Publications by authors named "Sandra Erbs"

85 Publications

Candidate genes in coronary syndromes: seeing the bigger picture.

Authors:
Marcus Sandri Katharina Kirsch Sandra Erbs Holger Thiele

Eur J Prev Cardiol 2020 Jul 2. Epub 2020 Jul 2.

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http://dx.doi.org/10.1177/2047487320934262DOI Listing
July 2020

Candidate genes in coronary syndromes: seeing the bigger picture.

Authors:
Marcus Sandri Katharina Kirsch Sandra Erbs Holger Thiele

Eur J Prev Cardiol 2020 Jul 1:2047487320934262. Epub 2020 Jul 1.

Department of Internal Medicine/Cardiology, Heart Center Leipzig at University of Leipzig, Germany.

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http://dx.doi.org/10.1177/2047487320934262DOI Listing
July 2020

Incidence and characteristics of ventricular tachycardia in patients after percutaneous coronary revascularization of chronic total occlusions.

Authors:
Sebastian König Enno Boudriot Arash Arya Julia-Anna Lurz Marcus Sandri Sandra Erbs Holger Thiele Gerhard Hindricks Borislav Dinov

PLoS One 2019 22;14(11):e0225580. Epub 2019 Nov 22.

Department of Electrophysiology, Heart Center Leipzig at University of Leipzig, Leipzig, Sachsen, Germany.

Objectives: This study sought to investigate the prevalence of ventricular tachycardia after percutaneous coronary intervention (PCI) of chronic total occlusion (CTO).

Background: PCI of a CTO is associated with improvement of the left ventricular ejection fraction and possibly associated with reduced mortality. However, benefits of CTO-PCI must be weighed against a higher risk of procedure-related complications. The incidence of new-onset ventricular tachycardia after a successful CTO-PCI has not been investigated so far. In this retrospective registry we seek to describe characteristics and predictors of occurrence of post-procedural ventricular tachycardias.

Methods And Results: Between 2010 and 2015, 485 patients underwent successful CTO-PCI at Heart Center Leipzig. Of them, 342 had complete follow-up and were further analyzed. Ventricular tachycardias were detected in 9 (2.6%) patients. All of them were monomorphic ventricular tachycardias occurring in median 1 day (interquartile range [IQR] 0.25-4.75 days) after PCI and caused prolongation of the hospital stay. Patients with ventricular tachycardia were older, had worse left ventricular ejection fraction (mean 33.1%, SD 5.9%) and more frequently a CTO of an infarct-related artery. The target vessel was not associated with the occurrence of ventricular arrhythmias. In multivariable analysis, only impaired left ventricular systolic function was an independent predictor for procedure-related ventricular tachycardia. Mortality rates were not different between patients with or without ventricular tachycardia.

Conclusion: Ventricular tachycardia can occur early after CTO-PCI as possible reperfusion arrhythmia and poorer left ventricular ejection fraction is the only independent predictor for onset. Although the occurrence of ventricular tachycardia after CTO-PCI seems not to influence mortality, awareness of this possible complication and longer monitoring may be recommended.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0225580PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6874319PMC
March 2020

Myeloperoxidase in atrial fibrillation: association with progression, origin and influence of renin-angiotensin system antagonists.

Authors:
Erik Holzwirth Jelena Kornej Sandra Erbs Danilo Obradovic Andreas Bollmann Gerhard Hindricks Holger Thiele Petra Büttner

Clin Res Cardiol 2020 Mar 24;109(3):324-330. Epub 2019 Jun 24.

Department of Cardiology, Heart Center Leipzig at University Leipzig, Strümpellstraße 39, 04289, Leipzig, Germany.

Background: Myeloperoxidase (MPO), secreted by neutrophils under inflammatory conditions, is elevated in atrial fibrillation (AF). MPO may be involved in atrial remodeling that underpins AF progression characterized by a switch from paroxysmal to persistent AF and the formation of low-voltage areas (LVA). MPO levels are modulated by renin-angiotensin system antagonists (RAS-A), commonly used to treat AF comorbidities, and are associated with reduced AF incidence, implicating a potential link.

Objective: We investigated MPO levels in progressing AF in peripheral and left atrial (LA) blood and analyzed a potential effect of RAS-A.

Methods: Samples of AF patients were collected from the femoral vein and the LA during catheter ablation (n = 121) and at follow-up (n = 23). No-AF probands (n = 37) served as controls. MPO was determined using commercial ELISA.

Results: MPO levels were significantly increased in AF patients compared to controls (median, 27.7 ng/ml (IQR 14.3-66.6) versus 12.6 (IQR 9.9-17.7), p < 0.001), without differences between clinical AF progression phenotypes. MPO concentration was tenfold higher in LA than periphery (279.2 ng/ml (IQR 202.2-342.9) versus 27.7 ng/ml (IQR 14.3-65.9), p < 0.001). MPO remained increased at midterm follow-up irrespective of rhythm outcome. RAS-A was associated with significantly lower peripheral (22.2 ng/ml (IQR 12.7-48.2) versus 37.1 ng/ml (IQR 18.2-85.2), p < 0.05) MPO levels in AF patients.

Conclusion: The pro-fibrotic enzyme MPO is generally elevated in AF patients irrespective of AF type, the presence of LVA or midterm rhythm outcome. Our data suggest that MPO may directly originate from the LA. RAS-A decrease peripheral MPO levels in AF patients.
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http://dx.doi.org/10.1007/s00392-019-01512-zDOI Listing
March 2020

Identification of Coronary Vasospasm as a Cause of Recurrent Acute Coronary Syndrome.

Authors:
Nicolas Majunke Maximilian von Roeder Stephan Schürer Sandra Erbs

J Invasive Cardiol 2018 10;30(10):E100

Heart Center Leipzig - University Hospital, Struempellstrasse 39, 04289 Leipzig, Germany.

A case highlighting the importance of nitrate administration, as routinely performed during coronary arteriography.
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October 2018

Impact of Weight Reduction During Adolescence on Parameters of Cardiac Geometry and Function in Obese Children.

Authors:
Sandra Erbs Henriette Broniecki Kathrin Scheuermann Ephraim Winzer Jennifer Adam Ulrike Spielau Felix Woitek Marcus Sandri Marion Zimmer Christian Besler Wieland Kiess Axel Linke Antje Körner Norman Mangner

JACC Cardiovasc Imaging 2018 12 18;11(12):1915-1917. Epub 2018 Jul 18.

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http://dx.doi.org/10.1016/j.jcmg.2018.05.023DOI Listing
December 2018

Mild Hypothermia in Cardiogenic Shock Complicating Myocardial Infarction.

Authors:
Georg Fuernau Johannes Beck Steffen Desch Ingo Eitel Christian Jung Sandra Erbs Norman Mangner Philipp Lurz Karl Fengler Alexander Jobs Reinhard Vonthein Suzanne de Waha-Thiele Marcus Sandri Gerhard Schuler Holger Thiele

Circulation 2019 01;139(4):448-457

Department of Internal Medicine/Cardiology, Heart Center Leipzig-University Hospital, Germany (G.F., J.B., S.D., I.E., S.E., N.M., P.L., K.F., S.d.W.-T, M.S., G.S., H.T.).

Background: Experimental trials suggest improved outcome by mild therapeutic hypothermia for cardiogenic shock after acute myocardial infarction. The objective of this study was to investigate the hemodynamic effects of mild therapeutic hypothermia in patients with cardiogenic shock complicating acute myocardial infarction.

Methods: Patients (n=40) with cardiogenic shock undergoing primary percutaneous coronary intervention without classic indications for mild therapeutic hypothermia underwent randomization in a 1:1 fashion to mild therapeutic hypothermia for 24 hours or control. The primary end point was cardiac power index at 24 hours; secondary end points included other hemodynamic parameters and serial measurements of arterial lactate.

Results: No relevant differences were observed for the primary end point of cardiac power index at 24 hours (mild therapeutic hypothermia versus control: 0.41 [interquartile range, 0.31-0.52] versus 0.36 [interquartile range, 0.31-0.48] W/m; P=0.50; median difference, -0.025 W/m; 95% CI, -0.12 to 0.06). Similarly, all other hemodynamic measurements were not statistically different. Arterial lactate levels at 6, 8, and 10 hours were significantly higher in patients in the mild therapeutic hypothermia group with a slower decline ( P for interaction=0.03). There were no differences in 30-day mortality (60% versus 50%; hazard ratio, 1.27; 95% CI, 0.55-2.94; P=0.55).

