@article{UngethuemWiedmannWagneretal.2023,
  author    = {Ungeth{\"u}m, K. and Wiedmann, S. and Wagner, M. and Leyh, R. and Ertl, G. and Frantz, S. and Geisler, T. and Karmann, W. and Prondzinsky, R. and Herdeg, C. and Noutsias, M. and Ludwig, T. and K{\"a}s, J. and Klocke, B. and Krapp, J. and Wood, D. and Kotseva, K. and St{\"o}rk, S. and Heuschmann, P. U.},
  title     = {Secondary prevention in diabetic and nondiabetic coronary heart disease patients: insights from the German subset of the hospital arm of the EUROASPIRE IV and V surveys},
  series = {Clinical Research in Cardiology},
  volume    = {112},
  journal   = {Clinical Research in Cardiology},
  number    = {2},
  doi       = {10.1007/s00392-022-02093-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324037},
  pages     = {285-298},
  year      = {2023},
  abstract  = {Background Patients with coronary heart disease (CHD) with and without diabetes mellitus have an increased risk of recurrent events requiring multifactorial secondary prevention of cardiovascular risk factors. We compared prevalences of cardiovascular risk factors and its determinants including lifestyle, pharmacotherapy and diabetes mellitus among patients with chronic CHD examined within the fourth and fifth EUROASPIRE surveys (EA-IV, 2012-13; and EA-V, 2016-17) in Germany. Methods The EA initiative iteratively conducts European-wide multicenter surveys investigating the quality of secondary prevention in chronic CHD patients aged 18 to 79 years. The data collection in Germany was performed during a comprehensive baseline visit at study centers in W{\"u}rzburg (EA-IV, EA-V), Halle (EA-V), and T{\"u}bingen (EA-V). Results 384 EA-V participants (median age 69.0 years, 81.3\% male) and 536 EA-IV participants (median age 68.7 years, 82.3\% male) were examined. Comparing EA-IV and EA-V, no relevant differences in risk factor prevalence and lifestyle changes were observed with the exception of lower LDL cholesterol levels in EA-V. Prevalence of unrecognized diabetes was significantly lower in EA-V as compared to EA-IV (11.8\% vs. 19.6\%) while the proportion of prediabetes was similarly high in the remaining population (62.1\% vs. 61.0\%). Conclusion Between 2012 and 2017, a modest decrease in LDL cholesterol levels was observed, while no differences in blood pressure control and body weight were apparent in chronic CHD patients in Germany. Although the prevalence of unrecognized diabetes decreased in the later study period, the proportion of normoglycemic patients was low. As pharmacotherapy appeared fairly well implemented, stronger efforts towards lifestyle interventions, mental health programs and cardiac rehabilitation might help to improve risk factor profiles in chronic CHD patients.},
  language  = {en}
}
@article{BeningHamoudaLeyh2016,
  author    = {Bening, C. and Hamouda, K. and Leyh, R.},
  title     = {Sex differences in volume overload in skinned fibers},
  series = {BMC Cardiovascular Disorders},
  volume    = {16},
  journal   = {BMC Cardiovascular Disorders},
  number    = {197},
  doi       = {10.1186/s12872-016-0370-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147896},
  year      = {2016},
  abstract  = {Background The impact of sex on cardiac morphology and function in chronic volume overload has been described in detail. However, the relation between sex and contractile properties at the actin-myosin level has not been well defined. Therefore, we evaluated the influence of sex on the contractile capacities of patients with chronic volume overload. Methods In 36 patients (18 males, 65 ± 9 years; 18 females, 65 ± 13 years) scheduled for elective mitral valve surgery due to severe mitral regurgitation (MR) with preserved left ventricular function, right auricle samples were obtained prior to extracorporal circulation. The fibers were prepared and skinned and exposed to a gradual increase in the calcium concentration (from pCa of 6.5-4.0) for calcium-induced force-developing measurements. Calcium sensitivity was also measured and recorded. Results The pCa-force relationship of the fibers obtained from males and females was significantly different, with the force values of the female fibers greater than those of male fibers at maximum calcium concentrations (pCa of 4.0: 3.6 ± 0.3 mN versus 3.2 ± 0.4 mN, p 