Transthyretin Amyloidosis (ATTR): a systematic review of diagnostic and therapeutic evidence – 2025

Abstract

Introduction: Transthyretin amyloidosis (ATTR), in its hereditary (ATTRv) and wild-type (ATTRwt) forms, has emerged as a prevalent cause of cardiomyopathy and progressive neuropathy in adults, especially the elderly. Diagnostic advances and the development of disease-modifying therapies have transformed clinical management. Objective: To systematically evaluate contemporary evidence on the epidemiology, diagnosis, and treatment of ATTR, focusing on randomized studies and international guidelines. Methods: A systematic review of studies published in the PubMed/MEDLINE and ClinicalTrials.gov databases up to November 2025 was conducted using the descriptors transthyretin amyloidosis, ATTR cardiomyopathy, hereditary transthyretin amyloidosis, tafamidis, patisiran, vutrisiran, inotersen, eplontersen, acoramidis. Randomized clinical trials, cohorts with n≥20, and guidelines were included. Case reports and narrative studies were excluded. Results: 112 relevant studies were included. Diagnosis was based on an integrated algorithm involving exclusion of AL amyloidosis, bone scintigraphy with 99mTc-PYP/DPD/HMDP, and TTR gene genotyping. Tafamidis remains the TTR stabilizer with the strongest evidence for ATTR-CM. RNA silencers (patisiran, vutrisiran, inotersen, eplontersen) have demonstrated robust benefit in ATTRv-PN, and recent data on vutrisiran suggest a reduction in mortality and cardiovascular events in ATTR-CM. Acoramidis emerges as a new effective option. Emerging therapies include fibril-clearing antibodies and CRISPR gene editing. Conclusion: ATTR has become a treatable disease, with effective therapies and increasingly accessible diagnosis. Early management and evaluation in specialized centers remain essential to optimize survival and quality of life.