Recent advances in the pharmacotherapy of TTR amyloidosis of the heart

Abstract

Transthyretin amyloidosis of the heart, or transthyretin amyloid cardiomyopathy (ATTR-CM), once thought to be a rare disease, is now increasingly recognized as a common causing of restrictive cardiomyopathy, particularly in elderly patients and patients with heart failure with preserved ejection fraction. ATTR-CM is caused by an aggregation of misfolded transthyretin (TTR) protein amyloid fibrils in the myocardium. The TTR protein itself can be either wild-type (ATTRwt) or one of many pathologic variants (ATTRv). Recognition of ATTR-CM has been aided by rapid advances in technologies to diagnose the disease more accurately. Several advances in pharmacotherapeutic treatments have significantly reduced the morbidity and mortality of the disease. Treatments broadly fall into three categories: (1) TTR silencing through mRNA knockdown or silencing; (2) TTR stabilization; and (3) TTR resorption or extraction. This review article provides a survey of the pharmacokinetic and clinical data on all currently available treatments.