Showing papers by "Heart and Diabetes Center North Rhine-Westphalia published in 2017"

Antifibrinolytic Therapy and Perioperative Considerations

Abstract: Fibrinolysis is a physiologic component of hemostasis that functions to limit clot formation. However, after trauma or surgery, excessive fibrinolysis may contribute to coagulopathy, bleeding, and inflammatory responses. Antifibrinolytic agents are increasingly used to reduce bleeding, allogeneic blood administration, and adverse clinical outcomes. Tranexamic acid is the agent most extensively studied and used in most countries. This review will explore the role of fibrinolysis as a pathologic mechanism, review the different pharmacologic agents used to inhibit fibrinolysis, and focus on the role of tranexamic acid as a therapeutic agent to reduce bleeding in patients after surgery and trauma.

Phenotyping of Sleep-Disordered Breathing in Patients With Chronic Heart Failure With Reduced Ejection Fraction-the SchlaHF Registry

Abstract: Background-Different sleep-disordered breathing (SDB) phenotypes, including coexisting obstructive and central sleep apnea (OSA-CSA), have not yet been characterized in a large sample of patients with heart failure and reduced ejection fraction (HFrEF) receiving guideline-based therapies. Therefore, the aim of the present study was to determine the proportion of OSA, CSA, and OSA-CSA, as well as periodic breathing, in HFrEF patients with SDB. Methods and Results-The German SchlaHF registry enrolled patients with HFrEF receiving guideline-based therapies, who underwent portable SDB monitoring. Polysomnography (n=2365) was performed in patients with suspected SDB. Type of SDB (OSA, CSA, or OSA-CSA), the occurrence of periodic breathing (proportion of Cheyne-Stokes respiration >= 20%), and blood gases were determined in 1557 HFrEF patients with confirmed SDB. OSA, OSA-CSA, and CSA were found in 29%, 40%, and 31% of patients, respectively; 41% showed periodic breathing. Characteristics differed significantly among SDB groups and in those with versus without periodic breathing. There was a relationship between greater proportions of CSA and the presence of periodic breathing. Risk factors for having CSA rather than OSA were male sex, older age, presence of atrial fibrillation, lower ejection fraction, and lower awake carbon dioxide pressure (PCO2). Periodic breathing was more likely in men, patients with atrial fibrillation, older patients, and as left ventricular ejection fraction and awake PCO2 decreased, and less likely as body mass index increased and minimum oxygen saturation decreased. Conclusions-SchlaHF data show that there is wide interindividual variability in the SDB phenotype of HFrEF patients, suggesting that individualized management is appropriate.

Adherence of Heart Transplant Recipients to Prescribed Medication and Recommended Lifestyle Habits.

Abstract: Introduction:Nonadherence may cause severe health problems in heart transplant (HTx) recipients.Research Questions:The present study aimed to investigate adherence to prescribed medication and reco...

The Biphasic Effect of Vitamin D on the Musculoskeletal and Cardiovascular System.

Abstract: This narrative review summarizes beneficial and harmful vitamin D effects on the musculoskeletal and cardiovascular system. Special attention is paid to the dose-response relationship of vitamin D with clinical outcomes. In infants and adults, the risk of musculoskeletal diseases is highest at circulating 25-hydroxyvitamin D (25OHD) concentrations below 25 nmol/L and is low if 40-60 nmol/L are achieved. However, evidence is also accumulating that in elderly people the risk of falls and fractures increases again at circulating 25OHD levels > 100 nmol/L. Cohort studies report a progressive increase in cardiovascular disease (CVD) events at 25OHD levels 100 nmol/L, but the threshold may be influenced by the level of physical activity. In conclusion, dose-response relationships indicate deleterious effects on the musculoskeletal system and probably on the cardiovascular system at circulating 25OHD levels 100 nmol/L. Future studies should focus on populations with 25OHD levels 100 nmol/L.

Quantitative Fundus Autofluorescence in Pseudoxanthoma Elasticum.

