Effects of a novel inotropic agent (OPC-18790) on systolic and diastolic function in patients with severe heart failure.
A double-blind placebo-controlled study to determine the acute hemodynamic and cardiac mechanical effects of the quinolinone derivative OPC-18790 was performed in 12 patients with New York Heart Association class III or IV congestive heart failure. Simultaneous echocardiographic, Doppler, and invasive hemodynamic studies were performed before and after a 6-hour intravenous infusion of drug at 2.5, 5.0, or 10.0 micrograms/kg/min or of placebo. OPC-18790 (mean dose 5.9 +/- 3.5 mg) caused significant increases in left ventricular (LV) ejection fraction (15% +/- 4% vs 23% +/- 5%; p < 0.05) and cardiac index (1.7 +/- 0.4 vs 2.5 +/- 0.6 L/min/m2; p < 0.05) and a rightward and upward shift in the stress-shortening relation. LV end-diastolic volume and heart rate were unchanged. LV filling and posterior LV wall thinning rates from digitized M-mode echocardiographic studies (0.49 +/- 0.16 vs 0.75 +/- 0.21 cm/sec and 2.0 +/- 0.9 vs 3.0 +/- 1.4 cm/sec, respectively; both p < 0.05), transmitral deceleration time (67 +/- 24 vs 81 +/- 19 msec, p < 0.05), and atrial filling fraction (31.0% +/- 11.2% vs 38.9% +/- 13.9%, p < 0.05) increased with OPC-18790 infusion. Despite a significant decrease in pulmonary capillary wedge pressure (28 +/- 9 vs 18 +/- 10 mm Hg) there was no change in the velocity-time integral of early diastolic filling (53 +/- 12 vs 59 +/- 22 cm), suggesting improved LV relaxation. Hemodynamics and parameters of LV function were unchanged in the 3 patients receiving placebo.(ABSTRACT TRUNCATED AT 250 WORDS)
Hoit
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BD
Department of Internal Medicine, University of Cincinnati Medical Center, OH 45267-0542.
Burwig
S
S
Eppert
D
D
Bhat
G
G
Walsh
R A
RA
D000328:Adult; D000368:Aged; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003971:Diastole / Q000187:drug effects*; D004311:Double-Blind Method; D004452:Echocardiography; D005260:Female; D006325:Heart Atria / Q000187:drug effects; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D015363:Quinolones / Q000494:pharmacology / Q000627:therapeutic use*; D015635:Radionuclide Ventriculography; D013318:Stroke Volume / Q000187:drug effects; D013599:Systole / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects*
D002316:Cardiotonic Agents; D015363:Quinolones; C077543:toborinone