Patients may be asymptomatic, but once diagnosed, pseudoaneurysms should be urgently repaired, lest they expand or become unstable.

References 1. Damluji AA, van Diepen S, Katz JN, Menon V, Tamis-Holland JE, Bakitas M, Cohen MG, Balsam LB, Chikwe J; on behalf of the American Heart Association Council on Clinical Cardiology; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular Surgery and Anesthesia; and Council on Cardiovascular and Stroke Nursing. Mechanical complications of acute myocardial infarction: a scientific statement from the American Heart Association. Circulation. 2021;144:e16–e35. doi: 10.1161/CIR.0000000000000985 2. Chang C et al. Transcatheter Edge-to-Edge Repair for Acute Mitral Regurgitation due to Postinfarction Papillary Muscle Rupture. JSCAI (2022) 100431. 3. Kilic A et al. Mitral Valve Surgery for Papillary Muscle Rupture: Outcomes in 1342 Patients From The Society of Thoracic Surgeons Database. The Annals of Thoracic Surgery Volume 110, Issue 6, December 2020, Pages 1975-1981 4. van Diepen S, Katz JN, Albert NM, Henry TD, Jacobs AK, Kapur NK, Kilic A, Menon V, Ohman EM, Sweitzer NK, Thiele H, Washam JB, Cohen MG; on behalf of the American Heart Association Council on Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; Council on Quality of Care and Outcomes Research; and Mission: Lifeline. Contemporary management of cardiogenic shock: a scientific statement from the American Heart Association. Circulation. 2017;136:e232–e268. doi: 10.1161/CIR.0000000000000525 5. Zoghbi, W. A., Adams, D., Bonow, R. O., Enriquez-Sarano, M., Foster, E., Grayburn, P. A., Hahn, R. T., Han, Y., Hung, J., Lang, R. M., Little, S. H., Shah, D. J., Shernan, S., Thavendiranathan, P., Thomas, J. D., & Weissman, N. J. (2017). Recommendations for noninvasive evaluation of native valvular regurgitation. Journal of the American Society of Echocardiography, 30(4), 303–371. https://doi.org/10.1016/j.echo.2017.01.007

View Details

CardioNerds cofounder, Amit Goyal joins Dr. Belal Suleiman, Dr. Nkiru Osude, and Dr. David Elliott from Duke University. They discuss a case of severe mitral paravalvular regurgitation complicated by hemolytic anemia. Expert commentary is provided by Dr. Andrew Wang. Audio editing by CardioNerds Academy Intern, student doctor Adriana Mares

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.

CardioNerds Case Reports Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll

CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!

Case Media – Severe Mitral Paravalvular Regurgitation Complicated by Hemolytic Anemia – Duke University

View Details

CardioNerds cofounders, Dan Ambinder joins Drs. Aishwarya Pastapur, Oyinkansola Osobamiro, and Rafik Issa from the University of Michigan for drinks in Ann Arbor. They discuss the following case of pericardial decompression syndrome. Expert commentary is provided by Dr. Brett Wanamaker. Notes were drafted by Dr. Aishwarya Pastapur and Dr. Rafik Issa. The episode audio was engineered by CardioNerds Intern student Dr. Atefeh Ghorbanzadeh.

A woman in her 50s with a past medical history of stage IV lung cancer (with metastatic involvement of the liver, bone, and brain), previous saddle pulmonary emboli, pericardial effusion, and malignant pleural effusions presents with dyspnea. She was found to have a pericardial effusion with tamponade physiology relieved by pericardiocentesis. We discuss the management of cardiac tamponade, indications for pericardiocentesis, how to monitor for post-pericardiocentesis complications, and what to keep on your differential diagnosis for decompensation after pericardiocentesis. We discuss the epidemiology, pathophysiology, diagnosis, and management of pericardial decompression syndrome.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.

CardioNerds Case Reports Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll

CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!

Case Media – Pericardial Decompression SyndromePearls – Pericardial Decompression Syndrome* Diminished heart sounds, a low-voltage EKG with electrical alternans, elevated jugular venous pressure/pulsations (JVP), and the presence of pulses paradoxes are important findings that could suggest tamponade. * McConnell sign is strongly concerning for right ventricular failure and pulmonary hypertension, potentially due to acute pulmonary embolism. * Mechanical thrombectomy for pulmonary embolism is not feasible if the emboli are diffusely scattered without a central lesion to target. * For patients who experience decompensation following pericardiocentesis, consider perforation, tamponade re-accumulation, or pericardial decompression syndrome (PDS). * When possible, avoid draining more than 1L of pericardial fluid at once to minimize the risk of PDS.

Notes – Pericardial Decompression SyndromeWhat is Pericardial Decompression Syndrome (PDS), and how does it present?

Pericardial decompression syndrome is a rare, life-threatening syndrome occurring in about 5-10% of cases with paradoxical worsening of hemodynamics after pericardial drainage.
- The clinical presentation ranges from pulmonary edema to cardiogenic shock to death, occurring a few hours to days after a successful pericardiocentesis.

What is the underlying mechanism for PDS?

The pathophysiology behind PDS is debated, but there are three proposed mechanisms:

Paradoxical Hemodynamic Derangement: After pericardiocentesis, venous return to the RV rapidly increases, resulting in RV expansion and potentially septal deviation towards the LV. Subsequently, the LV experiences decreased preload while still facing increased afterload as a compensatory response to obstructive shock, leading to decompensation.
1. Myocardial Ischemia: Increased intrapericardial pressure may impair coronary perfusion, leading to myocardial ischemia. Upon pericardiocentesis, there is myocardial stunning with increased demand due to increased venous return and cardiac output
2. Sympathetic Withdrawal: Withdrawal of sympathetic activation after drainage of pericardial fluid can trigger cardiovascular collapse

What are the risk factors for developing PDS, and how can we mitigate those risks for prevention?

Generally, patients with long-standing pericardial effusion with chronic compression of the heart, such as those with malignant pericardial effusions, are more vulnerable to developing PDS after pericardiocentesis.
- Additionally, rapid fluid removal increases the risk. In terms of prevention, removing fluid to normalize CVP and MAP and letting the rest of the fluid drain slowly may mitigate the risk.

How do we manage a patient with PDS?

The management of PDS is supportive, focusing on addressing hemodynamic and respiratory derangements.
- The underlying pathophysiology should resolve in 24-48 hours.

What is the prevalence and prognosis of PDS?

PDS affects 5-10% of pericardiocentesis procedures, although the exact frequency is difficult to ascertain.
- It is a self-resolving process as the heart re-adapts to the new hemodynamics.
- However, during the episode of PDS, mortality can be as high as 30% per some studies.

References – Pericardial Decompression Syndrome1. Schnur M. Understanding Pulsus Paradoxus. Accessed February 27, 2024. https://nursingcenter.com/ncblog/august-2021/understanding-pulsus-paradoxus 2. Carlini’ ’Caterina Chiara De, Maggiolini’ ’Stefano. Pericardiocentesis in cardiac tamponade: indications and practical aspects. Accessed February 27, 2024. https://www.escardio.org/Journals/E-Journal-of-Cardiology-Practice/Volume-15/Pericardiocentesis-in-cardiac-tamponade-indications-and-practical-aspects 3. Angouras DC, Dosios T. Pericardial Decompression Syndrome: A Term for a Well-Defined but Rather Underreported Complication of Pericardial Drainage. The Annals of Thoracic Surgery. 2010;89(5):1702-1703. doi:10.1016/j.athoracsur.2009.11.073 4. Imazio M. Pericardial decompression syndrome: A rare but potentially fatal complication of pericardial drainage to be recognized and prevented. European Heart Journal Acute Cardiovascular Care. 2015;4(2):121-123. doi:10.1177/2048872614557771 5. Prabhakar Y, Goyal A, Khalid N, et al. Pericardial decompression syndrome: A comprehensive review. World Journal of Cardiology. 2019;11(12):282-291. doi:10.4330/wjc.v11.i12.282 6. Sobieski C, Herner M, Goyal N, et al. Pericardial Decompression Syndrome After Drainage of Chronic Pericardial Effusions. JACC: Case Reports. 2022;4(22):1515-1521. doi:10.1016/j.jaccas.2022.08.023 7. Chhabra L. Pericardial Decompression Syndrome. American College of Cardiology. Accessed February 27, 2024. https://www.acc.org/Latest-in-Cardiology/Articles/2020/04/13/09/05/http%3a%2f%2fwww.acc.org%2fLatest-in-Cardiology%2fArticles%2f2020%2f04%2f13%2f09%2f05%2fPericardial-Decompression-Syndrome 8. Pradhan R, Okabe T, Yoshida K, Angouras DC, DeCaro MV, Marhefka GD. Patient characteristics and predictors of mortality associated with pericardial decompression syndrome: a comprehensive analysis of published cases. European Heart Journal Acute Cardiovascular Care. 2015;4(2):113-120. doi:10.1177/2048872614547975 9. Amro A, Mansoor K, Amro M, et al. A Comprehensive Systemic Literature Review of Pericardial Decompression Syndrome: Often Unrecognized and Potentially Fatal Syndrome. Current Cardiology Reviews. 17(1):101-110.

View Details

This case report explores the intricacies of familial hypercholesterolemia (FH), delving into its genetic basis, atherosclerotic cascade, and early-onset cardiovascular complications. It examines established diagnostic criteria and emphasizes personalized management, including statins, novel therapies, and lifestyle modifications.

CardioNerds cofounders (Drs. Amit Goyal and Danial Ambinder) join Dr. Irfan Shafi, Dr. Preeya Prakash, and Dr. Rebecca Theisen from the Wayne State University/DMC and Central Michigan University at Campus Martius in Downtown Detroit for some holiday ice-skating! They discuss an interesting pediatric case (see case synopsis below). Dr. Luis C Afonso provides the Expert CardioNerd Perspectives & Review segment for this episode. Audio editing by CardioNerds academy intern, Pace Wetstein.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.

CardioNerds Case Reports Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll

CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!

Case SynopsisFH, a 9-year-old female with no previous medical history, recently moved back to the US from Iraq. She presented to establish care and discuss new-onset chest pain and dyspnea. A systolic ejection murmur was noted during her initial visit to the pediatrician, prompting cholesterol testing and a cardiology referral. Testing revealed, alarming cholesterol levels (Total Cholesterol: 802 mg/dL, LDL: 731 mg/dL, Triglycerides: 123 mg/dL) prompted concern for cardiac involvement.

Due to persistent symptoms, FH was transferred to Children’s Hospital of Michigan. Despite normal findings on EKG and chest x-ray, a 2/6 systolic murmur was noted. She was discharged with a cardiology clinic follow-up.

However, two days later, FH experienced severe chest pain at rest, sweating, and difficulty breathing. She was transported to Children’s Hospital again, and her troponin level measured 3000, and her total cholesterol was 695 mg/dL. An echocardiogram revealed valvar and supravalvar aortic stenosis, necessitating collaboration between Pediatric and Adult cardiology teams.

CTA thorax revealed severe supravalvular stenosis, a hypoplastic right coronary artery, and significant coronary artery obstructions. Diagnostic cardiac catheterization confirmed severe aortic stenosis and coronary artery disease, leading to the decision for surgical intervention.

FH underwent the Ross operation, left main coronary artery augmentation, and right coronary artery reimplantation. Intraoperatively, atherosclerotic plaques were observed in multiple cardiac structures.

FH’s recovery was uneventful, discharged on a regimen including Atorvastatin, Ezetimibe, evolocumab, and antiplatelet therapy. Persistent high LDL levels required regular plasmapheresis. Plans for evaluations in Genetics, Lipid Clinic, Endocrine, and Gastroenterology were made, potentially leading to a liver transplant assessment. Given the severity of her condition, a heart/liver transplant might be considered in the future.

Conclusion:

This case of FH highlights the complex presentation of severe aortic stenosis and coronary artery disease in a pediatric patient. Urgent diagnosis, interdisciplinary collaboration, and aggressive management were crucial. The case underscores the importance of comprehensive care for pediatric patients with rare cardiac conditions, emphasizing collaboration between specialties for optimal outcomes and long-term well-being.

Case MediaPearls – Familial Hypercholesterolemia * Mutations in LDLR, ApoB, or PCSK9 genes disrupt LDL-C clearance, leading to a cascade of events culminating in accelerated atherosclerosis and early-onset cardiovascular complications (e.g., CAD, aortic stenosis, PAD, stroke). * Diagnosis of familial hypercholesterolemia relies on a combination of clinical features (xanthomas, corneal arcus, high LDL-C), family history, and genetic testing guided by established criteria like DCLN or NLA recommendations. * Supravalvular aortic stenosis, while common in many congenital cases, should raise suspicion of homozygous familial hypercholesterolemia in the setting of extensively elevated LDL and unexpected coronary artery disease. * A multidisciplinary approach, including involvement of pediatric and adult cardiology teams, lipid specialists and cardiothoracic surgeons, should be involved in the overall evaluation and management of these patients, both at initiation of diagnosis, and in an outpatient setting. * In patients with FH, it is important to delineate between homozygous and heterozygous manifestations, as this can have extensive implications on treatment, management and the overall clinical prognosis and further disease sequelae that the patient may experience.

References – Familial Hypercholesterolemia 1. Shah, N. (2020). Familial hypercholesterolemia: Early diagnosis and treatment is key for cardiovascular prevention.Cleveland Clinic Journal of Medicine, 87(5), 109-120. https://pubmed.ncbi.nlm.nih.gov/23469913/ 2. Turgeon, R. D., Barry, A. R., & Pearson, G. J. (2023). Familial hypercholesterolemia: Review of diagnosis,screening, and treatment. American Journal of Health-System Pharmacy, 80(11), 917-929.https://pubmed.ncbi.nlm.nih.gov/26796832/ 3. Collins, R. T. (2018). Cardiovascular disease in Williams syndrome. Current Opinion in Pediatrics, 30(5), 609-615. https://www.ncbi.nlm.nih.gov/books/NBK544278/ 4. Collins, R. T., Kaplan, P., Somes, G. W., & Rome, J. J. (2010). Long-term outcomes of patients with cardiovascular abnormalities and Williams syndrome. American Journal of Cardiology, 105(6), 874-878.https://pubmed.ncbi.nlm.nih.gov/30045083/ 5. Honjo, R. S., Monteleone, V. F., Aiello, V. D., Wagenfuhr, J., Issa, V. S., Pomerantzeff, P. M. A., Furusawa, E. A.,Zanardo, E. A., Kulikowski, L. D., Bertola, D. R., & Kim, C. A. (2022). Cardiovascular findings in Williams-Beuren Syndrome: Experience of a single center with 127 cases. American Journal of Medical Genetics. Part A,188(3), 676-682. https://www.ncbi.nlm.nih.gov/books/NBK544278/ 6. Pham, P. P., Moller, J. H., Hills, C., Larson, V., & Pyles, L. (2009). Cardiac catheterization and operative outcomes from a multicenter consortium for children with Williams syndrome. Pediatric Cardiology, 30(1), 9-14.https://pubmed.ncbi.nlm.nih.gov/19052807/ 7. Olsen, M., Fahy, C. J., Costi, D. A., Kelly, A. J., & Burgoyne, L. L. (2014). Anaesthesia-related haemodynamic complications in Williams syndrome patients: A review of one institution’s experience. Anaesthesia and Intensive Care, 42(6), 619-624. https://pubmed.ncbi.nlm.nih.gov/25233176/ 8. Harada-Shiba, M., Arai, H., Ishigaki, Y., Ishibashi, S., Okamura, T., Ogura, M., Dobashi, K., Nohara, A., Bujo, H.,Miyauchi, K., Yamashita, S., & Yokote, K. (2018). Guidelines for diagnosis and treatment of familial hypercholesterolemia 2017. Journal of Atherosclerosis and Thrombosis, 25(8), 751-770.https://pubmed.ncbi.nlm.nih.gov/29877295/ 9. Alnouri, F., & Santos, R. D. (2022). New trends and therapies for familial hypercholesterolemia. Journal of Clinical Medicine, 11(22), 6638. https://pubmed.ncbi.nlm.nih.gov/36431115/

View Details

CardioNerds (Dr. Jessie Holtzman, Chair for the CardioNerds Women’s Heart Disease Committee, and Dr. Naima Maqsood, Chair for the CardioNerds Electrophysiology Committee) join Dr. Ritika Gadodia, Dr. Namratha Meda, and Dr. Tsion Aberra from the Medstar Washington Hospital Center/Georgetown University Program for the National Cherry Blossom Festival. They discuss involving a patient with Chagas cardiomyopathy. Dr. Rachel Marcus provides the Expert CardioNerd Perspectives & Review segment for this episode. Episode audio was edited by Dr. Diane Masket.

A 79-year-old male with a history of cardiomyopathy presented with recurrent ventricular tachycardia (VT) post-CRT-D placement. On arrival, the patient was in cardiogenic shock. Initial treatment with amiodarone and milrinone failed, necessitating the addition of mexiletine. Imaging was suggestive of a left ventricular ejection fraction of 20-25% with severe global hypokinesis. Prior coronary angiogram had shown nonobstructive coronary artery disease. Further non-ischemic cardiomyopathy evaluation was unrevealing. Given his El Salvadorian origins, Chagas serology results revealed Chronic Chagas Cardiomyopathy (CCM) confirmed by CDC testing. This case underscores the importance of suspecting CCM in patients with risk factors. An early diagnosis of CCM, can prevent catastrophic events (heart blocks, ventricular arrhythmias, thromboembolic events).

In summary, this case takes the learner through the journey of a patient with non-ischemic cardiomyopathy and emphasizes the importance of approaching it with a wide range of differentials.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.

CardioNerds Case Reports Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll

CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!

Case MediaPearls – Chronic Chagas Cardiomyopathy with Recurrent Ventricular Tachyarrhythmia1. Always consider Chagas cardiomyopathy when you have a patient from Latin America who presents with non-ischemic cardiomyopathy. 2. Chagas cardiomyopathy is associated with an unfavorable prognosis and serves as an independent predictor of mortality. 3. Chagas cardiomyopathy is arrhythmogenic and requires consideration for ICD and, when appropriate, catheter based ventricular tachycardia ablation. 4. It is crucial to treat patients with nifurtimox and benznidazole when appropriate. 5. Provide screening for first-degree family members or close relatives who may have lived in the same environment.

Show Notes – Chronic Chagas Cardiomyopathy with Recurrent Ventricular TachyarrhythmiaWhat is the disease progression in Chagas disease5?

Acute Stage:
- Initial infection occurs through contact with infected triatomine bug feces or contaminated blood products.
- Symptoms may be mild or absent but can include fever, fatigue, body aches, and swelling at the injection site (chagoma).
- Parasitemia is high during this stage.
Intermediate/Indeterminate Stage:
- The infection becomes chronic if left untreated.
- Many individuals enter this stage with no noticeable symptoms.
- Parasitemia levels decrease, but the parasite remains in the body, mainly in muscle and cardiac tissue.
- This stage can last for years to decades.
Chronic Stage:
- Some individuals will remain asymptomatic throughout their lives.
- Cardiac complications (chronic Chagas cardiomyopathy) can lead to arrhythmias, congestive heart failure, and sudden death.
- Digestive complications can result in enlarged esophagus (megaesophagus) and colon (megacolon), leading to difficulties in swallowing and digestion.

When do we suspect, and who do we screen, for Chagas disease?

The seroprevalence of CCM in the USA is as high as 19%16. Among patients with LVEF<50%, the rate of positive serology was 28%. Similarly, the seropositivity among patients who reported recognizing the reduviid bug was 31%.
Individuals who have lived in endemic countries of Mexico, Central and South America, excluding the Caribbean islands.
T. cruzi seroprevalence is highest in Bolivia, Argentina, Paraguay, Ecuador, El Salvador, and Guatemala6.
Close relatives and those born to women from endemic countries7.
Persons with a history of bite/exposure to the vector responsible for transmission.
EKG abnormalities suggestive of infection even in the absence of symptoms.
TTE changes: regional wall motion abnormalities (particularly basal inferolateral, apical aneurysm)4

What diagnostic tests can confirm the diagnosis of chronic Chagas cardiomyopathy?

Serologic testing: no available assay has sufficient sensitivity and specificity to be used alone. Two serologic tests based on different antigens and/or techniques (e.g., ELISA and IFA) are used in parallel to increase the accuracy of the diagnosis8.
EKG: RBBB, LAFB, AV block, atrial fibrillation, ventricular tachycardias
TTE: dilated cardiomyopathy, reduced ejection fracture, regional wall motion abnormalities, left ventricular apical aneurysm
Cardiac MRI: myocardial fibrosis is a striking feature of CCM and LGE is used to detect and qualify the extent. Myocardial fibrosis also plays a role in risk stratification of CCM9.

What are the indications for treatment of Chagas disease?

Acute phase.
Early chronic phase, including women of childbearing age.
Reactivated infection (e.g., after immunosuppression).
Adults <50 years of age who do not have advanced cardiomyopathy (stage B1)10.
In all other cases, the potential benefit of medication in delaying the development of Chagas disease should be weighed against potential adverse reactions- benznidazole and nifurtimox should not be taken by pregnant women or people with kidney or liver failure.

What are the benefits of screening and early diagnosis?

Effective treatment, particularly in the acute phase.
The BENEFIT trial showed that Trypanocidal therapy with benznidazole in patients with CCM did not significantly reduce cardiac deterioration11.
Screening of family members/friends who grew up in the same environment.
Reduction of transmission due to blood transfusions and congenital transmission.
Early initiation of GDMT (guideline-directed medical therapy) for clinical heart failure 2/2 CCM.
Ongoing surveillance for cardiomyopathy can prevent catastrophic events (heart blocks, ventricular arrhythmias, thromboembolic events).
Cost effectiveness: Early diagnosis and treatment may reduce healthcare costs compared to the treatment of complications that arise from the chronic phase of the disease. Early diagnosis may also reduce the number of endomyocardial biopsies.

How is the management of VT unique in chronic Chagas cardiomyopathy?

In comparison to cardiomyopathies of other etiologies, CCM is associated with a higher risk of life-threatening ventricular arrhythmias and an unfavorable prognosis12,14.
Per ESC guidelines, the greatest benefit of ICD in CCM is in patients with an LVEF ≤40%15.
Per Gali et al, most patients with an ICD received appropriate ICD shocks/therapies regardless of their LV systolic function13.
Ablation of VT requires extensive mapping because multiple discrete circuits are typically present. The most common site of origin is the LV basal inferolateral wall. However, 1/3rd of the foci is located on the epicardial surface. This necessitates epicardial mapping to achieve successful ablation6.

References – Chronic Chagas Cardiomyopathy with Recurrent Ventricular Tachyarrhythmia1. Ghzally Y, Mahajan K. Implantable Defibrillator. In: StatPearls. StatPearls Publishing; 2023. Accessed October 7, 2023. http://www.ncbi.nlm.nih.gov/books/NBK459196/ 2. Vrettos A, Panoulas V. Diagnosing STEMI in the presence of paced rhythm: dispelling the myth of the ‘uninterpretable paced ECG.’ BMJ Case Rep. 2021;14(7):e242546. doi:10.1136/bcr-2021-242546 3. 3. Bozkurt B, Colvin M, Cook J, et al. Current Diagnostic and Treatment Strategies for Specific Dilated Cardiomyopathies: A Scientific Statement From the American Heart Association. Circulation. 2016;134(23). doi:10.1161/CIR.0000000000000455 4. Forsyth CJ, Manne-Goehler J, Bern C, et al. Recommendations for Screening and Diagnosis of Chagas Disease in the United States. The Journal of Infectious Diseases. 2022;225(9):1601-1610. doi:10.1093/infdis/jiab513 5. CDC – Chagas Disease – Disease. Accessed October 7, 2023. https://www.cdc.gov/parasites/chagas/disease.html 6. Chagas Cardiomyopathy: An Update of Current Clinical Knowledge and Management: A Scientific Statement From the American Heart Association | Circulation. Accessed October 7, 2023. https://www.ahajournals.org/doi/10.1161/CIR.0000000000000599 7. Montgomery SP, Parise ME, Dotson EM, Bialek SR. What Do We Know About Chagas Disease in the United States? The American Journal of Tropical Medicine and Hygiene. 2016;95(6):1225-1227. doi:10.4269/ajtmh.16-0213 8. Malone CJ. A Rapid Review on the Efficacy and Safety. Pan American Health Organization (PAHO) and the World Health Organization (WHO); 2021. 9. Nunes MCP, Badano LP, Marin-Neto JA, et al. Multimodality imaging evaluation of Chagas disease: an expert consensus of Brazilian Cardiovascular Imaging Department (DIC) and the European Association of Cardiovascular Imaging (EACVI). European Heart Journal – Cardiovascular Imaging. 2018;19(4):459-460n. doi:10.1093/ehjci/jex154 10. 10. Prevention CC for DC and. CDC – Chagas Disease – Resources for Health Professionals – Antiparasitic Treatment. Published April 11, 2022. Accessed October 7, 2023. https://www.cdc.gov/parasites/chagas/health_professionals/tx.html 11. 11. Morillo CA, Marin-Neto JA, Avezum A, et al. Randomized Trial of Benznidazole for Chronic Chagas’ Cardiomyopathy. N Engl J Med. 2015;373(14):1295-1306. doi:10.1056/NEJMoa1507574 12. 12. Probability of Occurrence of Life‐Threatening Ventricular Arrhythmias in Chagas’ Disease versus Non‐Chagas’ Disease – FILHO – 2000 – Pacing and Clinical Electrophysiology – Wiley Online Library. Accessed October 7, 2023. https://onlinelibrary.wiley.com/doi/10.1111/j.1540-8159.2000.tb07058.x 13. 13. Implantable cardioverter-defibrillators for treatment of sustained ventricular arrhythmias in patients with Chagas’ heart disease: comparison with a control group treated with amiodarone alone | EP Europace | Oxford Academic. Accessed October 7, 2023. https://academic.oup.com/europace/article/16/5/674/484618?login=fals 14. 14. Barbosa MPT, Da Costa Rocha MO, De Oliveira AB, Lombardi F, Ribeiro ALP. Efficacy and safety of implantable cardioverter-defibrillators in patients with Chagas disease. EP Europace. 2013;15(7):957-962. doi:10.1093/europace/eut011 15. 15. Requena-Méndez A, Aldasoro E, De Lazzari E, et al. Prevalence of Chagas Disease in Latin-American Migrants Living in Europe: A Systematic Review and Meta-analysis. Rodrigues MM, ed. PLoS Negl Trop Dis. 2015;9(2):e0003540. doi:10.1371/journal.pntd.0003540 16. 16. Gadodia R, Kerai A, Aberra T, et al. SEROPREVALENCE OF CHAGAS CARDIOMYOPATHY IN LATIN AMERICAN IMMIGRANTS IN THE WASHINGTON DC METRO AREA. Journal of the American College of Cardiology. 2023;81(8):318. doi:10.1016/S0735-1097(23)00762-3

View Details

CardioNerds Dr. Josh Saef and Dr. Tommy Das join Dr. Omkar Betageri, Dr. Andrew Geissler, Dr. Philip Lacombe, and Dr. Cashel O’Brien from the Maine Medical Center in Portland, Maine to enjoy an afternoon by the famous Portland headlight. They discuss a case of a patient who presents with obstructive cardiogenic shock. Dr. Bram Geller and Dr. Jon Donnelly provide the Expert CardioNerd Perspectives & Review segment for this episode. Dr. Maxwell Afari, the Maine Medical Center cardiology fellowship program director highlights the fellowship program. Audio editing by CardioNerds Academy Intern, student doctor Tina Reddy.

