Comparison of Contemporary Risk Scores in All Groups of Pulmonary Hypertension: A Pulmonary Vascular Research Institute GoDeep Meta-Registry Analysis.

BACKGROUND: Pulmonary hypertension (PH) is a heterogeneous disease with a poor prognosis. Accurate risk stratification is essential for guiding treatment decisions in pulmonary arterial hypertension (PAH). Although various risk models have been developed for PAH, their comparative prognostic potential requires further exploration. Additionally, the applicability of risk scores in PH groups beyond group 1 remains to be investigated. RESEARCH QUESTION: Are risk scores originally developed for PAH predictive in PH groups 1 through 4? STUDY DESIGN AND METHODS: We conducted a comprehensive analysis of outcomes among patients with incident PH enrolled in the multicenter worldwide Pulmonary Vascular Research Institute GoDeep meta-registry. Analyses were performed across PH groups 1 through 4 and further subgroups to evaluate the predictive value of PAH risk scores, including the Registry to Evaluate Early and Long-Term PAH Disease Mangement (REVEAL) Lite 2, REVEAL 2.0, European Society of Cardiology/European Respiratory Society 2022, Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) 3-strata, and COMPERA 4-strata. RESULTS: Eight thousand five hundred sixty-five patients were included in the study, of whom 3,537 patients were assigned to group 1 PH, whereas 1,807 patients, 1,635 patients, and 1,586 patients were assigned to group 2 PH, group 3 PH, and group 4 PH, respectively. Pulmonary hemodynamics were impaired with median mean pulmonary arterial pressure of 42 mm Hg (interquartile range, 33-52 mm Hg) and pulmonary vascular resistance of 7 Wood units (WU) (interquartile range, 4-11 WU). All risk scores were prognostic in the entire PH population and in each of the PH groups 1 through 4. The REVEAL scores, when used as continuous prediction models, demonstrated the highest statistical prognostic power and granularity; the COMPERA 4-strata risk score provided subdifferentiation of the intermediate-risk group. Similar results were obtained when separately analyzing various subgroups (PH subgroups 1.1, 1.4.1, and 1.4.4; PH subgroups 3.1 and 3.2; group 2 with isolated postcapillary PH vs combined precapillary and postcapillary PH; patients of all groups with concomitant cardiac comorbidities; and severe [> 5 WU] vs nonsevere PH). INTERPRETATION: This comprehensive study with real-world data from 15 PH centers showed that PAH-designed risk scores possess predictive power in a large PH cohort, whether considered as common to the group or calculated separately for each PH group (1-4) and various subgroups. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT05329714; URL: www. CLINICALTRIALS: gov.

Phosphodiesterase-5 Inhibitor Treatment is Associated with Improved Survival in Pulmonary Hypertension Associated with COPD in the PVRI GoDeep Meta-Registry.

BACKGROUND: Patients with COPD frequently develop pulmonary hypertension (PH-COPD). Severe PH-COPD, identified by a pulmonary vascular resistance (PVR) >5 Wood Units (WU), is closely linked to impaired transplant-free survival. The impact of PH-targeting pharmacotherapy in this context remains unclear. RESEARCH QUESTION: Is PH-targeted therapy associated with improved transplant-free survival in PH-COPD? STUDY DESIGN AND METHODS: This study included PVRI GoDeep meta-registry patients with PH-COPD and available right heart catheterization at diagnosis. We investigated PH-targeted therapy prevalence and its association with transplant-free survival using diverse statistical methods, including Cox regression and subgroup analyses based on PH severity, comorbidities, and pulmonary function tests. Immortal time bias was addressed through a landmark approach. RESULTS: As of December 2023, the GoDeep meta-registry included 26981 patients (28% PH-Group 1, 13% PH-Group 2, 12% PH-Group 3, 10% PH-Group 4, 2% PH-Group 5, 26% undefined and 9% control). Out of these, 836 patients were diagnosed as PH-COPD and included in this analysis, with median age 66 [59,73]years, FEV1 51 [34,69]%predicted, mPAP 35 [28,44]mmHg, PVR 5 [4,8]WU, cardiac index 2.5 [2.0,2.9]L/min.m2, and mostly WHO functional class III were included. 5-year transplant-free survival was 42%, significantly worse than group 1 PH. A multivariable Cox proportional hazards model identified PVR, but not FEV1 as a major predictor of outcome. 418 patients (50%) received phosphodiesterase-5 inhibitor (PDE5i) therapy, which was associated with significantly reduced mortality: hazard ratio 0.65 [0.57,0.75] for the entire PH-COPD cohort and 0.83 [0.74,0.94] when performing landmark analysis. This PDE5i effect was robustly reproduced when performing subgroup analyses for patients with moderate/severe PH, various comorbidities, and supplemental oxygen requirement, and when assessing the impact of unobserved confounders. INTERPRETATION: PH-COPD patients exhibit poor transplant-free survival, with PVR being a predictor of mortality. In this meta-registry, PDE5i therapy was associated with a significant reduction in mortality across all tested models.

