Renal denervation with standard radiofrequency ablation catheter is effective in 24-hour ambulatory blood pressure reduction - follow-up at 1/3/6/12 months.

AIMS: To examine the effect of renal denervation (RDN) on 24­h ambulatory blood pressure (ABP) with a standard radiofrequency ablation catheter (RF catheter). METHODS: Seventy-five patients with resistant hypertension received bilateral RDN with an RF catheter (6 RF applications, 1 minute each, 8-12 watts). Seventy patients fulfilled inclusion criteria with mean systolic ABP ≥140 mmHg (mean 165/89) despite treatment with ≥3 antihypertensive drugs (mean 5.9) including a diuretic, and were further analysed for ABP changes. Follow-up at 1/3/6/12 months comprised biochemical evaluations and ABP measurement. At 6/12 months, duplex sonography of the renal arteries was additionally performed. RESULTS: At 1/3/6/12 months we observed a significant reduction in systolic ABP of -15/-17/-18/-15 mmHg (n = 55/53/57/50; non-parametric Friedman test, p < 0.001) and diastolic ABP of -6/-9/-10/-7 mmHg (p < 0.001). Of the patients, 70 %/64 % showed a systolic ABP reduction of ≥10 mmHg, and 77 %/70 % of ≥5 mmHg at 6/12-month follow-up. Two patients (2.7 %) developed renal artery stenosis (>70 %) with subsequent stenting without complications. Logistic regression analysis with systolic ABP reduction ≥10 mmHg at 12 months follow-up as criterion revealed that only the mean baseline systolic ABP was significant, OR = 2.174. CONCLUSIONS: RDN with a standard RF catheter can be used safely to reduce mean ABP in resistant hypertension as shown in long-term follow-up.

Prediction of atrial fibrillation recurrence after cardioversion-interaction analysis of cardiac autonomic regulation.

Today atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice accounting for approximately one third of hospitalizations and accompanied with a 5 fold increased risk for ischemic stroke and a 1.5 fold increased mortality risk. The role of the cardiac regulation system in AF recurrence after electrical cardioversion (CV) is still unclear. The aim of this study was to investigate the autonomic regulation by analyzing the interaction between heart rate and blood pressure using novel methods of nonlinear interaction dynamics, namely joint symbolic dynamics (JSD) and segmented Poincaré plot analysis (SPPA). For the first time, we applied SPPA to analyze the interaction between two time series. Introducing a parameter set of two indices, one derived from JSD and one from SPPA, the linear discriminant function analysis revealed an overall accuracy of 89% (sensitivity 91.7%, specificity 86.7%) for the classification between patients with stable sinus rhythm (group SR, n = 15) and with AF recurrence (group REZ, n = 12). This study proves that the assessment of the autonomic regulation by analyzing the coupling of heart rate and systolic blood pressure provides a potential tool for the prediction of AF recurrence after CV and could aid in the adjustment of therapeutic options for patients with AF.

[Incessant or recurrent ventricular tachycardia. Indications for emergency ablation]. / Unaufhörliche oder rezidivierende ventrikuläre Tachykardien. Wann ist die Notfallablation indiziert?

Incessant ventricular tachycardia and "electrical storms" are emergencies, requiring urgent action in a close cooperation between critical care physicians and cardiologists. The leading cause of such events is advanced cardiac disease. Besides the patient's history, an ECG and, if applicable, an implantable cardioverter-defibrillator (ICD) interrogation is required for a reliable diagnosis. Further diagnostics include laboratory parameters, an echocardiogram, and possibly a coronary angiography. The medical therapy, consisting of amiodarone and ß-blockers, should immediately be initiated after diagnosis. In the case of failed drug therapy, urgent catheter ablation is indicated. This is a complex procedure, in which the clinical tachycardia or the electrical substrate is modified by using an irrigated catheter. The acute success rate of this life-saving procedure is high. However, there might also be complications due to the required extensive procedures.

Heart rate variability - a potential early marker of sub-acute post-stroke infections.

OBJECTIVE: Infection is the most relevant complication after acute ischemic stroke. Activity of the autonomic nervous system seems to control post-stroke immunodepression. We investigated heart rate variability (HRV) indices that reflect autonomic readjustments as predictors of post-stroke infection. MATERIALS AND METHODS: Forty-three patients with acute ischemic stroke were enrolled in a prospective study. The predictability of sub-acute infections (day 4 ± 1 after admission) was investigated in 34 patients without acute infection by means of HRV indices obtained in the acute period (48 h after admission). RESULTS: Sub-acute infection could be predicted in patients without clinical or paraclinical (white blood cell count and C-reactive protein) signs of infection in the acute period at (i) day: increased HFnorm, reduced LFnorm and LF/HF; (ii) night: reduced LF and VLF (P < 0.05). CONCLUSIONS: HRV indices are candidates for early markers of developing post-stroke infections, preceding routine blood samples. Thus, HRV-based early diagnosis of post-stroke infection should be investigated in more detail as it may have implications as a novel tool for timely and appropriate treatment. A corresponding continuous HRV-based risk assessment using the ECG provided by the routine stroke monitoring system would be possible without any additional burden for patients and staff.