This is the case of a 42 year-old woman born with complicated Tetralogy of Fallot repair culminating in a 29mm Edwards Sapiens (ES) S3 valve placement within a pulmonary homograft for graft failure who was admitted to the cardiac ICU for progressive cardiogenic shock requiring vasopressors and inotropic support. Initial workup showed lactic acidosis, acute kidney injury, elevated NT-proBNP, and negative blood cultures. TTE showed at least moderate biventricular systolic dysfunction. She was placed on furosemide infusion, blood cultures were drawn and empiric antibiotics initiated. Right heart catheterization demonstrated elevated right sided filling pressures, blunted PA pressures with low PCWP, low cardiac index, and low pulmonary artery pulsatility index. Intracardiac echocardiography (ICE) showed a large mass within the ES valve apparatus causing restrictive valve motion with a low gradient across the pulmonic valve in the setting of poor RV function. Angiography revealed a large filling defect and balloon valvuloplasty was performed with immediate hemodynamic improvement. Blood cultures remained negative, she was gradually weaned off of inotropic and vasopressor support, and discharged. Despite empiric treatment for culture negative endocarditis and ongoing anticoagulation, she was readmitted for recurrent shock one month later at which time the pulmonic mass was revisualized on ICE. A valve-in-valve transcatheter pulmonary valve (29mm ES S3) was placed to compress what was likely pannus, with an excellent hemodynamic result and no visible mass on ICE.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.

CardioNerds Case Reports Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll

CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!

Case MediaPearls – Obstructive Cardiogenic ShocK1. Tetralogy of Fallot is the most common cyanotic defect and can lead to long term complications after surgical repair including chronic pulmonary insufficiency, RV dysfunction, residual RVOT obstruction and branch pulmonary artery stenoses. 2. Chronic RV failure may be more indicative of a structural defect and therefore require interventional or surgical management. 3. Valve thrombosis, infective endocarditis and obstructive pannus formation should be considered in the differential of a patient with obstructive shock with a prosthetic valve. 4. Bioprosthetic pulmonic valve obstruction may be effectively managed with balloon valvuloplasty in patients who present in acute extremis but TCPV will likely provide a more lasting result. 5. While valvular gradients are typically assessed via echocardiography, invasive hemodynamics can serve as a critical adjunctive tool in its characterization.

Show Notes – Obstructive Cardiogenic ShocKNotes were drafted by Drs. Omkar Betageri, Philip Lacombe, Cashel O’Brien, and Andrew Geissler.

What are the common therapies and management for Tetralogy of Fallot?

Tetralogy of Fallot is the most common cyanotic defect in children beyond the age of one year
Anatomic Abnormalities: Anterior and Superior deviation of the conal septum creating a SubAo VSD and encroachment on the RVOT. The Ao follows the conal septum anteriorly to override the VSD and RVH is a consequence of an RV chamber that is at systemic pressure.
The need for medical intervention is dependent on the degree of RVOT obstruction, pulmonary regurgitation, and/or peripheral pulmonary artery obstruction.
Many patients are minimally cyanotic in newborn period and clinical follow-up with elective surgical correction between 3 months and 6 months of age is a preferred approach.
Total surgical correction typically involves placing patients on cardiopulmonary bypass, relieving right sided obstruction (sometimes utilizing trans-annular patch), and connecting left ventricular blood flow with aortic, with VSD closure.
Hypercyanotic “Tet” spells can occur in the neonatal period when there is an acute muscular spasm in the RVOT, fall in SVR or increase in PVR to facilitate right to left shunting at the VSD. It is managed medically with a stepwise approach placing the patient in knee-chest position, administer oxygen, IV fluids and a dose of narcotics, IV beta blocker, IV phenylephrine, ECMO
Long term complications post-surgical repair include chronic pulmonary insufficiency, RV dysfunction, residual RVOT obstruction, peripheral PA obstruction, aortic root dilation, endocarditis, arrhythmias, and sudden cardiac death.

How should we approach the management of chronic right ventricular failure?

Briefly, RV failure can result in chamber dilatation, bowing of the interventricular septum to the LV, impairing LV stroke volume, and ultimately causing hemodynamic collapse. This is the frequently referenced “RV spiral”
The primary step in management of RV cardiogenic shock should be to identify and reverse the primary etiology
While patients in acute RV failure may respond well to therapies such as fluid resuscitation, inotropes and vasopressors, or inhaled nitric oxide, patients with chronic RV failure (such as in our case) are more likely to have structural defects driving their decompensation
Chronic RV failure can result from etiologies related to preload (ASD, tricuspid and pulmonic insufficiency), afterload (pulmonic or pulmonary artery stenosis, pulmonary vascular disease, and left heart disease) or contractility (RV myopathy or ARVC).

VSD is not volume loading to RV and Eisenmenger’s would be a pressure load b/c of increased PVR and actually volume unload the RV with R to L VSD shunting. * In acute stabilization, it is reasonable to utilize methods used to manage acute RV failure, with the understanding that interventional/surgical management will ultimately be necessary for definitive management

When should bioprosthetic valve obstruction be suspected and what is the differential for this? What is the initial workup?

Obstruction should be suspected in any patient with a history of prosthetic valve placement who presents with a new murmur, new history of exercise intolerance, syncope/presyncope, or evidence of heart failure on exam.
Differential diagnosis includes pannus ingrowth, thrombus, and vegetation. The anterior location of a surgically replaced RVOT/PV also makes it susceptible to compressive forces from the chest wall anteriorly and dilated Ao posteriorly, particularly in growing children. For bioprosthetic valves pannus is more common than acute thrombosis. Age of the valve, risk factors for infection, and anticoagulation status are clinical signs that may help differentiate.
Diagnosis is typically made by transthoracic echocardiology (TTE): Increased gradients across the PV, RV hypertrophy, dilatation or dysfunction, increasing TR volume with elevated gradients from RV to RA.
Cardiac CT or CMRI can also be helpful in characterizing the stenosis (discreet or long-segment, singular or stenoses in series).
Invasive hemodynamic assessment in the catheterization laboratory can be especially helpful to more specifically characterize the degree and location of the obstruction as well as perform intervention (balloon, stent placement, TCPV) to relieve the obstruction. It is not uncommon that distal pulmonary artery stenting is required at the time of ballooning of the valve or valve-in-valve TCPVR.
Lab testing sometimes performed includes INR, hemoglobin level, hemolysis labs, NT-BNP. If acute thrombosis of the bioprosthetic valve is diagnosed, a hypercoaguable work-up to include familial thrombophilia should be performed
FDG PET may be an adjunctive tool to help evaluate for prosthetic valve endocarditis by detection of acute inflammation.

What are the indications for management of valve obstruction? What are the primary management strategies?

As previously discussed the differential diagnosis of bioprosthetic valve obstruction includes BPVT, pannus, and vegetation. Valve intervention is indicated for symptomatic severe stenosis and treatment strategy depends on the underlying cause.
- BPVT: If stable, can trial anticoagulation therapy. If unstable immediate therapy is required which requires surgery or fibrinolytics.
- Pannus: Severe stenosis caused by soft tissue overgrowth with degeneration and calcium requires stenting open the obstructive valve in the catheterization laboratory followed by a valve-in-valve TCPV placement. It is increasingly rare that an obstructed bioprosthetic PV cannot be managed in this fashion and surgical PVR is needed. Medical therapy is ineffective in treating the underlying cause although can treat consequences from heart failure.
- Vegetation: Endocarditis with vegetation causing severe stenosis is usually treated with surgical intervention. Decisions regarding surgical indications for endocarditis are complex and a trial of medical therapy is reasonable in less severe disease.
For native pulmonic valve obstruction many patients are amenable to balloon valvuloplasty and recurrent stenosis is rare. Patients are usually left with some degree of pulmonic insufficiency. Balloon valvuloplasty alone is rarely an effective long-term solution for bioprosthetic valve stenosis.

What is the role of right heart catheterization in valvular obstructive shock?

Typically valve gradients are obtained by TTE in a parasternal short axis view but hemodynamic gradients measured in the cath lab can provide supportive information
Additionally right heart catheterization can assist in the characterization of the degree of shock (through calculation of cardiac indices, pulmonary artery pulmonary index, and cardiac power output).
In pulmonary stenosis, the narrowed valve creates a pressure differential between the RV and PA such that a peak pressure difference RVSP-PASP >64 mmHg is considered severe or mean difference of >35 mmHg
As in this case, catheterization also allows for therapeutic intervention either through balloon valvuloplasty or TCPVP.

References – Obstructive Cardiogenic ShocK1. Egbe AC, Pislaru SV, Pellikka PA, et al. Bioprosthetic Valve Thrombosis Versus Structural Failure: Clinical and Echocardiographic Predictors. J Am Coll Cardiol. 2015;66(21):2285-2294. doi:10.1016/j.jacc.2015.09.022 2. McElhinney DB, Zhang Y, Levi DS, et al. Reintervention and Survival After Transcatheter Pulmonary Valve Replacement. J Am Coll Cardiol. 2022;79(1):18-32. doi:10.1016/j.jacc.2021.10.031 3. Nishimura RA, Carabello BA. Hemodynamics in the cardiac catheterization laboratory of the 21st century. Circulation. 2012;125(17):2138-2150. doi:10.1161/CIRCULATIONAHA.111.060319 4. Otto, Catherine M et al. “2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.” Circulation vol. 143,5 (2021): e35-e71. doi:10.1161/CIR.0000000000000932 5. Rao PS. Management of Congenital Heart Disease: State of the Art-Part II-Cyanotic Heart Defects. Children (Basel). 2019;6(4):54. Published 2019 Apr 4. doi:10.3390/children6040054 6. Stout, Karen K et al. “2018 AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.” Journal of the American College of Cardiology vol. 73,12 (2019): 1494-1563. doi:10.1016/j.jacc.2018.08.1028 7. VARC-3 WRITING COMMITTEE et al. “Valve Academic Research Consortium 3: updated endpoint definitions for aortic valve clinical research.” European heart journal vol. 42,19 (2021): 1825-1857. doi:10.1093/eurheartj/ehaa799 8. Arrigo, M., Huber, L. C., Winnik, S., Mikulicic, F., Guidetti, F., Frank, M., Flammer, A. J., & Ruschitzka, F. (2019). Right ventricular failure: Pathophysiology, diagnosis and treatment. Cardiac Failure Review, 5(3), 140–146. https://doi.org/10.15420/cfr.2019.15.2 9. Kanwar, M. K., Everett, K. D., Gulati, G., Brener, M. I., & Kapur, N. K. (2022). Epidemiology and management of right ventricular-predominant heart failure and shock in the cardiac intensive care unit. European Heart Journal. Acute Cardiovascular Care, 11(7), 584–594. https://doi.org/10.1093/ehjacc/zuac063

View Details

CardioNerds, Dr. Richard Ferraro and Dr. Dan ambinder join Dr. Li Pang, Dr. Emily Hendricks, and Dr. Bei Jiang from West Virginia University to discuss the following case that features apical obliteration with biventricular thrombus. Dr. Christopher Bianco provides the Expert CardioNerd Perspectives & Review (E-CPR) for this episode. Audio editing by CardioNerds Academy Intern, student doctor Tina Reddy.

A 37-year-old Caucasian man with a history of tobacco smoking and hypertension who presented with chest pain and elevated troponin was admitted for non-ST elevation myocardial infarction (NSTEMI). Ischemic evaluation with an invasive coronary angiogram was negative. He was treated as NSTEMI and scheduled for outpatient cardiac MRI (CMR). The patient came back 2 months later with right arm weakness and confusion and was found to have an embolic stroke. Labs showed positive troponin with a flat trend and hypereosinophilia. Transthoracic echocardiogram (TTE) showed obliteration of LV and RV apex with thrombus and reduced LV systolic function. CMR was consistent with myocarditis with biventricular thrombus. The patient was started on corticosteroids and warfarin. Hypereosinophilia workup was positive for PDGFRA alpha rearrangement. He was diagnosed with primary hypereosinophila syndrome. Imatinib was initiated. The patient was followed up with the hematology clinic, achieved a complete hematologic response with normalized cell count, and remained free from any cardiovascular event at the 8-month follow-up.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.

CardioNerds Case Reports Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll

CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!

Case MediaPearls – Apical Obliteration with Biventricular Thrombus1. Cardiac MRI is a valuable test for patients presenting with myocardial infarction with non-obstructive coronary arteries (MINOCA). 2. Obliterated apex with apical thrombus on TTE with hypereosinophilia should raise high suspicion for eosinophilic myocarditis. 3. Initiation of corticosteroids is the first-line treatment for eosinophilic myocarditis, which is associated with lower mortality in patients with myocarditis. For other potential complications, such as heart failure, intracardiac thrombus, arrhythmia, and pericardial effusion, the standard of care for each disorder is recommended. 4. Hypereosinophilia can be seen in parasitic infections, vasculitis, asthma, allergy, hematological malignancies, and as a primary disorder.

Show Notes – Apical Obliteration with Biventricular ThrombusWhat is the differential diagnosis for patients with elevated troponin and nonobstructive CAD?

The occurrence of acute myocardial infarction (AMI) without significant CAD was reported 80 years ago. However, the term MINOCA (myocardial infarction with non-obstructive coronary arteries) has only been used recently to describe these patients. It involves ischemic and nonischemic etiologies. First, overlooked ischemic etiologies need to be ruled out by reconciling the angiogram images such as spontaneous coronary artery dissection (SCAD) and plaque disruption. Intracoronary imaging, such as intravascular ultrasound (IVUS) or optical coherence tomography (OCT), may be applied to evaluate for SCAD and subtypes of plaque disruption when indicated.
The investigation continues with nonischemic causes such as stress cardiomyopathy, myocarditis, pulmonary embolism, demand ischemia from sepsis, anemia, chest trauma, heart failure exacerbation, arrhythmia, and stroke.
The diagnosis of MINOCA is established when it fulfills the following criteria: First, it is AMI by the Fourth Universal Definition; Second, less than 50% of stenotic lesion on angiogram; Third, there is no alternate diagnosis. MINOCA etiologies include coronary artery spasms and microvascular dysfunction.
It is recommended to perform CMR in all MINOCA patients without an obvious underlying cause.

What are the common causes of LV thrombus?

The incidence of LV thrombus has been reported between 4-39% after anterior MI. The temporal incidence has been decreasing. It is also commonly seen in dilated cardiomyopathy with an incidence of 2-36%.
The pathophysiology of intracardiac thrombus formation obeys Virchow’s triad rule, which states that endocardial injury, hypercoagulability/inflammation, and stasis lead to thrombogenesis.
Other etiologies of LV thrombus include eosinophilic myocarditis and LV noncompaction.

What are the characteristic echocardiographic and CMR findings of eosinophilic myocarditis (EM)?

During the acute necrotic stage, there is increased subendocardial echogenicity, wall thickening, impaired regional wall motion, and pericardial effusion; there is edema without fibrosis on CMR.
During the thrombotic stage, intracardiac thrombus is often detected in the ventricles on TTE; on CMR, there is endomyocardial involvement and intracardiac thrombus.
During the fibrotic stage, in addition to the cumulative findings from previous stages, restrictive physiology, valvular thickening, and restricted motion can occur on TTE; on CMR, endomyocardial fibrosis with LGE is present.

What is the management for eosinophilic myocarditis (EM)?

Two aspects must be considered in the treatment of eosinophilic myocarditis: the management of acute cardiac conditions and the treatment of underlying causes.
Corticosteroids are the first-line treatment for EM. A meta-analysis of 179 cases showed that steroid use is associated with a lower mortality rate. No clinical trial data are available for the treatment of eosinophilic myocarditis. The dose and duration of corticosteroids in each individual case can be different.
For intracardiac thrombus, vitamin K antagonists (VKAs) are the drugs of choice. Complete gradual resolution of intracardiac thrombus with VKA in eosinophilic myocarditis was reported at the 18-month follow-up. The INR target was 2-3. Emerging data showed the noninferiority of using DOAC for LV thrombus compared to warfarin as an alternative for stroke prevention. There is an increased risk of stroke in patients on VKA but with subtherapeutic INR levels. The guidelines recommend DOAC as a reasonable alternative to VKA to treat LV thrombus.
For other potential complications such as heart failure, intracardiac thrombus, arrhythmia, and pericardial effusion, the standard of care for each complication is recommended. There is no large data to suggest a specific approach in eosinophilic myocarditis. It has been reported to achieve full recovery with GDMT in addition to treating the underlying cause in a case report of eosinophilic myocarditis with severely reduced LV systolic function.

What is hypereosinophilic syndrome (HES)?

HES is pleomorphic in clinical presentation and can be idiopathic or associated with a variety of underlying conditions, including allergic, rheumatologic, infectious, and neoplastic disorders.
There are 4 groups. In primary HES, the hypereosinophilia is driven by a clonal process in stem cell or myeloid lineage. Patients usually present with a myeloid neoplasm and myeloid proliferative disorder. Besides eosinophilia, they may have other cytopenias, blasts, or dysplastic cells in peripheral blood. They can present with constitutional symptoms or hepatosplenomegaly. Some of these patients have disease-defining mutations or chromosome translocation. They require treatment for their underlying hematologic condition. Secondary HES usually have polyclonal eosinophilia secondary to some stimulus. The stimulus may be infections, rheumatology conditions, solid tumors, and lymphoid neoplasm. The underlying condition increases eosinophilic cytokines leading to an increase in eosinophil production. The third group is familial HES results from certain genetic factors. If no cause of HES can be identified, they fall into the category of idiopathic HES.
Patients with HES secondary to myeloid and lymphoid disorders need to follow up with a hematology specialist. References – Apical Obliteration with Biventricular Thrombus1. Bondue A, Carpentier C, Roufosse F. Hypereosinophilic syndrome: considerations for the cardiologist. Heart 2022;108:164-171.
Merlo M, Gagno G, Baritussio A et al. Clinical application of CMR in cardiomyopathies: evolving concepts and techniques : A position paper of myocardial and pericardial diseases and cardiac magnetic resonance working groups of Italian society of cardiology. Heart Fail Rev 2023;28:77-95.
Murthy SB. Troponin Elevation After Ischemic Stroke and Future Cardiovascular Risk: Is the Heart in the Right Place? Journal of the American Heart Association 2021;10:e021474.
Dhaliwal JSS, Ansari SA, Ghosh S, Chitkara A, Khizer U. Duet of Death: Biventricular Thrombus in a Methamphetamine User. Cureus 2023;15:e39917.
Levine GN, McEvoy JW, Fang JC et al. Management of Patients at Risk for and With Left Ventricular Thrombus: A Scientific Statement From the American Heart Association. Circulation 2022;146:e205-e223.
Parrillo JE. Heart Disease and the Eosinophil. New England Journal of Medicine 1990;323:1560-1561.
Wright BL, Leiferman KM, Gleich GJ. Eosinophil Granule Protein Localization in Eosinophilic Endomyocardial Disease. New England Journal of Medicine 2011;365:187-188.
Polte CL, Bobbio E, Bollano E et al. Cardiovascular Magnetic Resonance in Myocarditis. Diagnostics 2022;12:399.
Ammirati E, Frigerio M, Adler ED et al. Management of Acute Myocarditis and Chronic Inflammatory Cardiomyopathy: An Expert Consensus Document. Circ Heart Fail 2020;13:e007405.
Ito S, Isotani A, Yamaji K, Ando K. Follow-up magnetic resonance imaging of Löffler endocarditis: a case report. Eur Heart J Case Rep 2020;4:1-4.
Miller T, Gabriel A, Bianco C, Hamirani Yasmin S. ACUTE EOSINOPHILIC MYOCARDITIS: AN ATYPICAL PRESENTATION DIAGNOSED BY COMBINED CARDIAC MAGNETIC RESONANCE IMAGING AND ENDOMYOCARDIAL BIOPSY WITH FULL RECOVERY. Journal of the American College of Cardiology 2022;79:2298-2298.

View Details

CardioNerds join Dr. Inbar Raber and Dr. Susan Mcilvaine from the Beth Israel Deaconess Medical Center for a Fenway game. They discuss the following case: A 72-year-old man presents with two weeks of progressive dyspnea, orthopnea, nausea, vomiting, diarrhea, and right upper quadrant pain. He has a history of essential thrombocytosis, Barrett’s esophagus, basal cell skin cancer, and hypertension treated with hydralazine. He is found to have bilateral pleural effusions and a pericardial effusion. He undergoes a work-up, including pericardial cytology, which is negative, and blood tests reveal a positive ANA and positive anti-histone antibody. He is diagnosed with drug-induced lupus due to hydralazine and starts treatment with intravenous steroids, resulting in an improvement in his symptoms. Expert commentary is provided by UT Southwestern internal medicine residency program director Dr. Salahuddin (“Dino”) Kazi.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.

CardioNerds Case Reports Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll

CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!

Case MediaPearls – A Drug’s Adverse Effect Unleashes the Wolf1. The differential diagnosis for pericardial effusion includes metabolic, malignant, medication-induced, traumatic, rheumatologic, and infectious etiologies. 2. While pericardial cytology can aid in securing a diagnosis of cancer in patients with malignant pericardial effusions, the sensitivity of the test is limited at around 50%. 3. Common symptoms of drug-induced lupus include fever, arthralgias, myalgias, rash, and/or serositis. 4. Anti-histone antibodies are typically present in drug-induced lupus, while anti-dsDNA antibodies are typically absent (unlike in systemic lupus erythematosus, SLE). 5. Hydralazine-induced lupus has a prevalence of 5-10%, with a higher risk for patients on higher doses or longer durations of drug exposure. Onset is usually months to years after drug initiation.

