Fünderich, Meike

ABSTRACT In 567 PH‐COPD patients from the PVRI GoDeep Meta‐Registry, ACE inhibitor use was associated with improved survival only in severe PH (PVR > 5 WU), supporting prospective trials targeting this high‐risk subgroup.

Abstract Rationale Pulmonary hypertension (PH) in interstitial lung disease (ILD) lacks approved therapies. Objectives The Pulmonary Vascular Research Institute GoDeep metaregistry collects real-world data of patients with PH from international PH referral centers. Methods Patients with ILD-PH and relevant subgroups (idiopathic interstitial pneumonia [IIP], idiopathic pulmonary fibrosis [IPF]) were stratified by pulmonary vascular resistance (PVR). Kaplan-Meier survival analyses and adjusted Cox proportional hazards models were employed, additionally accounting for immortal time bias, sensitivity analyses, Heller explained relative risk statistics, and target trial emulation framework analysis. Measurements and Main Results Among 34,482 patients, 940 with hemodynamically fully characterized incident ILD-PH (median age, 67 [IQR, 59–74] yr) were identified. A total of 62% had severe ILD-PH with PVR >5 Wood units (WU) and poor survival rates (29% and 18% at 3 and 5 yr), significantly worse than patients with ILD-PH with PVR ≤5 WU and patients with pulmonary arterial hypertension. Survival was poorest in severe IPF-PH. A total of 59% of all patients ILD-PH received PH-targeted therapy, predominantly phosphodiesterase-5 inhibitors (PDE5is). PDE5i treatment was consistently associated with significantly improved survival in patients with severe PH (hazard ratios of 0.537 [0.370–0.781], 0.461 [0.233–0.913], and 0.435 [0.215–0.8] for IIP-PH, IPF-PH, and IIP-PH with nintedanib/pirfenidone background therapy), but not in patients with less severe hemodynamic impairment, supported by sensitivity analyses, Heller statistics, and target trial emulation framework analysis. The survival statistics of patients with PDE5i-treated IIP-PH or IPF-PH were validated in the independent COMPERA registry. Combination therapy with PDE5is and inhaled prostacyclin analogues was superior to monotherapy using PDE5is (hazard ratio, 0.341; 0.205–0.566). Conclusions Prognosis in ILD-PH was generally very poor and was related to PH severity. PDE5i treatment in severe IIP-PH and IPF-PH was associated with improved survival, which is to be further verified in controlled trials.

ABSTRACTPortopulmonary hypertension (PoPH), a type of pulmonary arterial hypertension (PAH) in patients with liver disease, is associated with high morbidity and mortality. The relationship between cardiopulmonary hemodynamics, PAH therapy, and survival in PoPH remains unclear. We performed a retrospective cohort study of PoPH patients from the international pulmonary hypertension (PH) meta‐registry, PVRI GoDeep. PAH was defined by a mean pulmonary arterial pressure > 20 mmHg, pulmonary arterial wedge pressure ≤ 15 mmHg, and a pulmonary vascular resistance (PVR) > 2 Wood Units. PoPH diagnoses were assigned by each center's PH specialist based on international guidelines at the time of enrollment. 246 incident PoPH patients met eligibility criteria and were included in the analysis, equally split between males (51%) and females (49%), with a median age of 54 years. When compared to both patients with IPAH and those with other subtypes of PAH (not classified as PoPH or IPAH), those with PoPH had significantly lower 5‐year survival rates (46% vs. 68% vs. 65%, log‐rank p < 0.001). Amongst the PoPH patients, however, there was no significant difference in 5‐year survival when dichotomized by disease severity, either by a PVR of 5 Wood Units or a CI of 2.5 L/min/m2. Treatment of the PoPH patients with PAH‐targeted therapies was associated with significantly higher 5‐year survival rates compared to those not receiving such treatments, as shown by Kaplan–Meier analysis. This survival benefit was observed for PDE5i (50% vs. 34%, log‐rank p = 0.029), ERA (58% vs. 34%, log‐rank p < 0.001), and the combination of PDE5i and/or ERA (51% vs. 22%, log‐rank p < 0.001), as well as any PAH‐targeting treatment (50% vs. 26%, log‐rank p = 0.007). Corresponding survival advantage was noted when including only PoPH patients with MELD Score ≥ 13. PoPH is a disease with significantly worse long‐term survival than other PAH subtypes, but targeted PAH therapy is associated with a robust survival benefit. Survival did not differ across high‐risk PVR and cardiac index thresholds, suggesting the factors that influence prognosis and survival in PoPH may be unique as compared to other PAH subtypes, and warrant further investigation.

AbstractThe Pulmonary Vascular Research Institute GoDeep meta‐registry is a collaboration of pulmonary hypertension (PH) reference centers across the globe. Merging worldwide PH data in a central meta‐registry to allow advanced analysis of the heterogeneity of PH and its groups/subgroups on a worldwide geographical, ethnical, and etiological landscape (ClinTrial. gov NCT05329714). Retrospective and prospective PH patient data (diagnosis based on catheterization; individuals with exclusion of PH are included as a comparator group) are mapped to a common clinical parameter set of more than 350 items, anonymized and electronically exported to a central server. Use and access is decided by the GoDeep steering board, where each center has one vote. As of April 2022, GoDeep comprised 15,742 individuals with 1.9 million data points from eight PH centers. Geographic distribution comprises 3990 enrollees (25%) from America and 11,752 (75%) from Europe. Eighty‐nine perecent were diagnosed with PH and 11% were classified as not PH and provided a comparator group. The retrospective observation period is an average of 3.5 years (standard error of the mean 0.04), with 1159 PH patients followed for over 10 years. Pulmonary arterial hypertension represents the largest PH group (42.6%), followed by Group 2 (21.7%), Group 3 (17.3%), Group 4 (15.2%), and Group 5 (3.3%). The age distribution spans several decades, with patients 60 years or older comprising 60%. The majority of patients met an intermediate risk profile upon diagnosis. Data entry from a further six centers is ongoing, and negotiations with >10 centers worldwide have commenced. Using electronic interface‐based automated retrospective and prospective data transfer, GoDeep aims to provide in‐depth epidemiological and etiological understanding of PH and its various groups/subgroups on a global scale, offering insights for improved management.