54. Case Report: Wild type aTTR Cardiac Amyloid – Washington University in St. Louis

CardioNerd (Amit Goyal) join Washington University in St. Louis cardiology fellows (Adam Lick, Manny Rivera Maza, and Sam Lindner) for some amazing local St. Louis craft brews! They discuss a fascinating case of  wild-type aTTR cardiac amyloid. Prior to meeting up with the group, Amit bumps into Rachita Navara: a Wash U #FIT, aspiring electrophysiologist, & a rock star of the band “The Pacemakers” (be sure to check out their performance at the end of the episode!) who shares thoughts about the program and her cutting edge contributions to the field of EP. Dr. Katie Zhang provides the E-CPR and program director Dr. Andy Kates provides a message for applicants. Episode notes were developed by Johns Hopkins internal medicine resident Colin Blumenthal with mentorship from University of Maryland cardiology fellow Karan Desai.  

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CardioNerd (Amit Goyal) join Washington University in St. Louis cardiology fellows (Adam Lick, Manny Rivera Maza, and Sam Lindner) for some amazing local St. Louis craft brews! They discuss a fascinating case of  wild-type aTTR cardiac amyloid. Prior to meeting up with the group, Amit bumps into Rachita Navara: a Wash U #FIT, aspiring electrophysiologist, & a rock star of the band "The Pacemakers" (be sure to check out their performance at the end of the episode!) who shares thoughts about the program and her cutting edge contributions to the field of EP.  Dr. Katie Zhang provides the E-CPR and program director Dr. Andy Kates provides a message for applicants. Episode notes were developed by Johns Hopkins internal medicine resident Colin Blumenthal with mentorship from University of Maryland cardiology fellow Karan Desai.
Episode graphic by Dr. Carine Hamo

The CardioNerds Cardiology Case Reports series shines light on the hidden curriculum of medical storytelling. We learn together while discussing fascinating cases in this fun, engaging, and educational format. Each episode ends with an “Expert CardioNerd Perspectives & Review” (E-CPR) for a nuanced teaching from a content expert. We truly believe that hearing about a patient is the singular theme that unifies everyone at every level, from the student to the professor emeritus.

We are teaming up with the ACC FIT Section to use the #CNCR episodes to showcase CV education across the country in the era of virtual recruitment. As part of the recruitment series, each episode features fellows from a given program discussing and teaching about an interesting case as well as sharing what makes their hearts flutter about their fellowship training. The case discussion is followed by both an E-CPR segment and a message from the program director.

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Cardionerds Cardiology Podcast Presents CardioNerds Case Report Series

Patient Summary

A man in his early 70s, with a history of hypertension, a bicuspid aortic valve, chronic kidney disease and carpal tunnel syndrome presents with two weeks of worsening dyspnea on exertion. At baseline, he is an avid cyclist and noticed he can now only bike ½ mile when before he could bike extended distances. In addition, he noted abdominal swelling and palpitations. Vitals signs showed mild tachycardia, irregularly irregular rhythm, and no clear evidence of volume overload. Labs demonstrated acute on chronic kidney disease, an elevated NT-proBNP and elevated troponin. ECG demonstrated atrial flutter with variable conduction block. TTE demonstrated marked concentric left ventricular hypertrophy with preserved ejection fraction, biatrial enlargement, reduced global longitudinal strain with apical sparing, and bicuspid aortic valve with moderate aortic stenosis. Further diagnostics revealed normal serum kappa/lambda light chains and PYP scan was positive. Patient underwent EMB which demonstrated ATTR amyloid deposition and genetic screening did not show mutations commonly associated with hereditary ATTR. 


Case Media

A. CXR: Stable mild enlargement of the cardiac silhouette; mildly tortuous aorta. Lung fields are clear, no pneumonia, pleural effusions, or pneumothorax.
B. AV continuous wave Doppler
C. Strain Image
D. Tc-99 PYP Scan

TTE 1
TTE 4
TTE 2
TTE 5
TTE 3
TC-99 PYP Scan
Strain video 1
Strain video 2
Strain video 3