Show Notes – A Drug’s Adverse Effect Unleashes the Wolf1. There is a broad differential diagnosis for pericardial effusion which includes metabolic, malignant, medication-induced, traumatic, rheumatologic, and infectious etiologies. Metabolic etiologies include renal failure and thyroid disease. Certain malignancies are more likely to cause pericardial effusions, including lung cancer, lymphoma, breast cancer, sarcoma, and melanoma. Radiation therapy to treat chest malignancies can also result in a pericardial effusion. Medications can cause pericardial effusion, including immune checkpoint inhibitors, which can cause myocarditis or pericarditis, and medications associated with drug-induced lupus, such as procainamide, hydralazine, phenytoin, minoxidil, or isoniazid. Trauma can cause pericardial effusions, including blunt chest trauma, cardiac surgery, or cardiac catheterization. Rheumatologic etiologies include lupus, rheumatoid arthritis, systemic sclerosis, sarcoid, and vasculitis. Many different types of infections can cause pericardial effusions, including viruses (e.g., coxsackievirus, echovirus, adenovirus, human immunodeficiency virus, and influenza), bacteria (TB, staphylococcus, streptococcus, and pneumococcus), and fungi. Other must-not-miss etiologies include emergencies like type A aortic dissection and myocardial infarction. 2. In a retrospective study of all patients who presented with a hemodynamically significant pericardial effusion and underwent pericardiocentesis, 33% of patients were found to have an underlying malignancy(Ben-Horin et al). Bloody effusion and frank tamponade were significantly more common among patients with malignant effusion, but the overlap was significant, and no epidemiologic or clinical parameter was found useful to differentiate between cancerous and noncancerous effusions. Although this patient’s pericardial fluid cytology was negative, cytology is typically only positive in around 50% of malignant effusions (Ben-Horin et al). 3. The risk of drug-induced lupus (DIL) with hydralazine is high, approaching 10% of all treated patients. Another more commonly implicated cardiovascular drug is procainamide, with an incidence of 15-20%. Anti-histone antibodies are typically positive in DIL caused by hydralazine or procainamide, whereas anti-double stranded DNA antibodies are typically absent (in contrast to systemic lupus erythematosus). The most common symptoms of DIL include fever, arthralgias, myalgias, rash, and/or serositis with onset after months to years of drug exposure. If serositis is present, it is more often pleuritis, +/- pericarditis. 4. In addition to stopping the offending medication, treatment is extrapolated from the treatment of idiopathic systemic lupus and can include NSAIDs, hydroxychloroquine, and/or systemic steroids, depending on disease severity. References – A Drug’s Adverse Effect Unleashes the Wolf1. Ben-Horin, Bank, Guetta, & Livneh, A. (2006). Large symptomatic pericardial effusion as the presentation of unrecognized cancer – A study in 173 consecutive patients undergoing pericardiocentesis. Medicine (Baltimore), 85(1), 49–53. 2. Borchers, A.T., Keen, C.L. and Gershwin, M.E. (2007), Drug-Induced Lupus. Annals of the New York Academy of Sciences, 1108: 166-182. 3. Feng, Glockner, J., et al. (2011). Cardiac Magnetic Resonance Imaging Pericardial Late Gadolinium Enhancement and Elevated Inflammatory Markers Can Predict the Reversibility of Constrictive Pericarditis After Antiinflammatory Medical Therapy A Pilot Study. Circulation (New York, N.Y.), 124(17), 1830–1837

View Details

CardioNerds cofounder Dr. Dan Ambinder joins Dr. Angie Molina, Dr. Cullen Soares, and Dr. Andrew Lutz from the University of Maryland Medical Center for some beers and history by Fort McHenry. They discuss a case of disseminated haemophilus influenza
presumed fulminant bacterial myocarditis with mixed septic/cardiogenic shock. Expert commentary is provided by Dr. Stanley Liu (Assistant Professor, Division of Cardiovascular Medicine, University of Maryland School of Medicine). Episode audio was edited by Dr. Chelsea Amo-Tweneboah.

A woman in her twenties with a history of intravenous drug use presented with acute onset fevers and sore throat, subsequently developed respiratory distress and cardiac arrest, and was noted to have epiglottic edema on intubation. She developed shock and multiorgan failure. ECG showed diffuse ST elevations, TTE revealed biventricular dysfunction, and pleural fluid culture grew Haemophilus influenza. Right heart catheterization showed evidence of cardiogenic shock. She improved with supportive care and antibiotics.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.

CardioNerds Case Reports Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll

CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!

Pearls – Sore Throat, Fever, and Myocarditis – It’s not always COVID-191. The post-cardiac arrest ECG provides helpful information for diagnosing the underlying etiology. 2. Be aware of diagnostic biases – availability and anchoring biases are particularly common during respiratory viral (such as COVID-19, RSV) surges. 3. Consider a broad differential diagnosis in evaluating myocarditis, including non-viral etiologies. 4. Right heart catheterization provides crucial information for diagnosis and management of undifferentiated shock. 5. When assessing the need for mechanical circulatory support, consider the current hemodynamics, type of support needed, and risks associated with each type.

Show Notes – Sore Throat, Fever, and Myocarditis – It’s not always COVID-191. ECG findings consistent with pericarditis include diffuse concave-up ST elevations and downsloping T-P segment (Spodick’s sign) as well as PR depression (lead II), and PR elevation (lead aVR). In contrast, regional ST elevations with “reciprocal” ST depressions and/or Q-waves should raise concern for myocardial ischemia as the etiology. 2. Biventricular dysfunction and elevated troponin are commonly seen post-cardiac arrest and may be secondary findings. However, an elevation in troponin that is out of proportion to expected demand ischemia, ECG changes (pericarditis, ischemic ST elevations), and cardiogenic shock suggest a primary cardiac etiology for cardiac arrest. 3. The differential diagnosis of infectious myopericarditis includes, most commonly, viral infection (respiratory viruses) and, more rarely, bacterial, fungal, or parasitic. Noninfectious myopericarditis may be autoimmune (such as lupus, sarcoidosis, checkpoint inhibitors), toxin-induced (alcohol, cocaine), and medication-induced (anthracyclines and others). 4. Right heart catheterization can help diagnose the etiology of undifferentiated shock, including distinguishing between septic and cardiogenic shock, by providing right and left-sided filling pressures, pulmonary and systemic vascular resistance, and cardiac output. 5. Mechanical circulatory support (MCS) is indicated for patients in cardiogenic shock with worsening end-organ perfusion despite inotropic and pressor support. MCS includes intra-aortic balloon pump, percutaneous VAD, TandemHeart, and VA-ECMO. The decision to use specific types of MCS should be individualized to each patient with their comorbidities and hemodynamic profile. Shock teams are vital to guide decision-making. References 1. Witting MD, Hu KM, Westreich AA, Tewelde S, Farzad A, Mattu A. Evaluation of Spodick’s Sign and Other Electrocardiographic Findings as Indicators of STEMI and Pericarditis. J Emerg Med. 2020;58(4):562-569. doi:10.1016/j.jemermed.2020.01.017 2. Ferrero P, Piazza I, Lorini LF, Senni M. Epidemiologic and clinical profiles of bacterial myocarditis. Report of two cases and data from a pooled analysis. Indian Heart J. 2020;72(2):82-92. doi:10.1016/j.ihj.2020.04.005 3. Pollack A, Kontorovich AR, Fuster V, Dec GW. Viral myocarditis–diagnosis, treatment options, and current controversies. Nat Rev Cardiol. 2015;12(11):670-680. doi:10.1038/nrcardio.2015.108 4. Hsu S, Fang JC, Borlaug BA. Hemodynamics for the Heart Failure Clinician: A State-of-the-Art Review. J Card Fail. 2022;28(1):133-148. doi:10.1016/j.cardfail.2021.07.012 5. Korabathina R., Heffernan K.S., Paruchuri V., Patel A.R., Mudd J.O., Prutkin J.M., et al: The pulmonary artery pulsatility index identifies severe right ventricular dysfunction in acute inferior myocardial infarction. Catheter Cardiovasc Interv 2012; 80: pp. 593-600. https://pubmed.ncbi.nlm.nih.gov/21954053/ 6. Drazner MH, Velez-Martinez M, Ayers CR, et al. Relationship of right- to left-sided ventricular filling pressures in advanced heart failure: insights from the ESCAPE trial. Circ Heart Fail. 2013;6(2):264-270. doi:10.1161/CIRCHEARTFAILURE.112.000204

View Details

CardioNerds join Dr. Ethan Fraser and Dr. Austin Culver from the MedStar Georgetown University Hospital internal medicine and cardiology programs in our nation’s capital. They discuss the following case involving an unusual case of rapidly progressive heart failure. Episode audio was edited by CardioNerds Academy Intern and student Dr. Pacey Wetstein. Expert commentary was provided by advanced heart failure cardiologist Dr. Richa Gupta.

A 55-year-old male comes to the clinic (and eventually into the hospital) for what appears to be a straightforward decompensation of his underlying cardiac disease. However, things aren’t as simple as they might appear. In this episode, we will discuss the outpatient workup for non-ischemic cardiomyopathy and discuss the clinical indicators that we as clinicians should be aware of in these sick patients. Furthermore, we will discuss the differential for NICM, the management of patients with this rare disease, and how this disease can mimic other cardiomyopathies.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.

CardioNerds Case Reports Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll

CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!

Case Media – Rapidly Progressive Heart FailurePearls – Rapidly Progressive Heart Failure* The non-ischemic cardiomyopathy workup should incorporate targeted multimodal imaging, thorough history taking, broad laboratory testing, genetic testing if suspicion exists for a hereditary cause, and a deep understanding of which populations are at higher risk for certain disease states. + Key Point: Always challenge and question the etiology of an unknown cardiomyopathy – do not assume an etiology based on history/patient story alone. * Unexplained conduction disease in either a young or middle-aged individual in the setting of a known cardiomyopathy should raise suspicion for an infiltrative cardiomyopathy and set off a referral to an advanced heart failure program. + Key Point: Consider early/more aggressive imaging for these patients and early electrophysiology referral for primary/secondary prevention. * Giant Cell Myocarditis is a rapidly progressive cardiomyopathy characterized by high mortality (70% in the first year), conduction disease, and classically presents in young/middle-aged men. + Key Point: If you have a younger male with rapidly progressive cardiomyopathy (anywhere as quickly as 1-2 months, weeks in some cases) and conduction disease, consider early endomyocardial biopsy, even before other advanced imaging modalities. * The Diagnosis of Giant Cell Myocarditis is time-sensitive – early identification and treatment are essential to survival. + Key Point: The median timeframe from the time the disease is diagnosed to the time of death is approximately 6 months. 90% of patients are either deceased by the end of 1 year or have received a heart transplant. * The treatment of Giant Cell Myocarditis is still governed largely by expert opinion, but the key components include high-dose steroids and cyclosporine, largely as a bridge to transplantation or advanced heart failure therapies. + Key Point: Multi-disciplinary care is essential in delivering excellent care in the diagnostic/pre-transplant period, including involvement by cardiology, cardiac surgery, radiology, critical care, allergy/immunology, case management, advanced heart failure, and shock teams if necessary. * There remains significant clinical overlap between Giant Cell Myocarditis and sarcoidosis, making managing equivocal cases challenging. + Key Point: Consider early FDG-PET imaging in equivocal cases, as management during the pre-transplant period and evaluation of transplant candidacy can vary drastically between the two.

Show Notes – Rapidly Progressive Heart Failure1. What is Giant Cell Myocarditis?

Giant cell myocarditis is a rare and rapidly progressive cause of heart failure due to T-cell lymphocyte mediated myocardial inflammation. The pathogenesis of GCM is incompletely understood – histologically, there is infiltration of the myocardium by T-lymphocytes and macrophages, and there is typically evidence of upregulation of IL-17 and TNF-a. Classically, the disease state is associated with electrical (e.g., ventricular tachycardia, high-grade AV block) and hemodynamic instability – all of which typically progresses rapidly over a period of weeks to months. This male-predominant disease tends to occur in young and middle-aged patients – with a mean age between 42 and 60 based on several registries. While a rare disease, a high index of suspicion is necessary when patients present with rapidly progressive or fulminant heart failure, as a missed diagnosis of giant cell myocarditis is invariably fatal. Early and rapid identification of this uniquely high-risk group of heart failure patients and prompt initiation of therapy targeted towards the underlying autoimmune process, as well as management at a center with advanced heart failure and cardiovascular ICU support, is necessary.

2. How is Giant Cell Myocarditis Diagnosed?

Establishing a diagnosis requires an endomyocardial biopsy (EMB), although EMB has imperfect sensitivity for GCM. Cardiac biomarkers and imaging serve an adjunct role in diagnosis; TTE findings can be variable, with either normal or dilated LV cavity size and increased wall thickness, which may be related to acute edema and inflammation. Worse LVEF on presentation has been shown to correlate with shorter transplant-free survival time. Troponin levels may be elevated, but case series have shown a lack of correlation between prognosis and troponin elevation in GCM, and importantly, in some cases, troponin values have been negative in patients later found to have GCM by biopsy. Advanced imaging is not always practical as these patients are often hemodynamically unstable, but CMR can demonstrate findings typical of myocarditis (i.e. the 2018 Lake Louise criteria).

3. What is the treatment for Giant Cell Myocarditis, and what are the future steps for disease management?

Cyclosporine-based combination immunosuppressive therapy, in addition to standard heart failure guideline-directed medical and procedural therapy and management of arrhythmias, can improve outcomes in these patients. Typical regimens include cyclosporine, high-dose steroids as the mainstay, and azathioprine or alemtuzumab (an anti-CD52 monoclonal antibody) as adjunctive agents. Patients are often co-managed by advanced heart failure, cardiac intensivists, and rheumatology. As the disease progresses, patients often develop sustained or symptomatic ventricular tachycardia, conduction abnormalities refractory HF with a dilated LV phenotype and many require mechanical circulatory support and/or cardiac transplantation.

GCM can remit and relapse, sometimes many years after initial diagnosis; an advanced heart failure team should follow these patients and should continue some immunosuppression (usually a calcineurin inhibitor) for at least 2 years. Overall, our understanding of the mechanism and management of GCM continues to evolve; high-grade evidence such as randomized controlled trials are extremely difficult to perform due to the rarity and high acuity of these presentations, therefore enrolling these patients in shared multicenter registries where able is essential to shrinking our knowledge gaps of this rare disease state.

4. What else should one consider in presumed cases of Giant Cell Myocarditis?

There exists a significant clinical overlap between Giant Cell Myocarditis and Cardiac Sarcoidosis, so much so that some argue the two diseases exist on opposite ends of one disease spectrum. Both notably present with significant arrhythmia burden and advanced heart failure symptoms, although they are both treated quite differently and present with different time courses (mean time to onset of symptoms 0.3 months for GCM, 7 months for CS). Furthermore, data from Nordenswan et al. from Finland reveals that the diagnosis of GCM on histology was recategorized to CS in 62% of their studies reviewed upon secondary pathology review. To this end, it is important that clinicians consider further advanced imaging modalities (i.e., FDG-PET) in equivocal cases and consider expert pathology evaluation of endomyocardial biopsy samples as proper escalation of care and rapid identification can prevent significant treatment delays.

References – Rapidly Progressive Heart Failure1. Amancherla, Kaushik, Juan Qin, Yu Wang, Margaret L. Axelrod, Justin M. Balko, Kelly H. Schlendorf, Robert D. Hoffman, Yaomin Xu, JoAnn Lindenfeld, and Javid Moslehi. “RNA-Sequencing Reveals a Distinct Transcriptomic Signature for Giant Cell Myocarditis and Identifies Novel Druggable Targets.” Circulation Research 129, no. 3 (2021): 451–53. https://doi.org/10.1161/CIRCRESAHA.121.319317. 2. Bang, Vigyan, Sarju Ganatra, Sachin P. Shah, Sourbha S. Dani, Tomas G. Neilan, Paaladinesh Thavendiranathan, Frederic S. Resnic, et al. “Management of Patients With Giant Cell Myocarditis.” Journal of the American College of Cardiology 77, no. 8 (2021): 1122–34. https://doi.org/10.1016/j.jacc.2020.11.074. 3. Birnie, David H., Vidhya Nair, and John P. Veinot. “Cardiac Sarcoidosis and Giant Cell Myocarditis: Actually, 2 Ends of the Same Disease?” Journal of the American Heart Association 10, no. 6 (2021): e020542. https://doi.org/10.1161/JAHA.121.020542. 4. Bobbio, Emanuele, Marie Björkenstam, Bright I. Nwaru, Francesco Giallauria, Eva Hessman, Niklas Bergh, Christian L. Polte, Jukka Lehtonen, Kristjan Karason, and Entela Bollano. “Short- and Long-Term Outcomes after Heart Transplantation in Cardiac Sarcoidosis and Giant-Cell Myocarditis: A Systematic Review and Meta-Analysis.” Clinical Research in Cardiology 111, no. 2 (February 1, 2022): 125–40. https://doi.org/10.1007/s00392-021-01920-0. 5. Brailovsky, Yevgeniy, Amirali Masoumi, Rachel Bijou, Estefania Oliveros, Gabriel Sayer, Koji Takeda, and Nir Uriel. “Fulminant Giant Cell Myocarditis Requiring Bridge With Mechanical Circulatory Support to Heart Transplantation.” JACC: Case Reports 4, no. 5 (2022): 265–70. https://doi.org/10.1016/j.jaccas.2021.11.013. 6. Cooper, Leslie T., Gerald J. Berry, and Ralph Shabetai. “Idiopathic Giant-Cell Myocarditis — Natural History and Treatment.” New England Journal of Medicine 336, no. 26 (1997): 1860–66. https://doi.org/10.1056/nejm199706263362603. 7. Ekström K, Lehtonen J, Kandolin R, Räisänen-Sokolowski A, Salmenkivi K, Kupari M. Incidence, Risk Factors, and Outcome of Life-Threatening Ventricular Arrhythmias in Giant Cell Myocarditis. Circulation: Arrhythmia and Electrophysiology. 2016;9(12):e004559. doi:10.1161/CIRCEP.116.004559 8. Fallon, J. M., A. M. Parker, S. P. Dunn, and J. L. W. Kennedy. “A Giant Mystery in Giant Cell Myocarditis: Navigating Diagnosis, Immunosuppression, and Mechanical Circulatory Support.” ESC Heart Fail 7, no. 1 (February 2020): 315–19. https://doi.org/10.1002/ehf2.12564. 9. Ghaly, Medhat, Danise Schiliro, and Jadwiga Stepczynski. “Giant Cell Myocarditis: A Time Sensitive Distant Diagnosis.” Cureus 12, no. 1 (2020): e6712–e6712. https://doi.org/10.7759/cureus.6712. 10. Gilotra NA, Minkove N, Bennett MK, et al. Lack of Relationship Between Serum Cardiac Troponin I Level and Giant Cell Myocarditis Diagnosis and Outcomes. Journal of Cardiac Failure. 2016;22(7):583-585. doi:10.1016/j.cardfail.2015.12.022 11. Heymans S, Eriksson U, Lehtonen J, Cooper LT. The Quest for New Approaches in Myocarditis and Inflammatory Cardiomyopathy. Journal of the American College of Cardiology. 2016;68(21):2348-2364. doi:10.1016/j.jacc.2016.09.937 12. Kandolin, Riina, Jukka Lehtonen, Kaisa Salmenkivi, Anne Räisänen-Sokolowski, Jyri Lommi, and Markku Kupari. “Diagnosis, Treatment, and Outcome of Giant-Cell Myocarditis in the Era of Combined Immunosuppression.” Circulation: Heart Failure 6, no. 1 (2013): 15–22. https://doi.org/10.1161/CIRCHEARTFAILURE.112.969261. 13. Kociol, Robb D., Leslie T. Cooper, James C. Fang, Javid J. Moslehi, Peter S. Pang, Marwa A. Sabe, Ravi V. Shah, Daniel B. Sims, Gaetano Thiene, and Orly Vardeny. “Recognition and Initial Management of Fulminant Myocarditis.” Circulation 141, no. 6 (2020): e69–92. https://doi.org/10.1161/CIR.0000000000000745. 14. Kondo, Toru, Takahiro Okumura, Naoki Shibata, Takahiro Imaizumi, Kaoru Dohi, Hideo Izawa, Nobuyuki Ohte, Tetsuya Amano, and Toyoaki Murohara. “Differences in Prognosis and Cardiac Function According to Required Percutaneous Mechanical Circulatory Support and Histological Findings in Patients With Fulminant Myocarditis: Insights From the CHANGE PUMP 2 Study.” Journal of the American Heart Association 11, no. 4 (2022): e023719. https://doi.org/10.1161/JAHA.121.023719. 15. Nordenswan, Hanna‐Kaisa, Jukka Lehtonen, Kaj Ekström, Anne Räisänen‐Sokolowski, Mikko I. Mäyränpää, Tapani Vihinen, Heikki Miettinen, et al. “Manifestations and Outcome of Cardiac Sarcoidosis and Idiopathic Giant Cell Myocarditis by 25‐Year Nationwide Cohorts.” Journal of the American Heart Association 10, no. 6 (2021): e019415. https://doi.org/10.1161/JAHA.120.019415. 16. Paitazoglou, Christina, Martin W. Bergmann, Katharina Tiemann, Andrea Wiese, Ulrich Schäfer, Arne Schwarz, Ingo Eitel, and Moritz Montenbruck. “Atrial Giant Cell Myocarditis as a Cause of Heart Failure.” JACC: Case Reports 4, no. 1 (2022): 66–71. https://doi.org/10.1016/j.jaccas.2021.11.007. 17. PALMER, HARLEY P., and ISAAC E. MICHAEL. “Giant-Cell Myocarditis With Multiple Organ Involvement.” Archives of Internal Medicine 116, no. 3 (1965): 444–47. https://doi.org/10.1001/archinte.1965.03870030124022. 18. Polte, Christian L., Entela Bollano, Anders Oldfors, Anna Dudás, Kerstin M. Lagerstrand, Jakob Himmelman, Emanuele Bobbio, Kristjan Karason, Martijn van Essen, and Niklas Bergh. “Somatostatin Receptor Positron Emission Tomography/Computed Tomography in Giant Cell Myocarditis: A Promising Approach to Molecular Myocardial Inflammation Imaging.” Circulation: Cardiovascular Imaging 15, no. 1 (2022): e013551. https://doi.org/10.1161/CIRCIMAGING.121.013551. 19. Sujino, Yasumori, Fumiko Kimura, Jun Tanno, Shintaro Nakano, Eriko Yamaguchi, Michio Shimizu, Nanami Okano, et al. “Cardiac Magnetic Resonance Imaging in Giant Cell Myocarditis.” Circulation 129, no. 17 (2014): e467–69. https://doi.org/10.1161/CIRCULATIONAHA.113.005059. 20. Xu, J., and E. G. Brooks. “Giant Cell Myocarditis: A Brief Review.” Arch Pathol Lab Med 140, no. 12 (December 2016): 1429–34. https://doi.org/10.5858/arpa.2016-0068-RS. 21. Yang, S., X. Chen, J. Li, Y. Sun, J. Song, H. Wang, and S. Zhao. “Late Gadolinium Enhancement Characteristics in Giant Cell Myocarditis.” ESC Heart Fail 8, no. 3 (June 2021): 2320–27. https://doi.org/10.1002/ehf2.13276.

View Details

CardioNerds nerd out with Drs. Karishma Rahman (Mount Siani Vascular Medicine fellow), Shu Min Lao (Mount Sinai Rheumatology fellow), and Constantine Troupes (Mount Sinai Vascular Surgery fellow). They discuss the following case: A 20-year-old woman with a history of hypertension (HTN), initially thought to be secondary to a mid-aortic syndrome that resolved after aortic stenting, presents with a re-occurrence of HTN. The case will go through the differential diagnosis of early onset HTN focusing on structural etiologies of HTN, including mid-aortic syndrome and aortitis. We will also discuss the multi-modality imaging used for diagnosis and surveillance, indications and types of procedural intervention, and how to diagnose and treat an underlying inflammatory disorder leading to aortitis. The expert commentary was provided by Dr. Daniella Kadian-Dodov, Associate Professor of Medicine and Vascular Medicine specialist at the Icahn School of Medicine at Mount Sinai. Audo editing was performed by Dr. Chelsea Amo-Tweneboah, CardioNerds Academy Intern and medicine resident at Stony Brook University Hospital.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.

CardioNerds Case Reports Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll

CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!

Case Media – Hypertension With a TwistPearls – Hypertension With a Twist1. Early onset hypertension (HTN) and lower extremity claudication should raise suspicion for aortic stenosis (including mid-aortic syndrome). Initial evaluation should include arterial duplex ultrasound and cross-sectional imaging such as CT or MR angiogram of the chest, abdomen, and pelvis to assess for arterial stenosis involving the aorta and/or branching vessels. 2. Mid-aortic syndrome can have multiple underlying etiologies. Concentric aortic wall thickening should raise suspicion for an underlying inflammatory disorder. Initial evaluation should include inflammatory markers such as ESR, CRP, and IL-6, but normal values do not exclude underlying aortitis. 3. While Takayasu arteritis is the most common inflammatory disorder associated with mid-aortic syndrome, IgG4-RD should also be a part of the differential diagnosis. IgG subclass panel can detect IgG4-RD with elevated serum IgG4 levels, but some cases can require pathology for diagnosis. 4. Catheter based intervention is a safe and effective treatment of aortic stenosis for both primary aortic stenosis and post-procedural re-stenosis. 5. Multi-modality imaging, including cross-sectional imaging and duplex ultrasound, plays a central role for the diagnosis, management, and post-procedural surveillance of aortic disease. 6. A multi-disciplinary team (as exemplified by the participants of this podcast!) is essential for the management of complex aortopathy cases to optimize clinical outcomes.

Show Notes – Hypertension With a Twist1. Early onset HTN can have multiple etiologies – aortic stenosis (including but not limited to secondary to congenital aortic coarctation and mid–aortic syndrome, as well as in stent re-stenosis if there is a history of aortic stenting), thrombosis, infection, inflammatory/autoimmune disorders, renovascular disease, polycystic kidney disease, and endocrine disorders.

