Background Pulmonary hypertension (PH) is a common and morbid complication of left heart disease with 2 subtypes: isolated post-capillary PH (Ipc-PH) and combined post-capillary and pre-capillary PH (Cpc-PH). Little is known about the clinical or physiological characteristics that distinguish these 2 subphenotypes, and if Cpc-PH shares molecular similarities to pulmonary arterial hypertension (PAH). Objectives We sought to test the hypothesis that the hemodynamic and genetic profile of Cpc-PH would more closely resemble PAH than Ipc-PH. Methods We used Vanderbilt’s electronic medical record linked to a DNA biorepository to extract demographics, clinical data, invasive hemodynamics, echocardiography, and vital status for all patients referred for right heart catheterization between 1998 and 2014. We identified shared genetic variants between PAH and Cpc-PH compared with Ipc-PH using pre-existing single-nucleotide polymorphism data. Results We identified 2,817 patients with PH (13% Cpc-PH, 52% Ipc-PH, and 20% PAH). Cpc-PH patients were on average 6 years younger, with more severe pulmonary vascular disease than Ipc-PH patients, despite similar comorbidities and prevalence, severity, and chronicity of left heart disease. After adjusting for relevant covariates, the risk of death was similar between Cpc-PH and Ipc-PH (HR: 1.14, 95% CI: 0.96 to 1.35, p = 0.15) when defined by diastolic pressure gradient. We identified 75 shared exonic single-nucleotide polymorphisms between Cpc-PH and PAH enriched in pathways involving cell structure, extracellular matrix, and immune function. These genes are expressed, on average, 32% higher in lungs relative to other tissues. Conclusions Cpc-PH patients develop pulmonary vascular disease similar to PAH patients, despite younger age and similar prevalence of obesity, diabetes mellitus, and left heart disease compared with Ipc-PH patients. An exploratory genetic analysis in Cpc-PH identified genes and biological pathways in the lung known to contribute to PAH pathophysiology, suggesting that Cpc-PH may be a distinct and highly morbid PH subphenotype.

Borderline PH is common in patients undergoing RHC and is associated with significant comorbidities, progression to overt PH, and decreased survival. Small increases in mPAP, even at values currently considered normal, are independently associated with increased mortality. Prospective studies are warranted to determine whether early intervention or closer monitoring improves clinical outcomes in these patients.

Among patients without HF, plasma BNP level is a stronger predictor of death than traditional risk factors. The risk for death associated with any given BNP level is similar between patients with and those without HF, particularly in the acute care setting.

IMPORTANCE Current guidelines recommend evaluation for echocardiographically estimated right ventricular systolic pressure (RVSP) greater than 40 mm Hg; however, this threshold does not capture all patients at risk.OBJECTIVES To determine if mild echocardiographic pulmonary hypertension (ePH) is associated with reduced right ventricular (RV) function and increased risk of mortality.

Although commonly encountered, patients with combined postcapillary and precapillary pulmonary hypertension (Cpc-PH) have poorly understood pulmonary vascular properties. The product of pulmonary vascular resistance and compliance, resistance-compliance (RC) time, is a measure of pulmonary vascular physiology. While RC time is lower in postcapillary PH than in precapillary PH, the RC time in Cpc-PH and the effect of pulmonary wedge pressure (PWP) on RC time are unknown. We tested the hypothesis that Cpc-PH has an RC time that resembles that in pulmonary arterial hypertension (PAH) more than that in isolated postcapillary PH (Ipc-PH). We analyzed the hemodynamics of 282 consecutive patients with PH referred for right heart catheterization (RHC) with a fluid challenge from 2004 to 2013 (cohort A) and 4,382 patients who underwent RHC between 1998 and 2014 for validation (cohort B). Baseline RC time in Cpc-PH was higher than that in Ipc-PH and lower than that in PAH in both cohorts (P < 0.001). In cohort A, RC time decreased after fluid challenge in patients with Ipc-PH but not in those with PAH or Cpc-PH (P < 0.001). In cohort B, the inverse relationship of pulmonary vascular compliance and resistance, as well as that of RC time and PWP, in Cpc-PH was similar to that in PAH and distinct from that in Ipc-PH. Our findings demonstrate that patients with Cpc-PH have pulmonary vascular physiology that resembles that of patients with PAH more than that of Ipc-PH patients. Further study is warranted to identify determinants of vascular remodeling and assess therapeutic response in this subset of PH.