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Previous studies demonstrated that the coronary sinus (CS) is an important target for ablation in persistent atrial fibrillation. However, radiofrequency ablation in the CS is associated with coronary vessel damage and tamponade. Animal data suggest irreversible electroporation (IRE) ablation can be a safe ablation modality in vicinity of coronary arteries. We investigated the feasibility of IRE in the CS in a porcine model.Ablation and pacing was performed in the CS in six pigs (weight 60-75 kg) using a modified 9-French steerable linear hexapolar Tip-Versatile Ablation Catheter. Pacing maneuvers were performed from distal to proximal segments of the CS to assess atrial capture thresholds before and after IRE application. IRE ablations were performed with 100 J IRE pulses. After 3-week survival animals were euthanized and histological sections from the CS were analyzed.A total of 27 IRE applications in six animals were performed. Mean peak voltage was 1509 ± 36 V, with a mean peak current of 22.9 ± 1.0 A. No complications occurred during procedure and 3-week survival. At 30 min post ablation 100% isolation was achieved in all animals. At 3 weeks follow-up pacing thresholds were significant higher as compared to baseline. Histological analysis showed transmural ablation lesions in muscular sleeves surrounding the CS.IRE ablation of the musculature along the CS using a multi-electrode catheter is feasible in a porcine model.

Obesity is related to left ventricular hypertrophy (LVH). Whether LVH on electrocardiography (ECG-LVH) is a result of increased cardiac electrical activity or due to increased left ventricular mass (LVM) remains to be determined. The aims of the present study were to investigate the relation between obesity and ECG-LVH and LVM by magnetic resonance imaging (MRI-LVM) in patients with hypertension and to investigate the relation of insulin resistance (IR) and LVH. Patients with hypertension (n = 421) were evaluated using Sokolow-Lyon voltage, Cornell voltage, and cardiac magnetic resonance imaging. Waist circumference was used as a measure of abdominal obesity. Linear regression analysis revealed an inverse relation (adjusted β = -0.02, 95% confidence interval -0.02 to -0.01) between waist circumference and Sokolow-Lyon voltage, indicating a decrease of 0.02 mV per 1-cm increase in waist circumference. There was a positive relation between waist circumference and MRI-LVM (β = 0.49, 95% confidence interval 0.32 to 0.67). Patients in the highest quartile of LVM had a worse metabolic profile than patients with the Sokolow-Lyon voltage criterion. The relations of IR with ECG-LVH and MRI-LVM were similar to those of waist circumference in relation to ECG-LVH and MRI-LVM. In conclusion, there is an inverse relation between waist circumference and ECG-LVH and a positive relation between waist circumference and MRI-LVM. This study indicates that obesity has a different relation to voltage criteria for LVH compared to anatomic criteria for LVH, supporting the hypothesis that IR decreases electrocardiographic voltages, despite an increase in MRI-LVM. The clinical implication is that especially in patients with IR, Sokolow-Lyon voltage is low in contrast to high MRI-LVM.

Atherosclerotic plaque disruption accounts for the major part of cardiovascular mortality and the risk of disruption appears to depend on plaque composition. Carotid plaques in patients, scheduled for endarterectomy, have been successfully characterised with MRI. MRI has the advantage of combining information about morphology and function. Unfortunately, the tortuosity and size of the coronary arteries, and the respiratory and cardiac motion hinder the in vivo characterisation of human coronary plaque. In addition to plaque composition several molecular markers of the different processes involved in atherosclerosis, such as integrins, matrix metalloproteinases and fibrin seem to correlate with risk of plaque rupture and clinical outcome. These molecular markers can be targeted with antibodies coupled to carriers, which are loaded with gadolinium for detection (molecular MRI). Several cellular/molecular MRI studies in animal models and some in human patients have been conducted with varying levels of success. The advent of clinical high field magnets, the development of contrast agent carriers with high relaxivity and the development of relatively new MR contrast techniques are promising in the field of plaque imaging. Future MRI studies will have to focus on the molecular target of the atherosclerotic process, which has the highest prognostic value with regard to acute coronary syndromes and on the most suitable contrast agent to visualize that target.

Variation in theNOS3gene has been related to the development of restenosis. The Glu298Asp polymorphism has previously been investigated for its effect on NO levels and the development of restenosis. However, the variability of findings gave rise to the hypothesis that the functional significance of this polymorphism may only become manifest under conditions of endothelial dysfunction. Since patients with the metabolic syndrome are known to have endothelial dysfunction, we aimed to investigate if the significance ofNOS3polymorphisms may depend on the presence of the metabolic syndrome.We examined the impact of the -949 A/G, the -716 C/T and the Glu298Asp polymorphisms in theNOS3gene on the risk of clinical restenosis in a previously described subpopulation of the GENDER-study, a multicenter prospective study design that enrolled consecutive patients after successful PCI. This subpopulation consisted of 901 patients of whom sufficient data were available to establish absence or presence of the metabolic syndrome. Of these patients, 448 had the metabolic syndrome. Clinical restenosis, defined as target vessel revascularization (TVR), was the primary endpoint.We demonstrated that the minor -949G, -716T and 298Asp alleles were associated with a significantly increased risk of TVR in patients with the metabolic syndrome (HR: 1.58 [95%CI: 1.04–2.40], HR: 1.95 [95%CI: 1.02–3.70] and HR: 1.67 [95%CI: 1.09–2.54], respectively). In the group without the metabolic syndrome we observed no association between the three polymorphisms and TVR.

We sought to examine the frequency of abnormal echocardiographic findings in patients with tuberous sclerosis complex. In a retrospective cohort study, we included all patients with known tuberous sclerosis complex who had been sent to our cardiology department for echocardiographic screening from 1995 through August 2003 (n=56). Two research scientists independently reviewed the reports of the echocardiographic screening examinations for abnormal findings. We used descriptive statistics, the Mann-Whitney U test, and the chi(2) test. The mean age of patients included in the study was 35 years (range, 12-73 yr); 23 patients were male. Abnormal findings were seen in 22 patients (39%). The most common abnormal findings were focal areas of increased intramyocardial echogenicity, which were seen in 16 patients (29%). The clinical consequence of this finding is still unknown. We conclude that echocardiographic abnormalities are common in patients with tuberous sclerosis complex.

Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease with a clinical prevalence of 1 in 500. HCM is a monogenetic disease and is inherited autosomal dominantly. The disease can manifest itself at any age. Clinical presentation varies from symptom-free to severe dyspnoea and sudden cardiac death from ventricular arrhythmia. Diagnosis is mainly based on echocardiography and on MRI if necessary. In 50-60% of patients, molecular genetic investigation reveals a pathogenic mutation in one of the sarcomeric protein genes. The treatment of HCM depends on the symptoms and the potential presence of an obstruction in the left ventricular outflow tract. The risk of sudden cardiac death must be evaluated in order to determine if a prophylactic intracardiac defibrillator is necessary. In view of its mendelian form of inheritance, in the Netherlands practice guidelines have been issued recently regarding genetic counselling of the patient and his or her family and to initiate and coordinate research within the family.

Anemia is common in patients with the combination of chronic heart failure and chronic kidney disease and is associated with increased mortality. Recent clinical studies suggest that recombinant human erythropoietin (EPO) treatment has desirable as well as undesirable effects, related to its hematopoietic or nonhematopoietic effects. Therefore a translational study is needed to elucidate mechanistic aspects of EPO treatment.In this open-label randomized 12-month trial (the Mechanisms of Erythropoietin Action in the Cardiorenal Syndrome [EPOCARES]), patients with the combination of chronic heart failure and chronic kidney disease (glomerular filtration rate 20-70 ml/min) and mild anemia (hemoglobin 10.3-12.6 g/dL in men, and 10.3-11.9 g/dL in women) are being randomized into 3 groups: 1 group (n=25) receives a fixed dose of 50 IU/kg per week EPO to increase hemoglobin level to a maximum of 13.7 g/dL for men and 13.4 g/dL for women; another group (n=25) is treated with 50 IU/kg per week EPO maintaining baseline hemoglobin levels for the first 6 months by phlebotomy. The control group (n=25) receives standard care without EPO.Cardiac and renal function as well as a panel of biomarkers and iron parameters are being assessed. Furthermore, the effects of EPO on monocyte gene expression profiles and on endothelial progenitor cells are being evaluated.This translational study is designed primarily to discern hematopoietic from nonhematopoietic effects of EPO in cardiorenal patients. The study will add insights into the mechanisms that could explain the fragile balance between desirable and undesirable effects of EPO (Trial registration: ClinicalTrials.gov identifier NCT00356733).

Since activation of the haemostatic system is an important feature of the wound healing response triggered by arterial injury, variations in genes involved in thrombus formation may play a role in restenosis after percutaneous coronary interventions (PCI). Therefore, our aim was to examine the relationship between polymorphisms that are known to play a role in the haemostatic system and the risk of clinical restenosis in the GENetic DEterminants of Restenosis (GENDER) study, a multicenter prospective study design that enrolled 3,104 consecutive patients after successful PCI. Target vessel revascularization (TVR) was the primary endpoint. All patients were genotyped for six polymorphisms in the Factor II, Factor V, Factor VII and PAI-1 genes. The PAI-1 4G variant was associated with an increased risk of TVR. When compared to 5G/5G homozygotes, heterozygous patients were at higher risk for TVR (HR: 1.46, 95% CI: 1.05-2.03), whereas patients with the 4G/4G genotype had an even further increased risk (HR: 1.69, 95% CI: 1.19-2.41). In contrast, the factor V 506Gln (factor V Leiden) amino acid substitution was associated with a decreased risk of TVR (HR: 0.41, 95% CI: 0.19-0.86). Our findings indicate that polymorphisms in the factorV and PAI-1 genes may play a role in the process of restenosis.