First‐phase ejection fraction and ventricular‐arterial coupling across the lifespan: An in silico analysis

First-phase ejection fraction (EF1), the left ventricular ejection fraction (LVEF) up to maximal ventricular fiber shortening, has shown strong prognostic value in cardiovascular diseases, outperforming conventional LVEF, but remains uncharacterised in healthy individuals. An in silico cohort of healthy adults (n = 3837), from 25 to 75 years old was analyzed, showing good agreement with in vivo data. EF1 was derived from aortic flow waves as the proportion of end-diastolic volume ejected up to peak aortic flow. Contractility (Ees) and afterload (Ea) were derived from pressure-volume loops. Correlations were quantified using Pearson's coefficient and determinants were assessed using linear regression, adjusted for age and heart rate. Mean EF1 was 50 ± 3% versus LVEF 67 ± 2%, and EF1 was less influenced by age (β: 0.09 [95% confidence interval] [0.05, 0.12] vs. β: -0.27 [-0.30, -0.23]). EF1 correlated strongly with Ees compared to LVEF (r: 0.72 vs. 0.46, p < 0.001) and showed minimal correlation with Ea in contrast to LVEF (r: -0.10 vs. -0.37, p < 0.001). In regression, β was larger for Ees and Ea/Ees, and Ea smaller, in EF1 compared to LVEF. In conclusion, EF1 demonstrated a strong association with contractility and a negligible relationship with afterload, highlighting its potential as a sensitive, afterload-independent measure of myocardial contractility.