CardioNerds (Drs. Amit Goyal, Elizabeth Davis, and Keerthi Gondi) discuss the approach to asymptomatic severe aortic stenosis with expert faculty Drs. Parth Desai and Tony Bavry.  

They review the natural history of aortic stenosis, current guidelines for treating severe aortic stenosis, multiparametric risk stratification, trial data on aortic valve replacement for patients with asymptomatic severe aortic stenosis, and a practical approach for our patients today.  

This episode was supported by an educational grant from Edwards Lifesciences. All CardioNerds education is planned, produced, and reviewed solely by CardioNerds. Managing asymptomatic severe aortic stenosis | AKH CME

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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.  

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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 5x10 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,

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. 

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. 

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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,

CardioNerds (Drs. Rick Ferraro and Georgia Vasilakis Tsatiris) discuss ATTR cardiac amyloidosis with expert Dr. Justin Grodin. This episode is a must-listen for all who want to know how to diagnose and treat ATTR with current available therapies, as well as management of concomitant diseases through a multidisciplinary approach. We take a deep dive into the importance of genetic testing, not only for patients and families, but also for gene-specific therapies on the horizon. Dr. Grodin draws us a roadmap, guiding us through new experimental therapies that may reverse the amyloidosis disease process once and for all.  Audio editing by CardioNerds academy intern, Christiana Dangas.

This episode was developed in collaboration with the American Society of Preventive Cardiology and supported by an educational grant from BridgeBio. 

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Pearls:

You must THINK about your patient having amyloid to recognize the pattern and make the diagnosis. Start with a routine ECG and TTE, and look for a disproportionately large heart muscle with relatively low voltages on the ECG. 

Before you diagnose ATTR amyloidosis, AL amyloidosis must be ruled out (or ruled in) with serum light chains, serum/urine immunofixation, and/or tissue biopsy. 

Genetic testing is standard of care for all patients and families with ATTR amyloidosis, and the future is promising for gene-specific treatments. Current FDA-approved treatments for TTR amyloidosis are TTR stabilizers and TTR silencers, but TTR fibril-depleting agents are on their way. 

Early diagnosis of ATTR affords patients maximal benefit from current amyloidosis therapies.  

TTR amyloidosis patients require a multidisciplinary approach for success, given the high number of concomitant diseases with cardiomyopathy. 

Notes:

Notes: Notes drafted by Dr. Georgia Vasilakis Tsatiris. 

What makes you most suspicious of a diagnosis of cardiac amyloidosis from the typical heart failure patient? 

You must have a strong index of suspicion, meaning you THINK that the patient could have cardiac amyloidosis, to consider it diagnostically. Some characteristics or “red flags” to not miss:  

Disproportionately thick heart muscle with a relatively low voltages on EKG  

Bilateral carpal tunnel syndrome – estimated that 1 in 10 people >65 years old will have amyloidosis  

Previously tolerated antihypertensive medications 

Atraumatic biceps tendon rupture  

Bilateral carpal tunnel syndrome 

Spinal stenosis  

Concomitant with other diseases: HFpEF, low-flow low-gradient aortic stenosis 

How would you work up a patient for cardiac amyloidosis?  

Start with a routine ECG (looking for disproportionally low voltage) and routine TTE (looking for thick heart muscle) 

CBC, serum chemistries, hepatic function panel, NT proBNP, and troponin levels 

NOTE: It is critical to differentiate between amyloid light chain (AL amyloidosis) and transthyretin ATTR amyloidosis, as both make up 95-99% of amyloidosis cases.  

Obtain serum free light chains, serum & urine electrophoresis, and serum & urine immunofixation to rule out AL amyloidosis. (See table below) 

AL Amyloidosis ATTR Amyloidosis  → Positive serum free light chains and immunofixation (Abnormal M protein) → Tissue biopsy (endomyocardial, fat pad) to confirm diagnosis → Negative serum free light chains and immunofixation (ruled out AL amyloidosis) → Cardiac scintigraphy (Technetium pyrophosphate with SPECT imaging) 

What treatment options do we have to offer now for ATTR CM, and how has this compared to prior years?  

Before 2019, treatment options were limited outside of cardiac transplantation and prophylactic liver transplants for hereditary ATTR amyloidosis. 

Treatments since 2019 have utilized the amyloidogenic cascade: 

TTR protein is formed in the liver and circulates in the bloodstream.  

