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

Abstract

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.

Keywords: biomarker; left heart disease; pulmonary circulation; vascular remodeling.

Figure 1

Schematic representing the initial data set and subsequent criteria used to create the two comparison groups. Cpc‐PH, combined pre‐ and postcapillary pulmonary hypertension; Ipc‐PH, isolated postcapillary pulmonary hypertension; PH, pulmonary hypertension; PH‐LHD, pulmonary hypertension due to left heart disease; RHC, right heart catheterization.

Figure 2

Multivariable regression analysis to identify characteristics associated with progression to Cpc‐PH. Data reflect comorbidities and values at the time of repeat RHC reported as age‐ and sex‐adjusted odds ratio (95% confidence interval) with respective p value and C‐statistic. BMI, body mass index; CAD, coronary artery disease; COPD, chronic obstructive pulmonary disease; Cpc‐PH, combined pre‐ and postcapillary pulmonary hypertension; DPG, diastolic pressure gradient; EF, ejection fraction; HDL, high‐density lipoproteins; LDL, low‐density lipoproteins; OSA, obstructive sleep apnea; PVR, pulmonary vascular resistance; RAP, mean right atrial pressure; RHC, right heart catheterization; TG‐HDL, triglyceride to HDL ratio.