Conclusions: In this randomized trial, mild therapeutic hypothermia failed to show a substantial beneficial effect on cardiac power index at 24 hours in patients with cardiogenic shock after acute myocardial infarction.

Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01890317.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.117.032722DOI Listing
January 2019

Frequency and clinical course of cerebral embolism in patients undergoing transcatheter left atrial appendage closure.

Authors:
Nicolas Majunke Franziska Eplinius Matthias Gutberlet Sven Moebius-Winkler Ingo Daehnert Matthias Grothoff Stephan Schürer Norman Mangner Philipp Lurz Sandra Erbs Katharina Kirsch Gerhard Schuler Marcus Sandri

EuroIntervention 2017 May;13(1):124-130

University of Leipzig, Heart Center, Department of Internal Medicine/Cardiology, Leipzig, Germany.

Aims: The aim of this study was to assess silent and clinically apparent cerebral embolic events in patients undergoing transcatheter left atrial appendage closure.

Methods And Results: In this prospective single-centre study, 28 patients underwent percutaneous closure of the left atrial appendage. In all patients, a diffusion-weighted magnetic resonance imaging (DW-MRI) study was performed before, the day after the procedure, and during routine follow-up after 45 days. All patients underwent neurological assessment at the time of DW-MRI. Additionally, transcranial Doppler ultrasound monitoring (TCD) for the detection of microembolic material during the procedure was performed. The procedure was successfully completed in all patients. New embolic lesions were detected in nine patients (32%) after the procedure, of which three (33%) were detectable as gliotic lesions at follow-up. One (3.6%) new lesion was observed at 45-day follow-up. Neurological assessment showed no neurological deficits. We observed no relationship between the numbers of microembolic signals on TCD monitoring and the occurrence of cerebral infarctions on DW-MRI.

Conclusions: New cerebral embolic events occur after transcatheter closure of the left atrial appendage. However, most of the lesions demonstrate no gliotic transformation at follow-up. In all patients, the cerebral lesions were clinically unapparent.
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http://dx.doi.org/10.4244/EIJ-D-16-00776DOI Listing
May 2017

Endothelial Function in Children and Adolescents Is Mainly Influenced by Age, Sex and Physical Activity　- An Analysis of Reactive Hyperemic Peripheral Artery Tonometry.

Authors:
Ulrike M Mueller Claudia Walther Jennifer Adam Kati Fikenzer Sandra Erbs Meinhard Mende Volker Adams Axel Linke Gerhard Schuler

Circ J 2017 Apr 11;81(5):717-725. Epub 2017 Feb 11.

Department of Internal Medicine/Cardiology, University Leipzig - Heart Center.

Background: As adolescents rarely experience cardiovascular events, surrogate markers of atherosclerosis are useful to justify and monitor effects of primary prevention and therapy of risk factors. Endothelial function assessed by reactive hyperemic peripheral arterial tonometry (RH-PAT) resulting in a reactive hyperemic index (RHI) is a noninvasive method with limited data for use in children and adolescents.Methods and Results:We performed a total of 931 RHI measurements in 445 high-school students, aged 10-17 years, over a time period of 5 years. Students were randomized by class to 60 min physical exercise (PE) at school daily (intervention group), or 2 units of 45-min PE weekly (control group). To characterize the factors influencing the RHI, anthropometry, cardiopulmonary exercise testing, blood cholesterol and quality of life were assessed and used to build mixed linear models. Main influential factors were age, with an increase of RHI from 1.53±0.42 in the youngest to 1.96±0.59 in the oldest students, sex, with higher values in girls, and physical activity. This increase adjusted by age and sex was estimated as 0.11 [0.08, 0.14] per year. RHI was higher in the intervention group by 0.09 [-0.05, 0.23] in comparison with the control group.

Conclusions: If RH-PAT is used in research or as a clinical tool in adolescents, the shown age- and sex-dependence of RHI have to be taken in account.
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http://dx.doi.org/10.1253/circj.CJ-16-0994DOI Listing
April 2017

Osteopontin is BMI-independently Related to Early Endothelial Dysfunction in Children.

Authors:
Moritz Schreier Julian Tristan Schwartze Kathrin Landgraf Kathrin Scheuermann Sandra Erbs Gunda Herberth J Andrew Pospisilik Jürgen Kratzsch Wieland Kiess Antje Körner

J Clin Endocrinol Metab 2016 11 29;101(11):4161-4169. Epub 2016 Aug 29.

Center for Pediatric Research Leipzig, Hospital for Children & Adolescents (M.S., J.T.S., K.L., K.S., W.K., A.K.), University of Leipzig, 04103 Leipzig, Germany; Integrated Research and Treatment Center (IFB) Adiposity Diseases (K.L., A.K.), University of Leipzig, 04103 Leipzig, Germany; Heart Centre, Department of Cardiology (S.E.), University of Leipzig, 04109 Leipzig, Germany; Department of Environmental Immunology (G.H.), UFZ Helmholtz Centre for Environmental Research Leipzig, 04318 Leipzig, Germany; Max Planck Institute of Immunology and Epigenetics (J.A.P.), 79108 Freiburg, Germany; and Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics (J.K.), University of Leipzig, 04109 Leipzig, Germany.

Context: Osteopontin (OPN) has been proposed to predict adverse cardiac events in patients with adult type 2 diabetes.

Objective: We investigated potential associations of circulating OPN and OPN expression in adipose tissue (AT) with obesity and early metabolic and cardiovascular dysfunction in children. Furthermore, we assessed the functional relevance of OPN on primary human endothelial cells.

Design: Serum OPN was determined in healthy lean (n = 65) and obese (n = 100) children by ELISA. Expression levels were assessed in sc AT samples from healthy lean (n = 33) and overweight and obese (n = 31) children by qRT-PCR. Direct effects of recombinant (rh) OPN on adhesion molecule and ENOS expression were assessed in human coronary arterial endothelial cells.

Results: OPN serum concentrations decreased with pubertal development in lean children. The degree of obesity was negatively associated with OPN serum levels. Multiple regression analysis revealed that body mass index (BMI) standard deviation score (SDS), next to pubertal status, was the strongest independent predictor for OPN serum concentrations. Metabolically, the homeostasis model assessment index and circulating plasma insulin were negatively correlated with OPN serum levels secondary to obesity. In contrast, independent from BMI, OPN was positively related to VCAM-1 levels, intima media thickening, and negatively associated with endothelial function. Functionally, full-length rhOPN did not affect adhesion molecule and ENOS mRNA expression in primary human coronary arterial endothelial cells. In addition, OPN expression levels in AT positively correlated with BMI SDS, AT inflammation, and markers of metabolic dysfunction but were not related to OPN serum levels.

Conclusion: Our findings suggest that OPN levels are BMI-independently related to markers of early endothelial dysfunction in children.
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http://dx.doi.org/10.1210/jc.2016-2238DOI Listing
November 2016

Comparison of Percutaneous Closure Versus Surgical Femoral Cutdown for Decannulation of Large-Sized Arterial and Venous Access Sites in Adults After Successful Weaning of Veno-Arterial Extracorporeal Membrane Oxygenation.

Authors:
Nicolas Majunke Norman Mangner Axel Linke Enno Boudriot Sandra Erbs Franziska Tietz Sabrina Wolff Stephan Schürer Gerhard Schuler Marcus Sandri

J Invasive Cardiol 2016 Oct;28(10):415-419

University of Leipzig, Heart Center, Department of Internal Medicine/Cardiology, Strümpellstrasse 39, 04289 Leipzig, Germany.

Objective: Surgical femoral cutdown for decannulation after veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is considered standard practice. However, access-site complications with this technique are not rare. The objective of this study is to evaluate feasibility, safety, and efficacy of a complete percutaneous decannulation procedure after VA-ECMO compared with the conventional surgical cutdown approach.