Current treatments aim to either slow ATTR progression by stopping deposition or clearing amyloid deposits 

Only FDA-approved treatments are for stopping deposition, while agents that clear amyloid deposits remain investigational. Two classes of agents that stop amyloid deposition are TTR stabilizers and TTR Silencers. (See table below) 

TTR Stabilizers TTR Silencers Tafamidis (ATTR-ACT, 2018) Acoramidis (ATTRibute-CM, 2024)  Inotersen (Clinical Trial, 2018) Eplontersen (Clinical Trial, 2023) Patisiran (Clinical Trial, 2018)  Vutrisiran* (Clinical Trial, 2022)   Mechanism: prevents dissociation of, or stabilizes, the TTR tetramer to halt disease progression Mechanism: inhibit the liver’s production of TTR in the bloodstream via small interfering RNAs (siRNAs)/antisense oligonucleotides Route of administration: PO (pills) Route of Administration: IV infusions *Vutrisiran is a subQ injection q3months Outcomes: improve morbidity and mortality in both wildtype (wtATTR) and hereditary ATTR (hATTR) amyloidosis Outcomes: only approved for treatment of hATTR with polyneuropathy 

Agents that clear amyloid deposits are still in clinical trials (ALXN2200, Coramitug PRX004). 

Liver transplantation is the only method of clearing amyloid fibril deposits until the FDA approves a fibril-depleting agent, as perhaps one of the aforementioned agents.  

How do you use genetic testing in your practice? How does the role of genetic testing impact treatment options for patients and their families?  

Genetic testing = standard of care; everyone with ATTR-CM should get genetic sequencing! 

Family screening is also important, as hATTR is an autosomal dominant disease. Patients and families can be referred to genetic counseling, become educated on the GINA Act, and choose to start cascade screening for family members. 

Family members can be affected in different ways, as penetrance can occur at different ages  

Due to current FDA labeling patients must have hereditary ATTR with polyneuropathy and a pathologic variant to qualify for TTR silencer treatment. Patients can have concomitant cardiomyopathy but must also have polyneuropathy and pathologic variant.  

TTR stabilizers are approved for ATTR cardiomyopathy regardless of the presence of the pathogenic TTR variant.  

Are there differences in treatment response between wtATTR or hATTR? What about differences in men and women? 

Epidemiological studies suggest variant (hereditary) ATTR patients have more aggressive disease than wildtype ATTR patients.  

Since current treatments do not cure the disease and work to slow progression, patients with advanced stages of disease do not show much benefit from current therapies. 

Whether it is wild type or hereditary, diagnosing ATTR as early as possible will afford patients the greatest therapeutic impact of current treatments.  

The current data does not suggest a therapeutic difference in response between men and women with ATTR cardiac amyloidosis 

What is the role of CRISPR/Cas9 in the treatment of cardiac amyloidosis?  

ATTR amyloidosis is an elegant disease model because it is one gene responsible for one protein and ultimately one disease process. 

NTLA 2001 (currently in a phase-three clinical trial, link to phase one) is an agent administered in a single infusion to silence hepatic production of TTR indefinitely. 

We are awaiting promising results from this trial at the time of this recording. 

How can we best call on our friends in other subspecialities to take care of the concomitant diseases – peripheral neuropathy, symptomatic atrial fibrillation, aortic stenosis? Do any ATTR specific treatments show improvement in these manifestations? 

TTR amyloidosis patients need a multidisciplinary care model for success. 

Carpal tunnel syndrome is common in ATTR amyloidosis, so referrals to neurology and hand surgery are common 

Patients with autonomic dysfunction secondary to autonomic neuropathy could benefit from neurology referral for blood pressure strategies and gastroenterology due to gut dysmotility and constipation. 

Electrophysiology (EP) referral is common for atrial fibrillation and atrial flutter 

ATTR is a disease of aging, so collaborating with geriatricians is important to help coordinate care and establish the patient’s individualized goals.  

 What is your management of subclinical ATTR and strategies for early detection? 

Again, having a strong index of suspicion for cardiac amyloidosis is prudent.   

The most common TTR variant that causes hATTR on earth is the V122I mutation (PV142I), which is very common in Western African ancestry. We suspect 1.5 million carriers of this variant in the USA alone, which puts individuals at 2-3x higher risk for heart failure than their age, sex, and race-matched non-carrier controls. 

Expert consensus suggests monitoring individuals with this variant about 10 years before when the proband (i.e. if patient was diagnosed at 70, family members start screening at 60).  

