Risk of Group 2 Pulmonary Hypertension in Newly Diagnosed Heart Failure: An EHR-Based Cohort Analysis

BackgroundGroup 2 pulmonary hypertension (PH) is associated with poor clinical outcomes. Comprehensive epidemiological data on the incidence of Group 2 PH following heart failure (HF) with preserved versus reduced ejection fraction (HFpEF vs. HFrEF) are limited. ObjectivesTo investigate the differential associations of HFpEF vs. HFrEF with incident Group 2 PH. Methods17,212 newly diagnosed HF patients were examined from University of Pittsburgh Medical Center between 10/01/2015 and 03/31/2021. The cumulative incidence of PH was estimated using the Nelson-Aalen method, and associations with clinical risk factors were assessed using Cox proportional hazards models. Men and women were analyzed separately, given established sex differences in HF subtypes. ResultsMean age was 71.7{+/-}13.0 years, 46.3% were women, and 1,636 incident cases of PH were identified up to 4.5-years of follow-up. The cumulative incidence of PH was initially higher in HFrEF but was surpassed by HFpEF after 2 years. The cumulative incidence (95% CI) was 33.51% (32.36%-34.65%) in HFpEF and 30.87% (29.04%-32.65%) in HFrEF. The incidence was higher in women 36.25% (34.84%-37.62%) than in men 29.69% (28.33%-31.02%). HFpEF in women was associated with a 23% higher risk of incident PH vs. HFrEF (HR: 1.23; 95% CI: 1.01-1.50). This differential risk by HF subtype was not seen in men. ConclusionThis study highlights the significant burden of the development of PH in HF with HFpEF showing higher risk, especially in women. These findings suggest that HF subtype and sex may influence PH development through distinct pathways. Condensed abstractGroup 2 pulmonary hypertension (PH) worsens heart failure (HF) outcomes, but its incidence by HF subtype is unclear. In 17,212 UPMC HF patients, PH was initially more common in HFrEF but surpassed by HFpEF after two years. Women had higher PH incidence, with HFpEF increasing PH risk by 23% in women but not in men. These findings highlight the need for PH screening in all HF patients, especially those with HFpEF and women. Integrating PH risk stratification into HF care may support earlier intervention, guide treatment decisions, and improve long-term outcomes in this growing, high-risk population.