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Background Atrial fibrillation (AF), a disease of the elderly, occasionally occurs at younger age. Pathophysiology of AF in younger patients is diverse, including channelopathies and cardiomyopathies. Data on the significance and complications of AF in young patients are scarce. Hypothesis Atrial fibrillation is the first manifestation of cardiovascular disease (CVD) in young patients. Methods From 11 888 patients in a university hospital database, patients age ≤35 years were identified. A composite of stroke/transient ischemic attack, thromboembolic events, major bleeding, and death was the primary endpoint. Stroke/transient ischemic attack, thromboembolic events, major bleeding, death, AF during follow-up, diagnosis of arrhythmia other than AF, and new diagnosis of any CVD were secondary endpoints. Endpoints were compared between patients with and without comorbidities. Results We identified 124 patients (29.1± 5 years). Of those, 84 were followed over 48.4 ± 39.8 months. Comorbidities were present in 40.5%. Incidence of the primary endpoint was not different between the groups. Arrhythmias other than AF were more common in patients without comorbidities (36% vs 14.7%; P = 0.032). A supraventricular tachycardia (SVT) was found in 57.1% of patients who underwent electrophysiological testing and was treated with catheter ablation. None of those patients had AF during follow-up. Conclusions Atrial fibrillation occurs in young patients with and without structural heart disease. Young AF patients without comorbidities rarely develop CVD during the first years after diagnosis. Yet, an SVT is found in a high proportion of young AF patients; AF may be first manifestation of SVT. Therefore, young patients should undergo further evaluation for SVT

Background Identification of a possible ventriculoatrial (VA) dissociation in wide QRS complex tachycardias is one of the most reliable criteria for differentiation of tachycardia origin. The Lewis lead has been proposed for detection of atrial activity during ventricular tachycardias. Hypothesis A modified Lewis-lead-ECG will be superior to the standard-lead ECG for detection of ventriculoatrial conduction during ventricular tachycardia. Methods Forty-seven patients underwent electrophysiological study, stimulated with a fixed cycle length of 400 ms in the ventricle. During stimulation, a standard-lead ECG and a modified Lewis-lead ECG were recorded. Simultaneously, VA conduction was documented by intracardiac electrograms. Surface ECGs were presented to 6 blinded examiners for VA conduction assessment. Results Type of VA conduction was correctly diagnosed in significantly more ECGs in the Lewis-lead ECG group (mean, 35.0 [75%]) than in the standard-lead ECG group (mean, 29.2 [62%]; P = 0.045). Ventriculoatrial dissociation also was significantly more often correctly diagnosed in the Lewis-lead ECG group (mean, 17.7 [71%]) than in the standard-lead ECG group (mean, 12.7 [49%]; P = 0.014). Interobserver agreement was moderate in both groups (κ = 0.45 and κ = 0.49, respectively). Conclusions Compared with standard-lead ECG, modified Lewis-lead ECG is associated with significantly improved detection of VA conduction type during fast ventricular pacing and thus may help improve ECG diagnosis.

Pulmonary arterial hypertension (PAH) is a fatal disease with limited therapeutic options. Pathophysiological changes comprise obliterative vascular remodelling of small pulmonary arteries, elevated mean pulmonary arterial systolic pressure (PASP) due to elevated resistance of pulmonary vasculature, adverse right ventricular remodelling, and heart failure. Recent findings also indicate a role of increased inflammation and insulin resistance underlying the development of PAH. We hypothesized that treatment of this condition with the peroxisome proliferator-activated receptor-γ (PPARγ) activator pioglitazone, known to regulate the expression of different genes addressing insulin resistance, inflammatory changes, and vascular remodelling, could be a beneficial approach. PAH was induced in adult rats by a single subcutaneous injection of monocrotaline (MCT). Pioglitazone was administered for 2 weeks starting 3 weeks after MCT-injection. At day 35, hemodynamics, organ weights, and -indices were measured. We performed morphological and molecular characterization of the pulmonary vasculature, including analysis of the degree of muscularization, proliferation rates, and medial wall thickness of the small pulmonary arteries. Furthermore, markers of cardiac injury, collagen content, and cardiomyocyte size were analyzed. Survival rates were monitored throughout the experimental period. Pioglitazone treatment improved survival, reduced PASP, muscularization of small pulmonary arteries, and medial wall thickness. Further, MCT-induced right ventricular hypertrophy and fibrosis were attenuated. This was accompanied with reduced cardiac expression of brain natriuretic peptide, as well as decreased cardiomyocyte size. Finally, pulmonary macrophage content and osteopontin gene expression were attenuated. Based on the beneficial impact of pioglitazone, activation of PPARγ might be a promising treatment option in PAH.

Background Implantable loop recorders (ILRs) allow continuous cardiac monitoring for 3–6 years and are a valuable tool for the investigation of syncopal episodes, palpitations, and atrial fibrillations as well as risk stratification after myocardial infarction. Although magnetic resonance imaging (MRI) in patients with ILRs has been shown to be safe, the impact of ILRs on cardiac MRI image quality has not been investigated yet. Thus, we tested the diagnostic value of cardiac MRI in patients with various types of ILRs. Methods Two patients with an ILR and a clinical indication to assess myocardial burden of scarring and fibrosis or stress-induced myocardial ischemia underwent cardiac MRI. Device interrogation was performed prior to, immediately after, and 3 months after cardiac MRI. Results The post-MRI follow-ups revealed no change in programmed ILR parameters, sensing fidelity, and battery parameters. However, ILRs caused significant, uninterpretable hyperintensity artifacts in cardiac MRI. Conclusions Further clinical studies are warranted to investigate whether modified MRI techniques are helpful to eliminate imaging artifacts.

This publication is intended to present the current state of research on the rebound effect. First, a systematic literature review is carried out to outline (current) scientific models and theories. Research Question 1 follows with a mathematical introduction of the rebound effect, which shows the interdependence of consumer behaviour, technological progress, and interwoven effects for both. Thereupon, the research field is analysed for gaps and limitations by a systematic literature review. To ensure quantitative and qualitative results, a review protocol is used that integrates two different stages and covers all relevant publications released between 2000 and 2019. Accordingly, 392 publications were identified that deal with the rebound effect. These papers were reviewed to obtain relevant information on the two research questions. The literature review shows that research on the rebound effect is not yet comprehensive and focuses mainly on the effect itself rather than solutions to avoid it. Research Question 2 finds that the main gap, and thus the limitations, is that not much research has been published on the actual avoidance of the rebound effect yet. This is a major limitation for practical application by decision-makers and politicians. Therefore, a theoretical analysis was carried out to identify potential theories and ideas to avoid the rebound effect. The most obvious idea to solve this problem is the theory of a Steady-State Economy (SSE), which has been described and reviewed.

