Daniel Sürder1, Robert Manka2, Tiziano Moccetti2, Viviana Lo Cicero2, Maximilian Y Emmert2, Catherine Klersy2, Sabrina Soncin2, Lucia Turchetto2, Marina Radrizzani2, Michel Zuber2, Stephan Windecker2, Aris Moschovitis2, Ines Bühler2, Sebastian Kozerke2, Paul Erne2, Thomas F Lüscher2, Roberto Corti2. 1. From the Department of Cardiology, Cardiovascular Center (D.S., R.M., M.Z., I.B., P.E., T.F.L., R.C.) and Clinic for Cardiac Surgery, Cardiovascular Center (M.Y.E.), University Hospital Zurich, Zurich, Switzerland; Department of Cardiology, Fondazione Cardiocentro Ticino, Lugano, Switzerland (D.S., T.M., V.L.C., S.S., L.T., M.R.); Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland (R.M., S.K.); IRCCS Fondazione Policlinico San Matteo, Servizio di Biometria e Statistica, Pavia, Italy (C.K.); Department of Cardiology, Cantonal Hospital, Lucerne, Switzerland (M.Z., P.E.); and Department of Cardiology, Bern University Hospital, Bern, Switzerland (S.W., A.M.). daniel.suerder@cardiocentro.org. 2. From the Department of Cardiology, Cardiovascular Center (D.S., R.M., M.Z., I.B., P.E., T.F.L., R.C.) and Clinic for Cardiac Surgery, Cardiovascular Center (M.Y.E.), University Hospital Zurich, Zurich, Switzerland; Department of Cardiology, Fondazione Cardiocentro Ticino, Lugano, Switzerland (D.S., T.M., V.L.C., S.S., L.T., M.R.); Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland (R.M., S.K.); IRCCS Fondazione Policlinico San Matteo, Servizio di Biometria e Statistica, Pavia, Italy (C.K.); Department of Cardiology, Cantonal Hospital, Lucerne, Switzerland (M.Z., P.E.); and Department of Cardiology, Bern University Hospital, Bern, Switzerland (S.W., A.M.).
Abstract
RATIONALE: Intracoronary delivery of autologous bone marrow-derived mononuclear cells (BM-MNC) may improve remodeling of the left ventricle (LV) after acute myocardial infarction (AMI). OBJECTIVE: To demonstrate long-term efficacy of BM-MNC treatment after AMI. METHODS AND RESULTS: In a multicenter study, we randomized 200 patients with large AMI in a 1:1:1 pattern into an open-labeled control and 2 BM-MNC treatment groups. In the BM-MNC groups, cells were either administered 5 to 7 days (early) or 3 to 4 weeks (late) after AMI. Cardiac magnetic resonance imaging was performed at baseline and after 12 months. The current analysis investigates the change from baseline to 12 months in global LV ejection fraction, LV volumes, scar size, and N-terminal pro-brain natriuretic peptide values comparing the 2 treatment groups with control in a linear regression model. Besides the complete case analysis, multiple imputation analysis was performed to address for missing data. Furthermore, the long-term clinical event rate was computed. The absolute change in LV ejection fraction from baseline to 12 months was -1.9±9.8% for control (mean±SD), -0.9±10.5% for the early treatment group, and -0.7±10.1% for the late treatment group. The difference between the groups was not significant, both for complete case analysis and multiple imputation analysis. A combined clinical end point occurred equally in all the groups. Overall, 1-year mortality was low (2.25%). CONCLUSIONS: Among patients with AMI and LV dysfunction, treatment with BM-MNC either 5 to 7 days or 3 to 4 weeks after AMI did not improve LV function at 12 months, compared with control. The results are limited by an important drop out rate. CLINICAL TRIAL REGISTRATION INFORMATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00355186.
RCT Entities:
RATIONALE: Intracoronary delivery of autologous bone marrow-derived mononuclear cells (BM-MNC) may improve remodeling of the left ventricle (LV) after acute myocardial infarction (AMI). OBJECTIVE: To demonstrate long-term efficacy of BM-MNC treatment after AMI. METHODS AND RESULTS: In a multicenter study, we randomized 200 patients with large AMI in a 1:1:1 pattern into an open-labeled control and 2 BM-MNC treatment groups. In the BM-MNC groups, cells were either administered 5 to 7 days (early) or 3 to 4 weeks (late) after AMI. Cardiac magnetic resonance imaging was performed at baseline and after 12 months. The current analysis investigates the change from baseline to 12 months in global LV ejection fraction, LV volumes, scar size, and N-terminal pro-brain natriuretic peptide values comparing the 2 treatment groups with control in a linear regression model. Besides the complete case analysis, multiple imputation analysis was performed to address for missing data. Furthermore, the long-term clinical event rate was computed. The absolute change in LV ejection fraction from baseline to 12 months was -1.9±9.8% for control (mean±SD), -0.9±10.5% for the early treatment group, and -0.7±10.1% for the late treatment group. The difference between the groups was not significant, both for complete case analysis and multiple imputation analysis. A combined clinical end point occurred equally in all the groups. Overall, 1-year mortality was low (2.25%). CONCLUSIONS: Among patients with AMI and LV dysfunction, treatment with BM-MNC either 5 to 7 days or 3 to 4 weeks after AMI did not improve LV function at 12 months, compared with control. The results are limited by an important drop out rate. CLINICAL TRIAL REGISTRATION INFORMATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00355186.
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