Abstract: Purpose To quantify lipofuscin-associated fundus autofluorescence in patients with pseudoxanthoma elasticum (PXE), a model disease for Bruch's membrane pathology. Methods In this prospective, monocenter, cross-sectional case-control study, 49 patients with PXE (mean age: 46 years, range 18-62) underwent quantitative fundus autofluorescence (qAF) imaging with a modified scanning laser ophthalmoscope containing an internal fluorescent reference for normalization of images. The mean qAF values of a circular ring centered on the fovea (qAF8) were measured and compared to 108 healthy controls (mean age 40 years, range 18-64). Results Overall, patients with PXE showed lower qAF8 values compared to controls (difference from controls -23%, 95% confidence interval [CI] -29% to -16%, P < 0.001). The reduction was most pronounced in patients older than 40 years (-30%, 95% CI -36% to -23%, P < 0.001) and was negatively correlated with the extent of Bruch's membrane calcification (r = -0.49, 95% CI: -0.67 to -0.22). The topographic distribution revealed a greater reduction of qAF values toward the optic disc than temporally compared to controls (P < 0.001). The phenotype of patients with reduced qAF values was characterized by pattern-dystrophy-like changes (71%; 10 of 14), reticular pseudodrusen (71%; 10 of 14) and limited areas of atrophy (29%, 4 of 14). Conclusions Reduced qAF8 values are a characteristic finding in patients with PXE, indicating that Bruch's membrane disease may result in a modification of the accumulation, distribution, or composition (or a combination thereof) of lipofuscin in retinal pigment epithelial cells.

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.

Third generation drug eluting stent (DES) with biodegradable polymer in diabetic patients: 5 years follow-up

Abstract: To report the long-term safety and efficacy data of a third generation drug eluting stent (DES) with biodegradable polymer in the complex patient population of diabetes mellitus after a follow-up period of 5 years. After percutaneous coronary intervention patients with diabetes mellitus are under higher risk of death, restenosis and stent thrombosis (ST) compared to non-diabetic patients. In 126 centers worldwide 3067 patients were enrolled in the NOBORI 2 registry, 888 patients suffered from diabetes mellitus (DM), 213 of them (14%) being insulin dependent (IDDM). Five years follow-up has been completed in this study. At 5 years, 89.3% of the patients were available for follow-up. The reported target lesion failure (TLF) rates at 5 years were 12.39% in DM group and 7.34% in non-DM group; (p < 0.0001). In the DM group, the TLF rate in patients with IDDM was significantly higher than in the non-IDDM subgroup (17.84 vs. 10.67%; p < 0.01). The rate of ST at 5 years was not different among diabetic versus non-diabetic patients or IDDM versus NIDDM. Only 10 (<0.4%) very late stent thrombotic events beyond 12 months occurred. The Nobori DES performed well in patients with DM. As expected patients with DM, particularly those with IDDM, had worse outcomes. However, the very low rate of very late stent thrombosis in IDDM patients might have significant clinical value in the treatment of these patients. Clinical trial registration ISRCTN81649913; http://www.controlled-trials.com/isrctn/search.html?srch=81649913&sort=3&dir=desc&max=10

Independent associations of vitamin D metabolites with anemia in patients referred to coronary angiography: the LURIC study

Abstract: Purpose Anemia and vitamin D deficiency are both frequent in adult patients. Whether low vitamin D metabolite levels are an independent risk factor for different subtypes of anemia remains to be studied in detail.

FLNC (Filamin-C): A New(er) Player in the Field of Genetic Cardiomyopathies.

Abstract: In 1990, the Seidman group identified the first pathogenic cardiomyopathy mutation in a large 4-generation family, where several members were affected by hypertrophic cardiomyopathy.1 Since this first report, the number of genes and mutations associated with different cardiomyopathies is increasing from year to year. Currently, mutations in >170 genes associated with different cardiomyopathies, channelopathies, or syndromes with cardiac involvement are described. The huge number of different genes and mutations involved in cardiomyopathies limited routine genetic diagnostics for a long time. For example, Sanger sequencing of TTN, encoding the giant sarcomere protein titin, was difficult, expensive, and time consuming and limited the routine genetic diagnosis.2,3 Therefore, it was not surprising that the development of efficient next-generation sequencing technology pushed also the genetic diagnostics of cardiovascular diseases. Today, cardiovascular next-generation sequencing techniques are implemented in many diagnostic laboratories.4 The availability of next-generation sequencing technology has in the meantime provided the important insight that cardiomyopathies are remarkable heterogeneous disorders with different expressivity and penetrance. The challenges for the future remain the identification of phenotype–genotype relationships and consequences of genotyping for the development of personalized therapies. See Article Tucker and McLellan et al In this context, the contribution of a genetic pathogenesis to restrictive cardiomyopathy (RCM) is incompletely understood. Besides genetic factors, RCM might be a secondary cardiomyopathy and part of a systemic disease like the mineralization disorder pseudoxanthoma elasticum or cardiac amyloidosis. First mutations associated with familial RCM were identified in TNNI3 by the research group of William McKenna in 2003.5 During the …