Episode Schematics & Teaching


The CardioNerds 5! – 5 major takeaways from the #CNCR case

  1. Cardiac amyloidosis can have a range of cardiac and extra-cardiac findings as amyloid fibrils can deposit in many different tissues, depending on the amyloid protein involved. The first step in diagnosis is maintaining a high index of suspicion. 
    1. The presence of prominent right-sided HF symptoms, low voltage on ECG, biatrial enlargement, ventricular hypertrophy, conduction disease, and pericardial effusion should prompt a high suspicion for cardiac amyloid. These are typical features of infiltrative or storage restrictive cardiomyopathies. PEARL: ATTR CM can cause asymmetric LVH and is an important HCM phenocopy! 
    2. Remember, amyloidosis is a systemic disease and extra-cardiac findings are common. ATTR amyloid has a predilection for the musculoskeletal system (including bilateral carpal tunnel syndrome, lumbar spinal stenosis, and biceps tendon rupture) and peripheral nerves. Conversely, AL amyloid is widely deposited outside the CNS an can result in protean manifestations, including periorbital ecchymoses from vascular fragility, macroglossia, and visceral organ involvement (including nephrotic syndrome, hepatic infiltration, and gut amyloid). 
  2. When considering cardiac amyloid, there are four primary etiologies: 
    1. Wild-Type (non-hereditary) ATTR amyloidosis is caused by deposition of misfolded transthyretin proteins. It is an under-recognized cause of HFpEF, with incidence increasing with age. 
    2. Hereditary ATTR is caused by a genetic mutation that leads to instability of the transthyretin tetramer. The most common mutation is the Val30Met variant. Specific mutations tend to have templated organ manifestations, natural history, and prognosis.  
    3. AL amyloidosis is caused by deposition of light-chains from a clonal plasma cell dyscrasia. 
    4. AA amyloidosis is a rare form of cardiac amyloid caused by deposition of the acute phase reactant serum amyloid A protein due to a chronic inflammatory process. 
  3. Evaluating for AL amyloid with appropriate lab workup is crucial. “Missing AL amyloid is like missing a STEMI” – Dr. Paul Cremer (Episode #8)! Workup should include SPEP, UPEP, serum/urine immunofixation, and serum kappa/lambda free light chains to maximize sensitivity. Note: SPEP and UPEP alone are insensitive and inadequate! 
  4. Like many cardiac diseases, multimodal diagnostics are key in the diagnosis of cardiac amyloid 
    1. ECG: Low voltage, pseudoinfarct pattern, variable conduction disease, atrial arrhythmias. PEARL: 10% of patients with cardiac amyloid may have high voltages on ECG. LVH on imaging out of proportion to EKG voltages is a red flag! 
    2. TTE: We have discussed typical features of an infiltrative or storage restrictive cardiomyopathy previously , including marked LVH with normal LV volumes and bi-atrial enlargement. Other features include: RV hypertrophy, thickened valve leaflets, thick interatrial septum, speckled appearance of the myocardium, and small pericardial effusion. Bi-atrial enlargement may lead to functional MR and TR as well as atrial arrhythmias. Mitral inflow pattern and tissue doppler will show varying degrees of diastolic dysfunction depending on stage. Systolic function may be borderline and progressively decline in “burned-out” disease. Reduced global longitudinal strain with apical sparing may help differentiate cardiac amyloid from hypertensive heart disease. There is an overlap with aortic stenosis which will frequently manifest as a low flow and/or low gradient phenotype due to reduce stroke volumes. 
    3. Cardiac MRI: There are characteristic findings of early subendocardial late gadolinium enhancement (LGE) and later transmural LGE with abnormal blood-pool-to-myocardial nulling (an MRI technique to accentuate pathology).  
    4. PYP scan: >99% sensitivity for cardiac ATTR amyloid. If monoclonal gammopathy is excluded, the positive predictive value is 100%. 
    5. RHC +/- EMBx: the hemodynamic profile is that of restrictive cardiomyopathy with elevated filling pressures, blunted x descent, and steep y descent. There may be diastolic pressure equalization. If EMBx is pursued, pathology will reveal amyloid protein as a salmon-pink color when congo red stain is applied and when placed under polarized light the amyloid proteins have an apple-green birefringence. Amyloid fibrils are seen with electron microscopic study.  Mass spec for protein identification. 
  5. Cardiac amyloid can be very difficult to treat with typical HF regimens, as beta blockers and ACE-I/ARB can lead to excessive hypotension in the setting of autonomic neuropathy and restrictive hemodynamics.  For TTR amyloid, there are treatment options like tafamidis (a transthyretin protein stabilizer) which can reduce mortality considerably in selected patients.  Investigational RNA-targeted therapies (i.e., patisiran) are increasing the options for treating TTR, but cost remains a major barrier to care. For AL amyloid, a multidisciplinary cardio-oncology team is vital to coordinate chemotherapy and cardiovascular care. Heart transplant +/- bone marrow transplant may be options in advanced stages of disease. The challenges of managing advanced disease highlight the importance of early recognition.  