Initial work-up should include standard tests: ECG, echocardiogram, blood work. 

Upcoming clinical trial will enroll patients in this critical 10-year window and randomize them into acoramadis vs placebo to see if treatment before symptom/disease onset can prevent amyloid disease. 

References

Arbelo E, Protonotarios A, Gimeno JR, et al. 2023 ESC Guidelines for the management of cardiomyopathies: Developed by the task force on the management of cardiomyopathies of the European Society of Cardiology (ESC). Eur Heart J. 2023;44(37):3503-3626. doi:10.1093/eurheartj/ehad194 

Maron MS, Masri A, Nassif ME, et al.

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.  

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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

Drs. Rick Ferraro and Sneha Nandy discuss ‘Diagnosis of ATTR Cardiac Amyloidosis’ with Dr. Venkatesh Murthy.  In this episode, we explore the diagnosis of ATTR cardiac amyloidosis, a condition once considered rare but now increasingly recognized due to advances in imaging and the availability of effective therapies. Dr. Venkatesh Murthy, a leader in multimodality imaging, discusses key clinical and laboratory features that should raise suspicion for the disease. We also examine the role of nuclear imaging and genetic testing in confirming the diagnosis, as well as the importance of early detection. Tune in for expert insights on navigating this challenging diagnosis and look out for our next episode on treatment approaches for cardiac amyloidosis! Audio editing for this episode was performed by CardioNerds Intern, Julia Marques Fernandes.

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Pearls: - Diagnosis of Transthyretin amyloid cardiomyopathy

1. Recognizing the Red Flags – ATTR cardiac amyloidosis often presents with subtle but telling signs, such as bilateral carpal tunnel syndrome, low-voltage ECG, and a history of lumbar spinal stenosis or biceps tendon rupture. If you see these features in a patient with heart failure symptoms, think amyloidosis!  

 2. “Vanilla Ice Cream with a Cherry on Top” – On strain echocardiography, apical sparing is a classic pattern for cardiac amyloidosis. While helpful, it’s not foolproof—multimodal imaging and clinical suspicion are key!  

3. Nuclear Imaging is a Game-Changer – When suspicion for cardiac amyloidosis is high à a positive PYP scan with SPECT imaging (grade 2 or 3 myocardial uptake) in the absence of monoclonal protein (ruled out by SPEP, UPEP, and free light chains) is diagnostic for ATTR amyloidosis—no biopsy needed!  

4. Wild-Type vs. Hereditary? Know the Clues – Older patients (70+) are more likely to have wild-type ATTR, while younger patients (40s-60s), especially those with neuropathy and a family history of heart failure, should raise suspicion for hereditary ATTR. Genetic testing is crucial for distinguishing between the two. Note that some ATTR variants may predispose to a false negative PYP scan! 

5. Missing Amyloidosis = Missed Opportunity – With multiple disease-modifying therapies now available, early diagnosis is critical. If you suspect cardiac amyloidosis, don’t delay the workup—early treatment improves outcomes!  

Notes - Diagnosis of Transthyretin amyloid cardiomyopathy

What clinical features should raise suspicion for ATTR cardiac amyloidosis?  

ATTR cardiac amyloidosis is underdiagnosed because symptoms overlap with other forms of heart failure.  

Red flags include bilateral carpal tunnel syndrome (often years before cardiac symptoms), low-voltage ECG despite increased LV wall thickness, heart failure with preserved ejection fraction (HFpEF) with a restrictive pattern, and history of lumbar spinal stenosis, biceps tendon rupture, and/or peripheral neuropathy, including possible autonomic dysfunction (e.g., orthostatic hypotension). 

Remember: If an older patient presents with heart failure and unexplained symptoms like neuropathy or musculoskeletal issues, think amyloidosis!  

What is the differential diagnosis for a thick left ventricle (LVH) and how does ATTR amyloidosis fit into it?   

Hypertension: Most common cause of LVH, typically with a history of uncontrolled high blood pressure.  

Aortic stenosis: May present with concentric LVH.  

Hypertrophic cardiomyopathy (HCM): Genetic disorder typically presenting with asymmetric LVH, especially in younger patients.  

Infiltrative cardiomyopathy: Often due to amyloidosis, sarcoidosis, or hemochromatosis. 

Storage disorder: Fabry’s, Danon, Pompe, etc. 

What are the key imaging modalities used to diagnose ATTR cardiac amyloidosis?  

