178. Case Report: Occam’s Razor or Hickam’s Dictum? Cardiogenic Shock With Severe Biventricular Heart Failure – Northwestern University

CardioNerds (Amit Goyal and Daniel Ambinder) join Dr. Loie Farina (Northwestern University CardioNerds Ambassador), Dr. Josh Cheema, and Dr. Graham Peigh from Northwestern University for drinks along the shores of Lake Michigan at North Avenue Beach. They discuss a case of a 52-year-old woman with limited cutaneous systemic sclerosis who presents with progressive symptoms of heart failure and is found to have a severe, non-ischemic cardiomyopathy. The etiology of her cardiomyopathy is not clear until her untimely death. She is ultimately diagnosed with cardiac AL amyloidosis with isolated vascular involvement a real occam’s razor or hickam’s dictum conundrum. We discuss the work-up and management of her condition including a detailed discussion of the differential diagnosis, the underlying features of systemic sclerosis with cardiac involvement as well as cardiac amyloidosis, the role of a shock team in managing cardiogenic shock, and how to identify those with advanced or stage D heart failure. Advanced heart failure expert Dr. Yasmin Raza (Northwestern University) provides the ECPR segment. Episode introduction by CardioNerds Clinical Trialist Dr. Liane Arcinas. Audio editing by CardioNerds Academy Intern, Christian Faaborg-Andersen. Claim free CME just for enjoying this episode! Disclosures: NoneJump to: Pearls - Notes - References CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Case Summary - Occam’s Razor or Hickam’s Dictum? This is a case of a 52-year-old woman with limited cutaneous systemic sclerosis who presented with progressive dyspnea on exertion and weight loss over the course of 1 year. Her initial work-up was notable for abnormal PFTs and finding of interstitial pneumonia on high-resolution CT, an ECG with frequent PVCs and normal voltage, a transthoracic echocardiogram with a mildly reduced ejection fraction of 40%, and a right/left heart catheterization with normal coronary arteries, filling pressures, and cardiac output. Scleroderma-related cardiac involvement is suspected. She is placed on GDMT, but her condition worsens over the next several months, and repeat echocardiogram shows severely reduced biventricular function, reduced LV global longitudinal strain (GLS) with apical preservation of strain, severely reduced mitral annular tissue Doppler velocities, and a normal left ventricular wall thickness. Scleroderma-related cardiac involvement remains highest on the differential, but because of some findings on the echo that are concerning for cardiac amyloidosis, an endomyocardial biopsy was obtained. It showed vascular amyloid deposition without interstitial involvement. The diagnosis of cardiac amyloid was discussed but deemed unlikely due to lack of interstitial involvement. However, a serologic work-up soon revealed a monoclonal serum lambda light chain and a follow-up bone marrow biopsy showed 20% plasma cells. She was discharged with very near-term follow-up in oncology clinic with a presumptive diagnosis of AL amyloidosis, but she unfortunately returned in shock and suffered a cardiac arrest. She initially survived and underwent emergent veno-arterial extracorporeal membrane oxygenation (VA ECMO) cannulation with subsequent left ventricular assist device placement (LVAD). However, she passed away due to post-operative hemorrhage. Autopsy was consistent with a final diagnosis of cardiac AL amyloidosis with isolated vascular involvement. Case Media - Occam’s Razor or Hickam’s Dictum? EKG CXR TTE Pathology CMR Episode Teaching -Occam’s Razor or Hickam’s Dictum? Pearls Scleroderma causes repeated focal ischemia-reperfusion injuries which result in patchy myocardial fibrosis. Cardiac involvement in scleroderma is frequent but often not clinically evident; when symptomatic, it is associated with a poor prognosis. Myocardial dysfunction in cardiac AL amyloidosis can result from myocardial infiltration, vascular deposition causing microvascular dysfunction and ischemia, and direct cardiotoxicity from circulating light chains. While isolated vascular amyloid is very rare, it can occur and can be seen without key characteristics of interstitial amyloid deposition, namely left ventricular hypertrophy and low voltage on an ECG. Cardiogenic shock outcomes are improved by multi-disciplinary discussions, commonly referred to as a “shock team call.” Heart failure is a progressive, morbid, and potentially fatal condition. LVADs and heart transplantation improve life expectancy and decrease morbidity among patients with stage D heart failure. Identification of patients with advanced heart failure can be challenging – a helpful mnemonic is “I NEED HELP Notes - Occam’s Razor or Hickam’s Dictum? 