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).

Passion for Life: Lived Experiences of Patients after Coronary Artery Bypass Graft.

BACKGROUND: Coronary artery bypass graft surgery (CABG) improves the quality of life, increases survival, and influences the patient's mental and emotional aspects. Little information is available on the lived experience of Iranian patients after this surgery. Understanding the lived experiences of patients will help health professionals with better provision of high quality care. METHODS: This hermeneutic phenomenological study aimed to understand the lived experience of patients after CABG. Van Manen's method was used to conduct the study. A semi-structured, face-to-face interview technique was employed to explore the experiences of the patients following surgery. Seven men and 4 women between 49 and 80 years old were interviewed. RESULTS: Passion for life was the main theme extracted from the participants' interviews. This theme comprised the three sub-themes of receiving attention from family, being hopeful, and being spiritually oriented. CONCLUSION: The results showed that the participants experienced passion for life after their surgery. This finding reveals that patients tend to find a new perspective on life and their health after surgery.

Mutation in CYP27A1 identified in family with coronary artery disease.

Coronary artery disease (CAD) is a leading cause of death worldwide. Myocardial infarction is the most severe outcome of CAD. Despite extensive efforts, the genetics of CAD is poorly understood. We aimed to identify the genetic cause of CAD in a pedigree with several affected individuals. Exome sequencing led to identification of a mutation in CYP27A1 that causes p.Arg225His in the encoded protein sterol 27-hydroxylase as the likely cause of CAD in the pedigree. The enzyme is multifunctional, and several of its functions including its functions in vitamin D metabolism and reverse cholesterol transport (RCT) are relevant to the CAD phenotype. Measurements of vitamin D levels suggested that the mutation does not affect CAD by affecting this parameter. We suggest that the mutation may cause CAD by affecting RCT. Screening of all coding regions of the CYP27A1 in 100 additional patients led to finding four variations (p.Arg14Gly, p.Arg26Lys, p.Ala27Arg, and p.Val86Met) in seven patients that may contribute to their CAD status. CYP27A1 is the known causative gene of cerebrotendinous xanthomatosis, a disorder which is sometimes accompanied by early onset atherosclerosis. This and the observation of potentially harmful variations in unrelated CAD patients provide additional evidence for the suggested causative role of the p.Arg225His mutation in CAD.

Impact of Angiotensin-converting enzyme inhibitors and Angiotensin receptor blockers on mortality of coronary artery bypass grafting.

BACKGROUND: There is controversy over the potential benefits/harms of the usage of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) as regards the postoperative mortality of coronary artery bypass grafting (CABG). This study investigates the correlation between the in-hospital mortality of CABG and the preoperative administration of ACEI/ARB. METHODS: Out of 10055 consecutive patients with isolated CABG from 2006 to 2009, 4664 (46.38%) patients received preoperative ACEI/ARB. Data were gathered from the Cardiac Surgery Registry of Tehran Heart Center. In-hospital mortality was defined as death within the same admission for surgery. Adjusted for confounders, multivariable logistic regression models were used to evaluate the impact of preoperative ACEI/ARB therapy on in-hospital death. RESULTS: The mean age of the patients was 60.04 ± 9.51 years and 7364 (73.23%) were male. Eighty-seven (0.86%) patients expired within 30 days. Multivariate analysis revealed that the administration of ACEI/ARB significantly protected against in-hospital deaths inasmuch as there were 33 (0.70%) vs. 54 (1.0%) deaths in the ACEI/ARB positive and negative groups, respectively (OR: 0.628; p value = 0.09). Patients without ACEI/ARB were more likely to have a higher global ejection fraction. CONCLUSION: Preoperative ACEI usage in patients undergoing CABG can be associated with decreased in-hospital mortality. Large-scale randomized clinical trials are suggested.