Andréa Ferreira Haddad

Autologous bone-marrow mononuclear cell transplantation after acute myocardial infarction: comparison of two delivery techniques.

The objective of this study was to investigate safety and feasibility of autologous bone marrow mononuclear cells (BMMNC) transplantation in ST elevation myocardial infarction (STEMI), comparing anterograde intracoronary artery (ICA) delivery with retrograde intracoronary vein (ICV) approach. An open labeled, randomized controlled trial of 30 patients admitted with STEMI was used. Patients were enrolled if they 1) were successfully reperfused within 24 h from symptoms onset and 2) had infarct size larger than 10% of the left ventricle (LV). One hundred million BMMNC were injected in the infarct-related artery (intra-arterial group) or vein (intravenous group), 1% of which was labeled with Tc99m-hexamethylpropylenamineoxime. Cell distribution was evaluated 4 and 24 h after injection. Baseline MRI was performed in order to evaluate microbstruction pattern. Baseline radionuclide ventriculography was performed before cell transfer and after 3 and 6 months. All the treated patients were submitted to repeat coronary angiography after 3 months. Thirty patients (57 ± 11 years, 70% males) were randomly assigned to ICA (n = 14), ICV (n = 10), or control (n = 6) groups. No serious adverse events related to the procedure were observed. Early and late retention of radiolabeled cells was higher in the ICA than in the ICV group, independently of microcirculation obstruction. An increase of EF was observed in the ICA group (p = 0.02) compared to baseline. Injection procedures through anterograde and retrograde approaches seem to be feasible and safe. BMMNC retention by damaged heart tissue was apparently higher when the anterograde approach was used. Further studies are required to confirm these initial data.

Systolic function of patients with myocardial infarction undergoing autologous bone marrow transplantation

BACKGROUND Several studies have been published on the effect of bone-marrow stem cells on the left ventricle when acting on post- acute myocardial infarction remodeling. However, the results have been controversial. OBJECTIVE To carry out an echocardiographic analysis of the systolic function of patients with acute myocardial infarction after autologous mononuclear bone marrow cell transplantation (AMBMCT) as performed via the intracoronary and intravenous routes. METHODS This is an open-label, prospective, randomized study. INCLUSION CRITERIA patients admitted for ST-elevation acute myocardial infarction (MI) who had undergone mechanical or chemical reperfusion within 24 hours of the onset of symptoms and whose echocardiogram showed decreased segmental wall motion and fixed perfusion defect related to the culprit artery. Autologous bone marrow was aspirated from the posterior iliac crest under sedation and analgesia of the patients randomly assigned for the treatment group. After laboratory manipulation, intracoronary or intravenous injection of 100 x 106 mononuclear cells was performed. Echocardiography (Vivid 7) was used to assess ventricular function before and three and six months after cell infusion. RESULTS A total of 30 patients were included, 14 in the arterial group (AG), 10 in the venous group (VG), and six in the control group (CG). No statistical difference was found between the groups for the echocardiographic parameters studied. CONCLUSION Autologous mononuclear bone marrow cell transplantation did not improve the echocardiographic parameters of systolic function.FUNDAMENTO: Diversos estudos foram publicados sobre a acao de celulas tronco da medula ossea no ventriculo esquerdo, ao atuarem no remodelamento pos-infarto agudo do miocardio. Os resultados, no entanto, tem se mostrado controversos. OBJETIVO: Avaliar atraves do ecocardiograma a funcao sistolica de pacientes com infarto agudo do miocardio apos o Transplante Autologo de Celulas Mononucleares da Medula Ossea (TACMMO) atraves de duas vias injecao: intracoronariana e intravenosa. METODOS: Estudo aberto, prospectivo, randomizado. Foram incluidos pacientes admitidos por infarto agudo do miocardio (IAM) com supradesnivelamento do segmento ST e submetidos a reperfusao mecânica ou quimica, dentro de 24 horas apos o inicio dos sintomas, que apresentavam ao ecocardiograma reducao da contratilidade segmentar e defeito fixo da perfusao relacionada a arteria culpada pelo IAM. A medula ossea autologa foi aspirada da crista iliaca posterior sob sedacao e analgesia, nos pacientes randomizados para o grupo tratado. Apos manipulacao laboratorial, 100 milhoes de celulas mononucleares foram injetadas por via intracoronariana ou intravenosa. Utilizamos o ecocardiograma (Vivid 7) para avaliar a funcao ventricular antes e apos tres e seis meses da infusao de celulas. RESULTADOS: Foram incluidos trinta pacientes, 14 no grupo arterial (GA), dez no grupo venoso (GV) e seis no grupo controle (GC). Nao houve diferenca estatistica dos parâmetros ecocardiograficos estudados entre os grupos. CONCLUSAO: O transplante autologo de celulas mononucleares da medula ossea nao demonstrou melhora dos parâmetros ecocardiograficos da funcao sistolica.

