Cardionerds: A Cardiology Podcast

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. Enjoy this Circulation Paths to Discovery article to learn more about the CardioNerds mission and journey.  US Cardiology Review is now the official journal of CardioNerds! Submit your manuscripts here.  CardioNerds Cardiac Amyloid PageCardioNerds Episode Page 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

Joining the discussion are Su Yuan, an adult congenital heart disease expert from New York Presbyterian, alongside first-year fellows Ayan Purkayastha and David Song. They explore an intriguing case of a 53-year-old woman with atypical chest pain linked to congenitally corrected transposition of the great arteries. The team dives into the complexities of diagnosing dextrocardia and managing unique cardiac conditions in adults. Insightful reflections on patient communication and ongoing care highlight the challenges and innovations in treating congenital heart disease.

Dr. Monica Mukherjee, an associate professor at Johns Hopkins, specializes in advanced cardiac imaging and rheumatology. In this discussion, she highlights the crucial link between systemic inflammation and cardiovascular disease risk. They explore advanced imaging techniques, like CMR, that aid in early detection of heart complications in conditions such as lupus and arthritis. The importance of tailored treatment plans and collaboration between cardiologists and rheumatologists is emphasized, showcasing innovative approaches to improve patient outcomes.

Dr. Anu Lala, an expert in heart failure research, and Dr. Martha Gulati, a renowned prevention specialist and author, explore the complexities of heart failure with preserved ejection fraction (HFpEF) in women. They discuss unique clinical presentations and the significance of gender-specific risk factors, including obesity and sleep apnea. The conversation highlights innovative treatment strategies, such as SGLT2 inhibitors, and emphasizes the need for a holistic, multidisciplinary approach to improve outcomes for women facing HFpEF.

Dr. Navin Kapur, a leader in cardiogenic shock research, and Dr. Shashank Sinha, an expert in heart failure, join forces to delve into recent advancements in LV unloading for acute myocardial infarction. They discuss a complex case of a woman with a rare coronary anomaly and the challenges faced in managing cardiogenic shock. Highlights include new guidelines, the significance of advanced interventions like ECMO and Impella CP, and the importance of interdisciplinary collaboration in emergency cardiac care.

Yash Patel, a dedicated third-year resident nearing his chief year, and Tanmay Swadia, an interventional cardiologist and Cath Lab Director, delve into a gripping case involving a 36-year-old man who faced severe complications after ocular surgery. They discuss the rare occurrence of pulmonary air embolism leading to right heart failure and cardiac arrest. The duo highlights the critical importance of early recognition, utilizing advanced hemodynamic support like the Impella RP device, and the need for a multidisciplinary approach in trauma cases.

In this engaging discussion, Dr. Allison Tsao, an interventional cardiologist, shares insights on cutting-edge techniques in congenital heart disease care. Dr. Jill Steiner emphasizes the importance of palliative care, focusing on the emotional well-being of patients. Dr. Katherine Salciccioli explores the intersection of ACHD and cardio-obstetrics, discussing the complexities of pregnancy for patients with congenital heart issues. Together, they tackle the emotional landscape of care, the significance of building trust, and the essential role of compassion in patient-provider relationships.

In this discussion, Dr. Namrita Ashokprabhu, a clinical research coordinator at the Women's Heart Center, Dr. Mehmet Yildiz, a second-year cardiology fellow, and Dr. Yulith Roca Alvarez, a physician starting her cardiology fellowship, dive into the complexities of MINOCA. They explore the critical role of cardiac MRI in diagnosing coronary vasospasm and myocarditis. The team emphasizes the importance of tailored treatments like calcium channel blockers and the challenges of invasive testing methods to manage this intricate cardiovascular condition.

Join Spencer Weintraub, Chief Resident of Internal Medicine, Michael Albosta, a third-year resident, and Zahid Ahmad, an Associate Professor specializing in lipid disorders, as they unravel a compelling case of hypertriglyceridemia. They discuss its link to acute pancreatitis in a woman with a complex medical history, emphasizing diagnosis challenges and management strategies. The conversation dives into lifestyle changes, innovative therapies, and the critical role of nutrition in controlling triglyceride levels, offering valuable insights for preventing cardiovascular complications.

Dr. Sri Mandava, a cardiology fellow at Mount Sinai Medical Center, and Dr. Pranav Venkataraman, an attending physician, delve into a gripping case involving cardiac sarcoidosis presenting as a STEMI in a 57-year-old man. They discuss the challenges of diagnosing unusual STEMI without typical coronary artery disease, emphasizing the role of advanced imaging techniques. The complexities of managing cardiac sarcoidosis and the importance of interdisciplinary collaboration to prevent sudden cardiac events are also highlighted, showcasing critical decision-making in cardiology.