Treatment strategies for myocardial recovery in heart failure

Abstract

Heart failure is a progressive disorder characterized by adverse left ventricular remodeling. Until recently, this has been thought to be an irreversible process. Mechanical unloading with a left ventricular assist device (LVAD), particularly if combined with neurohormonal blockade with heart failure medications, can lead to a reversal of the heart failure phenotype, a process called "reverse remodeling." Reverse remodeling refers to the regression of pathologic myocardial hypertrophy and improvement in LV chamber size that can occur in response to treatment. Myocardial recovery is the sustained normalization of structural, molecular, and hemodynamic changes sufficient to allow explant of the LVAD. Despite the fact that reverse remodeling is commonly seen in LVAD patients in clinical practice, myocardial recovery sufficient to allow device explantation is still rare. Previous experience suggests that young patients with short duration of heart failure and less myocardial fibrosis may be more likely to recover. Alternatively, it may just be that clinicians make a greater effort to recover these subgroups. A combined approach of mechanical unloading with LVADs and pharmacological management, together with regular testing of underlying myocardial function with the pump reduced to a speed at which it is not contributing, can increase the frequency of sustained recovery from heart failure. The goal is to achieve optimal unloading of the myocardium, combined with pharmacologic therapy aimed at promoting reverse remodeling. Myocardial recovery must be considered as a therapeutic target. Clinical variables such as pump speed and blood pressure must be optimized to promote maximal unloading, leading to reverse remodeling and myocardial recovery. Frequent echocardiographic and hemodynamic evaluation of underlying myocardial function must be performed. The combination of LVAD therapy with optimal neurohormonal blockade appears promising as an approach to myocardial recovery. In addition, there is a growing body of translational research which, when combined with LVADs, may further promote more durable recovery. Strategies to thicken the myocardium to enhance the durability of recovery prior to explantation, such as clenbuterol (which induces "physiological hypertrophy"), or intermittently reducing the pump speed to increase myocardial load may be beneficial. Emergence of cardiac stem cells and alternative biologic agents, when added to current therapies, may have a complementary role in promoting and maintaining myocardial recovery. This review will summarize both current strategies and emerging therapies.