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

Abstract

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, could precisely detect abnormal cardiopulmonary function in PH-HFpEF. Can Z_C with exercise detect abnormal pulmonary vascular response and RV-PA uncoupling in PH-HFpEF? 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 RV pressure-volume loops). Analysis included disease-specific autoregressive correlation structure of order 1 (for repeated measures in time-series analysis). Metrics of steady pulmonary hemodynamics with exercise changed in a similar fashion in the 2 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). 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 may be key to RV failure in left-sided heart disease.