Present and future of endomyocardial biopsy in cardiac amyloidosis

Cardiac amyloidosis (CA) affects the myocardium, vessels, valves, and epi-pericardium. Guidelines and expert consensus documents provide recommendations for the diagnostic work-up, which has the dual purpose of confirming the presence of amyloid deposits and characterizing the amyloidogenic protein. Amyloid typing is essential for treatments targeting the different types of amyloidosis, mainly transthyretin (ATTR, the most common type) and light chain, and less commonly reactive-serum amyloid-A, and beta2-microglobulin. Endomyocardial biopsy (EMB), still considered the gold standard for diagnosing and typing amyloid, is primarily reserved for cases where non-invasive tools do not provide a definitive diagnosis. Interestingly, while EMB was expected to decline, its numbers have increased globally over the past decade. This trend was driven by the greater awareness of CA, the novel epidemiology of CA with exponentially increased ATTRwt, the limitations of non-invasive methods in diagnosing early-stage ATTR CA, and the need to diagnose and type CAs that are not identified through alternative tools. Looking ahead, it is anticipated that EMB will continue to play a crucial role in diagnosing CA. This review explores the current diagnostic role of EMB, and potential applications in early CA, in differential diagnoses, in detecting and typing rare CA, as well as in incidental findings.