Universität zu Köln

Bonderman, Diana, Pretsch, Ingrid, Steringer-Mascherbauer, Regina, Jansa, Pavel ORCID: 0000-0002-3711-7064, Rosenkranz, Stephan, Tufaro, Caroline, Bojic, Andja, Lam, Carolyn S. P., Frey, Reiner, Kilama, Michael Ochan, Unger, Sigrun, Roessig, Lothar and Lang, Irene M. (2014). Acute Hemodynamic Effects of Riociguat in Patients With Pulmonary Hypertension Associated With Diastolic Heart Failure (DILATE-1). Chest, 146 (5). S. 1274 - 1286. AMSTERDAM: ELSEVIER SCIENCE BV. ISSN 0012-3692

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Abstract

BACKGROUND: Deficient nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate signaling results from endothelial dysfunction and may underlie impaired cardiac relaxation in patients with heart failure with preserved left ventricular ejection fraction (HFpEF) and pulmonary hypertension (PH). The acute hemodynamic effects of riociguat, a novel soluble guanylate cyclase stimulator, were characterized in patients with PH and HFpEF. METHODS: Clinically stable patients receiving standard HF therapy with a left ventricular ejection fraction. 50%, mean pulmonary artery pressure (mPAP) >= 25 mm Hg, and pulmonary arterial wedge pressure (PAWP). 15 mm Hg at rest were randomized to single oral doses of placebo or riociguat (0.5, 1, or 2 mg). The primary efficacy variable was the peak decrease in mPAP from baseline up to 6 h. Secondary outcomes included hemodynamic and echocardiographic parameters, safety, and pharmacokinetics. RESULTS: There was no significant change in peak decrease in mPAP with riociguat 2 mg (n = 10) vs placebo (n = 11, P = .6). However, riociguat 2 mg significantly increased stroke volume (1 9 mL [95% CI, 0.4-17]; P = .04) and decreased systolic BP (-12 mm Hg [95% CI, -22 to -1]; P = .03) and right ventricular end-diastolic area (-5.6 cm(2) [95% CI, -11 to -0.3]; P = .04), without significantly changing heart rate, PAWP, transpulmonary pressure gradient, or pulmonary vascular resistance. Riociguat was well tolerated. CONCLUSIONS: In patients with HFpEF and PH, riociguat was well tolerated, had no significant effect on mPAP, and improved exploratory hemodynamic and echocardiographic parameters.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Bonderman, Diana UNSPECIFIED UNSPECIFIED UNSPECIFIED Pretsch, Ingrid UNSPECIFIED UNSPECIFIED UNSPECIFIED Steringer-Mascherbauer, Regina UNSPECIFIED UNSPECIFIED UNSPECIFIED Jansa, Pavel UNSPECIFIED orcid.org/0000-0002-3711-7064 UNSPECIFIED Rosenkranz, Stephan UNSPECIFIED UNSPECIFIED UNSPECIFIED Tufaro, Caroline UNSPECIFIED UNSPECIFIED UNSPECIFIED Bojic, Andja UNSPECIFIED UNSPECIFIED UNSPECIFIED Lam, Carolyn S. P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Frey, Reiner UNSPECIFIED UNSPECIFIED UNSPECIFIED Kilama, Michael Ochan UNSPECIFIED UNSPECIFIED UNSPECIFIED Unger, Sigrun UNSPECIFIED UNSPECIFIED UNSPECIFIED Roessig, Lothar UNSPECIFIED UNSPECIFIED UNSPECIFIED Lang, Irene M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-425060
DOI:	10.1378/chest.14-0106
Journal or Publication Title:	Chest
Volume:	146
Number:	5
Page Range:	S. 1274 - 1286
Date:	2014
Publisher:	ELSEVIER SCIENCE BV
Place of Publication:	AMSTERDAM
ISSN:	0012-3692
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PRESERVED EJECTION FRACTION; SOLUBLE GUANYLATE-CYCLASE; ENDOTHELIAL DYSFUNCTION; PHOSPHODIESTERASE-5 INHIBITION; NITRIC-OXIDE; GUIDELINES; COMMUNITY; DIAGNOSIS; GENDER; TARGET Multiple languages Critical Care Medicine; Respiratory System Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/42506