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February 8, 2026European Heart Journal0 citations

First-phase ejection fraction across the lifespan in healthy adults: an in-silico analysis

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ELE LongUniversity College LondonJFJ L Flores-GuerreroUniversity College London

Key Result

EF1 remains stable with age and correlates more strongly with LV contractility (Ees) than LVEF, especially in adults >55 years, making EF1 a superior LV function measure.

Key Points

  • To determine reference values for first-phase ejection fraction (EF1) and assess variations across the lifespan in healthy individuals.
  • Utilized a synthetic dataset modeling haemodynamics and pulse waves validated in vivo.
  • Calculated left ventricular ejection fraction (LVEF) from aortic root pressure waveforms.
  • Measured stroke volume (SV) at peak aortic velocity to derive EF1.
  • Assessed effects of age on EF1 and LVEF using linear regression and Spearman’s correlation coefficient.
  • Included 3837 individuals aged 48.6±17.0 years.
  • EF1 remained virtually unchanged with age, differing from LVEF which declined with age.
  • Moderate correlation found between EF1 and LVEF (ρ: 0.46).
  • EF1 demonstrated stronger correlation with end-systolic elastance (Ees), especially in older adults.

Structured PICO

Does first-phase ejection fraction (EF1) provide a more stable and superior measure of LV contractility across the lifespan compared to LVEF in healthy adults?

P
Population
3837 healthy individuals from a synthetic dataset modelling haemodynamics and pulse waves, mean age 48.6±17.0 years.
I
Intervention
Calculation of first-phase ejection fraction (EF1)
C
Comparator
Left ventricular ejection fraction (LVEF)
O
Outcome
Reference values of EF1, its variation across the lifespan, and correlation with end-systolic elastance (Ees)surrogate

First-phase ejection fraction (EF1) is less affected by age than LVEF and serves as a superior surrogate of LV contractile function, particularly in older adults.

Abstract

Abstract Background First-phase ejection fraction (EF1), the ejection fraction (EF) up to peak aortic velocity (dQ/dt+), is a novel biomarker of left ventricular (LV) function, which can be measured non-invasively on echocardiography. At the onset of myocardial dysfunction, cardiomyocytes may preserve LVEF by compensating with slower, sustained contraction. EF1 is able to quantify this altered physiology and has been shown to outperform conventional measurements of LV function in the prediction of future systolic dysfunction and major adverse cardiac events 1. To the best of our knowledge, no studies have assessed EF1 in non-diseased individuals. Purpose To calculate reference values of EF1, investigate if it varies across the lifespan, and compare it with LVEF alongside the gold-standard measure of LV contractility, end-systolic elastance (Ees), in healthy individuals. Methods A synthetic dataset modelling haemodynamics and pulse waves 2, validated in vivo, was used in this analysis. LVEF was derived from aortic root pressure waveforms using a circulatory model validated in vivo 3. As the area under the aortic flow wave is proportional to stroke volume (SV), SV at dQ/dt+ (SV1) was derived as the area under the aortic flow wave up to dQ/dt+. EF1 was then calculated as SV1 / end-diastolic volume x 100 (Figure 1). Ees was calculated as aortic root end-systolic pressure / end-systolic volume. The effect of age on EF1 and LVEF was assessed using linear regression. Relationships between age, EF1, LVEF, and Ees were quantified using Spearman’s correlation coefficient. Summary statistics are presented as mean ± standard deviation. Results 3837 individuals spread evenly across the lifespan were included in this analysis (age: 48.6±17.0y, LVEF: 67.0±1.7%, EF1: 50.0±3.1%, Ees: 3.68±0.8). With ageing, EF1 remained virtually unchanged (25y: 49.6±3.26, 35y: 49.8±3.0, 45y: 49.9±3.0, 55y: 50.1± 3.1, 65y: 50.4 ±3.1, 75y: 50.4 ± 3.2) and was less related to age than LVEF (β: 0.16 95% Confidence Interval 0.10,0.22 vs β: -0.27 -0.30,-0.24, both per 10y increase, both p0.001) (Figure 2). LVEF was moderately correlated with EF1 (ρ: 0.46) and there was a significant interaction with age (p0.001). The correlation between LVEF and EF1 decreased with ageing, especially in individuals 55y (25y: 0.69, 35y: 0.55, 45y: 0.49, 55y: 0.45, 65y: 0.36, 75y: 0.32 all ρ). EF1 had a stronger correlation with Ees than LVEF, notably in older adults (25y: 0.77 vs 0.62, 35y: 0.77 vs 0.54, 45y: 0.74 vs 0.51, 55y: 0.73 vs 0.42, 65y: 0.70 vs 0.28, 75y: 0.65 vs 0.13 all ρ) demonstrating it to be a superior measure of LV contractility. Conclusion For the first time, we have described standard reference values for EF1 - which can be used to inform abnormality thresholds - and the evolution of EF1 across the lifespan. We have also shown EF1 is less affected by age than LVEF and serves as a superior surrogate of LV contractile function, particularly in older adults.Figure 1 Figure 2

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Cite This Study

Long et al. (2025) studied this question. EF1 remains stable with age and correlates more strongly with LV contractility (Ees) than LVEF, especially in adults >55 years, making EF1 a superior LV function measure.

synapsesocial.com/papers/698827b40fc35cd7a8846958https://doi.org/10.1093/eurheartj/ehaf784.3582
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