1. How does scleroderma affect the heart? Scleroderma is a connective tissue disorder characterized by extracellular matrix deposition, with widespread fibrosis of the skin and visceral organs, microvascular injury, and evidence of immune system activation. Cardiac involvement is common, although likely underestimated as it is often subclinical, and the estimated prevalence varies widely. Myocardial involvement is identified in up to 80% of patients in histological studies and clinical myocardial dysfunction is recognized in 15-25%. When clinically evident, cardiac involvement portends a poor prognosis, with up to a 70% mortality at 5 years. Approximately 25% of scleroderma-related deaths are due to cardiac causes. Primary involvement is thought to be mediated by repeated focal ischemic-reperfusion injury, impaired microcirculation, inflammation, and eventual focal irreversible fibrosis leading to heart failure and arrhythmias. Cardiac involvement can also occur secondary to lung or renal disease, pulmonary arterial hypertension, or other cardiovascular risk factors. Cardiac manifestations: Myocardial failure: diastolic dysfunction is frequently reported but less commonly associated with diastolic heart failure. Systolic dysfunction can also occur, but severe systolic dysfunction is rare. Electrical failure: arrhythmias and conduction disorders Pericardial failure: pericarditis and pericardial effusion Coronary failure: coronary microvascular dysfunction Valvular failure: valvular involvement (uncommon) 2. What is cardiac amyloidosis (CA) and what is the pathophysiology? For an in-depth review of Cardiac Amyloidosis, enjoy the CardioNerds Cardiac Amyloid Series! Amyloidosis is a process in which proteins misfold, aggregate, and form amyloid fibrils that deposit in various organs, thereby causing tissue injury and organ malfunction. The most common types of cardiac amyloidosis are AL (light chain) and TTR (transthyretin). AL amyloidosis is a hematologic disorder of clonal plasma cells that overproduce light chains, which may deposit in any organ sparing the central nervous system, and commonly deposit in the heart and kidneys. Delayed diagnoses are common, with an estimated one-third of patients visiting five or more physicians before receiving the diagnosis. Cardiac involvement with heart failure portends a particularly poor prognosis, with a median survival from onset of heart failure of less than six months without treatment. Stem cell transplantation has been shown to improve survival if performed prior to the diagnosis of advanced heart failure. Unfortunately, about 80% of patients are not candidates for aggressive therapy due to advanced stage of disease. In CA, amyloid deposits infiltrate and expand the extracellular space which results in increased ventricular wall thickness and classically manifests as a restrictive cardiomyopathy with relatively preserved EF; however, a subset of patients may present with reduced LVEF and minimal or no ventricular wall thickening. Patients with AL cardiac amyloidosis tend to have greater severity of heart failure than TTR despite less morphological involvement (in terms of LV wall thickness), felt due to the toxic effect of light chain amyloid fibrils on the tissue resulting in a toxic-infiltrative cardiomyopathy. Additional mechanisms thought to play a major contributing role in cardiac AL amyloidosis: Circulating light chains cause direct cardiotoxicity through cardiomyocyte oxidant stress and abnormal vascular reactivity, impairing vasodilation Vascular amyloid deposition in the small intramural coronary vessels results in microvascular dysfunction and global myocardial ischemia. Vascular involvement is common in AL cardiac amyloidosis (much more common than in TTR cardiac amyloid). A pathology study demonstrated obstructive intramural coronary amyloidosis in 63 of 96 patients (66%) and 86% of these patients had microscopic evidence of myocardial ischemia. Isolated vascular involvement, however, is rare - 97% of patients in this study had interstitial involvement. Coronary microvascular dysfunction occurs via 3 major mechanisms: Structural - with amyloid deposition in the vessel wall causing wall thickening and luminal stenosis Extravascular - through extrinsic compression of the microvasculature from perivascular and interstitial amyloid deposits and decreased diastolic perfusion Functional - through autonomic and endothelial dysfunction 3. What are common cardiac MRI (CMR) findings in scleroderma heart disease and cardiac amyloidosis? First, a review of a few key concepts in CMR (also, enjoy Episode #33. Cardiac MRI with Dr. Deborah Kwon): Native T1 signals are increased by edema (e.g. acute infarction) and an increase in interstitial space (e.g. fibrosis, amyloidosis). T1 signals are decreased by lipid and iron overload.