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The article discusses a study on the impact of intracoronary delivery of autologous bone marrow mononuclear cells (BMCs) on left ventricular (LV) function when administered two to three weeks after myocardial infarction (MI). The study was a randomized controlled trial known as the LateTIME trial in the U.S. involving 87 patients who had LV dysfunction following primary percutaneous coronary intervention (PCI). Cardiac magnetic resonance imaging was used to measure changes in global and regional LV function. The researchers found that intracoronary infusion of autologous BMCs had no significant impact on global or regional LV function at six months compared with intracoronary placebo infusion.

Presents letters to the editor on medical topics. Medical services planning for end of life care; Incidence of congenital heart disease in the United States; Revascularization methods for coronary artery disease; Prevention of firearm injuries; Others.

The author salutes professional staff and employees of the Texas Heart Institute (THI) at St. Luke's Episcopal Hospital in Houston for their different roles in maintaining and improving the ranking of the THI among "America's Best Hospitals" for 2009. He says the institute was ranked by the periodical "U.S. News & World Report" among the top 10 centers for heart and heart surgery in the country. He lists the other top-ranked centers for the year. He adds that the periodical examines the performance of medical centers in complex and demanding situations.

Introduces a symposium, which reviews the progress of influenza infection in the U.S. since 1918. Background on the influenza pandemic in Spain from 1918 to 1919; Prevalence of the infection in the U.S. since its first appearance in March 1918; Celebrities who died from influenza infection.

Although coronary revascularization is common in both Japan and the United States (US), no direct comparison has been performed to demonstrate differences in the clinical characteristics and long-term outcomes of patients in these 2 countries. We analyzed the preprocedural, in-hospital, and long-term data from the Coronary Revascularization Demonstrating Outcome registry (Kyoto, Japan) and the Texas Heart Institute Research Database (Houston, Texas) of 16,100 patients who had undergone elective, initial percutaneous coronary intervention or coronary artery bypass grafting. The Japanese procedures were performed from 2000 to 2002 (n = 8,871, follow-up period 3.5 years, interquartile range 2.6 to 4.3) and the US procedures from 1999 to 2003 (n = 7,229, follow-up period 5.2 years, interquartile range 3.8 to 6.5). The Japanese patients tended to be older (mean age 67.2 vs 62.7 years; p <0.001), to smoke (52.9% vs 46.0%; p <0.001), and to have diabetes (39.2% vs 31.0%; p <0.001) and stroke (16.4% vs 5.0%; p <0.001). The US patients were more obese (body mass index 23.7 vs 29.3 kg/m2; p <0.001), with greater rates of systemic atherosclerotic disease. Both groups had a similar in-hospital mortality rate (Japanese patients 0.9% vs US patients 1.1%; p = 0.19) and crude long-term mortality rate (Japanese patients 27.7/1,000 person-years, US patients 28.2/1,000 person-years; p = 0.35). After adjustment for known predictors, the US group had greater long-term mortality than the Japanese group (hazard ratio 1.71, 95% confidence interval 1.50 to 1.95; p <0.001). This finding was consistent among all high-risk subgroups. In conclusion, the 2 registries showed similar crude outcomes but important differences in patient risk factors such as obesity. In the adjusted analysis, the Japanese patients had better outcomes than did the US patients. Additional study is needed to assess the effect of ethnic and risk factor variations on coronary artery disease. [Copyright &y& Elsevier]

It is not known whether genetic variants in the cholesteryl ester transfer protein (CETP) gene are associated with recurrent coronary heart disease events or mortality in secondary prevention patients. Among 3,717 patients with acute coronary syndrome or coronary artery bypass grafting (CABG) enrolled in a prospective genetic registry, we evaluated whether CETP gene variants previously shown to be associated with reduced CETP activity and high-density lipoprotein cholesterol increase ("A" allele for both TaqIB [rs708272] and rs12149545) are associated with a reduction in recurrent myocardial infarction (MI), recurrent revascularization, or death. At 4.5 years of follow-up, 439 recurrent MI, 698 recurrent revascularizations, and 756 deaths occurred. Using an additive model of inheritance, the "A" allele for rs708272 was not associated with recurrent MI (hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.78 to 1.17 for AG; HR 0.89, 95% CI 0.67 to 1.19 for AA; compared with GG genotype), recurrent revascularization (HR 1.13, 95% CI 0.95 to 1.33 for AG; HR 1.05, 95% CI 0.84 to 1.32 for AA), or mortality (HR 1.02, 95% CI 0.86 to 1.19 for AG; HR 1.11, 95% CI 0.91 to 1.37 for AA) in the overall cohort. Similar results were seen for the "A" allele for rs12149545. In the CABG subgroup, AG genotype for rs708272 was associated with an increased mortality (HR 1.38, 95% CI 1.06 to 1.79) compared with GG genotype. Results remained consistent using dominant model of inheritance. In conclusion, genetic CETP variants were not associated with recurrent MI or recurrent revascularization in overall cohort with a possible mortality increase in patients who underwent CABG., (Published by Elsevier Inc.)

