Unmasking the Hidden Culprit: Advances in Diagnosis and Treatment of Transthyretin Amyloid Cardiomyopathy

Transthyretin amyloid cardiomyopathy (ATTR-CM) is an increasingly recognized but historically underdiagnosed cause of heart failure, particularly in elderly populations. ATTR-CM results from extracellular deposition of misfolded transthyretin protein, which exists in either a hereditary (ATTRv) or wild-type (ATTRwt) form. Alongside light-chain (AL) amyloidosis, it constitutes an important cause of heart failure. The disease often presents as restrictive cardiomyopathy with preserved ejection fraction, left ventricular hypertrophy, arrhythmias, and conduction disturbances, frequently accompanied by systemic features such as bilateral carpal tunnel syndrome or autonomic dysfunction. Electrocardiography, echocardiography, and cardiac magnetic resonance imaging are the main diagnostic tools. However, medical advances—particularly in cardiac imaging and bone scintigraphy—have facilitated earlier, non-invasive detection and differentiation between ATTR and AL amyloidosis, which is critical given their divergent therapeutic strategies. Tafamidis, a transthyretin stabilizer, is the first disease-modifying treatment shown to reduce mortality and hospitalizations in early-stage ATTR-CM. Other emerging therapies, including TTR gene silencers and stabilizers like acoramidis, are under investigation. Standard heart failure therapies are often poorly tolerated, and careful symptom management remains essential. Early diagnosis, accurate subtype identification, and timely intervention are vital for improving outcomes in patients with ATTR-CM.