Echocardiography: Thickened LV walls (>12 mm) with a restrictive filling pattern, Speckled appearance on 2D echo (not specific), apical sparing on strain imaging (“Vanilla ice cream with a cherry on top”). 

Cardiac MRI (CMR): Late gadolinium enhancement (LGE) in a global subendocardial pattern, T1 mapping & extracellular volume (ECV) expansion are supportive findings. 

Nuclear Scintigraphy (99mTc-PYP scan): Gold standard noninvasive test for ATTR. Grade 2 or 3 uptake (equal to or greater than bone uptake) is diagnostic if monoclonal protein is absent in the right clinical scenario.  

What lab tests are used to diagnose ATTR cardiac amyloidosis?  

Check troponin and NTproBNP (useful for staging) 

Rule out AL amyloidosis with monoclonal protein studies like serum protein electrophoresis (SPEP) and urine protein electrophoresis (UPEP) with immunofixation and serum free light chain (FLC) assay (to detect clonal plasma cell disorders)  

Why is ruling out AL amyloidosis critical before diagnosing ATTR?  

They are treated very differently- AL amyloidosis is an oncologic emergency requiring chemotherapy, while ATTR is treated with medications. 

If workup for AL amyloidosis, such as SPEP/UPEP or serum free light chains ratio, comes back positive, you do not need to pursue further testing for ATTR amyloidosis.  

When should genetic testing be performed in suspected ATTR amyloidosis?  

All patients diagnosed with ATTR amyloidosis should undergo genetic testing to distinguish wild-type from hereditary forms.  

Wild-type ATTR:  More common in older men (≥70 years), no known mutation, sporadic occurrence, often presents with predominantly cardiac involvement  

Familial ATTR: Autosomal dominant inheritance, more common in Black patients (V122I mutation), more likely to have neuropathy and earlier onset of heart failure (4th or 5th decade). Specific variants have typical geographic distribution and predilection to causing neuropathy and/or cardiomyopathy. 

When is a biopsy necessary to confirm ATTR amyloidosis?   

Biopsy is not needed if PYP scan is positive (Grade 2-3) and AL amyloidosis is ruled out.  

If the diagnosis remains uncertain, a biopsy can be performed of either a fat pad or salivary gland biopsy (easier, lower sensitivity) or an endomyocardial biopsy (gold standard but invasive). 

References - Diagnosis of Transthyretin amyloid cardiomyopathy

Dorbala S, Ando Y, Bokhari S, et al. ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI expert consensus recommendations for multimodality imaging in cardiac amyloidosis: Part 1 of 2-evidence base and standardized methods of imaging [published correction appears in J Nucl Cardiol. 2021 Aug;28(4):1761-1762. doi: 10.1007/s12350-021-02711-w.]. J Nucl Cardiol. 2019;26(6):2065-2123. doi:10.1007/s12350-019-01760-6 

https://pubmed.ncbi.nlm.nih.gov/31468376

Writing Committee, Kittleson MM, Ruberg FL, et al. 2023 ACC Expert Consensus Decision Pathway on Comprehensive Multidisciplinary Care for the Patient With Cardiac Amyloidosis: A Report of the American College of Cardiology Solution Set Oversight Committee [published correction appears in J Am Coll Cardiol. 2023 Mar 21;81(11):1135. doi: 10.1016/j.jacc.2023.02.013.]. J Am Coll Cardiol. 2023;81(11):1076-1126. doi:10.1016/j.jacc.2022.11.022 

https://pubmed.ncbi.nlm.nih.gov/36697326

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.  

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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.

In this episode, CardioNerds Dr. Gurleen Kaur, Dr. Richard Ferraro, and Dr. Jake Roberts are joined by Cardio-Rheumatology expert, Dr. Monica Mukherjee, to discuss the role of utilizing multimodal imaging for cardiovascular disease risk stratification, monitoring, and management in patients with chronic systemic inflammation. The team delves into the contexts for utilizing advanced imaging to assess systemic inflammation with cardiac involvement, as well as the role of imaging in monitoring various specific cardiovascular complications that may develop due to inflammatory diseases. Audio editing by CardioNerds academy intern, Christiana Dangas.

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Pearls - Cardiovascular Multimodality Imaging & Systemic Inflammation

Systemic inflammatory diseases are associated with an elevated CVD risk that has significant implications for early detection, risk stratification, and implementation of therapeutic strategies to address these risks and disease-specific complications. As an example, patients with SLE have a 48-fold increased risk for developing ASCVD compared to the general population. They may also develop disease-specific complications, such as pericarditis, that require focused imaging approaches to detect.

