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Autologous BON e Marrow Mononucleated Cell Infusion for A cute M yocardial I nfarction

Autologous BON e Marrow Mononucleated Cell Infusion for A cute M yocardial I nfarction in Patients with Severe Left Ventricular Dysfunction:. Results of the BONAMI trial (ClinicalTrials.gov number NCT00200707). J Roncalli, F Mouquet, C Piot, JN Trochu, Y Neuder, E Teiger,

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Autologous BON e Marrow Mononucleated Cell Infusion for A cute M yocardial I nfarction

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  1. Autologous BONe Marrow Mononucleated Cell Infusion for Acute Myocardial Infarction in Patients with Severe Left Ventricular Dysfunction: Results of the BONAMI trial (ClinicalTrials.gov number NCT00200707) J Roncalli, F Mouquet, C Piot, JN Trochu, Y Neuder, E Teiger, P Lemarchand* on behalf of the BONAMI investigators. Toulouse, Lille, Montpellier, Nantes, Grenoble, and Creteil University Hospital, FRANCE *Principal investigator and corresponding author

  2. receiving cell therapy at least 5 days after MI BACKGROUND • Previous trials that assessed the efficacy of intracoronary administration of autologous bone marrow cells (BMCs) after acute myocardial infarction have yield mixed results. • REPAIR-AMI: cell-based therapy seems to be more effective in patients with decreased left ventricular ejection fraction BONAMI trial, Madrid 2009 N Engl J Med 2006;355:1210-21

  3. AIM OF THE BONAMI TRIAL To assess the beneficial effectof cell therapy in patients with decreased left ventricular ejection fraction after acute myocardial infarction, and to identify predictive factors of successful therapy. BONAMI trial, Madrid 2009

  4. STUDY DESIGN Randomized, multicenter controlled trial 6 academic hospitals in France LV segmentation • Main inclusion criteria: • Inaugural acute MI • Single coronary lesion and successful angioplasty • - LVEF ≤ 45% • - Impairment of myocardial viability: > 2/17 non viable segments 1 7 2 6 13 8 12 17 14 16 11 15 9 5 3 10 Main exclusion criteria: - Multivessel disease - Drug eluting stent 4 AHA Writing Group on Myocardial Segmentation and Registration for Cardiac Imaging. Cerqueira MD et al, Circ 2002;105:539-542. BONAMI trial, Madrid 2009

  5. Short- axis apical median basal M0 M3 100% 50% 0% PRIMARY ENDPOINT • Myocardial viability at 3 months after MI evaluated by resting Thallium 201-SPECT - Criterion for cell therapy success: viability improvement of ≥ 2/17 segments(2 non viable become viable) - All measurements were performed by 2 blinded investigators of an independent core lab. BONAMI trial, Madrid 2009

  6. DESIGN OF THE BONAMI TRIAL Day 0 Acute MI, Primary angioplasty Echo LVEF ≤ 50% (n= 122) Day 0-4 SPECT and radionuclide angio Day 4-7 (n= 21) Myocardial viability, or LVEF >45% >2/17 non viable segments and LVEF ≤45% Randomization (n=101)  Diabetes  Revascularization < 12h Control (n= 49) BMC (n= 52) Day 7-10 BM harvest Intra coronary injection SPECT, radionuclide angio Month 3 BONAMI trial, Madrid 2009

  7. CELL THERAPY PROCEDURE • Cell therapy product: • 50 cc of bone marrow were harvested under local anesthesia • Bone marrow mononucleated cells were isolated by ficoll gradient • 100 x 106 autologous mononucleated cells (in 10cc) • Intra coronary cell injection: • The same day as BM collection • Mean delay btw acute MI and BMC infusion: 9.3 ± 1.7 days BONAMI trial, Madrid 2009

