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.

Measurement of Circulating 1,25-Dihydroxyvitamin D: Comparison of an Automated Method with a Liquid Chromatography Tandem Mass Spectrometry Method

Abstract: Background. The clinical relevance of circulating 1,25-dihydroxyvitamin D (1,25(OH)2D) is probably underappreciated, but variations in the measurement of this difficult analyte between different methods limit comparison of results. Methods. In 129 clinical samples, we compared a new automated assay with a commercially available liquid chromatography tandem mass spectrometry (LC-MS/MS) kit. Results. Median (interquartile range) 1,25(OH)2D concentrations with the automated assay and the LC-MS/MS method were 26.6 pg/mL (18.5–39.0 pg/mL) and 23.6 pg/mL (16.1–31.3 pg/mL), respectively ( ). Using the method-specific cut-offs for deficient 1,25(OH)2D levels (<20 pg/mL for the automated assay and <17 pg/mL for the LC-MS/MS method), the percentage of patients classified as 1,25(OH)2D deficient was 28.7% and 27.1%, respectively. However, concordance between the two methods for deficient levels was only 62% and the concordance correlation coefficient was poor (0.534). The regression equation resulted in an intercept of −1.99 (95% CI: −7.33–1.31) and a slope of 1.27 (95% CI: 1.04–1.52) for the automated assay. The mean bias with respect to the mean of the two methods was −3.8 (1.96 SD: −28.3–20.8) pg/mL for the LC-MS/MS method minus the automated assay. Conclusions. The two methods show only modest correlation and further standardization is required to improve reliability and comparability of 1,25(OH)2D test procedures.

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.

Interventional closure of atrial septal defects in adult patients with Ebstein's anomaly.

Abstract: Ebstein's anomaly is frequently associated with interatrial communications. In patients with severe tricuspid regurgitation standard treatment is the surgical repair or replacement of the tricuspid valve and patch closure of the atrial septal defect. We sought to evaluate the feasibility and short-term outcome of interventional device closure of interatrial communications in Ebstein patients with mild to moderate tricuspid regurgitation and various degrees of clinical symptoms. In this case series of 9 patients the device closure could be performed safely and 8 of 9 patients improved in their exercise capacity or clinical condition. However, the patients need to be selected carefully and appropriately for this palliative method. In those with predominant left-to-right shunting, ASD-closure reduces the volume load of the right ventricle and can be performed according to routine procedures. In those patients with cyanosis and right-to-left shunting however, test occlusion of the interatrial communication with adequate balloon size followed by careful examination of the hemodynamics at rest and under catecholamine stimulation is compulsatory to evaluate the feasibility of device closure. The tricuspid regurgitation should not exceed moderate level, the right atrial and ventricular pressure should be within normal range for an adequate time during test occlusion and the systemic blood pressure and cardiac output maintained safely.

Cardiomyocyte Hypertrophy in Arrhythmogenic Cardiomyopathy

Abstract: Arrhythmogenic cardiomyopathy (AC) is a hereditary disease leading to sudden cardiac death or heart failure. AC pathology is characterized by cardiomyocyte loss and replacement fibrosis. Our goal was to determine whether cardiomyocytes respond to AC progression by pathological hypertrophy. To this end, we examined tissue samples from AC patients with end-stage heart failure and tissue samples that were collected at different disease stages from desmoglein 2-mutant mice, a well characterized AC model. We find that cardiomyocyte diameters are significantly increased in right ventricles of AC patients. Increased mRNA expression of the cardiac stress marker natriuretic peptide B is also observed in the right ventricle of AC patients. Elevated myosin heavy chain 7 mRNA expression is detected in left ventricles. In desmoglein 2-mutant mice, cardiomyocyte diameters are normal during the concealed disease phase but increase significantly after acute disease onset on cardiomyocyte death and fibrotic myocardial remodeling. Hypertrophy progresses further during the chronic disease stage. In parallel, mRNA expression of myosin heavy chain 7 and natriuretic peptide B is up-regulated in both ventricles with right ventricular preference. Calcineurin/nuclear factor of activated T cells (Nfat) signaling, which is linked to pathological hypertrophy, is observed during AC progression, as evidenced by Nfatc2 and Nfatc3 mRNA in cardiomyocytes and increased mRNA of the Nfat target regulator of calcineurin 1. Taken together, we demonstrate that pathological hypertrophy occurs in AC and is secondary to cardiomyocyte loss and cardiac remodeling.

Calciotropic and phosphaturic hormones in heart failure.

Abstract: Aims Despite adherence to evidence-based guidelines, heart failure [HF] still results in 5-year mortality rates of 50%, indicating a need to implement additional preventive/intervention strategies. This review summarizes data on alterations in the calciotropic and phosphaturic hormones 1,25-dihydroxyvitamin D [1,25(OH) 2 D] and fibroblast growth factors-23 [FGF-23] in HF and discusses non-pharmacological measures for targeting these hormones. Data synthesis The role of 1,25(OH) 2 D in the regulation of calcium and phosphate homeostasis is central. 1,25(OH) 2 D also plays a pivotal role in cardiac function, but is downregulated by FGF-23. There is accumulating evidence from epidemiological data that HF is associated with decreased circulating 1,25(OH) 2 D and elevated FGF-23 levels. In patients with failing hearts, very low 1,25(OH) 2 D and extremely high FGF-23 levels have been reported. Experimental data support the assumption that vitamin D deficiency and high serum phosphate/FGF-23 levels increase the risk of HF. This review provides a hypothesis of how vitamin D deficiency, high calcium/phosphorus intake, physical inactivity, and age-related renal impairment may all contribute to HF by adversely affecting calcium- and phosphate-regulating hormones. Several case series in infants and a meta-analysis of randomized controlled trials in adults have already reported successful treatment of or a significant risk reduction in HF by vitamin D supplements. The association of calcium/phosphorus intake, physical activity, or renal function with calciotropic/phosphaturic hormones and HF is however less well documented. Conclusions More attention should be paid in future to the association of circulating 1,25(OH) 2 D and FGF-23 levels with HF and to (non-pharmacological) measures for targeting these calciotropic/phosphaturic hormones.