In addition to increasing the risk for CAD, systemic inflammatory diseases can also result in cardiac complications, including myocardial, pericardial, and valvular involvement. Assessment of these complications requires the use of different imaging techniques, with the modality and serial studies selected based on the suspected disease process involved.

In most contexts, echocardiography remains the starting point for evaluating cardiac involvement in systemic inflammatory diseases and can inform the next steps in terms of diagnostic study selection for the assessment of specific cardiac processes. For example, if echocardiography is completed in an SLE patient and demonstrates potential myocardial or pericardial inflammation, the next steps in evaluation may include completing a cardiac MRI for better characterization.

While no current guidelines or standards of care directly guide our selection of advanced imaging studies for screening and management of CVD in patients with systemic inflammatory diseases, our understanding of cardiac involvement in these patients continues to improve and will likely lead to future guideline development.

Due to the vast heterogeneity of cardiac involvement both across and within different systemic inflammatory diseases, a personalized approach to caring for each individual patient remains central to CVD evaluation and management in these patients. For example, patients with systemic sclerosis and symptoms of shortness of breath may experience these symptoms due to a range of causes. Echocardiography can be a central guiding tool in assessing these patients for potential concerns related to pulmonary hypertension or diastolic dysfunction. Based on the initial echocardiogram, the next steps in evaluation may involve further ischemic evaluation or right heart catheterization, depending on the pathology of concern.

Show notes - Cardiovascular Multimodality Imaging & Systemic Inflammation

Episode notes drafted by Dr. Jake Roberts.

What are the contexts in which we should consider pursuing multimodal cardiac imaging, and are there certain inflammatory disorders associated with systemic inflammation and higher associated CVD risk for which advanced imaging can help guide early intervention?

Systemic inflammatory diseases are associated with elevated CVD risk, which has significant implications for early detection, risk stratification, prognostication, and implementation of therapeutic strategies to address CVD risk and complications in these patient populations.The most well-characterized autoimmune diseases with an association between systemic inflammation and CVD risk are inflammatory arthritic conditions such as rheumatoid arthritis. Additional inflammatory diseases with elevated CVD risk include spondyloarthropathies and psoriatic arthritis.Patients with rheumatoid arthritis have a 1.5- 2x risk of developing coronary artery disease compared to the general population.The mechanism of elevated CVD risk in inflammatory disease patients is likely related to a combination of abnormalities in lipid metabolism, endothelial dysfunction, and vascular inflammation.

Conditions including systemic lupus erythematosus (SLE), myositis, vasculitis disorders, and systemic sclerosis may have additional cardiovascular complications beyond CAD, including pericarditis, myocarditis, electrical, and valvular complications.

Are there any established or emerging technologies to help with improving early detection or characterization of cardiac involvement in systemic inflammatory diseases?

Echocardiography remains the most common and useful starting point for screening and early detection of cardiac involvement in systemic inflammatory diseases due to its widespread availability, real-time interpretation, low cost, and noninvasive nature. Furthermore, echocardiography remains a crucial tool in serial monitoring for disease progression and the detection of therapeutic effects. This modality additionally provides significant utility for early detection and screening of pericardial and valvular involvement.

Given that patients with inflammatory disorders have an elevated risk for developing CAD, utilizing CAC scores and CCTA are often additionally helpful for CAD detection in these patient populations.

Are there different imaging techniques that should be used to assess complications specific to different systemic inflammatory diseases?

Based on the specific disease involved, the choice of imaging technique may vary depending on the clinical context and the cardiovascular complication requiring further investigation.

As an example, in systemic sclerosis, there can be a wide range of variable cardiac manifestations that emerge depending on the subtype of the disease, with the cardiac complications developing either because of the fibrotic disease process or from other secondary effects of the disease. Specifically, if the patient's phenotype involves interstitial lung disease, the right ventricle of the heart will encounter chronic increased afterload, which can lead to adverse adaptive responses and remodeling over time. As a result, screening tools such as echocardiography can be very useful in this patient population, with these patients often requiring regular annual screening echocardiograms coupled with pulmonary function testing to screen for coupled changes in individual patients’ physiology. When these patients develop complications of their disease, including pulmonary hypertension, echocardiography can help evaluate the underlying cause of this complication and inform subsequent diagnostic steps.

