Key Information
Cardiac amyloidosis (CA) is a progressive condition resulting from the deposition of misfolded proteins in the heart as amyloid fibrils, leading to structural and functional impairment. The two main subtypes are light-chain (AL) amyloidosis, caused by the accumulation of immunoglobulin light chains, and transthyretin (ATTR) amyloidosis, involving either wild-type (wt) or mutated (variant, v) transthyretin (TTR). Early diagnosis is crucial for effective management due to the irreversible damage caused by amyloid deposits.1 This review summarizes the recent advances in diagnostic tools, including imaging techniques such as positron emission tomography (PET) and novel applications of artificial intelligence (AI), as well as innovations in treatments, including use of monoclonal antibodies and gene silencing therapies.
Diagnosis of CA
Current diagnostic algorithm
The diagnostic algorithm of CA begins with a suspicion triggered by specific ‘red flags’. Cardiac-related red flags include low QRS voltages relative to left ventricular (LV) mass, pseudonecrosis Q waves, atrioventricular conduction system disorders on electrocardiogram (ECG), disproportionate LV wall thickening without a clearly identifiable cause (pseudohypertrophy), sustained plasma elevation of N-terminal pro-B-type natriuretic peptide (NT-proBNP), and troponin I or T levels.2 Signs such as unexplained right heart failure or pericardial effusion may also raise suspicion. Extracardiac red flags, such as musculoskeletal alterations (e.g. carpal tunnel syndrome, spontaneous tendon rupture, lumbar spinal stenosis), are often early indicators of CA, especially in ATTR amyloidosis. Although proteinuria, macroglossia, and arterial hypotension and other symptoms of autonomic dysfunction may hint at AL-CA, they often occur when the disease is already at an advanced stage.2
The diagnostic work-up aims at differentiating the two main subtypes of AL-CA and ATTR-CA because treatment differs. This goal is achieved through the use of scintigraphy using bone tracers like technetium-labeled pyrophosphate or diphosphonates, which help detect ATTR deposits in the heart.3,4 Serum and urine protein immunofixation and serum free light chain (FLC) assays are performed to check for the presence of monoclonal proteins, which may indicate AL amyloidosis.5,6 Different guidelines from various medical societies (e.g. European Society of Cardiology, American Heart Association) emphasize the need for early diagnosis since patient outcomes depend largely on early initiation of therapy, especially in AL-CA.2,7–11 They agree on the use of scintigraphy and monoclonal protein tests but differ slightly in the sequence of tests.