Objectives: The safety and efficacy of direct intramuscular injections of aldehyde dehydrogenase bright (ALDH(br)) cells isolated from autologous bone marrow mononuclear cells (ABMMNCs) and ABMMNCs were studied in patients with critical limb ischemia (CLI) who were not eligible for percutaneous or surgical revascularization., Background: Many CLI patients are not candidates for current revascularization procedures, and amputation rates are high in these patients. Cell therapy may be a viable option for CLI patients., Methods: Safety was the primary objective and was evaluated by occurrence of adverse events. Efficacy, the secondary objective, was evaluated by assessment of Rutherford category, ankle-brachial index (ABI), transcutaneous partial pressure of oxygen (TcPO(2)), quality of life, and pain., Results: ALDH(br) cells and ABMMNCs were successfully administered to all patients. No therapy-related serious adverse events occurred. Patients treated with ALDH(br) cells (n = 11) showed significant improvements in Rutherford category from baseline to 12 weeks (mean, 4.09 ± 0.30 to 3.46 ± 1.04; P = 0.05) and in ABI at 6 (mean, 0.22 ± 0.19 to 0.30 ± 0.24; P = 0.02), and 12 weeks (mean, 0.36 ± 0.18; P = 0.03) compared with baseline. Patients in the ABMMNC group (n = 10) showed no significant improvements at 6 or 12 weeks in Rutherford category but did show improvement in ABI from baseline to 12 weeks (0.38 ± 0.06 to 0.52 ± 0.16; P = 0.03). No significant changes from baseline were noted in ischemic ulcer grade or TcPO(2) in either group., Conclusions: Administration of autologous ALDH(br) cells appears to be safe and warrants further study in patients with CLI., (Copyright © 2011 Wiley Periodicals, Inc.)

The emerging sciences of stem cell biology and cellular plasticity have led to the development of cell-based therapies for advanced human disease. Pre-clinical studies which defined the potential of bone marrow-derived mononuclear cells to repair damaged and dysfunctional myocardium led to the rapid advancement of these strategies to the clinic. Such rapid advancement has led to controversy regarding the appropriate conduct of such studies. In the United States, the National Heart, Lung, and Blood Institute established the Cardiovascular Cell Therapy Research Network (CCTRN) to facilitate the early translation of clinical trials of cell therapy for left ventricular dysfunction. The premise upon which the CCTRN was established was that multiple clinical trial sites would interact effectively with a Data Coordinating Center to perform early phase 1 and 2 clinical trials within a highly coordinated network structure. In order to develop this network, the unmet needs of the community needed to be defined, the clinical trials identified, and the structure to perform the studies needed to be established. This manuscript highlights the challenges in the development of the CCTRN and the approaches faced to define a network to perform clinical trials in human cell therapy of cardiovascular disease.

A realistic goal for cardiac cell therapy may be to attenuate left ventricular remodeling following acute myocardial infarction to prevent the development of congestive heart failure. Initial clinical trials of cell therapy have delivered cells 1 to 7 days after acute myocardial infarction. However, many patients at risk of developing congestive heart failure may not be ready for cell delivery at that time-point because of clinical instability or hospitalization at facilities without access to cell therapy. Experience with cell delivery 2 to 3 weeks after acute myocardial infarction has not to date been explored in a clinical trial. The objective of the LateTIME study is to evaluate by cardiac magnetic resonance the effect on global and regional left ventricular function, between baseline and 6 months, of a single intracoronary infusion of 150 × 106 autologous bone marrow mononuclear cells (compared with placebo) when that infusion is administered 2 to 3 weeks after moderate-to-large acute myocardial infarction. The 5 clinical sites of the Cardiovascular Cell Therapy Research Network (CCTRN) will enroll a total of 87 eligible patients in a 2:1 bone marrow mononuclear cells-to-placebo patient ratio; these 87 will have undergone successful percutaneous coronary intervention of a major coronary artery and have left ventricular ejection fractions ≤0.45 by echocardiography. When the results become available, this study should provide insight into the clinical feasibility and appropriate timing of autologous cell therapy in high-risk patients after acute myocardial infarction and percutaneous coronary intervention.

Recent studies have evaluated whether incorporating nontraditional risk factors improves coronary heart disease (CHD) prediction models. This 1986-2001 US study aggregated the contribution of multiple single nucleotide polymorphisms into a genetic risk score (GRS) and assessed whether the GRS plus traditional risk factors predict CHD better than traditional risk factors alone. The Atherosclerosis Risk in Communities (ARIC) cohort was followed for a median of 13 years for CHD events (n = 1,452). Individuals were genotyped for 116 single nucleotide polymorphisms associated with CHD in multiple case-control studies. Single nucleotide polymorphisms nominally predicting incident CHD in the ARIC study were included in the GRS. The GRS was significantly associated with incident CHD in Blacks (hazard rate ratio = 1.20, 95% confidence interval: 1.11, 1.29) and Whites (hazard rate ratio = 1.10, 95% confidence interval: 1.06, 1.14) as well as in each tertile defined by the traditional cardiovascular risk score (p < or = 0.02). When receiver operating characteristic curves based on traditional risk factors were recalculated after the GRS was added, the increase in the area under the receiver operating characteristic curve was statistically significant for Blacks and suggestive of improved CHD prediction for Whites. This study demonstrates the concept of aggregating information from multiple single nucleotide polymorphisms into a risk score and indicates that it can improve prediction of incident CHD in the ARIC study.