Transthyretin Amyloid Cardiomyopathy–2025 Update: Current Diagnostic Approaches and Emerging Therapeutic Options

Transthyretin‐related (ATTR) amyloidosis is a progressive and life‐threatening disease caused by the systemic accumulation of amyloid fibril deposits composed of misfolded transthyretin (TTR) monomers. Clinical manifestations are highly heterogeneous, including symptoms of cardiomyopathy and/or polyneuropathy, depending on the composition and location of fibril deposits. Although ATTR amyloidosis is considered a rare disease, the clinical relevance of the disease in daily practice becomes more and more apparent. Especially in older patients with unexplained heart failure it is increasingly recognized as an underdiagnosed condition. ATTR amyloidosis can be hereditary (ATTRv), resulting from mutations in the TTR gene, or due to misfolded wild‐type TTR (ATTRwt), affecting mainly male patients over 70 years of age. Advances in understanding the pathogenesis have led to the development of disease‐specific therapies that can significantly slow disease progression and improve survival. This review focuses on diagnostic strategies and therapeutic options for patients with ATTR cardiomyopathy (ATTR‐CM), including mixed phenotypes with additional polyneuropathy (ATTR‐PN). We discuss emerging and newly approved second‐generation therapies such as acoramidis, vutrisiran and eplontersen, as well as promising future treatment options such as gene editing and ATTR‐directed monoclonal antibodies. The growing arsenal of specific therapies underlines the importance of earlier diagnosis and raises crucial questions: What is the best first‐line therapy for each patient? How should we manage non‐ responders, and how can we optimize treatment strategies for patients with mixed phenotypes or advanced disease?