Intravenous sildenafil acutely improves hemodynamic response to exercise in patients with connective tissue disease
Hemodynamic assessment during exercise may unmask an impaired functional reserve of the right ventricle and the pulmonary vasculature in patients with connective tissue disease. We assessed the effect of intravenous sildenafil on the hemodynamic response to exercise in patients with connective tissu...
Saved in:
| Published in | PloS one Vol. 13; no. 9; p. e0203947 |
|---|---|
| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Public Library of Science
20.09.2018
Public Library of Science (PLoS) |
| Subjects | |
| Online Access | Get full text |
Cover
Loading…
| Summary: | Hemodynamic assessment during exercise may unmask an impaired functional reserve of the right ventricle and the pulmonary vasculature in patients with connective tissue disease. We assessed the effect of intravenous sildenafil on the hemodynamic response to exercise in patients with connective tissue disease.
In this proof-of-concept study, patients with connective tissue disease and mean pulmonary arterial pressure (mPAP) >20 mm Hg were subjected to a supine exercise hemodynamic evaluation before and after administration of intravenous sildenafil 10 mg.
Ten patients (four with moderately elevated mPAP 21-24 mm Hg; six with mPAP >25 mm Hg) underwent hemodynamic assessment. All of them showed markedly abnormal exercise hemodynamics. Intravenous sildenafil was well tolerated and had significant hemodynamic effects at rest and during exercise, although without pulmonary selectivity. Sildenafil reduced median total pulmonary resistance during exercise from 6.22 (IQR 4.61-8.54) to 5.24 (3.95-6.96) mm Hg·min·L-1 (p = 0.005) and increased median pulmonary arterial capacitance during exercise from 1.59 (0.93-2.28) to 1.74 (1.12-2.69) mL/mm Hg (p = 0.005).
In patients with connective tissue disease who have an abnormal hemodynamic response to exercise, intravenous sildenafil improved adaption of the right ventricular-pulmonary vascular unit to exercise independent of resting mPAP. The impact of acute pharmacological interventions on exercise hemodynamics in patients with pulmonary vascular disease warrants further investigation.
Clinicaltrials.gov NCT01889966. |
|---|---|
| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: The study was funded by a commercial source, Pfizer Inc. The funder had the following influence on the study design: the patient group investigated as well as the focus on acute sildenafil effects and drug safety of intravenous administration was discussed with a representative of the company. The funder did not have influence on the collection, analysis, or interpretation of data, the writing of the paper, or the decision to submit for publication. The funding does not alter our adherence to PLOS ONE policies on sharing data and materials. AJR has received a research grant from Pfizer via the Kerckhoff-Klinik Forschungsgesellschaft mbH, speaker fees from Servier, St. Jude Medical, Cardiokinetix, and Actelion, and travel grants from Actelion and Orion Pharma. MJR has received support from United Therapeutics and Bayer Pharma AG, and speaker fees from Actelion, Mundipharma, Roche, and United Therapeutics. AB and MF declare no conflicts of interest. IHT has received speaker fees from Pfizer. VM has received consultation fees and honoraria from Bayer Healthcare AG, Novartis Pharma, Cardiorentis Ltd. and Bristol- Myers Squibb. CWH has received honoraria for lectures from AstraZeneca, Bayer, Boehringer Ingelheim, CVRx, Daiichi Sankyo, Lilly, MSD, Sanofi Aventis, Pfizer, Roche, and Servier and honoraria for advisory board activities from AstraZeneca, Bayer, CVRx, and Boehringer Ingelheim. On behalf of all authors, the corresponding author declares that there are no further competing interests. |
| ISSN: | 1932-6203 1932-6203 |
| DOI: | 10.1371/journal.pone.0203947 |