Risk assessment according to the presence of left heart disease phenotype in pulmonary arterial hypertension patients: a multicenter cohort study

Abstract

Abstract Introduction Subclinical left heart disease (LHD) may impact the management of pulmonary arterial hypertension (PAH) [1]. Purpose To evaluate the influence of a LHD phenotype on PAH risk stratification. Methods We retrospectively reviewed the data of consecutive PAH patients followed at 7 tertiary centers from 2001 to 2021, and selected those with all parameters available to determine risk of death by means of the COMPERA and COMPERA 2.0 scores, both at baseline and at the first disease reassessment including right heart catheterization. These subjects were classified as no-LHD or LHD according to the AMBITION trial criteria, i.e. absence or presence, respectively, of ≥ 3 among body mass index ≥ 30 kg/m2, systemic hypertension, diabetes mellitus, and coronary artery disease; and/or pulmonary vascular resistance between 3 and 3.75 WU or between 3.75 and 6.25 WU together with pulmonary artery wedge pressure (PAWP) between 13 and 15 mmHg [2,3]. The characteristics between the 2 groups were compared by chi-square test, T-test, or Mann-Whitney test, and Kaplan-Meier curves for overall survival by log-rank test. Results Of 286 patients included in the analysis, 57 (20%) had a LHD phenotype. The first complete reassessment was performed 7 ± 5 months after baseline. Compared with no-LHD, subjects with LHD were older, had more often cardiovascular comorbidities, and had higher E/e’ ratio, left atrial area and PAWP, but had lower brain natriuretic peptide concentrations and better right ventricular function and pulmonary hemodynamics (Figure 1). They were also less commonly treated with phosphodiesterase inhibitors or riociguat (54% vs 70%, P=0.03) and dual oral therapy (26% vs 43%, P=0.03), while they used more beta-blockers (47% vs 16%, P<0.001) and ACE inhibitors or angiotensin receptor blockers (40% vs 21%, P=0.004). At baseline, the proportion of patients with low vs high risk was greater in LHD than in no-LHD with COMPERA, but not with COMPERA 2.0. Moreover, risk profile significantly improved during follow-up only in no-LHD with COMPERA, but in both groups with COMPERA 2.0 (Figure 1). While all-cause mortality was significantly different across baseline COMPERA and COMPERA 2.0 risk strata in no-LHD, either approach for risk stratification failed to discriminate LHD subgroups with different prognosis (Figure 2). However, both COMPERA and COMPERA 2.0 risk categories differentiated mortality in LHD at the first disease reassessment (log-rank P <0.001, not shown). Conclusions This study suggests that the performance of risk stratification scores COMPERA and COMPERA 2.0 in PAH subjects with a LHD phenotype is limited, although the former may retain value during follow-up. Alternative tools may be needed for prognostication in this patient subset.