Recent Advances and Current Dilemmas in the Diagnosis and Management of Transthyretin Cardiac Amyloidosis

Abstract

Cardiac amyloidosis (CA) is an increasingly recognized cause of heart failure, arrhythmias, and sudden cardiac death. While CA was previously rapidly fatal, recent advances in diagnosis and treatment have significantly improved outcomes. Advances in cardiac imaging and biomarkers have critically improved the accuracy and efficiency with which CA is diagnosed, even allowing for the noninvasive diagnosis of transthyretin CA. Cardiac magnetic resonance imaging, technetium nuclear imaging, echocardiography, and blood‐based biomarkers have established important and complementary roles in the management and advancement of care. At the same time, the development of novel targeted amyloid therapies has allowed patients with CA to live longer and potentially achieve better quality of life. Still, despite this significant progress, there remain critical ongoing questions in the field. Accordingly, within this review we will highlight recent advances in cardiac imaging and therapeutics for CA, while focusing on key opportunities for further optimization of care and outcomes among this growing population. Specifically, we will discuss ongoing debates in the diagnosis of CA, including the interpretation of indeterminate cardiac imaging findings, the best technique to screen asymptomatic transthyretin amyloidosis gene mutation carriers for cardiac involvement, and the ideal method for monitoring response to CA treatment. We will additionally focus on recent advances in treatment for transthyretin amyloidosis‐CA, including a discussion of available agents as well as highlighting ongoing clinical trials. Together, these data will allow clinicians to emerge with a greater understanding of the present and future of diagnosis, management, and potentially enhanced outcomes in this rapidly advancing field.

Suspicion, screening, and diagnosis of wild‐type transthyretin amyloid cardiomyopathy: a systematic literature review

“…Among the 50 articles containing a diagnostic pathway for ATTRwt CM, 36 articles were review studies 4,10–44 . The 14 remaining articles were consensus recommendation papers, 2,5,45–51 cohort studies, 52–56 or guidelines 57 .…”

“…The speciality areas of the journals publishing the included articles can be considered an indicator of the clinical societies focusing on ATTRwt CM patients. Notably, 43 of 50 articles were published in a journal within cardiology or haematology, 2,4,10–28,32–38,40–43,45–49,51–57 while the remaining seven articles were published in papers of general or internal medicine 5,29–31,39,50 or oncology 44 . No articles were published in journals within neurology or orthopaedics.…”

“…All but four 26,29,52,54 articles included a biopsy as a part of their diagnostic pathway. As illustrated in Figure , 20 of these articles argued that a biopsy is needed in case of inconclusive results from the bone scintigraphy and/or abnormal results from the tests conducted to exclude AL amyloidosis 2,4,12,13,15–18,20–23,25,27,33,35–41,43,45–51,53,55,56 . Also, 28 articles 2,4,5,10,12,14,16–19,21–25,28,30,32,34,38–41,45,46,49,51,57 suggested that one way to diagnose ATTR‐CM is with a biopsy after a positive monoclonal protein test ( Figure ).…”

“…Eighteen articles focused specifically on ATTRwt CM or on ATTRwt CM plus ATTRv CM (in the following referred to as ATTR-CM), 4,5,10,11,13,17,19,21,25,32,35,37,39,40,45,49,52,53 while the rest covered CA in general, including ATTR-CM.…”

“…Aortic stenosis was mentioned in 23 articles, 2,3,10,[20][21][22]24,32,35,[37][38][39][40][42][43][44][46][47][48][49][50][51]56,57 21 of which were published after 2019. The increased attention of aortic stenosis in patients with ATTRwt CM is based on the original studies referred to, which are all prospective and have been published in 2016 or later.…”