The Experts below are selected from a list of 72 Experts worldwide ranked by ideXlab platform
Jay H Traverse - One of the best experts on this subject based on the ideXlab platform.
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consistently inconsistent bone marrow Mononuclear Stem Cell therapy following acute myocardial infarction
Circulation Research, 2016Co-Authors: Timothy D Henry, Lemuel A Moye, Jay H TraverseAbstract:A decade ago, 3 potentially groundbreaking trials were published that ushered in a new era of cardiovascular regenerative medicine.1–3 Using autologous bone marrow Mononuclear Cells (BMCs) in patients with acute ST-segment–elevation myocardial infarction (StemI), the trials were notable for their clear signal of safety, but discordant in their findings of benefit. Unfortunately, the 1-year results of the SWISS-AMI trial (Swiss Multicenter Intracoronary Stem Cells Study in Acute Myocardial Infarction)4 reported in this issue of Circulation Research again remind us about the inability of BMC therapy in patients with StemI to demonstrate consistent benefit. Why are there such disparate results in trials using a similar Cell product in a similar patient population? Article, see p 481 REPAIR-AMI (Reinfusion of Enriched Progenitor Cells and Infarct Remodeling in Acute Myocardial Infarction),1 remains the largest (n=204) and landmark trial to demonstrate that BMCs improve left ventricular (LV) function in patients after StemI. Patients were randomized to intracoronary delivery (using stop-flow technique) of BMC versus placebo 3 to 7 days after successful percutaneous coronary intervention (PCI). At 4 months, BMC-treated patients had a significant improvement in ejection fraction (EF) measured by left ventriculography at 4 months compared with placebo (5.5±7.3% versus 3.0±6.5%; P =0.01). In subgroup analyses, the improvement in LVEF was most significant in patients with a baseline LVEF below the median value of 48.9% and in patients treated ≥4 days post MI. At 1 year, there was a significant reduction in the prespecified combined clinical end point of death, recurrent MI, and any revascularization procedure (5.8% versus 1.9%; P =0.01). This trial generated excitement for the potential of cardiovascular Stem Cell therapy for AMI (as well as other cardiovascular diseases), but this excitement was tempered by the results of a second study, ASTAMI (Autologous Stem Cell Transplantation in …
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is the measurement of left ventricular ejection fraction the proper end point for Cell therapy trials an analysis of the effect of bone marrow Mononuclear Stem Cell administration on left ventricular ejection fraction after st segment elevation myoca
American Heart Journal, 2011Co-Authors: Timothy D Henry, Jay H Traverse, Lemuel A MoyeAbstract:Background The measurement of left ventricular (LV) ejection fraction (LVEF) is a strong predictor of cardiovascular adverse events and mortality in patients with LV dysfunction and has become the most common primary end point in cardiovascular Cell therapy trials after ST-segment elevation myocardial infarction (StemI). Multiple small trials have been performed using bone marrow Mononuclear Stem Cells (BMCs) in this setting with several meta-analyses demonstrating that BMC administration results in a small improvement in LVEF and may attenuate adverse LV remodeling. However, individual trial results have not been uniform, and the measurement of LVEF in these trials has relied on a variety of imaging techniques including LV angiograpnhy, single-photon emission computed tomography, echocardiography, or cardiac magnetic resonance imaging (cMRI). Methods Because cMRI provides the most accurate measurement of LVEF, LV volumes, and infarct size in patients after StemI, we reviewed all randomized cardiovascular Stem Cell trials (N = 10) that administered intracoronary BMCs versus placebo/control to 686 patients after primary percutaneous coronary intervention treatment of StemI that used cMRI as their principal imaging measurement of LVEF at baseline and 3 to 6 months later. Results Administration of BMCs was associated with a nonsignificant 0.9% ± 0.8% absolute increase in LVEF compared with placebo or control (95% CI −0.7 to 2.4) with a small but nonsignificant decrease LV end-diastolic and LV end-systolic volumes (LV end-diastolic volume −1.1 ± 1.5 mL/m2, LV end-systolic volume −1.6 ± 1.4 mL/m2). Although infarct size uniformly decreased over time, the reduction was not improved by BMC administration (−0.3 ± 1.7 g). Conclusions The benefit of BMC administration after StemI on LVEF, LV volumes, and infarct size is small when assessed by cMRI.
