The Association Between Pulmonary Vascular Resistance and Clinical Outcomes in Patients with Pulmonary Hypertension: A Retrospective Cohort Study

Background: In pulmonary hypertension (PH) subgroups, elevated pulmonary vascular resistance (PVR) ≥3.0 WU is associated with poor prognosis. However, the spectrum of PVR risk in PH is not known. To address this area of uncertainty, we aimed to analyze the relationship between PVR and adverse clinical outcomes in PH. Methods: We analyzed retrospectively all patients undergoing right heart catheterization (RHC) in the Veterans Affairs healthcare system (2008–2016; 1,153 [570–1,971] days median follow-up). Cox proportional hazards models were used to assess the association between PVR and outcomes, and the mortality hazard was validated in a RHC cohort from Vanderbilt University Medical Center (1998–2014; 1,752 [1,281–2,999] days median follow-up). Findings: The primary cohort (N=40,082; male, N=38,751 [96.7%]; 66.5 [61.1–73.5] yr) included patients with a history of heart failure (N=23,201 [57.9%]) and chronic obstructive pulmonary disease (N=13,348 [33.3%]). We focused on patients at risk for PH based on mean pulmonary artery pressure (mPAP) ≥19 mmHg (N=32,725 of 40,082 [81.6%]). When modeled as a continuous variable, the all-cause mortality hazard for PVR was increased at ~2.2 WU compared to PVR=1.0 WU. Among patients with ≥19 mmHg and pulmonary artery wedge pressure ≤15 mmHg, the adjusted hazard ratios for mortality and heart failure hospitalization were 1.71 (95% CI: 1.59–1.84, P<0.0001) and 1.27 (95% CI: 1.13–1.43, P=0.0001), respectively, when comparing PVR ≥2.2 WU to <2.2 WU. The validation cohort (N=3,699, male, N=1,860 [50.3%] male, 60.4 [49.5–69.2] yr) included N=2,870 patients [77.6%] with mPAP ≥19 mmHg (male, N=1,418 [49.4%]). The adjusted mortality hazard ratio PVR ≥2.2 WU for patients with PAWP ≤15 mmHg in the mPAP ≥19 mmHg group (N=1,221 of 2,870 [42.5%]) was 1.81 (95% CI: 1.33–2.47, P=0.0002). Interpretation: These data widen the PVR risk continuum associated with mortality and heart failure hospitalization to ~2.2 WU among patients referred for RHC with elevated pulmonary artery pressure. Testing the generalizability of these findings in at-risk populations with fewer cardiopulmonary comorbidities is warranted. time of right heart catheterization as particularly vulnerable. Overall, these results suggest that reconsidering the hemodynamic parameters that define PH in patients with cardiopulmonary disease is warranted, and identify a need for developing early detection strategies to capture this large and vulnerable population. model included the following clinical variables: categorical age, sex, race, categorical body mass index, and history of systemic hypertension, congestive heart failure, left heart failure, diabetes mellitus, coronary artery disease, chronic obstructive pulmonary disease (COPD), liver cirrhosis, chronic kidney disease included the patient receiving renal replacement therapy, portal hypertension, connective tissue disease, atrial arrhythmia, interstitial lung disease, pulmonary embolism, valvular disease, use, psychiatric obstructive sleep apnea, and inpatient status at the heart catheterization. For the validation cohort, following variables the adjustment used in the primary cohort analysis were available included: age, sex, race, diabetes mellitus, body mass index, coronary artery disease, valvular heart disease, COPD, atrial arrhythmia, interstitial lung disease, connective tissue disease, systemic hypertension, chronic kidney disease, obstructive sleep apnea, congestive heart failure. both the primary and validation cohorts, the for analyses of patients PAWP included the co-variate of