Supplemental Digital Content is available in the text.

Disclosures:Professor Moon has received an unrestricted research grant from GSK. He has also been paid a consultancy fee for trial design.

Quantification of ECV measures cardiac amyloid deposition in both types of amyloidosis and shows that amyloid deposition is more extensive in patients with ATTR than in those with AL; however, ATTR is associated with higher cell volume, which suggests concomitant cell hypertrophy.

Supplemental Digital Content is available in the text.

Specific functional and structural abnormalities characterize different burdens of cardiac amyloid deposition. In a multimodality imaging assessment of a large cohort of amyloidosis patients, CMR-derived TAPSE and indexed stroke volume are the strongest prognostic cardiac functional markers.

Synthetic ECV provides validated noninvasive quantification of the myocardial extracellular space without blood sampling and is associated with cardiovascular outcomes.

Myocardial edema is present in cardiac amyloidosis by histology and cardiovascular magnetic resonance T2 mapping. T2 is higher in untreated AL amyloidosis compared with treated AL and ATTR amyloidosis, and is a predictor of prognosis in AL amyloidosis. This suggests mechanisms additional to amyloid infiltration contributing to mortality in amyloidosis.

These data suggest that myocyte storage starts in childhood and accumulates faster in men before triggering 2 processes: a sex-independent scar/inflammation regional response (LGE) and, in men, apparent myocyte hypertrophy diluting the T1 lowering of sphingolipid.