Mid-aortic syndrome is characterized by segmental or diffuse narrowing of the abdominal and/or distal descending aorta with involvement of the branches of the proximal abdominal aorta (renal artery, celiac artery, superior mesenteric artery) and represents approximately 0.5 to 2% of all cases of aortic narrowing. Underlying etiologies include genetic syndromes, inflammatory, non-inflammatory, and idiopathic. It is important to have a high suspicion of underlying inflammatory disorders if cross-sectional imaging reveals concentric aortic wall thickening1,2.
The current treatment options for aortic stenosis (of the aorta here…not the aortic valve) include balloon angioplasty, aortic stenting, and surgical repair. While studies show the efficacy of balloon angioplasty and aortic stenting, data is limited as studies were mostly done in children3,4.
Aortitis5-16 can have multiple etiologies including infectious (such as TB, syphilis, HIV, bacterial, fungal), inflammatory disorders (such as large vessel vasculitis, IgG4-RD, Behcet syndrome, relapsing polychondritis, spondyloarthritis, SLE, and rheumatoid arthritis), and idiopathic. Sometimes, hereditary connective tissue disorders (such Marfan syndrome,, Ehlers-Danlos syndrome, and Loeys-Dietz syndrome) are included in the differential diagnosis, however, they would present as an aortic intramural hematoma (IMH) that typically would appears as eccentric wall thickening (rather than concentric wall thickening more consistent with aortitis).
While Takayasu arteritis is the most common inflammatory disorder associated with mid-aortic syndrome, IgG4-RD should also be a part of the differential diagnosis. IgG4-RD is characterized by lymphoplasmacytic infiltrates featuring IgG4 positive plasma cells. It presents in predominantly males between ages 40-70 years of age. The rate of vascular involvement is approximately 8% for aortitis and 20-36% periaortitis. It can be diagnosed with elevated serum IgG4 levels or from tissue biopsy where pathology would show dense lymphoplasmacytic infiltrates in a storiform fibrosis pattern with obliterative phlebitis and >40% plasma calls and >10 positive plasma cells/high power field. It is treated initially treated with high dose steroids with transition to steroid sparing agents such as Rituximab (RTX), azathioprine, mycophenolate, and methotrexate with RTX being the preferred agent10,14.
In cases of re-stenosis after initial balloon angioplasty and stenting, indications for re-intervention include hypertension in the setting of imaging evidence of re-stenosis (e.g. > 50% percent aortic narrowing relative to the aortic diameter at the diaphragm level) and

pressure gradient across the coarctation > 20 mmHg. The timing of re-intervention in cases of aortitis secondary to underlying inflammatory disorders will require a multi-disciplinary discussion to determine when underlying inflammatory disorder is sufficiently controlled for re-intervention.

References – Hypertension With a Twist1. Bacha E, Hijazi ZM. Management of Coarctation of the Aorta. U: UpToDate, Fulton DR ed UpToDate [Internet] Waltham, MA: UpToDate. 2020. 2. Lazea C, Al-Khzouz C, Sufana C, et al. Diagnosis and management of genetic causes of middle aortic syndrome in children: a comprehensive literature review. Therapeutics and Clinical Risk Management. 2022:233-248. 3. Rodés-Cabau J, Miró J, Dancea A, et al. Comparison of surgical and transcatheter treatment for native coarctation of the aorta in patients≥ 1 year old. The Quebec Native Coarctation of the Aorta Study. American heart journal. 2007;154(1):186-192. 4. Meadows J, Minahan M, McElhinney DB, McEnaney K, Ringel R. Intermediate outcomes in the prospective, multicenter Coarctation of the Aorta Stent Trial (COAST). Circulation. 2015;131(19):1656-1664. 5. Nikiphorou E, Galloway J, Fragoulis GE. Overview of IgG4-related aortitis and periaortitis. A decade since their first description. Autoimmunity reviews. 2020;19(12):102694. 6. Kadian-Dodov D, Seo P, Robson PM, Fayad ZA, Olin JW. Inflammatory Diseases of the Aorta: JACC Focus Seminar, Part 2. Journal of the American College of Cardiology. 2022;80(8):832-844. 7. Sohrabi B, Jamshidi P, Yaghoubi A, et al. Comparison between covered and bare Cheatham-Platinum stents for endovascular treatment of patients with native post-ductal aortic coarctation: immediate and intermediate-term results. JACC: Cardiovascular Interventions. 2014;7(4):416-423. 8. Marvisi C, Buttini EA, Vaglio A. Aortitis and periaortitis: the puzzling spectrum of inflammatory aortic diseases. La Presse Médicale. 2020;49(1):104018. 9. Bossone E, Pluchinotta FR, Andreas M, et al. Aortitis. Vascular pharmacology. 2016;80:1-10. 10. Carruthers MN, Topazian MD, Khosroshahi A, et al. Rituximab for IgG4-related disease: a prospective, open-label trial. Annals of the rheumatic diseases. 2015;74(6):1171-1177. 11. Wallace ZS, Perugino C, Matza M, Deshpande V, Sharma A, Stone JH. Immunoglobulin G4–related disease. Clinics in chest medicine. 2019;40(3):583-597. 12. Wallace ZS, Naden RP, Chari S, et al. The 2019 American College of Rheumatology/European league against rheumatism classification criteria for IgG4‐related disease. Arthritis & Rheumatology. 2020;72(1):7-19. 13. Onen F, Akkoc N. Epidemiology of Takayasu arteritis. La Presse Médicale. 2017;46(7-8):e197-e203. 14. Ebbo M, Grados A, Samson M, et al. Long-term efficacy and safety of rituximab in IgG4-related disease: data from a French nationwide study of thirty-three patients. PLoS One. 2017;12(9):e0183844. 15. Maz M, Chung SA, Abril A, et al. 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of giant cell arteritis and Takayasu arteritis. Arthritis Care & Research. 2021;73(8):1071-1087. 16. Lupi-Herrera E, Sanchez-Torres G, Marcushamer J, Mispireta J, Horwitz S, Vela JE. Takayasu’s arteritis. Clinical study of 107 cases. American heart journal. 1977;93(1):94-103.

View Details

CardioNerds (Dr. Amit Goyal) join Dr. Anureet Malhotra, Dr. John Fritzlen, and Dr. Tarun Dalia from the University of Kansas School of Medicine for some of Kansas City’s famous barbeque. They discuss a case of Hydroxychloroquine induced cardiomyopathy. Notes were drafted by Dr. Anureet Malhotra, Dr. John Fritzlen, and Dr. Tarun Dalia. Expert commentary was provided by Dr. Pradeep Mammen. The episode audio was edited by Dr. Akiva Rosenzveig.

Drug-induced cardiomyopathy remains an important and under-recognized etiology of cardiomyopathy and heart failure.Hydroxychloroquine is a disease-modifying antirheumatic drug used for various rheumatological conditions, and its long-term use is well-known to have toxic effects on cardiac muscle cells. Multiple cardiac manifestations of these drugs have been identified, the most prominent being electrophysiological disturbances.

In this episode, we discuss a biopsy-proven case of hydroxychloroquine-induced cardiotoxicity with detailed histopathological and imaging findings. We develop a roadmap for the diagnosis of hydroxychloroquine-induced cardiomyopathy and discuss the various differentials of drug-induced cardiomyopathy. We highlight the importance of clinical monitoring and early consideration of drug-induced toxicities as a culprit for heart failure.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.

This episode is made possible with support from Glass.Health – The first digital notebook designed for doctors. Follow @GlassHealthHQ for the latest product updates!

CardioNerds Case Reports Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll

CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!

Case Media – Hydroxychloroquine induced cardiomyopathyPearls – Hydroxychloroquine induced cardiomyopathy1. Continued decline in left ventricular systolic function despite appropriate guideline directed medical therapy should prompt a thorough evaluation for unrecognized etiologies and warrants an early referral to advanced heart failure specialists. 2. Transthoracic echocardiogram is a valuable non-invasive screening tool for suspected pulmonary hypertension, but right heart catheterization is required for definitive diagnosis. 3. Cardiac MRI can be used for better characterization of myocardial tissue and can aid in the evaluation of patients with non-ischemic cardiomyopathy. 4. Hydroxychloroquine (HCQ) is a commonly used DMARD that remains an underrecognized etiology of cardiomyopathy and heart failure. In addition to ophthalmological screening, annual ECG, as well as echocardiography screening for patients on long-term HCQ therapy, should be considered in patients at risk for cardiovascular toxicity, including those with pre-existing cardiovascular disease, older age, female sex, longer duration of therapy, and renal impairment. 5. Management of hydroxychloroquine-associated cardiomyopathy consists of discontinuing hydroxychloroquine and standard guideline-directed medical therapy for heart failure. HCQ cardiomyopathy may persist despite medical therapy, and advanced therapy options may have to be considered in those with refractory heart failure.

Show Notes – Hydroxychloroquine induced cardiomyopathyWhat are the various cardiotoxic effects of hydroxychloroquine (HCQ) and the mechanism of HCQ-mediated cardiomyopathy?

One of the most frequently prescribed disease-modifying antirheumatic drugs (DMARDs), HCQ is an immunomodulatory and anti-inflammatory agent that remains an integral part of treatment for a myriad of rheumatological conditions. Its efficacy is linked to inhibiting lysosomal antigen processing, MHC-II antigen presentation, and TLR functions.8 The known cardiac manifestations of HCQ-induced toxicity include conduction abnormalities, ventricular hypertrophy, hypokinesia, and lastly, cardiomyopathy.

Conduction Abnormalities – by binding to and inhibiting the human ether-à-go-go-related gene (hERG) voltage-gated potassium channel, also known as Ikr channel, HCQ can lead to prolongation of corrected QT (QTc) interval. This can lead to an increased risk of drug-induced Torsades de pointes and other lethal ventricular arrhythmias.
Cardiomyopathy – HCQ is a lipophilic drug that easily permeates myocytes and binds to lysosomal phospholipids, leading to lysosomal accumulation of phospholipids. Furthermore, by increasing the pH of the lysosome, HCQ inhibits lysosomal enzymes, which interferes with lysosomal function and exocytosis, leading to an acquired lysosomal storage disorder. This results in myofibrillar disorganization, atrophy, and fibrosis, which may lead to cardiomyopathy. Risk factors for the development of cardiotoxicity are thought to be pre-existing cardiovascular disease, older age, female sex, longer duration of therapy, and renal impairment. 8
Extracardiac side effects – With long term use, HCQ can also lead to ocular toxicity, neuropathy, and myopathy with similar pathogenesis as cardiotoxicity, i.e., acquired lysosomal storage disorder.

What are the histopathological findings of HCQ induced Cardiomyopathy?

HCQ causes an acquired lysosomal storage disorder due to the inhibition of constitutive autophagy present in normal cardiac myocytes. On histopathology, this presents itself as cytoplasmic vacuoles, lamellar bodies and curvilinear inclusion bodies in cytoplasm that can be visualized with electron microscopy. Of these findings, curvilinear bodies are thought to be pathognomonic for HCQ induced cardiotoxicity. On histopathology, these findings can resemble inherited lysosomal storage disorders including Anderson- Fabry disease except for the presence of curvilinear bodies. 9

What is the differential diagnosis for HCQ induced cardiomyopathy?

Differentials of HCQ mediated cardiomyopathy include storage disorders like Fabry disease, adult-onset Pompe disease (acid maltase deficiency), and Danon disease. Many drug-induced myopathies such as amiodarone, rituximab, prednisone, cocaine, cobalt, and several chemotherapeutic agents can also resemble HCQ mediated cardiotoxicity.

Furthermore, amyloidosis, sarcoidosis and myocarditis also merit consideration as they can lead to restrictive physiology and present similar echocardiographic findings. They can be differentiated using advanced cardiac imaging such as cardiac MRI and histopathological findings on endomyocardial biopsy.

How can Cardiac MRI (CMR) assist in the work up of non-ischemic cardiomyopathy?

CMR can enhance visualization of cardiac structures that may be poorly seen on echocardiogram due to location or poor acoustic windows. CMR also uniquely provides detailed tissue characterization. CMR can be used for assessing many pathologies, including aortic disease, coronary artery disease, cardiomyopathies, pericardial disease, and congenital heart disease. 4 CMR is also considered the gold standard for assessing cardiac function and can be used to assess valvular pathologies with flow assessment.

Late gadolinium enhancement (LGE) refers to the discrimination of regions of scar, necrosis, or inflammation from normal tissue by the prolonged retention of gadolinium-based contrast agents. The pattern of LGE, as well as T1 and T2 mapping, aid in tissue characterization and accurate diagnosis. Key take-home points are as follows:

The presence of LGE in a coronary distribution can support the diagnosis of prior myocardial infarction and aid in the assessment of myocardial viability.
LGE in the mid-wall and sub-epicardium of the LV is characteristic of viral myocarditis. In addition, T1 mapping helps estimate the extracellular volume, and T2 weighted imaging can show myocardial edema in patients with myocarditis.
In amyloidosis, the classic CMR findings include thick LV walls, valves, and interatrial septum and the presence of a pericardial effusion. They may also have the existence of amyloid protein in the myocardial interstitium associated with characteristic patterns of circumferential subendocardial LGE.

What is the management of HCQ induced cardiomyopathy?

Diagnosis – HCQ cardiomyopathy diagnosis requires a high level of suspicion. A detailed history is an essential first step. CMR can aid in tissue characterization and is a helpful non-invasive tool. Definitive diagnosis can be established by obtaining an endomyocardial biopsy, given its distinctive histopathological findings, and ruling out close mimics of HCQ-induced cardiotoxicity.
Treatment – the potentially reversible nature of HCQ cardiomyopathy makes early diagnosis and discontinuation of the offending drug the mainstays of treatment along with guideline directed medical therapy for heart failure. Recovery is variable and may take months or even years for LV function to improve. In some cases, there may be partial or no recovery, requiring advanced therapies evaluations. References – Hydroxychloroquine induced cardiomyopathy1. Greiner S, Jud A, Aurich M, et al. Reliability of Noninvasive Assessment of Systolic Pulmonary Artery Pressure by Doppler Echocardiography Compared to Right Heart Catheterization: Analysis in a Large Patient Population. Journal of the American Heart Association.2014;3(4).10.1161/JAHA.114.001103
Augustine DX, Coates-Bradshaw LD, Willis J, et al. Echocardiographic assessment of pulmonary hypertension: a guideline protocol from the British Society of Echocardiography. Echo research and practice. 2018;5(3):G11-G24. 10.1530/ERP-17-0071
Page RL, O’Bryant CL, Cheng D, et al. Drugs That May Cause or Exacerbate Heart Failure. Circulation. 2016;134(6).https://doi.org/10.1161/CIR.0000000000000426
Kramer CM. Role of Cardiac MR Imaging in Cardiomyopathies. Journal of Nuclear Medicine. 2015;56(Supplement_4):39S45S.10.2967/jnumed.114.142729.
Joyce E, Fabre A, Mahon N. Hydroxychloroquine cardiotoxicity presenting as a rapidly evolving biventricular cardiomyopathy: key diagnostic features and literature review. European Heart Journal Acute Cardiovascular Care. 2013;2(1):77-83. https://doi.org/10.1177/2048872612471215
Ezzeddine FM, Giudicessi JR, Maleszewski JJ, Lin PT, Borlaug BA, Geske JB. Unmasking Hydroxychloroquine Cardiotoxicity in a Patient With Heart Failure and Chronotropic Incompetence. JACC: Case Reports. 2021;3(7):997-1001. https://doi.org/10.1016/j.jaccas.2021.03.003
Humbert M, Kovacs G, Hoeper MM, et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. European Heart Journal. Published online August 26, 2022. https://doi.org/10.1093/eurheartj/ehac237
Bansal P, Goyal A, Cusick A, et al. Hydroxychloroquine: a comprehensive review and its controversial role in coronavirus disease 2019. Annals of Medicine. 2020;53(1):117-134. 10.1080/07853890.2020.1839959.
Roos JM, Aubry MC, Edwards WD. Chloroquine cardiotoxicity: Clinicopathologic features in three patients and comparison with three patients with Fabry disease. Cardiovascular Pathology. 2002;11(5):277-283. https://doi.org/10.1016/s1054-8807(02)00118-7

View Details

CardioNerds meet with fellows from The Christ Hospital, Drs. Hanad Bashir, Hyunsoo Chung, and Dalia Aziz to discuss the following case that highlights angioleiomyoma:

A 60-year-old woman with a past medical history significant for breast cancer (on tamoxifen) presented as a transfer to our facility for a clot-in-transit. She had initially presented to the outside hospital after progressive dyspnea on exertion and recent syncope. She was found on an echocardiogram to have a right atrial mass spanning into the right ventricle. CTA of the chest and abdomen/pelvis demonstrated extensive thrombus burden spanning from the IVC into the right ventricle. She was transferred to our facility for intervention.

Endovascular attempts were unsuccessful, at which point she underwent surgical thrombectomy. Gross examination of the mass revealed a cylindrical shape, homogeneous tan color, rubbery soft tissue, measuring 25.5 cm in length and 2.3 cm in diameter. Histology confirmed the presence of angioleiomyoma. A second, smaller mass (5.2cm long and 4mm in diameter) was removed from under the tricuspid valve, with histology consistent with leiomyoma. Estrogen receptor and progesterone receptor staining were strongly positive, leading to the discontinuation of tamoxifen. Given the presence of uterine fibroids identified on the CT scan, there was concern about a uterine origin. A hysterectomy is planned for her in the near future.

Expert commentary is provided by Dr. Wojciech Mazur. Episode audio was edited by student Dr. Adriana Mares.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.

CardioNerds Case Reports Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll

CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!

Case Media – The Tall Tail Heart: Angioleiomyoma – The Christ HospitalPearls – The Tall Tail Heart: Angioleiomyoma – The Christ Hospital1. Although evaluation of cardiac mass by echocardiography can provide information such as size, location, and morphology, adjunctive cross-sectional imaging may be used depending on the need for further temporal resolution (CT) or tissue characterization via cardiac MRI (CMR). If suspicious for elevated metabolic activity, there should be consideration of FDG-PET. 2. Tamoxifen (a selective estrogen receptor modulator) is an agent used for breast cancer therapy. However, its use has been associated with endometrial hyperplasia, uterine fibroids, endometrial and uterine malignancy. Increased risk of malignancy has been seen more often in post-menopausal women and is dose and time-dependent. 3. Clot in transient is a mobile thrombus, typically within the right heart structures. It is estimated to occur in 4-18% of patients with pulmonary embolism and is associated with elevated morbidity and mortality. Treatment includes surgical embolectomy, endovascular embolectomy, systemic thrombolysis, catheter-directed thrombolysis, or systemic anticoagulation. 4. Angioleiomyoma is a rare benign pericystic tumor that most commonly affects the extremities. There are case reports of other affected sites, including the uterus. Invasion into the cardiac structures is exceedingly rare. 5. The only established treatment for angioleiomyoma is surgical resection.

Show Notes – The Tall Tail Heart: Angioleiomyoma – The Christ HospitalSyncope

Syncope is a transient loss of consciousness secondary to reduced blood flow to the brain. Often, certain presentations are mislabeled as syncope, such as seizure disorders, posttraumatic loss of consciousness, and cataplexy.
An organized diagnostic approach should be used to reduce hospital admissions and medical costs and increase diagnostic accuracy.
Syncope can be divided into five general subgroups.

1) Neurally mediated reflex syncope (carotid sinus syndrome, vasovagal)

2) Orthostatic syncope

3) Cardiac arrhythmias

4) Structural cardiac and pulmonary causes

5) Cerebrovascular disorders.

Initial evaluation should include thorough H&P, including orthostatic vitals and ECG. If diagnosis remains uncertain after initial evaluation, patients’ syncope should be risk stratified into three groups: high, intermediate, and low risk.
Additionally, the 2017 ACC/AHA/HRS guidelines stratify patient risk based on short-term (<30 days) and long-term (>30 days) morbidity and mortality based on initial examination and history.
Patients presenting with high-risk and short-term syncope features should be immediately hospitalized for further diagnostic testing and treatment. High-risk features are usually indicative of underlying cardiovascular causes that could lead to sudden death; this includes but is not limited to life-threatening arrhythmias and acute coronary syndrome.
Risk stratification also determines the selection of diagnostic tests. When underlying cardiac etiology is suspected, diagnostic tests such as echocardiography, CT angiography, cardiac magnetic resonance, electrophysiology study, exercise stress testing, and coronary angiography may be valuable in establishing timely diagnosis in high-risk patients.
Choice of study modality varies greatly based on patient presentation and risk factors. In contrast to patients presenting with high-risk syncope, low-risk patients are discharged home with re-assurance and follow-up.

Strategy for Intracardiac Masses

First, take into account the patient’s age at the time of presentation, as certain medical conditions like rhabdomyomas and fibromas are more commonly observed among pediatric patients.
Second, assess the likelihood from an epidemiological perspective and consider the clinical probability. For instance, if a patient has recently experienced an anterior wall myocardial infarction and exhibits an akinetic ventricular apex, the presence of a cardiac mass during echocardiography could indicate the possibility of an intracardiac thrombus.
Third, factor in the location of the tumor. If the mass is detected on the valves, potential diagnoses to consider include thrombus or vegetation. While masses within the heart chambers might still indicate thrombus, it’s also important to contemplate other possibilities, such as myxomas, lymphomas, and metastases.
Fourth, delve into the tissue characteristics of the mass using additional diagnostic imaging methods like cardiac magnetic resonance imaging.

Imaging Modalities for Intracardiac Masses

Transthoracic echocardiography (TTE) is readily available and non-invasive. Transesophageal echocardiography (TEE) offers insights into size, shape, attachment site, extension, and hemodynamic effects. Ultrasound-enhancing agents in echocardiography help differentiate various masses. Thrombi and benign tumors display a non or low-enhancing pattern. Malignancies and highly vascular tumors display a hyperenhancing pattern. Doppler velocities aid in assessing the hemodynamic impact.
Cardiac MRI (CMR) is invaluable in the assessment of cardiac masses. In addition to anatomy, dimensions, and mass consistency, using different signal sequences like T1, T2, early and late gadolinium enhancement differentiate tissue characteristics and unveil fatty presence, necrosis, bleeding, inflammation, and vascularity within a mass.
Cardiac CT provides high spatial and temporal resolution, multiplanar image reconstruction, and rapid acquisition. The broad field of view allows for the evaluation of the chest, lung tissue, vascular structures, and potential masses within the chest. Cardiac CT can be used to detect calcifications within the mass, although it has less soft tissue resolution compared with CMR.
FDG-PET/CT can help gauge tumors’ metabolic activity. When CT alone doesn’t decisively determine benign or malignant nature, PET/CT steps in, aiding in malignancy diagnosis and guiding biopsy locations, staging, and cancer therapy planning.

Cardiac tumors

Cardiac tumors can be categorized into primary and secondary tumors.
Secondary tumors, arising from metastasis, are more prevalent and often stem from cancers like melanoma, breast, or lung cancer.
Secondary tumors can lead to issues like pericardial effusion with or without cardiac tamponade, myocardial infiltration, obstruction, or embolization. Primary tumors include benign (about 80%) and malignant (about 20%) types.
Malignant tumors are mainly sarcomas, such as angiosarcomas and rhabdomyosarcomas.
Benign tumors encompass myxomas, gelatinous masses with scattered myxoma cells; papillary fibroelastomas, frond-like masses typically on valves; lipomas, composed of fat cells; fibromas, containing fibroblasts and mostly found in the left ventricle; and rhabdomyomas, made of maldeveloped cardiac myocytes and often seen in ventricles. Other rare tumors include Purkinje cell tumors. However, the latter three mentioned are more common in children.

Clot-in-transit

Clot-in-transit (CIT) is the presence of mobile echogenic material in the right atrium or ventricle as seen on ultrasound.
Right heart clots are classified into three types based on their morphology:
- Type A (common and carries a high risk of pulmonary embolization)
- Type B (assumed to originate from the atrium or ventricle)
- Type C (rare and migratory, resembling cardiac myxomas)
Intervention options for CIT include catheter-based thrombolysis, systemic (IV) thrombolysis, surgical/endovascular embolectomy, and anticoagulation therapy.
Catheter-based thrombolysis involves high-frequency ultrasound exposure, catheter-directed thrombolysis, mechanical thrombectomy, and endovascular clot suction. It has a high success rate but may not work for bulky thrombi.
Surgical embolectomy is recommended for hemodynamically unstable patients with CIT and provides an opportunity to address right-to-left heart communication. It requires substantial surgery and cardiopulmonary bypass.
In cases of concomitant CIT and pulmonary embolism (PE), simultaneous treatment is essential to prevent further PE episodes.
Anticoagulants are an option for patients in whom surgery is contraindicated, but they do not affect existing clots and may lead to bleeding or thrombus fragmentation.
Systemic thrombolysis can improve right ventricular function, reduce pulmonary hypertension, and dissolve clots in multiple locations but carries a risk of thrombus embolization as well as bleeding complications.
Management plans for CIT should consider individual patient factors like hemodynamic stability, right heart function, patent foramen ovale (PFO), and malignancy.
There are no definitive guidelines. As a result, treatment decisions should be made on a case-by-case basis. An algorithm for CIT treatment may be helpful in clinical decision-making. PE response teams (PERT) are invaluable for complex decision making.

Angioleiomyoma

These are rare, benign tumors that are classified as pericytic (perivascular) soft tissue tumors.
There appears to be no consensus on incidence and prevalence, though there have been reports of this tumor accounting for around 5% of benign soft tissue tumors. Women are more affected than men. The age of diagnosis tends to be in the 4th to 6th decade.
They typically arise in the extremities, particularly the lower extremities. However, the prevalence of uterine, cardiac, and major vascular deposition (IVC) is unknown.
Typically, when present in the extremities, patients complain of discomfort due to the nodules. That said, location and size will determine symptoms. Pulmonary angioleiomyomas causing dyspnea have been reported. If involving the uterus, patients may present with menorrhagia, abdominal pain, and abdominal mass. Those masses can be submucosal, intramural, subserosal. As in this case, excessive burden in the IVC and right heart can lead to hemodynamic limitations, ultimately leading to symptoms of dyspnea and syncope.
There is no agreement on the pathophysiology of this tumor. However, there are hypotheses, including trauma to the area, venous stasis, and hormonal factors causing the propagation of abnormal cell growth. Proposed histological types include capillary type (narrow vessels interlaced with thick fascicles of smooth muscles), venous type (thick vessels interspersed with fascicles of smooth muscle), and cavernous type (widened vessels with less smooth muscles).
Although echo, CT, and MRI imaging could help evaluate the characteristics of this mass, pathology is required for a definitive diagnosis.
The mainstay treatment is surgical excision of the tumor. This has been effective in preventing recurrence. However, in this case, the treating team should be cognizant of any potential medications leading to the proliferation of this tumor.