The possible treatment strategies for defects of the pace-sense (P/S) part of a defibrillation lead are either implantation of a new high-voltage (HV)-P/S lead, with or without extraction of the malfunctioning lead, or implantation of a P/S lead. We conducted a Web-based survey across cardiac implantable electronic device (CIED) centers to investigate their procedural practice and decision-making process in cases of failure of the P/S portion of defibrillation leads. In particular, we focused on the question of whether the integrity of the HV circuit is confirmed by a test shock before decision-making. The questionnaire included 14 questions and was sent to 951 German, 341 Austrian, and 120 Swiss centers. The survey was completed by 183 of the 1412 centers surveyed (12.7% response rate). Most centers (90.2%) do not conduct a test shock to confirm the integrity of the HV circuit before decision-making. Procedural practice in lead management varies depending on the presentation of lead failure and whether the center applies a test shock. In centers that do not conduct a test shock, the majority (69.9%) implant a new HV-P/S lead. Most centers (61.7%) that test the integrity of the HV system implant a P/S lead. The majority of centers favor DF-4 connectors (74.1%) over DF-1 connectors (25.9%) at first CIED implantation. Either implanting a new HV-P/S lead or placing an additional P/S lead are selected strategies if the implantable cardioverter-defibrillator lead failure is localized to the P/S portion. However, conducting a test shock to confirm the integrity of the HV component is rarely performed.

Introduction The extent of left atrial (LA) adverse remodeling as a cardiac disease marker has become increasingly important. In patients with atrial fibrillation (AF), atrial remodeling (AR) is accompanied by increased mortality. The relation between LA function and the extent of low-voltage areas (LVAs) has not yet been systematically investigated. Methods In patients with AF undergoing catheter-ablation, LA was studied using echocardiography and ultra-high-density mapping (Rhythmia®). Fibrosis (i.e. extent of LVAs) was estimated by quantifying areas with bipolar electrogram amplitudes of ≤0.5, ≤0.4, ≤0.3, ≤0.2 or ≤0.1 mV. Results A total of 22 patients with a mean LVEF of 53 ± 2% was studied. Mean LA volume index (LAVI) was significantly increased at 39 ± 3 ml/m2 indicating AR. Size of LVAs was 57 ± 7 cm2 representing 47 ± 5% of the total LA area (low-voltage set to ≤0.5 mV). With low-voltage set to ≤0.4, ≤0.3, ≤0.2 and ≤0.1, total area decreased to 34 ± 6, 28 ± 6, 22 ± 5 and 12 ± 3 cm2. LAVI positively correlated with the extent of LVAs at all cut-offs. Mean LA emptying fraction was 42 ± 3% and showed a negative correlation with LVAs with low-voltage set to ≤0.4 mV. Moreover, mean LA strain was 13 ± 2% and correlated with LVAs with low-voltage at all cut-offs further supporting the notion that the extent of LVAs impacts LA function. Notably, with low-voltage set to ≤0.2, ≤0.3 and ≤0.4 mV impaired LA strain was detected with an accuracy of >76% (p Conclusion Structural (i.e. LAVI) and functional (i.e. LA emptying fraction and LA strain) parameters of the LA correlate with the extent of LVAs.

Background Recent clinical trials have shown that pulmonary artery pressure-guided therapy via the CardioMEMS™ system reduces the risk of recurrent hospitalizations in chronic heart failure (HF) patients. The CardioMEMS™ pressure sensor is percutaneously implanted in a branch of the pulmonary artery and allows telemetric pressure monitoring via a receiver. According to the most recent ESC guidelines, this technology has currently a class IIb indication in patients with class III New York Heart Association symptoms and a previous hospitalization for congestive heart failure within the last year, regardless of ejection fraction. Aim of this guided-therapy is multifold, including an early prediction of upcoming decompensation, optimization of patients’ therapy and thereby avoidance of hospital admissions. In addition, it can be used during acute decompensation events as a novel tool to direct intra-hospital therapeutic interventions such as inotropes infusion or left ventricular (LV) assist device monitoring, with the aim of achieving an optimal volume status. Case presentation We present a case series of three end-stage HF patients with reduced ejection fraction (HFrEF) who received a CardioMEMS™ device as an aid in their clinical management. The CardioMEMS™ system enabled a closer non-invasive hemodynamic monitoring of these patients and guided the extent of therapeutic interventions. Patients were free from device- or system-related complications. In addition, no pressure-sensor failure was observed. Two patients received a 24-h infusion of the calcium sensitizer levosimendan. One patient showed a refractory acute decompensation and underwent LV assist device (LVAD) implantation as a bridge to cardiac transplantation. Switching a patient with recurrent hospitalizations to the Angiotensin Receptor Neprilysin Inhibitor (ARNI, Sacubitril-Valsartan) on top of the optimal heart failure-therapy improved its subjective condition and hemodynamics, avoiding further hospitalization. Conclusions Our case series underlines the potential impact of CardioMEMS™ derived data in the daily clinical management of end-stage HF patients. The new concept to combine CardioMEMS™ in the setting of an outpatient levosimendan program as well as a bridge to LVAD-implantation/heart transplantation looks promising but needs further investigations. Electronic supplementary material The online version of this article (10.1186/s12872-018-0883-4) contains supplementary material, which is available to authorized users.

Catheter tissue contact force (CF) is an important factor for durable lesion formation during radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF). Since CF varies in the beating heart, atrial rhythm during RFCA may influence CF. A high-density map and RFCA points were obtained in 25 patients undergoing RFCA of AF using a CF-sensing catheter (Tacticath, St. Jude Medical). The operators were blinded to the CF information. Contact type was classified into three categories: constant, variable, and intermittent contact. Average CF and contact type were analyzed according to atrial rhythm (SR vs. AF) and anatomical location. A total of 1364 points (891 points during SR and 473 points during AF) were analyzed. Average CFs showed no significant difference between SR (17.2 ± 11.3 g) and AF (17.2 ± 13.3 g; p = 0.99). The distribution of points with an average CF of ≥20 and

Context: Congenital coronary anomalies, including anomalous origin, distribution, intercoronary communications, and coronary fistulae occur at a rate of approximately 1% in the general population and are the most incidental findings. Case Report: A 49-year-old male patient presented to the emergency department with exercise-induced dyspnea and atypical angina pectoris. Coronary angiography (CAG) and contrast-enhanced 320-slice multidetector cardiac computed tomography with subsequent three-dimensional reconstructions revealed a single coronary artery (SCA) arising from the right sinus of Valsalva with a proximal branch giving rise to the left anterior descending coronary artery. The left anterior descending coronary artery shows severe atherosclerotic lesions and it is occluded afterwards. Adenosine stress perfusion cardiac magnetic resonance imaging (MRI) revealed a stress myocardial ischemia at the anterior wall without signs of fibrosis, scar, or necrosis. Conclusion: We present an extremely rare case of a SCA, with the solitary vessel arising from the right sinus of Valsalva. In our patient's case, the atherosclerotic lesions and occlusion in the branch supplying the anterior wall were considered eligible for neither percutaneous intervention nor bypass graft surgery.

