LVAD Conditioning for Cardiac Recovery

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.

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

- Neither the subject nor the subject's representative understands spoken English

- Subjects with adverse events leading to hospitalization during the optimum unloading
phase are excluded from participation in the controlled reloading phase