Smelling heart failure from human skin odor with an electronic nose.

The human body odor contains different volatile organic compounds which can be used as biomarkers for various diseases. The early detection of heart failure (HF) through periodical screening provides an early treatment application. Therefore we have developed a completely new non-invasive method to identify HF applying an "electronic nose" (e-nose) which provides a "smelling" of the disease based on the analysis of sweat volatile gases from the skin surface. For this e-nose a special applicator carrying the sensor chip was developed which can be applied directly on the skin surface. 27 patients with decompensated HF (DHF), 25 patients with compensated HF (CHF, mean age 70.72 ± 12.02) and 28 controls (CON) were enrolled in this first pilot study.

[Implantation of a re-synchronization device in a patient with persistent left superior vena cava-a case report]. / Implantation eines Resynchronisationssystems bei persistierender oberer Hohlvene Ein Fallbericht.

We report an implantation of a cardiac re-synchronization system in a patient with persistent left superior vena cava. This anomaly occurs in 0.3 to 0.5% of healthy individuals and remains usually asymptomatic. Variations of the superior vena cava should be considered in venous catheterization and other procedures such as implantation of pacemaker and ICD systems as well as port catheter insertion. In re-synchronization systems, persistent left superior vena cava can be an obstacle for cannulation of the coronary sinus and placement of a transvenous left ventricular lead.

K(ATP) channel current increases in postinfarction remodeled cardiomyocytes.

Adenosintriphosphate-sensitive potassium channels (K(ATP) channels) are an important linkage between the metabolic state of a cell and electrophysiological membrane properties. In this study, K(ATP) channels were studied in myocytes of normal and remodeled myocardium of the rat. Myocardial infarction was induced by ligature of the left anterior descending artery. Remodeled myocytes were obtained from the hypertrophied posterior left ventricular wall and interventricular septum 3 months after infarction. The current through K(ATP) channels was measured in whole-cell and inside-out patches by using the patch-clamp technique. After myocardial infarction, the heart weight/body weight ratio was doubled and the myocytes were hypertrophied yielding a cell capacitance of 266+/-16 pF compared to 122+/-12 pF in control cells. The amount of Kir6.2 protein was indistinguishable in corresponding regions of control and remodeled hearts. The ATP sensitivity of K(ATP) channels in remodeled cells was significantly lower than in control cells (half maximum block at 115 micromol/l ATP in remodeled and at 71 mumol/l ATP in control cells). The maximum I (KATP) density induced by metabolic inhibition was higher in small remodeled (176+/-15 pA/pF) than in control cells (127+/-11 pA/pF), but was unchanged in large remodeled cells. Both, the higher I (KATP) density and the lower sensitivity of the K(ATP) channels to ATP suggest that remodeled cardiomyocytes develop an improved tolerance to ischemia by stabilizing the resting potential and decreasing excitability.

Systemic macrophage activation in locally-induced experimental arthritis.

Local and systemic macrophage activation was examined during the course of monoarticular murine antigen-induced arthritis (AIA), induced by systemic immunization and subsequent local induction. The levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6, IL-12p70, and nitric oxide (NO) were determined in joints, sera, and supernatants of peritoneal macrophages (the latter unstimulated or stimulated ex vivo with LPS/IFN-gamma). In comparison with normal mice, systemic immunization (day 0) was associated to significant rise of TNF-alpha in serum, IL-1beta in the joints, IL-6 in unstimulated macrophages and IL-12p70 in stimulated macrophages. Local induction led to a further significant increase of: (i) TNF-alpha, IL-1beta, and IL-6 in the joints; and (ii) IL-1beta, and IL-6 in sera and stimulated macrophages during acute and/or early chronic AIA (days 1 to 7). Unstimulated macrophages showed increased NO release (day 3), while stimulated macrophages significantly increased secretion of IL-12p70 (day 1). In late chronic AIA (day 21), cytokine/NO expression returned to immunization levels or below at all sites; solely IL-1beta in the joints remained significantly above normal levels. Therefore, the prevalently local AIA model is characterized by a mixture of local and systemic activation of the mononuclear phagocyte system (MPS). While systemic MPS activation preceding arthritis induction can be attributed to systemic immunization, further systemic activation during arthritis appears an integral pathogenetic component of AIA.

Localization of late potential sources in myocardial infarction.

