LV-assist Device: Bridge to Myocardial Recovery?
Abstract & Commentary
By Michael H. Crawford, MD
Sources: Birks EJ, et al. Reversal of severe heart failure with a continuous-flow left ventricular assist device and pharmacological therapy: A prospective study. Circulation. 2011;123:381-390; Maybaum S. Cardiac recovery during continuous-flow left ventricular assist device support: Some good news from across the Atlantic. Circulation. 2011;123:355-357.
The heartmate ii left ventricular assist device (LVAD) is a continuous flow device compared to the pulsatile flow Heartmate I. It is smaller, less traumatic, quieter, and more durable than the prior LVAD. These investigators from the Harefield Hospital in the United Kingdom implanted 33 of these new devices over a 3-year period in patients hospitalized for severe heart failure requiring LVAD support. Twenty-three of these patients had non-ischemic dilated cardiomyopathy and were considered candidates for a two-staged recovery protocol. The first stage consisted of maximal medical therapy with ACE inhibitors, angiotensin II blockers, aldosterone antagonists, beta-blockers, and digoxin. When maximum reversed LV remodeling was achieved by echocardiography, the beta blocker was switched to a beta 1 blocker and clenbuterol was administered to stimulate physiologic hypertrophy. When prespecified hemodynamic and echocardiographic criteria of myocardial recovery were met, LVAD explantation was performed and the stage one medications were resumed.
Twenty patients survived LVAD placement and are the subjects of this report. The mean age of the 20 patients was 35 years and 16 were men. Preoperatively, mean cardiac index was 1.44 mm/m2, pulmonary wedge pressure was 32 mmHg, and ejection fraction was 15%. Explanation criteria were met in 12 patients after a mean of 286 days, and their 3-year survival was 83%. Both deaths (2 of 12) were within the first 30 days after explantation. In the 10 survivors, no heart failure occurred on maximal drug therapy in the 3 years of follow-up. The authors concluded that up to one half of patients with severe heart failure due to dilated non-ischemic cardiomyopathy can be bridged to recovery with a Heartmate II and maximal medical therapy.
Commentary
The shortage of donor hearts has increased efforts to mechanically support selected heart failure subjects and try to stimulate myocardial recovery. Use of the older generation pulsatile LVADs has shown variable recovery in up to 25% of patients with non-ischemic cardiomyopathy. This report suggests that up to one half of such patients may be recoverable with the newer continuous flow LVADs and maximal medical therapy. This is encouraging news and opens up a whole new dynamic in severe heart failure management.
The caveat is that this is a small group of relatively young (16 to 58 years) patients who have non-ischemic dilated cardiomyopathy. Also, two-thirds of them had heart failure symptoms for < 6 months. On the other hand, they had severe LV dysfunction (EF 7%-34%) and were on at least one positive inotropic agent intravenously. The majority of patients in the United States with advanced heart failure have ischemic cardiomyopathy and often have less advanced systolic dysfunction, but advanced diastolic dysfunction. Thus, this approach may only apply to a minority of advanced U.S. heart-failure patients.
This study did not establish that the new continuous flow LVADs are superior to the older pulsatile ones with regard to outcomes, since LVAD therapy was coupled with aggressive medical therapy and there was no comparison group. Maximum tolerated doses of ACE inhibitors, angiotensin II blockers, aldosterone blockers, beta-blockers and digoxin were used in Phase 1. Phase 2 continued these agents, but switched carvedilol, a non selected beta blocker, to the beta I selective blocker bisoprolol and added the beta agonist clenbuterol at 25 times the usual asthma therapy dose, to stimulate physiologic hypertrophy of the LV. The importance of Phase 2 is difficult to ascertain from the study and Clenbuterol is not available in the United States. Another way to potentially increase physiologic hypertrophy is to decrease the LVAD continuous flow to allow the LV to open the aortic valve and experience afterload.
Perhaps the most remarkable thing about this study was the demonstrated durability of the recovery in those who survived explantation. In more than 3 years of follow-up, there were no deaths, transplantation, or heart failure recurrences in these patients. Thus, it would appear that these patients completely recovered. Of course they were still on medical therapy, and it is not known if they would have normal LV function off medications. Also, we do not know if these results could be obtained in a similar group of patients treated with a different protocol. The promise of this approach stimulated a U.S. Harefield Recovery Protocol Study (HARPS) which will be reported shortly.