Inotropic therapy for refractory congestive heart failure with oral fenoximone (MDL-17,043): poor long-term results despite early hemodynamic and clinical improvement.
Thirteen male patients with NYHA class IV congestive heart failure refractory to conventional therapy were treated with oral fenoximone, a new imidazole compound with inotropic and vasodilator effects, for a mean duration of 11 weeks (range 2 to 34). On initial hemodynamic evaluation, the effects of oral fenoximone were comparable to those of the intravenous form and included a significant (p = .0001) increase in cardiac index (mean +/- SD) (1.7 +/- 0.4 to 3.0 +/- 0.7 liters/min/m2) and a significant (p = .0001) but modest decrease in pulmonary capillary wedge pressure (27 +/- 6 to 23 +/- 6 mm Hg), with only minor overall changes in heart rate and arterial blood pressure. Symptomatic improvement by at least one NYHA class was observed in all patients during the first week of therapy with fenoximone; however, severe and symptomatic congestive heart failure recurred in seven patients within an average of 8 weeks after initiation of therapy, resulting in death in all seven. Of the remaining six patients, two died suddenly at home within 3 weeks of initiation of therapy, one died from ventricular fibrillation in the hospital 7 weeks after initiation of therapy, and two died from noncardiac causes. One patient is currently alive with NYHA class II heart failure 21 weeks after the initiation of therapy. Partial or complete attenuation of hemodynamic efficacy of oral fenoximone during long-term administration was demonstrated during repeat hemodynamic evaluation in six of eight patients. We conclude that despite short-term hemodynamic and clinical benefits, oral fenoximone therapy in patients with NYHA class IV congestive heart failure does not produce sustained clinical or hemodynamic benefit and is associated with a high mortality.
Shah
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Amin
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Hulse
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Shellock
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Swan
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HJ
D000284:Administration, Oral; D000368:Aged; D017335:Enoximone; D005500:Follow-Up Studies; D006333:Heart Failure / Q000188:drug therapy*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects*; D013268:Stimulation, Chemical
D007093:Imidazoles; D017335:Enoximone