  8. RESULTS: Baseline Characteristics BONAMI trial, Madrid 2009

  9. 3 4 % 1 6 % RESULTS: Assessment of Cell Therapy Success - Prespecified criterion of cell therapy success = 2 non viable segments becoming viable 3 months after myocardial infarction ≥ 2/17 segments 4 0 p=0.06 n= 16/47 3 0 Percentage of patients 2 0 n= 7/43 1 0 0 control BMC - The number of patients with myocardial viability improvement was twice greater in the BMC group BONAMI trial, Madrid 2009

  10. Control P<0.01 BMC P<0.01 60 0 6 55 5 5 50 5 0 45 4 5 40 4 LV Ejection Fraction (%) 0 35 3 5 30 0 3 25 2 5 20 0 2 15 1 5 10 1 0 Day 0 3 Mo Day 0 3 Mo J0 J0 3 Mo 3 Mo Time after myocardial infarction p=0.62 = + 4.3% = + 3.3% Secondary Endpoint: Change of Ejection Fraction BONAMI trial, Madrid 2009

  11. . Tobacco status: non smoker, former smoker Tobacco status: smoker 4 , 5 4 . 5 n=9 Control 4 4 BMC 3 . 5 3 , 5 3 3 2.89 n = 4 2 . 5 2 , 5 (95% IC) increase in viable segment number n = 8 n=12 2 2 n = 5 1 . 5 1 , 5 n=3 n=19 n=17 1 0.88 1 1 0.8 0.83 0.5 0.53 0 . 5 5 0.58 0 0 n o y e s n o y e s Segment(s) with no-reflow Segment(s) with no-reflow PREDICTIVE FACTORS OF CELL THERAPY SUCCESS Multiple linear regression (n=77) Significant interaction between Tobacco, no-reflow and treatment group (p=0.01)

  12. CONCLUSION - The BONAMI trial is a randomized multicenter trial aimed to investigate the beneficial effect of coronary injection of autologous BMC on myocardial viability as a primary endpoint. - In this trial, coronary autologous BMC injection, 9 days after acute MI, to patients with low EF, failed to reach the primary endpoint, although a strong trend was observed. - The negative impact of active smokingand relative role of no-reflow on myocardial viability after cardiac cell therapy should be further documented. BONAMI trial, Madrid 2009

  13. Nantes - P. Lemarchand - J-N. Trochu - D. Crochet - A. Tirouvanziam - A. Bammert - Y. Goueffic - G. Lamirault - V. Probst - S. Abbey - F. Valette - J Hélias - C. Perigaud - V. Forest - M. Audrain - C. Hémont - G. Follea - J-M. Nguyen - B Delasalle Lille - F. Mouquet - E. Van Belle - S. Susen - P-V. Ennezat - T. Le Tourneau - V. Gaxotte - C. Foucher - J-P. Jouet - F. Villard - I. Yakoub-Agha - J-P. Bérégi - P. Asseman - J-J. Bauchart - B. Jude Toulouse - J. Roncalli - M. Galinier - A. Parini - P. Bourin - A. Huynh - M. Attal - D. Carrié - M. Elbaz - JM. Fauvel - P. Massabuau - R. Cagnac - MJ. Allibeli-Chemarin - V. Chabbert - H. Rousseau - L. Daudé - H. Coulier - S. Cappellesso-Fleury - C. Rage - J. Gaudé Grenoble - Y. Neuder - G. Vanzetto - M. Favrot - MJ. Richard - C. Saunier - D. Fagret - A. Calizzano - JY. Cahn - CE. Bulabois - F.Garban - F. Thony - S. Mouret - S. Bouzon H. Mondor - E. Teiger - J-L. Dubois-Randé - P. Le Corvoisier - S. Champagne - L. Boudali - O. Montagne - JL. Monin - J. Rosso - JF. Deux - C. Focseneanu - ML. Bourhis Montpellier - Ch. Piot - B. Klein - ZH. Lu - M. Baudard - JF. Rossi - D. Dietz - JC. Macia - D. Mariano-Goulart SPECT core lab - D. Agostini - A. Manrique Sponsors: Ministère de la Santé, Fondation de France, Association Française contre les Myopathies (AFM)

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