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Aims: The study assessed 4-year outcomes of intramyocardial injections of autologous bone marrow-derived mesenchymal stromal cells (MSCs) in patients with ischaemic heart failure.Methods and Results: The MSC-HF trial was a randomized, double-blind, placebo-controlled trial. Patients were randomized 2:1 to intramyocardial injections of MSCs or placebo. The primary endpoint was change in left ventricular end-systolic volume (LVESV), measured by magnetic resonance imaging or computed tomography. Sixty patients aged 30-80 years with ischaemic heart failure, New York Heart Association class II-III, left ventricular ejection fraction (LVEF) <45% and no further treatment options were randomized. Patients were followed clinically for 12 months and in addition 4-year data of hospitalizations and survival were retrieved. After 12 months, LVESV was significantly reduced in the MSC group and not in the placebo group, with difference between groups of 17.0 ± 16.2 mL (95% confidence interval 8.3-25.7, P = 0.0002). There were also significant improvements in LVEF of 6.2% (P < 0.0001), stroke volume of 16.1 mL (P < 0.0001) and myocardial mass (P = 0.009) between groups. A significant dose-response effect was also observed. Moreover, a significant reduction in the amount of scar tissue and quality of life score in the MSC group but not in the placebo group was observed. After 4 years, there were significantly fewer hospitalizations for angina in the MSC group and otherwise no differences in hospitalizations or survival. No side effects were identified.Conclusions: Intramyocardial injections of autologous bone marrow-derived MSCs improved myocardial function and myocardial mass in patients with ischaemic heart failure. [ABSTRACT FROM AUTHOR]

Introduction. To evaluate survival and engraftment of mesenchymal stromal cells (MSCs) in vivo, it is necessary to track implanted cells non-invasively with a method, which does not influence cellular ultrastructure and functional characteristics. Iron-oxide particles have been applied for cell tracking for years, but knowledge regarding possible cytotoxic ultrastructural changes subsequent to iron-oxide particle labeling is limited. Hence, the purpose of this study was to label MSCs with dextran-coated ultrasmall super-paramagnetic iron-oxide (USPIO) particles conjugated with the transduction sequence of trans-activator of transcription (TAT) (IODEX-TAT) and evaluate the effect of labeling on ultrastructure, viability, phenotype and proliferative capacity of the cells. Materials and methods. MSCs were labeled with 5 and 10 µg IODEX-TAT/105 cells for 2, 6 and 21 hours. IODEX-TAT uptake and cellular ultrastructure were determined by electron microscopy. Cell viability was determined by propidium iodide staining and cell proliferation capacity by 5-bromo-2-deoxyuridine (BrdU) incorporation. Maintenance of stem cell surface markers was determined by flow cytometry. Results. IODEX-TAT labeling for 2, 6 and 21 h did not influence cellular ultrastructure or viability. Moreover, neither stem cell surface markers nor cell proliferation capacity was affected by labeling with IODEX-TAT. Conclusion. Our results demonstrate that labeling of MSCs for 21 h with a clinically relevant dose of 10 µg IODEXTAT/105 cells is feasible and does not affect MSC ultrastructure, viability, phenotype or proliferation capacity. [ABSTRACT FROM AUTHOR]

Aims The left atrium (LA) transfers blood to the left ventricle in a complex manner. LA function is characterized by passive emptying (LA passive fraction), active emptying (LA ejection fraction), and total emptying (LA fractional change). Despite this complexity, the clinical relevance of the LA is based almost exclusively on LA maximal volume (LAmax), which may not glean the full prognostic potential. Cardiovascular magnetic resonance (CMR) is considered the most accurate method for studying LA function and size. The aim of the present study was to evaluate the prognostic importance of LA function in patients following ST elevation myocardial infarction (STEMI). Methods and results In 199 patients, a CMR scan was performed within 1–3 days after STEMI to measure LAmax and minimal volume (LAmin) and LA function. The incidence of death, re-infarction, stroke, and admission for heart failure [major adverse cardiac event (MACE)] were registered during the follow-up period [2.3 years (inter-quartile range: 2.0–2.5)]. A total of 40 patients (20%) met the clinical endpoint of MACE during follow-up. In a Cox regression analysis adjusting for known risk factors, LA fractional change remained independently associated with MACE [adjusted hazard ratio: 0.66 (95% confidence interval: 0.46–0.95)]. LAmax, LAmin, or LA passive fraction was not independently associated with MACE. Furthermore, LA fractional change provided incremental prognostic value to LAmax and other known predictors (Wald χ2 31.0 vs. 39.9, P= 0.016). Conclusion In STEMI patients, impaired LA fractional change is independently associated with outcome and provide incremental prognostic information to established predictors including LAmax. [ABSTRACT FROM PUBLISHER]

Aims Exenatide, a glucagon-like-peptide-1 analogue, increases myocardial salvage in experimental settings with coronary occlusion and subsequent reperfusion. We evaluated the cardioprotective effect of exenatide at the time of reperfusion in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). Methods and results A total of 172 patients with STEMI and Thrombolysis in Myocardial Infarction flow 0/1 were randomly assigned to exenatide or placebo (saline) intravenously. Study treatment was commenced 15 min before intervention and maintained for 6 h after the procedure. The primary endpoint was salvage index calculated from myocardial area at risk (AAR), measured in the acute phase, and final infarct size measured 90 ± 21 days after pPCI by cardiac magnetic resonance (CMR). In 105 patients evaluated with CMR, a significantly larger salvage index was found in the exenatide group than in the placebo group (0.71 ± 0.13 vs. 0.62 ± 0.16; P= 0.003). Infarct size in relation to AAR was also smaller in the exenatide group (0.30 ± 0.15 vs. 0.39 ± 0.15; P= 0.003). In a regression analysis, there was a significant correlation between the infarct size and the AAR for both treatment groups and an analysis of covariance showed that datapoints in the exenatide group lay significantly lower than for the placebo group (P= 0.011). There was a trend towards smaller absolute infarct size in the exenatide group (13 ± 9 vs. 17 ± 14 g; P= 0.11). No difference was observed in left ventricular function or 30-day clinical events. No adverse effects of exenatide were observed. Conclusion In patients with STEMI undergoing pPCI, administration of exenatide at the time of reperfusion increases myocardial salvage. [ABSTRACT FROM PUBLISHER]

