PDE5A inhibitor treatment of persistent pulmonary hypertension after mechanical circulatory support.
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.


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.
Tedford
Ryan J
RJ
Divisions of Cardiology and Pulmonary and Critical Care Medicine, Department of Medicine, The Johns Hopkins Medical Institutions, Johns Hopkins University, 720 Rutland Avenue, Baltimore, MD 21205, USA.
Hemnes
Anna R
AR
Russell
Stuart D
SD
Wittstein
Ilan S
IS
Mahmud
Mobusher
M
Zaiman
Ari L
AL
Mathai
Stephen C
SC
Thiemann
David R
DR
Hassoun
Paul M
PM
Girgis
Reda E
RE
Orens
Jonathan B
JB
Shah
Ashish S
AS
Yuh
David
D
Conte
John V
JV
Champion
Hunter C
HC
D000328:Adult; D005260:Female; D006353:Heart-Assist Devices; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects; D018487:Ventricular Dysfunction, Left / Q000150:complications* / Q000503:physiopathology / Q000628:therapy*
D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors