1Herzzentrum der Universität zu Köln Klinik III für Innere Medizin Köln, Deutschland
Background: Tricuspid regurgitation (TR) is a common condition, and severe TR is associated with worsening heart failure and impaired survival. Aetiology is secondary in >90% of cases, and associated with pressure and/or volume load. While TR is frequent in patients with pulmonary arterial hypertension (PAH), the impact of guideline-directed targeted PAH therapy on TR severity and echocardiographic right heart parameters has not thoroughly been studied.
Methods: In a retrospective observational study, we analyzed the effect of early sequential dual combination therapy with phospodiesterase type 5 inhibitors and endothelin receptor antagonists on TR severity (overall grading, vena contracta [VC], tricuspid valve [TV] annulus), right heart dimensions/function (right atrial [RA] area, right ventricular [RV] end-diastolic diameter [RVEDD], tricuspid annular plane systolic excursion [TAPSE], fractional area change [FAC]), systolic pulmonary arterial pressure [sPAP] and RV-pulmonary arterial (PA) coupling. Clinical parameters such as WHO-functional class (FC), 6 minute walking distance (MWD), NTproBNP levels and ESC/ERS risk status were assessed at baseline and 6 months after initiation of therapy. Cardiopulmonary haemodynamics were invasively evaluated by right heart catheterization (RHC) in all patients at diagnosis and upon treatment initiation at 6 month follow-up.
Results: A total of 90 patients with newly diagnosed PAH were included into the study. Mean age was 58.7 ± 17.4 years (61 % female), and the majority had idiopathic PAH (84 %). At diagnosis, the mean pulmonary artery pressure (PAPm) was 49.8 ± 13.8 mmHg, pulmonary vascular resistance (PVR) 10.9 ± 5.3 WU, and stroke volume index (SVI) 25.1 ± 10.3 ml/m². Repeat RHC at follow-up revealed significant improvement of cardiopulmonary haemodynamics (PAPm 38.0 ± 11.0 mmHg, PVR 5.4 ± 2.9 WU, SVI 38.1 ± 10.2 ml/m²; all p < 0.001). This was associated with substantial reduction of TR (VC 4.7 ± 2.8 mm vs. 3.0 ± 2.1 mm; TV annulus: 36.3 ± 6.1 mm vs. 33.0 ± 5.5 mm, both p < 0.001). Moreover, we observed significant improvements in right heart dimensions (RA area 23.7 ± 9.0 vs. 20.5 ± 7.2 cm², RVEDD 45.4 ± 7.7 vs. 41.2 ± 6.9 mm, both p < 0.001) and longitudinal (TAPSE 17.3 ± 4.4 vs. 21.9 ± 4.3 mm, p < 0.001; and radial (FAC 25.5 ± 11.3 % vs. 32.3 ± 8.8 %, p < 0.001) RV function as well as sPAP (73.3 ± 27.1 mmHg vs. 52.2 ± 20.5 mmHg, p < 0.001), which accordingly had a significant effect on RV–PA coupling as assessed by the TAPSE/sPAP ratio (0.28 ± 0.18 vs. 0.48 ± 0.28 mm/mmHg, p < 0.001). After 6 month of dual combination therapy, WHO-FC (3.0 ± 0.6 vs. 2.0 ± 0.6, p < 0.001), 6 MWD (335 ± 153 vs. 408 ± 128 m, p < 0.001), NTproBNP values (2400 ± 282 vs. 655 ± 715 ng/l, p < 0.001) and ESC/ERS risk status significantly improved.
Conclusions: Data indicate that PAH may represent an underlying cause of functional TR, and improvement of hemodynamics by initiation of targeted medical therapy leads to substantial reduction of TR severity, along with improvements of right heart dimensions, RV function, RV–PA coupling, and clinical measures. In view of the increasing interventional treatment options for high-grade TR, these findings emphasize the importance of a comprehensive diagnostic work-up including invasive hemodynamic evaluation prior to interventional therapy, and medical therapy may be indicated in selected cases with PAH.