Clinical significance of reactive post-capillary pulmonary hypertension in patients with left heart disease

Background: Post-capillary pulmonary hypertension (pc-PH) is a disorder with elevated pulmonary arterial pressure and pulmonary vascular resistance (PVR) because of left heart disease (LHD), and is classified as reactive (PVR >2.5 WU) or passive (PVR ≤2.5 WU). However, the clinical significance of these pc-PH subtypes remains to be elucidated. Methods and Results: We examined 676 consecutive patients with chronic heart failure (CHF) (NYHA ≥2), and found that 158 (23%) had pc-PH: reactive pc-PH in 58 and passive pc-PH in 100. Univariate analysis showed that 4 factors were significantly associated with reactive pc-PH and multivariate analysis showed that female sex was the only independent predictor of reactive pc-PH (odds ratio 2.12, 95% confidence interval (CI) 1.05-4.30, P=0.03). During the mean follow-up period of 2.6 years, 125 CHF patients (18%) died, including 22 with reactive pc-PH and 24 with passive pc-PH (P<0.001). Multivariate Cox regression analysis showed that elevated PVR was independently associated with higher mortality (hazard ratio 1.18, 95%CI 1.03-1.35, P=0.02). Kaplan-Meier analysis demonstrated that the prognosis of patients with reactive pc-PH was significantly worse than for those with no PH or passive pc-PH. Reactive pc-PH was a significant prognostic factor regardless of CHF etiology (ischemic vs. non-ischemic) or reduced/preserved LV ejection fraction (HFrEF vs. HFpEF). Conclusions: Reactive pc-PH is characterized by predominant female sex and is a significant prognostic factor of LHD with PH.