Background: Postmortem interrogations of cardiac implantable electronic devices (CIEDs), recommended at autopsy in suspected cases of sudden cardiac death, are rarely performed, and data on systematic postmortem CIED analysis in the forensic pathology are missing. The aim of the study was to determine whether nonselective postmortem CIED interrogations and data analysis are useful to the forensic pathologist to determine the cause, mechanism, and time of death and to detect potential CIED-related safety issues. Methods: From February 2012 to April 2017, all autopsy subjects in the department of forensic medicine at the University Hospital Charité who had a CIED underwent device removal and interrogation. Over the study period, 5368 autopsies were performed. One hundred fifty subjects had in total 151 CIEDs, including 109 pacemakers, 35 defibrillators, and 7 implantable loop recorders. Results: In 40 cases (26.7%) time of death and in 51 cases (34.0%) cause of death could not be determined by forensic autopsy. Of these, CIED interrogation facilitated the determination of time of death in 70.0% of the cases and clarified the cause of death in 60.8%. Device concerns were identified in 9 cases (6.0%), including 3 hardware, 4 programming, and 2 algorithm issues. One CIED was submitted to the manufacturer for a detailed technical analysis. Conclusions: Our data demonstrate the necessity of systematic postmortem CIED interrogation in forensic medicine to determine the cause and timing of death more accurately. In addition, CIED analysis is an important tool to detect potential CIED-related safety issues.

Peroxisome proliferator-activated receptors are regulators of inflammatory signaling. This has fostered hope that PPAR agonists might have neuroprotective potential. We hypothesized that PPARδ activation by the novel orally administered lipophilic PPARδ agonist SAR145 may improve short- and long-term outcome after focal brain ischemia. We induced ischemia by transient filamentous middle cerebral artery occlusion (MCAo) in 227 C57BL/6 mice and administered SAR145 in varying doses and time windows post-injury. Outcome was assessed by three functional tests and histologically determining ischemic lesion sizes. In a second experiment, we tested SAR145 treatment in 40 PPARδ-knockout mice using the same procedures. Three independent groups treated with 10 mg/kg bodyweight SAR145 directly after filament removal showed a mean reduction in lesion sizes of 18 ± 10% compared to vehicle-treated groups. We did not observe a consistent improvement in the long-term functional outcome by SAR145-treatment. PPARδ-knockout mice showed a significantly higher mortality after MCAo. As expected, we did not find a reduction of lesion size by SAR145-treatment in PPARδ-knockout mice. In summary, we found no evidence of a long-term neuroprotective effect of post-injury SAR145 treatment in cerebral ischemia. However, PPARδ appears to play a pathophysiologic role in acute infarct development and overall mortality after brain ischemia.

Background Obesity is associated with increased complications and potentially worse outcomes for various cardiac interventions. This study analyzed the success rate and complication rates associated with implantation of cardiac implantable electronic devices (CIEDs) in obese patients. Hypothesis Success rates are lower and complication rates higher in obese patients. Methods Consecutive patients undergoing CIED implantation between 2011 and 2015 in our hospital were included. Patients were categorized into obese and nonobese groups according to body mass index (BMI); cutoff was 30 kg/m2. Patient characteristics, complication rates, procedural duration, and fluoroscopy data were compared between the 2 groups. Results A total of 965 patients (mean age, 69.0 ± 12.9 years; 67% male) were included. Of these, 249 (25.8%) patients were classified obese and 716 (74.2%) nonobese. Mean BMI was 34.7 ± 4.7 kg/m2 vs 25.1 ± 3.0 kg/m2, respectively. There was no difference in procedural success rates between the 2 groups (97.2% vs 97.1%, respectively). Major complications were significantly lower in the obese group compared with the nonobese group (11 [4.4%] vs 62 [8.7%]; P < 0.05). Procedural duration and fluoroscopy duration were not different between the 2 groups, but the total dose-area product was significantly higher in obese patients vs nonobese patients (4012 ± 5416 cGcm2 vs 2692 ± 5277 cGcm2 ; P < 0.005). Conclusions CIED implantation can be safely and effectively achieved in patients with BMI >30 kg/m2. However, total radiation dose was significantly higher in the obese group, emphasizing that efforts should be made to reduce radiation exposure in these patients.

In patients with complex coronary anatomy, coronary artery bypass grafting has been the recommended revascularization strategy; however, due to their comorbidities many of these patients have a high operative mortality. Percutaneous coronary intervention (PCI) may then be a viable alternative for these patients with high-risk features. Prophylactic partial hemodynamic support with a micro axial percutaneous left ventricular assist device (ImpellaTM) during PCI might be beneficial in these patients. The ImpellaTM 2.5 blood pump has been shown to be safe and effective in elective and urgent high-risk PCI patients by reducing peri-and post-procedural adverse events. Here, we present several cases of ImpellaTM 2.5 guided high-risk coronary intervention of unprotected left main. The hemodynamic support enabled preserving the mean arterial pressure (MAP) in all cases during repeated coronary manipulations and could be removed due to stable hemodynamic condition of the patients immediately after completion of the intervention. No site insertion or other complications occurred. Further studies are necessary to determine whether these observations can be replicated in a larger cohort.

Ab-independent effector functions of B cells, such as Ag presentation and cytokine production, have been shown to play an important role in a variety of immune-mediated conditions such as autoimmune diseases, transplant rejection, and graft-versus-host disease. Most current immunosuppressive treatments target T cells, are relatively unspecific, and result in profound immunosuppression that places patients at an increased risk of developing severe infections and cancer. Therapeutic strategies, which interfere with B cell activation, could therefore be a useful addition to the current immunosuppressive armamentarium. Using a transcriptomic approach, we identified upregulation of genes that belong to the mevalonate pathway as a key molecular event following CD40-mediated activation of B cells. Inhibition of 3-hydroxy-3-methylglutaryl CoA reductase, the rate-limiting enzyme of the mevalonate pathway, by lipophilic statins such as simvastatin and atorvastatin resulted in a specific inhibition of B cell activation via CD40 and impaired their ability to act as stimulatory APCs for allospecific T cells. Mechanistically, the inhibitory effect resulted from the inhibition of protein geranylgeranylation subsequent to the depletion of mevalonate, the metabolic precursor for geranylgeranyl. Thus, inhibition of geranylgeranylation either directly through geranylgeranyl transferase inhibitors or indirectly through statins represents a promising therapeutic approach for the treatment of diseases in which Ag presentation by B cells plays a role.

