Autologous Bone Marrow Mononuclear Cell Transplantation and Coronary Bypass Surgery for Treatment of Ischemic Heart Failure

............................................................................................................................. 5 List of original publications ............................................................................................... 7 Abbreviations .................................................................................................................... 8 1 Introduction .................................................................................................................. 11 2 Review of the literature ................................................................................................ 12 2.1 Heart failure ....................................................................................................................... 12 2.1.1 Epidemiology and etiology .................................................................................................. 12 2.1.2 Coronary artery disease ........................................................................................................ 12 2.1.3 Systolic and diastolic heart failure ....................................................................................... 13 2.1.4 Cardiac remodeling .............................................................................................................. 14 2.1.5 Symptoms and clinical course of heart failure ..................................................................... 15 2.1.6 Medical treatment for ischemic heart failure ....................................................................... 16 2.1.7 Interventional treatment for ischemic heart failure .............................................................. 17 2.1.8 Cardiac imaging of heart failure .......................................................................................... 19 2.2 Heart regeneration ............................................................................................................. 23 2.3 Cell therapy for heart failure ............................................................................................. 24 2.3.1 Bone marrow cells ............................................................................................................... 24 2.3.2 Timing ................................................................................................................................. 25 2.3.3 Cell delivery routes .............................................................................................................. 25 2.3.4 Other cell types .................................................................................................................... 26 3 Aims of the study .......................................................................................................... 29 4 Methods ........................................................................................................................ 30 4.1 Agreements and notifications ............................................................................................. 30 4.2 Patient selection .................................................................................................................. 30 4.3 Cell transplantation procedure .......................................................................................... 30 4.3.1 BMMC harvesting ............................................................................................................... 30 4.3.2 Randomization ..................................................................................................................... 31 4.3.3 Operation ............................................................................................................................. 31 4.3.3 Hemodynamic monitoring during surgery (Study II) ........................................................... 32 4.4 Intensive-care unit stay (Study II) ...................................................................................... 32 4.5 Follow-up ............................................................................................................................ 32 4.6 Cardiac MRI (Studies I, III, IV) ......................................................................................... 33 4.7 Nuclear imaging with SPECT and PET (Studies I, III) ..................................................... 33 4.7.1 Evaluation of nuclear imaging data ..................................................................................... 34 4.8 Laboratory parameters, NYHA class, and health-related quality of life (Studies I, II, IV) 35 4.9 Statistical analysis .............................................................................................................. 35 5 Results .......................................................................................................................... 36 5.1 Patient characteristics ........................................................................................................ 36 5.2 Perioperative safety of intramyocardial BMMC therapy (Study II) .................................. 38