Echocardiographic characterization of combined postcapillary and precapillary pulmonary hypertension in systemic sclerosis with preserved ejection fraction.

Abstract

BACKGROUND: Systemic sclerosis (SSc) is a multisystem autoimmune disease frequently complicated by pre- and post-capillary pulmonary hypertension (PH). Within SSc, progressive diastolic dysfunction and heart failure with preserved ejection fraction (HFpEF) are key contributors, often presenting as isolated postcapillary PH (Ipc-PH) or combined pre- and postcapillary PH (Cpc-PH). The ability to differentiate these hemodynamic phenotypes is critical for risk stratification, yet echocardiographic markers specific to each subtype in SSc-HFpEF are poorly defined. METHODS: We investigated 147 adults with SSc-HFpEF with echocardiograms and right heart catheterization (RHC) assessments performed within one year. Patients were classified as Ipc-PH (n = 46) or Cpc-PH (n = 101) based on guideline-defined hemodynamic criteria. Echocardiographic parameters, including conventional measures, strain indices, and coupling metrics were analyzed. A random forest (RF) classifier was used to identify top echocardiographic predictors of Cpc-PH, and further assessed using multivariable logistic regression. Separate RF models and Cox regression analyses were used to determine echocardiographic predictors of mortality within each group. Survival was assessed using Kaplan-Meier analysis. RESULTS: Patients with Cpc-PH exhibited significantly greater right heart remodeling, higher pulmonary pressures, and impaired right ventricle (RV)-pulmonary artery (PA) coupling. The top echocardiographic predictors of Cpc-PH included reduced RV free wall strain (RVFWS), decreased RVFWS/PA systolic pressure (PASP) and fractional area change (FAC)/PASP ratios, elevated PASP, lower septal e′ velocity, and higher systolic LV eccentricity index (LV EI). In adjusted Cox models, elevated LVEI (HR 1.39), increased RV internal diastolic diameter (HR 2.15), and reduced left and right atrial strain (HR 0.91 and 0.94, respectively) were independently associated with mortality in Cpc-PH. In Ipc-PH, mortality was linked to reduced FAC/PASP, lower left ventricular global longitudinal strain (LVGLS), increased LV mass index, elevated PASP, and lower RVFWS. CONCLUSION: In the present study, we demonstrate key echocardiographic differences between Ipc-PH and Cpc-PH within the SSc-HFpEF population, emphasizing the central role of right heart remodeling, RV-PA coupling, atrial and septal mechanics in phenotypic differentiation and prognostication. Strain-based parameters and RV-PA coupling indices offer incremental value for risk stratification and may guide more tailored therapeutic strategies in this heterogeneous population.