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Can an LVAD plus Drugs Reverse Advanced Systolic Heart Failure?

A British study showed great promise for this strategy, despite lack of a control group and other limitations.

Advanced systolic heart failure (HF) is generally progressive and is associated with extremely high mortality rates. Left-ventricular assist devices (LVADs), which mechanically unload the left ventricle, can result in reverse LV remodeling and improve functional capacity. However, mortality rates in clinical LVAD trials remain high, and relatively few LVAD recipients proceed to successful LVAD explantation.

In a single-center, nonrandomized study funded partly by an LVAD manufacturer, researchers in Britain assessed outcomes with LVAD therapy as a platform for multidrug HF treatment. They enrolled 24 patients with nonischemic cardiomyopathy and advanced systolic HF that was unresponsive to intensive medical therapy including inotropes. The study did not include a control group. The primary analysis excluded 4 severely ill patients who underwent LVAD implantation for compassionate use and 5 patients who were unable to tolerate the drug regimen.

After LVAD implantation, the remaining 15 patients received a combination of lisinopril, losartan, spironolactone, and the nonselective ß-blocker carvedilol. After achieving maximal regression of LV dilatation, patients received clenbuterol, a selective ß₂-agonist intended to reduce myocardial atrophy due to hemodynamic unloading, and carvedilol was replaced with the selective ß₁-blocker bisoprolol. If adequate recovery of LV systolic function and regression of LV enlargement occurred with drug therapy, the LVAD was explanted, and the original four-drug regimen was reinstituted.

Of the 15 patients who tolerated the drug regimen, 4 required heart transplantation. Of the 11 who underwent LVAD explantation, 1 died shortly thereafter, and another died of cancer more than 2 years later. The remaining 9 patients survived through 4-year follow up with a mean LV ejection fraction of 64% and excellent quality-of-life scores.

Comment: Although excluding patients who did not tolerate the drug regimen from the primary analysis inflates apparent success rates, a remarkable proportion of patients with advanced systolic HF experienced sustained recovery of myocardial function in this study. Given the design, however, the data cannot conclusively support the tested strategy. Furthermore, we don’t know which components of the multidrug regimen contributed to the benefit. Nevertheless, the editorialists are cautiously optimistic about the value of an LVAD as a platform to enable drug treatment to reverse LV remodeling. Randomized trials of this approach are anxiously anticipated, given that the prognosis for patients with advanced systolic HF is so poor.

— Frederick A. Masoudi, MD, MSPH

Published in Journal Watch Cardiology November 1, 2006

Citation(s):

Birks EJ et al. Left ventricular assist device and drug therapy for the reversal of heart failure. N Engl J Med 2006 Nov 2; 355:1873-84.

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• Medline abstract (Free)

Renlund DG and Kfoury AG. When the failing, end-stage heart is not end-stage. N Engl J Med 2006 Nov 2; 355:1922-5.

• Original article (Subscription may be required)
• Medline abstract (Free)