Key result
Ivabradine increases E/e′ ratio by ~1.0 in HFpEF despite lowering resting heart rate.
Why the study?
Heart rate reduction is commonly proposed to improve diastolic filling and reduce LV filling pressure in HFpEF, but it is unclear if HR reduction alone achieves this effect.
Does selective heart rate reduction with ivabradine improve left ventricular filling pressure and diastolic function in patients with HFpEF?
Meta-Analysis (n=258)
Does selective heart rate reduction with ivabradine improve left ventricular filling pressure and diastolic function in patients with HFpEF?
Mean Difference: 1.02 (95% CI 0.22–1.82)
In patients with HFpEF, selective heart rate reduction with ivabradine fails to improve and may paradoxically worsen noninvasive indices of left ventricular filling pressure.
Ivabradine may worsen LV filling pressures in HFpEF despite HR reduction; challenges the hypothesis that isolated rate slowing improves diastolic function.
Background: Heart rate (HR) reduction is commonly proposed to improve diastolic filling and reduce left ventricular (LV) filling pressure in heart failure with preserved ejection fraction (HFpEF). Ivabradine selectively lowers HR without direct myocardial effects, providing a mechanistic model to examine whether HR reduction alone translates into improved LV filling pressure. This study aims to evaluate whether selective HR reduction with ivabradine improves LV filling pressure and diastolic function in patients with HFpEF. Methods: MEDLINE and CENTRAL were systematically searched for randomized controlled trials comparing ivabradine with placebo or standard therapy in HFpEF. Outcomes included diastolic echocardiographic parameters (E/e′, e′ velocity, and left atrial volume index [LAVI]), resting HR, natriuretic peptides, and peak oxygen consumption (peak VO 2 ). Pooled mean differences (MDs) with 95% confidence intervals (CIs) were calculated using random-effects models. Results: Three RCTs (258 patients) were included. Ivabradine significantly reduced resting HR (MD −12.03 bpm; 95% CI −18.43 to −5.63), yet was associated with a signifi cant increase in E/e′ (MD 1.02; 95% CI 0.22 to 1.82). Septal e′ modestly increased, while no significant differences were observed for lateral or mean e′, LAVI, natriuretic peptides, or peak VO 2 . Conclusions: These findings suggest a dissociation between HR reduction and LV filling pressure, underscoring the limited role of isolated chronotropic modulation in the pathophysiology of HFpE
No takes yet. Share an insight, caveat, or question.
Wedharga et al. (2026) conducted a meta-analysis in Heart failure with preserved ejection fraction (HFpEF) (n=258). Ivabradine vs. Placebo was evaluated on E/e′ ratio (echocardiographic index of left ventricular filling pressure) (MD 1.02, 95% CI 0.22 to 1.82). Ivabradine significantly reduced resting heart rate but was associated with a significant increase in the E/e′ ratio (MD 1.02), indicating a dissociation between heart rate reduction and left ventricular filling pressure in HFpEF.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: