CYP4A11 polymorphism correlates with coronary endothelial dysfunction in patients with coronary artery disease--the ENCORE Trials.

BACKGROUND: Cytochrome P450 (CYP) is expressed in the human endothelium and metabolizes arachidonic acid into vasoactive epoxyeicosatrienoic and 20-hydroxyeicosatetraenoic acids. CYP enzymes have been linked to hypertension and generation of reactive oxygen species. Thus, we investigated the impact of several CYP polymorphisms on coronary endothelial function in patients with coronary artery disease (CAD). METHODS AND RESULTS: We determined CYP4A11 F434S, CYP2C9 I359L, CYP2C9 G144C and CYP 2J2 promotor -50G>T polymorphisms in 734 patients with CAD undergoing percutaneous coronary intervention. Increasing concentrations of acetylcholine were infused in a coronary segment without angiographically significant CAD and the coronary artery vasomotor response was measured by quantitative angiography. Patients with substitution of phenylalanine 434 by serine (434SS, n=15, 2.04%) in CYP4A11 F434 demonstrated significantly augmented endothelium-dependent vasoconstriction (p=0.044 after Bonferroni correction) compared to patients with the 434FS (n=193, 26.29%) and 434FF genotype (n=526, 71.66%) before and after adjustment for blood pressure and HDL-cholesterol. In addition, patients with the 434SS genotype had higher systolic blood pressure levels (p=0.039) compared to the two other groups. The CYP 2C9 and CYP 2J2 polymorphisms did not show any correlation with coronary vasoconstriction, hypertension, diabetes mellitus, blood pressure or cholesterol. CONCLUSION: In patients with established and stable coronary artery disease the 434SS variant of CYP4A11 F434 is associated with pronounced coronary vasoconstriction.

Should human chondrocytes fly? The impact of electromagnetic irradiation on chondrocyte viability and implications for their use in tissue engineering.

A significant logistic factor as to the successful clinical application of the autologous tissue engineering concept is efficient transportation: the donor cells need to be delivered to tissue processing facilities which in most cases requires air transportation. This study was designed to evaluate how human chondrocytes react to X-ray exposure. Primary cell cultures were established, cultured, incubated and exposed to different doses and time periods of radiation. Subsequently, quantitative cell proliferation assays were done and qualitative evaluation of cellular protein production were performed. Our results show that after irradiation of chondrocytes with different doses, no significant differences in terms of cellular viability occurred compared with the control group. These results were obtained when chondrocytes were exposed to luggage transillumination doses as well as exposure to clinically used radiation doses. Any damage affecting cell growth or quality was not observed in our study. However, information about damage of cellular DNA remains incomplete.

[Diagnostic yield of the implantable loop recorder to detect the mechanism of syncope--a single center long term experience of a tertiary care center]. / Synkopenabklärung mittels implantierbarem Loop Recorder--Langzeiterfahrung eines Zentrumspitals.

AIM: The aim of this study was to investigate the usefulness in providing diagnostic information about syncope by implantation of a loop recorder (ILR). METHODS AND RESULTS: The study population consisted of 48 consecutive patients (23 male, 25 female, mean age 42 +/- 17) with unexplained syncope who presented between 1998 and 2002 and underwent extensive cardiological screening and were followed with an implantable loop recorder (Reveal or Reveal Plus). The mean follow-up duration was 9 +/- 6 months. During this follow-up in 17 (35%) patients syncope recurred. Arrhythmia correlating with syncope was documented in 15 (88%) of these patients, in 2 (12%) patients an arrhythmia could be excluded. Of these 15 patients with arrhythmogenic cause of syncope 5 (33%) patients revealed higher degree AV-Block, 7 (47%) patients sinus bradycardia or sinus pauses, 4 (27%) due to sick sinus syndrome and 3 (20%) due to neurally mediated syncope, 3 (20%) patients had atrial tachycardias or atrial fibrillation with rapid AV-conduction. As a result of ILR findings 12 pacemakers were implanted and 2 radiofrequency ablations were performed. CONCLUSION: The ILR is a valuable and effective tool to establish an arrhythmic cause for unexplained syncope. In these cases they have an impact on subsequent clinical decision making. ILR can also be useful in ruling out arrhythmias as cause of syncope and presyncope.

Transoesophageal echocardiography is unreliable for cardiac output assessment after cardiac surgery compared with thermodilution.

