BACKGROUND Pulmonary hypertension (PH) secondary to left heart failure portends a poor prognosis and is a relative contraindication to heart transplantation at many centers. We tested the hypothesis that when PH persists after adequate left ventricle (LV) unloading via recent left ventricular assist device (LVAD) therapy, phosphodiesterase type 5A (PDE5A) inhibition would decrease PH in this population. METHODS AND RESULTS We performed an open-label clinical trial using control patients not receiving therapy. Between 1999 and 2007, one hundred thirty-eight consecutive patients undergoing cardiac transplantation evaluation with advanced left ventricular dysfunction, an elevated pulmonary capillary wedge pressure (PCWP), and PH (defined by a pulmonary vascular resistance (PVR) > 3 Woods Units), were treated with LVAD therapy. Fifty-eight of these patients reduced their PCWP to a value < 15 mmHg (11.8 +/− 2.0 mmHg from baseline 23.2 +/− 6.2 mmHg) one to two weeks after LVAD implantation, but despite this improvement, the PVR of these patients was only minimally affected (5.65 +/−3.00 to 5.39 +/− 1.78 Wood Units). Twenty-six consecutive patients from this group with persistently elevated PVR were started on oral PDE5A inhibition with sildenafil and titrated to an average of dose of 51.9 mg by mouth three times per day. The average PVR in the sildenafil treated group fell from 5.87 +/− 1.93 to 2.96 +/− 0.92 Wood Units (P<0.001) and the mean pulmonary artery pressure (mPAP) fell from 36.5 +/− 8.6 to 24.3 +/− 3.6mmHg (P<0.0001) and was significantly lower when compared to the thirty-two LVAD recipients not receiving sildenafil at weeks 12–15 after the initial post LVAD hemodynamic measurements (13 to 17 weeks post LVAD implantation). In addition, hemodynamic measurements of right ventricular (RV) function in sildenafil treated patients was also improved compared with patients not receiving sildenafil. CONCLUSIONS In patients with persistent PH after recent LVAD placement, PDE5A inhibition in this open label trial resulted in a significant decrease in PVR as compared with control patients.

The PDE5 activity in systemic and pulmonary vasculature increases in HF rendering hemodynamic responses to PDE5 inhibition identical to those from BNP infusion. Natriuretic peptide desensitization in HF relates, in part, to increased PDE5 activity, supporting a therapeutic role for PDE5 inhibition.

Right heart failure most commonly results from the complication of left heart failure (systolic or nonsystolic dysfunction) or pulmonary hypertension. Over the past decade, greater attention has been paid to the role of right ventricular failure in the morbidity and mortality associated with cardiomyopathy and pulmonary hypertension. The right ventricle is distinct from the left ventricle not only in its spatial localization, but also in its response to increased afterload and signaling mechanisms. This article discusses the role of right ventricular failure in the setting of heart failure as well as the clinical diagnosis and management of right ventricular failure.