Bone Marrow Cell Transplantation to Improve Heart Function in Individuals With End-Stage Heart Failure

• Functional status [ Time Frame: Measured 90 days post-intervention ] [ Designated as safety issue: Yes ]
  

• Echocardiographic assessments of myocardial size and function by transthoracic echocardiography with the LVAD at full support, and as tolerated at 1, 5, 10, and 15 minutes following initiation of hand pumping [ Time Frame: Measured at baseline, Days 45 and 90 post-intervention, every 60 days thereafter until transplant ] [ Designated as safety issue: Yes ]
  
• Six Minute Walk [ Time Frame: Measured at Days 45 and 90 post-intervention, every 60 days thereafter until transplant ] [ Designated as safety issue: Yes ]
  
• Duration of ability to tolerate wean [ Time Frame: Measured at Days 45 and 90 post-intervention, every 60 days thereafter until transplant ] [ Designated as safety issue: Yes ]
  
• Neuronal function (specialized centers only) [ Time Frame: Measured at Days 45 and 90 post-intervention, every 60 days thereafter until transplant ] [ Designated as safety issue: Yes ]
  
• Incidence of anti-HLA antibody sensitization while on LVAD support [ Time Frame: Measured at baseline, Days 7, 21, 45, and 90 days post-intervention, and every 60 days thereafter until transplant ] [ Designated as safety issue: Yes ]
  
• Incidence of serious adverse events [ Time Frame: Event driven ] [ Designated as safety issue: Yes ]
  
• Neovascularization and cardiomyocyte regeneration [ Time Frame: Measured at LVAD implant, at transplant, and at autopsy (if applicable) ] [ Designated as safety issue: Yes ]
  
• Ability to tolerate wean from LVAD support for 30 minutes [ Time Frame: Measured at Days 45 and 90 post-intervention, every 60 days thereafter until transplant ] [ Designated as safety issue: Yes ]
  
• Relationship of age to quantity of CD34+ bone marrow cells [ Time Frame: Measured post-implant ] [ Designated as safety issue: Yes ]
  

Congestive heart failure affects 5 million people in the United States, and over 60,000 are diagnosed with end-stage heart failure. Treatment options for these individuals are extremely limited. Because of a limited supply of donor organs, fewer than 3,000 people receive heart transplants each year. LVADs are battery-operated devices that can act as a temporary solution until a donor heart becomes available. Upon being surgically implanted into a weakened heart, the LVAD mechanically pumps blood from the heart to the rest of the body. There are, however, serious risks associated with LVADs, including infection, blood clots, and stroke. Early removal of the LVAD may be possible by injecting stem cells to regenerate new heart cells and improve heart function. The purpose of this study is to compare the safety and effectiveness of two types of bone marrow cells -- bone marrow mononuclear cells (BMCs) and immunoselected CD34+ hematopoietic stem cells -- in improving heart function in individuals with end-stage heart failure.

This study will enroll individuals undergoing surgery to receive an LVAD. Participants will be randomly assigned to one of following three groups:

Group 1 (n=30): participants will undergo intramyocardial injection of bone marrow mononuclear cells (BMCs) during LVAD implantation

Group 2 (n=30): participants will undergo intramyocardial injection of immunoselected CD34+ hematopoietic stem cells during LVAD implantation

Group 3 (n=15): participants will undergo LVAD implantation

Prior to LVAD implantation, participants in Groups 1 and 2 will have a sample of bone marrow removed. Following LVAD implantation, study visits will occur at Days 45 and 90, and then every 60 days thereafter until participants receive a heart transplant. At each visit, participants will undergo a LVAD wean procedure, during which the mechanical pump of the LVAD will be gradually turned off, and the LVAD will be operated with a hand pump. The length of time that a participant tolerates the wean procedure will be evaluated. Heart size and function, blood flow, and nerve function will also be assessed. Some participants will undergo a 6-minute walk test. At the time of heart transplant surgery, the LVAD will be removed, and heart cell regeneration and heart function will be evaluated.