Reappraising cardiac function with myocardial contraction fraction: normal values, disease detection and prognostication

Abstract Background Assessing cardiac function is critical for managing cardiovascular disease, guiding treatment, monitoring progression, and risk stratification. While left ventricular ejection fraction (LVEF) is firmly established, it has limitations. Myocardial contraction fraction (MCF) - the ratio of stroke volume to myocardial volume, is simple to compute without additional analysis and offers a promising alternative to LVEF. Methods MCF was assessed across four datasets spanning healthy controls and chronic structural cardiac disease, with direct comparison to LVEF. Association between age, sex and MCF were investigated in 3,541 healthy subjects from the UK Biobank and sex-specific reference ranges derived. Several cohorts were recruited to investigate the discriminative power of MCF and LVEF between health and physiological adaption (n=278 veteran athletes), pathological hypertrophy (hypertrophic cardiomyopathy, amyloid, Fabry, severe aortic stenosis, and hypertension; n=633) and dilatation (n=103 dilated cardiomyopathy). Ability to track disease severity was assessed by looking at 41,558 subjects from the UK Biobank. Finally, prognostication was assessed on 1,277 consecutive patients from an independent external dataset. All images were analysed using the same validated AI algorithm. Results MCF varied with sex (mean MCF: 0.94 male; 1.1 female) but not age. Sex-specific reference ranges were established: 0.68-1.20 for male, 0.82-1.38 for female. MCF decreased in pathological disease (e.g. mean MCF: 0.72 HCM; 0.69 severe AS; 0.5 amyloid; 0.9 hypertension) but there was no significant decrease in LVEF other than in amyloid (mean EF: 76% HCM; 64% severe AS; amyloid 56%; 65% hypertension). Both MCF and EF decreased in DCM (EF 34%; MCF 0.58). MCF decreased with worsening hypertension, whereas LVEF increased (P0.05). MCF had superior prognostic ability to LVEF (MCF vs LVEF: HR=0.772 vs HR=0.816; χ²=198 vs χ²=151; p0.001). Conclusions We established MCF reference ranges, showing superior performance for detecting early disease and tracking progression compared to LVEF. MCF offers enhanced prognostic utility, complementing established metrics of LV function.