Heart and Diabetes Center North Rhine-Westphalia

About: Heart and Diabetes Center North Rhine-Westphalia is a healthcare organization based out in Bad Oeynhausen, Germany. It is known for research contribution in the topics: Heart failure & Vitamin D and neurology. The organization has 288 authors who have published 357 publications receiving 9276 citations.

Echo-guided percutaneous coil embolization of a symptomatic massive metastasis of a renal cell carcinoma in the right ventricular outflow tract

Abstract: We present the case of a 41-year-old woman who was admitted to our centre with progressive symptoms of congestive heart failure (NYHA class III) 5 years after a radical nephrectomy for renal cell carcinoma. Magnetic resonance imaging demonstrated a 5 × 3 cm homogeneous intracardial mass causing right ventricular outflow tract obstruction, not accessible to surgical resection. Serial echo-guided, percutaneous coil embolization of the cardial metastasis was performed with Contour SE Microparticles® (150–250 or 300–500 μm) after identification of the target region of the metastasis by contrast injection (Levovist®) through the balloon catheter into the coronary artery under transoesophageal echocardiographic control prior to induction of the necrosis, corresponding to the technique which has been described for septal ablation in hypertrophic obstructive cardiomyopathy. Follow-up after serial embolization showed a good haemodynamic and a marked clinical response (dyspnoea NYHA I–II) which lasted during the 19 month of survival after the index procedure.

Synthesis, radiosynthesis, in vitro and first in vivo evaluation of a new matrix metalloproteinase inhibitor based on γ-fluorinated α-sulfonylaminohydroxamic acid

Abstract: To study MMP activity in vivo in disease, several radiolabeled MMP inhibitors functioning as radiotracers have been evaluated by means of SPECT and PET. Unfortunately, most of them suffer from metabolic instability, mainly hepatobiliary clearance and insufficient target binding. The introduction of a fluorine atom into MMPIs could contribute to target binding, enhance the metabolic stability and might shift the clearance towards more renal elimination. Recently developed α-sulfonylaminohydroxamic acid based γ-fluorinated inhibitors of MMP-2 and -9 provide promising fluorine interactions with the enzyme active site and high MMP inhibition potencies. The aim of this study is the (radio)synthesis of a γ-fluorinated MMP-2 and -9 inhibitor to evaluate its potential as a radiotracer to image MMP activity in vivo. Two new fluorine-containing, enantiomerically pure inhibitors for MMP-2 and -9 were synthesized in a six step sequence. Both enantiomers exhibited equal inhibition potencies in the low nanomolar and subnanomolar range. LogD value indicated better water solubility compared to the CGS 25966 based analog. The most potent inhibitor was successfully radiofluorinated. In vivo biodistribution in wild type mice revealed predominantly hepatobiliary clearance. Two major radioactive metabolites were found in different organs. Defluorination of the radiotracer was not observed. (Radio)synthesis of a CGS based γ-fluorinated MMP inhibitor was successfully accomplished. The (S)-enantiomer, which normally shows no biological activity, also exhibited high MMP inhibition potencies, which may be attributed to additional interactions of fluorine with enzyme’s active site. Despite higher hydrophilicity no significant differences in the clearance characteristics compared to non-fluorinated MMPIs was observed. Metabolically stabilizing effect of the fluorine was not monitored in vivo in wild type mice.

Vitamin D Metabolites and Fibroblast Growth Factor-23 in Patients with Left Ventricular Assist Device Implants: Association with Stroke and Mortality Risk

Abstract: Stroke and mortality risk in patients with left ventricular assist device (LVAD) implants continue to be high. Whether nonclassical cardiovascular risk markers such as vitamin D metabolites and fibroblast growth factor (FGF)-23 contribute to this risk remains to be studied, and this was the objective of our work. In 154 LVAD patients (91 HeartWare and 63 HeartMate II implants), we measured circulating 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D3 (1,25[OH]2D3), parathyroid hormone (PTH) and FGF-23 shortly before LVAD implantation and investigated their association with stroke and mortality risk during 1-year follow-up. Of the study cohort, 34.4 and 92.2 %, respectively, had deficient 25OHD ( 6.7 pmol/l) and FGF-23 values above the reference range (100 RU/ml). One-year freedom from stroke was 80.9 %, and 1-year survival was 64.3 %. The multivariable-adjusted hazard ratio of stroke was 2.44 (95 % CI: 1.09–5.45; P = 0.03) for the subgroup of 25OHD levels <25 nmol/l (reference group: 25OHD levels ≥25 nmol/l). The multivariable-adjusted hazard ratio of 1-year mortality was 2.78 (95 % CI: 1.52–5.09; P = 0.001) for patients with 25OHD levels <25 nmol/l compared with patients with 25OHD levels ≥25 nmol/l. PTH, FGF-23 and 1,25(OH)2D3 were not associated with stroke or mortality risk. In LVAD patients, deficient 25OHD levels are independently associated with high stroke and mortality risk. If confirmed in randomized controlled trials, preoperative correction of deficient vitamin D status could be a promising measure to reduce stroke and mortality risk in LVAD patients.