Y-box Binding Protein-1 Enhances Oncogenic Transforming Growth Factor β Signaling in Breast Cancer Cells via Triggering Phospho-Activation of Smad2.

Abstract: Background/aim Transforming growth factor β (TGFβ) plays a role in diverse oncogenic pathways including cell proliferation and cell motility and is regulated by the pleiotropic factor Y-box binding protein-1 (YB-1). In breast cancer, Sma/Mad related protein 2 (Smad2) represents the most common downstream transducer in TGFβ signaling. Materials and methods Here, YB-1's impact on Smad2 phospho-activation was characterized by incubation of the breast cancer cell line MCF-7 with or without TGFβ1 in the absence or presence of overexpressed YB-1 protein. The phospho-status of Smad2 was assessed via western blotting. Results Analysis of MCF-7 cells revealed no induction of total Smad2 neither in the presence of TGFβ1, nor during YB-1 overexpression. In contrast, incubation with TGFβ1 led to an increase of phosphorylated Smad2 forms which was significantly amplified by simultaneously overexpressed YB-1 (2.8±0.2-fold). Conclusion Oncogenic YB-1 indirectly enhances TGFβ signaling cascades via Smad2 phospho-activation and may represent a promising factor for future diagnosis and therapy of breast cancer.

Comparative assessment of "plaque/media" change on three modalities of IVUS immediately after implantation of either everolimus-eluting bioresorbable vascular scaffold or everolimus-eluting metallic stent in Absorb II study.

Abstract: The purpose of the study to assess the comparability of immediate changes in plaque/media volume (PV) on three modalities of intravascular ultrasound (IVUS) after implantation of either bioresorbable vascular scaffold (BVS) or everolimus-eluting metallic stent (EES) in Absorb II Study. The two devices have different device volume and ultrasound backscattering that may interfere with the “plaque/media” assessed by three modalities on IVUS: grayscale, backscattering of radiofrequency and brightness function. In a multicenter randomized controlled trial, 501 patients with stable or unstable angina underwent documentary IVUS pre- and post- implantation. The change in plaque/media volume (PV) was categorized into three groups according to the relative PV change in device segment: PV “increased” >+5% (PVI), PV unchanged ±5% (PVU), and PV decreased <−5% (PVD). The change in PV was re-evaluated three times: after subtraction of theoretical device volume, after analysis of echogenicity based on brightness function. In 449 patients, 483 lesions were analyzed pre- and post-implantation. “PVI” was more frequently observed in BVS (53.8%) than EES group (39.4%), p = 0.006. After subtraction of the theoretical device volume, the frequency of “PVI” decreased in both BVS (36.2%) and EES (32.1%) groups and became comparable (p = 0.581). In addition, the percentage of “PVI” was further reduced in both device groups after correction for either radiofrequency backscattering (BVS 34.4% vs. EES 22.6%) or echogenicity (BVS 25.2% vs. EES 9.7%). PV change in device segment was differently affected by BVS and EES devices implantation due to their differences in device volume and ultrasound backscattering. It implies that the lumen volume was also artifactually affected by the type of device implanted. Comparative IVUS assessment of lumen and plaque/media volume changes following implantation of BVS and EES requires specific methodological adjustment.

