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Contrast-induced acute kidney injury (CI-AKI) occurs in up to 13% of patients undergoing percutaneous coronary intervention (PCI). Neutrophil gelatinase-associated lipocalin (NGAL) is an early biomarker for renal impairment. We investigated whether increased urinary NGAL concentrations were predictive of CI-AKI within 2 days after PCI or of a higher re-hospitalization rate within 9 months.Consecutive patients (n = 128), with stable coronary heart disease and eGFR ≥ 30 mL/min/1.73 m(2), undergoing PCI were included. Venous serum samples for measurement of creatinine, blood urea nitrogen, and cystatin C and urine samples for NGAL measurement were collected 4 hours and 1 and 2 days after contrast medium application. Patients were followed over 9 months to determine clinical endpoints.CI-AKI was observed in 14 patients (10.9%) after PCI. NGAL concentrations before PCI were significantly higher in patients with subsequent CI-AKI (19.8 ng/mL [14.4-35.8] vs. 11.6 ng/mL [5.6-28.2]; p = 0.04). There was no significant difference in NGAL concentrations 4 h after PCI between patients with and without CI-AKI. One day after PCI, NGAL concentrations were significant higher in patients developing CI-AKI (100.1 ng/mL [41.5-129.2] vs. 16.6 ng/mL [9.1-28.1]; p0.001). Compared to common biomarkers, NGAL best predicted CI-AKI (AUC 0.939 [95% CI 0.89-0.99; p0.001]). The re-hospitalization rate due to progressive renal insufficiency within 9 months was higher in the group with CI-AKI than the group without (4 [28.6%] vs. 4 [3.5%], p0.01).Urinary NGAL is a biomarker for predicting CI-AKI when measured 1 day after PCI.

ObjectivesThis study sought to evaluate exact release kinetics of microRNAs (miRNAs) in acute myocardial infarction (AMI).BackgroundmiRNAs may be useful as novel biomarkers in patients with cardiovascular disease, although it is difficult to establish the detailed release kinetics of miRNAs in patients with AMI.MethodsWe analyzed the release kinetics of circulating cardiac-specific (miR-21, miR-208a) and muscle-enriched (miR-1, miR-133a) miRNAs using the TaqMan polymerase chain reaction in patients with hypertrophic obstructive cardiomyopathy who were undergoing transcoronary ablation of septal hypertrophy (TASH), a procedure mimicking AMI. Consecutive patients (n = 21) undergoing TASH were included. Serum samples were collected prior to and at 15, 30, 45, 60, 75, 90, and 105 min and 2, 4, 8, and 24 h after TASH.ResultsCirculating concentrations of miR-1 were significantly increased (>3-fold; p = 0.01) after 15 min, with a peak after 75 min (>60-fold; p < 0.001). The miR-21 concentrations were not increased at any time point. Concentrations of miR-133a were significantly increased at 15 min (2.9-fold; p < 0.001) and reached a plateau between 75 and 480 min (>50-fold change). The miR-208a concentrations were elevated at 105 min (>2-fold; p = 0.01), without a further increase.ConclusionsmiR-1, miR-133a, and miR-208a were continuously increased during the first 4 h after the induction of MI. In particular, miR-1 and miR-133a were significantly increased at early time points. These results demonstrate the release kinetics of miRNAs, which are helpful for developing their potential use as biomarkers in patients with acute coronary syndromes.

Background Therapy-resistant arterial hypertension causing psychosocial stress and is associated with cardiovascular morbidity and mortality. The aim of the study was to evaluate the effect on quality of life (QoL) in patients with resistant hypertension undergoing renal sympathetic denervation (RSD). Methods and Results We analyzed responses to the SF-36 Quality of Life Questionnaire provided by patients with resistant arterial hypertension after RSD. Thirty consecutive patients from 2 centers were included in this study, from October 2011 until February 2012. The phone interview was performed after the 3-month follow-up. A significant reduction (26 ± 13.5 mmHg) in systolic blood pressure (BP) was detected at the 3-month follow-up (142.0 ± 15.1 mmHg vs 168.0 ± 13.7 mmHg; P

Stress cardiomyopathy is a form of reversible systolic dysfunction of the mid and apical left ventricle with pathologic changes of the electrocardiogram in the absence of an obstructive coronary artery disease. The prevalence of stress cardiomyopathy among patients with symptoms suggestive of myocardial infarction is 0.7% to 2.5%, and it is found predominantly in postmenopausal women (90%). No large studies have confirmed the cause of stress cardiomyopathy. Published data suggest that substantially elevated plasma catecholamine levels, due to emotional or physical stress, may be relevant.