0.02) and pCa of 4.5 2.6 ± 0.6 versus 2.0 ± 0.5, p 0.002). In contrast, the force values of female fibers were lower at mean calcium concentrations compared to those of male fibers (at 5.5 and pCa of 6.0: 1.0 ± 0.3 mN versus 1.2 ± 0.5 mN, p 0.04; 0.61 ± 0.05 versus 0.88 ± 0.09, p 0.04). Calcium sensitivity was observed at pCa of 5.0 in females and pCa of 4.5 in males. Conclusion This study demonstrated that female fibers from patients exposed to chronic volume overload developed higher force values at a given calcium concentration compared to fibers from male patients. We assume that female patients might tap the full force potential, which is required when exposed to the highest calcium concentrations in our experimental cycle. The calcium sensitivity among genders was significantly different, with the results suggesting that males have higher calcium sensitivity and might compensate for lower force values at maximal calcium concentrations by a higher affinity for calcium. Hence, female patients with MR seem to work more "energy efficient".},
  language  = {en}
}
@article{BeningSalesAlhussinietal.2021,
  author    = {Bening, Constanze and Sales, Virna L. and Alhussini, Khaled and Radakovic, Dejan and Cris Benitez, R. and Madrahimov, Nodir and Keller, Daria M. and Leyh, Rainer},
  title     = {Clinically inapparent right heart dysfunction is associated with reduced myofilament force development in coronary artery disease},
  series = {BMC Cardiovascular Disorders},
  volume    = {21},
  journal   = {BMC Cardiovascular Disorders},
  number    = {1},
  doi       = {10.1186/s12872-021-01926-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259213},
  pages     = {125},
  year      = {2021},
  abstract  = {Background Right ventricular dysfunction after CABG is associated with poor peri- and postoperative outcomes. We aimed to identify clinical and experimental predictors for preoperative inapparent right ventricular dysfunction and therefore hypothesized that reduced myofilament force development as well as altered levels of biomarkers might predict inapparent right ventricular dysfunction. Methods From 08/2016 to 02/2018, 218 patients scheduled for CABG were divided into two groups (TAPSE ≥ 20 mm, n = 178; TAPSE < 20 mm, n = 40). Baseline serum samples for biomarkers (Galectin, TGFß1, N Acyl-SDMA, Arginine, ADMA and Pentraxin-3), clinical laboratory and transthoracic echocardiographic parameters were evaluated. To examine the myocardial apparatus of the right ventricle intraoperative right auricular tissue was harvested for stepwise skinned fiber force measurements. Results Patients with TAPSE < 20 mm had a higher incidence of DM (55 vs. 34\%, p = 0.018), preoperative AFib (43 vs. 16\%, p < 0.001), reduced GFR (67 ± 18 vs. 77 ± 24 ml/min/1.73 m\(^2\), p = 0.013), larger LA area (22 ± 6 vs. 20 ± 5 cm\(^2\), p = 0.005) and reduced LVEF (50 vs. 55\%, p = 0.008). Furthermore, higher serum ADMA (0.70 ± 0.13 vs. 0.65 ± 0.15 µmol/l, p = 0.046) and higher serum Pentraxin-3 levels (3371 ± 1068 vs. 2681 ± 1353 pg/dl, p = 0.004) were observed in these patients. Skinned fiber force measurements showed significant lower values at almost every step of calcium concentration (pCa 4.52 to pCa 5.5, p < 0.01 and pCa 5.75-6.0, p < 0.05). Multivariable analysis revealed DM (OR 2.53, CI 1.12-5.73, Euro Score II (OR 1.34, CI 1.02-1.78), preoperative AF (OR 4.86, CI 2.06-11.47), GFR (OR 7.72, CI 1.87-31.96), albumin (OR 1.56, CI 0.52-2.60), Pentraxin-3 (OR 19.68, CI 14.13-25.24), depressed LVEF (OR 8.61, CI 6.37-10.86), lower force values: (pCa 5.4; OR 2.34, CI 0.40-4.29 and pCa 5.2; OR 2.00, CI 0.39-3.60) as predictors for clinical inapparent right heart dysfunction. Conclusions These preliminary data showed that inapparent right heart dysfunction in CAD is already associated with reduced force development of the contractile apparatus.},
  language  = {en}
}
@article{RadakovicReboredoHelmetal.2017,
  author    = {Radakovic, D. and Reboredo, J. and Helm, M. and Weigel, T. and Sch{\"u}rlein, S. and Kupczyk, E. and Leyh, R. G. and Walles, H. and Hansmann, J.},
  title     = {A multilayered electrospun graft as vascular access for hemodialysis},
  series = {PLoS ONE},
  volume    = {12},
  journal   = {PLoS ONE},
  number    = {10},
  doi       = {10.1371/journal.pone.0185916},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159102},
