Effect of Bone Marrow-Derived Mononuclear Cell Treatment, Early or Late After Acute Myocardial Infarction: Twelve Months CMR and Long-Term Clinical Results.
BACKGROUND
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.


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.


BACKGROUND
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00355186.
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.
Daniel
D
Sürder
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.).
Robert
R
Manka
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.).
Tiziano
T
Moccetti
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.).
Viviana
V
Lo Cicero
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.).
Maximilian Y
MY
Emmert
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.).
Catherine
C
Klersy
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.).
Sabrina
S
Soncin
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.).
Lucia
L
Turchetto
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.).
Marina
M
Radrizzani
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.).
Michel
M
Zuber
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.).
Stephan
S
Windecker
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.).
Aris
A
Moschovitis
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.).
Ines
I
Bühler
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.).
Sebastian
S
Kozerke
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.).
Paul
P
Erne
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.).
Thomas F
TF
Lüscher
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.).
Roberto
R
Corti
D016026:Bone Marrow Transplantation / Q000379:methods* / Q000639:trends; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000637:transplantation*; D019028:Magnetic Resonance Imaging, Cine / Q000379:methods* / Q000639:trends; D008297:Male; D009203:Myocardial Infarction / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000628:therapy*; D013557:Switzerland / Q000453:epidemiology; D013997:Time Factors; D016896:Treatment Outcome
bone marrow; cell transplantation; magnetic resonance imaging; myocardial infarction; stem cell