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

## TL;DR

This study shows that early systolic dysfunction, measured by EF1, occurs before diastolic changes in mouse models of heart failure with preserved ejection fraction.

## Contribution

The study introduces EF1 as an early marker of systolic dysfunction in HFpEF progression in mice.

## Key findings

- EF1 decreases early in both afterload-induced and HFpEF models, preceding changes in EF and GLS.
- IVRT prolongation occurs before LA enlargement in the HFpEF model.
- Systolic and diastolic dysfunction interplay is evident in the progression of HFpEF.

## 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.