Published Paper Details:

ABSTRACT- Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressively recognized form of infiltrative cardiomyopathy due to the extracellular deposition of aberrantly folded transthyretin protein fibrils in the myocardium. Historically, ATTR-CM was perceived as a rare disease and was frequently diagnosed post-mortem. However, with the advent of multimodality imaging and molecular therapies, ATTR-CM has emerged as a potentially treatable disease. The aim of this narrative clinical review is to offer a comprehensive clinical perspective on ATTR-CM, including its epidemiology, molecular mechanisms, clinical manifestations, diagnostic strategies, therapeutic developments, preventive measures, prognosis, and future prospects. This narrative clinical review integrates the latest knowledge from the literature, consensus statements, and major clinical trials assessing the efficacy of transthyretin stabilizers, gene-silencing therapies, and ATTR-CM has two prevalent presentations: wild-type (ATTRwt), which mainly occurs in elderly men, and hereditary (ATTRv), due to autosomal dominant mutations in the TTR gene. The pathophysiology involves tetramer instability, monomer misfolding, and amyloid fibril accumulation, culminating in restrictive cardiomyopathy and systemic involvement. Red flags such as bilateral carpal tunnel syndrome, incongruent ECG-echo changes, and idiopathic HFpEF are essential for prompt diagnosis. Non-invasive bone scintigraphy using technetium-labeled agents has largely supplanted endomyocardial biopsy for diagnosis. Prognostic therapies such as tafamidis, RNA interference agents (patisiran, vutrisiran), antisense oligonucleotides (inotersen, eplontersen), and CRISPR/Cas9 gene editing (NTLA-2001) are revolutionizing prognosis. ATTR-CM is rapidly evolving from a fatal, underdiagnosed cardiomyopathy to a chronic, treatable disease. Early diagnosis, genetic testing, and prompt initiation of disease-modifying therapy are essential. The next horizon of research will focus on not only arresting disease progression but also reversing amyloid accumulation and potentially curing the hereditary variant.