  pages     = {e0185916},
  year      = {2017},
  abstract  = {Despite medical achievements, the number of patients with end-stage kidney disease keeps steadily raising, thereby entailing a high number of surgical and interventional procedures to establish and maintain arteriovenous vascular access for hemodialysis. Due to vascular disease, aneurysms or infection, the preferred access—an autogenous arteriovenous fistula—is not always available and appropriate. Moreover, when replacing small diameter blood vessels, synthetic vascular grafts possess well-known disadvantages. A continuous multilayered gradient electrospinning was used to produce vascular grafts made of collagen type I nanofibers on luminal and adventitial graft side, and poly-ɛ-caprolactone as medial layer. Therefore, a custom-made electrospinner with robust environmental control was developed. The morphology of electrospun grafts was characterized by scanning electron microscopy and measurement of mechanical properties. Human microvascular endothelial cells were cultured in the graft under static culture conditions and compared to cultures obtained from dynamic continuous flow bioreactors. Immunofluorescent analysis showed that endothelial cells form a continuous luminal layer and functional characteristics were confirmed by uptake of acetylated low-density-lipoprotein. Incorporation of vancomycin and gentamicin to the medial graft layer allowed antimicrobial inhibition without exhibiting an adverse impact on cell viability. Most striking a physiological hemocompatibility was achieved for the multilayered grafts.},
  language  = {en}
}
@article{BeningGenserKelleretal.2023,
  author    = {Bening, C. and Genser, B. and Keller, D. and M{\"u}ller-Altrock, S. and Radakovic, D. and Penov, K. and Hassan, M. and Aleksic, I. and Leyh, R. and Madrahimov, N.},
  title     = {Impact of estradiol, testosterone and their ratio on left and right auricular myofilament function in male and female patients undergoing coronary artery bypass grafting},
  series = {BMC Cardiovascular Disorders},
  volume    = {23},
  journal   = {BMC Cardiovascular Disorders},
  doi       = {10.1186/s12872-023-03582-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357368},
  year      = {2023},
  abstract  = {Background The impact of sex hormones on right and left auricular contractile apparatus function is largely unknown. We evaluated the impact of sex hormones on left and right heart contractility at the level of myocardial filaments harvested from left and right auricles during elective coronary artery bypass surgery. Methods 150 patients (132 male; 18 female) were enrolled. Preoperative testosterone and estradiol levels were measured with Immunoassay. Calcium induced force measurements were performed with left- and right auricular myofilaments in a skinned fiber model. Correlation analysis was used for comparison of force values and levels of sex hormones and their ratio. Results Low testosterone was associated with higher top force values in right-sided myofilaments but not in left-sided myofilaments for both sexes (p = 0.000 in males, p = 0.001 in females). Low estradiol levels were associated with higher top force values in right-sided myofilaments (p 0.000) in females and only borderline significantly associated with higher top force values in males (p 0.056). In females, low estradiol levels correlated with higher top force values in left sided myofilaments (p 0.000). In males, higher Estradiol/Testosterone ratio (E/T ratio) was only associated with higher top force values from right auricular myofilaments (p 0.04) In contrast, in females higher E/T ratio was associated with lower right auricular myofilament top force values (p 0.03) and higher top force values in left-sided myofilaments (p 0.000). Conclusions This study shows that patients' comorbidities influence left and right sided contractility and may blur results concerning influence of sex hormones if not eliminated. A sex hormone dependent influence is obvious with different effects on the left and right ventricle. The E/T ratio and its impact on myofilament top force showed divergent results between genders, and may partially explain gender differences in patients with cardiovascular disease.},
  language  = {en}
}