Methods: In 35 patients who were successfully weaned from VA-ECMO support, femoral artery and vein access sites were closed using a completely percutaneous approach in 15 patients, whereas 20 patients had conventional surgical cutdown for access-site closure. Data concerning all 35 patients were collected retrospectively and analyzed regarding immediate vascular closure success, associated complications, and clinical outcomes.

Results: Technical deployment success of the percutaneous vascular closure devices was achieved in all patients. Immediate success of closure was achieved more frequently in the surgical group (29% vs 100%; P<.05). Severe wound complications requiring surgery occurred only in the surgical group (0% vs 35%; P=NS). Surgical cutdown was associated with a significantly greater need for transfusion of packed red blood cells (1.6 ± 1.4 vs 2.2 ± 1.2; P<.05). Mean hospital stay was shorter in the percutaneous group (32 ± 18 days vs 36 ± 12 days; P=NS). One patient in the surgical group complained about sustained paresthesia after discharge.

Conclusions: Complete percutaneous closure of the femoral access site after VA-ECMO is feasible, effective, and safe when compared with conventional surgical closure and performed by experienced operators.
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October 2016

Impact of Rosuvastatin Treatment on HDL-Induced PKC-βII and eNOS Phosphorylation in Endothelial Cells and Its Relation to Flow-Mediated Dilatation in Patients with Chronic Heart Failure.

Authors:
Ephraim B Winzer Pauline Gaida Robert Höllriegel Tina Fischer Axel Linke Gerhard Schuler Volker Adams Sandra Erbs

Cardiol Res Pract 2016 2;2016:4826102. Epub 2016 Aug 2.

Leipzig Heart Center, Department of Cardiology, Leipzig University, 04289 Leipzig, Germany.

Background. Endothelial function is impaired in chronic heart failure (CHF). Statins upregulate endothelial NO synthase (eNOS) and improve endothelial function. Recent studies demonstrated that HDL stimulates NO production due to eNOS phosphorylation at Ser(1177), dephosphorylation at Thr(495), and diminished phosphorylation of PKC-βII at Ser(660). The aim of this study was to elucidate the impact of rosuvastatin on HDL mediated eNOS and PKC-βII phosphorylation and its relation to endothelial function. Methods. 18 CHF patients were randomized to 12 weeks of rosuvastatin or placebo. At baseline, 12 weeks, and 4 weeks after treatment cessation we determined lipid levels and isolated HDL. Human aortic endothelial cells (HAEC) were incubated with isolated HDL and phosphorylation of eNOS and PKC-βII was evaluated. Flow-mediated dilatation (FMD) was measured at the radial artery. Results. Rosuvastatin improved FMD significantly. This effect was blunted after treatment cessation. LDL plasma levels were reduced after rosuvastatin treatment whereas drug withdrawal resulted in significant increase. HDL levels remained unaffected. Incubation of HAEC with HDL had no impact on phosphorylation of eNOS or PKC-βII. Conclusion. HDL mediated eNOS and PKC-βII phosphorylation levels in endothelial cells do not change with rosuvastatin in CHF patients and do not mediate the marked improvement in endothelial function.
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http://dx.doi.org/10.1155/2016/4826102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4985575PMC
August 2016

Coronary Collateral Growth Induced by Physical Exercise: Results of the Impact of Intensive Exercise Training on Coronary Collateral Circulation in Patients With Stable Coronary Artery Disease (EXCITE) Trial.

Authors:
Sven Möbius-Winkler Madlen Uhlemann Volker Adams Marcus Sandri Sandra Erbs Karsten Lenk Norman Mangner Ulrike Mueller Jennifer Adam Martin Grunze Susanne Brunner Thomas Hilberg Meinhard Mende Axel P Linke Gerhard Schuler

Circulation 2016 Apr 15;133(15):1438-48; discussion 1448. Epub 2016 Mar 15.

From University of Leipzig, Heart Centre, Department of Internal Medicine/Cardiology, Germany (A.M.-W., M.U., V.A., M.S., S.E., K.L., N.M., U.M., J.A., A.P.L., G.S.); Asklepios Clinic Weißenfels, Germany (S.M.-W., K.L.); MediClin Dünenwald Klinik Trassenheide, Germany (M.G., S.B.); Department of Sports Medicine, University Wuppertal, Germany (T.H.); and Coordination Centre for Clinical Trials, University of Leipzig, Germany (M.M.).

Background: A well-developed coronary collateral circulation provides a potential source of blood supply in coronary artery disease. However, the prognostic importance and functional relevance of coronary collaterals is controversial with the association between exercise training and collateral growth still unclear.

Methods And Results: This prospective, open-label study randomly assigned 60 patients with significant coronary artery disease (fractional flow reserve ≤0.75) to high-intensity exercise (group A, 20 patients) or moderate-intensity exercise (group B, 20 patients) for 4 weeks or to a control group (group C, 20 patients). The primary end point was the change of the coronary collateral flow index (CFI) after 4 weeks. Analysis was based on the intention to treat. After 4 weeks, baseline CFI increased significantly by 39.4% in group A (from 0.142±0.07 at beginning to 0.198±0.09 at 4 weeks) in comparison with 41.3% in group B (from 0.143±0.06 to 0.202±0.09), whereas CFI in the control group remained unchanged (0.7%, from 0.149±0.09 to 0.150±0.08). High-intensity exercise did not lead to a greater CFI than moderate-intensity training. After 4 weeks, exercise capacity, Vo2 peak and ischemic threshold increased significantly in group A and group B in comparison with group C with no difference between group A and group B.

Conclusions: A significant improvement in CFI was demonstrated in response to moderate- and high-intensity exercise performed for 10 hours per week.

Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01209637.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.115.016442DOI Listing
April 2016

Long-Term Exercise Training in Patients With Advanced Chronic Heart Failure: SUSTAINED BENEFITS ON LEFT VENTRICULAR PERFORMANCE AND EXERCISE CAPACITY.

Authors:
Robert Höllriegel Ephraim B Winzer Axel Linke Volker Adams Norman Mangner Marcus Sandri T Scott Bowen Rainer Hambrecht Gerhard Schuler Sandra Erbs

J Cardiopulm Rehabil Prev 2016 Mar-Apr;36(2):117-24

Department of Internal Medicine/Cardiology (Drs Höllriegel, Winzer, Linke, Adams, Mangner, Sandri, Bowen, Schuler, and Erbs), University of Leipzig-Heart Center, Leipzig, Germany; and Heart Center Bremen (Dr Hambrecht), Klinikum Links der Weser, Bremen, Germany.

Purpose: In moderately impaired, stable chronic heart failure (CHF) patients, exercise training (ET) enhances exercise capacity. In contrast, the therapeutic benefits of regular ET in patients with advanced CHF, especially in the long-term, are limited or conflicting. Therefore, the aim of the present investigation was to elucidate whether ET performed over 12 months would improve left ventricular performance and exercise capacity in patients with advanced CHF.

Methods: Thirty-seven patients with CHF and New York Heart Association (NYHA) class IIIb were randomized to a sedentary lifestyle or daily ET on a cycle ergometer (in-hospital and home-based at 50%-60% of maximal exercise capacity). Cardiopulmonary exercise testing and echocardiography were performed at baseline, 3, 6, and 12 months.

Results: Exercise training resulted in continuous decreases in left ventricular end-diastolic diameter at 3, 6, and 12 months versus baseline (all P < .05). This was accompanied by a significant increase in resting left ventricular ejection fraction from 24.1% ± 1.2% at baseline to 38.4% ± 2.0% at 12-month followup (P < .05). Moreover, ET patients increased exercise capacity measured by maximal oxygen uptake (Equation is included in full-text article.)O2max at 3, 6, and 12 months compared with baseline: 15.3 ± 0.8 mL/min/kg, 17.8 ± 0.8 mL/min/kg, 19.0 ± 0.7 mL/min/kg, and 19.5 ± 0.9 mL/min/kg, respectively (all P < .05 vs baseline). This was associated with a reduced NYHA classification.

Conclusions: Exercise training over 12 months resulted in an improvement in exercise capacity and reversing of left ventricular remodeling in patients with advanced CHF (NYHA IIIb). These beneficial adaptations continued to improve up to 6 months and remained stable thereafter.
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http://dx.doi.org/10.1097/HCR.0000000000000165DOI Listing
December 2016

Long term impact of one daily unit of physical exercise at school on cardiovascular risk factors in school children.