References


CardioNerds Case Reports: Recruitment Edition Series Production Team

10. AL (Light-Chain) Cardiac Amyloidosis with Dr. Ronald (Ron) Witteles

Dr. Ron Witteles from Standford university provides an approach to cardiac amyloid and specifically AL (Light-Chain) Cardiac Amyloidosis. The discussion is lead by Amit and Dr. Ashley Bock. This episode is the fourth and final part of our immersive journey into the jungle of beta-pleated sheets in the heart. We focus on AL amyloidosis in this episode. Flutter moment by Lois Adamski.

On the CardioNerds Cardiac Amyloid Topic Page you will find podcast episodes, infographic, references, guest contributors, flutter stars, and so much more.

Take me to the Amyloid Topic Page
Take me to episode topics page

Cardiac imaging for Amyloid – Youtube 

Dr. Ronald Witteles is a graduate of Northwestern University where he earned his B.A. in Biology, and of the University of Chicago Pritzker School of Medicine, where he earned his M.D. with Honors.  He then moved west to Stanford University where he completed IM residency and Cardiology fellowship training, serving as both Chief Resident and Chief Fellow. He subsequently joined the faculty at Stanford, and is currently appointed as Professor of Medicine (Cardiovascular Medicine). He has served as Program Director for the Stanford University Internal Medicine Residency Training Program for more than 10 years, where he leads a residency program of approximately 140 residents.  He is Co-Director of the Stanford Amyloid Center – one of the nation’s largest centers in the country which specializes in the treatment of patients with amyloidosis, and he leads an active research program in this area. He also serves as Co-Director of the Stanford Multidisciplinary Sarcoidosis Program, and he is a national leader in Cardio-Oncology, serving as Associate Editor for the country’s premier journal dedicated to the field, JACC: CardioOncology. 

Dr. Ashley Bock earned her medical degree at the University of Colorado and completed her internal medicine residency training at Duke University.  From there she came to the Cleveland Clinic for general cardiology fellowship and advanced heart failure training. She joins our team today to discuss AL cardiac amyloidosis with Dr. Witelles.

9. Cardiac Amyloid Associated with HFpEF & Cardiac ATTR treatment with Drs. Virginia Hahn & Joban Vaishnav ​

Cardionerds (Daniel Ambinder and Carine Hamo) chat with Dr. Virginia Hahn about her work profiling HFpEF patients via endomyocardial biopsy only to find a significant proportion of patients with unsuspected cardiac amyloid. This is followed by a high yield discussion with Dr. Joban Vaishnav about ATTR cardiac amyloid treatment and management options. Flutter moment by David Ambinder (MS IV).

Drs. Joban Vaishnov and Virginia Hahn from Johns Hopkins Cardiology join the Cardionerds Cardiology Podcast

On the CardioNerds Cardiac Amyloid Topic Page you will find podcast episodes, infographic, references, guest contributors, flutter stars, and so much more.

Take me to the Amyloid Topic Page
Take me to episode topics page

Cardiac imaging for Amyloid – Youtube 

Dr. Virginia Shalkey Hahn is a fourth-year Cardiology fellow at Johns Hopkins in Baltimore, MD. She earned her medical degree from the Perelman School of Medicine at the University of Pennsylvania, where she stayed for residency. She moved to Johns Hopkins for Cardiology fellowship (after a 1 year hiatus as an ICU hospitalist). During fellowship, she completed 2 years on the NIH T32 Training grant and one year as chief fellow. She feels passionate about translational heart failure research and mothering her 2 young children.

Dr. Joban Vaishnav completed her undergraduate and medical school training at St. Louis University. She has since been at Johns Hopkins for residency, cardiology fellowship, and advanced heart failure fellowship. Her early research pursuits were in heart failure with preserved ejection fraction. From this, and from her advanced heart failure training, she developed a strong clinical interest and research interest in early diagnosis and treatment of cardiac amyloidosis.

