Monitoring heart involvement in treated and untreated transthyretin amyloidosis.

Abstract

Transthyretin amyloidosis (ATTR) with heart involvement is a progressive, life-threatening condition characterized by amyloid fibril deposition in the myocardium, leading to heart failure, substantial morbidity, and increased mortality. Tafamidis, a transthyretin stabilizer, has been the first and for years the only available disease-modifying therapy, with proven survival benefit. However, a significant proportion of patients continue to experience clinical deterioration, underscoring the need for effective monitoring strategies to guide individual patient management and to serve as surrogate endpoints in clinical trials and in real-world clinical follow up. Current approaches to disease monitoring are largely adapted from heart failure management and include periodic assessment of clinical status, biomarkers, imaging, and functional capacity. Nevertheless, real-world data highlight important limitations, particularly in detecting early disease progression among treated patients. As novel therapies become increasingly available, early identification of suboptimal treatment response is critical to inform timely therapeutic decisions. Developing and validating a reproducible, easy framework for disease monitoring thus remain an urgent research priority. This narrative review summarizes current evidence on monitoring patients with ATTR and heart involvement, including both treated and untreated individuals. It also outlines future directions in this evolving field, emphasizing key knowledge gaps and opportunities for improvement.