Temporal changes in first-phase ejection fraction during evolution of heart failure with preserved ejection fraction and afterload-induced heart failure in mice

Q: What is the clinical evidence from this study?

Population: Heart failure with preserved ejection fraction (HFpEF) and pressure overload. Intervention: Abdominal aortic banding (AAB) or DOCA/salt with high fat diet (HFpEF model) vs. Sham surgery and chow diet. Primary outcome: First-phase ejection fraction (EF1) at week 1 in AAB model (p=<0.001).

Q: What does this research mean for the field?

First-phase ejection fraction (EF1) significantly decreases from 24.3% at baseline to 13.9% by week 6 in the afterload-induced heart failure model (p<0.001). Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Haotian Gu; Norman Catibog; Yue Zhao; Asjad Visnagri; Philip J. Chowienczyk; Ajay M. Shah; Min Zhang

doi:10.1007/s13105-026-01138-6

February 4, 2026Journal of Physiology and BiochemistryOpen Access

Temporal changes in first-phase ejection fraction during evolution of heart failure with preserved ejection fraction and afterload-induced heart failure in mice

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Key result

In mouse models, first-phase ejection fraction (EF1) significantly decreased early in abdominal aortic banding (18.8% vs 24.3%) and HFpEF (19.1% vs 25.8%) compared to controls.

Figures

Why the study?

The interplay between systolic and diastolic dysfunction in HFpEF progression is unclear, prompting investigation of temporal changes in these relationships using first-phase ejection fraction.

Does first-phase ejection fraction (EF1) decrease earlier than conventional systolic and diastolic markers in mouse models of HFpEF and pressure overload?

Key Points

To examine temporal changes in first-phase ejection fraction and evaluate systolic-diastolic interactions during the progression of HFpEF and afterload-induced heart failure in mice.
Randomly allocated male C57BL/6J mice to either an abdominal aortic banding (AAB) model of chronic pressure overload or a two-hit HFpEF model (unilateral nephrectomy, DOCA pellet, 1% NaCl drinking water, and high-fat diet).
Conducted serial echocardiography and speckle tracking analysis at weeks 1, 3, and 6 post-surgery in AAB mice, and at weeks 1, 2, and 3 post-surgery in HFpEF mice.
In AAB mice, EF1 decreased at week 1 (18.8 ± 1.2 vs 24.3 ± 0.8%, p<0.001) versus controls, declining further at week 3 (16.8 ± 0.6%, p<0.001) and week 6 (13.9 ± 0.9%, p<0.001), while EF, GLS, and LSR remained unchanged until week 3.
In HFpEF mice, EF1 dropped at week 2 (19.1 ± 1.1 vs 25.8 ± 1.0%, p<0.001) while EF, GLS, and LSR were unchanged, followed by a further drop at week 3 (18.1 ± 0.7%) alongside reduced GLS (p<0.01).
Isovolumic relaxation time was prolonged early in both models as the initial diastolic abnormality, whereas left atrial enlargement developed later.

Structured PICO

Does first-phase ejection fraction (EF1) decrease earlier than conventional systolic and diastolic markers in mouse models of HFpEF and pressure overload?

P

Population

Male C57BL/6J mice aged 10-12 weeks, allocated to abdominal aortic banding (AAB) model of pressure overload or a two-hit model of HFpEF (DOCA/salt-induced hypertension and high fat diet).

I

Intervention

Abdominal aortic banding (AAB) or HFpEF induction (unilateral nephrectomy, DOCA pellet, 1% NaCl drinking water, and high fat diet).

C

Comparator

Sham surgery for AAB; control surgery without nephrectomy/DOCA/salt and fed chow diet for HFpEF.

O

Outcome

Temporal changes in first-phase ejection fraction (EF1) and other echocardiographic parameters of systolic and diastolic function.surrogate

Main Result

Absolute Event Rate: 18.8% vs 24.3%

p-value: p=<0.001

Limitations

Only male mice were used, limiting generalizability to females who have a higher prevalence of HFpEF.
Lack of invasive haemodynamic data to serially track disease progression.
PV loop analysis is a terminal procedure limiting its value.
Baseline phenotypes of the HFpEF mouse model warrant further characterisation.
Mice have fast heart rates, different myocardial structures, and pathophysiologies compared to humans.
Only male mice were used, limiting generalizability given higher HFpEF prevalence in women.
Lack of invasive haemodynamic data (PV loop analysis).

Implication

First-phase ejection fraction (EF1) is a sensitive, early marker of systolic impairment that decreases before conventional markers in mouse models of HFpEF and pressure overload, paralleling early diastolic changes.

Abstract

The interplay between systolic and diastolic dysfunction in heart failure with preserved ejection fraction (HFpEF) progression is unclear. First-phase ejection fraction (EF1), a sensitive marker of early systolic function, aids in assessing systolic-diastolic relationships in human hypertension and aortic stenosis. This study examines temporal changes in these relationships in mouse models of HFpEF and elevated afterload. Mouse models of abdominal aortic banding (AAB) and HFpEF (induced by hypertension and high fat feeding) underwent comprehensive serial echocardiography. In AAB, EF1 significantly decreased at week 1 post-surgery (18.8 ± 1.2 vs 24.3 ± 0.8%, p<0.001) compared to controls, with further reduction at week 3 (16.8 ± 0.6%) and week 6 (13.9 ± 0.9%, both p<0.001). EF, global longitudinal strain (GLS) and longitudinal strain rate (LSR) remained unchanged until week 3. Isovolumic relaxation time (IVRT) was the only abnormal index of diastolic function at week 1. In the HFpEF model, EF1 significantly decreased at week 2 (19.1 ± 1.1 vs 25.8 ± 1.0%, p<0.001) compared to controls, while EF, GLS, and LSR were unaltered. At week 3, EF1 decreased further (18.1 ± 0.7%) alongside a significant reduction in GLS (p<0.01), while EF and LSR remained unchanged. IVRT increased early in the HFpEF model, followed by later left atrial (LA) enlargement. EF1, an early marker of systolic impairment, decreases early in HFpEF and afterload-induced dysfunction, accompanied by IVRT prolongation. LA dilatation appears later. These findings highlight the interplay between systolic and diastolic dysfunction in HFpEF progression.

Discussion

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Cite This Study

Gu et al. (2026) studied Heart failure with preserved ejection fraction (HFpEF) and pressure overload. Abdominal aortic banding (AAB) or DOCA/salt with high fat diet (HFpEF model) vs. Sham surgery and chow diet was evaluated on First-phase ejection fraction (EF1) at week 1 in AAB model (p=<0.001). In mouse models, first-phase ejection fraction (EF1) significantly decreased early in abdominal aortic banding (18.8% vs 24.3%) and HFpEF (19.1% vs 25.8%) compared to controls.

synapsesocial.com/papers/698586118f7c464f23009e34 https://doi.org/10.1007/s13105-026-01138-6

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Temporal changes in first-phase ejection fraction during evolution of heart failure with preserved ejection fraction and afterload-induced heart failure in mice

Figures

Key Points

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Temporal changes in first-phase ejection fraction during evolution of heart failure with preserved ejection fraction and afterload-induced heart failure in mice

Figures

Key Points

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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