Exercise Cardiovascular Magnetic Resonance Work-Volume Loop Model in Heart Failure with Preserved Ejection Fraction

Heart failure with preserved ejection fraction (HFpEF) is a hemodynamically heterogeneous syndrome including stage C HFpEF (overt) and exercise-induced HFpEF. While impaired compliance reserve is well recognized, contractile reserve remains underexplored. In addition, distinguishing exercise-induced HFpEF from non-cardiac dyspnea (NCD) remains challenging. Exercise cardiovascular magnetic resonance (Ex-CMR) enables quantification of reserve metrics, yet standardizing exercise protocol in dyspneic patients with limited capacity is challenging. This study aimed to establish an analytic framework for deriving non-invasive compliance and contractile reserve metrics independent of fixed exercise thresholds using Ex-CMR, and to evaluate their utility for pathophysiological differentiation among NCD, exercise-induced HFpEF, and stage C HFpEF.

We proposed a non-invasive work-volume (W-V) loop model from Ex-CMR using left ventricular end-diastolic (LVEDV) and end-systolic volumes (LVESV) at rest and stress, along with maximum workload during supine cycle ergometer exercise, to construct a trapezoidal loop. The loop's base angles θ₁ and θ₂ represent effort-adjusted compliance and contractile reserve, respectively. In a retrospective analysis of a prospective multi-center Ex-CMR study, these markers were calculated in healthy controls, NCD, exercise-induced HFpEF, and stage C HFpEF groups. Patient cohorts were defined based on invasive hemodynamic exercise-testing thresholds and non-invasive data. ANOVA and post hoc testing were performed. Reproducibility was assessed.

Among 120 participants (40 healthy controls, 27 NCD, 20 exercise-induced HFpEF, 33 stage C HFpEF), effort-adjusted compliance reserve was impaired in both HFpEF subgroups compared with healthy controls and NCD (p<0.0001). Effort-adjusted contractile reserve was significantly higher in exercise-induced HFpEF than in healthy controls, NCD, and stage C HFpEF (p=0.018, 0.006, and <0.0001, respectively), despite comparable absolute ΔLVESV to NCD and lower ΔLVESV than healthy controls. In contrast, stage C HFpEF demonstrated depressed contractile reserve compared with other groups (p<0.0001). Reproducibility of reserve markers was good to excellent.

Ex-CMR-derived W-V loop geometry reveals distinctive features across HFpEF subgroups and provides pathophysiological insight from an imaging perspective, demonstrating universal impairment of compliance reserve in HFpEF and a newly identified hypercontractile profile characteristic of exercise-induced HFpEF. Elevated θ₂ in exercise-induced HFpEF may identify a window for intervention before contractile reserve becomes compromised.