Background. YKL-40 is a glycoprotein secreted by macrophages and neutrophils in tissues with inflammation. Plasma YKL-40 is increased in patients with coronary artery disease (CAD) and associated with cardiovascular and all-cause mortality. Furthermore, plasma YKL-40 seems related to the number of diseased main vessels in patients with stable CAD. The aim was to further study the relation between YKL-40 and stenosis degree, stenosis type and actual ischemia in stable CAD patients. Methods. Plasma YKL-40 and hsCRP levels were determined from 206 consecutive patients with stable angina pectoris admitted for coronary angiography. Plasma YKL-40 in 245 healthy subjects was used for comparison. In addition to one to three vessel stenosis scores, two new scores for evaluating coronary angiographies were established for discriminating between focal and diffuse CAD and the extent of myocardial ischemia. Results. YKL-40 levels in CAD patients (median: 52 μg/L and quartiles: 37-85 μg/L) were significantly increased ( p < 0.001) compared to the healthy controls. In univariate analyses plasma YKL-40 was significantly associated with ischemic myocardium score, age, hypertension, peripheral vascular disease and serum creatinine levels. In multivariate analyses YKL-40 was related to hsCRP, peripheral artery disease, hypertension, and statin treatment. Conclusions. Plasma YKL-40 was increased in patients with CAD compared to controls. YKL-40 was related to the ischemic myocardium, but not to degree of CAD using different scoring systems. Therefore, YKL-40 is not related to the extent of CAD, but to some other pathophysiological mechanisms of importance for the prognosis. [ABSTRACT FROM AUTHOR]

Aims. We evaluated the feasibility, safety and efficacy of intra-myocardial injection of autologous mesenchymal stromal cells derived endothelial progenitor cell (MSC) in patients with stable coronary artery disease (CAD) and refractory angina in this first in man trial. Methods and results. A total of 31 patients with stable CAD, moderate to severe angina and no further revascularization options, were included. Bone marrow MSC were isolated and culture expanded for 6--8 weeks. It was feasible and safe to establish in-hospital culture expansion of autologous MSC and perform intra-myocardial injection of MSC. After six months follow-up myocardial perfusion was unaltered, but the patients increased exercise capacity (p < 0.001), reduction in CCS Class (p < 0.001), angina attacks (p < 0.001) and nitroglycerin consumption (p < 0.001), and improved Seattle Angina Questionnaire (SAQ) evaluations (p < 0.001). For all parameters there was a tendency towards improved outcome with increasing numbers of cells injected. In the MRI substudy: ejection fraction (p < 0.001), systolic wall thickness (p == 0.03) and wall thickening (p == 0.03) all improved. Conclusions. The study demonstrated that it was safe to treat patients with stable CAD with autologous culture expanded MSC. Moreover, MSC treated patients had significant improvement in left ventricular function and exercise capacity, in addition to an improvement in clinical symptoms and SAQ evaluations. [ABSTRACT FROM AUTHOR]

Background. Patients with stable coronary artery disease (CAD) have a poor prognosis. The aim of the study was to evaluate the extent to which serum high-sensitivity C-reactive protein (hs-CRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurement alone or together could be prognostic biomarkers in patients with stable CAD. Materials and methods. During the 2.6-year follow-up period 270 patients among the 4264 patients with stable CAD in the CLARICOR trial suffered myocardial infarction (MI) and 377 died (187 cardiovascular deaths (CVD)). Results. Serum NT-proBNP was significantly associated with MI (hazard ratio (HR), 1. 65 (refers to a 2.72 fold increase in serum level, p = 0.0005), CVD (HR, 2.42, p < 0.0005) and non-CVD (HR, 1.79, p < 0.0005). When correcting for hs-CRP, NT-proBNP was still significantly associated with MI (HR, 1.63, p = 0.0005), CVD (HR, 2.36, p < 0.0005) and non-CVD (HR, 1.66, p < 0.0005). Serum hs-CRP was compared to NT-proBNP less associated with MI (HR, 1.20, p = 0.001), CVD (HR, 1.39, p < 0.0005) and non-CVD (HR, 1.67, p < 0.0005). When corrected for NT-proBNP, hs-CRP was only associated with non-CVD (HR, 1.51, p < 0.0005). When adjusting for cardiovascular risk factors hs-CRP predicted non-CVD (HR, 1.46) and all-cause death (HR, 1.24) and NT-proBNP predicted MI (HR, 1.50), CVD (HR, 1.98), non-CVD (HR, 1.39), and all-cause death (HR, 1.62)( p < 0.0005 for all). Conclusion. Increased serum NT-proBNP was a stronger predictor of MI, cardiovascular death and non-cardiovascular death than hs-CRP in patients with stable CAD. Once NT-proBNP was taken into account, hs-CRP did not improve predictions. [ABSTRACT FROM AUTHOR]

An abstract of the paper "Myocardium Area at Risk Measured With Delayed Enhancement After Scar Remodelling Compared With T2-Weighted Cardiac Magnetic Resonance Imaging," by Niels Vejlstrup and colleagues is presented.