Authors:
Ulrike M Müller Claudia Walther Volker Adams Meinhard Mende Jennifer Adam Kati Fikenzer Katharina C Machalica Sandra Erbs Axel Linke Gerhard Schuler

Eur J Prev Cardiol 2016 09 11;23(13):1444-52. Epub 2016 Feb 11.

Department of Internal Medicine/Cardiology, Heart Centre Leipzig, University of Leipzig, Germany.

Background: Obesity and physical inactivity in children correlate with the presence of cardiovascular risk factors. The aim of this prospective, randomised, interventional study was to examine the long term impact of additional physical exercise lessons at school on fitness and cardiovascular risk factors.

Methods: We randomly assigned 366 5th and 6th grade students class-wise into an intervention group that participated in one-daily physical exercise unit at school and a control group, participating in conventional school sports twice a week. The intervention duration was 4 years. At baseline and yearly follow-up, anthropometric measurements, body coordination tests, spiroergometry, questionnaires and blood samples were performed.

Results: A total of 236 children qualified for analysis of the intervention effect after 4 years. At the beginning students of the intervention and control groups had similar values for fitness assessed by peak oxygen uptake. Peak oxygen uptake was significantly better in the intervention group at first and second follow-up. After 4 years we found no difference in fitness any longer. Students in the intervention group were more likely to have healthy body mass index percentiles in comparison to the control group (within 10th to 90th percentile: intervention 86.4%, control 78.2%, P = 0.13).

Conclusion: Over a period of 1-2 years, additional physical exercise lessons at school resulted in an improvement of fitness. However, long-term follow-up failed to demonstrate ongoing improvement of performance in the intervention compared with the control group. Nevertheless, the intervention group had lower rates of body mass index above the 90th percentile throughout the entire follow-up. Therefore more physical exercise units at school seem justified.
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http://dx.doi.org/10.1177/2047487316632966DOI Listing
September 2016

Thrombus Aspiration in Patients With ST-Segment Elevation Myocardial Infarction Presenting Late After Symptom Onset.

Authors:
Steffen Desch Thomas Stiermaier Suzanne de Waha Philipp Lurz Matthias Gutberlet Marcus Sandri Norman Mangner Enno Boudriot Michael Woinke Sandra Erbs Gerhard Schuler Georg Fuernau Ingo Eitel Holger Thiele

JACC Cardiovasc Interv 2016 Jan;9(2):113-22

University Heart Center Lübeck, Medical Clinic II (Cardiology/Angiology/Intensive Care Medicine), University Hospital Schleswig-Holstein, Lübeck, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Lübeck, Germany.

Objectives: The aim of this study was to examine whether manual thrombus aspiration reduces microvascular obstruction assessed by cardiac magnetic resonance imaging in patients with ST-segment elevation myocardial infarction (STEMI) presenting late after symptom onset.

Background: Thrombus aspiration is an established treatment option in patients with STEMI undergoing primary percutaneous coronary intervention (PCI). However, there are only limited data on the efficacy of thrombus aspiration in patients with STEMI presenting ≥12 h after symptom onset.

Methods: Patients with subacute STEMI presenting ≥12 and ≤48 h after symptom onset were randomized to primary PCI with or without manual thrombus aspiration in a 1:1 ratio. Patients underwent cardiac magnetic resonance imaging 1 to 4 days after randomization. The primary endpoint was the extent of microvascular obstruction.

Results: A total of 152 patients underwent randomization. The mean time between symptom onset and PCI was 28 ± 12 h. Baseline characteristics were comparable between groups. The majority of patients (60%) showed at least a moderate amount of viable myocardium in the affected region. Extent of microvascular obstruction was not significantly different between patients assigned to thrombus aspiration and the control group (2.5 ± 4.0% vs. 3.1 ± 4.4% of left ventricular mass, p = 0.47). There were also no significant differences in infarct size, myocardial salvage, left ventricular ejection fraction, and angiographic and clinical endpoints between groups.

Conclusions: In this first randomized trial of thrombectomy in patients with STEMI presenting late after symptom onset, routine thrombus aspiration before PCI failed to show a benefit for markers of reperfusion success. (Effect of Thrombus Aspiration in Patients With Myocardial Infarction Presenting Late After Symptom Onset; NCT01379248).
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http://dx.doi.org/10.1016/j.jcin.2015.09.010DOI Listing
January 2016

Skeletal muscle alterations in chronic heart failure: differential effects on quadriceps and diaphragm.

Authors:
Norman Mangner Bettina Weikert T Scott Bowen Marcus Sandri Robert Höllriegel Sandra Erbs Rainer Hambrecht Gerhard Schuler Axel Linke Stephan Gielen Volker Adams

J Cachexia Sarcopenia Muscle 2015 Dec 30;6(4):381-90. Epub 2015 Apr 30.

Department of Internal Medicine/Cardiology, University of Leipzig-Heart Center Leipzig, Germany.

Background: Chronic heart failure (CHF) results in limb and respiratory muscle weakness, which contributes to exercise intolerance and increased morbidity and mortality, yet the molecular mechanisms remain poorly understood. Therefore, we aimed to compare parameters of antioxidative capacity, energy metabolism, and catabolic/anabolic balance in diaphragm and quadriceps muscle in an animal model of CHF.

Methods: Ligation of the left anterior descending coronary artery (n = 13) or sham operation (n = 11) was performed on Wistar Kyoto rats. After 12 weeks, echocardiography and invasive determination of maximal rates of left ventricular (LV) pressure change were performed. Antioxidative and metabolic enzyme activities and expression of catabolic/anabolic markers were assessed in quadriceps and diaphragm muscle.

Results: Ligated rats developed CHF (i.e. severe LV dilatation, reduced LV ejection fraction, and impaired maximal rates of LV pressure change; P < 0.001). There was a divergent response for antioxidant enzymes between the diaphragm and quadriceps in CHF rats, with glutathione peroxidase and manganese superoxide dismutase activity increased in the diaphragm but reduced in the quadriceps relative to shams (P < 0.01). Metabolic enzymes were unaltered in the diaphragm, but cytochrome c oxidase activity (P < 0.01) decreased and lactate dehydrogenase activity (P < 0.05) increased in the quadriceps of CHF animals. Protein expression of the E3 ligase muscle ring finger 1 and proteasome activity were increased (P < 0.05) in both the diaphragm and quadriceps in CHF rats compared with shams.

Conclusion: Chronic heart failure induced divergent antioxidative and metabolic but similar catabolic responses between the diaphragm and quadriceps. Despite the quadriceps demonstrating significant impairments in CHF, apparent beneficial adaptations of an increased antioxidative capacity were induced in the diaphragm. Nevertheless, muscle ring finger 1 and proteasome activity (markers of protein degradation) were elevated and oxidative enzyme activity failed to increase in the diaphragm of CHF rats, which suggest that a myopathy is likely present in respiratory muscle in CHF, despite its constant activation.
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http://dx.doi.org/10.1002/jcsm.12034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4670747PMC
December 2015

The Leipzig Prospective Drug-Eluting Balloon-Registry - Outcome of 484 Consecutive Patients Treated for Coronary In-Stent Restenosis and De Novo Lesions Using Paclitaxel-Coated Balloons.

Authors:
Madlen Uhlemann Sven Möbius-Winkler Jennifer Adam Sandra Erbs Norman Mangner Marcus Sandri Enno Boudriot Michael Woinke Gerhard C Schuler Axel Linke

Circ J 2016 2;80(2):379-86. Epub 2015 Dec 2.

Heart Centre, Department of Internal Medicine/Cardiology, University of Leipzig, University of Leipzig.

Background: Drug-eluting balloons (DEB) are an alternative treatment of in-stent restenosis (ISR), but data regarding outcomes of DEB in de novo lesions are lacking.

