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1.  Contact force mapping during catheter ablation for atrial fibrillation: procedural data and one-year follow-up 
Archives of Medical Science : AMS  2014;10(2):266-272.
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.
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).
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.
PMCID: PMC4042046  PMID: 24904659
catheter-tissue contact; atrial fibrillation; pulmonary vein isolation
2.  Cost-effectiveness of cardiovascular magnetic resonance and single-photon emission computed tomography for diagnosis of coronary artery disease in Germany 
Recent studies have demonstrated a superior diagnostic accuracy of cardiovascular magnetic resonance (CMR) for the detection of coronary artery disease (CAD). We aimed to determine the comparative cost-effectiveness of CMR versus single-photon emission computed tomography (SPECT).
Based on Bayes’ theorem, a mathematical model was developed to compare the cost-effectiveness and utility of CMR with SPECT in patients with suspected CAD. Invasive coronary angiography served as the standard of reference. Effectiveness was defined as the accurate detection of CAD, and utility as the number of quality-adjusted life-years (QALYs) gained. Model input parameters were derived from the literature, and the cost analysis was conducted from a German health care payer’s perspective. Extensive sensitivity analyses were performed.
Reimbursement fees represented only a minor fraction of the total costs incurred by a diagnostic strategy. Increases in the prevalence of CAD were generally associated with improved cost-effectiveness and decreased costs per utility unit (ΔQALY). By comparison, CMR was consistently more cost-effective than SPECT, and showed lower costs per QALY gained. Given a CAD prevalence of 0.50, CMR was associated with total costs of €6,120 for one patient correctly diagnosed as having CAD and with €2,246 per ΔQALY gained versus €7,065 and €2,931 for SPECT, respectively. Above a threshold value of CAD prevalence of 0.60, proceeding directly to invasive angiography was the most cost-effective approach.
In patients with low to intermediate CAD probabilities, CMR is more cost-effective than SPECT. Moreover, lower costs per utility unit indicate a superior clinical utility of CMR.
PMCID: PMC3688498  PMID: 23574690
Cost-effectiveness; Cardiovascular magnetic resonance; Scintigraphy; Coronary angiography; Coronary artery disease
3.  In vitro Modeling of Ryanodine Receptor 2 Dysfunction Using Human Induced Pluripotent Stem Cells 
Background/Aims: Induced pluripotent stem (iPS) cells generated from accessible adult cells of patients with genetic diseases open unprecedented opportunities for exploring the pathophysiology of human diseases in vitro. Catecholaminergic polymorphic ventricular tachycardia type 1 (CPVT1) is an inherited cardiac disorder that is caused by mutations in the cardiac ryanodine receptor type 2 gene (RYR2) and is characterized by stress-induced ventricular arrhythmia that can lead to sudden cardiac death in young individuals. The aim of this study was to generate iPS cells from a patient with CPVT1 and determine whether iPS cell-derived cardiomyocytes carrying patient specific RYR2 mutation recapitulate the disease phenotype in vitro. Methods: iPS cells were derived from dermal fibroblasts of healthy donors and a patient with CPVT1 carrying the novel heterozygous autosomal dominant mutation p.F2483I in the RYR2. Functional properties of iPS cell derived-cardiomyocytes were analyzed by using whole-cell current and voltage clamp and calcium imaging techniques. Results: Patch-clamp recordings revealed arrhythmias and delayed afterdepolarizations (DADs) after catecholaminergic stimulation of CPVT1-iPS cell-derived cardiomyocytes. Calcium imaging studies showed that, compared to healthy cardiomyocytes, CPVT1-cardiomyocytes exhibit higher amplitudes and longer durations of spontaneous Ca2+ release events at basal state. In addition, in CPVT1-cardiomyocytes the Ca2+-induced Ca2+-release events continued after repolarization and were abolished by increasing the cytosolic cAMP levels with forskolin. Conclusion: This study demonstrates the suitability of iPS cells in modeling RYR2-related cardiac disorders in vitro and opens new opportunities for investigating the disease mechanism in vitro, developing new drugs, predicting their toxicity, and optimizing current treatment strategies.
PMCID: PMC3709175  PMID: 22178870
iPS cells; Cardiomyocytes; Catecholaminergic polymorphic ventricular tachycardia; RYR2; Delayed afterdepolarizations; Patch clamp; Calcium; Disease modelling; Heart
4.  Rate of cardiac arrhythmias and silent brain lesions in experienced marathon runners: rationale, design and baseline data of the Berlin Beat of Running study 
Regular exercise is beneficial for cardiovascular health but a recent meta-analysis indicated a relationship between extensive endurance sport and a higher risk of atrial fibrillation, an independent risk factor for stroke. However, data on the frequency of cardiac arrhythmias or (clinically silent) brain lesions during and after marathon running are missing.
