Treatment of Secondary Pulmonary Hypertension with Bosentan after Left Ventricular Assist Device Implantation

Abstract

SUMMARYIntroduction: Secondary pulmonary hypertension (PH) and right ventricular dysfunction are common and associated with poor prognosis in HF patients with left ventricular assist devices (LVADs). The role of pulmonary vasodilator therapy for these patients is currently unclear. Aims: We sought to evaluate the safety and clinical course of patients treated with bosentan, an endothelin receptor antagonist, after the implementation of a LVAD. Results: Between 10/2008 and 5/2011, 50 consecutive patients with mean PAP >25 mmHg were treated with bosentan after LVAD implantation for a mean duration of 15.7 (AE12.4) months. Ten patients discontinued the drug for possible side effects, including three for LFT abnormalities. Comparison of baseline to 6-month follow-up data revealed laboratory evidence for decongestion with a decrease in bilirubin (2.3-0.6, P < 0.0001) and an improvement in pulmonary hemodynamics with echocardiographically calculated mean PVR decreasing 1.4 woods units (3.93 AE 1.53 to 2.58 AE 1.05, P < 0.0001). Conclusion: In this single-centered retrospective case series, we provide evidence that the tolerability of bosentan in LVAD-supported patients with secondary PH is comparable to prior experience in patients with heart failure.

Decoupling Between Diastolic Pulmonary Artery Pressure and Pulmonary Capillary Wedge Pressure as a Prognostic Factor After Continuous Flow Ventricular Assist Device Implantation

“…11 Very limited data exist on their efficacy in LVAD recipients with residual PH, likely because of their side effects including liver and renal dysfunction. 12,13 …”

Vascular Function in Continuous Flow LVADs: Implications for Clinical Practice

“…RV failure occurs in 10 to 40% of LVAD patients and represents an important cause of morbidity and mortality [ 87 , 88 , 89 , 90 , 91 ]. It is well known that some patients continue to have elevated PVR after LVAD implantation [ 92 , 93 , 94 ]. The reduced pulmonary arterial compliance associated with high PVR impairs RV output and subsequently precipitates systemic congestion in the settings of the high RV preload following LVAD implantation.…”

“…Although mounting evidence supports PVR reduction after LVAD implantation, there is a significant subset of patients who continue to have elevated PVR after LVAD [ 92 , 93 , 94 ]. Management of persistent PH in these patients is important to reduce RV dysfunction and enhance PVR reduction in preparation for HT.…”

“…Although guidelines recommend PDE-5 inhibitor use in LVAD patients with persistent PH and RV dysfunction, there is no strong evidence to support the benefits of this approach [ 119 ]. Nevertheless, there is a growing body of evidence from observational and non-randomized studies suggesting good tolerability and possible beneficial effects of long-term use of pulmonary vasodilators to reduce PVR and RV failure [ 92 , 93 , 120 ]. Tedford et al illustrated that the use of sildenafil reduces PVR in LVAD patients and allows bridging to transplant [ 93 ].…”

Influence of Mechanical Circulatory Support on Endothelin Receptor Expression in Human Left Ventricular Myocardium from Patients with Dilated Cardiomyopathy (DCM)

“…Hypertension, pulmonary hypertension and heart failure is associated with changes of the endothelin system [12, 13]. Bosentan, a dual endothelin receptor antagonist is used for treatment of secondary pulmonary hypertension in patients with mechanical circulatory support (MCS) [14] or awaiting heart transplantation [15]. …”