Benign metastasizing leiomyoma

The origins of the tumor are typically uterine leiomyomas. These are inherently mitotically inactive smooth muscle cells without atypia, which have migrated to extra-uterine sites.
Although rare, these are mostly seen in patients of reproductive age and frequently involve the lungs, whereby it is called pulmonary benign metastasizing leiomyoma.
Patients may present with incidental extra-uterine leiomyoma found on exam. If there is hemodynamic change in the cardiac chambers or if involving the lungs, patients may present with symptoms including dyspnea, cough, and chest discomfort.
There is evidence to suggest chromosome deletions, particularly in 19q and 22q, may predispose leiomyomas to metastatic potential.
When present in the lung, this needs to be differentiated from pulmonary lymphangioleiomyomatosis (LAM), which on histology demonstrates perivascular epithelioid cells along bronchial interstitium.
Leiomyomas beyond the uterus have been classified as intravenous, benign metastasizing, diffuse peritoneal, retroperitoneal, and parasitic. Incidence is approximately 0.25% to 0.4% for those with leiomyomas.
For patients with symptomatic disease, resection of the leiomyoma, anti-hormonal agents, and anti-angiogenesis agents can be used for tumor treatment.

References – 1. Schaal SF, Nelson SD, Boudoulas H, Lewis RP. Syncope. Curr Probl Cardiol. 1992 Apr;17(4):205-64. doi: 10.1016/0146-2806(92)90002-6. PMID: 1563273. 2. Writing Committee Members; Shen WK, Sheldon RS, Benditt DG, Cohen MI, Forman DE, Goldberger ZD, Grubb BP, Hamdan MH, Krahn AD, Link MS, Olshansky B, Raj SR, Sandhu RK, Sorajja D, Sun BC, Yancy CW. 2017 ACC/AHA/HRS guideline for the evaluation and management of patients with syncope: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Heart Rhythm. 2017 Aug;14(8):e155-e217. doi: 10.1016/j.hrthm.2017.03.004. Epub 2017 Mar 9. PMID: 28286247. 3. Sutton R, Ricci F, Fedorowski A. Risk stratification of syncope: Current syncope guidelines and beyond. Auton Neurosci. 2021 Dec 23;238:102929. doi: 10.1016/j.autneu.2021.102929. Epub ahead of print. PMID: 34968831. 4. Motwani M, Kidambi A, Herzog BA, Uddin A, Greenwood JP, Plein S. MR imaging of cardiac tumors and masses: a review of methods and clinical applications. Radiology. 2013 Jul;268(1):26-43. doi: 10.1148/radiol.13121239. PMID: 23793590. 5. Tyebally S, Chen D, Bhattacharyya S, Mughrabi A, Hussain Z, Manisty C, Westwood M, Ghosh AK, Guha A. Cardiac Tumors: JACC CardioOncology State-of-the-Art Review. JACC CardioOncol. 2020 Jun 16;2(2):293-311. doi: 10.1016/j.jaccao.2020.05.009. PMID: 34396236; PMCID: PMC8352246. 6. Lopez-Mattei JC, Lu Y. Multimodality Imaging in Cardiac Masses: To Standardize Recommendations, The Time Is Now! JACC Cardiovasc Imaging. 2020 Nov;13(11):2412-2414. doi: 10.1016/j.jcmg.2020.04.009. Epub 2020 Jun 17. PMID: 32563655 7. Patel AN, Amrutiya RJ, Manvar BN. A Proposed Approach for the Management of Clot-in-Transit. Cureus. 2022 Aug 27;14(8):e28481. doi: 10.7759/cureus.28481. PMID: 36176887; PMCID: PMC9512516. 8. Hu Y, Ren S, Tan S, Chen C, Wang X, Liang Q, Yu F, Liu W. Angioleiomyoma of the pulmonary artery: a case report and literature review. J Cardiothorac Surg. 2020 Aug 28;15(1):230. doi: 10.1186/s13019-020-01275-z. PMID: 32859240; PMCID: PMC7456385. 9. Sikora-Szczęśniak DL. Uterine angioleiomyoma – a rare variant of uterine leiomyoma: review of literature and case reports. Prz Menopauzalny. 2016 Nov;15(3):165-169. doi: 10.5114/pm.2016.63496. Epub 2016 Nov 15. PMID: 27980528; PMCID: PMC5137480. 10. Zhang JZ, Zhou J, Zhang ZC. Subcutaneous Angioleiomyoma: Clinical and Sonographic Features With Histopathologic Correlation. J Ultrasound Med. 2016 Aug;35(8):1669-73. doi: 10.7863/ultra.15.06056. Epub 2016 Jul 1. PMID: 27371376. 11. Kang BS, Shim HS, Kim JH, Kim YM, Bang M, Lim S, Park GM, Lee TY, Ha ND, Kwon WJ. Angioleiomyoma of the Extremities: Findings on Ultrasonography and Magnetic Resonance Imaging. J Ultrasound Med. 2019 May;38(5):1201-1208. doi: 10.1002/jum.14798. Epub 2018 Sep 12. PMID: 30208227. 12. Kumar S, Hasan R, Maddukuri SB, Mathew M. Angiomyoma presenting as a painful subcutaneous mass: a diagnostic challenge. BMJ Case Rep. 2014 Oct 16;2014:bcr2014206606. doi: 10.1136/bcr-2014-206606. PMID: 25323285; PMCID: PMC4202094. 13. Morimoto Y, Sato M, Yamada A, Gan K. Large right ventricle cardiac leiomyoma metastasis from uterine leiomyoma. BMJ Case Rep. 2022 Dec 8;15(12):e252389. doi: 10.1136/bcr-2022-252389. PMID: 36593619; PMCID: PMC9743285. 14. Galvin SD, Wademan B, Chu J, Bunton RW. Benign metastasizing leiomyoma: a rare metastatic lesion in the right ventricle. Ann Thorac Surg. 2010 Jan;89(1):279-81. doi: 10.1016/j.athoracsur.2009.06.050. PMID: 20103256. 15. Pacheco-Rodriguez G, Taveira-DaSilva AM, Moss J. Benign Metastasizing Leiomyoma. Clin Chest Med. 2016 Sep;37(3):589-95. doi: 10.1016/j.ccm.2016.04.019. Epub 2016 Jun 25. PMID: 27514603. 16. Barnaś E, Książek M, Raś R, Skręt A, Skręt-Magierło J, Dmoch-Gajzlerska E. Benign metastasizing leiomyoma: A review of current literature in respect to the time and type of previous gynecological surgery. PLoS One. 2017 Apr 20;12(4):e0175875. doi: 10.1371/journal.pone.0175875. PMID: 28426767; PMCID: PMC5398563. 17. Mustafa A, Obholz J, Ghanim M, Congello S. Clot in Transit: Therapy via Peripherally Inserted Central Catheter Line. Cureus. 2022 Jan 28;14(1):e21691. doi: 10.7759/cureus.21691. PMID: 35237484; PMCID: PMC8882343.

View Details

CardioNerds cofounder Dr. Amit Goyal and cardiology fellows from the Cleveland Clinic (Drs. Alejandro Duran Crane, Gary Parizher, and Simrat Kaur) discuss the following case: A 61-year-old man presented with symptoms of heart failure and left ventricular hypertrophy. He was given a diagnosis of obstructive hypertrophic cardiomyopathy. He eventually underwent septal myectomy, mitral valve replacement, aortic aneurysm repair, and aortic valve replacement with findings of Fabry’s disease on surgical pathology. The case discussion focuses on the differential diagnosis for LVH and covers Fabry disease as an HCM mimic. Expert commentary was provided by Dr. Angelika Ewrin. The episode audio was edited by student Dr. Diane Masket.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.

CardioNerds Case Reports Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll

CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!

Case Media – An Unusual Cause of Hypertrophic Cardiomyopathy – Cleveland ClinicPearls – An Unusual Cause of Hypertrophic Cardiomyopathy – Cleveland Clinic1. Left ventricular hypertrophy is a cardiac manifestation of several different systemic and cardiac processes, and its etiology should be clarified to avoid missed diagnosis and treatment opportunities. 2. Fabry disease is a rare, X-linked inherited disease that can present cardiac and extra-cardiac manifestations, the former of which include hypertrophic cardiomyopathy, conduction defects, coronary artery disease, conduction abnormalities, arrhythmias, and heart failure. 3. The diagnosis of Fabry disease includes measurement of alpha-galactosidase enzyme activity as well as genetic testing to evaluate for pathogenic variants or variants of unknown significance in the GLA gene. Family members of patients diagnosed with Fabry disease should be screened based on the inheritance pattern. 4. Multimodality imaging can be helpful in the diagnosis of Fabry disease. Echocardiography can show left ventricular hypertrophy (LVH), reduced global strain, aortic and mitral valve thickening, and aortic root dilation with associated mild to moderate aortic regurgitation. Cardiac MRI can show hypertrophy of papillary muscles, mid-wall late gadolinium enhancement and low-native T1 signal. 5. The treatment of Fabry disease involves a multi-disciplinary approach with geneticists, nephrologists, cardiologists, nephrologists, and primary care doctors. Enzyme replacement therapy can delay the progression of cardiac disease.

Show Notes – An Unusual Cause of Hypertrophic Cardiomyopathy – Cleveland ClinicWhat are the causes of left ventricular hypertrophy?

LVH is extremely common. It is present in 15-20% of the general population, and is more common in Black individuals, the elderly, obese or hypertensive individuals, with most cases being secondary to hypertension and aortic valve stenosis. In general terms, it is helpful to divide the causes of LVH into three main groups: high afterload states, obstruction to LV ejection, and intrinsic myocardial problems. Increased afterload states include both primary and secondary hypertension and renal artery stenosis. Mechanical obstruction includes aortic stenosis, subaortic stenosis, and coarctation of the aorta. Lastly, several intrinsic problems of the myocardium can cause LV hypertrophy, such as athletic heart with physiological LVH, hypertrophic cardiomyopathy with or without outflow obstruction, and infiltrative or storage diseases such as cardiac amyloidosis, Fabry’s disease, or Danon disease, among others.

How does Fabry disease present?

Fabry disease is present in all races and is an X-linked lysosomal storage disorder caused by pathogenic variants in the GLA gene that result in reduced alpha-galactosidase enzyme activity, leading to accumulation of lysosomal globotriaosylceramide (Gb3) globotriaosylsphingosine (lyso-Gb3) in affected tissues, including the heart, kidneys, vasculature, and peripheral nervous system. The reported incidence of this disease is said to be between 1 in 40,000 and 1 in 117,000 individuals, but screening in newborns suggests that this incidence may be underestimated, as it is present in up to 1 in 8,800 newborns. Depending on the variant of the mutation or the presence of mosaicism in females, the disease can have variable expression with early-onset presentations in the classical form or late-onset presentations in individuals who have residual a-galactosidase enzyme activity.

Fabry disease can have multiple cardiac and extracardiac manifestations. Accumulation of Gb3 occurs in all cell types of the heart, including smooth muscle cells of the endothelium, myocytes, conduction cells, and valvular fibroblasts. Accumulation of glycosphingolipids also leads to biochemical changes in cell function that lead to apoptosis, cellular necrosis, inflammation, and altered membrane ion channel properties that may lead to increased conduction velocities. In the myocardium, cell damage produces LVH and diastolic dysfunction. Damage to endothelial cells leads to coronary artery disease and myocardial ischemia. Together, these changes may eventually lead to myocardial fibrosis and systolic dysfunction. Involvement of the conduction cells can manifest as conduction abnormalities and ventricular arrhythmias. Other electrocardiographic findings are a short PQ interval or chronotropic incompetence. Aortic remodeling in FD has been well described and often presents as sinus of Valsalva dilatation or ascending aortic aneurysm, which in turn may lead to secondary aortic regurgitation.

Extracardiac manifestations of Fabry disease include neuropathy, gastrointestinal symptoms, angiokeratomas, cornea verticillata (golden-brown or gray discoloration of the corneal epithelium), hypohidrosis and exercise intolerance, proteinuria and renal failure, juvenile or cryptogenic stroke, hearing loss, chronic white matter hyperintensities in brain MRI, and lymphedema.

How is Fabry disease diagnosed?

Diagnosis of Fabry disease should be suspected in patients with unexplained LVH, especially when there are any extracardiac red flags. LVH presents in more than half of men and more than a third of women after the third decade of life. Other electrocardiographic findings besides high QRS voltages may include inferolateral negative T-waves, short PQ intervals, and a reduced P wave duration. The diagnosis is confirmed through genetic testing that may identify pathogenic variants as well as variants of unknown significance. Enzymatic level activities should be measured as well for confirmation. Absent or reduced alpha-galactosidase activity levels coupled with pathogenic variants in genetic testing confirm a diagnosis of FD. Variants of uncertain significance might require confirmation by endomyocardial biopsy and by lyso-Gb3 level assessment.

What is the role of cardiovascular imaging in the diagnosis of Fabry disease?

Multimodality imaging may be helpful in the diagnosis and staging of FD. Echocardiography typically reveals LVH with disproportionate hypertrophy of the papillary muscles, loss of base-to-apex circumferential strain gradient, and right-ventricular hypertrophy with normal systolic function. There may also be abnormal thickening of the aortic and mitral valves. Global longitudinal strain and speckle tracking may allow for early detection of cardiac involvement in patients with pathogenic variants.

Cardiac MRI (CMR) may help with tissue characterization. Typical CMR findings of FD include late gadolinium enhancement (LGE), initially in the basal inferolateral wall, and low native T1 signal intensity, likely reflecting glycosphingolipid myocardial storage and occurring before the development of significant LVH. Tissue characterization by CMR also allows for staging of FD cardiomyopathy in different and progressive stages of accumulation, with progressive lowering of T1 signal intensity; inflammation and hypertrophy, with low T1, initial LVH, and T2 mapping showing inflammation in the basal inferolateral segment associated with LGE; and fibrosis, with increasing T1 values or pseudo-normalization and LGE with wall thinning in the basal inferolateral segment.

What is the management for Fabry disease?

The main objective in the treatment of FD is prevention of disease progression and end-organ damage. The mainstay of therapy is enzyme replacement therapy (ERT) with agalsidase-alfa or beta intravenous injections every other week. Agalsidase-alfa is produced in human cell lines, while the beta form of the enzyme is produced by recombinant DNA technology using mammalian cells.

ERT is indicated in patients with late-onset FD who have the presence of laboratory, histological, or imaging evidence of injury to the heart, kidney, or central nervous system. It can delay the progression of cardiac disease and reduce the cardiovascular event rate in patients with FD.

Another available pharmacological agent is the chaperone agent migalastat, which can be helpful for specific genetic variants of FD by stabilizing the translated form of alpha-galactosidase. This chaperone agent is given in oral tablets every other day. There is ongoing development of novel therapies for FD with second-generation ERTs, substrate reduction therapies, and gene and mRNA therapies.

References – An Unusual Cause of Hypertrophic Cardiomyopathy – Cleveland Clinic1. Weidemann F, Strotmann JM, Niemann M, et al. Heart Valve Involvement in Fabry Cardiomyopathy. Ultrasound in Medicine and Biology. 2009;35(5):730-735. doi:10.1016/j.ultrasmedbio.2008.10.010 2. Pieroni M, Moon JC, Arbustini E, et al. Cardiac Involvement in Fabry Disease: JACC Review Topic of the Week. Journal of the American College of Cardiology. 2021;77(7):922-936. doi:https://doi.org/10.1016/j.jacc.2020.12.024 3. Barbey F, Qanadli SD, Juli C, et al. Aortic remodelling in Fabry disease. European heart journal. 2010;31(3):347-353. doi:10.1093/eurheartj/ehp426 4. Chimenti C, Morgante E, Tanzilli G, et al. Angina in fabry disease reflects coronary small vessel disease. Circulation Heart failure. 2008;1(3):161-169. doi:10.1161/CIRCHEARTFAILURE.108.769729 5. Linhart A, Germain DP, Olivotto I, et al. An expert consensus document on the management of cardiovascular manifestations of Fabry disease. European Journal of Heart Failure. 2020;22(7):1076-1096. doi:https://doi.org/10.1002/ejhf.1960 6. Tower-Rader A, Jaber WA. Multimodality Imaging Assessment of Fabry Disease. Circulation Cardiovascular imaging. 2019;12(11):e009013. doi:10.1161/CIRCIMAGING.119.009013 7. Germain DP, Charrow J, Desnick RJ, et al. Ten-year outcome of enzyme replacement therapy with agalsidase beta in patients with Fabry disease. Journal of Medical Genetics. 2015;52(5):353 LP – 358. doi:10.1136/jmedgenet-2014-102797 8. Pieroni M, Moon JC, Arbustini E, et al. Cardiac Involvement in Fabry Disease: JACC Review Topic of the Week. J Am Coll Cardiol. 2021;77(7):922-936. doi:10.1016/J.JACC.2020.12.024 9. Maron BJ, Desai MY, Nishimura RA, et al. Diagnosis and Evaluation of Hypertrophic Cardiomyopathy: JACC State-of-the-Art Review. J Am Coll Cardiol. 2022;79(4):372-389. doi:10.1016/J.JACC.2021.12.002 10. Bornstein AB, Rao SS, Marwaha K. Left Ventricular Hypertrophy. StatPearls [Internet] Treasure Island (FL). Published online August 8, 2022. Accessed April 1, 2023. https://www.ncbi.nlm.nih.gov/books/NBK557534/

View Details

CardioNerds (Daniel Ambinder) joins Dr. Priyanka Ghosh and Dr. Ahmad Lone from the Guthrie Robert Packer Hospital for a day in the Finger Lakes region of New York. They discuss the following case. A 35-year-old man with nonspecific symptoms of headache, fatigue, and chest wall pain was found to have elevated troponin levels, elevated inflammatory markers, EKG with inferior and anterolateral ST depressions, and no obstructive coronary artery disease on cardiac catheterization. His peripheral eosinophilia, cardiac MRI results, and bone marrow biopsy revealed eosinophilic myocarditis from acute leukemia with eosinophilia. This episode discusses this rare type of myocardial inflammation, its potential causes, and the diagnostic workup with the mention of how this patient was ultimately treated for his acute leukemia and myocarditis. Expert commentary is provided by Dr. Saurabh Sharma. Audio editing by CardioNerds academy intern, student doctor Pace Wetstein.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.

CardioNerds Case Reports Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll

CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!

Case Media – Guthrie Robert Packer HospitalPearls – Guthrie Robert Packer Hospital1. Myocarditis, especially eosinophilic myocarditis, requires a high level of clinical suspicion. 2. Eosinophilic myocarditis should be considered in a patient presenting with chest pain, normal coronary arteries, and pronounced eosinophilia levels. 3. Causes of eosinophilic myocarditis can vary, and diagnosis requires a thorough, detailed history, which cannot be determined many times. 4. Treatment of eosinophilic myocarditis focuses on the underlying etiology, acute management, and therapy for concomitant heart failure or cardiomyopathy. 5. Consider the whole-patient and cardiac manifestations of non-cardiac illnesses.

Show Notes – Guthrie Robert Packer HospitalWhat is eosinophilic myocarditis?

Eosinophilic myocarditis is a type of myocardial inflammation involving eosinophilic cell infiltration and an entity that is likely under-recognized. It requires a high level of suspicion as, many times, patients may not initially present with peripheral eosinophilia, which may develop over the course of their disease process. The presentation can vary from mild cardiac injury to fulminant cardiogenic shock depending on the degree of infiltration and concurrent other organ involvement. The presentation can include heart failure symptoms as well as electrical conduction abnormalities.

How is eosinophilic myocarditis diagnosed?

Eosinophilic myocarditis is diagnosed by a thorough history including new medications, exposures, travel, prior allergy history, physical exam, lab work including a complete blood count differential, inflammatory markers, cardiac biomarkers, and cardiac diagnostics which should include a 12-lead ECG and transthoracic echocardiogram as well as potentially cardiac MRI and/or endomyocardial biopsy.

What are the causes of eosinophilic myocarditis?

The causes of eosinophilic myocarditis include medication-induced, hypersensitivity reactions, infections, malignancy, and immune-mediated disorders such as eosinophilic granulomatosis with polyangiitis and hypereosinophilic syndromes. The hypersensitivity subtype has been reported to be the most common cause. Potential offending medications can include antibiotics, sulfonamides, anticonvulsants, anti-inflammatory medications, and diuretics.

What is the treatment for eosinophilic myocarditis?

Treatment for eosinophilic myocarditis is multi-faceted, including focusing on the etiology and withdrawal of any potential offending agents, management of the acute clinical presentation, and treatment of any concomitant heart failure or cardiomyopathy. Immunosuppressive therapy has been controversial; however, many case reports have successfully used methylprednisolone, and some patients with cardiogenic shock from eosinophilic myocarditis have received therapy with azathioprine.

References 1. Al Ali AM, Straatman LP, Allard MF, Ignaszewski AP. Eosinophilic myocarditis: case series and review of literature. Can J Cardiol. 2006 Dec;22(14):1233-7. doi: 10.1016/s0828-282x(06)70965-5. PMID: 17151774; PMCID: PMC2569073. 2. Takkenberg JJ, Czer LS, Fishbein MC, Luthringer DJ, Quartel AW, Mirocha J, Queral CA, Blanche C, Trento A. Eosinophilic myocarditis in patients awaiting heart transplantation. Crit Care Med. 2004 Mar;32(3):714-21. doi: 10.1097/01.ccm.0000114818.58877.06. PMID: 15090952. 3. Morimoto S, Kubo N, Hiramitsu S, Uemura A, Ohtsuki M, Kato S, Kato Y, Sugiura A, Miyagishima K, Mori N, Yoshida Y, Hishida H. Changes in the peripheral eosinophil count in patients with acute eosinophilic myocarditis. Heart Vessels. 2003 Sep;18(4):193-6. doi: 10.1007/s00380-003-0721-0. PMID: 14520487. 4. Burke AP, Saenger J, Mullick F, Virmani R. Hypersensitivity myocarditis. Arch Pathol Lab Med. 1991 Aug;115(8):764-9. PMID: 1863186. 5. Fozing T, Zouri N, Tost A, Breit R, Seeck G, Koch C, Oezbek C. Management of a patient with eosinophilic myocarditis and normal peripheral eosinophil count: case report and literature review. Circ Heart Fail. 2014 Jul;7(4):692-4. doi: 10.1161/CIRCHEARTFAILURE.114.001130. PMID: 25028351. 6. Brambatti M, Matassini MV, Adler ED, Klingel K, Camici PG, Ammirati E. Eosinophilic Myocarditis: Characteristics, Treatment, and Outcomes. J Am Coll Cardiol. 2017 Nov 7;70(19):2363-2375. doi: 10.1016/j.jacc.2017.09.023. PMID: 29096807. 7. Cheung CC, Constantine M, Ahmadi A, Shiau C, Chen LYC. Eosinophilic Myocarditis. Am J Med Sci. 2017 Nov;354(5):486-492. doi: 10.1016/j.amjms.2017.04.002. Epub 2017 Apr 6. PMID: 29173361. 8. Aggarwal A, Bergin P, Jessup P, Kaye D. Hypersensitivity myocarditis presenting as cardiogenic shock. J Heart Lung Transplant. 2001 Nov;20(11):1241-4. doi: 10.1016/s1053-2498(01)00313-8. PMID: 11704488. 9. Kounis NG, Zavras GM, Soufras GD, Kitrou MP. Hypersensitivity myocarditis. Ann Allergy. 1989 Feb;62(2):71-4. PMID: 2645814. 10. Li H, Dai Z, Wang B, Huang W. A case report of eosinophilic myocarditis and a review of the relevant literature. BMC Cardiovasc Disord. 2015 Feb 26;15:15. doi: 10.1186/s12872-015-0003-7. PMID: 25887327; PMCID: PMC4359588.

View Details

CardioNerds (Dr. Josh Saef and Dr. Sumeet Vaikunth) join Dr. Sheng Fu, Dr. Payton Kendsersky, and Dr. Aniqa Shahrier from the Medical University of South Carolina for some off-shore fishing. They discuss the following featuring a patient with D-TGA and Eisenmenger’s syndrome treated with a Heartmate 3. Expert commentary was provided by Dr. Brian Houston. The episode audio was edited by student Dr. Adriana Mares.

A 39-year-old woman with a history of D-transposition of the great arteries (D-TGA) with prior atrial switch repair (Mustard) was admitted from the clinic with cardiogenic shock. She underwent right heart catheterization which demonstrated elevated biventricular filling pressures and low cardiac index. An intra-aortic balloon pump was placed, and the patient was evaluated for advanced therapies. A liver biopsy showed grade 3 fibrosis, which, in combination with her shock state, made her a high-risk candidate for isolated heart or combined heart-liver transplantation. After a multi-disciplinary discussion, the patient underwent a Heartmate III left ventricular assist device (LVAD) implant in her systemic right ventricle. Although she did well post-operatively, she was admitted after a month with recurrent cardiogenic shock, with imaging showing her inflow cannula had become perpendicular to the septum. The patient and family eventually decided to pursue comfort measures, and the patient passed.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.

CardioNerds Case Reports Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll

CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!