Methods/ Design
In the prospective observational “Berlin Beat of Running” study experienced endurance athletes underwent clinical examination (CE), 3 Tesla brain magnetic resonance imaging (MRI), carotid ultrasound imaging (CUI) and serial blood sampling (BS) within 2-3 days prior (CE, MRI, CUI, BS), directly after (CE, BS) and within 2 days after (CE, MRI, BS) the 38th BMW BERLIN-MARATHON 2011. All participants wore a portable electrocardiogram (ECG)-recorder throughout the 4 to 5 days baseline study period. Participants with pathological MRI findings after the marathon, troponin elevations or detected cardiac arrhythmias will be asked to undergo cardiac MRI to rule out structural abnormalities. A follow-up is scheduled after one year.
Here we report the baseline data of the enrolled 110 athletes aged 36-61 years. Their mean age was 48.8 ± 6.0 years, 24.5% were female, 8.2% had hypertension and 2.7% had hyperlipidaemia. Participants have attended a mean of 7.5 ± 6.6 marathon races within the last 5 years and a mean of 16 ± 36 marathon races in total. Their weekly running distance prior to the 38th BMW BERLIN-MARATHON was 65 ± 17 km. Finally, 108 (98.2%) Berlin Beat-Study participants successfully completed the 38th BMW BERLIN-MARATHON 2011.
Findings from the “Berlin Beats of Running” study will help to balance the benefits and risks of extensive endurance sport. ECG-recording during the marathon might contribute to identify athletes at risk for cardiovascular events. MRI results will give new insights into the link between physical stress and brain damage.
Trial registration NCT01428778
PMCID: PMC3458995  PMID: 22938148
Marathon running; ECG-recording; Magnetic resonance imaging; Blood sampling; Cardiac arrhythmia
5.  Ventricular tachycardia as the first manifestation of cardiac sarcoidosis 
BMJ Case Reports  2009;2009:bcr08.2008.0810.
The case of a 32-year-old man with sustained ventricular tachycardia and hypotension is described. Following pharmacological treatment the patient switched to a sinus rhythm and was transferred to a university hospital for further diagnostic procedures and treatment. Cardiac catherisation ruled out underlying coronary artery disease, and cardiac MRI as well as echocardiography demonstrated a moderately reduced left ventricular ejection fraction, marked thickening of the interventricular septum and extensive intramural and epicardial infiltration of both ventricles. Endomyocardial biopsies were inconclusive; an implantable cardioverter defibrillator (ICD) was implanted in order to prevent a fatal arrhythmic event. Only repeated lymph node biopsies revealed typical findings of granulomatous disease, which together with the clinical course and the cardiac MRI findings strongly supported cardiac sarcoidosis. A few days after initiation of therapy with corticosteroids, the patient experienced the first of a number of ICD discharges, demanding aggressive anti-arrhythmic treatment regimen for the future.
PMCID: PMC3028065  PMID: 21686620
7.  Update on the Cardiac Safety of Moxifloxacin 
Current Drug Safety  2012;7(2):149-163.
Cardiac safety was compared in patients receiving moxifloxacin and other antimicrobials in a large patient population from Phase II–IV randomized active-controlled clinical trials. Moxifloxacin 400 mg once-daily monotherapy was administered orally (PO) or sequentially (intravenous/oral, IV/PO). Across 64 trials, 21,298 patients received PO therapy (10,613 moxifloxacin, 10,685 comparators) while 6846 received sequential IV/PO therapy (3431 moxifloxacin, 3415 comparators). Treatment-emergent cardiac adverse event (AE) rates were similar for moxifloxacin and comparators in PO (6.6% vs 5.8%) and IV/PO (11.0% vs 12.0%) trials. Treatment-emergent cardiac adverse drug reactions were rare in PO (moxifloxacin 3.2% vs comparators 2.4%) and IV/PO (moxifloxacin 1.4% vs comparators 1.5%) patients. There were five (<0.02%) treatment-emergent drug-related deaths due to cardiac events out of 28,144 patients; one PO patient died treated with comparators, one patient died treated with IV/PO moxifloxacin, and three patients died after treatment with IV/PO comparators. Only one case of treatment-related non-fatal torsade de pointes occurred in the comparator arm. Incidence rates of cardiac AEs remained low in populations at elevated risk of cardiac events predisposed to QTc prolongation (i.e. community-acquired pneumonia patients admitted to the intensive care unit and/or mechanical ventilation, patients with documented prolongation of baseline QTc interval, women, and patients ≥ 65 years old). There was no evidence of unexpected cardiac events. After moxifloxacin treatment, an expected small prolongation in QTcB and QTcF was found. This analysis of numerous clinical trials shows the favorable cardiac safety profile of moxifloxacin, when used appropriately and according to its label, versus other antibiotics.
PMCID: PMC3480699  PMID: 22873499
Cardiac safety; comparator antimicrobials; moxifloxacin; oral therapy; Phase II–IV clinical trials; QTc prolongation; sequential intravenous/oral therapy.

Results 1-7 (7)