Determinants of Abnormal Pulmonary Vasodilatory Response With Exercise in HFpEF: Pulmonary Vascular-Left Atrial Axis...

Inability to decrease pulmonary vascular resistance (PVR) with exercise may lead to right ventricular failure. In this two-step study, we define an unfavorable exercise PVR response among a broad cohort and then determine its high-risk correlates in HFpEF.

164 participants (80 HFpEF, 57 pre-capillary PH, 27 non-cardiac dyspnea) underwent invasive cardiopulmonary exercise test. Dichotomous groups were created with a stepwise approach: "unfavorable exercise PVR" (n = 85, HFpEF = 46) defined as exercise PVR > 1.74Woods unit (WU) and ∆PVR decrease with exercise of < 22%, the remainder of the cohort was labeled as "favorable exercise PVR" (n = 79, HFpEF = 34). Stepwise approach included: physiological groups (tertiles) using exercise PVR cutoff = 1.74 WU and median approach with ∆PVR decrease with exercise.

In unfavorable (vs. favorable) PVR HFpEF subgroups, rest PVR = 3.4 ± 2.0 vs. 2.9 ± 2.0WU, exercise PVR = 3.7 ± 2.6 vs. 2.0 ± 1.3WU, and ∆PVR = +11% ± 39% vs. -26% ± 22%. Correlates of unfavorable exercise PVR with univariate regression were: atrial fibrillation, COPD, increased LAVI, lower TAPSE, and lower TAPSE/PASP. Multivariate model (including clinical data: age, sex, BMI) revealed that atrial fibrillation (β-estimate = 1.93, p = 0.003) and COPD (β-estimate = 1.74, p = 0.03) were significant. However, with multivariate model (including LAVI and TAPSE), COPD remained significant (β-estimate = 3.26, p = 0.02), while atrial fibrillation (β-estimate = 1.60, p = 0.06) and LAVI (β-estimate = 0.05, p = 0.09) approached significance. The unfavorable versus favorable exercise PVR HFpEF subgroups had similar biventricular morphology by cardiac MRI (p < 0.30).

Compared to traditional cardiometabolic comorbidities, COPD and atrial fibrillation are uniquely linked to pulmonary vascular remodeling in HFpEF. The impact of these two comorbidities on pulmonary vascular-left atrial axis is highlighted by the shared biventricular morphology among HFpEF subgroups.