Cardinal Lessons in Cardiac Amyloidosis: Diagnostic Pitfalls Across Three Cases: A Case Report

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ID: 326933
2026
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Abstract
Abstract Background Cardiac amyloidosis (CA) is an infiltrative cardiomyopathy caused by extracellular deposition of misfolded amyloid fibrils within the myocardium, resulting in progressive ventricular wall thickening and heart failure. Transthyretin (ATTR) and immunoglobulin light-chain (AL) amyloidosis account for approximately 95% of cases. Despite advances in diagnostic imaging and laboratory testing, CA remains underrecognized, often leading to misdiagnosis or delayed diagnosis. Timely and accurate diagnosis, including amyloid subtyping, is critical to guide appropriate therapy and improve clinical outcomes, as prognosis and management vary substantially among amyloid subtypes. Case Summary We present a three-case series illustrating distinct diagnostic and clinical challenges in CA, including a false-positive diagnosis of ATTR cardiomyopathy (ATTR-CM) based on planar technetium-99m pyrophosphate (PYP) scintigraphy that was subsequently ruled out by single-photon emission computed tomography (SPECT) imaging and further evaluation, a delayed diagnosis of AL amyloidosis in a patient with progressive heart failure initially attributed to nonischemic cardiomyopathy, and recurrent left atrial appendage thrombus despite therapeutic anticoagulation in a patient with AL amyloidosis. Discussion These three cases demonstrate the broad spectrum of diagnostic and clinical challenges encountered in CA. The first case underscores the importance of SPECT imaging in differentiating true myocardial radiotracer uptake from blood pool activity, a common source of false-positive planar PYP studies. The second emphasizes the critical role of comprehensive monoclonal protein screening in patients with suspected amyloidosis as delayed diagnosis of AL amyloidosis may adversely affect outcomes. The third illustrates the heightened thromboembolic risk associated with CA, even in the setting of therapeutic anticoagulation, and supports consideration of transesophageal echocardiography (TEE) before cardioversion in this high-risk population.
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Authors Ghasaq Saleh, Omar F. AbouEzzeddine, Fadi Adel
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Journal European Heart Journal - Case Reports
Year 2026
DOI
10.1093/ehjcr/ytag654
URL
https://doi.org/10.1093/ehjcr/ytag654
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