In terms of assessing myocardial disease and inflammation in myocardial tissue, cardiac MRI remains a valuable tool in detecting subclinical myocardial disease and can identify areas of low-grade myocardial inflammation. One of the advantages of cardiac MRI over other imaging techniques involves its ability to allow for noninvasive tissue characterization.

For disease complications such as pericarditis, which can commonly develop in SLE, 2D echocardiography remains the first-line imaging modality of choice to detect pericardial disease involvement. In SLE patients who have long-standing pericardial disease with progression, they can also develop constrictive symptoms resulting from this process. In those cases, either CT or cardiac MRI can assist in defining the pericardial or myocardial anatomy.

As an example, what would be the approach to utilizing advanced imaging to assess for CVD detection and monitoring in a patient with SLE with relatively well-controlled symptoms on chronic immunosuppressive agents and no prior history of heart failure or CVD?

As a starting point, all patients with systemic inflammatory diseases should undergo comprehensive ASCVD risk assessment. Initial stratification involves completing a laboratory assessment with a standard lipid panel and diabetes screening studies. Further evaluation of any symptoms that a patient may describe, which could indicate potential early cardiovascular disease processes, should also be thoroughly assessed and may influence the next steps in screening.

In the context of SLE, pericardial disease is common, and therefore, obtaining a baseline echocardiogram to assess for any early pericardial involvement should be the initial step in evaluation. If the patient also has an elevated ASCVD risk, they should also undergo assessment for coronary artery disease.

What should be the approach to the sequence of imaging technique selection, serial imaging, monitoring, and follow-up in patients with systemic inflammatory disorders undergoing evaluation of CVD screening and monitoring?

The initial selection of imaging modality should be based on what is suspected to be the primary driver of the patient’s symptoms or as the primary underlying process of concern that requires further evaluation.

As an important consideration in the context of systemic inflammatory diseases such as SLE, ischemic disease may involve atypical presentations due to underlying myocardial dysfunction and microvascular disease. Therefore, imaging and other diagnostic studies may be warranted to assess for reversible ischemia. There is emerging evidence that cardiac PET perfusion and cardiac MRI may be particularly useful in this patient population to assess coronary flow reserve to evaluate for coronary microvascular disease.

In this episode, CardioNerds Dr. Anna Radakrishnan and Dr. Apoorva Gangavelli are joined by prevention expert Dr. Martha Gulati and heart failure expert Dr. Anu Lala to discuss heart failure with preserved ejection fraction (HFpEF), a multifactorial, evolving challenge, particularly in women. In this episode, we delve into the distinctive clinical presentation and pathophysiology of HFpEF among women, exploring both traditional and gender-specific risk factors, from metabolic and inflammatory processes to the impact of obesity, sleep apnea, and gender-specific conditions. We also discussed the latest evidence on prevention strategies and emerging therapies that not only target HFpEF symptoms but also address underlying risk factors. This conversation highlights the importance of multidisciplinary, holistic care to advance diagnosis, management, and ultimately, patient outcomes for women with HFpEF. Audio editing by CardioNerds academy intern, Christiana Dangas. 

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Pearls - HFpEF in Women

HFpEF Is a Multisystem Syndrome:HFpEF in women involves more than just diastolic dysfunction—it represents a convergence of metabolic, inflammatory, and hormonal factors that make its diagnosis and management uniquely challenging.

Visceral Adiposity Drives Risk:Obesity isn’t just excess weight; central or visceral adiposity actively promotes inflammation, insulin resistance, and microvascular dysfunction, which are crucial in triggering HFpEF in women.

Early Identification Is Key:Recognizing—and treating—subtle risk factors such as sleep-disordered breathing, hypertension, and subtle metabolic dysfunction early, especially in women who may underreport symptoms, can prevent progression to HFpEF.

Holistic, Lifespan Approach Matters:Effective HFpEF care involves managing the whole cardiometabolic profile with tailored lifestyle interventions, advanced medications (e.g., SGLT2 inhibitors, GLP-1 agonists), and even cardiac rehabilitation, which remain critical at every stage, even after diagnosis.

Tailoring Prevention to Unique Risks in Women:Gender-specific factors such as postmenopausal hormonal changes, pregnancy-related complications, and autoimmune conditions demand a customized prevention strategy, reminding us that prevention isn’t one-size-fits-all.

