0000000000189465
AUTHOR
Thomas F. Lüscher
Murine tissue factor disulfide mutation causes a bleeding phenotype with sex specific organ pathology and lethality.
Tissue factor is highly expressed in sub-endothelial tissue. The extracellular allosteric disulfide bond Cys186-Cys209 of human tissue factor shows high evolutionary conservation and in vitro evidence suggests that it significantly contributes to tissue factor procoagulant activity. To investigate the role of this allosteric disulfide bond in vivo, we generated a C213G mutant tissue factor mouse by replacing Cys213 of the corresponding disulfide Cys190-Cys213 in murine tissue factor. A bleeding phenotype was prominent in homozygous C213G tissue factor mice. Pre-natal lethality of 1/3rd of homozygous offspring was observed between E9.5 and E14.5 associated with placental hemorrhages. After b…
Improvement in Risk Stratification in Transcatheter Aortic Valve Implantation Using a Combination of the Tumor Marker CA125 and the Logistic EuroSCORE
Conventional risk scores have not been accurate in predicting peri- and postprocedural risk of patients undergoing transcatheter aortic valve implantation (TAVI). Elevated levels of the tumor marker carbohydrate antigen 125 (CA125) have been linked to adverse outcomes after TAVI. We studied the additional value of CA125 to that of the EuroSCORE in predicting long-term mortality after TAVI.During a median follow-up of 59 weeks, 115 of 422 patients (27%) died after TAVI. Mortality was higher with elevated CA125 (30 U/mL) and EuroSCORE (median) (47% vs 20%, P.001 and 38% vs 16%, P.001, respectively). In the multivariable analysis, CA125 (30 U/mL) remained an independent predictor of mortality …
Percutaneous coronary intervention of chronic total occlusions in patients with low left ventricular ejection fraction
Abstract Objectives The study sought to assess the outcome of percutaneous coronary intervention (PCI) of chronic total occlusions (CTOs) in patients with low left ventricular ejection fraction (LVEF) (≤35%). Background Data regarding the outcome of PCI in patients with low LVEF affected by CTO are scarcely reported. Methods The authors performed a prospective longitudinal multicenter study including consecutive patients undergoing elective PCI of CTOs. Patients were subdivided into 3 groups: group 1 (LVEF ≥50%), group 2 (LVEF 35% to 50%), and group 3 (LVEF ≤35%). Results A total of 839 patients (mean 64.6 ± 10.5 years of age, 87.7% men) underwent CTO PCI attempts. Baseline LVEF ≤35% was pr…
Proceedings from the European clinical consensus conference for renal denervation: considerations on future clinical trial design: Figure 1
Approximately 8–18% of all patients with high blood pressure (BP) are apparently resistant to drug treatment.1,2 In this situation, new strategies to help reduce BP are urgently needed but the complex pathophysiology of resistant hypertension makes this search difficult. Not surprisingly in this context, the latest non-drug treatment which triggered controversy is catheter-based renal denervation (RDN).3,4 The method uses radiofrequency energy, or alternatively ultrasound or chemical denervation, to disrupt renal nerves within the renal artery wall, thereby reducing sympathetic efferent and sensory afferent signalling to and from the kidneys.5,6 Various experimental models of hypertension s…
Mejora en la estratificación del riesgo tras el implante percutáneo de válvula aórtica mediante una combinación de marcador tumoral CA125 y EuroSCORE logístico
ResumenIntroduccion y objetivos El rendimiento de las puntuaciones de riesgo tradicionales para predecir el riesgo tras el implante percutaneo valvula aortica (TAVI) no es adecuado. Las altas concentraciones plasmaticas de antigeno carbohidrato 125 (CA125) se han asociado a un aumento del riesgo de eventos adversos tras TAVI. En este trabajo se evalua el valor pronostico adicional del CA125 sobre la puntuacion EuroSCORE para la prediccion de riesgo a largo plazo. Metodos y resultados Durante una mediana de seguimento de 59 semanas, murieron 115 de 422 pacientes (27%) despues de la TAVI. La mortalidad fue mayor entre aquellos con CA125 elevado (> 30 U/ml) y EuroSCORE ≥ mediana (el 47 frente …
Management of refractory angina: an update.
