Chest

Chest

Volume 127, Issue 5, May 2005, Pages 1647-1653
Journal home page for Chest

Clinical Investigations
Hemodynamic Effects of Sildenafil in Patients With Congestive Heart Failure and Pulmonary Hypertension: Combined Administration With Inhaled Nitric Oxide

https://doi.org/10.1378/chest.127.5.1647Get rights and content

Study objectives

In patients with pulmonary hypertension (PH) secondary to congestive heart failure, inhaled nitric oxide (NO) increases pulmonary vascular smooth-muscle intracellular cyclic guanosine monophosphate (cGMP) concentration, thereby decreasing pulmonary vascular resistance (PVR) and increasing cardiac index (CI). However, these beneficial effects of inhaled NO are limited in magnitude and duration, at least in part due to cGMP hydrolysis by the type 5 isoform of phosphodiesterase (PDE5). The goal of this study was to determine the acute pulmonary and systemic hemodynamic effects of the selective PDE5 inhibitor, sildenafil, administered alone or in combination with inhaled NO in patients with congestive heart failure and PH.

Design

Single center, case series, pharmacohemodynamic study.

Setting

Cardiac catheterization laboratory of a tertiary care academic teaching hospital.

Patients

We studied 11 patients with left ventricular systolic dysfunction due to coronary artery disease or idiopathic dilated cardiomyopathy who had PH.

Interventions

We administered oral sildenafil (50 mg), inhaled NO (80 ppm), and the combination of sildenafil and inhaled NO during right-heart and micromanometer left-heart catheterization.

Measurements and results

Sildenafil administered alone decreased mean pulmonary artery pressure by 12 ± 5%, PVR by 12 ± 5%, systemic vascular resistance (SVR) by 13 ± 6%, and pulmonary capillary wedge pressure by 12 ± 7%, and increased CI by 14 ± 5% (all p < 0.05) [± SEM]. The combination of inhaled NO and sildenafil decreased PVR by 50 ± 4%, decreased SVR by 24 ± 3%, and increased CI by 30 ± 4% (all p < 0.01). These effects were greater than those observed with either agent alone (p < 0.05). In addition, sildenafil prolonged the pulmonary vasodilator effect of inhaled NO. Administration of sildenafil alone or in combination with inhaled NO did not change systemic arterial pressure or indexes of myocardial systolic or diastolic function.

Conclusions

PDE5 inhibition with sildenafil improves cardiac output by balanced pulmonary and systemic vasodilation, and augments and prolongs the hemodynamic effects of inhaled NO in patients with chronic congestive heart failure and PH.

Section snippets

Inclusion and Exclusion Criteria

All patients under the care of the Massachusetts General Hospital Heart Failure Service who required hemodynamic assessment as part of a cardiac transplant evaluation were eligible for study. Inclusion criteria were a ≥ 12-month history of symptomatic heart failure; a LV ejection fraction < 0.40, as identified by echocardiography within 1 month; and a mean pulmonary artery pressure of at least 25 mm Hg. Exclusion criteria included the presence of acutely decompensated heart failure (systemic

Study Population and Baseline Hemodynamic Findings

We studied 11 heart failure patients (9 men and 2 women; mean age, 56 ± 3 years [± SEM] [Table 1]. Six patients had idiopathic dilated cardiomyopathy, and five patients had coronary artery disease. Seven patients were New York Heart Association (NYHA) functional class III, and four patients were NYHA functional class IV. At baseline, the PCWP was elevated, and the LV ejection fraction and CI were depressed. PH was present with a mean pulmonary artery pressure of 37 ± 2 mm Hg and PVR of 301 ± 44

Discussion

In this study, we evaluated the systemic and pulmonary vasodilator effects of inhaled NO, sildenafil, and their combination in 11 patients with PH secondary to severe chronic left heart failure. The major findings of the study were that sildenafil administered alone increased CI by producing balanced systemic and pulmonary vasodilatation, and that inhaled NO administered in combination with sildenafil produced additional pulmonary vasodilatation and further increased CI. Importantly, the

References (22)

  • LohE et al.

    Cardiovascular effects of inhaled nitric oxide in patients with left ventricular dysfunction

    Circulation

    (1994)

    • Cited by (0)

    This work was supported by grants HL-42397 (Dr. Zapol), HL-57172 and HL-70896 (Dr. Bloch), and HL-04021 (Dr. Semigran) from the National Heart, Lung, and Blood Institute. Massachusetts General Hospital holds a patent for the therapeutic use of inhaled NO and may receive royalties. Dr. Zapol receives royalties on inhaled NO and is chair of the iNO Therapeutics Scientific Advisory Board. Dr. Bloch has a sponsored research agreement with iNO Therapeutics, and Dr. Semigran has a sponsored research agreement with Pfizer Inc. Manuscript received May 21, 2004; revision accepted October 29, 2004.

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestjournal.org/misc/reprints.shtml).

    View full text
    Copyright © 2005 The American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.