Die antithrombozytare Therapie stellt einen Eckpfeiler in der Sekundarprophylaxe bei Patienten nach akutem Koronarsyndrom dar. Die langjahrige Praxis der festen Kombination aus Acetylsalicylsaure und Clopidogrel steht vor einem Umbruch – neue antithrombozytare Medikamente wie Ticagrelor und Prasugrel sind zugelassen und haben aufgrund nachgewiesener Uberlegenheit gegenuber Clopidogrel Einzug in die Leitlinien gefunden. Weitere Wirkstoffe sind in der klinischen Erprobung. Der nachfolgende Artikel soll einen Uberblick uber Wirkung und Nebenwirkungen, pharmakokinetische Eigenschaften sowie aktuelle Entwicklungen im Bereich der pharmakologischen Forschung der Thrombozyteninhibierung liefern.

Background: Atrial fibrillation (AF) is a frequent arrhythmia associated with an adverse prognostic value in patients with ACS. Risk stratification as well as diagnosis of ACS is strongly supported by biomarkers. High sensitivity CRP (hs-CRP) is known to be elevated in patients presenting with ACS as well as with AF.Methods: In total, 2034 consecutive patients with an ACS were analysed. The incidence of AF in the setting of ACS, the prognostic value of hs-CRP and the clinical outcome within 6 months were subject of the study. Death after 6 months was considered as primary endpoint. Results: The frequency of AF among patients admitted with suspected ACS was 124 (6.1%). During 6-month follow-up the mortality rate among patients with AF was significantly higher (20 [16.1%] vs 133 [6.9%]; log-rank 13.72; p 0.001) compared to patients without AF. Cox regression analysis revealed an increased risk for ACS patients with AF with an adjusted HR of 2.63 (95% CI 1.48 - 3.78; p 0.001). Patients with AF showed significant higher levels of hs-CRP than patients without AF (6.01mg/dl IQR [1.7 - 17.8] vs 3.3mg/dl IQR [1.37 - 9.83]; p = 0.003). By the use of multivariate Cox regression analysis, risk of mortality was higher when AF patients had higher concentrations of hs-CRP (HR 1.076; 95% CI 1.02 - 1.13; p = 0.002).Conclusions: AF is a strong and independent indicator for increased mortality in patients presenting with ACS. hs-CRP predicts mortality in AF patients and should be considered for risk stratification in clinical routine.

Recently, we demonstrated that a fully differentiated tissue developed on a ventricular septal occluder that had been implanted due to infarct-related septum rupture. We suggested that this tissue originated from circulating stem cells. The aim of the present study was to evaluate this hypothesis and to investigate the physiological differentiation and transdifferentiation potential of circulating stem cells. We developed an animal model in which a freely floating membrane was inserted into each the left ventricle and the descending aorta. Membranes were removed after pre-specified intervals of 3 days, and 2, 6 and 12 weeks; the newly developed tissue was evaluated using quantitative RT-PCR, immunohistochemistry and in situ hybridization. The contribution of stem cells was directly evaluated in another group of animals that were by treated with granulocyte macrophage colony-stimulating factor (GM-CSF) early after implantation. We demonstrated the time-dependent generation of a fully differentiated tissue composed of fibroblasts, myofibroblasts, smooth muscle cells, endothelial cells and new blood vessels. Cells differentiated into early cardiomyocytes on membranes implanted in the left ventricles but not on those implanted in the aortas. Stem cell mobilization with GM-CSF led to more rapid tissue growth and differentiation. The GM-CSF effect on cell proliferation outlasted the treat ment period by several weeks. Circulating stem cells contributed to the development of a fully differentiated tissue on membranes placed within the left ventricle or descending aorta under physiological conditions. Early cardiomyocyte generation was identified only on membranes positioned within the left ventricle.

Therapy-resistant arterial hypertension causing psychosocial stress and is associated with cardiovascular morbidity and mortality. The aim of the study was to evaluate the effect on quality of life (QoL) in patients with resistant hypertension undergoing renal sympathetic denervation (RSD).We analyzed responses to the SF-36 Quality of Life Questionnaire provided by patients with resistant arterial hypertension after RSD. Thirty consecutive patients from 2 centers were included in this study, from October 2011 until February 2012. The phone interview was performed after the 3-month follow-up. A significant reduction (26 ± 13.5 mmHg) in systolic blood pressure (BP) was detected at the 3-month follow-up (142.0 ± 15.1 mmHg vs 168.0 ± 13.7 mmHg; P 0.001). Seventy-five percent of the patients indicated that their health situation was a lot better (better, 21%; equal to, 4%) 3 months after RSD compared to the time before the therapeutic procedure. Furthermore, the majority of patients felt full of pep (always, 29%; mostly, 58%; quite often, 8%; sometimes, 4%), and full of energy (always, 25%; mostly, 54%; quite often, 16.7%; sometimes, 4.2%) after the procedure. Recipients of RSD indicated that they felt more light and healthy, and nearly all recipients (93%) described a loss of anxiety and indisposition.This investigation revealed that sufficient BP reduction by RSD and time following therapeutic success lead to significant improvements in patient QoL.

