Characteristic Pulmonary Impedance With Exercise Detects Abnormal Pulmonary Vascular Response and Uncoupling in Pulmonary Hypertension Resulting From Heart Failure With Preserved Ejection Fraction.

Background: Pulmonary 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 (Z_C), 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 Z_C, precisely detect abnormal cardiopulmonary function in PH-HFpEF.

Research question: Can Z_C with exercise detect abnormal pulmonary vascular response and RV-PA uncoupling in PH-HFpEF?

Study design and methods: Our 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 (Z_C, from invasive cardiopulmonary exercise and echocardiography for pulmonary vascular pressure flow) and coupling (end systolic elastance [E_es] to effective arterial elastance [E_a] 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).

Results: Metrics 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), Z_C was low (0.22 [0.14] mm Hg/L/min vs 0.70 [0.20] mm Hg/L/min; P < .0001) and E_es to E_a ratio was high (1.10 [0.36] vs 0.58 [0.22]; P = .0007). During exercise in PH-HFpEF, Z_C increased and E_es to E_a ratio decreased, but both remained unchanged in precapillary PH. In PH-HFpEF, a significant negative correlation was found between Z_C and E_es to E_a ratio (slope, -0.96; r² = 0.18; P < .0001) that was absent in precapillary PH (slope, -0.20; r² = 0.11; P = .53).

Interpretation: Despite the small sample size, RV-PA uncoupling with exercise was significantly negatively correlated with Z_C 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.