Introduction Pulmonary vein isolation (PVI) is the state-of-the-art treatment of atrial fibrillation (AF). Pulmonary vein reconnection is one of the main mechanisms of AF recurrence after ablation. Catheter-tissue contact is essential for effective ablation lesions. The aim of this study was to evaluate the impact of catheter contact monitoring during PVI on AF recurrence rate. Material and methods One hundred and forty-three patients who underwent PVI were analysed. In 31 patients, PVI was performed by monitoring the catheter-tissue contact with a contact force (CF) sensing catheter. One hundred and twelve patients in whom conventional PVI was performed without CF information served as the control group. Procedural data and recurrence rate within 12-month follow-up were compared. Results A significant reduction in procedure duration was seen in the CF mapping group (128.4 ±29 min vs. 157.7 ±30.8 min, p = 0.001). Complete pulmonary vein isolation was achieved in 100% of the patients. Rate of AF recurrence within 12 months after ablation was significantly lower in the contact force group (16.1%) when compared to the standard ablation group (36.6%) (p = 0.031). Conclusions Pulmonary vein isolation with the use of contact force information results in a shorter procedure duration and a lower rate of AF recurrence after 12 months compared to conventional PVI without this information. Catheter-tissue contact monitoring may have a beneficial effect on mid-term and long-term results of PVI procedures.

Aims Despite the use of 3D mapping systems and new developments of non-fluoroscopic options, most centres still rely at least in part on fluoroscopy for catheter visualization during catheter ablations. The purpose of this study was to assess the feasibility of using an ultra-low frame rate and antiscatter grid-less radiation protocol during complex left atrial ablations to minimize radiation exposure for the patient and staff. Methods and results A total of 150 consecutive patients undergoing left atrial ablations in our hospital were included in the analysis. The procedures were performed between January 2015 and November 2016. Of the included patients 75 (50%) underwent ablation before and 75 (50%) after the ultra-low frame rate (reduced from 4 to 2 FPS) and antiscatter grid-less radiation protocol was established. Procedures performed after the dose reduction protocol was established showed a 64% reduction of the dose area product (630.28 ± 550.96 vs. 226.44 ± 277.44 µGym2, P

Background Avalanche transceivers are essentials tools in locating persons who were buried by an avalanche. In the past few years, avalanche transceivers have become widely available and affordable, but it is largely unknown whether they are a source of electromagnetic interference for implanted cardiac devices. We aimed to determine the potential interaction between avalanche transceivers and pacemakers or implantable cardioverter defibrillators (ICDs). Methods One hundred and one patients, 41 with pacemakers and 60 with ICDs, were enrolled (mean age 66 ± 15 years). Four avalanche transceivers (Pieps DSP [Pieps GmbH, Lebring, Austria], Ortovox x1, Ortovox m2, and Ortovox f1 [Otovox Sportartikel GmbH, Taufkirchen, Germany]) were evaluated in transmit as well as in receive mode. Surface electrocardiograms, intracardiac electrograms, and marker channels were continuously recorded and observed by an experienced physician. Electromagnetic interference events were categorized as direct interference with the function of the implanted device itself or as interference with the telemetric communication without compromising device function. Results Among all patients, there was no interference with the intrinsic function of their pacemakers or ICDs. A total of 120 episodes of telemetry interference occurred in 48% of the patients. Of those episodes, 112 of 404 (28%) were observed in transmit and eight of 404 (2%) in receive mode (P < 0.0001). The digital avalanche transceiver (Pieps DSP) was associated with significantly less telemetry interference (20/202; 10%) than the analog transceiver (Ortovox f1) (39/202; 19%) (P = 0.0108). Conclusions Avalanche transceivers are safe for patients with pacemakers and ICDs. Despite the observed telemetry interferences, the intrinsic function of the implanted devices was never compromised.

Implantable loop recorders (ILR) are valuable tools for the investigation of patients with suspected arrhythmias. The BioMonitor 2-AF is a novel insertable ILR with enhanced atrial fibrillation (AF) detection algorithm and remote monitoring capability.The objective of this first-in-human study with the BioMonitor 2-AF was to analyze course of P-wave sensing performance and R-wave amplitude, prevalence of false and correctly sensed and classified episodes, and effectiveness of remote monitoring.All 19 patients who underwent ILR insertion were included in the BIOTRONIK Home Monitoring® system (BIOTRONIK GmbH, Berlin, Germany). Daily changes in P-wave and R-wave sensing were analyzed over 6 weeks. A breathing test (in- and expiration) was performed in two different body positions at baseline and during a 6-week in-house follow-up to investigate alterations of P-wave and R-wave sensing.R-wave amplitude and the high P-wave visibility (94.4%) remained unchanged during the follow-up period. In most patients both an increase and decrease of R-wave amplitude, and in some cases a complete R-wave vector change (31.6%), was documented during the "breathing test." Change of body position did not alter R-wave sensing amplitude mostly. "Breathing test" and change of body position had no effect on P-wave sensing performance. In 15.8% of the patients, misclassification of episodes as AF or high ventricular rates due to P-wave oversensing occurred. No ILR-related complication occurred. Automatic transmission via BIOTRONIK Home Monitoring® was successful 100% of the time.This study demonstrates that the BioMonitor 2-AF is a safe and effective tool for continuous cardiac monitoring.

A 73-year-old woman first presented with heart failure, symptom class NYHA III, and fatigue that had gradually worsened over the course of 2 years despite medical outpatient therapy. She had a history of intermittent third-degree atrioventricular block that led to the …

Hypertrophic cardiomyopathy (HCM) is a hereditary disease characterized by left ventricular hypertrophy with or without concomitant outflow tract obstruction. Identification of patients with HCM who are at high risk of sudden cardiac death (SCD) is crucial as those patients are likely to benefit from an implantable cardioverter defibrillator (ICD). Based on the HCM Risk-SCD study published in 2013, that included 3675 HCM patients with 24 313 years of follow up, a new clinical risk prediction model for sudden cardiac death was developed. This model was included in the recently released 2014 ESC guidelines. This review summarizes the changes in the prediction model and the resulting recommendations and discusses potential risks and limitations of the new score.

Aims For cardiac implantable electronic device (CIED) implantations, visualization of lead placement is necessary and fluoroscopy remains by far the most commonly used technique. With simple changes in the X-ray system settings, total radiation dose can be reduced significantly. The purpose of this study was to assess the safety and efficacy of various CIED implantations performed after implementation of a new dose reduction protocol (DRP). Methods and results We conducted a retrospective chart review of 584 patients undergoing CIED implantation or revision in our hospital. Of these patients, 280 (48%) underwent the implantation prior to and 304 (52%) after the DRP introduction. The DRP included various changes for optimized image processing and exposure system settings to enable dose reduction, as well as a reduced frame rates (4 FPS for fluoroscopy and 7.5 FPS for cinematographic images). Of the 584 patients, 53 (9.1%) had a one-chamber pacemaker, 232 (39.7%) a two-chamber pacemaker, 133 (22.8%) a one-chamber ICD, 35 (6.0%) a two-chamber ICD, 82 (14.0%) a CRT ( de novo ) implantation, and 49 (8.3%) had an upgrade to a CRT device. DRP was associated with a 64% reduction of the dose-area product (1372 ± 2659 vs. 3792 ± 5025 cGcm2, P < 0.001), while fluoroscopy duration (13 ± 15 vs. 13 ± 15 min) and procedural duration (93 ± 52 vs. 92 ± 52 min.) did not significantly increase. Complication rates did not differ significantly between the two groups. Conclusion The DRP proved to effectively reduce radiation dose for all types of CIED implantations. Fluoroscopy time, total procedure time, and the number of complications did not increase after introducing the DRP.

