Stage-specific pulmonary pressure response and RV–PA coupling during exercise in HFpEF

Background Heart failure with preserved ejection fraction (HFpEF) is characterized by exertional intolerance and abnormal exercise hemodynamics. Although elevated left ventricular filling pressure is a hallmark of HFpEF, the stage-specific pulmonary pressure response and right ventricular–pulmonary artery (RV–PA) coupling during exercise and recovery remain incompletely defined. Purpose We sought to characterize and compare stage-specific exercise hemodynamic responses, including pulmonary pressure dynamics and RV–PA coupling, between patients with HFpEF and asymptomatic controls using exercise stress echocardiography. Methods We prospectively enrolled 45 HFpEF patients and 28 controls who underwent staged supine bicycle stress echocardiography (baseline, 25W, 50W, 75W and recovery at 2 and 5 minutes). Changes (Δ) from baseline were calculated to assess exercise-induced responses. Changes (Δ) from baseline were calculated to assess exercise-induced responses. Stage-specific differences between groups and overall group × time interactions were evaluated using linear mixed models. Results At rest, HFpEF patients demonstrated higher average E/e′, TR Vmax, and RVSP compared with controls (all P < 0.01). Although E/e′ remained higher in HFpEF at rest and across all exercise stages, no significant group × time interaction was observed (P = 0.312). In contrast, during exercise, ΔRVSP increased markedly in HFpEF beginning at early exercise compared with controls (Δ25W: +16.8 ± 8.8 vs +8.6 ± 5.7 mmHg, P < 0.001), with significant group × time interactions (P < 0.001). Differences were most pronounced at peak exercise but attenuated during recovery. RV functional adaptation differed substantially. Controls demonstrated augmentation of RV free-wall strain at 25W (+1.35%), whereas HFpEF showed early impairment (−0.79%; stage P = 0.039; interaction P = 0.048). RV–PA coupling (ΔTAPSE/RVSP) declined more prominently in HFpEF, with a significant interaction (P = 0.033), consistent with exercise-induced RV–PA uncoupling. Conclusions In our cohort, HFpEF is characterized by elevated filling pressure accompanied by an early pulmonary pressure elevation and maladaptive RV response during exercise. These findings suggest that abnormal RV adaptation to pulmonary vascular load, in the setting of diastolic stiffness, may represent a key mechanistic phenotype in HFpEF.Table 1Figure 1