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

## TL;DR

Myocardial contraction fraction (MCF) is a new way to assess heart function that may be better than traditional methods for detecting disease and predicting outcomes.

## Contribution

The paper introduces MCF as a novel, dimensionless metric for cardiac function with established reference ranges and superior diagnostic and prognostic performance.

## Key findings

- MCF decreases in pathological conditions like hypertrophic cardiomyopathy and amyloid, while ejection fraction (LVEF) remains stable in most cases.
- MCF has better prognostic value than LVEF, with a lower hazard ratio and higher statistical significance in predicting outcomes.
- MCF declines with worsening hypertension, whereas LVEF paradoxically increases, highlighting MCF's sensitivity to disease progression.

## Abstract

Assessing cardiac function is critical for managing cardiovascular disease, guiding treatment, monitoring progression, and risk stratification. While left ventricular (LV) 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.

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 3541 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 (AS), and hypertension (HTN); n = 633], and dilatation [n = 103 dilated cardiomyopathy (DCM)]. Ability to track disease severity was assessed by looking at 41 558 subjects from the UK Biobank. Finally, prognostication was assessed on 1277 consecutive patients from an independent external dataset. All images were analysed using the same validated artificial intelligence algorithm. 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 and [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 HTN) but there was no significant decrease in LVEF other than in amyloid (mean EF: 76% HCM; 64% severe AS; amyloid 56%; 65% HTN). Both MCF and ejection fraction (EF) decreased in DCM (EF 34%; MCF 0.58). MCF decreased with worsening HTN, whereas LVEF increased (P < 0.05). MCF had superior prognostic ability to LVEF (MCF vs. LVEF: HR = 0.772 vs. HR = 0.816; χ2 = 198 vs. χ2 = 151; P < 0.001).

We established MCF reference ranges, showing superior performance for detecting early disease and tracking progression compared with LVEF. MCF offers enhanced prognostic utility, complementing established metrics of LV function.

Graphical AbstractMyocardial contraction fraction (MCF): a simple, dimensionless, and prognostic measure of cardiac function. Legend: This central illustration summarizes the key attributes of MCF as a metric for cardiac function assessment. (Top—Simple): MCF is derived from stroke volume and myocardial volume, with sex-specific normal reference ranges established from 3541 UK Biobank participants. (Middle—Dimensionless): Unlike LVEF, MCF incorporates mass and therefore is susceptible to impact of left ventricular geometry than LVEF and effectively distinguishes between normal, physiological adaptation, and pathological hypertrophy or dilation in 1035 local cohort participants. (Lower—Prognostic): In an external cohort of 1277 patients, MCF demonstrates superior prognostic ability compared with LVEF (HR = 0.77 vs. HR = 0.82, P < 0.001). (Bottom—Tracks Disease Severity): MCF declines with increasing blood pressure, while LVEF paradoxically rises, reinforcing its value as a more sensitive indicator of disease progression.For image description, please refer to the figure legend and surrounding text.

Myocardial contraction fraction (MCF): a simple, dimensionless, and prognostic measure of cardiac function. Legend: This central illustration summarizes the key attributes of MCF as a metric for cardiac function assessment. (Top—Simple): MCF is derived from stroke volume and myocardial volume, with sex-specific normal reference ranges established from 3541 UK Biobank participants. (Middle—Dimensionless): Unlike LVEF, MCF incorporates mass and therefore is susceptible to impact of left ventricular geometry than LVEF and effectively distinguishes between normal, physiological adaptation, and pathological hypertrophy or dilation in 1035 local cohort participants. (Lower—Prognostic): In an external cohort of 1277 patients, MCF demonstrates superior prognostic ability compared with LVEF (HR = 0.77 vs. HR = 0.82, P < 0.001). (Bottom—Tracks Disease Severity): MCF declines with increasing blood pressure, while LVEF paradoxically rises, reinforcing its value as a more sensitive indicator of disease progression.