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results of a phase 1 randomized double blind placebo controlled trial of bone marrow Mononuclear Stem Cell administration in patients following st elevation myocardial infarction
American Heart Journal, 2010Co-Authors: Jay H Traverse, David H Mckenna, Karen L Harvey, Beth C Jorgenso, Rachel E Olson, Nancy Bostrom, Diane Kadidlo, John R LesserAbstract:Background Initial clinical trials from Europe have demonstrated that the administration of bone marrow–derived Mononuclear Cells (BMCs) may improve left ventricular (LV) function in patients following ST-elevation myocardial infarction (StemI). However, results from trials performed in the United States have not yet been presented. Methods We developed a phase 1, randomized, placebo-controlled, double-blind trial to investigate the effects of BMC administration in patients following StemI on recovery of LV function using cardiac magnetic resonance imaging (cMRI). Forty patients with moderate to large anterior StemIs were randomized to 100 million intracoronary BMCs versus placebo 3 to 10 days following successful primary angioplasty and stenting (percutaneous coronary intervention) of the left anterior descending coronary artery. Results Administration of BMC was safely performed in a high-risk cohort with minimal major adverse clinical event rates, and all patients remain alive to date. Left ventricular ejection fraction increased from 49.0% ± 9.5% at baseline to 55.2% ± 9.8% at 6 months by cMRI in the BMC group ( P P 2 in the BMC group at 6 months but increased significantly in the placebo group (17 mL/m 2 , P Conclusions This phase 1 study from the United States confirms the ongoing safety profile of BMC administration in patients following StemI. The improvement in LV ejection fraction at 6 months by cMRI in the Cell therapy group was not different than the placebo group. However, BMC administration had a favorable effect on LV remodeling at 6 months.
Fadi G Hage - One of the best experts on this subject based on the ideXlab platform.
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the effect of bone marrow Mononuclear Stem Cell therapy on left ventricular function and myocardial perfusion
Journal of Nuclear Cardiology, 2014Co-Authors: Kamel Sadat, Sameer Ather, Wael A Aljaroudi, Jaekyeong Heo, Ami E Iskandrian, Fadi G HageAbstract:Background Bone morrow Stem Cell (BMC) transfer is an emerging therapy with potential to salvage cardiomyocytes during acute myocardial infarction and promote regeneration and endogenous repair of damaged myocardium in patients with left ventricular (LV) dysfunction. We performed a meta-analysis to examine the association between administration of BMC and LV functional recovery as assessed by imaging.
Martin Mistrik - One of the best experts on this subject based on the ideXlab platform.
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Improvement in asymmetric dimethylarginine and oxidative stress in patients with limb salvage after autologous Mononuclear Stem Cell application for critical limb ischemia
Stem Cell Research & Therapy, 2017Co-Authors: Juraj Madaric, Martina Valachovicova, Ludovit Paulis, Jana Pribojova, Renata Mateova, Katarina Sebekova, Luba Postulkova, Terezia Madaricova, Maria Bucova, Martin MistrikAbstract:Background Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, acts as an inhibitor of angiogenesis and is associated with an increased risk of cardiovascular mortality. Administration of Stem Cells may affect endogenous mechanisms that regulate ADMA production and metabolism. The aim of the present study was to analyze ADMA concentration and changes in oxidative stress in patients with advanced critical limb ischemia (CLI) after