lvad conditioning for cardiac recovery

Conditions: Heart Failure

Summary: the purpose of this study is to investigate the potential recovery of heart function in end-stage heart failure patients supported with a left ventricular assist device (lvad) through applying a myocardial conditioning protocol. during myocardial conditioning, lvad speed is reduced gradually in order to increase the work load of the heart. multiple previous studies have shown that interventions like this may improve heart function and give patients the opportunity for a better quality of life.

heart failure can be caused by various disorders, such as myocardial infarction, hypertension, viral infection, exposure to toxins, chemotherapy, or genetically transmitted muscular diseases. regardless of the etiology, these disorders initiate ventricular remodeling, an adaptive, compensatory process which becomes progressively maladaptive and the cause of functional and clinical deterioration, eventually leading to heart failure. local and systemic compensatory responses that initially allow surviving muscle to maintain hemodynamic function continue over time and due to this persistent compensatory over-activity the initially unaffected myocardium becomes dysfunctional. these compensatory responses to an abnormal cardiac load or myocardial injury involve several pathophysiological adaptations in the cardiac structure at the genetic, molecular, cellular, and tissue levels. furthermore, left ventricular pressure and volume overload has shown to alter metabolic substrate utilization, decrease mitochondrial function and reduce energy production in the failing heart. mechanical circulatory support with lvad has become a standard bridge to cardiac transplantation, and has also been approved in the united states as permanent (destination) therapy for selected patients presenting with end-stage heart failure. clinical experience with lvad support has shown that it can reverse the complex process of chronic left ventricular remodeling to a point where a subset of patients could be weaned from the device after restoration of basic cardiac function. lvad-induced mechanical unloading of the failing heart leads to reduced mitochondrial density, structure and function, and interventions that enhance mitochondrial biogenesis, function and structure, such as controlled cardiac reloading may enhance lvad-induced myocardial reverse remodeling and cardiac recovery. this study is designed to investigate gradual reduction in lvad speed within the range defined by the assist device manufacturer's manual as appropriate for regular clinic use, to determine the effect on reverse remodeling and myocardial recovery in end-stage heart failure patients.

Eligibility criteria:
inclusion criteria: * diagnosed with heart failure undergoing lvad implantation as a bridge to transplant * enrolled in the effects of mechanical unloading on myocardial function and structure study (irb 30622) exclusion criteria: * neither the subject nor the subject's representative is willing to provide written consent for participation * subjects with adverse events leading to hospitalization during the optimum unloading phase are excluded from participation in the controlled reloading phase

Keywords: lvad cardiac recovery