Chronic infusion of dobutamine and nitroprusside in patients with end-stage heart failure awaiting heart transplantation: safety and clinical outcome

Background: in patients with severe heart failure additional therapeutic su pport with intravenous inotropic or vasodilator drugs is frequently employe d in an attempt to obtain hemodynamic and clinical control. No data compari ng the use and efficacy of chronic intravenous inotropic and vasodilator th erapy in patients with advanced heart failure are available. Aims: we evalu ated, in a group of patients with advanced heart failure undergoing chronic infusion with dobutamine or nitroprusside, in addition to optimized oral t herapy, (1) the safety of chronic infusion, (2) the efficacy of both drugs in managing unloading therapy and (3) clinical outcome of the two therapeut ic strategies. Methods: one hundred and thirteen patients receiving optimiz ed oral therapy, in functional class III/IV with symptoms and signs of refr actory heart failure and requiring additional pharmacological support with either intravenous dobutamine or nitroprusside were evaluated. Clinical and therapeutic management and clinical outcome of the two groups were conside red. Results: dobutamine was administered for 12 h/day for 20 +/- 23 days a t a dosage of 7 +/- 3 mug/kg/min to 43 patients. The mean dose of nitroprus side was 0.76 +/- 0.99 mug/kg/min. The mean duration of use of this drug, a dministered as a 12-h/day infusion was 22 +/- 38 days. Nitroprusside infusi on allowed greater doses of short-term ACE-inhibitors to be used compared t o pre-infusion (ACE-inhibitor dose: 55 +/- 30 mg/day vs. 127 +/- 30 mg/day P < 0.0001) and during dobutamine infusion (ACE-inhibitor dose: 85 +/- 47 m g/day vs. 127 +/- 30 mg/day P < 0.002). Nitroprusside unlike dobutamine sig nificantly improved the NYHA functional class. Of the 113 patients, 109 (97 %) had a cardiac event during a mean follow-up of 337 +/- 264 days. Forty-f our patients required hospitalization for worsening congestive heart failur e, 45/113 (39%) patients died during the follow-up and 27/113 (24%) patient s had a heart transplant in status one. Hospitalization, because of worseni ng heart failure was less frequent in the nitroprusside than in the dobutam ine subgroup [29/51 (57%) vs. 19/22 (86%) P < 0.02]. The overall mortality was 28% (20/70) in the nitroprusside group and 58% (25/43) in the dobutamin e group (odds ratio 0.33 CI 0.16 to 0.73 P < 0.006). In the group treated w ith nitroprusside, heart transplantation in status one was performed in 16/ 33 patients (48%), while in the dobutamine group this was done in 11/14 pat ients (78%) (odds ratio 0.25 CI 0.06-1.02 P < 0.06). There was a significan t reduction in the combined end-point of mortality/heart transplantation in status one in patients treated with nitroprusside compared to those treate d with dobutamine (36/70 (51%) vs. 36/43 (84%) - (odds ratio 0.34 CI 0.14-0 .80 P < 0.01). The incidence of adverse events in the patients treated with nitroprusside was similar to that in those treated with dobutamine (20% vs . 17% P = ns). Conclusions: for patients awaiting heart transplantation chr onic intermittent nitroprusside infusions are more effective and safer than dobutamine in relieving symptoms, facilitating unloading therapy managemen t and improving survival. Whether chronic intermittent infusion of nitropru sside could represent a feasible medical strategy in out-patients with seve re heart failure remains to be investigated. (C) 2001 European Society of C ardiology. All rights reserved.