bone marrow-derived Mononuclear Cell (BM-MNC) therapy. Methods Fifty patients (age 64 ± 11 years, 44 males, 6 females) with advanced CLI (Rutherford category 5 or 6) not eligible for revascularization were treated by intramuscular ( n = 25) or intra-arterial ( n = 25) injection of 40 ml BM-MNC concentrate. Patients with limb salvage and improved wound healing after 6 months were considered responders to Cell therapy. The concentrations of markers of oxidative stress and angiogenesis were analyzed before, and at 3 and 6 months after BM-MNC delivery. Results At 6-month follow-up, four patients died of reasons unrelated to Stem Cell therapy. Among the survivors, 80% (37/46) showed limb salvage and improved wound healing. At 6 months follow-up, ADMA concentration significantly decreased in patients with limb salvage (1.74 ± 0.66 to 0.90 ± 0.49 μmol/L, p
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improvement in asymmetric dimethylarginine and oxidative stress in patients with limb salvage after autologous Mononuclear Stem Cell application for critical limb ischemia
Stem Cell Research & Therapy, 2017Co-Authors: Juraj Madaric, Martina Valachovicova, Ludovit Paulis, Jana Pribojova, Renata Mateova, Katarina Sebekova, Luba Postulkova, Terezia Madaricova, Maria Bucova, Martin MistrikAbstract:Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, acts as an inhibitor of angiogenesis and is associated with an increased risk of cardiovascular mortality. Administration of Stem Cells may affect endogenous mechanisms that regulate ADMA production and metabolism. The aim of the present study was to analyze ADMA concentration and changes in oxidative stress in patients with advanced critical limb ischemia (CLI) after bone marrow-derived Mononuclear Cell (BM-MNC) therapy. Fifty patients (age 64 ± 11 years, 44 males, 6 females) with advanced CLI (Rutherford category 5 or 6) not eligible for revascularization were treated by intramuscular (n = 25) or intra-arterial (n = 25) injection of 40 ml BM-MNC concentrate. Patients with limb salvage and improved wound healing after 6 months were considered responders to Cell therapy. The concentrations of markers of oxidative stress and angiogenesis were analyzed before, and at 3 and 6 months after BM-MNC delivery. At 6-month follow-up, four patients died of reasons unrelated to Stem Cell therapy. Among the survivors, 80% (37/46) showed limb salvage and improved wound healing. At 6 months follow-up, ADMA concentration significantly decreased in patients with limb salvage (1.74 ± 0.66 to 0.90 ± 0.49 μmol/L, p < 0.001), in parallel with decreased tumor necrosis factor (TNF)-α (2.22 ± 0.16 to 1.94 ± 0.38 pg/ml, p < 0.001), and increased reduced glutathione (6.96 ± 3.1 to 8.67 ± 4.2 μmol/L, p = 0.02), superoxide dismutase activity (168 ± 50 to 218 ± 37 U/L, p = 0.002), and coenzyme Q10 concentration (468 ± 182 to 598 ± 283 μg/L, p = 0.02). The number of delivered BM-MNCs significantly correlated with the decrease in ADMA concentration at 3 months (p = 0.004, r = −0.48) and the decrease in TNF-α concentration at 6 months (p = 0.03, r = −0.44) after Cell delivery. ADMA or TNF-α improvement did not correlate with the number of applied CD34+ Cells, C-reactive protein concentration, leukocyte count, or the dose of atorvastatin. The therapeutic benefit of BM-MNC therapy is associated with reduced ADMA levels and oxidative stress. Regulation of the ADMA-nitric oxide axis and improved antioxidant status may be involved in the beneficial effects of Stem Cell therapy. The study was approved and retrospectively registered by ISRCTN registry, ISRCTN16096154 . Registered on 26 July 2016.
Robert Gordon - One of the best experts on this subject based on the ideXlab platform.
