Impact of targeted therapies withPDE5 inhibitors, endothelin receptor antagonists and sotatercept on functional tricuspid regurgitation in pulmonary arterial hypertension
J Gentz, C Hohmann, J Adler, F Ballmann, P von Stein, S Baldus, S RosenkranzAbstract
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
We analyzed the impact of PAH therapies on the degree of TR in two scenarios: Group A comprised 88 patients with incident PAH, in whom upfront dual oral PAH combination therapy with a phosphodiesterase-5 inhibitor (PDE5i) and an endothelin receptor antagonist (ERA) was initiated; Group B consisted of 26 patients with prevalent PAH on stable background therapy who received the novel activin signaling inhibitor sotatercept as add-on therapy. All patients underwent structured follow-up, including repeat right heart catheterization (RHC) and echocardiography. TR severity was quantified as overall grading (0=none/trace, 1=mild, 2=moderate, 3=severe), vena contracta [VC], and tricuspid valve [TV] annulus.
Results
Patients´ mean age was 56.8±17.6 years, 65.8% were female, and 34.9/60.4% were in WHO-FC II/III, respectively. In group A, all patients were initiated on combination therapy (PDE5i and ERA), which led to improvements of mean pulmonary artery pressure (mPAP; 49.76±13.51 to 38.07±10.92 mmHg), pulmonary vascular resistance (PVR; 10.85±5.39 to 5.17±2.73 WU), and pulmonary artery compliance (PAC; 1.08±0.61 to 2.12±1.01 ml/mmHg) (all p<0.05). Concomitant reverse right heart remodeling was associated with reductions in TR grade (1.72±0.87 to 1.14±0.79), VC width (4.45±2.71 to 2.79±1.97 mm), and TV annulus (36.30±6.02 to 32.92±5.48 mm) (all p<0.05). In group B, add-on sotatercept to existing background therapy led to further improvements of mPAP (53.69±13.42 to 41.55±13.87 mmHg), PVR (11.08±5.03 to 7.49±4.25 WU), and PAC (1.19±0.60 to 1.96±0.98 ml/mmHg) (all p<0.05). Add-on Sotatercept was associated with reductions in TR severity (grade 2.12±0.82 to 1.00±0.94), VC (5.16±2.69 to 2.10±2.08 mm), and TV annulus (39.41±6.02 to 33.63±7.25 mm) (all p<0.05).
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.