Evaluating natural history and treatment response in cardiac amyloidosis: the evolving role of multimodality imaging

Cardiac amyloidosis, characterized by the accumulation of misfolded proteins in the heart, is a major cause of restrictive cardiomyopathy. It includes two main forms – transthyretin (ATTR) and immunoglobulin light chain (AL) amyloidosis – and carries a poor prognosis if left untreated. With emerging new therapies, the growing need to assess treatment response highlights imaging biomarkers as valuable and promising surrogate endpoints. This review discusses current evidence on changes in imaging markers following treatment, contrasting them with the natural progression of the disease. The focus is on magnetic resonance and single photon emission tomography (SPECT) metrics, which have been found to detect treatment responses early, even before functional changes or clinical events occur, thus playing a key role in the management of cardiac amyloidosis. Once validated in larger studies with more data on reproducibility and linked to clinical outcomes, magnetic resonance and SPECT imaging markers could significantly improve disease monitoring and enable personalized care in cardiac amyloidosis. In an outlook to the future, the disruptive potential of amyloid binding positron emission tomography (PET) for evaluating amyloid load and treatment response is discussed.