prognosis of patients with Acute Myocardial Infarction remains dismal

Stem Cell Therapy

The impact on: LEFT VENTRICULAR FUNCTION LEFT VENTRICULAR FUNCTION INFARCT SIZE INFARCT SIZE LV DIMENSIONS LV DIMENSIONS ….remains unclear. ….remains unclear.

OUTCOME OF INTRACORONARY STEM CELL THERAPY IN ACUTE MYOCARDIAL INFARCTION: META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS Arvisminda Luz G. Fernandez, MD. Chong Hua Hospital – Heart Institute May 24, 2012

General Objectives: To perform a meta-analysis on the impact of intracoronary bone marrow stem cell therapy in acute myocardial infarction

to assess if there is significant difference in the LV ejection fraction in patients with acute myocardial infarction who received bone marrow therapy versus control. to assess if there is significant difference in the LV end systolic volume in patients with acute myocardial infarction who received bone marrow therapy versus control.

REVIEW QUESTION AND STUDY PROTOCOL “What is the outcome of bone marrow stem cell transplantation in patients with acute myocardial infarction following percutaneous coronary intervention? This is a protocol-driven systematic review according to Quality of Reporting of Metaanalysis (QUOROM)

INCLUSION CRITERIA  RCTs with comparison of intracoronary stem cell transplantation versus control in patients with acute myocardial infarction  Intention- to- treat analysis  Follow-up ≥ 3 months from therapy EXCLUSION CRITERIA  Use of cytokines for mobilization of BMCs  Irretrievable or unclear data  Treatment of old myocardial infarction (>14 days)  Lack of control group  Duplicate reports  Ongoing or unpublished studies

 PubMed databases ( )  Cochrane Central Registry of Controlled Trials ( )  Clinicaltrials.gov Registry ( )  keywords:  keywords: “stem cells, acute myocardial infarction, randomized controlled trials”

 Study features extracted: outcome definitions. imaging modalities, patient baseline characteristics, and procedural data Primary endpoint: - change in left ventricular ejection fraction (LVEF) from baseline to follow-up Secondary endpoint: - change in left ventricular end systolic volumes

The criteria by Jüni et al

 Dichotomous variables as proportion and percentages.  Continuous variables as mean ± standard deviation or median.  Meta-regression and sensitivity analyses to explore heterogeneity.  Statistical significance for hypothesis testing set at the 0.05, 2-tailed level.

47 Citations Retrieved 16 Complete Articles Assessed Based on Criteria 12 Studies finally included in the systematic review 31 Titles/Abstracts non-relevant used cytokines for BMC mobilization mobilization -2 had MI treatment > 14 days - 1 irretrievable data REVIEW PROCESS

Characteristics of Studies Included in the Meta-analysis N = 934

Range of patients: Follow-up Duration Range: 3-18 months Average Timing of Cell Transplantation after PCI : 1-18 days # of Stem cell Use: 24.6±9.4x10 6 cells Characteristics of Studies Included in the Meta-analysis

Quality of Assessment Scale for Randomized Controlled Trials Included in the Meta-Analysis

Forrest plot of unadjusted difference in mean (with 95% confidence intervals [CIs]) improvement in left ventricular ejection fraction (LVEF) in patients treated with bone marrow–derived cells (BMCs) compared with controls Increase in LVEF of.72% p value <

Forrest plot of unadjusted difference in mean (with 95% confidence intervals [CIs]) improvement in left ventricular end systolic volume (LVESV) in patients treated with bone marrow–derived cells (BMCs) compared with controls Standard Mean Difference Decrease in LVESV of mL p value <

Intracoronary bone marrow stem cell resulted in:  modest yet significant increase in LV ejection fraction  significant decrease in LV end systolic volume ….in patients with acute myocardial infarction ….in patients with acute myocardial infarction