Injeção intracoronariana de células tronco após infarto do miocárdio: subestudo da microcirculação

BACKGROUND The injection of stem cells in the context of acute myocardial infarction (AMI) has been tested almost exclusively by anterograde intra-arterial coronary (IAC) delivery. The retrograde intravenous coronary (IVC) delivery may be an additional route. OBJECTIVE To compare the cell distribution and retention pattern in the anterograde and retrograde routes. To investigate the role of microvascular obstruction by magnetic resonance imaging in cell retention by cardiac tissue after the injection of bone marrow mononuclear cells (BMMC) in AMI. METHODS This was a prospective, open label, randomized study. Patients with AMI who presented: (1) successful chemical or mechanical reperfusion within 24 hours of symptom onset and (2) infarction involving more than 10% of the left ventricle (LV) at the myocardial scintigraphy were included in the study. One hundred million BMMC were injected into the infarction-related artery through IAC route, or vein through the IVC route. One percent of the injected cells were labeled with 99mTc-hexamethyl-propylene-amine-oxime (99mTc-HMPAO). Cell distribution was evaluated at 4 and 24 hours after the myocardial scintigraphy injection. Cardiac magnetic resonance imaging was performed before cell injection. RESULTS Thirty patients were randomized into three groups. There were no serious adverse events related to the procedure. The early and late retention of labeled cells was higher in the IAC group than in IVC group, regardless of the presence of microcirculation obstruction. CONCLUSION The injection using the retrograde approach was feasible and safe. Cell retention by cardiac tissue was higher using the anterograde approach. More studies are needed to confirm these findings.

Multicenter double blind trial of autologous bone marrow mononuclear cell transplantation through intracoronary injection post acute myocardium infarction – MiHeart/AMI study

BackgroundMyocardial infarction remains as a major cause of mortality worldwide and a high rate of survivors develop heart failure as a sequel, resulting in a high morbidity and elevated expenditures for health system resources. We have designed a multicenter trial to test for the efficacy of autologous bone marrow (ABM) mononuclear cell (MC) transplantation in this subgroup of patients. The main hypothesis to be tested is that treated patients will have a significantly higher ejection fraction (EF) improvement after 6 months than controls.MethodsA sample of 300 patients admitted with ST elevation acute myocardial infarction (STEMI) and left ventricle (LV) systolic dysfunction, and submitted to successful mechanical or chemical recanalization of the infarct-related coronary artery will be selected for inclusion and randomized to either treated or control group in a double blind manner. The former group will receive 100 × 106 MC suspended in saline with 5% autologous serum in the culprit vessel, while the latter will receive placebo (saline with 5% autologous serum).ImplicationsMany phase I/II clinical trials using cell therapy for STEMI have been reported, demonstrating that cell transplantation is safe and may lead to better preserved LV function. Patients with high risk to develop systolic dysfunction have the potential to benefit more. Larger randomized, double blind and controlled trials to test for the efficacy of cell therapies in patients with high risk for developing heart failure are required.Trial RegisterThis trial is registered at the NIH registry under the number NCT00350766.

Função sistólica de pacientes com infarto miocárdico submetidos a transplante autólogo da medula óssea

BACKGROUND Several studies have been published on the effect of bone-marrow stem cells on the left ventricle when acting on post- acute myocardial infarction remodeling. However, the results have been controversial. OBJECTIVE To carry out an echocardiographic analysis of the systolic function of patients with acute myocardial infarction after autologous mononuclear bone marrow cell transplantation (AMBMCT) as performed via the intracoronary and intravenous routes. METHODS This is an open-label, prospective, randomized study. INCLUSION CRITERIA patients admitted for ST-elevation acute myocardial infarction (MI) who had undergone mechanical or chemical reperfusion within 24 hours of the onset of symptoms and whose echocardiogram showed decreased segmental wall motion and fixed perfusion defect related to the culprit artery. Autologous bone marrow was aspirated from the posterior iliac crest under sedation and analgesia of the patients randomly assigned for the treatment group. After laboratory manipulation, intracoronary or intravenous injection of 100 x 106 mononuclear cells was performed. Echocardiography (Vivid 7) was used to assess ventricular function before and three and six months after cell infusion. RESULTS A total of 30 patients were included, 14 in the arterial group (AG), 10 in the venous group (VG), and six in the control group (CG). No statistical difference was found between the groups for the echocardiographic parameters studied. CONCLUSION Autologous mononuclear bone marrow cell transplantation did not improve the echocardiographic parameters of systolic function.FUNDAMENTO: Diversos estudos foram publicados sobre a acao de celulas tronco da medula ossea no ventriculo esquerdo, ao atuarem no remodelamento pos-infarto agudo do miocardio. Os resultados, no entanto, tem se mostrado controversos. OBJETIVO: Avaliar atraves do ecocardiograma a funcao sistolica de pacientes com infarto agudo do miocardio apos o Transplante Autologo de Celulas Mononucleares da Medula Ossea (TACMMO) atraves de duas vias injecao: intracoronariana e intravenosa. METODOS: Estudo aberto, prospectivo, randomizado. Foram incluidos pacientes admitidos por infarto agudo do miocardio (IAM) com supradesnivelamento do segmento ST e submetidos a reperfusao mecânica ou quimica, dentro de 24 horas apos o inicio dos sintomas, que apresentavam ao ecocardiograma reducao da contratilidade segmentar e defeito fixo da perfusao relacionada a arteria culpada pelo IAM. A medula ossea autologa foi aspirada da crista iliaca posterior sob sedacao e analgesia, nos pacientes randomizados para o grupo tratado. Apos manipulacao laboratorial, 100 milhoes de celulas mononucleares foram injetadas por via intracoronariana ou intravenosa. Utilizamos o ecocardiograma (Vivid 7) para avaliar a funcao ventricular antes e apos tres e seis meses da infusao de celulas. RESULTADOS: Foram incluidos trinta pacientes, 14 no grupo arterial (GA), dez no grupo venoso (GV) e seis no grupo controle (GC). Nao houve diferenca estatistica dos parâmetros ecocardiograficos estudados entre os grupos. CONCLUSAO: O transplante autologo de celulas mononucleares da medula ossea nao demonstrou melhora dos parâmetros ecocardiograficos da funcao sistolica.