This study aimed to identify predictors of mortality in patients with out-of-hospital cardiac arrest (OHCA) undergoing in-hospital extracorporeal life support system (ECLS) treatment.We retrospectively studied the characteristics and clinical outcomes of 28 patients (January 2010 and December 2011) with OHCA and veno-arterial ECLS implemented during ongoing cardiopulmonary resuscitation (CPR) upon admission to the cath lab. Baseline left ventricular ejection fraction (LVEF) was determined after ECLS implantation and then every 24 h during and after successful weaning from ECLS.Overall 30-day survival rate was 39.3 % (11 of 28 patients). Baseline characteristics, initial laboratory measurements, and LVEF on admission were not significantly different between survivors and non-survivors. There was no difference regarding median CPR duration [survivors 44.0 min (IQR 31.0-45.0) vs. non-survivors 53.0 min (IQR 40.0-61.3); P = 0.23]. Door-to-ECLS implantation time was significantly longer in non-survivors [42.5 min (IQR 28.0-56.5) vs. 25.0 min (IQR 21.0-30.0); P0.01]. ECLS treatment duration was not significantly different between the two groups [survivors: 4.0 days (IQR 1.5-7.5) vs. non-survivors 6.5 days (IQR 1.0-8.0); P = 0.69]. LVEF significantly improved in survivors during ECLS treatment (mean ± SD survivor 47.5 ± 14.7 % vs. non-survivor 23.3 ± 14.9 %; P0.01). The door-to-ECLS implantation time was the only significant and independent predictor of 30-day mortality in multivariate Cox regression analysis (P = 0.04). Kaplan-Meier survival analysis showed a benefit favouring patients with a door-to-ECLS implantation time30 min (log rank 6.29; P = 0.01).A door-to-ECLS implantation time30 min significantly improves 30-day outcomes in patients with OHCA.

Sebastian Szardien , Helge Mollmann , Matthias Willmer , Christoph Liebetrau , Sandra Voss , Christian Troidl , Jedrzej Hoffmann , Johannes Rixe , Albrecht Elsasser , Christian W. Hamm , Holger M. Nef a,b,c,⁎ a Kerckhoff Heart Center, Department of Cardiology, D-61231 Bad Nauheim, Germany b Department of Experimental Cardiology, Franz-Groedel-Institute of the Kerckhoff Heart Center, D-61231 Bad Nauheim, Germany c University of Giessen, Medical Clinic I, Department of Cardiology, D-39392 Giessen, Germany d Department of Cardiology, Klinikum Oldenburg, D-26121 Oldenburg, Germany

BACKGROUND The release kinetics of copeptin in patients with acute myocardial infarction (AMI) have been difficult to establish. METHODS We analyzed the release kinetics of copeptin in patients with hypertrophic obstructive cardiomyopathy undergoing transcoronary ablation of septal hypertrophy (TASH) as a model of AMI. We included 21 consecutive patients who underwent TASH. Blood samples were collected before and at 15, 30, 45, 60, 75, 90, and 105 min, and at 2, 4, 8, and 24 h after TASH. Serum copeptin was quantified by a sandwich immunoluminometric assay. RESULTS All patients had copeptin concentrations below the 99th percentile at baseline. The median copeptin concentration was significantly increased at 30 min [16.0 pmol/L; interquartile range (IQR), 13.4–20.2 pmol/L], compared with the median baseline concentration (6.6 pmol/L; IQR, 5.3–8.3 pmol/L; P = 0.002). The copeptin concentration peaked 90 min after induction of myocardial infarction and returned to baseline concentrations (median, 8.2 pmol/L; IQR, 6.3–10.1) after 24 h, compared with the above baseline values (P = 0.06). Serum creatine kinase (CK) activities were significantly increased above baseline values by 1 day after TASH [median maximal postprocedural CK activity, 935.0 U/L (IQR, 545.5–1115.0 U/L); median baseline CK activity, 80.0 U/L (IQR, 63.5–109.0 U/L); P < 0.001]. CONCLUSIONS Our results provide additional evidence that early rule-out of suspected AMI is possible by using the copeptin concentration in combination with cardiac troponin T.

