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Five-year follow-up after transepicardial implantation of autologous bone marrow mononuclear cells to ungraftable coronary territories for patients with ischaemic cardiomyopathy

^a Department of Cardiovascular Surgery, Ankara University School of Medicine, Ankara, Turkey
^b Department of Hematology, Ankara University School of Medicine, Ankara, Turkey
^c Department of Cardiology, Ankara University School of Medicine, Ankara, Turkey
^d Department of Nuclear Medicine, Ankara University School of Medicine, Ankara, Turkey
^e Department of Pathology, Ankara University School of Medicine, Ankara, Turkey

Received 14 November 2008; received in revised form 21 April 2009; accepted 21 April 2009.

^_* Corresponding author. Address: Department of Cardiovascular Surgery, Heart Centre, Ankara University School of Medicine, Dikimevi, Ankara 06340, Turkey. Tel.: +90 505 5279680; fax: +90 312 3625639. (Email: akarruchan{at}gmail.com).

Objective: Cell therapy for patients with ischaemic cardiomyopathy (IC) is still an open issue. We aimed to assess the long-term safety and therapeutic potency of autologous bone marrow mononuclear cell (ABMMNC) implantation into ungraftable coronary artery (UCA) territories in patients with IC. Methods: Bone marrow was aspirated from the iliac crest, and transepicardial ABMMNC implantation (n = 25, 24 men, aged 57 ± 7 years) as an adjunct to coronary artery bypass grafting (CABG) was performed into an area of reversible ischaemia within the territory of UCA (1.29 ± 0.09 x 10⁹ ABMMNCs). Control group (n = 25, 23 men, aged 59 ± 7 years) underwent incomplete CABG due to poor target vessel graftability. The study protocol consisted of coronary angiography, stress echocardiography, nuclear imaging and Holter monitoring at baseline and follow-up. The mean follow-up time was 988 ± 423 days. Results: There was no difference between the groups regarding postoperative complications and outcome. Overall 5-year survival for the ABMMNC group was 79 ± 10%, and 71 ± 12% for the controls (p = 0.48). Left ventricular ejection fraction (LVEF) at baseline was 24.8 ± 3.7 versus 25.9 ± 3.1 in the ABMMNC group and the controls, respectively. After 6 months, mean global LVEF increased to 36.3 ± 7.4 (p < 0.001) versus 31.4 ± 4.1 (p = 0.001), respectively. A significant difference was noted in delta LVEF between the groups (p < 0.001, 95% confidence interval (CI): 3.4–8.9) at 6 months, and (p = 0.001, 95% CI: 2.0–7.4) at 1 year. Accordingly, perfusion scores in UCA segments detected by single-photon emission computed tomography (SPECT) improved with ABMMNC therapy to 18.0 ± 24.4 from 7.1 ± 25.7 (p = 0.001 vs control UCA segments). Conclusion: Cellular therapy for IC within UCA could augment myocardial perfusion and contractility but does not improve overall survival. No adverse events were detected after cell therapy at mid-term follow-up.

Key Words: Heart failure • Stem cells • Ischaemia • Angiogenesis • Left ventricular function • Survival