The crucial role of tricuspid regurgitation in patients with pulmonary arterial hypertension

Abstract Introduction Pulmonary arterial hypertension (PAH) is a rare and progressive disease with high morbidity and mortality rate and its prognosis is critically affected by right ventricle (RV) dysfunction. Several studies have demonstrated that the presence of moderate-severe tricuspid regurgitation (TR) is associated with poor prognosis in PAH. However, the echocardiographic correlates and the impact on functional capacity of significant TR in PAH patients have not been thoroughly investigated. Purpose The aims of this study were to confirm the prognostic role of moderate-to-severe TR in PAH patients and to assess the effects of significant TR on remodelling of right cardiac chambers evaluated by echocardiography and on exercise capacity determined by six minute-walking-test (6MWT) and cardiopulmonary exercise testing (CPET). Methods This study is a retrospective longitudinal analysis of 103 patients with newly diagnosed PAH enrolled from 2010 to march 2021. Patients with portopulmonary PAH and with congenital heart disease PAH were excluded. Median follow up (FU) was 27 months and the primary endpoint was all-cause mortality. Results Our cohort was characterised by high BNP mean values (382 pg/mL), poor exercise capacity (260 mt at 6MWT, peak VO2 11 mL/kg/min at CPET), right ventricular dysfunction and severe PH at right heart catheterization (cardiac index 2.3 L/min/mq, mean pulmonary artery pressure 48 mmHg, pulmonary vascular resistance 12 WU). Sixty-nine percent (70/103) of the cohort had significant TR. Thirty percent of patients (30/103) died during follow-up. At Cox univariate regression, moderate to severe TR was significantly associated with higher risk of death (HR 4.48, p=0.004) (Figure 1). At bivariate analysis combining TR grade and TAPSE/sPAP, significant TR showed to be associated with higher risk of death (HR 3.59, p=0.05). In particular, the combination of normal TAPSE and mild TR identified a subgroup of patients who had no events during the follow-up period (Figure 2). At echocardiography patients with moderate-to-severe TR had more peripheral venous congestion, worse right ventricular function (TAPSE and TAPSE/sPAP), lower stroke volume index. The presence of moderate-to-severe TR promoted negative remodelling of the right atrium and of the right ventricle, which was more spherical, hypertrophic and stiff. Exercise capacity of patient with significant TR was significantly reduced both at CPET and at 6MWT. Conclusions Moderate-to-severe tricuspid regurgitation is associated with poor exercise capacity (both at CPET and at 6MWT) and poor survival in patients with PAH. Echocardiography can easily detect morphological and functional abnormalities associated with a worse prognosis in patients with PAH and represents an important non-invasive tool for risk stratification. Funding Acknowledgement Type of funding sources: None.