Amyloidosis has often been referred to as a "great masquerader," mimicking other systemic and cardiac diseases. As diagnostic techniques such as echocardiography with longitudinal strain, cardiac magnetic resonance imaging, and nuclear scintigraphy have advanced, identification of cardiac amyloidosis has become less daunting. This review covers the differential diagnosis and workup of patients with transthyretin cardiac amyloidosis, with a specific focus on developing a clinical suspicion through demographic, clinical, and echocardiographic features of the disease. The most common mimics of cardiac amyloidosis, i.e., conditions that likewise cause heart failure with preserved or mildly reduced ejection fraction, are also explored with respect to differential diagnosis, both for patients with normal and increased ventricular wall thickness. Ultimately, this review aims to demystify the diagnostic process by offering an algorithmic approach to the identification of transthyretin cardiac amyloidosis.
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