Methods and results: We investigated the effect of DEB on target lesion revascularization (TLR), procedural complications (coronary dissection/rupture, pericardial effusion, stent thrombosis, peri-interventional NSTEMI, stroke), major adverse cardiac and cerebrovascular events (all-cause mortality, myocardial infarction, TLR, stroke) in patients with ISR and de novo lesions in an all-comers setting. Between April 2009 and October 2013, 484 consecutive patients (mean age 68.4 years; 77.9% male) were enrolled in a prospective registry. TLR rate was 4.9% at 12 months and 8.7% at long-term follow-up of 2.3 years. Subgroup analysis confirmed a TLR rate of 8.9% after DEB treatment of ISR in bare-metal stents (21/235 lesions), 13.0% in drug-eluting stents (21/161 lesions) and 0% for de novo lesions (0/76 lesions). At long-term follow-up, all-cause mortality/cardiac mortality was 8.7% (42/484)/3.3% (16/484) and MACCE rate was 18.4% (89/484 patients), with no differences between DEB for ISR compared with de novo lesions.

Conclusions: DEB for ISR resulted in a low rate of TLR. Our data support DEB in ISR as an effective treatment option. DEB in small coronary vessels in our limited cohort appeared to be safe. Larger, randomized trials in small coronary vessels should be undertaken to verify the long-term results of the current trial.
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http://dx.doi.org/10.1253/circj.CJ-14-1352DOI Listing
October 2016

Cardioprotection by combined intrahospital remote ischaemic perconditioning and postconditioning in ST-elevation myocardial infarction: the randomized LIPSIA CONDITIONING trial.

Authors:
Ingo Eitel Thomas Stiermaier Karl P Rommel Georg Fuernau Marcus Sandri Norman Mangner Axel Linke Sandra Erbs Phillip Lurz Enno Boudriot Meinhard Mende Steffen Desch Gerhard Schuler Holger Thiele

Eur Heart J 2015 Nov 17;36(44):3049-57. Epub 2015 Sep 17.

University Heart Center Lübeck, Medical Clinic II (Cardiology/Angiology/Intensive Care Medicine), University Hospital Schleswig-Holstein, Ratzeburger Allee 160, 23538 Lübeck, Germany German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Lübeck, Germany.

Aims: Remote ischaemic conditioning (RIC) and postconditioning (PostC) are both potent activators of innate protection against ischaemia-reperfusion injury and have demonstrated cardioprotection in experimental and clinical ST-elevation myocardial infarction (STEMI) trials. However, their combined effects have not been studied in detail. The aim of this study was to evaluate if the co-application of intrahospital RIC and PostC has a more powerful effect on myocardial salvage compared with either PostC alone or control.

Methods And Results: This prospective, controlled, single-centre study randomized 696 STEMI patients to one of the following three groups: (i) combined intrahospital RIC + PostC in addition to primary percutaneous coronary intervention (PCI); (ii) PostC in addition to PCI; and (iii) conventional PCI (control). The primary endpoint myocardial salvage index was assessed by cardiac magnetic resonance (CMR) imaging within 3 days after infarction. Secondary endpoints included infarct size and microvascular obstruction (MVO) assessed by CMR. The combined clinical endpoint consisted of death, reinfarction, and new congestive heart failure within 6 months. The primary endpoint myocardial salvage index was significantly greater in the combined RIC + PostC group when compared with the control group (49 [interquartile range 30-72] vs. 40 [interquartile range 16-68], P = 0.02). Postconditioning alone failed to improve myocardial salvage when compared with conventional PCI (P = 0.39). The secondary endpoints, including infarct size and MVO, showed no significant differences between groups. Clinical follow-up at 6 months revealed no differences in the combined clinical endpoint between groups (P = 0.44).

Conclusion: Combined intrahospital RIC + PostC in conjunction with PCI in STEMI significantly improves myocardial salvage in comparison with control and PostC.

Clinicaltrialsgov: NCT02158468.
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http://dx.doi.org/10.1093/eurheartj/ehv463DOI Listing
November 2015

Chronic heart failure and aging - effects of exercise training on endothelial function and mechanisms of endothelial regeneration: Results from the Leipzig Exercise Intervention in Chronic heart failure and Aging (LEICA) study.

Authors:
Marcus Sandri Manuel Viehmann Volker Adams Kristin Rabald Norman Mangner Robert Höllriegel Philipp Lurz Sandra Erbs Axel Linke Katharina Kirsch Sven Möbius-Winkler Joachim Thiery Daniel Teupser Rainer Hambrecht Gerhard Schuler Stephan Gielen

Eur J Prev Cardiol 2016 Mar 26;23(4):349-58. Epub 2015 May 26.

Martin-Luther-University Halle/Wittenberg, University Hospital, Department of Internal Medicine III, Halle/Saale, Germany.

Background: A reduction in number and function of endothelial progenitor cells (EPCs) occurs in both physiologic aging and chronic heart failure (CHF). We assessed whether disease and aging have additive effects on EPCs or whether beneficial effects of exercise training are diminished in old age.

Methods: We randomized 60 patients with stable CHF and 60 referent controls to a training or a control group. To detect possible aging effects we included subjects below 55 (young) and above 65 years (older). Subjects in the training group exercised four times daily at 60% to 70% of VO2max for four weeks under supervision. At baseline and after the intervention the number and function of EPCs were assessed.

Results: As compared with young referent controls, older referent controls showed at baseline a reduced EPC number (young: 190 ± 37 CD34/KDR positive cells/ml blood; older: 131 ± 26 CD34/KDR positive cells/ml blood; p < 0.05) and function (young: 230 ± 41 migrated cells/1000 plated cells; older: 185 ± 28 cells/1000 plated cells; p < 0.05). In young and older CHF patients EPC-number (young: 85 ± 21 CD34/KDR positive cells/ml blood; older: 78 ± 20 CD34/KDR positive cells/ml blood) and EPC-function (young: 113 ± 26 cells/1000 plated cells; older: 120 ± 27 cells/1000 plated cells) were impaired. As a result of exercise training, EPC function improved by 24% in older referent controls (p < 0.05), while it remained unchanged in young training referent controls and controls respectively. In young and older patients with CHF four weeks of exercise training resulted in a significant improvement in EPC numbers and EPC function (young: number +66% function +43%; p < 0.05; older: number +69% function +36%; p < 0.05). These results were accompanied by a significant increase in flow mediated dilatation in the training groups of young/older CHF patients and in older referent controls.

Conclusions: Four weeks of exercise training are effective in improving EPC number and EPC function in CHF patients. These training effects were not impaired among older patients, emphasizing the potentials of rehabilitation interventions in a patient group where CHF has a high prevalence.
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http://dx.doi.org/10.1177/2047487315588391DOI Listing
March 2016

Serum irisin levels are regulated by acute strenuous exercise.

Authors:
Dennis Löffler Ulrike Müller Kathrin Scheuermann Daniela Friebe Julia Gesing Julia Bielitz Sandra Erbs Kathrin Landgraf Isabel Viola Wagner Wieland Kiess Antje Körner

J Clin Endocrinol Metab 2015 Apr 27;100(4):1289-99. Epub 2015 Jan 27.

Center for Paediatric Research Leipzig (D.L., K.S., D.F., J.G., J.B., K.L., I.V.W., W.K., A.K.), University Hospital for Children and Adolescents, Integrated Research and Treatment Center Adiposity Diseases (D.L., K.L., A.K.), and Leipzig Heart Centre (U.M., S.E.), Department of Cardiology, University of Leipzig, 04103 Leipzig, Germany.

Rationale: The newly discovered myokine irisin has been proposed to affect obesity and metabolism by promoting browning of white adipose tissue. However, clinical and functional studies on the association of irisin with obesity, muscle mass, and metabolic status remain controversial. Here we assessed the effect of 4 distinct exercise regimens on serum irisin levels in children and young adults and systematically evaluated the influence of diurnal rhythm, anthropometric and metabolic parameters, and exercise on irisin.

Results: Serum irisin levels did not show diurnal variations, nor were they affected by meal intake or defined glucose load during oral glucose tolerance testing. Irisin levels decreased with age. In adults, irisin levels were higher in men than in women, and obese subjects had significantly higher levels than lean control subjects. Irisin levels were closely correlated with muscle-associated bioimpedance parameters such as fat-free mass and body cell mass. Of the 4 exercise regimens that differed in duration and intensity, we identified a clear and immediate increase in serum irisin levels after acute strenuous exercise (cycling ergometry) and a 30-minute bout of intensive exercise in children and young adults, whereas longer (6 weeks) or chronic (1 year) increases in physical activity did not affect irisin levels.