INTRODUCTION: Late potentials (LP) are markers of arrhythmogenic events after myocardial infarction (MI). The localization of LP sources would help to identify arrhythmogenic myocardium. The purpose of this study was to localize these LP sources from non-invasive body surface mapping data. METHODS AND RESULTS: Six patients were investigated with cardiac MRI and signal averaged 62-lead magnetocardiography after MI. Three of them were suffering from sustained ventricular tachycardia (VT). Sophisticated computer algorithms were used in order to compute the current density on the surface of the left ventricle. We compared these current density distributions for the entire QRS complex and the high frequency LP signals. In the three patients which had premature ventricular complexes (PVCs) we localized the exit sites of these arrhythmias. We found a close matching of the low current density areas based on the QRS complexes and the high current density areas based on the LP signals. These areas predominantly corresponded to sites of the infarctions. Exit sites of PVCs were located close to these areas. CONCLUSIONS: By means of sophisticated computer algorithms we were able to localize LP sources. This would be useful in steering catheter ablation and coronary revascularization therapies. However, the method has to be proven with the help of invasive mapping in a larger number of patients.

Lack of association between 27-bp repeat polymorphism in intron 4 of the endothelial nitric oxide synthase gene and the risk of coronary artery disease.

The gene encoding endothelial nitric oxide synthase (ecNOS) is a candidate gene for the mediation of initial endothelial cell damage seen in arteriosclerosis. Although the association of ecNOS polymorphisms with hypertension has been studied extensively, there is little information regarding its association with coronary artery disease (CAD). We decided to study a 27 base-pair tandem repeat polymorphism in intron 4 of the ecNOS gene in 1043 individuals (413 controls, 630 patients with CAD) who consecutively underwent coronary angiography at our institution. The frequencies of the genotypes drawn from 1038 individuals were 0.69, 0.28 and 0.03 in the controls and 0.73, 0.25 and 0.02 in individulas with CAD for the ecNOS4b/b, ecNOS4b/a and ecNOS4a/a genotypes, respectively (p = n.s). There was no shift of the genotype frequencies from the expected distribution based on the Hardy-Weinberg equilibrium. Neither the rare ecNOS4a allele nor the ecNOS4a/a genotype conferred an independent risk factor for CAD in subgroups, e.g. smokers, diabetic individuals, hypertensive individuals and individuals with a low conventional risk for CAD. In five individuals we identified an additional 27-bp repeat in the ecNOS gene (ecNOS4c), which occurred heterozygous with the ecNOS4b allele (ecNOS4b/c genotype). In conclusion, the ecNOS4a allele as well as the ecNOS4a/a genotype did not show a general association with CAD in the studied European population. Even in high-risk subgroups the ecNOS4a/4a genotype did not represent an independent risk factor for CAD. In addition, the severity of CAD was not associated with the ecNOS4a allele/ecNOS4a/a genotype.

Angiotensin-I-converting enzyme DD genotype is a risk factor of coronary artery disease.

Coronary artery disease (CAD) is a polygenic disease whose phenotypic manifestation depends on the interaction of a number of environmental factors. A number of genes, including the angiotensin-I-converting enzyme (ACE) gene, have been implicated in the pathogenesis of CAD. ACE could affect smooth muscle cell and fibroblast migration and proliferation, low-density lipoprotein (LDL) oxidation and endothelial cell function; these are all important factors in atherosclerosis. A polymorphic variant of the ACE gene correlates with higher circulating ACE levels and carries an increased risk of myocardial infarction, and cardiomyopathies. In this study, we sought to determine the distribution of ACE genotypes and the frequency of allele D in patients undergoing coronary angiography at our institution. DNA from 196 patients with angiographically proven CAD and 96 controls without CAD was amplified by polymerase chain reaction (PCR). The primers flanked the region of the ACE gene (intron 16) where the insertion (I) or deletion (D) of a 287-bp fragment results in the I/D polymorphism. PCR amplification of alleles I and D resulted in 490- and 190-bp products, respectively. In the control group, the relative allele frequencies of the polymorphism were similar to those of previously published European studies. The ACE genotype DD was present in 37.3% of patients with CAD as compared to 23.4% in the controls (p < 0.001, odds ratio 1.95, 95% confidence intervals (CI) 1.06-3.57). There was no association with the history of prior myocardial infarction. The genotype distribution in patients with single-vessel involvement was not significantly different from controls (p = 0.14). However, the DD genotype was significantly more common in patients having multivessel CAD when compared to single-vessel disease, indicating an association of this polymorphism with the extent of CAD. ACE genotype DD is more common in patients with multivessel CAD as compared to controls and to patients with single-vessel involvement, indicating that genotype DD is a genetic risk factor for extensive, multivessel CAD.

Substance use among schizophrenic outpatients: prevalence, course, and relation to functional status.

The prevalence and course of alcohol and drug use were examined in a longitudinal, retrospective study of 100 schizophrenic outpatients. During the 18 month study period, problem substance use (abuse and dependence) was not associated with differential attrition from outpatient treatment. Thirty to forty percent of subjects were using drugs or alcohol during any evaluation period. The overall level of substance use and problem use of alcohol, marijuana, and other drugs remained stable, while problem use of cocaine and multiple substances increased over time. Problem substance use was associated with lower functional status and the detrimental effect of problem substance use appeared to increase with time. These findings underscore the need to address substance use problems in the context of outpatient schizophrenia treatment.