Coronary microvascular dysfunction as a predictor of left ventricular ejection fraction normalisation in HFrEF and HFmrEF

Background

Only limited evidence has been reported regarding the association between coronary microvascular dysfunction (CMD) and reverse remodelling in patients with heart failure with reduced ejection fraction (HFrEF)1. Moreover, no studies have demonstrated a link between CMD and normalisation of left ventricular ejection fraction (LVEF).

Purpose

This study aimed to investigate the association between CMD and LVEF normalisation in patients with HFrEF and heart failure with mildly reduced ejection fraction (HFmrEF).

Methods

This single-centre prospective study included patients who were newly diagnosed with heart failure and had a LVEF <50%, and who underwent invasive assessment for CMD between November 2022 and November 2025. The exclusion criteria were as follows: prior myocardial infarction; hemodialysis; physiologically significant ischemia or visually assessed stenosis >50% in the left anterior descending artery; emergent angiography or hemodynamic instability requiring catecholamine support; moderate or severe valvular disease; biopsy-confirmed primary cardiomyopathy; and stress-induced cardiomyopathy. All participants underwent coronary angiography within 1 month of the initial diagnosis and were followed in the outpatient department, where echocardiography was performed 3 to 12 months later.

CMD was defined as coronary flow reserve (CFR) <2.5. Normalised LVEF at follow-up was defined as an absolute increase of ≥10% in LVEF and a final LVEF >50%. We evaluated baseline echocardiographic parameters and their changes at follow-up. The primary endpoint was the association between the presence of CMD and normalized LVEF at follow-up. Secondary endpoints included clinical outcomes.

Results

Of the 64 eligible patients, 19 were excluded. Among the remaining 45 patients (34 HFrEF and 11 HFmrEF), 21 (47%) were classified as having CMD at baseline, and 21 (47%) achieved LVEF normalisation at follow-up. In the baseline clinical characteristics, the non-CMD group was younger (60.6 ± 16.6 vs. 71.1 ± 14.6 years, p = 0.03) and had a higher BMI (26.9 ± 7.0 vs. 22.3 ± 7.1 kg/m², p = 0.02).

LVEF normalisation was achieved in 16 patients (47%) in the non-CMD group and in 5 patients (24%) in the CMD group (p < 0.01). ΔLVEF was positively correlated with CFR (R = 0.44, p < 0.01). Multiple regression analysis demonstrated that CMD status was independently associated with ΔLVEF. Logistic regression analysis further showed that CFR value was an independent predictor of LVEF normalisation [odds ratio (OR) 1.5, 95% confidence interval (CI) 1.0–2.3, p = 0.03], whereas age (OR 1.0, 95% CI 0.9–1.1, p = 0.9) and body mass index (OR 1.0, 95% CI 0.9–1.2, p = 0.9) were not significant. No significant differences in clinical outcomes were observed.

Conclusion

This study suggests that CMD severity may serve as a predictor of LVEF normalisation in patients with HFmrEF and HFrEF.Result 1Result 2