Thorax-to-head ratio and defect diameter-to-head ratio in giant omphaloceles as predictor for fetal outcome

Abstract: To investigate the relationship between the thorax diameter and defect diameter of giant omphaloceles as a predictor for fetal outcome. In a retrospective study, 17 fetuses with isolated giant omphaloceles were included for evaluation. The anterior–posterior thorax diameter and the defect diameter were measured from ultrasound images. For analysis, the thorax-to-head ratio (T/HC), the defect diameter-to-head ratio (DD/HC), and the quotient of the defect diameter and the thorax diameter (DD/T) were calculated. The days of ventilation (t ventilation), the duration until hospital discharge (t hospital), and the type of treatment were recorded as outcome parameters. No relationship was found between the calculated ratios (T/HC, DD/HC, or DD/T) and neither t hospital (r = −0.418, p = 0.095; r = −0.153, p = 0.556; and r = −0.023, p = 0.929; respectively) nor t ventilation (r = −0.391, p = 0.121; r = 0.041, p = 0.875; and r = 0.121, p = 0.645, respectively). The type of postnatal treatment was not associated with the three calculated ratios or t hospital (r = 0.155, p = 0.553; r = 0.019, p = 0.942; and r = 0.012, p = 0.965; r = −0.009, p = 0.973, respectively). In 53% of cases, t hospital was delayed due to additional and independent postnatal complications. Thorax diameter or defect diameter of giant omphaloceles is not predictive for fetal outcome. The perinatal care of these abdominal wall defects still remains a multidisciplinary challenge, but the outcome of giant omphaloceles is favorable at experienced centers.

Understanding Potential Drug Side Effects: Can We Translate Molecular Mechanisms to Clinical Applications?

Abstract: Anesthesiology, V 127 • No 1 6 July 2017 C LINICAL pharmacology is one important basis of modern anesthesiology. In this month’s edition of ANESTHESIOLOGY, Lecker et al.1 report the results of an investigation of high concentrations of tranexamic acid (TXA) on N-methyl-D-aspartate (NMDA) and glutamate receptors in cultured murine hippocampal neurons. The investigation was prompted by reports of seizures in patients receiving TXA during cardiac surgery. It is an excellent example of “reverse translation”: taking clinical problems to the laboratory to understand their etiology and mechanism. The role of antifibrinolytic therapy for bleeding continues to expand in medical practice. The antifibrinolytic agent most extensively used in 2016 is the lysine analog TXA, a drug developed in the 1950s by Okamoto Utakoin in Japan when searching for a therapy to treat postpartum hemorrhage. From the late 1960s until today TXA has been used in a growing number of surgical and nonsurgical settings to reduce bleeding including menorrhagia, cardiac surgery, orthopedic surgery, and in trauma. The results of the Clinical Randomization of an Antifibrinolytic in Significant Hemorrhage 2 (CRASH-2) trial in trauma patients had a major impact on its growing use in clinical practice.2 TXA also is used for prophylaxis in patients with hereditary angioedema and may have important antiinflammatory effects as a protease inhibitor.3 Despite this extensive use, reported side effects are infrequent.4 In 2009 TXA acid was entered into the World Health Organization list of essential medicines. In 2010, reports began to emerge suggesting increased nonischemic clinical seizures after cardiac surgery and cardiopulmonary bypass (CPB) with the use of high-dose TXA infusions.5 Additional analyses from larger retrospective evaluations also reported an increase in convulsive seizures after CPB even when TXA was used at lower doses.5 Despite these reports, it is important to realize that case reports are anecdotal. Retrospective analyses of clinical databases and even the gold standard of clinical studies, a double-blind, randomized, placebo-controlled prospective trial, can only suggest a potential association or statistical probability between drug administration and adverse effects. After cardiac surgery, seizures have multiple causes that range from emboli to the cerebral circulation, producing cerebral anoxia to other potential drug-induced effects. However, a cause–effect relationship of adverse events is best proven by elucidation of the molecular/pathophysiologic mechanisms of the potential adverse effect. Multiple mechanisms may be responsible for TXA producing seizures. Current reports suggest TXA increases neuronal excitation by antagonizing inhibitory γ-aminobutyric acid neurotransmission and inhibits neural glycine receptors.6,7 When one examines the chemical structures of TXA, γ-aminobutyric acid, and glycine and their similarities, additional mechanisms may be involved; however, epsilon aminocaproic acid, another lysine analog antifibrinolytic agent, has not been reported to produce seizures.5 Lecker et al.1 report that high concentrations of TXA inhibit NMDA receptors. The NMDA receptor is an ion channel receptor present in neural cells that is activated after glutamic acid or glycine binding to control neurotransmission in what is called synaptic plasticity. Thus, inhibiting these receptors will allow for neuronal excitation and thus Understanding Potential Drug Side Effects