Emma J. Birks

Background—: We have previously shown that a specific combination of drug therapy and left ventricular assist device unloading results in significant myocardial recovery, sufficient to allow pump removal, in two thirds of patients with dilated cardiomyopathy receiving a Heartmate I pulsatile device. However, this protocol has not been used with nonpulsatile devices. Methods and Results—: We report the results of a prospective study of 20 patients who received a combination of angiotensin-converting enzymes, β-blockers, angiotensin II inhibitors, and aldosterone antagonists followed by the β ₂ -agonist clenbuterol and were regularly tested (echocardiograms, exercise tests, catheterizations) with the pump at low speed. Before left ventricular assist device insertion, patient age was 35.2±12.6 years (16 male patients), patients were on 2.0±0.9 inotropes, 7 (35) had an intra-aortic balloon pump, 2 were hemofiltered, 2 were ventilated, 3 had a prior Levitronix device, and 1 had extracorporeal membrane oxygenation. Cardiac index was 1.39±0.43 L · min ⁻¹ · m ⁻² , pulmonary capillary wedge pressure was 31.5±5.7 mm Hg, and heart failure history was 3.4±3.5 years. One patient was lost to follow-up and died after 240 days of support. Of the remaining 19 patients, 12 (63.2) were explanted after 286±97 days. Eight had symptomatic heart failure for ≤6 months and 4 for >6 months (48 to 132 months). Before explantation, at low flow for 15 minutes, ejection fraction was 70±7, left ventricular end-diastolic diameter was 48.6±5.7 mm, left ventricular end-systolic diameter was 32.3±5.7 mm, mV̇ o ₂ was 21.6±4 mL · kg ⁻¹ · min ⁻¹ , pulmonary capillary wedge pressure was 5.9±4.6 mm Hg, and cardiac index was 3.6±0.6 L · min ⁻¹ · m ⁻² . Estimated survival without heart failure recurrence was 83.3 at 1 and 3 years. After a 430.7±337.1-day follow-up, surviving explants had an ejection fraction of 58.1±13.8, left ventricular end-diastolic diameter of 59.0±9.3 mm, left ventricular end-systolic diameter of 42.0±10.7 mm, and mV̇ o ₂ of 22.6±5.3 mL · kg ⁻¹ · min ⁻¹ . Conclusions—: Reversal of end-stage heart failure secondary to nonischemic cardiomyopathy can be achieved in a substantial proportion of patients with nonpulsatile flow through the use of a combination of mechanical and pharmacological therapy.

Remodelling is the central feature that occurs in the progression of heart failure. However, unloading of the heart with a left ventricular assist device (LVAD) can lead to reversal of many of the remodelling changes even in patients with advanced heart failure. LVAD unloading can also lead to improved myocardial function and this improvement can be sufficient to allow removal of the device leaving the patient to lead a normal life. We review the molecular changes that have been demonstrated with LVAD unloading in patients bridged to transplantation and also those that have occurred in the myocardium of patients that have recovered their myocardial function enough to have the device removed. Changes in both the myocyte and the matrix are reviewed.

Patients with chronic advanced heart failure unloaded by left ventricular assist devices can show improvement in their myocardial function and some can show "reverse remodeling" to the extent that their myocardial function improves sufficiently for the device to be removed. Furthermore, recent data suggest that combining mechanical support with adjuvant drug therapy can increase the rate and proportion of recovery as well as its durability. This article will review the evidence for myocardial recovery in patients with chronic heart failure and whether it is a "real" phenomenon.

Left ventricular assist device (LVAD) insertion in patients with advanced heart failure with deteriorating clinical status is life saving, and LVADs are now being inserted into an increasing number of patients with advanced heart failure. They were initially inserted as a bridge to transplantation, and the decreased availability of donor hearts means that an increasing number of patients are requiring LVAD support for survival when their clinical status deteriorates. There is strong evidence that with LVAD unloading, particularly when combined with pharmacological treatment, the patients’ myocardial function can also recover, allowing device removal and avoiding the need for transplantation, immunosuppression and its associated complications. This indication, known as “bridge to recovery” is a newer and expanding indication. The future use of LVADs, particularly as survival continues to increase, is extending to their wider use as destination therapy, when the device is inserted lifelong as an alternative to transplantation, and this role is likely to increase further. LVAD technology is evolving quickly, survival is improving, the incidence of complications is decreasing and durability of the devices is improving.