Summary: We show that irisin levels are affected by age, sex, obesity, and particularly muscle mass, whereas diurnal rhythm and meals do not contribute to the variation in irisin levels. Short bouts of intensive exercise but not long-term elevations in physical activity, acutely and transiently increase serum irisin levels in children and adults.
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http://dx.doi.org/10.1210/jc.2014-2932DOI Listing
April 2015

Childhood obesity: impact on cardiac geometry and function.

Authors:
Norman Mangner Kathrin Scheuermann Ephraim Winzer Isabel Wagner Robert Hoellriegel Marcus Sandri Marion Zimmer Meinhard Mende Axel Linke Wieland Kiess Gerhard Schuler Antje Körner Sandra Erbs

JACC Cardiovasc Imaging 2014 Dec 8;7(12):1198-205. Epub 2014 Oct 8.

University of Leipzig, Heart Center Leipzig, Department of Internal Medicine/Cardiology, Leipzig, Germany.

Objectives: The aim of our study was to assess geometric and functional changes of the heart in obese compared with nonobese children and adolescents.

Background: Obesity in children and adolescents has increased over the past decades and is considered a strong risk factor for future cardiovascular morbidity and mortality. Obesity has been associated with myocardial structural alterations that may influence cardiac mechanics.

Methods: We prospectively recruited 61 obese (13.5 ± 2.7 years of age, 46% male sex, SD score body mass index, 2.52 ± 0.60) and 40 nonobese (14.1 ± 2.8 years of age, 50% male sex, SD score body mass index, -0.33 ± 0.83) consecutive, nonselected Caucasian children and adolescents. A standardized 2-dimensional (2D) echocardiography and 2D speckle-tracking analysis was performed in all children. Furthermore, blood chemistry including lipid and glucose metabolism was assessed in all children.

Results: Compared with nonobese children, blood pressure, low-density lipoprotein cholesterol, and parameters of glucose metabolism were significantly increased in obese children, whereas high-density lipoprotein cholesterol was significantly lower. Compared with nonobese children, obese children were characterized by enlarged left- and right-sided cardiac chambers, thicker left ventricular walls, and, consequently, increased left ventricular mass. Despite a comparable left ventricular ejection fraction, decreased tissue Doppler-derived peak systolic velocity and regional basoseptal strain were found in obese children compared with nonobese children. Beyond that, 2D speckle tracking-derived longitudinal (-18.2 ± 2.0 vs. -20.5 ± 2.3, p < 0.001) and circumferential (-17.0 ± 2.7 vs. -19.5 ± 2.9, p < 0.001) strain of the left ventricle was reduced in obese children compared with nonobese children. Diastolic function was also impaired in obese compared with nonobese children. Both longitudinal strain and circumferential strain were independently associated with obesity.

Conclusions: The results of this study demonstrate that childhood obesity is associated with significant changes in myocardial geometry and function, indicating an early onset of potentially unfavorable alterations in the myocardium.
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http://dx.doi.org/10.1016/j.jcmg.2014.08.006DOI Listing
December 2014

Exercise training improves high-density lipoprotein-mediated transcription of proangiogenic microRNA in endothelial cells.

Authors:
Saskia Riedel Stephan Radzanowski T Scott Bowen Sarah Werner Sandra Erbs Gerhard Schuler Volker Adams

Eur J Prev Cardiol 2015 Jul 23;22(7):899-903. Epub 2014 Jun 23.

Department of Cardiology, University Leipzig - Heart Center Leipzig, Leipzig, Germany

Background: The functional properties of endothelial cells (ECs) for regulating nitric oxide (NO) bioavailability are important for normal endothelial function. Micro-RNAs (miRs) and especially angiomiRs regulate vascular integrity and angiogenesis. Besides regulation of reverse cholesterol transport, high-density lipoprotein (HDL) also stimulates NO generation by ECs. This function is impaired in patients with chronic heart failure (CHF) and can be attenuated by exercise training. The aim of the present study was to evaluate if HDL-induced miR expression is altered in CHF and if exercise training has an impact.

Methods: HDL was isolated from CHF patients in NYHA-IIIb (HDLNYHA) and healthy subjects (HDLHealthy) before and after exercise training. Subsequently ECs were incubated for 24 h with the isolated HDL and miR expression was quantified by RT-PCR.

Results: HDL-induced expression of miR-126, miR-21 and miR-222 was significantly reduced in ECs incubated with HDLNYHA when compared to HDLHealthy. Exercise training attenuated this HDL-induced reduction of miR-126 and miR-21. HDL-induced expression of miR-221 and miR-214 was not altered in CHF compared to controls and no impact of exercise training was noted.

Conclusion: In conclusion, the present study shows that HDL isolated from CHF patients (NYHA-III) reduces the expression of pro-angiogenic miRs (i.e. miR-126 and miR-21), which may contribute to atherogenesis and endothelial dysfunction. However, exercise training was able to attenuate the HDL-induced reduction in pro-angiogenic miRs expression.
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http://dx.doi.org/10.1177/2047487314541036DOI Listing
July 2015

Long-term clinical outcome after intracoronary application of bone marrow-derived mononuclear cells for acute myocardial infarction: migratory capacity of administered cells determines event-free survival.

Authors:
Birgit Assmus David M Leistner Volker Schächinger Sandra Erbs Albrecht Elsässer Werner Haberbosch Rainer Hambrecht Daniel Sedding Jiangtao Yu Roberto Corti Detlef G Mathey Christine Barth Charlotte Mayer-Wehrstein Iris Burck Tim Sueselbeck Thorsten Dill Christian W Hamm Torsten Tonn Stefanie Dimmeler Andreas M Zeiher

Eur Heart J 2014 May 25;35(19):1275-83. Epub 2014 Feb 25.

Cardiology, Deptartment of Medicine III, Goethe University Frankfurt, Theodor-Stern-Kai 7, Frankfurt 60590, Germany.

Background: In the REPAIR-AMI trial, intracoronary infusion of bone marrow-derived cells (BMCs) was associated with a significantly greater recovery of contractile function in patients with acute myocardial infarction (AMI) at 4-month follow-up than placebo infusion. The current analysis investigates clinical outcome and predictors of event-free survival at 5 years.

Methods And Results: In the multicentre, placebo-controlled, double-blind REPAIR-AMI trial, 204 patients received intracoronary infusion of BMCs (n = 101) or placebo (n = 103) into the infarct vessel 3-7 days following successful percutaneous coronary intervention. Fifteen patients died in the placebo group compared with seven patients in the BMC group (P = 0.08). Nine placebo-treated patients and five BMC-treated patients required rehospitalization for chronic heart failure (P = 0.23). The combined endpoint cardiac/cardiovascular/unknown death or rehospitalisation for heart failure was more frequent in the placebo compared with the BMC group (18 vs. 10 events; P = 0.10). Univariate predictors of adverse outcomes were age, the CADILLAC risk score, aldosterone antagonist and diuretic treatment, changes in left ventricular ejection fraction, left ventricular end-systolic volume, and N-terminal pro-Brain Natriuretic Peptide (all P < 0.01) at 4 months in the entire cohort and in the placebo group. In contrast, in the BMC group, only the basal (P = 0.02) and the stromal cell-derived factor-1-induced (P = 0.05) migratory capacity of the administered BMC were associated with improved clinical outcome.

Conclusion: In patients of the REPAIR-AMI trial, established clinical parameters are associated with adverse outcome at 5 years exclusively in the placebo group, whereas the migratory capacity of the administered BMC determines event-free survival in the BMC-treated patients. These data disclose a potency-effect relationship between cell therapy and long-term outcome in patients with AMI.
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http://dx.doi.org/10.1093/eurheartj/ehu062DOI Listing
May 2014

Exercise training in patients with chronic heart failure promotes restoration of high-density lipoprotein functional properties.

