Case Presentation: A 50-year-old African American male with history of supraventricular tachycardia presented after an episode of chest pain and syncope. He endorsed progressive exertional dyspnea, paroxysmal orthopnea, and worsening abdominal swelling of several weeks duration. Exam findings included jugular venous distention, crackles to mid lungs, distended abdomen, and bilateral +3 pitting edema. EKG had low voltage complexes, Q-waves in leads V1-V2 and poor R-wave progression. Labs revealed grossly elevated b-natriuretic peptide >2500pg/mL and mildly elevated troponin. He was started on IV furosemide and admitted to telemetry where he had periodic episodes of non-sustained ventricular tachycardia. When compared to a stress echocardiogram from 3-months prior, transthoracic echocardiogram showed new-onset biventricular hypertrophy with systolic dysfunction (EF 35%) and “starry sky” myocardial enhancement. Cardiac catheterization was negative for coronary arterial disease. Cardiac-MRI confirmed infiltrative cardiomyopathy. Fat pad biopsy was Congo red positive, consistent with systemic amyloidosis, however negative for AL stains. Bone marrow biopsy showed normocellular marrow. No monoclonal proteins were identified in urine or serum. Technetium-pyrophosphate scan showed diffuse radiotracer intake suggestive of TTR-AC, however serum TTR mutation was negative. Mass spectrometry of repeat fat pad biopsy was diagnostic for AL-amyloidosis. Patient’s symptoms resolved over hospital course, and he was discharged with close follow up.
Discussion: Amyloid cardiomyopathy (AC) is an infiltrative cardiomyopathy and a greatly underdiagnosed cause of heart failure. AC is caused by systemic amyloidosis and is characterized by progressive mechanical and electrochemical disruptions of normal cardiac function, as amyloid proteins deposit into the myocardium. The majority of AC is caused by 1 of 2 proteins: light chains (AL) or transthyretin (TTR). Typical manifestations include restrictive myocardial thickening, conduction abnormalities, and systolic dysfunction. In patients with systemic amyloidosis, cardiac involvement is associated with poor prognosis and a mean survival of 6-months. AL-amyloidosis causes AC in up to 50% patients versus AA-amyloidosis that only affects the heart in 5%. Patients with AC commonly experience progressive heart failure, as well as syncope from arrhythmias or autonomic dysfunction. Diagnostic clues include a characteristic low voltage EKG with Q-waves in V1-V3 and biventricular hypertrophy on echocardiogram. Because of the poor prognosis and radical treatment differences among the different subtypes, it is critically important to identify the amyloid subtype by tissue biopsy.
Conclusions: Systemic amyloidoses are frequently undiagnosed, on average the diagnosis is established 1-year after symptom development. 67% of patients with amyloidosis visit at least 3 different physicians before obtaining a diagnosis and only 4% are diagnosed by their primary care provider, 18% by their cardiologist. Internists should have a wide differential when evaluating patients without atherosclerosis and new onset heart failure. A high degree of suspicion and thorough workup is necessary to identify the AC subtype and appropriately guide management.