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The efficacy of bone marrow Mononuclear Stem Cell transplantation in patients with non-ischemic dilated cardiomyopathy—a meta analysis
Heart Failure Reviews, 2021Co-Authors: Nso Nso, Kaveh Rezaei Bookani, Sostanie Takota Enoru, Farshid Radparvar, Robert GordonAbstract:Cardiomyopathy refers to a wide spectrum of heart pathologies that interfere with normal heart function. Management options of patients with cardiomyopathy depended mainly on the severity of the condition. Lifestyle modifications and regular exercise together with a healthy diet is compatible for mild conditions. Severe conditions, however, rely on medications or surgery. Here, we aim to investigate the efficacy of bone marrow Mononuclear Stem Cell transplantation in patients with dilated cardiomyopathy. We searched PubMed, Scopus, and Cochrane CENTRAL for relevant clinical trials and excluded observational studies. We performed the quality assessment of this study following GRADE guidelines. The assessment of the risk of bias was performed by the Cochrane’s risk of bias tool. We present an analysis of the following outcomes: left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), and six minutes walking test. Data were pooled as mean differences (MD) and relative confidence intervals (CI). The analysis of 667 patients from 11 studies receiving autologous bone marrow Cell therapy for non-ischemic dilated cardiomyopathy is presented. A total of 338 patients were allocated to the treatment group, and 329 participants entered the control group. The mean age of the patients in the treatment group is 52.4 ± 4.3 years, while that of the control is 53.7 ± 3.7 years. Seven studies (14.18–23) reported transplantation through the intracoronary route. Table 1 shows a summary of the baseline characteristics of the included studies and participants, the number of injected Cells, and the type of injected Cells in each trial. Table 2 summarizes and illustrates the previous treatment history of included patients in each trial, as well as the baseline values of different scores used as outcome measures in this analysis. We found that bone marrow Mononuclear Stem Cell therapy leads to significantly increased LVEF ( MD = 4.54%, 95% CI [3.52, 5.56], P
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the efficacy of bone marrow Mononuclear Stem Cell transplantation in patients with non ischemic dilated cardiomyopathy a meta analysis
Heart Failure Reviews, 2021Co-Authors: Nso Nso, Kaveh Rezaei Bookani, Sostanie Takota Enoru, Farshid Radparvar, Robert GordonAbstract:Cardiomyopathy refers to a wide spectrum of heart pathologies that interfere with normal heart function. Management options of patients with cardiomyopathy depended mainly on the severity of the condition. Lifestyle modifications and regular exercise together with a healthy diet is compatible for mild conditions. Severe conditions, however, rely on medications or surgery. Here, we aim to investigate the efficacy of bone marrow Mononuclear Stem Cell transplantation in patients with dilated cardiomyopathy. We searched PubMed, Scopus, and Cochrane CENTRAL for relevant clinical trials and excluded observational studies. We performed the quality assessment of this study following GRADE guidelines. The assessment of the risk of bias was performed by the Cochrane’s risk of bias tool. We present an analysis of the following outcomes: left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), and six minutes walking test. Data were pooled as mean differences (MD) and relative confidence intervals (CI). The analysis of 667 patients from 11 studies receiving autologous bone marrow Cell therapy for non-ischemic dilated cardiomyopathy is presented. A total of 338 patients were allocated to the treatment group, and 329 participants entered the control group. The mean age of the patients in the treatment group is 52.4 ± 4.3 years, while that of the control is 53.7 ± 3.7 years. Seven studies (14.18–23) reported transplantation through the intracoronary route. Table 1 shows a summary of the baseline characteristics of the included studies and participants, the number of injected Cells, and the type of injected Cells in each trial. Table 2 summarizes and illustrates the previous treatment history of included patients in each trial, as well as the baseline values of different scores used as outcome measures in this analysis. We found that bone marrow Mononuclear Stem Cell therapy leads to significantly increased LVEF (MD = 4.54%, 95% CI [3.52, 5.56], P < 0.0001). Patients in the transplant group experienced less left ventricular end-diastolic diameter (millimeter) than the control arm (MD = −1.86 mm, 95% CI [−4.01, 0.29], P = 0.09). Additionally, Patients in the transplant group could walk 28.53 m more than the controls (MD = 28.53 m, 95% CI [2.51, 54.55], P = 0.03). Transplantation of bone marrow Stem Cells yields acceptable results regarding left ventricular ejection fraction and lowers the left ventricular end-diastolic diameter. Additionally, the six minutes walking test is improved in the transplant group.
Timothy D Henry - One of the best experts on this subject based on the ideXlab platform.