Authors:
Volker Adams Christian Besler Tina Fischer Meliana Riwanto Friederike Noack Robert Höllriegel Andreas Oberbach Nico Jehmlich Uwe Völker Ephraim B Winzer Karsten Lenk Rainer Hambrecht Gerhard Schuler Axel Linke Ulf Landmesser Sandra Erbs

Circ Res 2013 Dec 20;113(12):1345-55. Epub 2013 Sep 20.

From the Departments of Cardiology (V.A., T.F., F.N., R.H., E.B.W., K.L., G.S., A.L., S.E.) and Cardiac Surgery (A.O.), Heart Center Leipzig, Leipzig University, Germany; Department of Cardiology, University Hospital Zürich, Switzerland (C.B., M.R., U.L.); Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Germany (N.J., U.V.); DZHK (German Center for Cardiovascular Research), Greifswald, Germany (U.V.); and Klinikum Links der Weser, Heart Center Bremen, Germany (R.H.).

Rationale: High-density lipoprotein (HDL) exerts endothelial-protective effects via stimulation of endothelial cell (EC) nitric oxide (NO) production. This function is impaired in patients with cardiovascular disease. Protective effects of exercise training (ET) on endothelial function have been demonstrated.

Objective: This study was performed to evaluate the impact of ET on HDL-mediated protective effects and the respective molecular pathways in patients with chronic heart failure (CHF).

Methods And Results: HDL was isolated from 16 healthy controls (HDL(healthy)) and 16 patients with CHF-NYHA-III (HDL(NYHA-IIIb)) before and after ET, as well as from 8 patients with CHF-NYHA-II (HDL(NYHA-II)). ECs were incubated with HDL, and phosphorylation of eNOS-Ser(1177), eNOS-Thr(495), PKC-βII-Ser(660), and p70S6K-Ser(411) was evaluated. HDL-bound malondialdehyde and HDL-induced NO production by EC were quantified. Endothelial function was assessed by flow-mediated dilatation. The proteome of HDL particles was profiled by shotgun LC-MS/MS. Incubation of EC with HDL(NYHA-IIIb) triggered a lower stimulation of phosphorylation at eNOS-Ser(1177) and a higher phosphorylation at eNOS-Thr(495) when compared with HDL(healthy). This was associated with lower NO production of EC. In addition, an elevated activation of p70S6K, PKC-βII by HDL(NYHA-IIIb), and a higher amount of malondialdehyde bound to HDL(NYHA-IIIb) compared with HDL(healthy) was measured. In healthy individuals, ET had no effect on HDL function, whereas ET of CHF-NYHA-IIIb significantly improved HDL function. A correlation between changes in HDL-induced NO production and flow-mediated dilatation improvement by ET was evident.

Conclusions: These results demonstrate that HDL function is impaired in CHF and that ET improved the HDL-mediated vascular effects. This may be one mechanism how ET exerts beneficial effects in CHF.
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http://dx.doi.org/10.1161/CIRCRESAHA.113.301684DOI Listing
December 2013

Impact of intracoronary bone marrow cell therapy on left ventricular function in the setting of ST-segment elevation myocardial infarction: a collaborative meta-analysis.

Authors:
Ronak Delewi Alexander Hirsch Jan G Tijssen Volker Schächinger Wojciech Wojakowski Jérôme Roncalli Svend Aakhus Sandra Erbs Birgit Assmus Michal Tendera R Goekmen Turan Roberto Corti Tim Henry Patricia Lemarchand Ketil Lunde Feng Cao Heikki V Huikuri Daniel Sürder Robert D Simari Stefan Janssens Kai C Wollert Michal Plewka Stefan Grajek Jay H Traverse Felix Zijlstra Jan J Piek

Eur Heart J 2014 Apr 11;35(15):989-98. Epub 2013 Sep 11.

Department of Cardiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105AZ Amsterdam, the Netherlands.

Aims: The objective of the present analysis was to systematically examine the effect of intracoronary bone marrow cell (BMC) therapy on left ventricular (LV) function after ST-segment elevation myocardial infarction in various subgroups of patients by performing a collaborative meta-analysis of randomized controlled trials.

Methods And Results: We identified all randomized controlled trials comparing intracoronary BMC infusion as treatment for ST-segment elevation myocardial infarction. We contacted the principal investigator for each participating trial to provide summary data with regard to different pre-specified subgroups [age, diabetes mellitus, time from symptoms to percutaneous coronary intervention, infarct-related artery, LV end-diastolic volume index (EDVI), LV ejection fraction (EF), infarct size, presence of microvascular obstruction, timing of cell infusion, and injected cell number] and three different endpoints [change in LVEF, LVEDVI, and LV end-systolic volume index (ESVI)]. Data from 16 studies were combined including 1641 patients (984 cell therapy, 657 controls). The absolute improvement in LVEF was greater among BMC-treated patients compared with controls: [2.55% increase, 95% confidence interval (CI) 1.83-3.26, P < 0.001]. Cell therapy significantly reduced LVEDVI and LVESVI (-3.17 mL/m², 95% CI: -4.86 to -1.47, P < 0.001; -2.60 mL/m², 95% CI -3.84 to -1.35, P < 0.001, respectively). Treatment benefit in terms of LVEF improvement was more pronounced in younger patients (age <55, 3.38%, 95% CI: 2.36-4.39) compared with older patients (age ≥ 55 years, 1.77%, 95% CI: 0.80-2.74, P = 0.03). This heterogeneity in treatment effect was also observed with respect to the reduction in LVEDVI and LVESVI. Moreover, patients with baseline LVEF <40% derived more benefit from intracoronary BMC therapy. LVEF improvement was 5.30%, 95% CI: 4.27-6.33 in patients with LVEF <40% compared with 1.45%, 95% CI: 0.60 to 2.31 in LVEF ≥ 40%, P < 0.001. No clear interaction was observed between other subgroups and outcomes.

Conclusion: Intracoronary BMC infusion is associated with improvement of LV function and remodelling in patients after ST-segment elevation myocardial infarction. Younger patients and patients with a more severely depressed LVEF at baseline derived most benefit from this adjunctive therapy.
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http://dx.doi.org/10.1093/eurheartj/eht372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4271100PMC
April 2014

Five-year clinical follow-up of a randomized comparison of a polymer-free sirolimus-eluting stent versus a polymer-based paclitaxel-eluting stent in patients with diabetes mellitus (LIPSIA Yukon trial).

Authors:
Thomas Stiermaier Anja Heinz Denis Schloma Klaus Kleinertz Wilfried Dänschel Sandra Erbs Axel Linke Enno Boudriot Bernward Lauer Gerhard Schuler Holger Thiele Steffen Desch

Catheter Cardiovasc Interv 2014 Feb 9;83(3):418-24. Epub 2013 Aug 9.

Department of Internal Medicine - Cardiology, University of Leipzig - Heart Center, Leipzig, Germany.

Objectives: The long-term performance of polymer-free stent systems in patients with diabetes mellitus has not been investigated extensively. This study reports long-term results of the LIPSIA Yukon trial which compared the polymer-free sirolimus-eluting Yukon Choice stent with the polymer-based paclitaxel-eluting Taxus Liberté stent in this subpopulation. At 9 months, the Yukon Choice stent failed to show non-inferiority in terms of the primary end point late lumen loss, while no significant difference in clinical outcome was detected.

Methods And Results: The LIPSIA Yukon trial randomized 240 patients with diabetes mellitus to a polymer-free sirolimus eluting stent (Yukon Choice, Translumina) versus a polymer-based paclitaxel-eluting stent (Taxus Liberté, Boston Scientific). Clinical follow-up was conducted with a standardized telephone follow-up and all events were centrally adjudicated. Follow-up was available for 98.3% of patients after a median of 5.0 years. The incidence of all-cause death (16.9% versus 14.0%, P = 0.67), respectively definite or presumed cardiovascular death (7.6% versus 8.8%, P = 0.94) were similar in the Yukon Choice and the Taxus Liberté group. There were no significant differences in the rates of myocardial infarction (9.3% versus 7.9%, P = 0.88), definite stent thrombosis (0.8% versus 0.9%, P = 1.0), target lesion revascularization (15.3% versus 15.8%, P = 1.0), target vessel revascularization (18.6% versus 23.7%, P = 0.44), non-target vessel revascularization (18.6% versus 26.3%, P = 0.21), and stroke (3.4% versus 4.4%, P = 0.96) between patients assigned to the Yukon Choice and the Taxus Liberté stent.

