Transthyretin amyloid cardiomyopathy: Literature review and red‐flag symptom clusters for each cardiology specialty

Abstract

Wild‐type transthyretin amyloid cardiomyopathy (ATTRwt‐CM) is a progressive and infiltrative cardiac disorder that may cause fatal consequences if left untreated. The estimated survival time from diagnosis is approximately 3–6 years. Because of the non‐specificity of initial symptom manifestation and insufficient awareness among treating physicians, approximately one‐third of patients with ATTRwt‐CM are initially misdiagnosed with other cardiac diseases. Although heart failure (HF) is the most common initial manifestation of ATTRwt‐CM, observed in nearly 70% of affected patients, patients may also present with other cardiologic symptoms, such as atrial fibrillation (AF) and aortic stenosis (AS). This non‐specific and diverse nature of the initial ATTRwt‐CM presentation indicates that various cardiology subspecialties are involved in patient diagnosis and management. Standard guideline‐directed pharmacological treatment for HF is not recommended for patients with ATTRwt‐CM because of its limited effectiveness. However, no established algorithms are available regarding HF management in this patient population. This literature review provides an overview of the red flags for ATTRwt‐CM and research findings regarding HF management in this patient population. In addition to commonly recognized red flags for ATTRwt‐CM (e.g., HF, AF and severe AS), published literature identified potential red flags such as coronary microvascular dysfunction. For HF management in patients with ATTRwt‐CM, the use of mineralocorticoid receptor antagonists (MRAs) was reported as a well‐tolerated option associated with a low discontinuation rate and reduced mortality. Although there is no concrete evidence for recommendations against sodium‐glucose cotransporter 2 inhibitor (SGLT2i) administration, research supporting its use is limited to small‐scale studies. Robust evidence is lacking for AF ablation, implantable cardioverter‐defibrillators and cardiac resynchronization therapy. Based on the published findings and our clinical experience as Japanese ATTRwt‐CM experts, red‐flag symptom clusters for each cardiology specialty (HF, arrhythmia and ischaemia/structural heart disease) and a treatment scheme for HF management are presented. As this research area remains at an exploratory stage, our observations would require further discussion among experts worldwide.