Show notes - HFpEF in Women

Notes drafted by Dr. Apoorva Gangavelli

1. What are the gender-based differences in HFpEF presentation?

HFpEF in women often presents with more subtle symptoms such as exertional dyspnea and fatigue, which may be mistakenly attributed to aging or obesity.

Women tend to have a higher prevalence of preserved ejection fraction despite a similar heart failure symptom burden to men.

The diagnostic challenge is compounded by lower natriuretic peptide levels influenced by hormonal factors, particularly postmenopausal estrogen deficiency, leading to false negatives and underdiagnosis.

2. How do traditional and gender-specific risk factors contribute to the development of HFpEF in women?

Traditional risk factors include obesity, hypertension, diabetes, and metabolic syndrome.

Gender-specific risk factors encompass pregnancy-related complications, menopause, and autoimmune diseases, which may uniquely affect cardiovascular structure and function in women.

The interaction between visceral adiposity and systemic inflammation is central in predisposing women to HFpEF.

3. What underlying pathophysiological mechanisms make women more susceptible to HFpEF?

Chronic inflammation and endothelial dysfunction contribute to myocardial stiffness and diastolic dysfunction.

Insulin resistance results in impaired myocardial metabolism and lipotoxicity.

Microvascular dysfunction, with reduced nitric oxide bioavailability, is more pronounced in women, exacerbating cardiac remodeling and fibrosis.

4. What prevention strategies can be tailored across different life stages to reduce HFpEF risk in women?

Early detection and aggressive management of traditional risk factors (e.g., blood pressure control, weight management) during perimenopause and early adulthood.

Incorporating lifestyle modifications such as structured exercise programs, improved dietary habits, and sleep optimization.

Preventive interventions might also include screening for gender-specific risk factors like pregnancy complications and autoimmune conditions early in life.

5. What current and emerging therapeutic approaches are used in the management of HFpEF in women?

Use of mineralocorticoid receptor antagonists and nonsteroidal alternatives shows promise, particularly in reducing hospitalizations.

Novel pharmacologic agents such as SGLT2 inhibitors and GLP-1 receptor agonists address both heart failure symptoms and metabolic dysfunction.

Cardiac rehabilitation is advocated to improve functional capacity and quality of life despite challenges with insurance coverage.

References - HFpEF in Women

Borlaug BA, Sharma K, Shah SJ, Ho J. Heart Failure With Preserved Ejection Fraction. Journal of the American College of Cardiology. 2023;81(18). doi:https://doi.org/10.1016/j.jacc.2023.01.049

‌Kittleson MM, Gurusher Panjrath, Kaushik Amancherla, et al. 2023 ACC Expert Consensus Decision Pathway on Management of Heart Failure With Preserved Ejection Fraction. Journal of the American College of Cardiology. 2023;81(18). doi:https://doi.org/10.1016/j.jacc.2023.03.393

Radakrishnan A, Agrawal S, Singh N, et al. Underpinnings of Heart Failure With Preserved Ejection Fraction in Women - From Prevention to Improving Function. A Co-publication With the American Journal of Preventive Cardiology and the Journal of Cardiac Failure. Journal of Cardiac Failure. Published online February 2025. doi:https://doi.org/10.1016/j.cardfail.2025.01.008

In this webinar, the CardioNerds collaborated with the Cardiogenic Shock Working Group (CSWG) to discuss LV unloading and the updated AMI guidelines, which upgraded transvalvular flow pumps to a Class 2A recommendation in AMI shock.

Dr. Rachel Goodman and Dr. Gurleen Kaur from CardioNerds were joined by Dr. Navin Kapur (Tufts Medical Center), Dr. Shashank Sinha (INOVA Fairfax Hospital), and Dr. Rachna Kataria (Brown University) from the CSWG.

Together, they explore a case of an older woman who presented with inferior STEMI and was found to have complete occlusion of an anomalous single coronary artery originating from the right coronary cusp and supplying the entire left ventricle. She was treated with DES to the anomalous RCA. Her course was complicated by AMI shock with re-occlusion of the DES, which was treated with thrombectomy and balloon angioplasty. An IABP was placed. After transfer to a tertiary care center, a pulmonary artery catheter revealed a CI of 0.96. With worsening shock, rising lactate, and end organ dysfunction, the team proceeded with VA-ECMO and Impella CP for LV unloading. Her lactate subsequently normalized.

Produced by CardioNerds in collaboration with the Cardiogenic Shock Working Group.

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