Conclusion: At 5 years of follow-up, clinical outcome was similar between the polymer-free sirolimus-eluting Yukon Choice stent and the polymer-based paclitaxel-eluting Taxus Liberté stent.
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http://dx.doi.org/10.1002/ccd.25131DOI Listing
February 2014

The REMEDEE trial: a randomized comparison of a combination sirolimus-eluting endothelial progenitor cell capture stent with a paclitaxel-eluting stent.

Authors:
Michael Haude Stephen W L Lee Stephen G Worthley Sigmund Silber Stefan Verheye Sandra Erbs Mohd Ali Rosli Roberto Botelho Ian Meredith Kui Hian Sim Pieter R Stella Huay-Cheem Tan Robert Whitbourn Sukumaran Thambar Alexandre Abizaid Tian Hai Koh Peter Den Heijer Helen Parise Ecaterina Cristea Akiko Maehara Roxana Mehran

JACC Cardiovasc Interv 2013 Apr 20;6(4):334-43. Epub 2013 Mar 20.

Städtische Kliniken Neuss, Lukaskrankenhaus GmbH, Neuss, Germany.

Objectives: This study sought to compare the efficacy and safety results after coronary implantation of a combined sirolimus-eluting CD34 antibody coated Combo stent (OrbusNeich Medical, Ft. Lauderdale, Florida) with the paclitaxel-eluting Taxus Liberté stent (PES) (Boston Scientific, Natick, Massachusetts). This report summarizes the first-in-man randomized, controlled multicenter REMEDEE trial (Randomized study to Evaluate the safety and effectiveness of an abluMinal sirolimus coatED bio-Engineered StEnt) angiographic, intravascular ultrasound, and clinical results up to 12 months.

Background: Drug-eluting stents have limited restenosis and reintervention but are complicated by especially late and very late stent thrombosis and accelerated neoatherosclerosis. Alternative or adjunct technologies should address these limitations.

Methods: One hundred eighty-three patients with de novo native coronary artery stenoses were randomized 2:1 to Combo stent or PES implantation. The primary endpoint is the angiographic in-stent late lumen loss at 9 months, which was tested for noninferiority between the 2 stent groups. Secondary endpoints include the occurrence of major adverse cardiac events.

Results: The Combo stent was found to be noninferior to the PES in 9-month angiographic in-stent late lumen loss with 0.39 ± 0.45 mm versus 0.44 ± 0.56 mm (pnoninferiority = 0.0012). At 12 months, the occurrence of major adverse cardiac events was 8.9% in the Combo group and 10.2% in the PES group (p = 0.80) with no difference in mortality, occurrence of myocardial infarction, or target lesion revascularization. No stent thrombosis was reported in either group.

Conclusions: In the REMEDEE trial the Combo stent has shown to be effective by meeting the primary noninferiority angiographic endpoint and safe, with an overall low rate of clinical events in both stent groups, including no stent thrombosis up to 12 months.
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http://dx.doi.org/10.1016/j.jcin.2012.10.018DOI Listing
April 2013

Impact of different exercise training modalities on the coronary collateral circulation and plaque composition in patients with significant coronary artery disease (EXCITE trial): study protocol for a randomized controlled trial.

Authors:
Madlen Uhlemann Volker Adams Karsten Lenk Axel Linke Sandra Erbs Jennifer Adam Holger Thiele Thomas Hilberg Matthias Gutberlet Martin Grunze Gerhard C Schuler Sven Möbius-Winkler

Trials 2012 Sep 14;13:167. Epub 2012 Sep 14.

Sports medicine, University Wuppertal, Wuppertal, Germany.

Background: Exercise training (ET) in addition to optimal medical therapy (OMT) in patients with stable coronary artery disease (CAD) has been demonstrated to be superior to percutaneous coronary interventions (PCI) with respect to the composite endpoint of death, myocardial infarction, stroke, revascularization and hospitalization due to worsening of angina. One mechanism leading to this superiority discussed in the literature is the increase in coronary collateral blood flow due to ET. Until now, data demonstrating the positive effect of ET on the collateral blood flow and the functional capacity of the coronary collateral circulation are still lacking.

Methods/design: The EXCITE trial is a three-armed randomized, prospective, single-center, open-label, controlled study enrolling 60 patients with stable CAD and at least one significant coronary stenosis (fractional flow reserve ≤0.75). The study is designed to compare the influence and efficacy of two different 4-week ET programs [high-intensity interval trainings (IT) versus moderate-intensity exercise training (MT) in addition to OMT] versus OMT only on collateral blood flow (CBF). The primary efficacy endpoint is the change of the CBF of the target vessel after 4 weeks as assessed by coronary catheterization with a pressure wire during interruption of the antegrade flow of the target vessel by balloon occlusion. Secondary endpoints include the change in plaque composition as assessed by intravascular ultrasound (IVUS) after 4 weeks, myocardial perfusion as analyzed in MRI after 4 weeks and 12 months, peak oxygen uptake (V02 peak), change in endothelial function and biomarkers after 4 weeks, 3, 6 and 12 months. The safety endpoint addresses major adverse cardiovascular events (death from cardiovascular cause, myocardial infarction, stroke, TIA, target vessel revascularization or hospitalization) after 12 months.

Discussion: The trial investigates whether ET for 4 weeks increases the CBF in patients with significant CAD compared to a sedentary control group. It also examines the impact of two intensities of ET on the CBF as well as the histological plaque composition. The trial started recruitment in June 2009 and will complete recruitment until June 2012. First results are expected in December 2012 (4-week follow-up), final results (12-month long-term secondary endpoint) in December 2013.

Trial Registration: Clinical trial registration information-URL: http://www.clinicaltrials.gov.Unique identifier: NCT01209637.
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http://dx.doi.org/10.1186/1745-6215-13-167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3495905PMC
September 2012

Adiponectin promotes the migration of circulating angiogenic cells through p38-mediated induction of the CXCR4 receptor.

Authors:
Volker Adams John T Heiker Robert Höllriegel Ephraim B Beck Felix J Woitek Sandra Erbs Matthias Blüher Michael Stumvoll Annette G Beck-Sickinger Gerhard Schuler Axel Linke

Int J Cardiol 2013 Sep 7;167(5):2039-46. Epub 2012 Jun 7.

Department of Internal Medicine/Cardiology, University Leipzig, Heart Center, Leipzig, Germany.

Aims: Adiponectin (adipo) and exercise training (ET) contribute to the maintenance of a normal vascular tone by influencing vascular NO bioavailability and concentration and function of circulating angiogenic cells (CAC). The molecular mechanisms are only partially understood. Aim of the present study was to elucidate the effects of adipo on CAC migration and the underlying signaling pathways. Furthermore, the impact of ET on adiponectin-mediated CAC migration was investigated.

Methods And Results: CACs were isolated from peripheral blood and exposed to different adipo concentrations. Adipo (5μg/ml) enhanced the ability of CACs to migrate following an SDF-1 gradient by 345%. This was associated with a significant increase in CXCR4 expression on the surface of CACs as compared to control (10.1 ± 1.5 vs. 33.2 ± 4.5% CXCR4 positive cells, p<0.05). Adiponectin-induced CAC migration and CXCR4-upregulation were mediated through adipo-receptor 1 (AdipoR1) and blocked by an inhibitor of PI3-kinase, p38MAP kinase and NFκb. Adipo-stimulated migration of CACs, CXCR4 expression and p38MAPK-activation is impaired in patients with coronary artery disease (CAD). ET over 4 weeks partially corrects adiponectin-stimulated CAC migration and CXCR4 expression in patients with CAD (n=10). No change was observed in the control group (n=10).

Conclusion: Adipo improves the migratory capacity of CACs in response to SDF1, partially through an upregulation of CXCR4. This is mediated through a pathway that involves binding of adipo to the AdipoR1 and subsequent PI3kinase/p38MAPK/ NFκb activation. In addition ET corrects the adiponectin responsiveness of CACs, and thereby might promote endogenous repair of damaged endothelium.
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http://dx.doi.org/10.1016/j.ijcard.2012.05.056DOI Listing
September 2013