COMPARE CPM-RMI Trial: Intramyocardial Transplantation of Autologous Bone Marrow-Derived CD133+ Cells and MNCs during CABG in Patients with Recent MI: A Phase II/III, Multicenter, Placebo-Controlled, Randomized, Double-Blind Clinical Trial.

This article published in Cell J (Yakhteh), Vol 20, No 2, Jul-Sep 2018, on pages 267-277, four affiliations (1, 4, 5, and 10) were changed based on authors request.

COMPARE CPM-RMI Trial: Intramyocardial Transplantation of Autologous Bone Marrow-Derived CD133+ Cells and MNCs during CABG in Patients with Recent MI: A Phase II/III, Multicenter, Placebo-Controlled, Randomized, Double-Blind Clinical Trial.

OBJECTIVES: The regenerative potential of bone marrow-derived mononuclear cells (MNCs) and CD133+ stem cells in the heart varies in terms of their pro-angiogenic effects. This phase II/III, multicenter and double-blind trial is designed to compare the functional effects of intramyocardial autologous transplantation of both cell types and placebo in patients with recent myocardial infarction (RMI) post-coronary artery bypass graft. MATERIALS AND METHODS: This was a phase II/III, randomized, double-blind, placebo-controlled trial COMPARE CPM-RMI (CD133, Placebo, MNCs - recent myocardial infarction) conducted in accordance with the Declaration of Helsinki that assessed the safety and efficacy of CD133 and MNCs compared to placebo in patients with RMI. We randomly assigned 77 eligible RMI patients selected from 5 hospitals to receive CD133+ cells, MNC, or a placebo. Patients underwent gated single photon emission computed tomography assessments at 6 and 18 months post-intramyocardial transplantation. We tested the normally distributed efficacy outcomes with a mixed analysis of variance model that used the entire data set of baseline and between-group comparisons as well as within subject (time) and group×time interaction terms. RESULTS: There were no related serious adverse events reported. The intramyocardial transplantation of both cell types increased left ventricular ejection fraction by 9% [95% confidence intervals (CI): 2.14% to 15.78%, P=0.01] and improved decreased systolic wall thickening by -3.7 (95% CI: -7.07 to -0.42, P=0.03). The CD133 group showed significantly decreased non-viable segments by 75% (P=0.001) compared to the placebo and 60% (P=0.01) compared to the MNC group. We observed this improvement at both the 6- and 18-month time points. CONCLUSIONS: Intramyocardial injections of CD133+ cells or MNCs appeared to be safe and efficient with superiority of CD133+ cells for patients with RMI. Although the sample size precluded a definitive statement about clinical outcomes, these results have provided the basis for larger studies to confirm definitive evidence about the efficacy of these cell types (Registration Number: NCT01167751).

Glycemic control in type 2 diabetes mellitus prevents coronary arterial wall infection.

BACKGROUND: Diabetes mellitus (DM) is a very well-known risk factor for development of atherosclerosis, and it has been hypothesized that poor glycemic control and hyperglycemia plays a major role in this process. In the current study, we aimed to evaluate the associates of poor glycemic control in Iranian patients who have already undergone coronary artery bypass grafting (CABG), with especial focus on the inhabitation of infectious agents within the coronary arterial wall. METHODS: In January 2010, 52 consecutive patients with type 2 DM who undergone CABG at the Department of Cardiovascular Surgery of Baqiyatallah University of Medical Sciences (Tehran, Iran) were included into this cross-sectional study and biopsy specimens from their coronary plaques were taken and analyzed by polymerase chain reaction (PCR) methods for detecting Helicobacter species, cytomegalovirus (CMV) and Chlamydia pneumoniae, and their potential relation to the glycemic control status in these patients. RESULTS: Compared to that in diabetic patients with mean fasting blood sugar (FBS) levels FBS < 126, atherosclerotic lesions in type 2 diabetic patients with poor glycemic control (FBS > 126) were significantly more likely to be positive for CMV PCR test (41% vs. 9%, respectively; P = 0.05). In laboratorial test results, mean triglyceride level was significantly higher among patients of poor glycemic control (168 ± 89 vs. 222 ± 125 mg/dl, respectively; P = 0.033). Hypertension was also significantly more prevalent in this population (73% vs. 36%, respectively; P = 0.034). CONCLUSION: Type 2 diabetic patients with poor glycemic control can be at higher risk for developing CMV infection in their coronary arterial wall, which can promote atherosclerosis formation process in this patient population. According to the findings of this study, we recommend better control of serum glucose levels in type 2 diabetic patients to prevent formation/progression of atherosclerosis.

