Reverse remodeling in heart failure ? fact or fiction?

Abstract

Maladaptive remodeling is associated with impaired prognosis in heart failure, and prevention of remodeling is an established therapeutic target. However, it is much less clear whether remodeling may be reversed once it has developed. In the last decade, anti-neuroendocrine therapy with ACE inhibitors, and even more potently, beta-blockers, was shown to improve surrogate markers for reverse remodeling, such as ejection fraction (EF), ventricular volumes, and mass. For beta-blockers, reverse molecular remodeling was also shown in biopsy specimens on the cellular and subcellular level. Both moderate endurance training and continuous positive airway pressure (CPAP) therapy in heart failure patients with sleep apnea induce reverse remodeling. Cardiac resynchronization therapy improves exercise capacity and quality of life in patients with ventricular dyssynchrony and is clearly associated with geometrical and functional reverse remodeling over time. Whether this translates into improved survival remains to be demonstrated. Surgical approaches for reverse remodeling, such as mitral valve replacement, aneurysmectomy, and volume reduction (Batista procedure) have been developed, but may also be associated with high perioperative mortality. Mechanical unloading of the failing ventricles by left ventricular assist systems (LVAD) induces well-characterized reverse remodeling on the cellular and subcellular level. However, persistent functional improvement in a significant subset of patients that would allow weaning form the device is still under debate. Novel, complementary approaches, such as gene transfer or stem cell therapy are under pre-clinical and clinical investigation. Taken together, reverse remodeling can be induced by pharmacological and non-pharmacological therapy and may serve as a surrogate parameter for therapeutic success in the individual patient. Since maladaptive remodeling is associated with poor prognosis, identification of novel strategies to reverse this process remains a promising target.