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Aims: Electrical cardioversion is one cornerstone for the rhythm control strategy of atrial fibrillation (AF), which is, however, hampered by immediate AF recurrence (IRAF) or failed electrical cardioversion (FECV). We aimed to investigate the potential role of vernakalant for facilitated electrical cardioversion in cardioversion-resistant AF., Methods and Results: The subjects of this study were 63 patients referred to the Heart Centre Leipzig between November 2011 and May 2014 for transthoracic electrical cardioversion of AF. All patients experienced after antiarrhythmic-naïve electrical cardioversion either IRAF (n = 44; 70%) or FECV (n = 19; 30%). After drug infusion, electrical cardioversion was successful in 66.7% of vernakalant-treated as opposed to 46.7% of amiodarone-treated patients (P = 0.109). Multivariate analysis revealed treatment with vernakalant (OR 0.057, 95% CI 0.006-0.540, P = 0.013), treatment with ACEI or ARB (OR 0.101, 95% CI 0.015-0.691 P = 0.019), and IRAF after initial CV (OR 0.047, 95% CI 0.004-0.498, P = 0.011) as predictors for successful, drug-facilitated electrical cardioversion. Subgroup analysis of 18 patients with previous AF ablation revealed a significantly higher success rate of electrical cardioversion after infusion of vernakalant than after infusion of amiodarone (66.7 vs. 11.1%, P = 0.016)., Conclusion: Vernakalant may therefore be considered as a useful agent for facilitated electrical cardioversion in cardioversion-resistant AF., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Purpose: Left atrium (LA) size is a common predictor of ablation outcomes in atrial fibrillation (AF), but different LA diameters have not been adequately studied yet. We aimed to find the best predictor of ablation outcomes using single-linear LA dimensions by computed tomography (CT) or echocardiography., Methods: Patients (n = 103, 72 males, 59 ± 9 years) undergoing AF ablation were analyzed. LA diameter (LA-D) was measured by transthoracic echocardiography (parasternal long axis). After 3D reconstruction of CT data (EnSite Verismo, SJM, MN), maximal LA dimensions were measured on a coronal plane (superior-inferior, SI, and transversal, TV) and a sagittal plane (anterior-posterior, AP). Volume (LAV) was rendered after LA appendage and pulmonary vein exclusion., Results: Patients with persistent AF (n = 40) had significantly larger LA size than those with paroxysmal AF (n = 63). After 26 ± 14 months, 31 (30 %) patients had AF recurrence. Univariate Cox regression analysis revealed that LA-D, LA-SI, LA-TV, LAV, and LAV-index (LAV/body surface area) were associated with AF recurrence. Multivariate Cox regression analysis revealed that LAV was the strongest independent predictor of AF recurrence (HR = 1.011 per ml, 95 % CI 1.003-1.020, p = 0.002). LA-TV had the best correlation with LAV (r = 0.69, p < 0.01) and was the strongest single-linear predictor (HR = 1.07 per mm, 95 % CI 1.022-1.121, p = 0.004). Independent of LA-D, an LA-TV>74.5 mm predicted AF recurrence similarly to LAV>126 ml., Conclusions: LA dilatation, especially on the coronal plane, is associated with reduced long-term success after catheter ablation. LA-TV is the best linear predictor of AF recurrence, stronger than the commonly used LA-D.

Introduction: The porcine model is generally accepted for the development and testing of new forms oftherapy including ablation of atrial fibrillation (AF). However, the challenging left atrial (LA) and pulmonary vein (PV) anatomy enables only limited percutaneous catheter-based PV access., Results: Here we present I) an alternative percutaneous transapical access, which enables easy and safe retrograde transmitral LA and PV mapping and ablation; II) early experience of LA mapping and successful circumferential PV isolation with novel mapping system (Rhythmia(TM)) and new generation of ablation catheter equipped with micro electrodes (IntellaTip MiFi)., Conclusion: Although the experience with the transapical approach is limited, the initial results are promising as this may offer an alternative approach for tasting new technologies and translational research.

Background: Females with atrial fibrillation (AF) are at increased risk for ischemic stroke but have been under-represented in AF ablation cohorts. Whether the incidence of TE in women after catheter ablation is higher is unknown. We aimed to analyze the predictive value of thromboembolic scores and other clinical variants for thromboembolism (TE) after AF catheter ablation, separately in women and men., Methods: TE was combined endpoint of early (within first month) and late (during long-term follow-up) stroke, transient ischemic attack, or systemic embolism. Oral anticoagulation was prescribed for 6 months after catheter ablation and discontinued if CHADS2 was <2 and no AF recurrences were documented., Results: The study population (n = 2,069, 66 % male, 60 ± 10 years; 62 % paroxysmal AF) was followed for a median of 18 months (IQR 12-29). Overall 31 TE (1.5 %) occurred with 16 events within 30 days of ablation and 15 TE during the follow-up. Fourteen females (2.0 %) and 17 males (1.2 %) suffered TE (p = 0.128). On multivariate analysis, higher CHADS2 (HR 1.65, 95 % CI 1.10-2.47, p = 0.015), CHA2DS2-VASc (HR 1.42, 95 % CI 1.03-1.96, p = 0.034), R2CHADS2 (HR 1.76, 95 % CI 1.32-2.35, p < 0.001) scores, and eGFR <60 ml/min/1.73 m(2) (HR 3.95, 95 % CI 1.23-12.7, p = 0.021) were significantly associated with TE in men. In females, LV-EF (HR 0.95, 95 % CI 0.91-0.99, p = 0.021) and CHA2DS2-VASc score (HR 1.52, 95 % CI 1.01-2.28, p = 0.044) remained significant predictors for TE., Conclusion: TE rates after AF catheter ablation are low in both genders. In females, LV-EF and CHA2DS2-VASc score and in males all three scores and renal dysfunction were associated with TE.