BACKGROUND The release kinetics of cardiac troponin T measured with conventional vs high-sensitivity cardiac troponin T (hs-cTnT) assays in patients with acute myocardial infarction (AMI) is difficult to establish. METHODS We analyzed the release kinetics of cTnT measured by fourth generation and high-sensitivity assays, creatine kinase-MB (CK-MB), and myoglobin in patients with hypertrophic obstructive cardiomyopathy undergoing transcoronary ablation of septal hypertrophy (TASH), a model of AMI. Consecutive patients (n = 21) undergoing TASH were included. Serum and EDTA-plasma samples were collected before and at 15, 30, 45, 60, 75, 90, and 105 min, and 2, 4, 8, and 24 h after TASH. RESULTS cTnT concentrations measured by the hs assay were significantly increased at 15 min [21.4 ng/L, interquartile range (IQR) 13.3–39.7 ng/L vs 11.3 ng/L, IQR 6.0–18.8 ng/L at baseline; P = 0.031]. In comparison, cTnT concentrations measured by the conventional fourth generation assay increased significantly at 60 min (30.0 ng/L, IQR 20.0–30.0 ng/L vs CONCLUSIONS cTnT concentrations measured by the hs assay were significantly increased after TASH at all of the time points, with a doubling at 15 min after induction of AMI, confirming earlier evidence of myocardial injury compared to the fourth generation cTnT assay and CK-MB and myoglobin.

The paradigm that cardiac myocytes are non-proliferating, terminally differentiated cells was recently challenged by studies reporting the ability of bone marrow-derived cells (BMCs) to differentiate into cardiomyocytes after myocardial damage. However, little knowledge exists about the role of BMCs in the heart during physiological aging. Twelve-week-old mice (n=36) were sublethally irradiated and bone marrow from littermates transgenic for enhanced green fluorescent protein (eGFP) was transplanted. After 4 weeks, 18 mice were sacrificed at the age of 4 months and served as controls (group A); the remaining mice were sacrificed at the age of 18 months (group B). Group A did not exhibit a significant number of eGFP+ cells, whereas 9.4±2.8 eGFP+ cells/mm2 was documented in group B. In total, only five eGFP+ cardiomyocytes were detected in 20 examined hearts, excluding a functional role of BM differentiation in cardiomyocytes. Similarly, a relevant differentiation of BMCs in endothelial or smooth muscle cells was excluded. In contrast, numerous BM-derived fibroblasts and myofibroblasts were observed in group B, but none were detected in group A. The present study demonstrates that BMCs transdifferentiate into fibroblasts and myofibroblasts in the aging murine myocardium, suggesting their contribution to the preservation of the structural integrity of the myocardium, while they do not account for regenerative processes of the heart.

An important goal in cardiology is to minimize myocardial necrosis and to support a discrete but resilient scar formation after myocardial infarction (MI). Macrophages are a type of cells that influence cardiac remodelling during MI. Therefore, the goal of the present study was to investigate their transcriptional profile and to identify the type of activation during scar tissue formation. Ligature of the left anterior descending coronary artery was performed in mice. Macrophages were isolated from infarcted tissue using magnetic cell sorting after 5 days. The total RNA of macrophages was subjected to microarray analysis and compared with RNA from MI and LV-control. mRNA abundance of relevant targets was validated by quantitative real-time PCR 2, 5 and 10 days after MI (qRT-PCR). Immunohistochemistry was performed to localize activation type-specific proteins. The genome scan revealed 68 targets predominantly expressed by macrophages after MI. Among these targets, an increased mRNA abundance of genes, involved in both the classically (tumour necrosis factor alpha, interleukin 6, interleukin 1beta) and the alternatively (arginase 1 and 2, mannose receptor C type 1, chitinase 3-like 3) activated phenotype of macrophages, was found 5 days after MI. This observation was confirmed by qRT-PCR. Using immunohistochemistry, we confirmed that tumour necrosis factor alpha, representing the classical activation, is strongly transcribed early after ligature (2 days). It was decreased after 5 and 10 days. Five days after MI, we found a fundamental change towards alternative activation of macrophages with up-regulation of arginase 1. Our results demonstrate that macrophages are differentially activated during different phases of scar tissue formation after MI. During the early inflammatory phase, macrophages are predominantly classically activated, whereas their phenotype changes during the important transition from inflammation to scar tissue formation into an alternatively activated type.