Abstract Despite the use of anti-anginal drugs and/or percutaneous coronary interventions (PCI) or coronary artery bypass grafting, the proportion of patients with coronary artery disease who have daily or weekly angina ranges from 2% to 24%. Refractory angina refers to long-lasting symptoms (for >3 months) due to established reversible ischaemia, which cannot be controlled by escalating medical therapy with the use of 2nd- and 3rd-line pharmacological agents, bypass grafting, or stenting. While there is uncertain prognostic benefit, the treatment of refractory angina is important to improve the quality of life of the patients affected. This review focuses on conventional pharmacolog…
PQ Interval in Patients With Fabry Disease
Fabry disease (FD) is an X-chromosomal inherited lysosomal storage disease resulting in intracellular storage of globotriaosylceramide. Cardiac involvement is most frequently manifested as left ventricular hypertrophy. However, patients with FD may also have from various conduction abnormalities particularly affecting atrioventricular (AV) conduction. The present study was designed to analyze primarily AV conduction abnormalities on baseline electrocardiograms of patients with FD and to investigate the correlation with echocardiographic findings. Electrocardiograms at rest of 207 patients with FD were compared to echocardiograms. PQ-interval shortening and first-degree AV block could be fou…
CKD NUTRITION, INFLAMMATION AND OXIDATIVE STRESS
Introduction and Aims: Serum p-cresyl sulfate associates with cardiovascular disease in patients at different stages of chronic kidney disease. p-Cresyl sulfate concentrations are determined by intestinal uptake of p-cresol, human metabolism to p-cresyl sulfate and renal clearance. Whether intestinal uptake of p-cresol itself is associated with cardiovascular disease in patients with renal disease has not been studied to date. Methods: We performed a prospective study in patients with chronic kidney disease stage 1-5 (clinicaltrials.gov NCT00441623). Intestinal uptake of p-cresol, under steady state conditions, was estimated from 24h urinary excretion of p-cresyl sulfate. Primary endpoint w…
Rationale and design of dal-VESSEL: a study to assess the safety and efficacy of dalcetrapib on endothelial function using brachial artery flow-mediated vasodilatation
Dalcetrapib increases high-density lipoprotein cholesterol (HDL-C) levels through effects on cholesteryl ester transfer protein (CETP). As part of the dalcetrapib dal-HEART clinical trial programme, the efficacy and safety of dalcetrapib is assessed in coronary heart disease (CHD) patients in the dal-VESSEL study (ClinicalTrials.gov identifier: NCT00655538), the design and methods of which are presented here. RESEARCH DESIGN AND STUDY METHOD: Men and women with CHD or CHD risk equivalent, with HDL-C levels50 mg/dL were recruited for a 36-week, double-blinded, placebo-controlled trial. After a pre-randomisation phase of up to 8 weeks, patients received dalcetrapib 600 mg/day or placebo in …
Ticagrelor, but not clopidogrel, reduces arterial thrombosis via endothelial tissue factor suppression
The P2Y12 antagonist ticagrelor reduces mortality in patients with acute coronary syndrome (ACS), compared with clopidogrel, and the mechanisms underlying this effect are not clearly understood. Arterial thrombosis is the key event in ACS; however, direct vascular effects of either ticagrelor or clopidogrel with focus on arterial thrombosis and its key trigger tissue factor have not been previously investigated.Methods and results: Human aortic endothelial cells were treated with ticagrelor or clopidogrel active metabolite (CAM) and stimulated with tumour necrosis factor-alpha (TNF-α); effects on procoagulant tissue factor (TF) expression and activity, its counter-player TF pathway inhibito…