Aims The purpose of this study was to test the hypothesis that left ventricular (LV) mechanical dyssynchrony deteriorates the longitudinal systolic and diastolic function of the left ventricle (LV) in patients with heart failure with a normal LV ejection fraction (HFNEF). Methods and results In patients with HFNEF and in a control group consisting of asymptomatic patients with LV diastolic dysfunction [LVDD], matched by age, gender, and LV ejection fraction, we assessed the global longitudinal systolic (global strain), diastolic [global early-diastolic strain rate (SRe)], and synchronous (standard deviation of time-to-peak systolic strain) function of the LV by two-dimensional speckle-tracking echocardiography using a 18-segment LV model. A total of 325 patients were included (85 with HFNEF and 240 with asymptomatic LVDD). Patients with HFNEF had a significant impairment of the longitudinal systolic and diastolic function of the LV as compared with the control group. Concerning the pathophysiological mechanisms linked to these findings, we found that HFNEF patients with asynchronous LV contractions had significantly more impaired longitudinal systolic and diastolic LV function (global strain −14.76 ± 3.44%, global SRe 0.79 ± 0.24 s−1) than patients without asynchronous LV contractions (global strain −18.57 ± 3.10%, global SRe 1.06 ± 0.32 s−1; all P < 0.0001). Accordingly, in HFNEF patients with LV mechanical dyssynchrony the rates of LV longitudinal systolic and diastolic dysfunction were 64 and 70%, respectively, whereas these rates were significantly lower (19.5 and 41.3%), respectively, in patients without asynchronous LV contractions. In addition, HFNEF patients with LV mechanical dyssynchrony presented higher LV filling pressures and worse NYHA functional class than those with normal LV contractions. Conclusion In patients with HFNEF, LV mechanical dyssynchrony is associated with an important impairment of the longitudinal systolic and diastolic function of the LV. Therefore, the restoration of asynchronous LV contractions could help to improve and/or correct both the systolic and the diastolic longitudinal dysfunction of the LV in HFNEF and thereby improve the symptomatology of these patients.

The authors hypothesized that in patients with heart failure with normal left ventricular (LV) ejection fraction (HFNEF), the same fibrotic processes that affect the subendocardial layer of the left ventricle could also alter the subendocardial fibers of the left atrium. Consequently, these fibrotic alterations, together with chronically elevated LV filling pressures, would lead to both systolic and diastolic subendocardial dysfunction of the left atrium (i.e., impaired left atrial [LA] longitudinal systolic and diastolic function) in patients with HFNEF.Patients with HFNEF and a control group consisting of asymptomatic patients with LV diastolic dysfunction (LVDD) matched by age, gender, and LV ejection fraction were studied using two-dimensional speckle-tracking echocardiography.A total of 420 patients were included (119 with HFNEF and 301 with asymptomatic LVDD). LA longitudinal systolic (LA late diastolic strain rate) and diastolic (LA systolic strain and strain rate) function was significantly more impaired in patients with HFNEF (LA late diastolic strain rate, -1.17 ± 0.63 s(-1); LA systolic strain, 19.9 ± 7.3%; LA systolic strain rate, 1.17 ± 0.46 s(-1)) compared with those with asymptomatic LVDD (-1.80 ± 0.70 s(-1), 30.8 ± 11.4%, and 1.67 ± 0.59 s(-1), respectively) (all P values.0001). On multiple regression analysis, LV global longitudinal systolic strain and diastolic strain rate were the most important independent predictors of LA longitudinal systolic and diastolic function, in contrast to noninvasive LV filling pressures (i.e., mitral E/e' average septal-lateral ratio), which were modestly related to LA longitudinal systolic and diastolic function. Furthermore, in patients with HFNEF, the subendocardial function of both the left atrium and the left ventricle was significantly impaired in high proportions. In that regard, in patients with HFNEF, the rate of LA longitudinal systolic and diastolic dysfunction was 65.5% and 28.5%, whereas the prevalence of LV longitudinal systolic and diastolic dysfunction was 81.5% and 58%, respectively. In addition, patients with both systolic and diastolic longitudinal dysfunction of the left atrium presented worse NYHA functional class as compared with those with normal LA longitudinal function.In patients with HFNEF, LA subendocardial systolic and diastolic dysfunction is common and possibly associated with the same fibrotic processes that affect the subendocardial fibers of the left ventricle and to a lesser extent with elevated LV filling pressures. Furthermore, these findings suggest that LA longitudinal systolic and diastolic dysfunction could be related to reduced functional capacity during effort in patients with HFNEF.

Aims The aim of the present multicentre study was to analyse a large cohort of healthy subjects and patients with a common condition such as heart failure (HF) with the purpose of determining the normal range and the usefulness of right ventricular (RV) systolic strain to detect subtle RV systolic abnormalities using 2D speckle-tracking echocardiography. Methods and results We analysed 238 healthy subjects and a cohort of 642 patients characterized by asymptomatic patients ( n = 216) and patients with HF with preserved (HFpEF) and reduced (HFrEF) ejection fraction ( n = 218 and n = 208, respectively) prospectively included in 10 centres. The normal range of RV systolic strain analysing the healthy subjects was as follows: RV global strain −24.5 ± 3.8 and RV free wall strain −28.5 ± 4.8 (lowest expected value −17 and −19%, respectively). Concerning the ability of these myocardial parameters to detect subtle RV systolic abnormalities, RV global and free wall systolic strain were able to detect subtle RV longitudinal systolic abnormalities in a significant proportion of patients with HFrEF and to a lesser extent in HFpEF despite preserved tricuspid annular plane systolic excursion, tricuspid lateral annular peak systolic velocity by pulsed tissue Doppler imaging, and RV fractional area change. In addition, RV global and free wall systolic strain were significantly linked to the symptomatic status of the patients. Conclusions The findings from this study provide important data regarding the normal range of RV global and free wall systolic strain and highlight the clinical relevance of these RV myocardial parameters to detect subtle RV systolic abnormalities in patients with HF.