In addition to the great discussion on Cardiac Amyloid ATTR treatment, we are excited to have Dan’s brother, David, join the Cardionerds cardiology podcast to share a special flutter moment! David Ambinder is a 4th year medical student at the University of Maryland and will be starting urology residency this coming July at Westchester Medical Center. He grew up in New York and graduated from Touro College before heading to Baltimore for medical school. He enjoys spending time with his wife Samantha and 3 lovely children.

8. Cardiac Amyloid Imaging & EP Considerations with Drs. Paul Cremer and Eoin Donnellan

Amit and Dr. Zach Il’Giovine learn about multimodality imaging in amyloid from Dr. Paul Cremer at the Cleveland Clinic. On their way to Dr. Cremer’s office, they run into Dr. Eoin Donnellan and discuss some incredible fellow research related to cardiac amyloid from an electrophysiologic perspective.

On the CardioNerds Cardiac Amyloid Topic Page you will find podcast episodes, infographic, references, guest contributors, flutter stars, and so much more.

Take me to the Amyloid Topic Page
Take me to episode topics page

Cardiac imaging for Amyloid – Youtube 

Dr. Paul Cremer earned a Bachelor’s degree in molecular biology from Princeton University, Princeton, NJ, and his medical degree from Harvard Medical School, Boston, MA. Following completion of his internal medicine residency at Massachusetts General Hospital, he worked as a physician for two years at the Navajo IHS Chinle Comprehensive Health Care Facility in Chinle, Ariz. He then continued his postdoctoral training with a three-year fellowship in cardiovascular medicine and a subsequent two-year fellowship in advanced cardiovascular imaging, both at Cleveland Clinic. He joined the Cleveland Clinic staff in 2017. He is the director of the Cleveland Clinic CCU.  He enjoys swimming and reading fantasy books with his daughters. He joins the cardionerds cardiology podcast to shed insight on cardiac amyloid imaging.

Dr. Eoin Donnellan is a 3rd year Cardiology Fellow at the Cleveland Clinic and all-around nice guy. He received his medical degree from University College Cork in Ireland before heading to the big city to continue his training at the Mater Hospital in Dublin. He completed his Internal Medicine Residency at the Cleveland Clinic and will start EP Fellowship this July. Outside of the hospital he enjoys long nature walks, whispering sweet nothings, searching for the deeper meaning in little things, and watching thought-provoking and highly entertaining television programs such as This is Us and The Bachelor.

Dr. Zachary Il’Giovine is a general cardiology fellow at the Cleveland Clinic. He received his medical degree from the Wright State University Boonshoft School of Medicine before completing internal medicine training at Duke University. He has clinical interests in advanced heart failure and cardiac critical care. Outside of the hospital he loves playing soccer and spending time with his wife Clare and son Luca.

7. Cardiac Amyloid part 1: case discussion

A new case of congestive heart failure due to cardiac amyloid is presented by Yuxuan Wang and discussed by Carine, Heather, Dan and Amit. Guest oncology star: Jackie Zimmerman. Flutter moment by Mark Heslin.

On the CardioNerds Cardiac Amyloid Topic Page you will find podcast episodes, infographic, references, guest contributors, flutter stars, and so much more.

Take me to the Amyloid Topic Page
Take me to episode topics page

Cardiac imaging for Amyloid – Youtube 

Dr. Yuxuan Wang completed her undergraduate studies at the University of Texas at Austin. She then received her MD and PhD degrees through the Medicine Scientist Training Program at Johns Hopkins School of Medicine. She trained under Bert Vogelstein, focusing on the early detection of cancer. She is currently finishing the last year of residency and fast-tracking into fellowship in Hematology-Oncology.

Dr. Jackie Zimmerman completed the Medical Scientist Training Program at University of Alabama School of Medicine. She completed her internal medicine training and served as assistant chief resident (ACS) for the Longcope firm at The Johns Hopkins Hospital. She is currently a medical oncology fellow at Johns Hopkins and investigating tumor-stromal interactions in pancreatic cancer in the lab of Dr Elizabeth Jaffee.

Mark Heslin is a current 3rd year medical student at Cooper Medical School of Rowan University in Camden, New Jersey. He completed his undergraduate studies at James Madison University with a degree in biology. Mark will be applying to internal medicine residency programs this upcoming fall with the hope of applying for a cardiology fellowship in the future. His clinical interests include clinical reasoning and the management of atherosclerotic cardiovascular disease. Outside of medical school, Mark enjoys spending time on Long Beach Island with his friends and family.