Helicobacter species in the atherosclerotic plaques of patients with coronary artery disease.

INTRODUCTION: Several epidemiological studies have proposed an association between Helicobacter pylori infection and coronary artery disease. In the current study, we aimed to evaluate the prevalence and relevance of H. pylori infection, using polymerase chain reaction (PCR) methods, in the coronary arterial wall of Iranian patients who have already undergone coronary bypass grafting (CABG). METHODS: A total of 105 consecutive patients who underwent CABG at the Department of Cardiovascular Surgery of Baqiyatallah University of Medical Sciences were included in the study, and biopsy specimens from their coronary plaques were taken and analyzed using the PCR methods for detecting Helicobacter species (H Spp.). Fifty-three specimens from biopsies of the left internal mamillary artery in the same patients were also collected and tested. RESULTS: H. Spp. PCR test result was positive for 31 (29.5%) specimens from coronary artery atherosclerotic plaques. Serologic test results also showed 25 (23.8%) positive cases for H. pylrori immunoglobulin A (IgA) and 56 (53.3%) positive for anti-H. pylori immunoglobulin G. None of the specimens from the mamillary artery were positive for H Spp. genome when it was evaluated using PCR (P<.0001). Patients with positive test result for H. pylori IgA were significantly more likely to have higher total cholesterol and low-density lipoprotein (LDL) levels than IgA-negative patients. CONCLUSION: H Spp. infection replication in the coronary arterial wall is associated with atherosclerotic plaque formation. Seropositivity for H. pylori IgA may also enhance blood values of total cholesterol and LDL in these patients.

A novel scoring system for identifying high-risk patients undergoing carotid stenting.

BACKGROUND/OBJECTIVE: In patients with severe concurrent coronary and carotid artery disease, two different treatment strategies may be used: simultaneous endarterectomy and coronary bypass surgery, and carotid stenting with delayed coronary bypass surgery after a few weeks. To evaluate the safety and efficacy of carotid stenting with delayed coronary bypass surgery after a few weeks in patients referred to Tehran Heart Center, Tehran, Iran and to determine the independent predictors that may be used to identify the appropriate treatment plan for such patients. METHODS: This prospective study was performed from December 2003 through October 2004. Symptomatic patients with >60% stenosis and asymptomatic patients with >80% stenosis were included in this study. The risks and benefits of carotid stenting were explained. Patients were excluded from the study if any of the following was applicable: age > or =85 years, history of a major stroke within the last week, pregnancy, intracranial tumor or arteriovenous malformation, severely disabled as a result of stroke or dementia, and intracranial stenosis that exceeded the severity of the extracranial stenosis. Thirty consecutive patients who underwent carotid stenting were enrolled in this study. RESULTS: The mean +/- SD age of patients was 66.3 +/- 8 years. The procedural success rate was 96.7%. During a mean +/- SD follow-up period of 5.6 +/- 3.2 months, 4 (17%) deaths occurred; none of which were attributed to a neurologic causes. Moreover, 1 (3%) patient developed a minor nonfatal stroke with transient cognitive disorder. Most of patients (80%) with major complications acquired a score of > or =26. CONCLUSION: To reduce the rate of carotid stenting complications in high-risk patients with heart disease, to optimize the patient selections, and to determine the best treatment strategy, based on the clinical and lesion characteristics of patients, we proposed a new scoring system.