BACKGROUND: Atrial fibrillation (AF), a disease of the elderly, occasionally occurs at younger age. Pathophysiology of AF in younger patients is diverse, including channelopathies and cardiomyopathies. Data on the significance and complications of AF in young patients are scarce. HYPOTHESIS: Atrial fibrillation is the first manifestation of cardiovascular disease (CVD) in young patients. METHODS: From 11 888 patients in a university hospital database, patients age ≤35 years were identified. A composite of stroke/transient ischemic attack, thromboembolic events, major bleeding, and death was the primary endpoint. Stroke/transient ischemic attack, thromboembolic events, major bleeding, death, AF during follow‐up, diagnosis of arrhythmia other than AF, and new diagnosis of any CVD were secondary endpoints. Endpoints were compared between patients with and without comorbidities. RESULTS: We identified 124 patients (29.1± 5 years). Of those, 84 were followed over 48.4 ± 39.8 months. Comorbidities were present in 40.5%. Incidence of the primary endpoint was not different between the groups. Arrhythmias other than AF were more common in patients without comorbidities (36% vs 14.7%; P = 0.032). A supraventricular tachycardia (SVT) was found in 57.1% of patients who underwent electrophysiological testing and was treated with catheter ablation. None of those patients had AF during follow‐up. CONCLUSIONS: Atrial fibrillation occurs in young patients with and without structural heart disease. Young AF patients without comorbidities rarely develop CVD during the first years after diagnosis. Yet, an SVT is found in a high proportion of young AF patients; AF may be first manifestation of SVT. Therefore, young patients should undergo further evaluation for SVT

A 31-year-old male patient with an implantable cardioverter defibrillator (ICD) experienced ventricular fibrillation. After resuscitation, no communication between the device and an ICD programmer was possible. The ICD was explanted, no signs of destruction were visible, and the ICD leads revealed normal values. A new ICD was implanted, interrogation values were stable. However, immediately after defibrillation testing the connection between programmer and ICD was interrupted and could not be established again. The device showed burn marks and a hole in the can. Analysis revealed an isolation defect of the ICD lead, which was not detectable with standard interrogation.

Catheter ablation of left atrial linear lesions is an effective treatment option for perimitral flutter and is often used as a substrate modification approach for persistent atrial fibrillation. The two most popular mitral isthmus lines are those of the anterior or the posterior mitral isthmus. A comparison of these two mitral isthmus ablation approaches is still pending. Patients undergoing catheter ablation either at the anterior or the posterior mitral isthmus were included. Procedural success, conduction block, procedure durations, complications, and the necessity of a coronary sinus ablation were analyzed. We investigated 80 consecutive patients, 40 (50 %) with an anterior and 40 (50 %) with a posterior mitral isthmus line. Twenty (25.0 %) patients had perimitral annulus flutter; the remainder of the patients had persistent atrial fibrillation. Bidirectional conduction block was achieved in the same proportion in the anterior group (36; 90.0 %) as it was in the posterior group (30; 75.0 %) (statistically insignificant). Duration of procedure (18 ± 12 vs. 34 ± 24 min, p = 0.001), radiofrequency application (11 ± 7 vs. 18 ± 11 min, p = 0.004), and fluoroscopy (2 ± 2 vs. 8 ± 8 min, p

Both type 1 and type 2 diabetes mellitus are associated with increased cardiovascular morbidity and mortality, and now affect more than 170 million individuals worldwide. The incidence of type 2 diabetes is growing rapidly and now accounts for 90 to 95 percent of all diabetes cases. Thiazolidinediones (TZDs), a class of insulin sensitizing agents commonly used in the treatment of patients who have type 2 diabetes, improve endothelial dysfunction and exert beneficial effects on lipid profiles by activating the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-γ). In addition, TZDs exhibit antiatherogenic effects, independent of their antidiabetic and lipid-lowering properties, by attenuating proinflammatory processes. The combination of increased insulin sensitivity, improved lipid profile, and reduced inflammation may explain the cardiovascular benefits of this class of drugs.

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily. The 3 PPAR isotypes, PPAR-α, PPAR-γ, and PPAR-δ, play a key role in the regulation of lipid and glucose metabolism. Obesity and the interrelated disorders of the metabolic syndrome have become a major worldwide health problem. In this review, we summarize the critical role of PPARs in regulating inflammation, lipoprotein metabolism, and glucose homeostasis and their potential implications for the treatment of obesity, diabetes, and atherosclerosis.

Objective: Angiotensin II (AII) promotes cardiac fibrosis by increased extracellular matrix production and enhanced interaction of matrix proteins with their cellular receptors, including integrins. AII and other growth factors augment h1-integrin-dependent adhesion and spreading by binside-out signalingQ without affecting the total number of integrin receptors. bInside-out signalingQ involves specific signaling pathways, including protein kinase C (PKC), leading to activation of h1-integrins. In the present study we investigated the mechanisms involved in AII-increased adhesion of adult rat cardiac fibroblasts (CFBs), obtained from Sprague–Dawley rats, to collagen I mediated by h1-integrin. Methods and results: Treatment of CFBs with AII induced a concentration-dependent increase in adhesion to collagen I (2.2-fold, pb0.01) within 3–6 h of treatment. This effect was mediated by h1-integrin via the angiotensin AT1 receptor and was significantly reduced by protein kinase C inhibition. AII significantly induced phosphorylation of PKC epsilon (PKCq), which is involved in h1-integrin-dependent adhesion and motility, and phosphorylation of the cytoplasmatic tail of h1-integrin at threonine 788/789, required for adhesion. Phosphorylation of h1integrin and an increase in adhesion was also induced by l-a-phosphatidylinositol-3,4,5-triphosphate (l-a-PIP3), an activator of endogeneous PKCq. AII failed to increase adhesion in myofibroblasts obtained from PKCq (/) mice, but not in cells obtained from control mice. Coimmunoprecipitation and double immunofluorescence demonstrated that AII induced a close association of PKCq with h1-integrin in CFBs. Conclusion: The present study demonstrates that AII increased h1-integrin-dependent adhesion to collagen I in cardiac fibroblasts by insideout signaling via PKCq and phosphorylation of the cytoplasmatic tail of the h1-integrin. D 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.

The metabolic syndrome is a worldwide epidemic, setting the stage for type 2 diabetes and its microvascular complications, and acceleration of macrovascular disease. Insulin resistance, hyperglycemia, dyslipidemia, hypertension, thrombotic disorders and adiposity define the metabolic syndrome and contribute to endothelial dysfunction and, subsequently, to accelerated atherosclerosis. Angiotensin II contributes to the development and progression of cardiovascular and renal endpoints and, as such, angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors demonstrate a protective effect. Ligands for the peroxisome proliferator-activated receptor gamma (PPAR gamma), appear to impact favourably on atherosclerosis through both direct and indirect mechanisms. In humans, these ligands improve endothelial function, attenuate albuminuria and hypertension, and potentially prevent conversion of prediabetes to type 2 diabetes. Statins also have proven benefit in decreasing overall cardiovascular and stroke mortality and morbidity. The combination of angiotensin II blockade, statin therapy and PPAR gamma activation might emerge as an important global therapeutic strategy in the metabolic syndrome and diabetes. Further studies are needed to determine whether they have synergistic effects to protect the vasculature.

