Ventricular stiffening and chamber contracture in heart failure with higher ejection fraction

Area of Science:

• Cardiology
• Cardiovascular Physiology

Background:

• Ancillary clinical trial analyses suggest reduced efficacy of neurohormonal antagonists in patients with heart failure with preserved ejection fraction (HFpEF) and higher ejection fraction (EF).
• Understanding the specific pathophysiological characteristics of HFpEF across the spectrum of EF is crucial for optimizing treatment strategies.

Purpose of the Study:

• To investigate the pathophysiological differences between HFpEF patients with low-normal EF (HFpEF<65%) and high-normal EF (HFpEF≥65%).
• To explore the relationship between EF ranges and left ventricular diastolic stiffness and end-diastolic pressure-volume relationship (EDPVR).

Main Methods:

• Compared 621 HFpEF patients (stratified by LVEF <65% and ≥65%) with 149 controls using echocardiography and invasive cardiopulmonary exercise testing.
• Performed a sensitivity analysis in a community-based cohort (244 HFpEF patients, 617 controls).
• Assessed left ventricular (LV) systolic function, EDPVR, and diastolic stiffness.

Main Results:

• Patients with HFpEF≥65% had smaller LV end-diastolic volume but similar LV systolic function compared to HFpEF<65%.
• HFpEF≥65% demonstrated a leftward-shifted EDPVR and increased LV diastolic stiffness (β) in both cohorts.
• Cardiac filling and pulmonary artery pressures were similarly abnormal across EF subgroups.

Conclusions:

• Key differences in HFpEF with higher EF include smaller heart size, increased LV diastolic stiffness, and a leftward EDPVR shift.
• These findings may explain the lack of efficacy of neurohormonal antagonists in this subgroup.
• Suggests that interventions promoting eccentric LV remodeling and enhancing diastolic capacitance could benefit HFpEF patients with higher EF.