Wild-type Cardiac Amyloidosis due to Transthyretin Protein - A Review.

Abstract

Transthyretin amyloid cardiomyopathy (ATTR-CM) arises from the accumulation of transthyretin amyloid fibrils in the myocardium, a consequence of instability and misfolding in wild-type or variant transthyretin protein. ATTR-CM should be suspected in older heart failure patients with raised myocardial wall thickness and diastolic dysfunction on echocardiography in the absence of hypertension or other known causes. This diagnosis can be further supported with late gadolinium enhancement on Cardiac MRI which indicates raised myocardial extracellular volume (ECV) hinting at the expansion of interstitial space by amyloid deposits. Diagnostic work up starts with blood and urine tests to rule out AL amyloidosis and monoclonal gammopathy of undetermined significance (MGUS) followed up by nuclear scintigraphy with Tc-99m tracer which shows increased relative tracer uptake by the myocardium on Single-photon emission computed tomography (SPECT). Genetic testing of the transthyretin (TTR) gene determines wild or variant type of ATTR amyloidosis. Tafamidis, a TTR protein stabilizer, is currently the sole approved disease-modifying therapy for ATTR cardiomyopathy. Management of ATTR-CM also involves managing heart failure, arrhythmias, and heart blocks.