Case Media – D-TGA and Eisenmenger’s syndrome treated with a Heartmate 3Pearls – D-TGA and Eisenmenger’s syndrome treated with a Heartmate 3* Early diagnosis of cyanotic congenital heart disease is paramount for treatment and prevention of future complications. * Adult congenital heart disease requires a multi-disciplinary team for management in consultation with an adult congenital cardiology specialist. * Eisenmenger syndrome is related to multiple systemic complications and has a high rate of mortality. * Advancement in PAH medical management can offer noninvasive treatment options for some patients. * Transthoracic echocardiography is the cornerstone for diagnosis. Other modalities (e.g. cardiac CT, cardiac MRI, invasive catheterization) can aid in diagnosis and management.

Pearls – D-TGA and Eisenmenger’s syndrome treated with a Heartmate 31. While advances in pediatric surgery have allowed many patients born with congenital heart disease to survive into adulthood, adult congenital heart disease (ACHD) patients are complex and prone to numerous adverse sequalae including arrhythmias, heart failure, valvular disease, and non-cardiac organ dysfunction. 2. Heart failure can be a challenging presentation in ACHD patients due to a longstanding history of clinical compensation. 3. Their unique and complex anatomy, as well as highly variable clinical presentation, present unique challenges when it comes to advanced heart failure options such as durable left ventricular assist devices (LVAD) or transplantation. 4. While durable LVAD implantation is possible in patients with systemic right ventricles, anatomic compatibility is paramount and poses ongoing challenges in their management. 5. Goals of care discussions should be had early, as options for treatment may be limited.

Show Notes – D-TGA and Eisenmenger’s syndrome treated with a Heartmate 3What are some common sequelae in ACHD patients?

ACHD patients are a heterogeneous population, but atrial tachycardias are extremely frequent in this patient population, often due to re-entrant pathways around surgical suture lines. These can often be treated with radiofrequency ablation while paying close attention to their challenging anatomy. Heart failure is also extremely common (up to 40% incidence) but has variable incidence dependent on the specific anatomy. Valvular heart disease, including infective endocarditis as well as non-cardiac organ dysfunction, are also important contributors to the overall prognosis of ACHD patients.

How does heart failure present in ACHD patients?

Heart failure presentations in ACHD patients tend to be subacute and insidious, as patients often have become accustomed to their symptoms. They are often unable to identify clear exercise limitations due to the slow, subacute nature of symptoms. However, acute presentations and shock can also be seen. Heart failure is the leading cause of death in ACHD patients.

What are the challenges for advanced therapies in the ACHD population?

First and foremost, risk stratification for these patients is often difficult due to often unreliable self-reporting of symptoms. Thus, early recognition becomes key, but even then, may not be enough. Several anatomic and physiological challenges remain. ACHD patients have often undergone multiple cardiac surgeries, increasing the surgical risk of redo sternotomies with severe adhesions. Due to the longstanding nature of their disease, ACHD patients often develop irreversible pulmonary hypertension (making transplant prohibitive) or end-organ dysfunction secondary to right heart failure (necessitating dual organ transplant).

Is durable LVAD a feasible option for patients with systemic right ventricles?

Isolated case reports demonstrate the feasibility of the off-label use of durable LVADs in systemic right ventricles. The complex anatomy of these patients has led to reports of alternative implant sites for the inflow cannula to minimize obstruction. Alternative surgical approaches, such as lateral thoracotomy, have also been described to try to avoid the adhesions that are often seen in these patients as a result of multiple prior cardiac surgeries. While the surgery is technically feasible, long-term data is not available, and this remains a “bail-out” therapy with current-generation LVAD designs.

What is the role of goals of care discussions in ACHD patients?

Advanced care planning is rarely discussed in routine clinic visits, and most providers wait until the condition has deteriorated significantly. Most ACHD patients want to discuss advanced care early before the disease progresses, but some do not, so it is important to ask about patient preferences. The majority of ACHD patients prefer to have advanced care discussions with their ACHD provider due to an already established and trusting relationship.

References 1. Gatzoulis MA, Webb GD, F. DPE, Hornung T, O’Donnell C. Transposition of the Great Arteries. In: Diagnosis and Management of Adult Congenital Heart Disease: Expert Consult – Online and Print. 3rd ed. Elsevier; 2018:513-527. 2. Stout KK, Daniels CJ, Aboulhosn JA, et al. 2018 AHA/ACC guideline for the management of adults with congenital heart disease: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139(14). 3. Schwerzmann M, Goossens E, Gallego P, et al. Recommendations for advance care planning in adults with congenital heart disease: A position paper from the ESC Working Group of adult congenital heart disease, the Association of Cardiovascular Nursing and Allied Professions (ACNAP), the European Association for Palliative Care (EAPC), and the International Society for Adult Congenital Heart Disease (ISACHD). European Heart Journal. 2020;41(43):4200-4210. doi:10.1093/eurheartj/ehaa614 4. Khairy P, Clair M, Fernandes SM, et al. Cardiovascular outcomes after the arterial switch operation for D-transposition of the great arteries. Circulation. Jan 22 2013;127(3):331-9. doi:10.1161/CIRCULATIONAHA.112.135046 5. Piran S, Veldtman G, Siu S, Webb GD, Liu PP. Heart failure and ventricular dysfunction in patients with single or systemic right ventricles. Circulation. Mar 12 2002;105(10):1189-94. doi:10.1161/hc1002.105182 6. Zandstra TE, Palmen M, Hazekamp MG, Meyns B, Beeres SLMA, Holman ER, Kiès P, Jongbloed MRM, Vliegen HW, Egorova AD, Schalij MJ, Tops LF. Ventricular assist device implantation in patients with a failing systemic right ventricle: a call to expand current practice. Neth Heart J. 2019 Dec;27(12):590-593. 7. Burchill LJ. Heart transplantation in adult congenital heart disease. Heart. 2016;102:1871–1877. doi: 10.1136/heartjnl-2015-309074.

View Details

CardioNerds (Dr. Josh Saef, Dr. Agnes Koczo) join Dr. Iva Minga, Dr. Kifah Hussain, and Dr. Kevin Lee from the University of Chicago – NorthShore to discuss a case of unrepaired congenital heart disease that involves D-TGA complicated by Eisenmenger syndrome. The ECPR was provided by Dr. Michael Earing. Audio editing by Dr. Akiva Rosenzveig.

A 25-year-old woman with an unknown congenital heart disease that was diagnosed in infancy in Pakistan presents to the hospital for abdominal pain and weakness. She is found to be profoundly hypoxemic, and an echocardiogram revealed D-transposition of the great arteries (D-TGA) with a large VSD. As this was not repaired in childhood, she has unfortunately developed Eisenmenger syndrome with elevated pulmonary vascular resistance. She is stabilized and treated medically for her cyanotic heart disease. Unfortunately given the severity and late presentation of her disease, she has limited long-term options for care. CardioNerds discuss the diagnosis of D-TGA and Eisenmenger’s syndrome, as well as long-term management and complications associated with this entity.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.

CardioNerds Case Reports Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll

CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!

Case Media – Unrepaired Congenital Heart DiseasePearls – Unrepaired Congenital Heart Disease* Early diagnosis of cyanotic congenital heart disease is paramount for treatment and prevention of future complications. * Adult congenital heart disease requires a multi-disciplinary team for management in consultation with an adult congenital cardiology specialist. * Eisenmenger syndrome is related to multiple systemic complications and has a high rate of mortality. * Advancement in PAH medical management can offer noninvasive treatment options for some patients. * Transthoracic echocardiography is the cornerstone for diagnosis. Other modalities (e.g. cardiac CT, cardiac MRI, invasive catheterization) can aid in diagnosis and management.

Show Notes – Unrepaired Congenital Heart DiseaseCyanotic congenital heart disease is often diagnosed in infancy and timely treatment is paramount. As these diseases progress over time, pulmonary over-circulation often pulmonary hypertension (PH), elevated pulmonary vascular resistance, and Eisenmenger syndrome will develop, which preclude definitive treatment. For D-TGA, before PH develops, there are surgical options such as the arterial switch procedure that can treat the disease. Unfortunately, once Eisenmenger syndrome develops, there are multiple systemic complications including hyperviscosity, thrombosis, bleeding, kidney disease, iron deficiency, arrhythmias, etc. that can occur. Management requires a multi-disciplinary team including an adult congenital cardiology specialist, but mortality rates remain high, with median survival reduced by 20 years, worse with complex cardiac defects. Bosentan is a first line treatment for patients with Eisenmenger syndrome, with PDE-5 inhibitors as a second line either by themselves or in combination with bosentan. Data are currently limited for latest-generation PH treatments in Eisenmenger syndrome and further study is still underway.

References 1. Ferencz C. Transposition of the great vessels. Pathophysiologic considerations based upon a study of the lungs. Circulation. 1966 Feb;33(2):232-41. 2. Arvanitaki A, Gatzoulis MA, Opotowsky AR, Khairy P, Dimopoulos K, Diller GP, Giannakoulas G, Brida M, Griselli M, Grünig E, Montanaro C, Alexander PD, Ameduri R, Mulder BJM, D’Alto M. Eisenmenger Syndrome: JACC State-of-the-Art Review. J Am Coll Cardiol. 2022 Mar 29;79(12):1183-1198. 3. Earing MG, Webb GD. Congenital heart disease and pregnancy: maternal and fetal risks. Clin Perinatol. 2005 Dec;32(4):913-9, viii-ix 4. Østergaard L, Valeur N, Ihlemann N, Bundgaard H, Gislason G, Torp-Pedersen C, Bruun NE, Søndergaard L, Køber L, Fosbøl EL. Incidence of infective endocarditis among patients considered at high risk. Eur Heart J. 2018 Feb 14;39(7):623-629 5. Opotowsky AR, Moko LE, Ginns J, Rosenbaum M, Greutmann M, Aboulhosn J, Hageman A, Kim Y, Deng LX, Grewal J, Zaidi AN, Almansoori G, Oechslin E, Earing M, Landzberg MJ, Singh MN, Wu F, Vaidya A. Pheochromocytoma and paraganglioma in cyanotic congenital heart disease. J Clin Endocrinol Metab. 2015 Apr;100(4):1325-34. 6. Jaïs X, D’Armini AM, Jansa P, Torbicki A, Delcroix M, Ghofrani HA, Hoeper MM, Lang IM, Mayer E, Pepke-Zaba J, Perchenet L, Morganti A, Simonneau G, Rubin LJ; Bosentan Effects in iNopErable Forms of chronIc Thromboembolic pulmonary hypertension Study Group. Bosentan for treatment of inoperable chronic thromboembolic pulmonary hypertension: BENEFiT (Bosentan Effects in iNopErable Forms of chronIc Thromboembolic pulmonary hypertension), a randomized, placebo-controlled trial. J Am Coll Cardiol. 2008 Dec 16;52(25):2127-34. 7. Gatzoulis MA, Landzberg M, Beghetti M, Berger RM, Efficace M, Gesang S, He J, Papadakis K, Pulido T, Galiè N; MAESTRO Study Investigators. Evaluation of Macitentan in Patients With Eisenmenger Syndrome. Circulation. 2019 Jan 2;139(1):51-63. 8. McLaughlin VV, Gaine SP, Howard LS, Leuchte HH, Mathier MA, Mehta S, Palazzini M, Park MH, Tapson VF, Sitbon O. Treatment goals of pulmonary hypertension. J Am Coll Cardiol. 2013 Dec 24;62(25 Suppl):D73-81. 9. Stoica SC, McNeil KD, Perreas K, Sharples LD, Satchithananda DK, Tsui SS, Large SR, Wallwork J. Heart-lung transplantation for Eisenmenger syndrome: early and long-term results. Ann Thorac Surg. 2001 Dec;72(6):1887-91.

View Details

CardioNerds co-founder Dr. Dan Ambinder joins CardioNerds join Dr. Pooja Prasad, Dr. Khoa Nguyen and expert Dr. Abigail Khan (Assistant Professor of Medicine, Division of Cardiovascular Medicine, School of Medicine) from Oregon Health & Science University and discuss a case of mechanical valve thrombosis. Audio editing by CardioNerds Academy Intern, student doctor Adriana Mares. A 23-year-old pregnant […]

View Details

CardioNerds co-founder Dr. Dan Ambinder joins Dr. Abdelrhman Abumoawad, Dr. Leili Behrooz from the Boston University Vascular Medicine over hot chocolate in Boston. They discuss two interesting cases of lower extremity edema caused by May-Thurner syndrome. Dr. Naomi Hamburg (Professor of Vascular Medicine and Cards at BU/BMC) provides the ECPR for this episode. Audio editing […]

View Details

CardioNerds cofounders Dr. Amit Goyal and Dr. Daniel Ambinder join Dr. Isabel Balachandran, Dr. Diego Celli from the Texas Heart Institute. They discuss the nuances of risk stratification management of intermediate risk pulmonary embolism. The ECPR for this episode was provided by Dr. Alam Mahboob (Associate Professor of Medicine at Baylor College of Medicine and […]

View Details

In this episode, CardioNerds co-founder Amit Goyal joins Dr. Iva Minga, Dr. Kevin Lee, and Dr. Juan Pablo Salazar Adum from the University of Chicago – Northshore in Evanston, IL to discuss a case of primary cardiac diffuse large B-cell lymphoma. The ECPR for this episode is provided by Dr. Amit Pursnani (Advanced Cardiac Imaging, […]

View Details

CardioNerds (Drs. Amit Goyal and Dan Ambinder) join Dr. Emily Lee (LAC+USC Internal medicine resident) and Dr. Charlie Lin (LAC+USC Cardiology fellow) as the discuss an important case of stimulant-related (methamphetamine) cardiovascular toxicity that manifested in right ventricular dysfunction due to severe pulmonary hypertension. Dr. Jonathan Davis (Director, Heart Failure Program at Zuckerberg San Francisco […]

View Details

CardioNerds (Drs. Amit Goyal and Dan Ambinder) join Dr. Mina Fares, Dr. Johannes Bergehr, and Dr. Christina Peter from Cambridge University Hospitals in the UK. They discuss a case involving a man man in his 40’s presented with progressive heart failure symptoms. He has extensive background cardiac history including prior episodes of myocarditis and complete heart block status post permanent pacemaker implantation. Ultimately a diagnosis of Danon disease is made. Dr. Sharon Wilson provides the E-CPR for this episode. Audio editing by CardioNerds Academy Intern, Hirsh Elhence.

CardioNerds is collaborating with Radcliffe Cardiology and US Cardiology Review journal (USC) for a ‘call for cases’, with the intention to co-publish high impact cardiovascular case reports, subject to double-blind peer review. Case Reports that are accepted in USC journal and published as the version of record (VOR), will also be indexed in Scopus and the Directory of Open Access Journals (DOAJ).

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

CardioNerds Case Reports Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll

CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!

Case Summary – A Presentation of Heart Failure and Heart Block with Elusive Genetic Origins – Cambridge UniversityA man in his 40s with a history of cardiac issues, including prior myocarditis and complete heart block, presented with progressive heart failure symptoms. Extensive cardiac investigations were conducted, revealing dilated left ventricle, mild to moderate left ventricular systolic dysfunction, normal coronaries, infero-lateral late gadolinium enhancement on cardiac MRI, and low-level uptake on PET-CT. Differential diagnosis included worsening underlying cardiomyopathy, recurrent myocarditis, tachycardia-related cardiomyopathy, pacemaker-induced LV dysfunction, and sarcoidosis. The patient’s condition improved with heart failure medications, and cardiac MRI showed a mildly dilated left ventricle with moderate systolic dysfunction and active inflammation in the anterior wall. Further evaluation indicated a family history of hereditary cardiomyopathy, and the patient exhibited phenotypic features such as early-onset heart disease, arrhythmias, family history of cardiomyopathy, learning problems, intellectual disability, and mild proximal myopathy. Genetic testing confirmed a LAMP2 mutation, leading to the diagnosis of Danon disease.

Case Media – A Presentation of Heart Failure and Heart Block with Elusive Genetic Origins – Cambridge UniversityShow Notes -A Presentation of Heart Failure and Heart Block with Elusive Genetic Origins – Cambridge UniversityReferences – 1. Danon, M. J., Oh, S. J., DiMauro, S., Miranda, A., De Vivo, D. C., & Rowland, L. P. (1981). Lysosomal glycogen storage disease with normal acid maltase. Neurology, 31(1), 51-7. 2. Nishino, I., Fu, J., Tanji, K., Nonaka, I., & Ozawa, T. (2000). Mutations in the gene encoding LAMP2 cause Danon disease. Nature, 406(6798), 906-10. 3. Tanaka, K., Nishino, I., Nonaka, I., Fu, J., & Ozawa, T. (2000). Danon disease is caused by mutations in the gene encoding LAMP2, a lysosomal membrane protein. Nature, 406(6798), 902-6. 4. Maron, B. J., Haas, T. S., Ackerman, M. J., Ahluwalia, A., Spirito, P., Nishino, I., … & Seidman, C. E. (2009). Hypertrophic cardiomyopathy and sudden death in a family with Danon disease. JAMA, 301(12), 1253-9. 5. Hashem, S., Zhang, J., Zhang, Y., Wang, H., Zhang, H., Liu, L., … & Wang, J. (2015). AAV-mediated gene transfer of LAMP2 improves cardiac function in Danon disease mice. Stem cells, 33(11), 2343-2350. 6. Chi, L., Wang, H., Zhang, J., Zhang, Y., Liu, L., Wang, J., … & Hashem, S. (2019). CRISPR/Cas9-mediated gene editing of LAMP2 in patient-derived iPSCs ameliorates Danon disease phenotypes. Proceedings of the National Academy of Sciences, 116(4), 556-565.

View Details

CardioNerds (Daniel Ambinder) join Dr. Tomio Tran, Dr. Vid Yogeswaran, and Dr. Amanda Cai from the University of Washington for a break from the rain at the waterfront near Pike Place Market. They discuss the following case: A 46-year-old woman presents with cardiac arrest and was found to have cor triatriatum sinistrum (CTS). CTS is a rare congenital cardiac malformation in which the left atrium is divided by a fenestrated membrane, which can restrict blood flow and cause symptoms of congestive heart failure. Rarely, the condition can present in adulthood. To date, there have been no cases of sudden cardiac death attributed to CTS. Dr. Jill Steiner provides the E-CPR for this episode. Audio editing by CardioNerds Academy Intern, student doctor Akiva Rosenzveig.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

CardioNerds Case Reports Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll

CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!

Case Media – A Sinister Cause of Sudden Cardiac Death – University of WashingtonA 40-year-old woman with a history of recurrent exertional syncope had sudden loss of consciousness while kissing her partner. The patient received bystander CPR while 911 was called. EMS arrived within 10 minutes of the call and found the patient apneic and unresponsive. Initial rhythm check showed narrow complex tachycardia at a rate of 136 BPM. ROSC was eventually achieved. A 12-lead ECG showed that the patient was in atrial fibrillation with rapid ventricular rate. The patient was intubated and brought to the emergency department. The patient spontaneously converted to sinus rhythm en route to the hospital.

In the emergency department, vital signs were remarkable for hypotension (76/64 mmHg) and sinus tachycardia (110 BPM). The physical exam was remarkable for an inability to follow commands. Laboratory data was remarkable for hypokalemia (2.5 mmol/L), transaminitis (AST 138 units/L, ALT 98 units/L), acidemia (pH 7.12), and hyperlactatemia (11.2 mmol/L). CT scan of the chest revealed a thin membrane within the left atrium. Transthoracic echocardiogram showed normal biventricular size and function, severe tricuspid regurgitation, pulmonary artery systolic pressure of 93 mmHg, and the presence of a membrane within the left atrium with a mean gradient of 25 mmHg between the proximal and distal left atrial chambers. Vasopressors and targeted temperature management were initiated.

The patient was able to be re-warmed with eventual discontinuation of vasopressors, however she had ongoing encephalopathy and seizures concerning for hypoxic brain injury. There was discussion with the adult congenital heart disease team about next steps in management, however the patient was too sick to undergo any definitive treatment for the intracardiac membrane within the left atrium. The patient developed ventilator associated pneumonia and antibiotics were initiated. The patient ultimately developed bradycardia and pulseless electrical activity; ROSC was unable to be achieved, resulting in death.

Autopsy was remarkable for the presence of a fenestrated intracardiac membrane within the left atrium and lack of other apparent congenital heart defects. There was right ventricular hypertrophy and pulmonary artery intimal thickening with interstitial fibrosis suggestive of pulmonary hypertension. There were bilateral acute subsegmental pulmonary emboli present. The cause of death was declared to be arrhythmia in the setting of pulmonary hypertension and right sided heart failure caused by cor triatriatum sinistrum with a significant contribution from acute subsegmental pulmonary emboli.

Case Media – A Sinister Cause of Sudden Cardiac Death – University of WashingtonPearls – A Sinister Cause of Sudden Cardiac Death – University of Washington1. In a patient presenting with syncope, the following feature may indicate an underlying cardiac etiology: exertional syncope, sudden syncope without a prodrome, structural heart disease, advanced age, and family history of sudden cardiac or unexplained death. 2. Cor triatriatum sinistrum is diagnosed by CT, echocardiography, or MRI and is often found incidentally in adults. 3. Acute management of CTS is similar to mitral stenosis and consists of 1) careful volume management to avoid both hypovolemia and hypervolemia, and 2) avoidance of tachycardia to allow for adequate LV filling during diastole. Surgical resection of the membrane is definitive. 4. A mean gradient of ≥ 8 mmHg across a CTS membrane is hemodynamically significant and should prompt surgical evaluation for membrane resection.

Show Notes -A Sinister Cause of Sudden Cardiac Death – University of Washington* Syncope + Loss of consciousness due to transient decrease in cerebral blood flow + Differential - Orthostatic - Neurally mediated - Cardiogenic - Mimickers of syncope: seizures, head trauma causing loss of consciousness, hypoglycemia + Red flag symptoms of cardiogenic syncope - Advanced age - Exertional or while lying down - Palpitations prior to event - Structural heart disease - Family history of unexplained or sudden cardiac death + Structural heart disease etiologies - Generally left sided and causes obstruction to blood flow - Valvular stenoses - Hypertrophic cardiomyopathy - Cardiac tumors + Arrhythmia etiologies - Can be caused by any brady- or tachyarrhythmia, especially in the setting of structural heart disease - Most commonly * Sinus node disease * High degree heart block * Ventricular arrhythmia * Pulse pressure + Difference between systolic and diastolic pressure + Normal ~ 40 mmHg + Narrow – <25% of systolic blood pressure + Wide – >100 mmHg + Wide pulse pressure etiologies - Physical conditioning (normal variant) - Aortic regurgitation - Severe iron deficiency anemia - Hyperthyroidism - Arteriosclerosis - Shunting from arteriovenous fistulas + Narrow pulse pressure etiologies – indicates low stroke volume/cardiac output - Heart failure - Hypovolemia - Blood loss - Valvular stenosis - Cardiac tamponade - Pulmonary embolism * Cor triatriatum sinister + Presence of a membrane within the left atrium that divides the left atrium into 2 chambers + Pathophysiology - Theorized to be caused by misincorporation of the pulmonary veins within the left atrium causing a membrane within the left atrium - If restrictive, sequelae include congestive heart failure, pulmonary hypertension, and right ventricular dysfunction - Often associated with other congenital heart disease (ASD, pulmonary venous return, mitral regurgitation) + Epidemiology - Among the rarest of all congenital heart disease (up to 0.4% of all congenital heart disease, but true incidence is unknown as many can be asymptomatic) - Found more often in infancy/childhood; often found incidentally in adults + Signs/symptoms - Many are asymptomatic - Over time, membrane may become fibrotic or calcified and cause significant obstruction - Infants/children – pulmonary congestion, respiratory infections, cyanosis, growth restriction - Adults – dyspnea, chest pain, palpitations, syncope * Thrombotic events are common likely from vascular injury and congestion/stasis * Atrial arrhythmia is associated with CTS, possibly from scarring of the membrane vs chronic elevation of left atrial pressure + Diagnosis - Made by imaging (CT chest/cardiac, echocardiography, MRI) - Primary competing differential diagnosis is supravalvular mitral ring * If intra-atrial membrane contains the left atrial appendage and pulmonary veins -> supravalvular mitral ring + Associated with Schone complex (supravalvular mitral ring, parachute mitral valve, subaortic stenosis, aortic coarctation + CTS rarely associated with Shone complex * If intra-atrial membrane contains only the pulmonary veins -> CTS + Can be found incidentally and cause technical issues in cardiac procedures that require transeptal atrial punctures - Quantify degree of restriction with echocardiography; gradients ≥ 8 mmHg are significant per AHA guidelines + Treatment - Acute: * Diuretics to treat congestion * Fluids to avoid hypovolemia due to preload dependence for cardiac output * Treat underlying causes of tachycardia to optimize diastolic filling * Treat tachyarrhythmia with anti-arrhythmis and AV nodal blockers - Chronic/definitive: * Surgical resection of the membrane offers a good and durable outcome + Low recurrence rate, residual gradients likely due to incomplete resection * Pulmonary hypertension + WHO classification - Group 1 – Pulmonary arterial hypertension (idiopathic, toxin induced, HIV, connective tissue disease, congenital heart disease * Congenital heart disease comprises a small portion of group 1, typically from shunt lesions - Group 2 – Left sided heart disease - Group 3 – Pulmonary disease - Group 4 – CTEPH - Group 5 – Unclear mechanisms (sickle cell, sarcoid, metabolic disease)

References – 1. Albassam OT, Redelmeier RJ, Shadowitz S, Husain AM, Simel D, Etchells EE. Did This Patient Have Cardiac Syncope?: The Rational Clinical Examination Systematic Review. JAMA. 2019;321(24):2448-2457. doi:10.1001/jama.2019.8001 2. Jegier W, Gibbons JE, Wigglesworth FW. Cortriatriatum: clinical, hemodynamic and pathological studies surgical correction in early life. Pediatrics. 1963;31:255-267. 3. Jha AK, Makhija N. Cor Triatriatum: A Review. Semin Cardiothorac Vasc Anesth. 2017;21(2):178-185. doi:10.1177/1089253216680495 4. Rudienė V, Hjortshøj CMS, Glaveckaitė S, et al. Cor triatriatum sinistrum diagnosed in the adulthood: a systematic review. Heart. 2019;105(15):1197-1202. doi:10.1136/heartjnl-2019-314714 5. Saxena P, Burkhart HM, Schaff HV, Daly R, Joyce LD, Dearani JA. Surgical repair of cor triatriatum sinister: the Mayo Clinic 50-year experience. Ann Thorac Surg. 2014;97(5):1659-1663. doi:10.1016/j.athoracsur.2013.12.046 6. Stout KK, Daniels CJ, Aboulhosn JA, et al. 2018 AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines [published correction appears in J Am Coll Cardiol. 2019 May 14;73(18):2361]. J Am Coll Cardiol. 2019;73(12):1494-1563. doi:10.1016/j.jacc.2018.08.1028 7. Yaroglu Kazanci S, Emani S, McElhinney DB. Outcome after repair of cor triatriatum. Am J Cardiol. 2012;109(3):412-416. doi:10.1016/j.amjcard.2011.09.029

View Details

CardioNerds join Dr. Samid Muhammad Farooqui, Dr. Hiba Hammad, and Dr. Syed Talal Hussain, from the University of Oklahoma Pulmonary and Critical Care Medicine Fellowship Program, in Oklahoma City. The fellows will take us in a fascinating discussion of a case of rapidly progressing dyspnea and pulmonary hypertension in a patient with metastatic breast cancer. They will then reveal an interesting etiology of pulmonary hypertension, where the secret was on the wedge! University of Oklahoma faculty and expert in pulmonary hypertension and right ventricular physiology, Dr. Roberto J. Bernardo provides the E-CPR for this episode. Audio editing by CardioNerds Academy Intern, Dr. Christian Faaborg-Andersen.

