Exercise cardiac magnetic resonance biventricular volumetric reserve in heart failure with preserved ejection fraction

Abstract Background and Aims Heart failure with preserved ejection fraction (HFpEF) is increasingly recognized as a syndrome of reserve dysfunction. However, integrated assessment of biventricular (LV/RV) volumetric reserve under physiological stress remains underexplored. We aimed to investigate whether exercise cardiac magnetic resonance (Ex-CMR) can reveal distinct volumetric reserve profiles across the HFpEF spectrum. Methods In this retrospective analysis of a prospective observational, multicentre study, supine ergometer Ex-CMR was performed in HFpEF patients across early to advanced stages (stage B, exercise-induced, stage C), along with healthy controls and a non-cardiac dyspnoea (NCD) group. Percentage changes in LV/RV end-diastolic (ΔEDV%) and end-systolic volumes (ΔESV%) from rest to stress defined EDV reserve and ESV reserve, respectively. Ventricular efficiency index (EI) was defined as ΔEDV%—ΔESV%; biventricular EI as LVEI + RVEI. Group comparisons were performed using ANOVA and post hoc testing. Multivariable general linear model analyses adjusted for age, sex, BMI, and exercise response. A composite phenotyping assessment incorporating all four key reserve parameters was explored. Results Among 140 participants (40 healthy, 27 NCD, and 73 HFpEF), all HFpEF subgroups showed impaired LVEDV reserve and reduced LVEI (P .0001). LVESV reserve was impaired only in stage C (P .0001). Exercise-induced RV dysfunction was a hallmark of HFpEF with pulmonary hypertension (P .0001). Biventricular EI declined progressively with advancing HFpEF stage (P .0001) and was significantly lower in NYHA II (P = .0006). Six distinct reserve phenotypes emerged. Conclusion Ex-CMR–based assessment of LV/RV volumetric reserve reveals progressive biventricular dysfunction across HFpEF stages and supports biventricular volumetric reserve–based phenotyping for characterizing HFpEF pathophysiology. Key Question Can the integration of left and right ventricular end-diastolic and end-systolic volume reserve under physiological stress reveal distinct profiles across the HFpEF spectrum and enhance our understanding of its haemodynamic heterogeneity? Key Findings Non-invasive assessment of biventricular volumetric reserve, along with their intra- and interventricular interactions using exercise CMR, revealed a significant, stepwise deterioration across HFpEF subgroups, worsening with NYHA class II. Exercise CMR enabled composite volumetric reserve–based phenotyping and identified six distinct reserve phenotypes. Take Home Message Biventricular volumetric reserve assessment is feasible through exercise CMR and may support future precision therapy strategies.