Clinical features do not identify risk of progression from isolated postcapillary pulmonary hypertension to combined pre- and postcapillary pulmonary hypertension.

Pulmonary hypertension is a common sequelae of left heart failure and may present as isolated postcapillary pulmonary hypertension (Ipc-PH) or combined pre- and postcapillary pulmonary hypertension (Cpc-PH). Clinical features associated with progression from Ipc-PH to Cpc-PH have not yet been described. We extracted clinical data from patients who underwent right heart catheterizations (RHC) on two separate occasions. Ipc-PH was defined as mean pulmonary pressure >20 mmHg, pulmonary capillary wedge pressure >15 mmHg, and pulmonary vascular resistance (PVR) < 3 WU. Progression to Cpc-PH required an increase in PVR to ≥3 WU. We performed a retrospective cohort study with repeated assessments comparing subjects that progressed to Cpc-PH to subjects that remained with Ipc-PH. Of 153 patients with Ipc-PH at baseline who underwent a repeat RHC after a median of 0.7 years (IQR 0.2, 2.1), 33% (50/153) had developed Cpc-PH. In univariate analysis comparing the two groups at baseline, body mass index (BMI) and right atrial pressure were lower, while the prevalence of moderate or worse mitral regurgitation (MR) was higher among those who progressed. In age- and sex-adjusted multivariable analysis, only BMI (OR 0.94, 95% CI 0.90-0.99, p = 0.017, C = 0.655) and moderate or worse MR (OR 3.00, 95% CI 1.37-6.60, p = 0.006, C = 0.654) predicted progression, but with poor discriminatory power. This study suggests that clinical features alone cannot distinguish patients at risk for development of Cpc-PH and support the need for molecular and genetic studies to identify biomarkers of progression.

Cardiometabolic Risk Factors Associated With Right Ventricular Function and Compensation in Patients Referred for Echocardiography.

Background Pulmonary hypertension and right ventricular (RV) dysfunction are drivers of adverse outcomes; however, modifiable risk factors for RV dysfunction are not well described. We investigated the association between clinical markers of metabolic syndrome and echocardiographic RV function in a large referral population. Methods and Results Using electronic health record data, we performed a retrospective cohort study of patients aged ≥18 years referred for transthoracic echocardiography between 2010 and 2020 with RV systolic pressure (RVSP) or tricuspid annular plane systolic excursion (TAPSE) values. Pulmonary hypertension was defined by RVSP >33 mm Hg and RV dysfunction by TAPSE ≤1.8 cm. Our sample included 37 203 patients of whom 19 495 (52%) were women, 29 752 (83%) were White, with a median age of 63 years (interquartile range, 51-73). Median (interquartile range) RVSP was 30.0 mm Hg (24.0-38.7), and median TAPSE was 2.1 cm (1.7-2.4). Within our sample, 40% had recorded RVSP >33 mm Hg, and 32% with TAPSE <1.8 cm. Increase in RVSP from normal (<33 mm Hg) to mildly elevated (33-39 mm Hg) or elevated (>39 mm Hg) was associated with lower low-density lipoprotein and high-density lipoprotein, and higher hemoglobin A1c and body mass index (P<0.001). A decrease in TAPSE between groups of TAPSE >1.8 cm, TAPSE 1.5-1.8 cm, and TAPSE <1.5 cm was associated with increased triglyceride:high-density lipoprotein ratio and hemoglobin A1c, and decreased body mass index, low-density lipoprotein, high-density lipoprotein, and systolic blood pressure (P<0.001). Most associations between cardiometabolic predictors and RVSP and TAPSE were nonlinear with clear inflection points associated with higher pulmonary pressure and lower RV function. Conclusions Clinical measures of cardiometabolic function were highly associated with echocardiographic measures of right ventricular function and pressure.

