Why the Diagnosis of ATTR-Cardiomyopathy May Be a Challenge for Physicians

Abstract

Cardiac amyloidosis is a rare but life-threatening group of disorders caused by the extracellular deposition of misfolded amyloid fibrils in cardiac tissue. Amyloid accumulation leads to cardiomyocyte toxicity, extracellular volume expansion, and ventricular pseudohypertrophy. Two types of amyloid protein are thought to be responsible for most disorders: immunoglobulin light chain, which causes light chain amyloidosis (AL); and transthyretin (TTR), which causes transthyretin amyloidosis (ATTR), of which there are two types: hereditary (hATTR) or wild-type (ATTRwt). Despite increasing clinical recognition of the disease, cardiac amyloidosis remains underdiagnosed. This article explores the epidemiology of AL and ATTR and the noninvasive techniques that help to improve diagnosis of the disorder. Cardiac amyloidosis is associated with mixed phenotype symptoms of polyneuropathy and cardiomyopathy which can lead to multiple misdiagnoses. As a result, patients can wait between 2 and 4 years for a correct diagnosis. Early diagnosis may be aided by recognising red flag symptom clusters. These include family history; neuropathy and sensory involvement; bilateral carpal tunnel syndrome; early autonomic dysfunction and gastrointestinal complaints; heart failure (HF) with preserved ejection fraction (HFpEF; without hypertension); cardiac hypertrophy, arrhythmias, ventricular blocks, right-sided or biventricular HF, or cardiomyopathy; renal abnormalities; and vitreous opacities. Noninvasive imaging techniques have increasingly been used as an alternative to biopsy to diagnose cardiac amyloidosis with the hope of allowing physicians to provide targeted therapy for these patients. Techniques include speckle tracking echocardiography, cardiac MRI, and nuclear scintigraphy, together with biomarkers such as N-terminal pro-brain natriuretic peptide and hepatocyte growth factor (HGF). It is hoped that greater understanding of patients with ATTR may lead to increased awareness of the disorder and improve patient outcomes.