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Original Articles

PDE5A Inhibitor Treatment of Persistent Pulmonary Hypertension After Mechanical Circulatory Support

Ryan J. Tedford, MD; Anna R. Hemnes, MD; Stuart D. Russell, MD; Ilan S. Wittstein, MD; Mobusher Mahmud, MD; Ari L. Zaiman, MD; Stephen C. Mathai, MD, MHS; David R. Thiemann, MD; Paul M. Hassoun, MD; Reda E. Girgis, MD; Jonathan B. Orens, MD; Ashish S. Shah, MD; David Yuh, MD; John V. Conte, MD and Hunter C. Champion, MD, PhD

From the Divisions of Cardiology and Pulmonary and Critical Care Medicine, Department of Medicine (R.J.T., A.R.H., S.D.R., I.S.W., M.M., A.L.Z., S.C.M., D.R.T., P.M.H., R.E.G., J.B.O., H.C.C.); and Division of Cardiac Surgery, Department of Surgery (A.S.S., D.Y., J.V.C.), The Johns Hopkins Medical Institutions, Baltimore, Md.

Correspondence to Hunter C. Champion, MD, PhD, Division of Cardiology, Department of Medicine, Johns Hopkins University, 720 Rutland Avenue, Ross 835, Baltimore, MD 21205. E-mail hcc{at}jhmi.edu

Received January 7, 2008; accepted September 25, 2008.

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 unloading via recent left ventricular assist device (LVAD) therapy, phosphodiesterase type 5A 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, 138 consecutive patients undergoing cardiac transplantation evaluation with advanced left ventricular dysfunction, an elevated pulmonary capillary wedge pressure, and PH (defined by a pulmonary vascular resistance (PVR) >3 Woods Units), were treated with LVAD therapy. Fifty-eight of these patients reduced their pulmonary capillary wedge pressure to a value <15 mm Hg (11.8±2.0 mm Hg from baseline 23.2±6.2 mm Hg) 1 to 2 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 phosphodiesterase type 5A inhibition with sildenafil and titrated to an average of dose of 51.9 mg by mouth 3 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 fell from 36.5±8.6 to 24.3±3.6 mm Hg (P<0.0001) and was significantly lower when compared with the 32 LVAD recipients not receiving sildenafil at weeks 12 to 15 after the initial post-LVAD hemodynamic measurements (13 to 17 weeks post-LVAD implantation). In addition, hemodynamic measurements of right ventricular function in sildenafil-treated patients was also improved compared with patients not receiving sildenafil.

Conclusions— In patients with persistent PH after recent LVAD placement, phosphodiesterase type 5A inhibition in this open-label trial resulted in a significant decrease in PVR when compared with control patients.

Key Words: heart failure • PDE5A inhibition • sildenafil • hypertension, pulmonary • transplantation

This article has been cited by other articles:

				M. J. Semigran Phosphodiesterase Type 5 Inhibition: A Support of the Left Ventricular Assist Device Bridge to Transplant Circ Heart Fail, November 1, 2008; 1(4): 211 - 212. [Full Text] [PDF]