Función sistólica de pacientes con infarto miocárdico sometidos a transplante autólogo de la médula ósea

BACKGROUND Several studies have been published on the effect of bone-marrow stem cells on the left ventricle when acting on post- acute myocardial infarction remodeling. However, the results have been controversial. OBJECTIVE To carry out an echocardiographic analysis of the systolic function of patients with acute myocardial infarction after autologous mononuclear bone marrow cell transplantation (AMBMCT) as performed via the intracoronary and intravenous routes. METHODS This is an open-label, prospective, randomized study. INCLUSION CRITERIA patients admitted for ST-elevation acute myocardial infarction (MI) who had undergone mechanical or chemical reperfusion within 24 hours of the onset of symptoms and whose echocardiogram showed decreased segmental wall motion and fixed perfusion defect related to the culprit artery. Autologous bone marrow was aspirated from the posterior iliac crest under sedation and analgesia of the patients randomly assigned for the treatment group. After laboratory manipulation, intracoronary or intravenous injection of 100 x 106 mononuclear cells was performed. Echocardiography (Vivid 7) was used to assess ventricular function before and three and six months after cell infusion. RESULTS A total of 30 patients were included, 14 in the arterial group (AG), 10 in the venous group (VG), and six in the control group (CG). No statistical difference was found between the groups for the echocardiographic parameters studied. CONCLUSION Autologous mononuclear bone marrow cell transplantation did not improve the echocardiographic parameters of systolic function.FUNDAMENTO: Diversos estudos foram publicados sobre a acao de celulas tronco da medula ossea no ventriculo esquerdo, ao atuarem no remodelamento pos-infarto agudo do miocardio. Os resultados, no entanto, tem se mostrado controversos. OBJETIVO: Avaliar atraves do ecocardiograma a funcao sistolica de pacientes com infarto agudo do miocardio apos o Transplante Autologo de Celulas Mononucleares da Medula Ossea (TACMMO) atraves de duas vias injecao: intracoronariana e intravenosa. METODOS: Estudo aberto, prospectivo, randomizado. Foram incluidos pacientes admitidos por infarto agudo do miocardio (IAM) com supradesnivelamento do segmento ST e submetidos a reperfusao mecânica ou quimica, dentro de 24 horas apos o inicio dos sintomas, que apresentavam ao ecocardiograma reducao da contratilidade segmentar e defeito fixo da perfusao relacionada a arteria culpada pelo IAM. A medula ossea autologa foi aspirada da crista iliaca posterior sob sedacao e analgesia, nos pacientes randomizados para o grupo tratado. Apos manipulacao laboratorial, 100 milhoes de celulas mononucleares foram injetadas por via intracoronariana ou intravenosa. Utilizamos o ecocardiograma (Vivid 7) para avaliar a funcao ventricular antes e apos tres e seis meses da infusao de celulas. RESULTADOS: Foram incluidos trinta pacientes, 14 no grupo arterial (GA), dez no grupo venoso (GV) e seis no grupo controle (GC). Nao houve diferenca estatistica dos parâmetros ecocardiograficos estudados entre os grupos. CONCLUSAO: O transplante autologo de celulas mononucleares da medula ossea nao demonstrou melhora dos parâmetros ecocardiograficos da funcao sistolica.