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consistently inconsistent bone marrow Mononuclear Stem Cell therapy following acute myocardial infarction
Circulation Research, 2016Co-Authors: Timothy D Henry, Lemuel A Moye, Jay H TraverseAbstract:A decade ago, 3 potentially groundbreaking trials were published that ushered in a new era of cardiovascular regenerative medicine.1–3 Using autologous bone marrow Mononuclear Cells (BMCs) in patients with acute ST-segment–elevation myocardial infarction (StemI), the trials were notable for their clear signal of safety, but discordant in their findings of benefit. Unfortunately, the 1-year results of the SWISS-AMI trial (Swiss Multicenter Intracoronary Stem Cells Study in Acute Myocardial Infarction)4 reported in this issue of Circulation Research again remind us about the inability of BMC therapy in patients with StemI to demonstrate consistent benefit. Why are there such disparate results in trials using a similar Cell product in a similar patient population? Article, see p 481 REPAIR-AMI (Reinfusion of Enriched Progenitor Cells and Infarct Remodeling in Acute Myocardial Infarction),1 remains the largest (n=204) and landmark trial to demonstrate that BMCs improve left ventricular (LV) function in patients after StemI. Patients were randomized to intracoronary delivery (using stop-flow technique) of BMC versus placebo 3 to 7 days after successful percutaneous coronary intervention (PCI). At 4 months, BMC-treated patients had a significant improvement in ejection fraction (EF) measured by left ventriculography at 4 months compared with placebo (5.5±7.3% versus 3.0±6.5%; P =0.01). In subgroup analyses, the improvement in LVEF was most significant in patients with a baseline LVEF below the median value of 48.9% and in patients treated ≥4 days post MI. At 1 year, there was a significant reduction in the prespecified combined clinical end point of death, recurrent MI, and any revascularization procedure (5.8% versus 1.9%; P =0.01). This trial generated excitement for the potential of cardiovascular Stem Cell therapy for AMI (as well as other cardiovascular diseases), but this excitement was tempered by the results of a second study, ASTAMI (Autologous Stem Cell Transplantation in …
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is the measurement of left ventricular ejection fraction the proper end point for Cell therapy trials an analysis of the effect of bone marrow Mononuclear Stem Cell administration on left ventricular ejection fraction after st segment elevation myoca
American Heart Journal, 2011Co-Authors: Timothy D Henry, Jay H Traverse, Lemuel A MoyeAbstract:Background The measurement of left ventricular (LV) ejection fraction (LVEF) is a strong predictor of cardiovascular adverse events and mortality in patients with LV dysfunction and has become the most common primary end point in cardiovascular Cell therapy trials after ST-segment elevation myocardial infarction (StemI). Multiple small trials have been performed using bone marrow Mononuclear Stem Cells (BMCs) in this setting with several meta-analyses demonstrating that BMC administration results in a small improvement in LVEF and may attenuate adverse LV remodeling. However, individual trial results have not been uniform, and the measurement of LVEF in these trials has relied on a variety of imaging techniques including LV angiograpnhy, single-photon emission computed tomography, echocardiography, or cardiac magnetic resonance imaging (cMRI). Methods Because cMRI provides the most accurate measurement of LVEF, LV volumes, and infarct size in patients after StemI, we reviewed all randomized cardiovascular Stem Cell trials (N = 10) that administered intracoronary BMCs versus placebo/control to 686 patients after primary percutaneous coronary intervention treatment of StemI that used cMRI as their principal imaging measurement of LVEF at baseline and 3 to 6 months later. Results Administration of BMCs was associated with a nonsignificant 0.9% ± 0.8% absolute increase in LVEF compared with placebo or control (95% CI −0.7 to 2.4) with a small but nonsignificant decrease LV end-diastolic and LV end-systolic volumes (LV end-diastolic volume −1.1 ± 1.5 mL/m2, LV end-systolic volume −1.6 ± 1.4 mL/m2). Although infarct size uniformly decreased over time, the reduction was not improved by BMC administration (−0.3 ± 1.7 g). Conclusions The benefit of BMC administration after StemI on LVEF, LV volumes, and infarct size is small when assessed by cMRI.