BACKGROUNDPulmonary hypertension (PH) resulting from heart failure with preserved ejection fraction (PH-HFpEF) can lead to right ventricular-pulmonary arterial (RV-PA) uncoupling despite normal steady hemodynamics (eg, pulmonary vascular resistance). Unsteady hemodynamics, quantified by characteristic pulmonary impedance (ZC), may be useful in differentiating those patients with PH-HFpEF who have sufficient coupling from those who have insufficient coupling. We hypothesized that abnormal pulsatile hemodynamics with exercise, quantified by ZC, precisely detect abnormal cardiopulmonary function in PH-HFpEF.RESEARCH QUESTIONCan ZC with exercise detect abnormal pulmonary vascular response and RV-PA uncoupling in PH-HFpEF?STUDY DESIGN AND METHODSOur approach was pilot tested in a small cohort of patients with PH-HFpEF (n = 8), precapillary PH (n = 5), and no PH (n = 2) who underwent rest-exercise (every 25 W)-recovery testing with repeated measurements of characteristic impedance (ZC, from invasive cardiopulmonary exercise and echocardiography for pulmonary vascular pressure flow) and coupling (end systolic elastance [Ees] to effective arterial elastance [Ea] ratio, from right ventricle [RV] pressure-volume loops). Analysis included disease-specific autoregressive correlation structure of order 1 (for repeated measures in time-series analysis).RESULTSMetrics of steady pulmonary hemodynamics with exercise changed in a similar fashion in the two disease groups. In contrast, at rest in PH-HFpEF (vs precapillary PH), ZC was low (0.22 [0.14] mm Hg/L/min vs 0.70 [0.20] mm Hg/L/min; P < .0001) and Ees to Ea ratio was high (1.10 [0.36] vs 0.58 [0.22]; P = .0007). During exercise in PH-HFpEF, ZC increased and Ees to Ea ratio decreased, but both remained unchanged in precapillary PH. In PH-HFpEF, a significant negative correlation was found between ZC and Ees to Ea ratio (slope, -0.96; r2 = 0.18; P < .0001) that was absent in precapillary PH (slope, -0.20; r2 = 0.11; P = .53).INTERPRETATIONDespite the small sample size, RV-PA uncoupling with exercise was significantly negatively correlated with ZC in PH-HFpEF, which was not evident in precapillary PH, suggesting that abnormal exercise pulsatile hemodynamics are key to RV failure in left heart disease.