Peroxisome proliferator-activated receptor γ (PPARγ) is a transcription factor belonging to the nuclear hormone receptor superfamily. PPARγ binds the insulin-sensitizing thiazolidinediones (TZDs) and is prominently upregulated in intimal vascular smooth muscle cells (VSMC) after mechanical injury to the vessel wall. Several TZD PPARγ ligands have been shown to inhibit neointima formation. Suppression of intimal hyperplasia by PPARγ ligands likely results from their activity to inhibit VSMC growth and to promote apoptosis. This review summarizes molecular pathways through which PPARγ regulates the expression and function of multiple cell cycle and apoptosis genes resulting in decreased VSMC proliferation and inhibition of neointima formation.

Many of the signaling events in VSMC stimulated by angiotensin II (AngII) are mediated by members of the mitogen-activated protein kinase (MAPK) family, including p38 MAPK. The role of p38 MAPK in AngII-mediated cell cycle regulation is poorly understood. Therefore, we examined the involvement of p38 MAPK signaling in AngII-stimulated DNA synthesis, phosphorylation of the retinoblastoma protein (Rb), and expression of the G1-phase cyclin D1 in human coronary artery smooth muscle cells (CASMC). AngII (1 microM) stimulated p38 MAPK and ERK1/2 activation. Pretreatment with the p38 MAPK inhibitors SB203580 (10 microM) (SB) or SKF-86002 (10 microM) (SKF) potently inhibited AngII-induced p38 MAPK activation, but enhanced AngII-mediated ERK1/2 activation. AngII-induced-phosphorylation of Rb (Ser 795 and Ser 807/811), -cyclin D1 expression, and -DNA synthesis was also markedly enhanced by pharmacological inhibition of the p38 MAPK pathway. The present study demonstrates that p38 MAPK negatively regulates AngII-induced ERK1/2 activity, Rb phosphorylation, cyclin D1 expression, and DNA-synthesis in human CASMC. These findings support an important role for p38 MAPK in modulating AngII-mediated VSMC hyperplasia.

HMG-CoA reductase inhibitors have direct vascular effects that contribute to plaque stability. In the current study, the authors demonstrate that the HMG-CoA reductase inhibitors atorvastatin and pravastatin augment the adhesion of human (HSMCs) and rat aortic smooth muscle cells (RASMCs) to collagen I via induction of alpha2beta1-integrin receptors. Atorvastatin (0.1 microM ) increased the adhesion of HSMCs to collagen I up to 2-fold (p < 0.01) and pravastatin (1.0 microM ) up to 1.8-fold (p < 0.01) after treatment of at least 24 h. This increase in adhesion was concentration dependent and was observed for treatment periods from 16 to 72 h. Inhibition of isoprenoid synthesis with mevalonate and geranyl-geraniol prevented the statin-induced effect on human and rat smooth muscle cells. Flow cytometry revealed an increased expression of alpha2- and beta1-integrins after treatment with atorvastatin (0.1 microM ) at 24 and 48 h. Atorvastatin increased levels of beta1-integrin mRNA after 12- and 24-h treatment in HSMCs, which was inhibited by mevalonate. Furthermore, atorvastatin (0.1 microM ) and pravastatin (1.0 microM ) inhibited chemotaxis of HSMCs on collagen I, which was also reversed by mevalonate treatment. In contrast, inhibition of beta1-integrins with a specific antibody nearly doubled (p < 0.01) the rate of chemotaxis. These data indicate that the chemotactic activity in HSMCs is inhibited in part by up-regulation of alpha2beta1-integrin receptors. The current study indicates that HMG-CoA reductase inhibitors increase cell-matrix interaction with collagen I via induction of alpha2beta1-integrins and increased adhesion to collagen I.

Peroxisome proliferator-activated receptors (PPARs) regulate lipid and glucose metabolism and exert several vascular effects that may provide a dual benefit of these receptors on metabolic disorders and atherosclerotic vascular disease. Endothelial cell migration is a key event in the pathogenesis of atherosclerosis. We therefore investigated the effects of lipid-lowering PPARa-activators (fenofibrate, WY14643) and antidiabetic PPARc-activators (troglitazone, ciglitazone) on this endothelial cell function. Both PPARa- and PPARc-activators significantly inhibited VEGF-induced migration of human umbilical vein endothelial cells (EC) in a concentration-dependent manner. Chemotactic signaling in EC is known to require activation of two signaling pathways: the phosphatidylinositol-3-kinase ðPI3K Þ! Akt- and the ERK1/2 mitogen-activated protein kinase (ERK MAPK) pathway. Using the pharmacological PI3K-inhibitor wortmannin and the ERK MAPK-pathway inhibitor PD98059, we observed a complete inhibition of VEGF-induced EC migration. VEGF-induced Akt phosphorylation was significantly inhibited by both PPARa- and c-activators. In contrast, VEGF-stimulated ERK MAPK-activation was not affected by any of the PPAR-activators, indicating that they inhibit migration either downstream of ERK MAPK or independent from this pathway. These results provide first evidence for the antimigratory effects of PPAR-activators in EC. By inhibiting EC migration PPAR-activators may protect the vasculature from pathological alterations associated with metabolic disorders. 2002 Elsevier Science (USA). All rights reserved.

We have recently demonstrated that furin, PC5, and PC7, members of the subtilisin/kexin-like mammalian proprotein convertases (PCs), are found in rodent aorta. These PCs have been identified to activate several growth factors, adhesion molecules and extracellular matrix compounds by endoproteolytic cleavage. In the present study, we investigated the regulation of PC5 in vascular smooth muscle cells (VSMCs) in vitro and in vivo. Stimulation of rat aortic VSMCs with platelet-derived growth factor (PDGF)-BB (20 ng/mL), angiotensin II (Ang II, 1 μmol/L), or 10% fetal calf serum (FCS) for 48 hours increased DNA synthesis, as assessed by proliferating cell nuclear antigen (PCNA) immunoblotting. PC5 was strongly upregulated by PDGF-BB and 10% FCS (both 8-fold, P s6 -kinase (both P s6 -kinase dependent. Thus, growth factors regulate the proprotein convertase PC5, which may play an important role during VSMC growth.

