Acute Hemodynamic Effects of Riociguat in Patients With Pulmonary Hypertension Associated With Diastolic Heart Failure (DILATE-1)

摘要: 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 preserved left ventricular ejection fraction (HFpEF) pulmonary hypertension (PH). The acute hemodynamic effects of riociguat, a novel soluble cyclase stimulator, were characterized PH HFpEF. METHODS Clinically stable receiving standard HF therapy > 50%, mean artery pressure (mPAP) ≥ 25 mm Hg, arterial wedge (PAWP) 15 Hg at rest randomized to single oral doses placebo or riociguat (0.5, 1, 2 mg). primary efficacy variable was the peak decrease mPAP baseline up 6 h. Secondary outcomes included echocardiographic parameters, safety, pharmacokinetics. RESULTS There no significant change mg (n = 10) vs 11,P= .6). However, significantly increased stroke volume (+9 mL [95% CI, 0.4-17];P= .04) decreased systolic BP (−12 −22 −1];P= .03) right end-diastolic area (−5.6 cm2[95% −11 −0.3];P= .04), without changing rate, PAWP, transpulmonary gradient, vascular resistance. Riociguat well tolerated. CONCLUSIONS In HFpEF PH, tolerated, had effect on mPAP, improved exploratory parameters. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01172756; URL:www.clinicaltrials.gov