Left ventricular assist device and drug therapy for the reversal of heart failure

N Engl J Med. 2006 Nov 2;355(18):1873-84. doi: 10.1056/NEJMoa053063.

Abstract

Background: In patients with severe heart failure, prolonged unloading of the myocardium with the use of a left ventricular assist device has been reported to lead to myocardial recovery in small numbers of patients for varying periods of time. Increasing the frequency and durability of myocardial recovery could reduce or postpone the need for subsequent heart transplantation.

Methods: We enrolled 15 patients with severe heart failure due to nonischemic cardiomyopathy and with no histologic evidence of active myocarditis. All had markedly reduced cardiac output and were receiving inotropes. The patients underwent implantation of left ventricular assist devices and were treated with lisinopril, carvedilol, spironolactone, and losartan to enhance reverse remodeling. Once regression of left ventricular enlargement had been achieved, the beta2-adrenergic-receptor agonist clenbuterol was administered to prevent myocardial atrophy.

Results: Eleven of the 15 patients had sufficient myocardial recovery to undergo explantation of the left ventricular assist device a mean (+/-SD) of 320+/-186 days after implantation of the device. One patient died of intractable arrhythmias 24 hours after explantation; another died of carcinoma of the lung 27 months after explantation. The cumulative rate of freedom from recurrent heart failure among the surviving patients was 100% and 88.9% 1 and 4 years after explantation, respectively. The quality of life as assessed by the Minnesota Living with Heart Failure Questionnaire score at 3 years was nearly normal. Fifty-nine months after explantation, the mean left ventricular ejection fraction was 64+/-12%, the mean left ventricular end-diastolic diameter was 59.4+/-12.1 mm, the mean left ventricular end-systolic diameter was 42.5+/-13.2 mm, and the mean maximal oxygen uptake with exercise was 26.3+/-6.0 ml per kilogram of body weight per minute.

Conclusions: In this single-center study, we found that sustained reversal of severe heart failure secondary to nonischemic cardiomyopathy could be achieved in selected patients with the use of a left ventricular assist device and a specific pharmacologic regimen.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenergic beta-2 Receptor Agonists
  • Adrenergic beta-Agonists / therapeutic use*
  • Adult
  • Blood Pressure
  • Cardiac Output
  • Cardiomyopathy, Dilated / drug therapy*
  • Cardiomyopathy, Dilated / mortality
  • Cardiomyopathy, Dilated / physiopathology
  • Cardiomyopathy, Dilated / surgery*
  • Cardiovascular Agents / therapeutic use*
  • Clenbuterol / therapeutic use
  • Combined Modality Therapy
  • Female
  • Heart Transplantation
  • Heart-Assist Devices* / adverse effects
  • Humans
  • Male
  • Middle Aged
  • Oxygen / blood
  • Prospective Studies
  • Prosthesis Failure
  • Survival Rate

Substances

  • Adrenergic beta-2 Receptor Agonists
  • Adrenergic beta-Agonists
  • Cardiovascular Agents
  • Oxygen
  • Clenbuterol