Introduction Success rates of catheter ablation (CA) of persistent atrial fibrillation (AF) are very variable. Identifying patients in whom sinus rhythm maintenance cannot be achieved after CA is a critical issue. Methods 2D speckle-tracking echocardiography was performed before the first CA procedure in consecutive patients with persistent AF. Left atrial (LA) strain was correlated with recurrence of atrial arrhythmias during the follow-up period of 15 months after one CA procedure with or without antiarrhythmic drugs (primary endpoint). In a secondary analysis, recurrences after two CA procedures were analysed. Results 102 patients were included. Patients with recurrence of atrial arrhythmias after one CA procedure (n=55) had significantly lower LA strain than those without recurrence (LA strain 9.7±2.4% vs 16.2±3.0%; p14.5% (97.7%, 42.1% and 10.3%, respectively; p

Pulmonary vein isolation (PVI) is widely established as a curative treatment option for atrial fibrillation (AF). A wide range of techniques to improve catheter manipulation and steerability has been developed over the past years. A new remote catheter system (RCS) has recently become available (Amigo Remote Catheter System, Catheter Robotics, Budd Lake, NJ, USA). Here, we present a dual-center study on the RCS for left atrial mapping and PVI in patients with paroxysmal AF compared to a control group undergoing conventional PVI. One hundred nineteen patients who underwent PVI for paroxysmal AF were studied. Forty patients underwent PVI with the use of the RCS. Seventy-nine patients, who underwent conventional PVI, served as control group. Procedural data were compared between the two groups. PVI was achieved in all patients. In the RCS group compared to standard ablation group, there were no significant differences in procedure duration (159.1 ± 45.4 vs. 146 ± 30.1 min, p = 0.19), total energy delivery (78,146.3 ± 26,992.4 vs. 87,963.9 ± 79,202.1 Ws, p = 0.57), and total fluoroscopy time (21.2 ± 8.6 vs. 23.9 ± 5.4 min, p = 0.15). Operator fluoroscopy exposure was significantly reduced in the RCS group (13.4 ± 6.1 vs. 23.9 ± 5.4 min, p

Neointima formation involves tissue expression of matrix proteins and growth factors. The role of αvβ3, but not αvβ5 integrin in vascular cells has been sufficiently investigated. The aim of the present study was to determine and compare the function of αvβ3 and αvβ5 integrins in rat aortic (RASMC) and human coronary vascular smooth muscle cells (HCSMC) and to characterize their expression accompanying neointima formation in vivo. RASMC and HCSMC express αvβ3 and αvβ5 integrin subunits. The αvβ5 integrin predominantly mediated adhesion of RASMCs to vitronectin and spreading on vitronectin via RGD-binding sequences. In contrast, the αvβ3 integrin did not contribute to the adhesion and spreading on fibronectin, vitronectin, gelatin or collagen I coated layers. PDGF-directed migration through gelatin coated membranes involved both αvβ3 and αvβ5 integrins. Selective blocking antibodies for αvβ3 and αvβ5 inhibited migration of RASMC and HCSMC by more than 60% (p < 0.01). Integrin expression was studied in vivo in thoracic aorta of Sprague Dawley rats before and after balloon injury. In situ hybridization demonstrated low signals for αvβ3 and β5 mRNA in uninjuried aorta, which increased significantly at 14 days, localized predominantly in the neointima. Northern analysis of aorta after 14 days of injury also demonstrated an upregulation of αvβ3 and β5 mRNA compared to uninjured aorta. Consistent with the increase in message levels, increased inegrin protein expression was seen in the neointima after 7 and 14 days. This study provides evidence that αvβ3 and αvβ5 are elevated during neointima formation in the rat and indicates a novel role for αvβ5 participating in mechanisms regulating smooth muscle cell migration.

CD40-CD154-mediated cell signalling is impor tant for T-cell function under various physiological and pathophysiological conditions. It has been re cently described to play a role in cellular functions of macrophages (MACs) and vascular smooth-muscle cells (VSMCs) in cardiovascular diseases. In the present study, the expression of CD40 receptor protein and its function was studied in VSMCs ob tained from human coronary arteries. In addition, we studied the expression and distribution of CD40 in atherosclerotic lesions of 43 patients. VSMCs isolated from human coronary arteries and aorta treated with interferon-g (INF-γ) demon strated a upregulation of CD40 compared to low basal expression. CD40 expressing VSMCs treated with CD154 (CD40 ligand) resulted in an increas ed expression of inflammatory proteins, such as vascular-cell adhesion molecule-1 (VCAM-1) and Interleukin-8 (Il-8). Serial immunohistological stainings of human iliac arteries from 43 patients were performed (from lesions according to WHO criteria) and CD40 expression and distribution was analyzed. Human atherosclerotic lesions revealed a significant increase of intimal thickness, number of inflammatory infiltrates, and CD40-positive MACs and VSMCs with progression of the lesions. A significant correlation between intimal thickness and CD40-positive MACs and CD40-positive VS-MCs was observed. Ligation of the cellular CD40 receptors on VSMCs contributes to inflammatory cellular events in the vascular wall. The histological data suggest a direct association of CD40 expres sion in atherosclerotic lesions with plaque develop ment and progression of atherosclerosis.

A 31-year-old male patient with an implantable cardioverter defibrillator (ICD) experienced ventricular fibrillation. After resuscitation, no communication between the device and an ICD programmer was possible. The ICD was explanted, no signs of destruction were visible, and the ICD leads revealed normal values. A new ICD was implanted, interrogation values were stable. However, immediately after defibrillation testing the connection between programmer and ICD was interrupted and could not be established again. The device showed burn marks and a hole in the can. Analysis revealed an isolation defect of the ICD lead, which was not detectable with standard interrogation.

Background Catheter ablation is a curative treatment option for ventricular premature contractions (VPC) and ventricular tachycardia (VT). Procedures require different sedation levels, depending on duration, ablation approach and patient characteristics. The aim of our study was to evaluate feasibility of minimal and deep sedation for ablation of VPC/VT. Methods Patients underwent catheter ablation of VPC/VT under minimal or deep sedation. Events of hypotension, hypoxia, bradycardia, procedural complications and VT inducibility were compared between the groups. Results 120 patients were included. In 42 patients (53.6±17.1years, 47.6% male) ablation was performed under minimal sedation with midazolam, and in 78 patients (54.2±17.5years, 67.9% male) ablation was performed under deep sedation with propofol/midazolam. There were significantly fewer patients with idiopathic VT (62.8 vs. 88.1%, p=0.011) in the deep sedation group, LVEF was significantly lower (47±14.4 vs. 53.1±11.7) and the procedure duration was significantly longer (201.9±85.9 vs. 137.9±98.7). No significant differences in procedural complications or sedation related events (hypotension: 0 vs. 3.8%, p=0.2, no hypoxia, no bradycardia) were detected. Conclusions Minimal sedation and deep sedation are both feasible during VPC/VT ablation procedures. Propofol does not increase complications even in a collective with pre-existing impairment of LVEF. Adequate monitoring and trained personnel should be present.