A septuagenarian female, with a past medical history of metastatic breast adenocarcinoma, presented to the hospital with worsening dyspnea over a period of 3 weeks. She was found to be in rapidly progressive hypoxic respiratory failure with unremarkable chest x-ray, CTA chest, and V/Q scan. Transthoracic echocardiogram revealed elevated RVSP and a subsequent right heart catheterization showed pre-capillary pulmonary hypertension with a low cardiac index. She was treated for rapidly progressive RV dysfunction with inotropic support and inhaled pulmonary vasodilators until she decided to pursue comfort measures. Wedge cytology came back positive for malignant cells, confirming a diagnosis of Pulmonary Tumoral Thrombotic Microangiopathy (PTTM).

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

CardioNerds Case Reports Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll

CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!

Case Media – When Tumors Take Your Breath Away – University of Oklahoma College of MedicinePearls – When Tumors Take Your Breath Away – University of Oklahoma College of Medicine1. Pulmonary arterial hypertension (PAH) is a progressive disorder of the pulmonary vasculature, characterized by progressive obliteration and remodeling of the pulmonary circulation, resulting in increased pulmonary vascular resistance and increased right ventricular (RV) wall stress, abnormal right ventricular mechanics, and eventually RV dysfunction and death. 2. Pulmonary hypertension (PH) is divided into pre-capillary and post-capillary profiles, where pre-capillary PH is hemodynamically characterized by a mean pulmonary artery pressure (mPAP) > 20 mmHg, pulmonary artery wedge pressure (PAWP) ≤ 15 mmHg and a pulmonary vascular resistance (PVR) ≥ 3 Woods Units (WU), and post-capillary PH is defined as mPAP > 20 mmHg, PAWP ≥ 15 mmHg, and PVR can be either < 3 WU (isolated post-capillary PH) or ≥ 3 WU (combined pre- and post-capillary PH). Pulmonary arterial hypertension (PAH) falls under the pre-capillary PH profile. 3. Dyspnea on exertion is the most common manifestation of PH, and the most common initial complain. Other symptoms and physical findings such as venous congestion, peripheral edema, signs of RV dysfunction or syncope present later in the disease course. As such, PH has to be considered in the differential diagnosis of dyspnea, especially in cases of undifferentiated or unexplained dyspnea. 4. PAH is a chronic but progressive condition, where symptoms progress over the course of months to years. Subacute or rapidly progressive forms of PH (symptoms rapidly worsening over the course of weeks) should warrant consideration for alternative etiologies (i.e., pulmonary embolism or a different cardiopulmonary disorder as the main driver of symptoms), or unique rapidly progressive phenotypes of PAH such as pulmonary tumor thrombotic microangiopathy (PTTM). 5. PH in the setting of malignancy warrants special consideration, where the pulmonary vascular disorder could be related to venous thromboembolic disease, external compression of the pulmonary vasculature (if the tumor directly compresses mediastinal structures), related to chemotherapeutic agents (such as tyrosine kinase inhibitors) or thoracic radiotherapy (ie. fibrosing mediastinitis), or related to tumor emboli per se, such as in PTTM. PTTM is a unique manifestation of PH in the setting of malignancy, known to be rapidly progressive, associated with poor RV adaptation, and almost universally fatal. The confirmatory testing of PTTM is by pathology (autopsy), although as in our case, sometimes tumor cells can be identified during cytology of pulmonary artery wedge samples.

Show Notes – When Tumors Take Your Breath Away – University of Oklahoma College of Medicine1. How do you approach dyspnea?

Dyspnea is a subjective sensation of uncomfortable breathing. It can be caused by pathologies in cardiac, pulmonary, neuromuscular systems as well as in systemic illnesses. Dyspnea is also a manifestation of psychogenic disorders.
Presentation of dyspnea can be divided into acute and chronic forms and the etiology can be identified by a thorough evaluation.
A detailed history and physical exam can help identify the organ system involved. Certain physical signs can be suggestive of the culprit organ system e.g., lower extremity edema in congestive heart failure, increased antero-posterior diameter of the chest in obstructive lung disease, etc. Imaging modalities can be very helpful in determining the cause of dyspnea. Chest radiographs, CT scans of the chest, and echocardiograms can help identify the etiology of dyspnea. Additionally, other testing like pulmonary functions tests can be used too.

2. What are the different Pulmonary Hypertension groups?

Pulmonary Hypertension (PH) is divided into 5 main groups in the WHO classification, as follows:

3. How do you approach a patient with Pulmonary Hypertension?

The goal is to discover an identifiable etiology for proper classification of pulmonary hypertension according to the WHO groups, in order to guide prognostication and management.
A thorough history and physical exam is the first step in the diagnosis of pulmonary hypertension. Exertional dyspnea is the most common presenting symptom. Due to the nonspecific symptoms, there is often a delay in the diagnosis. Other symptoms include chest pain, fatigue, edema. In severe cases, patients may have syncopal episodes.
Physical Exam findings concerning for pulmonary hypertension include signs of volume overload (i.e., edema, elevated JVP). Cardiac auscultation may reveal a loud P2 component.
Laboratory workup includes basic assessment of hematology along with testing for HIV and serological markers of connective tissue diseases. Biomarkers of cardiovascular system like BNP are important in identification and prognostication of pulmonary hypertension.
Radiological studies like chest radiographs, CT scans of the chest and ventilation/perfusion scans of the lung are used to identify pulmonary pathologies and the presence of thromboembolic disease respectively.
Echocardiographic assessments are important for diagnosis and assessment of pulmonary hypertension. It allows for the assessment of the left side as well as a detailed analysis of the right side which has diagnostic and prognostic value.
Finally, the gold standard for diagnosis is a right heart catheterization, which allows for accurate measurements of the pressure in the different chambers of the heart and allows for the phenotyping of pulmonary hypertension.

4. What are the considerations for Pulmonary Hypertension etiologies in patient with malignancy? How is Pulmonary Tumoral Thrombotic Microangiopathy diagnosed?

Pulmonary hypertension in a patient with malignancy requires special attention.
Apart from the common reasons for pulmonary hypertension, use of chemotherapeutic agents has been associated with the development of pulmonary arterial hypertension, particularly with Tyrosine Kinase Inhibitors.
Pulmonary Veno-Occlusive Disease (PVOD) can be precipitated by the use of many chemotherapeutic agents especially alkylating agents.
Detrimental effects of chemotherapeutic agents on myocytes can cause Group II pulmonary hypertension.
Chemotherapy and radiation therapy induced lung damage can also cause Group III pulmonary hypertension.
Large tumors may directly compress mediastinal structures causing elevated pulmonary pressures due to external compression.
In patients with adenocarcinoma, tumoral thrombotic microangiopathy can result in sub-acute pulmonary hypertension known as Pulmonary Tumoral Thrombotic Microangiopathy (PTTM).
PTTM results in rapid clinical deterioration and hence requires a high suspicion of index. It is mostly diagnosed postmortem, but can be diagnosed by performing wedge cytology.

5. What is the prognosis of PTTM and how is it treated?

PTTM carries a grave prognosis. It causes accelerated occlusion of pulmonary arteries resulting in acute to subacute pulmonary hypertension and ensuing RV dysfunction and failure.
The mainstay of treatment relies on pulmonary vasodilation and slowing the growth of malignant cells.
Pulmonary vasodilators, especially endothelin receptor antagonists, have been reported to be used.
Imatinib, a tyrosine kinase inhibitor, has been reported to be used with some improvement in survival.

References – 1. Vonk Noordegraaf A, Chin KM, Haddad F, et al. Pathophysiology of the right ventricle and of the pulmonary circulation in pulmonary hypertension: an update. Eur Respir J. Jan 2019;53(1):1801900. doi:10.1183/13993003.01900-2018. Link: 2. Bernardo RJ, Haddad F, Couture EJ, et al. Mechanics of right ventricular dysfunction in pulmonary arterial hypertension and heart failure with preserved ejection fraction. Cardiovasc Diagn Ther. Oct 2020;10(5):1580-1603. doi:10.21037/cdt-20-479. 3. Simonneau G, Montani D, Celermajer DS, et al. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. The European respiratory journal. 2019;53(1):1801913-1801913. doi:10.1183/13993003.01913-2018. 4. Dumitrescu D, Sitbon O, Weatherald J, Howard LS. Exertional dyspnoea in pulmonary arterial hypertension. Eur Respir Rev. Sep 30 2017;26(145)doi:10.1183/16000617.0039-2017. 5. Buser M, Felizeter-Kessler M, Lenggenhager D, Maeder MT. Rapidly progressive pulmonary hypertension in a patient with pulmonary tumor thrombotic microangiopathy. Am J Respir Crit Care Med. Mar 15 2015;191(6):711-2. doi:10.1164/rccm.201501-0004IM. 6. Price LC, Wells AU, Wort SJ. Pulmonary tumour thrombotic microangiopathy. Lippincott Williams and Wilkins; 2016. p. 421-428. 7. Price LC, Seckl MJ, Dorfmüller P, Wort SJ. Tumoral pulmonary hypertension. European Respiratory Review. 2019;28(151)doi:10.1183/16000617.0065-2018. 8. Shah AT, Bernardo RJ, Berry GJ, Kudelko K, Wakelee HA. Two Cases of Pulmonary Tumor Thrombotic Microangiopathy Associated with ROS1-Rearranged Non-Small-Cell Lung Cancer. Clin Lung Cancer. Mar 2021;22(2):e153-e156. doi:10.1016/j.cllc.2020.09.020. 9. Godbole RH, Saggar R, Kamangar N. Pulmonary tumor thrombotic microangiopathy: a systematic review. Pulm Circ. Apr-Jun 2019;9(2):2045894019851000. doi:10.1177/2045894019851000

View Details

CardioNerds (Amit and Dan) join Dr. Maria Pabon (cardiology fellow), Dr. Kevin Bersell (cardiology fellow), Dr. Saad Sultan Ghumman (interventional cardiology fellow), and Dr. Rhanderson Cardoso (cardiovascular imaging fellow) from Brigham and Women’s Hospital. Together, they explore a complex case of STEMI that was further complicated by ventricular free wall rupture. Additionally, Dr. Ajar Kochar, Program Director for Interventional Cardiology at Brigham and Women’s Hospital, provides an insightful “ECPR” segment, adding a unique perspective to the case. Audio editing by CardioNerds Academy Intern, student doctor Chelsea Amo Tweneboah.

This is the case of a patient who presented with STEMI and was found to have a moderate pericardial effusion with echogenic material within the pericardial space concerning for thrombus. Urgent CTA/CT surgery was engaged due to concern for dissection, but no evidence of dissection, rupture or intramural hematoma was found. The patient underwent an urgent pericardiocentesis which yielded 350cc of hemorrhagic fluid, leading to an improvement in hemodynamic status. A coronary angiogram was performed which showed a 100% thrombotic occlusion of OM 1, the culprit lesion for the STEMI. Due to the possibility of a delayed STEMI and high suspicion for mechanical complication of MI, aspirin and IV cangrelor were chosen as the preferred antiplatelet strategy. However, cangrelor was held and cardiac surgery was consulted, as LV free wall rupture was suspected. The patient underwent urgent repair of the LV free wall rupture, with an uneventful post-op recovery and discharge on day 8 to cardiac rehab.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

CardioNerds Case Reports Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll

CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!

Case MediaPearls – When Infarction Brings the Walls Down – Brigham and Women’s Hospital1. In the era of primary PCI, mechanical complications of MI are relatively rare. 2. Timely recognition using multi-modality imaging and prompt surgical intervention can result in favorable outcomes. 3. An approach that involves a Heart Team can be advantageous in optimizing outcomes in such complex cases.

Show Notes – When Infarction Brings the Walls Down – Brigham and Women’s Hospital1. Incidence of post AMI LV free wall rupture: * 0.1-1% 2. Risk factors for LV Free wall Rupture: * Older age * Female sex * Prior HTN * 1st lateral or Anterior Wall MI 3. Protective factors towards free wall rupture: * LV hypertrophy * CHF * Hx of prior infarcts * Chronic ischemic heart disease * Early use of beta blockers post MI * Timely intervention 4. Incidence of Mortality associated with mechanical rupture related to AMI: * 8-10% 5. When to suspect a mechanical complication of AMI: * AMI with shock/hypotension * New murmur * New pericardial effusion > 10mm on bedside echo 6. Other etiologies that can cause free wall rupture: * Trauma * Cardiac infection * Aortic dissection * Cardiac tumors * Infiltrative diseases * Iatrogenic from PCI or surgical procedures

References – When Infarction Brings the Walls Down – Brigham and Women’s Hospital1. Varghese S, Ohlow MA. Left ventricular free wall rupture in myocardial infarction: A retrospective analysis from a single tertiary center. JRSM Cardiovasc Dis. 2019 Jan-Dec;8:2048004019896692. doi: 10.1177/2048004019896692. PMID: 31970072. 2. Pineda-De Paz, D.O., Hernández-del Rio, J.E., González-Padilla, C. et al. Left ventricular free-wall rupture, a potentially lethal mechanical complication of acute myocardial infarction: an unusual and illustrative case report. BMC Cardiovasc Disord 19, 80 (2019). https://doi.org/10.1186/s12872-019-1063-x 3. Yip HK, Wu CJ, Chang HW, Wang CP, Cheng CI, Chua S, Chen MC. Cardiac rupture complicating acute myocardial infarction in the direct percutaneous coronary intervention reperfusion era. Chest 2003;124:565–71. doi: 10.1378/chest.124.2.565. PMID: 12907558. 4. Sutherland FW, Guell FJ, Pathi VL, Naik SK. Postinfarction ventricular free wall rupture: strategies for diagnosis and treatment. Ann Thorac Surg 1996;61:1281–5. doi: 10.1016/0003-4975(95)00953-6. PMID: 8627055. 5. Meta-analysis of corticosteroid treatment in acute myocardial infarction. Am J Cardiol 2003;91:1055–9. doi: 10.1016/S0002-9149(03)00216-4. PMID: 12745097.

View Details

CardioNerds (Amit and Dan) join Dr. Khaled Abdelrahman, Dr. Gurleen Kaur, and Dr. Danny Pipilas from the Brigham and Women’s Hospital Residency Program for Italian food and cannolis at the North End in Boston as they discuss the case of an elderly man with primary cardiac lymphoma. They review an approach to intracardiac masses, discuss advantages and disadvantages of various imaging modalities for the evaluation of intracardiac masses, and also delve into anthracycline toxicity. The E-CPR segment is provided by Dr. Ron Blankstein, Associate Director of the Cardiovascular Imaging Program and Director of Cardiac Computed Tomography at Brigham and Women’s Hospital. Audio editing by CardioNerds Academy Intern, student doctor Akiva Rosenzveig.

A 76-year-old man with a history of hyperlipidemia presented with one month of progressively worsening fatigue, weight loss, and dyspnea on exertion. Physical exam was notable for a 3/6 systolic murmur at the left upper sternal border, a flopping sound along the sternum heard throughout the cardiac cycle, and JVP elevated to the level of the mandible. TTE revealed a large heterogeneous echodensity in the right ventricular (RV) free wall that extended into the pericardium and into the RV myocardium with mobile components in the RV cavity and obstruction of the RV outflow tract. Nongated CT chest showed a solid nodule in the periphery of the left lower lung lobe. Gated cardiac CTA revealed a large heterogenous mass in the right atrioventricular groove that encased the proximal thoracic aorta and pulmonary artery and invaded the RV myocardium and RV outflow tract along with a large pericardial effusion. On cardiac MRI, the mass was isointense to the myocardium on T1-weighted images, hyperintense on T2-weighted images, and had heterogenous enhancement on late gadolinium enhancement images. Overall, the imaging findings were highly suspicious for cardiac lymphoma which was confirmed with biopsy of the lung nodule; pathology showed a large B cell lymphoma. The patient was treated with R-CHOP therapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), and TTE after 6 cycles of chemotherapy demonstrated resolution of the RV mass.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

CardioNerds Case Reports Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll

CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!

Case Media
1. There is a large homogeneous mass in the right atrioventricular groove that extends anterior to the right ventricular outflow tract, pulmonary artery, and ascending aorta, measuring up to 9.4 x 7.1 cm (axial) x 13 cm (craniocaudal). The mass encases the proximal thoracic aorta and pulmonary artery. The mass invades the right ventricular myocardium, the right ventricular outflow tract, the pulmonary artery, and proximal main pulmonary artery. There is severe stenosis of the right ventricular outflow tract due to obstruction by the mass. The mass encases the right coronary artery, without compression of the artery. There is enhancement of this mass on delayed contrast imaging. Collectively, these findings suggest cardiac lymphoma.
2. There is a large pericardial effusion, circumferential, measuring up to 2.2 cm adjacent to the right atrium and up to 2.3 cm anterior to the intraventricular septum. There is pericardial enhancement, indicative of pericardial inflammation.
3. This study was not optimized for the assessment of the coronary arteries. However, there are severe coronary artery calcifications. There is possible severe stenosis of the mid LAD.
4. Aneurysmal dilatation of the thoracic aorta, with measurements as reported in the narrative.
1. Normal left ventricular size and function.

There is a large homogenous, soft-tissue intensity mass in the right atrioventricular groove infiltrating the right ventricle free wall and cranially extending anterior to the aorta and main pulmonary artery. The mass encases the main pulmonary artery, the aortic root, the right coronary artery, and the left main coronary artery. The mass invades the right ventricular outflow tract and proximal main pulmonary artery, resulting in severe luminal narrowing at the level of the RVOT/pulmonary artery valve. For the dimensions of the mass, please refer to cardiac CT from 12/1/2021. The mass is isointense to myocardium on T1-weighted images and hyperintense on T2-weighted images. The mass avidly enhances on first-pass perfusion images. There is heterogeneous enhancement of the mass on late gadolinium enhancement images.
There is a large circumferential pericardial effusion, measuring up to 2.3 cm.The left ventricular cavity size and wall thickness are normal. Left ventricular systolic function is normal. There are no segmental left ventricular wall motion abnormalities noted. The estimated ejection fraction is 60%. The right ventricular size is normal. Right ventricular systolic function is mildly decreased. Mildly dilated ascending aorta. Mild AI. Mild MR. There is large heterogenous echodensity in the RV free wall that extends into the parietal pericardium and also into the RV myocardium with mobile components in the RV cavity apical to the tricuspid valve and immediately adjacent to the pulmonic valve. There is obstruction of flow out of the RVOT with a peak and mean gradient of 27 and 16 mmHg respectively. There appears to be some vascularity to this structure (seen best on clips 17 and 18) and overall findings are highly suspicious for tumor. There is a small to moderate pericardial effusion. Anterior to the RV there is a larger collection that is probably pleural in etiology. Recommend cross-sectional imaging for further evaluation. There is no RV chamber collapse to suggest tamponade physiology.
Intensely FDG avid infiltrative mediastinal most likely high-grade lymphoma..
Additional discrete mediastinal and hilar nodes, and left lower lobe nodule, most likely additional areas of lymphomatous involvement. Moderate uptake along right adrenal nodule may represent additional site of lymphomatous involvement
Small bilateral pleural effusions and small to moderate pericardial effusion.Pearls – A Rare Cause Of Fatigue, Dyspnea, And Weight Loss In An Elderly Man – Brigham and Women’s Hospital1. In the diagnostic approach for cardiac masses, consider: 1) age of patient at time of presentation, 2) epidemiologic likelihood and clinical probability, 3) location of tumor, and 4) tissue characterization of the mass on CMR.
CMR allows for better characterization of soft tissues and can assess mass morphology, dimensions, homogeneity, and infiltration into surrounding tissues.
On CMR, cardiac lymphoma typically shows isointensity on T1 imaging and hyperintensity on T2 images.
Cardiac CT allows for high spatial and temporal resolution, and can be useful to define cardiac masses that involve the coronary arteries; compared to CMR, cardiac CT has a greater ability to assess calcifications within a mass itself.
Cardiac lymphomas have a predilection of right heart chambers, especially right atrium and can affect the AV groove, encasing the right coronary artery.
Global systolic longitudinal myocardial strain on TTE is an indicator of early anthracycline-induced cardiomyopathy before overt reduction in ejection fraction. Show Notes – A Rare Cause Of Fatigue, Dyspnea, And Weight Loss In An Elderly Man – Brigham and Women’s Hospital1. What is the approach to an enlarged cardiac silhouette noted on chest x-ray?
1. Cardiothoracic ratio of greater than 50%.
2. Two possible “buckets” of diagnoses to consider are enlargement of heart related to cardiomegaly as opposed to a pericardial process like a pericardial effusion.
3. For cardiomegaly, it can be from dilated or hypertrophic cardiomyopathy with most common causes including coronary artery disease, hypertension, valvular heart disease, and arrythmia-induced cardiomyopathy. Other buckets to consider are inflammatory causes, either infectious or autoimmune, as well as infiltrative diseases like amyloid or sarcoid, toxins (alcohol, cocaine, medications), endocrine, and nutritional causes (like a B1 or selenium deficiency).
4. The most sensitive sign of a pericardial effusion on chest x-ray is enlargement of cardiac silhouette with a sensitivity of around 71%, but low specificity (1).
5. With pericardial effusion, symmetric expansion of the heart contour leads to a globular appearance which is commonly referred to as flask-shaped or the water bottle sign (1).
What is the approach to intracardiac masses?
- First, consider the age of the patient at the time of presentation since certain clinical entities like rhabdomyomas and fibromas are more common in the pediatric population (2).
- Second, consider the epidemiologic likelihood and clinical probability. In a patient with a recent anterior wall MI and akinetic ventricular apex, a cardiac mass on echo would raise concern for an intracardiac thrombus (2).
- Third, consider the location of the tumor. If the mass is on the valves, consider thrombus or a vegetation. While masses in the chambers can still represent thrombus, would also consider myxomas, lymphomas, and metastases (2).
- Fourth, consider the tissue characterization of the mass on further diagnostic imaging such as CMR (2).
What is the role of multimodality imaging in the evaluation of intracardiac masses?
TTE is the first modality utilized in evaluation of a cardiac mass. TEE is useful specifically when valvular lesions are suspected or in patients with atrial masses or with mobile valvular lesions. It can help to characterize size, morphology, attachment site, extension, and hemodynamic effects.
CMR allows for better characterization of soft tissue and can assess mass morphology, dimensions, homogeneity, infiltration in surrounding tissues. These can all help differentiate different types of masses and whether a mass is benign or malignant. Signal characteristics gathered from T1, T2, early gadolinium enhancement, and late gadolinium enhancement sequences can further assess fatty infiltration, necrosis, hemorrhage, and vascularity within a mass (3, 4).
Cardiac CT is another option and offers high spatial and temporal resolution, multiplanar image reconstruction capabilities, and fast acquisition times. The large field of view also allows for assessment of chest and lung tissue, vascular structures, and assessment for other masses in the chest. CT may also be more helpful in defining surgical approaches and assessing how masses may involve the coronary arteries and assess for coronary artery calcifications or obstructive coronary disease (4).
FDG-PET is also another valuable imaging option which offers evaluation of metabolic activity of tumors. PET imaging can also help guide biopsy location, staging, and planning for cancer therapy.
What are key features of Primary Cardiac Lymphoma?
- Diffuse large B-cell lymphoma is the most common subtype, though others like Burkitt lymphoma, low grade B –cell lymphoma, and T-cell lymphoma have also been described.
- They occur more commonly in immunocompromised individuals and in immunocompetent patients, only account for 1.3% of primary cardiac tumors
- Presenting symptoms are usually nonspecific. They may manifest as dysrhythmias like heart block, syncopal episodes, or even restrictive cardiomyopathy.
- Approximately 20% of patients may develop acute heart failure before other symptoms.
- On echocardiogram, these tumors appear homogeneous, with predilection of right heart chambers, especially right atrium. The AV groove can be affected, potentially encasing the right coronary artery (5).
- On CMR, tissue appears isointense on T1-weighted imaging. On T2-weighted imaging, lesions are mildly hyperintense due to diffuse edema (5).
What are risk factors associated with anthracycline toxicity and what are strategies for preventing and monitoring for cardiotoxicity when anthracycline therapy is planned?
- Up to 35% of patients receiving anthracycline therapy develop some form of cardiotoxicity (6).
- The risk of developing anthracycline induced cardiotoxicity is directly proportional to the dose of anthracycline received, and after studies demonstrated HF incidence of 26% with doxorubicin dose of 550mg/m2 as compared to 5% with dose of 400mg/m2, efforts have been made to limit cumulative anthracycline doses to 400 to 450mg/m2. In addition, hypertension, DM, and obesity are all associated with increased risk (6).
- There are two primary prevention strategies: using cardioprotective agents, and aiming to reduce potency of the anthracyclines. For cardioprotection, dexrazoxane is an FDA-approved cardioprotective agent for anthracycline induced cardiotoxicity (7).
- TTE is the most common modality used for detection and monitoring of anthracycline toxicity on the heart. While LV dysfunction is most commonly detected, recent investigations suggest that RV function is also significantly affected by anthracycline toxicity (8).
- Global systolic longitudinal myocardial strain on TTE has also emerged as a reproducible indicator of early anthracycline-related myocardial dysfunction and future reduction in LVEF (9).
- Enjoy Episodes 261 and 274 about CTRCD (cancer therapy related cardiac dysfunction) as part of the Cardio-Oncology Series.

