Multimodality imaging for cardiac amyloidosis: clinical applications and future directions

Cardiac amyloidosis (CA) is a progressive and underdiagnosed cause of heart failure, primarily due to transthyretin (ATTR) or immunoglobulin light-chain (AL) amyloid deposition. Non-invasive imaging has transformed the clinical approach to CA by improving early detection, risk stratification, and therapeutic monitoring. This narrative review summarizes the clinical value of multimodality imaging in CA, focusing on the diagnostic and prognostic contributions of echocardiography, cardiac magnetic resonance (CMR), bone scintigraphy, and positron emission tomography (PET). Echocardiography remains the first-line modality for identifying CA "red flags," including biventricular hypertrophy, diastolic dysfunction, and apical sparing of longitudinal strain. CMR offers superior tissue characterization through late gadolinium enhancement, native T1 and T2 mapping, and extracellular volume quantification (ECV), which correlate with disease severity and response to therapy. ECV can be assessed also by cardiac computed tomography. Bone scintigraphy allows non-invasive diagnosis of ATTR-CA in the absence of monoclonal protein. PET imaging with amyloid-binding tracers is emerging as a promising tool for early detection, quantification and differential diagnosis. Multimodality imaging offers complementary information that is essential for the diagnosis, staging, and longitudinal follow-up of patients with CA. Familiarity with the strengths and limitations of each diagnostic modality is essential to guide their appropriate use in clinical practice-not only for cardiologists, but also for internists, geriatricians, and general practitioners, who frequently manage these patients. Future advancements, including the integration of artificial intelligence, may further enhance the diagnostic and prognostic role of imaging in CA.