CMR-derived skeletal muscle T1 time and extracellular volume as novel diagnostic markers for cardiac amyloidosis

Introduction: Cardiac amyloidosis (CA) is a progressive cardiomyopathy caused by amyloid deposition, leading to heart failure and increased mortality. Cardiac magnetic resonance (CMR) identifies myocardial involvement via elevated native T1 relaxation time and extracellular volume (ECV). Although amyloid infiltration has also been observed in thoracic skeletal muscle, the diagnostic and prognostic relevance of thoracic skeletal muscle T1 time and ECV remain unclear. Aim: To compare native thoracic skeletal muscle T1 time and ECV between CA patients and controls and assess their diagnostic and prognostic value. Methods: In a prospective CMR registry, consecutive CA patients and controls underwent CMR with T1-mapping. Native and post-contrast T1 relaxation time and ECV were quantified in myocardium and thoracic skeletal muscles. Diagnostic performance was evaluated using ROC analysis and associations with mortality were assessed using Cox regression. Results: Among 1976 participants (267 CA, 1709 controls), CA patients showed significantly higher native myocardial T1 time and ECV, as well as elevated native thoracic skeletal muscle T1 time (919.4 vs. 868.5 ms, p < 0.001) and ECV (16.4 vs. 12.9%, p < 0.001). Native thoracic skeletal muscle T1 time demonstrated moderate diagnostic performance for CA (AUC = 0.70), with an optimal cutoff of 895 ms yielding a sensitivity of 61% and specificity of 59%. Higher native thoracic skeletal muscle T1 time predicted increased mortality (HR = 1.65 per 100 ms, p < 0.001), and this association remained significant after adjusting for age, sex and ventricular function (HR = 1.21 per 100 ms, p = 0.008). Conclusion: Native skeletal muscle T1 relaxation time and ECV indicate systemic amyloid involvement and provide additional diagnostic and prognostic information beyond myocardial assessment, potentially supporting improved detection and risk stratification in CA.