References – A Rare Cause Of Fatigue, Dyspnea, And Weight Loss In An Elderly Man – Brigham and Women’s Hospital1. https://www.acc.org/latest-in-cardiology/articles/2019/09/09/10/46/chest-radiograph-signs-suggestive-of-pericardial-disease 2. Tyebally S, Chen D, Bhattacharyya S, Mughrabi A, Hussain Z, Manisty C, Westwood M, Ghosh AK, Guha A. Cardiac Tumors: JACC CardioOncology State-of-the-Art Review. JACC CardioOncol. 2020 Jun 16;2(2):293- 3. Motwani M, Kidambi A, Herzog BA, Uddin A, Greenwood JP, Plein S. MR imaging of cardiac tumors and masses: a review of methods and clinical applications. Radiology. 2013 Jul;268(1):26-43. 4. Lopez-Mattei JC, Lu Y. Multimodality Imaging in Cardiac Masses: To Standardize Recommendations, The Time Is Now! JACC Cardiovasc Imaging. 2020 Nov;13(11):2412-2414. 5. Jeudy J, Kirsch J, Tavora F, Burke AP, Franks TJ, Mohammed TL, Frazier AA, Galvin JR. From the radiologic pathology archives: cardiac lymphoma: radiologic-pathologic correlation. Radiographics. 2012 Sep-Oct;32(5):1369-80. 6. Henriksen PA. Anthracycline cardiotoxicity: an update on mechanisms, monitoring and prevention. Heart. 2018 Jun;104(12):971-977. 7. Vejpongsa P, Yeh ET. Prevention of anthracycline-induced cardiotoxicity: challenges and opportunities. J Am Coll Cardiol. 2014 Sep 2;64(9):938-45 8. Liu JE. Anthracycline-Induced Cardiotoxicity: Remembering the Forgotten Ventricle. JACC CardioOncol. 2020;2(1):23-25. 9. Potter E, Marwick TH. Assessment of Left Ventricular Function by Echocardiography: The Case for Routinely Adding Global Longitudinal Strain to Ejection Fraction. JACC Cardiovasc Imaging. 2018 Feb;11(2 Pt 1):260-274.

View Details

CardioNerds co-founder Daniel Ambinder joins Dr. Essa Hariri, Dr. Anna Scandinaro, Dr. Beka Bekhdatze, and Dr. Ashley Kasper (Cleveland Clinic cardiology fellows) as well as Dr. Craig Parris from Ohio State University Medical Center for a walk at Edgewater Park in Cleveland, Ohio. Dr. Andrew Higgins (Crtitical Care Cardiology and Advanced HF / Transplant Cardiology at Cleveland Clinic) provides the ECPR for this episode. They discuss the following case involving a rare cause of non-ischemic cardiomyopathy. A young African American male was admitted for cardiogenic shock following an admission a month earlier for treatment resistant psychosis. He was diagnosed with medication-induced non-ischemic cardiomyopathy, which resolved with a remarkable recovery of his systolic function after discontinuation of the culprit medication, Clozapine. Episode notes were drafted by Dr. Essa Hariri. Audio editing by CardioNerds Academy Intern, student doctor Shivani Reddy.

Enjoy this case report co-published in US Cardiology Review: Clozapine-induced Cardiomyopathy: A Case Report

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

CardioNerds Case Reports Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll

CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!

Pearls – An Unusual Case of Non-ischemic Cardiomyopathy1. The diagnosis of drug-induced non-ischemic cardiomyopathy is usually one of exclusion. High clinical suspicion is needed to diagnose drug-induced cardiomyopathy. 2. Missing the culprit medication causing drug-induced cardiomyopathy could be detrimental as there is a high probability of reversing a systolic dysfunction after stopping the offending medication. 3. Clozapine is an effective medication for the treatment-resistant schizophrenia and is associated with reduced suicide risk. 4. Clozapine is reported to cause drug-induced cardiomyopathy and is more common with rapid drug titration. Clozapine is more commonly associated with myocarditis. 5. Close monitoring and vigilance are critical to preventing cardiac complications associated with initiating clozapine. 6. The management of clozapine-associated cardiomyopathy includes clozapine cessation and heart failure guideline-directed medical therapy. Show Notes – An Unusual Case of Non-ischemic CardiomyopathyWe treated a case of clozapine-associated cardiomyopathy presenting in cardiogenic shock. Drug-induced cardiomyopathy is a common yet under-recognized etiology of non-ischemic cardiomyopathy. Clozapine is an FDA-approved atypical antipsychotic medication frequently prescribed for treatment-resistant schizophrenia and the only antipsychotic agent that has been proven to significantly reduce suicide among this patient population.

However, Clozapine is reported to be associated with several forms of cardiotoxicity, including myocarditis (most common), subclinical clozapine associated cardiotoxicity, and least commonly, drug-induced cardiomyopathy. Clozapine-associated cardiomyopathy should be considered as a differential diagnosis in schizophrenic patients presenting with signs of acute heart failure.

Rapid titration of clozapine is a risk factor for clozapine-associated cardiomyopathy and clozapine-associated myocarditis. To date, there is no evidence or consensus supporting preemptive screening.According to the American Psychiatric Association, whenever clozapine-induced myocarditis or cardiomyopathy is suspected, a cardiology consult is warranted. Experts recommend, when initiating clozapine, to obtain baseline troponin, CRP, and echocardiography upon drug initiation. This is followed by daily symptom assessment and a hemodynamic assessment on every other day. A biochemical assessment of CRP and troponin levels is warranted every 7 days. The authors recommend clozapine caseation if troponin rises above twice the upper normal limit or if CRP levels exceeds 100 mg/L. Because clozapine is a highly effective medication in treating schizophrenia, close monitoring and vigilance is critical to prevent deleterious complications associated with drug cardiotoxicity. Several mechanisms have been proposed to explain the cardiotoxicities reported with clozapine. Most patients with clozapine-associated cardiotoxicity remain asymptomatic, while others may present with typical acute congestive heart failure. The most common presenting symptom was shortness of breath (60%) followed by palpitations (36%), and the main echocardiographic finding in all patients with this disease is systolic dysfunction with reduced ejection fraction.

The management of clozapine-associated cardiomyopathy includes clozapine cessation and heart failure guideline-directed medical therapy. Clozapine suspension along with conventional heart failure management have led to a significant improvement in left ventricular function. Decisions regarding resuming clozapine therapy are highly individualized and should consider weighing in the risks and benefits of treatment. Whenever clozapine is rechallenged, very close monitoring and frequent echocardiography may be warranted to prevent subsequent cardiotoxicity.

References – An Unusual Case of Non-ischemic Cardiomyopathy1. Tsao CW, Aday AW, Almarzooq ZI, et al. Heart Disease and Stroke Statistics-2022 Update: A Report from the American Heart Association. Circulation. 2022;145(8). doi:10.1161/CIR.0000000000001052

Heidenreich PA, Albert NM, Allen LA, et al. Forecasting the impact of heart failure in the united states a policy statement from the american heart association. Circ Heart Fail. 2013;6(3). doi:10.1161/HHF.0b013e318291329a
VanDyck TJ, Pinsky MR. Hemodynamic monitoring in cardiogenic shock. Curr Opin Crit Care. 2021;27(4). doi:10.1097/MCC.0000000000000838
Keepers GA, Fochtmann LJ, Anzia JM, et al. The American psychiatric association practice guideline for the treatment of patients with schizophrenia. American Journal of Psychiatry. 2020;177(9). doi:10.1176/appi.ajp.2020.177901
Hennen J, Baldessarini RJ. Suicidal risk during treatment with clozapine: A meta-analysis. Schizophr Res. 2005;73(2-3). doi:10.1016/j.schres.2004.05.015
Taipale H, Tanskanen A, Mehtälä J, Vattulainen P, Correll CU, Tiihonen J. 20-year follow-up study of physical morbidity and mortality in relationship to antipsychotic treatment in a nationwide cohort of 62,250 patients with schizophrenia (FIN20). World Psychiatry. 2020;19(1):61-68. doi:10.1002/wps.20699
Citrome L, McEvoy JP, Saklad SR. A guide to the management of clozapine-related tolerability and safety concerns. Clin Schizophr Relat Psychoses. 2016;10(3). doi:10.3371/1935-1232.10.3.163
Knoph KN, Morgan RJ, Palmer BA, et al. Clozapine-induced cardiomyopathy and myocarditis monitoring: A systematic review. Schizophr Res. 2018;199. doi:10.1016/j.schres.2018.03.006
Kanniah G, Kumar S. Clozapine associated cardiotoxicity: Issues, challenges and way forward. Asian J Psychiatr. 2020;50. doi:10.1016/j.ajp.2020.101950
Curto M, Girardi N, Lionetto L, Ciavarella GM, Ferracuti S, Baldessarini RJ. Systematic Review of Clozapine Cardiotoxicity. Curr Psychiatry Rep. 2016;18(7). doi:10.1007/s11920-016-0704-3
Baran DA, Grines CL, Bailey S, et al. SCAI clinical expert consensus statement on the classification of cardiogenic shock: This document was endorsed by the American College of Cardiology (ACC), the American Heart Association (AHA), the Society of Critical Care Medicine (SCCM), and the Society of Thoracic Surgeons (STS) in April 2019. Catheterization and Cardiovascular Interventions. 2019;94(1). doi:10.1002/ccd.28329
Alawami M, Wasywich C, Cicovic A, Kenedi C. A systematic review of clozapine induced cardiomyopathy. Int J Cardiol. 2014;176(2). doi:10.1016/j.ijcard.2014.07.103
Arzuk E, Karakuş F, Orhan H. Bioactivation of clozapine by mitochondria of the murine heart: Possible cause of cardiotoxicity. Toxicology. 2021;447. doi:10.1016/j.tox.2020.152628
Vaddadi KS, Soosai E, Vaddadi G. Low blood selenium concentrations in schizophrenic patients on clozapine. Br J Clin Pharmacol. 2003;55(3). doi:10.1046/j.1365-2125.2003.01773.x
Yost BL, Gleich GJ, Fryer AD. Ozone-induced hyperresponsiveness and blockade of M2 muscarinic receptors by eosinophil major basic protein. J Appl Physiol. 1999;87(4). doi:10.1152/jappl.1999.87.4.1272
Yuen JWY, Kim DD, Procyshyn RM, White RF, Honer WG, Barr AM. Clozapine-induced cardiovascular side effects and autonomic dysfunction: A systematic review. Front Neurosci. 2018;12(APR). doi:10.3389/fnins.2018.00203
Ronaldson KJ, Taylor AJ, Fitzgerald PB, Topliss DJ, Elsik M, McNeil JJ. Diagnostic characteristics of clozapine-induced myocarditis identified by an analysis of 38 cases and 47 controls. Journal of Clinical Psychiatry. 2010;71(8). doi:10.4088/JCP.09m05024yel
de Leon J, Tang YL, Baptista T, Cohen D, Schulte PFJ. Titrating clozapine amidst recommendations proposing high myocarditis risk and rapid titrations. Acta Psychiatr Scand. 2015;132(4). doi:10.1111/acps.12421
Ronaldson KJ, Fitzgerald PB, Taylor AJ, Topliss DJ, Wolfe R, McNeil JJ. Rapid clozapine dose titration and concomitant sodium valproate increase the risk of myocarditis with clozapine: A case-control study. Schizophr Res. 2012;141(2-3). doi:10.1016/j.schres.2012.08.018
Ronaldson KJ, Fitzgerald PB, Taylor AJ, Topliss DJ, McNeil JJ. A new monitoring protocol for clozapine-induced myocarditis based on an analysis of 75 cases and 94 controls. Australian and New Zealand Journal of Psychiatry. 2011;45(6). doi:10.3109/00048674.2011.572852
Patel RK, Moore AM, Piper S, et al. Clozapine and cardiotoxicity – A guide for psychiatrists written by cardiologists. Psychiatry Res. 2019;282. doi:10.1016/j.psychres.2019.112491
Cook SC, Ferguson BA, Cotes RO, Heinrich TW, Schwartz AC. Clozapine-Induced Myocarditis: Prevention and Considerations in Rechallenge. Psychosomatics. 2015;56(6). doi:10.1016/j.psym.2015.07.002
de Leon J, Schoretsanitis G, Smith RL, et al. An International Adult Guideline for Making Clozapine Titration Safer by Using Six Ancestry-Based Personalized Dosing Titrations, CRP, and Clozapine Levels [published correction appears in Pharmacopsychiatry. 2022 Jan 20;:]. Pharmacopsychiatry. 2022;55(2):73-86. doi:10.1055/a-1625-6388

View Details

CardioNerds Cofounder Dr. Amit Goyal join Dr. Usman Hasnie and Dr. Will Morgan from University of Alabama at Birmingham for a hike up Red Mountain. They discuss the following case: A 75-year-old woman with prior mitral valve ring annuloplasty presented with subacute, intermittent, self-limiting neurologic deficits. Brain MRI revealed multiple subacute embolic events consistent with cardioembolic phenomena. Transesophageal echochardiogram discovered a mobile mass on the mitral valve as the likely cause for cardioembolic stroke. She was taken for surgical repair of the mitral valve. Tissue biopsy confirmed that the mass was an IgG4-related pseudotumor. Expert commentary is provided by Dr. Neal Miller (Assistant Professor of Cardiology, University of Alabama at Birmingham). Audio editing by CardioNerds Academy Intern, student doctor Adriana Mares

Check out this published case report here: IgG4-Related Disease Masquerading as Culture-Negative Endocarditis!

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

This episode is made possible with support from Glass.Health – The first digital notebook designed for doctors. Follow @GlassHealthHQ for the latest product updates!

CardioNerds Case Reports Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll

CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!

Pearls – Cardioembolic Stroke due to an IgG4-related pseudotumor1. Surgical indications for endocarditis include severe heart failure, valvular dysfunction with severe hemodynamic compromise, prosthetic valve infection, invasion beyond the valve leaflets, recurrent systemic embolization, large mobile vegetations, or persistent sepsis (in infective endocarditis) despite adequate antibiotic therapy. 2. IgG4 related disease is rare, and likely underrecognized due to the lack of reliable biomarkers. Biopsy and histologic confirmation are imperative to clinch the diagnosis. 3. Cardiac manifestations of IgG4-related disease are rare but are often related to aortopathies. Valvular disease is extremely rare as a manifestation of the disease. 4. Treatment of IgG4 related disease includes steroids as the first line treatment. 5. IgG4 related disease requires a multi-disciplinary approach to both diagnose and treat. Show Notes – Cardioembolic Stroke due to an IgG4-related pseudotumorNotes were drafted by Dr. Hasnie and Dr. Morgan

IgG4-related disease has a very diverse presentation including mimicry of infection, malignancy and other autoimmune conditions. It is a fibroinflammatory condition that results in deposition of IgG4 positive plasma cells. It has been described in multiple organ systems including the pancreas, kidneys, lungs and salivary glands.
Cardiac manifestations are extremely rare and valvular disease even more so. There are thirteen cases of IgG4 related valvular disease, and of these only two had mitral valve involvement such as this case. The most commonly reported cardiovascular manifestations are related to aortopathies.
This disease remains poorly understood at this point. There are no true biomarkers that can be used to risk stratify the diagnosis for clinicians. Biopsy is imperative to the diagnosis. Even serum IgG4 levels are normal in 30% of cases despite meeting histologic criteria on biopsy making the diagnosis incredibly difficult to make.
While guidelines have not been developed to guide treatment of IgG4-related disease, steroids are considered the first line treatment option for patients. Often times dosing is 2-4 weeks with a prolonged taper. When looking for glucocorticoid sparing agents, azathioprine, mycophenolate mofetil, and methotrexate are considered alternatives.

References – Cardioembolic Stroke due to an IgG4-related pseudotumor1. Kamisawa T, Funata N, Hayashi Y, et al. A new clinicopathological entity of IgG4- related autoimmune disease. J Gastroenterol 2003;38:982-4.

Deshpande V, Zen Y, Chan JK, et al. Consensus statement on the pathology of IgG4-related disease. Mod Pathol. 2012;25(9):1181-1192. doi:10.1038/modpathol.2012.72
Dahlgren M, Khosroshahi A, Nielsen GP, Deshpande V, Stone JH. Riedel’s thyroiditis and multifocal fibrosclerosis are part of the IgG4-related systemic disease spectrum. Arthritis Care Res (Hoboken) 2010;62:1312-8.
Stone JH, Khosroshahi A, Hilgenberg A, Spooner A, Isselbacher EM, Stone JR. IgG4 related systemic disease and lymphoplasmacytic aortitis. Arthritis Rheum 2009;60:313945.
Saeki T, Saito A, Hiura T, et al. Lymphoplasmacytic infiltration of multiple organs with immunoreactivity for IgG4: IgG4-related systemic disease. Intern Med 2006;45:163-7.
Kamisawa T, Takuma K, Egawa N, Tsuruta K, Sasaki T. Autoimmune pancreatitis and IgG4-related sclerosing disease. Nat Rev Gastroenterol Hepatol 2010;7:401-9.
Shakir A, Wheeler Y, Krishnaswamy G. The enigmatic immunoglobulin G4-related disease and its varied cardiovascular manifestations. Heart. 2021;107(10):790-798. doi:10.1136/heartjnl-2020-318041
Tyebally S, Chen D, Bhattacharyya S, Mughrabi A, Hussain Z, Manisty C, et al. Cardiac tumors: JACC cardio oncology state-of-the-art review. J Am Coll Cardiol CardioOnc. 2020;2:293–311
Selkane C, Amahzoune B, Chavanis N, et al. Changing management of cardiac myxoma based on a series of 40 cases with long-term follow-up. Ann Thorac Surg. 2003;76(6):1935-1938. doi:10.1016/s0003-4975(03)01245-1
Sun JP, Asher CR, Yang XS, et al. Clinical and echocardiographic characteristics of papillary fibroelastomas: a retrospective and prospective study in 162 patients. Circulation. 2001;103(22):2687-2693. doi:10.1161/01.cir.103.22.
Stone JH, Zen Y, Deshpande V. IgG4-related disease. N Engl J Med. 2012;366(6):539-551. doi:10.1056/NEJMra1104650
Hasnie UA, Herrera LN, Morgan WS, Rodriguez JM, Litovsky S, Chatham WW, Winokur T, Muzny CA. IgG4-Related Disease Masquerading As Culture-Negative Endocarditis. AIM Clinical Cases. 2022;1. doi: 10.7326/aimcc.2022.0075
2016 ASE Guideline: https://www.asecho.org/wp-content/uploads/2016/01/2016_Cardiac-Source-of-Embolism.pdf
Shakir A, Wheeler Y, Krishnaswamy G. The enigmatic immunoglobulin G4-related disease and its varied cardiovascular manifestations Heart 2021;107:790-798.
Karadeniz H, Vaglio A. IgG4-related disease: a contemporary review. Turk J Med Sci. 2020 Nov 3;50(SI-2):1616-1631. doi: 10.3906/sag-2006-375. PMID: 32777900; PMCID: PMC7672352.

View Details

CardioNerds Cofounder Dr. Amit Goyal is joined by Dr. Douglas Salguero (Internal medicine resident), Dr. Francisco Ujueta (Cardiology fellow), and Dr. Priscilla Wessly (Chief cardiology fellow) from the Columbia University Division of Cardiology at Mount Sinai Medical Center in Miami to discuss a rare case of isolated non-compaction cardiomyopathy. Expert commentary is provided by Christos […]

View Details

CardioNerds Cofounder Dr. Amit Goyal is joined by an esteemed group of UCLA cardiology fellows – Dr. Patrick Zakka (CardioNerds Academy Chief), Dr. Negeen Shehandeh (Chief Fellow), and Dr. Adrian Castillo – to discuss a case of primary cardiac angiosarcoma. An expert commentary is provided by Dr. Eric Yang, beloved educator, associate clinical professor of […]

View Details

CardioNerds (Daniel Ambinder and Amit Goyal) join Dr. Arielle Schwartz (Emory University cardiology fellow), Dr. Joshua Zuniga (former Emory vascular medicine fellow and now USC cardiology fellow), and Dr. Patrick Zakka (UCLA cardiology fellow) from the Emory University School of Medicine. They discuss a case of a young woman with new onset hypertension refractory to […]

View Details

CardioNerds (Amit Goyal and Dan Ambinder) join Dr. Radi Zinoviev, Dr. Josh Cohen, and Dr. Tiffany Dong (CardioNerds Ambassador) from the Cleveland Clinic for a day on Edgewater beach. They discuss the following case of the evaluation and management of prosthetic tricuspid valve stenosis in a patient with a history of Ebstein Anomaly. The expert […]

View Details

CardioNerds (Amit and Dan) join join Dr. Andrew Dicks (Vascular medicine physician at Prisma Health, former fellow at Mass General Vascular) and Dr. Prateek Sharma (Vascular interventional & medicine fellow at MGH) for an ice-cold drinks at the Esplanade in Boston, MA to discuss a case about a patient who developed a pulmonary embolism and […]

View Details

CardioNerds (Amit and Dan) join Dr. Omid Amidi (CardioNerds Academy Graduate) and Dr. Marwah Shahid from the UCLA Cardiology Fellowship program along with Dr. Evelyn Song (CardioNerds Academy House Faculty and Heart Failure Hospitalist at UCSF) to discuss a complex case focused on management of severe coronary artery disease in a patient with Glanzmann thrombasthenia. […]

View Details

CardioNerds (Amit Goyal and Daniel Ambinder) join Dr. Phoo Pwint Nandar (former FIT Ambassador), Dr. Deep Shah (current FIT Ambassador), and Dr. Sugat Wagle from the Summa Health Cardiology Department for an afternoon at Cuyahoga National Valley Park. We discuss a case of a post-partum woman who presented with ventricular fibrillation arrest due to SCAD. She had ongoing […]

View Details

CardioNerds (Amit Goyal and Daniel Ambinder) join Dr. Sonu Abraham (Cardiology fellow, Lahey Hospital and Medical Center), Dr. Amitoj Singh (Internal Medicine Resident, Lahey Hospital and Medical Center), Dr. Ahmed Ghoneem (Internal Medicine Resident, Lahey Hospital and Medical Center, CardioNerds Academy Chief) and Dr. Aanika Balaji (Internal Medicine Resident, Johns Hopkins) for a scrumptious meal on the Boston […]

View Details

CardioNerds (Amit Goyal and Daniel Ambinder) and guest host, Dr. Priya Kothapalli (UT Austin fellow and CardioNerds Ambassador), join SUNY Downstate cardiology fellows, Dr. Eric Kupferstein and Dr. Gautham Upadhya to discuss a case about a patient who had coronary artery bypass grafting that was complicated by a LIMA grafted to the great cardiac vein. Dr. Alan Feit […]

View Details

CardioNerds (Amit Goyal & Karan Desai) join Dr. Matthew Delfiner (Cardiology fellow, Temple University Hospital) and Dr. Katie Vanchiere (Internal medicine resident, Temple University Hospital) in the beautiful Fairmount Park in Philadelphia. They discuss a case of a 53-year-old man with an LVAD who presents with progressive dyspnea since LVAD implant due to right-to-left shunting due to a […]

View Details

CardioNerds (Amit Goyal and Daniel Ambinder) join Dr. Loie Farina (Northwestern University CardioNerds Ambassador), Dr. Josh Cheema, and Dr. Graham Peigh from Northwestern University for drinks along the shores of Lake Michigan at North Avenue Beach. They discuss a case of a 52-year-old woman with limited cutaneous systemic sclerosis who presents with progressive symptoms of […]

CardioNerds Case Reports Archives - Cardionerds: Recent Episodes

CardioNerds