Background: Cardiopulmonary resuscitation (CPR) is associated with low success rates and high variability in outcomes. Extracorporeal life support (ECLS) systems provide sufficient perfusion of vital organs during treatment of the cardiac arrest (CA) cause. The routine use of ECLS is still under investigation. This study aimed to identify predictors of mortality in patients with in-hospital cardiac arrest (IHCA) undergoing ECLS treatment. Method: We retrospectively studied the characteristics and clinical outcomes of 48 patients with IHCA and veno-arterial ECLS treatment during on-going CPR treated between January 2009 and December 2012. Left ventricular ejection fraction (LVEF) and laboratory measurements were analysed. LVEF at baseline was taken from the medical report before CA and was further evaluated after ECLS implantation and then every 24 h during and after successful weaning from ECLS. Survival was determined from time of cardiac arrest to 30 days. Results: The 30-day survival rate was 31.3% (15 of 48 patients). Baseline characteristics, initial laboratory measurements, baseline LVEF as well as LVEF after ECLS treatment were not significantly different between survivors and non-survivors. There was no difference regarding median CPR duration (survivors 40.5 min [IQR 18.8-51.5] vs. non-survivors 31.0 min [IQR 20.0-49.0]; P=0.80) and duration of ECLS system implantation time (survivors 21.0 min [IQR 10.0-29.5] vs. non-survivors 15.0 min [IQR 9.5-22.5]; P=0.39). The interval between CA and start of ECLS system set up did not show a significant difference among the groups (survivor 21.5 min [IQR 10.0-32.3] vs. non-survivor 17.5 min [IQR 5.0-30.0]; P=0.56). ECLS treatment duration was not significantly different between the two groups (survivors: 69.0 hours [IQR 21.0–178.0] vs. non-survivors 39.0 hours [IQR 5.0–129.0]; P=0.24). Conclusion: In prolonged IHCA with failing conventional measures rapid initiation of an adequate organ perfusion by means of ECLS may help to improve the outcome.

Background: MicroRNAs (miR) have been proposed as novel biomarkers in patients with cardiovascular disease. The release kinetics of miRs in patients with acute myocardial infarction (AMI) are difficult to establish. Methods: We analyzed the release kinetics of circulating muscle-enriched miRs (miR-1, miR-21, miR-208a, miR-133a) measured by TaqMan polymerase chain reaction in patients with hypertrophic obstructive cardiomyopathy undergoing transcoronary ablation of septal hypertrophy (TASH), a procedure mimicking AMI. Consecutive patients (n=21) undergoing TASH were included. Serum samples were collected prior to and at 15, 30, 45, 60, 75, 90, and 105 min, and 2, 4, 8, and 24 h after TASH. Results: Circulating concentrations of miR-1 significant increased already after 15 min (>4-fold; P 60-fold; P 50-fold change) and decreases afterwards (30-fold change at 24 hours). MiR-208a concentrations rise the first 75 min (>2-fold; P=0.01) without further increase during all time points. Serum concentrations of miR-1 positively correlated with the hs-cTnT release during the first 120 min after induction of myocardial infarction (r2=0.95; P

Background: Half of the patients with congestive heart failure suffer from diastolic dysfunction with persistent left ventricular function (HFpEF). Until today different explanations exist, but the exact mechanism of HFpEF is still unclear. From human biopsies and different animal models it is known that in HFpEF the extracellular matrix underlies remodeling processes with increased fibrosis and disturbance of cardiac architecture. Our study aimed to characterize changes of the extracellular matrix in early cardiac fibrosis and diastolic dysfunction. Methods: In C57Bl/6-mice, osmotic minipumps were implanted with a continuous infusion of Angiotensin II (Ang, 0.5μg/kg/min) or NaCl (Sham). After assessment of systolic and diastolic parameters using echocardiography at day 7 or 28, mice were euthanized (Ang7d, n=22/Ang28d, n=27/Sham, n=20). Cardiac tissue was investigated with micro array technology, western blot, qRT-PCR and immunohistochemistry. Results: Echocardiography revealed a reliable induction of diastolic dysfunction with persistent LVEF in the Ang groups (E/E': Sham 25.9±1.0 vs. Ang28d 38.5±4.4; p

To the Editor: Renal sympathetic denervation (RSD) is an interventional treatment option for resistant arterial hypertension (HT) ([1][1]). Previous investigations of RSD excluded patients with progressive chronic kidney disease because of potential RSD-related kidney damage ([1,2][1]). Diagnosis