Role of tafamidis in reducing the effect and progression of transthyretin amyloid cardiomyopathy.

e15612 Background: Transthyretin Amyloid Cardiomyopathy (ATTR-CM) is a rare, life-threatening, progressive and underdiagnosed cause of restrictive cardiomyopathy and heart failure. ATTR-CM is a type of cardiac amyloidosis caused due to misfolded and destabilized transthyretin amyloid protein deposits in the myocardium. Tafamidis is a transthyretin (TTR) modifying targeted drug that stabilizes and prevents tetramer dissociation and amyloid deposits. Our aim is to conduct a review of literature to determine the effect of tafamidis on the structural progression of transthyretin cardiomyopathy while also looking into all-cause mortality outcomes. Methods: A systematic search was performed in PubMed, Embase, and Cochrane using the MESH terms "Tafamidis" and “Transthyretin Amyloid cardiomyopathy.” Two authors independently reviewed article titles and abstracts. Disagreements were resolved by consensus and then adjudicated by a third author. All articles published in English up to the year 2019 were eligible for inclusion. Data was tabulated and analyzed. Studies measuring mortality outcomes and echocardiogram findings with the use tafamidis in ATTR-CM were included. Studies that did not measure mortality outcomes were excluded as well as case reports and animal studies. Results: Out of the studies identified through databases (n = 57), only 6 studies met the inclusion criteria as earlier studies delved strictly into the tolerability and safety of the drug. The studies that were included in this analysis are heterogeneous, because ATTR-CM is phenotypically heterogeneous (wild type-ATTR-CM or mutant ATTR-CM) and has varying degrees of amyloid deposits and cardiac symptoms. The role of tafamidis in reducing the effect of cardiomyopathy in transthyretin amyloid cardiomyopathy is unclear. Effects on the structural changes of the myocardium including the ejection fraction remain inconsistent. A recent multicenter, international, phase 3 randomized controlled trial shows reduction in all-cause mortality comparing tafamidis vs placebo. (29.5% vs 42.9%). Conclusions: With the recent approval of tafamidis, it is vital to review and analyze the available data to study its effects on transthyretin amyloid cardiomyopathy. While structural improvements with tafamidis therapy are inconsistent, reduction in all-cause mortality with this novel drug is promising.