Navigating the emerging landscape of asymptomatic ATTR-CM: challenges, opportunities and the path ahead

Transthyretin amyloid cardiomyopathy (ATTR-CM) has long been considered a rare and inexorably fatal condition. However, advances in noninvasive diagnosis, disease awareness, and available treatments have enabled diagnosis in asymptomatic stages, before development of clinical heart failure (HF). The emerging entity of asymptomatic ATTR-CM presents both challenges and new opportunities for improving patient care. Data remain limited, as asymptomatic patients have been excluded from clinical trials, and their management currently relies on empirical judgment. Understanding the natural history of asymptomatic ATTR-CM is essential for guiding individualized clinical decisions at the patient level and for designing future clinical trials in this population. While these patients do not exhibit overt HF, recent evidence suggests that a subset may experience disease progression and develop significant morbidity and mortality within a relatively short time. This review explores the rapidly evolving landscape of asymptomatic ATTR-CM with regard to diagnostic pathways, phenotypic variability, natural history, and prognostic stratification. It also discusses current barriers encountered in clinical practice for timely diagnosis, the clinical role of imaging and biomarkers, and potential indications for early therapeutic interventions in this under-recognized population, which is projected to exponentially increase in the coming years.