Beneficial effects of TX45, a long-acting Fc-relaxin fusion, on right ventricular-pulmonary artery coupling in patients with pulmonary hypertension due to HFrEF
R Rogers, A Lacy, V Corcea, M Ruddy, A MuslinAbstract
Background
Increased right ventricular (RV) afterload can lead to RV-pulmonary artery (RV-PA) uncoupling and RV failure in pulmonary hypertension due to heart failure with reduced left ventricular ejection fraction (PH-HFrEF).
Purpose
This study evaluated the effect of TX45, a long-acting Fc-relaxin fusion, on RV-PA coupling and RV function in patients with PH-HFrEF.
Methods
14 patients with stable PH-HFrEF (LVEF≤40%) underwent right heart catheterization in this open label study. Baseline hemodynamics were acquired, and an intravenous dose of TX45 up to 3 mg/kg was administered. Hemodynamic measurements were obtained for 8 hours after dosing. Repeat echocardiograms were performed through Day 29.
Results
Baseline hemodynamics were consistent with PH-HFrEF (Table). TX45 was well-tolerated without serious adverse events, hypotension or congestion. TX45 dosing resulted in reduced RV and LV filling pressures and increased cardiac output. Measures of RV afterload, including pulmonary vascular resistance and pulmonary artery capacitance, decreased with TX45 dosing. Echocardiography through Day 29 showed a 36.3% increase in TAPSE/SPAP, suggesting improved RV-PA coupling, and a 20.3% increase in RVFAC, indicating better RV function.
Conclusion
PH-HFrEF patients exhibited a favorable hemodynamic response to TX45. Repeat echocardiography showed enhanced RV-PA coupling and RV function. These results in PH-HFrEF are like previous results in PH-HFpEF and support further clinical investigation.TableFor image description, please refer to the figure legend and surrounding text.