CardioNerds Case Reports Archives - Cardionerds

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CardioNerds Case Reports Archives - Cardionerds episodes

September 08, 2025426. Case Report: A Ruptured Saccular Aortic Aneurysm into the Right Ventricle – University of Tennessee, Nashville
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
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Check out CardioNerds SWAG!
Become a CardioNerds Patron!
Pearls
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.
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.
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.
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.
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 –
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.
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.
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.
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.
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
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.
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.
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.
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.
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.
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.
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.
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.
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
37 min
August 29, 2025425. Case Report: The Hidden Culprit – Unraveling the Cause of Malignant Ventricular Arrhythmias in a Young Adult – Trinity Health Livonia Hospital
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.
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.
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.
“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!
Pearls- Malignant Ventricular Arrhythmias
This 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 Arrhythmias
Notes were drafted by Juma Bin Firos.
1. 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
2. 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
3. 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
4. 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
5. 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 Arrhythmias
Al-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
55 min
August 03, 2025423. Case Report: The Malignant Murmur – More Than Meets the Echo in Nonbacterial Thrombotic Endocarditis – Baylor College of Medicine
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 Images
We 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.
“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!
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Pearls- Nonbacterial Thrombotic Endocarditis
Eliminate the Usual Suspects. NBTE is a diagnosis of exclusion! Always rule out infective endocarditis (IE) first with serial blood cultures and serologic tests.
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.
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.
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.
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 Endocarditis
Notes 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 Endocarditis
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.
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).
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.
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.
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.
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.
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.
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.
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
33 min
July 10, 2025421. Case Report: Switched at Birth: A Case of Congenital Heart Disease Presenting in Adulthood – New York Presbyterian Queens
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.
“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.
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Pearls- A Case of Congenital Heart Disease Presenting in Adulthood
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.
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.
CCTGA is frequently associated with ventricular septal defects, pulmonic stenosis, tricuspid valve abnormalities and dextrocardia.
CCTGA is often asymptomatic in childhood and can present later in adulthood with symptoms of morphologic right ventricular failure, tricuspid regurgitation, or cardiac arrhythmias.
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 Adulthood
Notes 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 Adulthood
1.        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
2.        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
3.        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
4.        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
5.        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
6.        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
7.        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
8.        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
9.        Maldjian PD, Saric M. Approach to dextrocardia in adults: Review. American Journal of Roentgenology. 2007;188(6 SUPPL.). doi:10.2214/AJR.06.1179
10.      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
11.      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
12.      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
30 min
May 09, 2025417. Case Report: Clear Vision, Clouded Heart: Ocular Venous Air Embolism with Pulmonary Air Embolism, RV Failure, and Cardiac Arrest – Trinity Health Ann Arbor
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.
“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
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Pearls- Clear Vision, Clouded Heart: Ocular Venous Air Embolism with Pulmonary Air Embolism, RV Failure, and Cardiac Arrest
Hypoxia, hypotension and tachycardia in a patient following ocular instrumentation are classic findings suggestive of pulmonary embolism from possible air embolism.
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.
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 Failure
Notes – 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.
2. 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.
3. 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)
4. 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.
References
Arrigo, 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.
239. CCC: Approach to RV Predominant Cardiogenic Shock with Dr. Ryan Tedford
20 min
April 10, 2025415. Case Report: Unraveling MINOCA: Role of Cardiac MRI and Functional Testing in Diagnosing Coronary Vasospasm – The Christ Hospital
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.
“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.
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Notes – Coronary Vasospasm
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.
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.
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 Vasospasm
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
43 min
March 25, 2025414. Case Report: Got Milky Blood? Hypertriglyceridemia Unveiled in a Case of Abdominal Pain – National Lipid Association
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.
“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
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Cardionerds Healy Honor Roll
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Pearls – Hypertriglyceridemia
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.
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.
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.
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.
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 – Hypertriglyceridemia
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.
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.
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.
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.
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 – Hypertriglyceridemia
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
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
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
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
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
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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).
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
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/
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
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
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
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=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
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/
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
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/
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=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org
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/
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
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
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
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
1 hr 18 min
March 13, 2025413. Case Report: Cardiac Sarcoidosis Presenting as STEMI – Mount Sinai Medical Center in Miami
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.
“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.
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Pearls – Cardiac Sarcoidosis Presenting as STEMI
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.
Conduction abnormalities, particularly AV block or ventricular arrhythmias, are common and may be the initial indication of cardiac involvement with sarcoidosis.
The additive value of Echocardiography, FDG-PET, and cardiac MR is indispensable in the diagnostic workup of suspected cardiac sarcoidosis.
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.
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 STEMI
1. 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.
References
1.) 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.
26 min
February 14, 2025410. Case Report: A Curious Case of Refractory Ventricular Tachycardia – Rutgers-Robert Wood Johnson
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.
“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!
Pearls – A Curious Case of Refractory Ventricular Tachycardia – Rutgers-Robert Wood Johnson
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.
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.
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.
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.
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.
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 Johnson
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.
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.
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.
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.
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
Family history of sudden cardiac death
Unexplained syncope
NSVT episodes on ambulatory monitoring when runs are frequent (≥ 3), longer (≥ 10 beats), and faster (≥ 200 bpm)
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
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
AHA HCM SCD Calculator
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
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
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
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
41 min
December 13, 2024405. Case Report: Like Mother, Like Son? Peripartum Cardiomyopathy and Infantile Hypertrophic Cardiomyopathy Lead to a Unifying Diagnosis – Mayo Clinic Arizona
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.
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Pearls
Peripartum cardiomyopathy is a diagnosis of exclusion – we must exclude other possible etiologies of heart failure!
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!
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.
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
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!).
Notes
What 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
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