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.

Keywords: arrhythmia; heart failure; ischaemia; management; red flags; transthyretin amyloid cardiomyopathy.

Figure 1

Red flags for suspected ATTRwt‐CM for cardiology subspecialties: Japanese experts' perspective. AS, aortic stenosis; ATTRwt‐CM, wild‐type transthyretin amyloid cardiomyopathy; CAD, coronary artery disease; CMR, cardiac magnetic resonance; CT, computed tomography; CTS, carpal tunnel syndrome; ECG, electrocardiogram; Echo, echocardiogram; ECV, extracellular volume; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; hs‐TnI, high‐sensitivity troponin I; hs‐TnT, high‐sensitivity troponin T; IVST, interventricular septal thickness; LV, left ventricular; NT‐proBNP, N‐terminal pro‐brain natriuretic peptide; RV, right ventricular; SHD, structural heart disease; TAVI, transcatheter aortic valve implantation; TAVR, transcatheter aortic valve replacement.

Figure 2

Management of HF medications based on the timing of ATTRwt‐CM diagnosis: Japanese experts' perspective. ACEi, angiotensin‐converting enzyme inhibitor; AF, atrial fibrillation; ARB, angiotensin receptor blocker; ARNI, angiotensin receptor–neprilysin inhibitor; ATTRwt‐CM, wild‐type transthyretin amyloid cardiomyopathy; BNP, brain natriuretic peptide; BP, blood pressure; EF, ejection fraction; HF, heart failure; HR, heart rate; MRA, mineralocorticoid receptor antagonist; NYHA, New York Heart Association; SGLT2i, sodium‐glucose cotransporter 2 inhibitor.