Association of Longitudinal Activity Measures and Diabetes Risk: An Analysis From the National Institutes of Health All of Us Research Program.

CONTEXT: Prior studies of the relationship between physical activity and incident type 2 diabetes mellitus (T2DM) relied primarily on questionnaires at a single time point. OBJECTIVE: We sought to investigate the relationship between physical activity and incident T2DM with an innovative approach using data from commercial wearable devices linked to electronic health records in a real-world population. METHODS: Using All of Us participants' accelerometer data from their personal Fitbit devices, we used a time-varying Cox proportional hazards models with repeated measures of physical activity for the outcome of incident T2DM. We evaluated for effect modification with age, sex, body mass index (BMI), and sedentary time using multiplicative interaction terms. RESULTS: From 5677 participants in the All of Us Research Program (median age 51 years; 74% female; 89% White), there were 97 (2%) cases of incident T2DM over a median follow-up period of 3.8 years between 2010 to 2021. In models adjusted for age, sex, and race, the hazard of incident diabetes was reduced by 44% (95% CI, 15%-63%; P = 0.01) when comparing those with an average daily step count of 10 700 to those with 6000. Similar benefits were seen comparing groups based on average duration of various intensities of activity (eg, lightly active, fairly active, very active). There was no evidence for effect modification by age, sex, BMI, or sedentary time. CONCLUSION: Greater time in any type of physical activity intensity was associated with lower risk of T2DM irrespective of age, sex, BMI, or sedentary time.

Clinical insights into pulmonary hypertension in chronic obstructive pulmonary disease.

Pulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD). Little is known about the prevalence and clinical profiles of patients with COPD-PH. We report the clinical characteristics, hemodynamic profiles, and prognosis in a large population of patients with COPD referred for right heart catheterization (RHC). We extracted data from all patients referred for RHC between 1997 and 2017 in Vanderbilt's deidentified medical record. PH was defined as mean pulmonary artery pressure >20 mmHg. Pre- and postcapillary PH were defined according to contemporary guidelines. COPD was identified using a validated rules-based algorithm requiring international classification of diseases codes relevant to COPD. We identified 6065 patients referred for RHC, of whom 1509 (24.9%) had COPD and 1213 had COPD and PH. Patients with COPD-PH had a higher prevalence of diabetes, atrial fibrillation, and heart failure compared with COPD without PH. Approximately 55% of patients with COPD-PH had elevated left ventricle (LV) filling pressure. Pulmonary function testing data from individuals with COPD-PH revealed subtype differences, with precapillary COPD-PH having lower diffusion capacity of the lungs for carbon monoxide (DLCO) values than the other COPD-PH subtypes. Patients with COPD-PH had significantly increased mortality compared with COPD alone (hazard ratio [HR]: 1.70, 95% confidence interval [CI]: 1.28-2.26) with the highest mortality among the combined pre- and postcapillary COPD-PH subgroup (HR: 2.39; 95% CI: 1.64-3.47). PH is common among patients with COPD referred for RHC. The etiology of PH in patients with COPD is often mixed due to multimorbidity and is associated with high mortality, which may have implications for risk factor management.