Diagnostic and prognostic value of miR-1 and miR-29b on adverse ventricular remodeling after acute myocardial infarction - The SITAGRAMI-miR analysis.

BACKGROUND: MicroRNAs (miRs) have shown to exert fibrotic and anti-fibrotic effects in preclinical models of acute myocardial infarction (AMI). The aim of this study was to evaluate miR-1, miR-21, miR-29b and miR-92a as circulating biomarkers for adverse ventricular remodeling (AVR) in post-AMI patients. METHODS: Plasma levels of miR-1, miR-21, miR-29b and miR-92a were measured in 44 patients of the SITAGRAMI trial population at day 4, day 9 and 6month after AMI and in 18 matched controls (CTL). MiR expression patterns were correlated with magnetic resonance imaging (MRI) parameters for AVR (absolute change (Δ) in infarct volume (IV), left ventricular ejection fraction (LVEF) and left ventricular end-diastolic volume (LVEDV) between day 4 and 6months after AMI) and a combined cardiovascular endpoint. RESULTS: Expression of miR-1, miR-21 and miR-29b but not miR-92a was increased in AMI vs. CTL cohort showing highest miR levels at d9. However, only miR-1 and miR-29b levels significantly correlated with ΔIV and showed a trend for correlation with ΔLVEF. Only miR-29b levels at day 9 correlated with ΔLVEDV at 6-month follow-up. There was no correlation of miR levels with an adverse outcome. CONCLUSION: Mir-1 and miR-29b plasma levels post-AMI correlate with IV changes. In addition, miR-29b levels are associated with changes of LVEDV over time. These results provide insights into the role of miRs as diagnostic AVR surrogate markers. Further large scale clinical trials will be needed to evaluate the real prognostic relevance of these miRs with respect to a clinical implication in the future.

Retrospective analysis of circulatory support with the Impella CP® device in patients with therapy refractory cardiogenic shock.

BACKGROUND: In cardiogenic shock (CS) the Impella CP® device provides a fast available left ventricular circulatory support of up to 4.0L/min. However, the use of the Impella CP® device was not systematically analysed yet. METHODS: We performed a retrospective analysis of 28 consecutive patients suffering from severe therapy refractory CS treated with Impella CP®. Mortality was estimated using the SAPS II-Score. Primary outcome was 30-day survival. We compared the different aetiologies of CS and the effect of additional extracorporeal life support (ECLS). RESULTS: Aetiology of CS was acute coronary syndrome (ACS) in 15 patients, 9 patients received additional therapy with ECLS. SAPS II was 73±14, representing an estimated mortality of 87.1%. 18 patients deceased representing a 30-day survival of 36%. Comparing the different aetiologies, ACS-CS patients show a trend towards better survival. Additional therapy with ECLS did not change 30-day survival. In 3 cases, vascular complication needing surgical treatment occurred. All other patients showed no relevant complications except for the commonly seen haemolysis with consecutive need of transfusion. CONCLUSION: Our data could demonstrate that the Impella CP® application in these severely diseased patients is feasible and safe. Compared to the estimated mortality, the 30-day survival seems to be improved.

DPP-4 inhibition ameliorates atherosclerosis by priming monocytes into M2 macrophages.

OBJECTIVE: Glipitins are widely used for the treatment of type 2 diabetic patients. In addition to their improvement of glycemic control, animal studies have suggested an independent anti-atherosclerotic effect of gliptins. Nevertheless, recent clinical trials regarding long-term effects of gliptin therapy on vascular events have been disappointing. This discrepancy led us to better dissect the functional role of SDF-1/CXCR4 signaling as a potential mechanism underlying gliptin action. The study should give improved understanding of the potential of gliptin therapy in the prevention and treatment of atherosclerosis. METHODS AND RESULTS: In an ApoE-/- mouse model on high cholesterol diet, long-term treatment with the DPP-4 inhibitor Sitagliptin significantly reduced atherosclerosic plaque load in the aorta. Flow cytometry analyses showed an enrichment of M2 macrophages in the aortic wall under gliptin therapy. Importantly, the number of recruited CD206+ macrophages was inversely correlated with total plaque area while no correlation was found for the overall macrophage population or M1 macrophages. Blockade of CXCR4/SDF-1 signaling by AMD3100 inhibited aortic M2 accumulation and the therapeutic effect of Sitagliptin. Correspondingly, Sitagliptin shifted the polarization profile of macrophages towards a M2-like phenotype. CONCLUSION: Sitagliptin-mediated inhibition of early atherosclerosis is based on M2-polarization during monocyte differentiation via the SDF-1/CXCR4 signaling. In contrast to earlier assumptions gliptin treatment might be especially effective in prevention of atherosclerosis.

[Stem cell therapy for chronic cardiac insufficiency--therapy of the future?]. / Stammzelltherapie bei chronischer Herzinsuffizienz: Organerneuerung nach Mass?

The incidence of chronic cardiac insufficiency is constantly increasing. However, the current therapeutic possibilities during the terminal stage are limited by a lack of donor organs. For this reason, stem cell therapy is seen as a potent therapeutic option for the future. Catheter application or cytokine-mediated mobilization of autologous adult stem cells is for acute myocardial infarction safe and potentially effective; however, for chronic cardiac insufficiency, the successes have not yet been verifiable. Hence, embryonic stem cells offer a therapeutic option that cannot be ignored: These cells are pluripotent and are, theoretically, able to continue dividing in cell culture indefinitely. Through "tissue engineering" they could generate new myocardium that could be transplanted into patients suffering from chronic cardiac insufficiency to support the pump function.