This randomised, single-blind, double-control study compared and established prospectively the best transoesophageal echocardiography methods for determining cardiac output in patients after cardiac surgery. Thirty patients undergoing coronary artery bypass grafting were included. Measurements were taken postoperatively, after stabilisation in the intensive care unit. Cardiac output was determined by transoesophageal echocardiography in randomised order through the aortic, mitral, and pulmonary valves, right and left ventricular outflow tracts, transgastric surface areas of the left ventricle and left ventricle two-dimensional volumes (Simpson's rules). 'Eyeball guessing' was done off-line. The best results were transaortic measurements using the triangular shape assumption of valve opening, but some values deviated considerably, and none of these approaches reached the limit of agreement set at 30% when compared to thermodilution. Eyeball guessing was comparable to the best transoesophageal echocardiography measurements. We conclude that transoesophageal echocardiography is an unreliable tool for determination of cardiac output in intensive care after cardiac surgery.

[Atrila fibrillation: a review]. / Vorhofflimmern: Eine Ubersicht.

Atrial fibrillation (AF) is the most common sustained arrhythmia and increases exponentially with age. The physiologic basis are certain triggers initiating multiple micro-reentry circuits, which require a certain amount of "myocardial mass" to be sustained. There are numerous predisposing factors for AF, mostly leading to dilatation or hypertrophy of the atrial myocardium. Lone AF, however, occurs in structurally normal hearts. In the management of AF it is mandatory to decide between medical or electrical cardioversion in persistent AF and rate control in permanent AF. Medical cardioversion or prophylaxis of recurrence can be performed with Class IA, IC or Class III antiarrhythmic drugs. The choice of drugs depends on the underlying cardiac pathology of the individual patient. Patients with long duration of poor rate control during AF are at risk for tachycardia-induced cardiomyopathy. Cardioversion is safe to be performed within 48 hours after the onset of AF without prior and--if there is no risk of recurrence--without consecutive anticoagulation. When AF persists longer than 48 hours, anticoagulation for three weeks is mandatory prior to attempted cardioversion, or alternatively, transesophageal echocardiography can be performed to exclude the presence of an intraatrial thrombus. Anticoagulation has to be maintained for a minimum of four weeks after the restoration of sinus rhythm. Anticoagulation is required for paroxysmal, persistent and permanent AF. Lone atrial fibrillation in patients under the age of 60 years is an exception to these rules and does not require anticoagulation. In case of refractory AF with poor rate control, catheter ablation of the AV node with pacemaker implantation is the treatment of last choice. Early attempts to provide a cure for AF included the surgical "Maze" procedure, followed by linear catheter ablation with the goal of reducing the atrial mass. Catheter ablation of the triggers of AF, which mainly originate at the pulmonary veins and the "substrate modification" have been introduced in the last couple of years and is performed increasingly in specialized EP centers.

[ICD therapy in patients with coronary artery disease--incidence of adequate interventions]. / ICD-therapie bei Patienten mit koronarer Herzkrankheit--Inzidenz adäquater Interventionen.

BACKGROUND: The Implantable Cardioverter/Defibrillator (ICD) represents the therapy of choice for patients at risk of malignant ventricular arrhythmias. The survival benefit of the ICD vs antiarrhythmic therapy in patients with coronary artery disease and ventricular tachycardia has been proven. Recently, the ICD therapy has also been established for primary prevention in high risk patients. We report about the incidence of adequate ICD therapies in patients with coronary artery disease, who underwent ICD implantation at the University Hospital Zurich. METHODS: 104 consecutive patients (97 men, 7 women, mean age of 67 +/- 10 years) with coronary artery disease, who underwent ICD implantation in accordance with the AHA/ACC/NASPE guidelines between January 2000 and July 2003 were included in the study. Follow-up was performed every three to six months, when all ICD therapies were documented. This documentation was used for analysis of adequate or inadequate ICD therapies. RESULTS: The mean follow-up time was 383 +/- 195 days. The time to the first adequate therapy was 201 +/- 283 days. The cumulative incidence for the first adequate therapy was 21% at six months, 39% at two years and 59% at four years. In 64% of patients, who experienced adequate ICD therapies, antitachycardia pacing (ATP) and in 36% an initial shock was delivered. ATP was successful in 83% of adequately delivered episodes. In the follow-up period 12 patients died. CONCLUSION: The benefit of the ICD was apparent in patients at risk for ventricular arrhythmias and coronary artery disease after a relatively short period of time, which underlines the important role of the ICD in primary and secondary prevention.