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CLINICAL RESEARCH: CLINICAL TRIAL

The BALANCE Study

Clinical Benefit and Long-Term Outcome After Intracoronary Autologous Bone Marrow Cell Transplantation in Patients With Acute Myocardial Infarction

Department of Medicine, Division of Cardiology, Pneumology and Angiology, Heinrich-Heine-University of Düsseldorf, Düsseldorf, Germany

Manuscript received November 14, 2008; revised manuscript received February 18, 2009, accepted February 23, 2009.

^_* Reprint requests and correspondence: Dr. Muhammad Yousef, Department of Medicine, Division of Cardiology, Pulmonary Disease and Angiology, Heinrich-Heine-University of Düsseldorf, Moorenstrasse 5, 40225 Düsseldorf, Germany (Email: muhammad.yousef{at}med.uni-duesseldorf.de).

Objectives: The aim of this study was to investigate the quantitative amount of improvement of ventricular hemodynamic status, geometry, and contractility as well as the long-term clinical outcome of cell-treated patients after acute myocardial infarction (AMI).

Background: Animal experiments as well as clinical studies have demonstrated that autologous bone marrow cell (BMC) transplantation might improve ventricular function and prevent remodeling.

Methods: Sixty-two patients underwent intracoronary autologous BMC transplantation 7 ± 2 days after AMI. Cells were infused directly into the infarct-related artery. The control group consisted of 62 patients with comparable left ventricular (LV) ejection fraction (EF) and diagnosis. All patients had several examinations (e.g., coronary angiography, right heart catheterization, biplane left ventriculography, electrocardiogram [ECG] at rest and exercise, echocardiography, late potential [LP], heart rate variability [HRV], and 24-h Holter ECG). The therapeutic follow-up was performed 3, 12, and 60 months after BMC therapy.

Results: Three months after BMC therapy there was significant improvement of EF and stroke volume index. The infarct size was significantly reduced by 8%. Contraction velocities (lengths/second, volumes/second) increased significantly and the slope of the ventricular function curve (systolic pressure/end-systolic volume) became steeper. There was significant improvement of contractility in the infarct zone, as evidenced by a 31% increase of LV velocity of shortening (VCF), preferably in the border zone of the infarct zone. In contrast, the noninfarcted area showed no difference in VCF before and after BMC therapy. Furthermore, decreases of abnormal HRV, LP, and ectopic beats were documented after BMC therapy. Twelve and 60 months after BMC therapy the parameters of contractility, hemodynamic status, and geometry of the LV were stable. The exercise capacity of treated patients was significantly augmented, and the mortality was significantly reduced in comparison with the control group.

Conclusions: BMC therapy leads to significant and longstanding improvements of LV performance as well as quality of life and mortality of patients after AMI. After BMC therapy, no side effects were observed, showing that BMC therapy is safe.

Key Words: acute myocardial infarction • intracoronary cell therapy • remodeling

Abbreviations and Acronyms   AMI = acute myocardial infarction   BMC = bone marrow cell   ECG = electrocardiogram   EDV = end-diastolic volume   EF = ejection fraction   ESV = end-systolic volume   HRV = heart rate variability   LP = late potential   LV = left ventricle/ventricular   SVI = stroke volume index   VCF = velocity of circumferential fiber shortening

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