A 74-year old was considered for atrioventricular (AV) nodal ablation in view of atrial fibrillation (AF) with poorly controlled ventricular rate despite being on amiodarone. Targeted AV nodal ablation was successfully performed after identifying the target site for ablation by reviewing an ultra high-density map of the His region produced by automatic electrogram annotation.

Aims: Although sinus node modification by catheter ablation is an established therapy for the treatment of inappropriate sinus tachycardia, there is incomplete understanding of sinus node anatomy and function but also limited electroanatomical mapping data. Recently, an automatic, ultra high-resolution mapping system has been presented to accurately and quickly identify right atrial (RA) geometry and activation patterns but detailed assessment of sinus node activation has not been performed which was one aim of this study. Preclinical experiences are compared with previous sinus node mapping studies in animals and humans, and potential clinical implications for catheter ablation are discussed., Methods and Results: In anaesthetized and ventilated 14 pigs, 30 endocardial and 2 eipcardial RA maps were generated using the Rhythmia™ mapping system without complications and earliest activation sites (EAS) and sinus break-out (SBO) were determined. At baseline, EAS and SBO were located anterior to the middle (n = 6) or lower third (n = 8) of the crista terminalis exhibiting a unicentric activation pattern in all cases. Conduction pathways were directed anterior, posterior, superior, or inferior with substantial inter-individual variation in direction, pathway distance, and conduction time. Orciprenaline, propranolol, or amiodarone shifted endocardial activation with considerable variation between animals with inconsistent patterns. Multicentric activation was found in one case after orciprenaline infusion. Sequential endocardial and epicardial high-density mapping of the RA was performed in two animals and showed a high congruence of the sinus node activation in the endo- and the epicardial map., Conclusion: Ultra high-density mapping allows fast, simple, and very detailed assessment of sinus node activation. Future studies are clearly needed to evaluate novel mapping and ablation strategies for an improved understanding of sinus node disease and better outcomes., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Invasive electrophysiology is a rapidly developing field of cardiovascular science with a constant need for inventions and testing of new technologies and concepts. Despite the swine model being an established tool in biomedical research no comprehensive guide for interventional electrophysiologists exists. The aim of the current article is to provide a practical overview of the pig anatomy, fluoroscopic views, and corresponding high density electroanatomic maps using a novel mapping system and a practical guide for interventions and techniques. In 17 pigs, fluoroscopic images of the right atrium, coronary sinus (CS), left atrium, and pulmonary veins as well as the right and left ventricles were obtained and correlated with ultra-high density electroanatomic maps and gross anatomy. Pitfalls of the porcine anatomy are precisely addressed, and alternative access techniques to overcome those issues are suggested. Important differences to human electrophysiological studies are highlighted. Complementary models such as cardiac ischemia induction or renal and pulmonary artery denervation are discussed in detail.

It has now been more than a quarter of a century since modulation of the sympathetic nervous system was proposed for the treatment of cardiac arrhythmias of different origins. But it has also been some time since some of the early surgical attempts have been abandoned. With the development of ablation techniques, however, new approaches and targets have been recently introduced that have revolutionized our way of thinking about sympathetic modulation. Renal nerve ablation technology is now being successfully used for the treatment of resistant hypertension, but the indication spectrum might broaden and new therapeutic options might arise in the near future. This review focuses on the possible impact of renal sympathetic system modulation on cardiac arrhythmias, the current evidence supporting this approach, and the ongoing trials of this method in electrophysiological laboratories. We will discuss the potential roles that sympathetic modulation may play in the future., (© 2014 Wiley Periodicals, Inc.)

The number of atrial fibrillation (AF) catheter ablations performed annually has been increasing exponentially in the western countries in the last few years. This is clearly related to technological advancements, which have greatly contributed to the improvements in catheter ablation of AF. In particular, state-of-the-art electroanatomical mapping systems have greatly facilitated mapping processes and have enabled complex AF ablation strategies. In this review, we outline contemporary and upcoming electroanatomical key technologies focusing on new mapping tools and strategies in the context of AF catheter ablation.

Aims: Atrial fibrillation (AF) is associated with frequent appropriate and inappropriate implantable cardioverter defibrillator (ICD) therapies. Catheter ablation of AF has been shown to reduce AF burden and improve left ventricular function in heart failure patients but the impact on ICD therapies has not yet been studied. The aim of this study was to test the hypothesis that AF ablation reduces ICD therapies in patients with cardiomyopathies., Methods and Results: In 73 consecutive patients (mean age 59 ± 10 years, 85% male) with previously implanted ICD due to ischaemic (n = 30) or dilated cardiomyopathy (n = 43) undergoing AF ablation, the prevalence and frequency of ICD therapies before and after AF ablation were compared. During the total follow-up of 3.3 ± 3 years prior to AF ablation, 5.1 ± 14.7 therapies per patient-year were delivered as opposed to 1.8 ± 10.9 in a period of 1.1 ± 0.9 years after ablation (P = 0.002). Prior to AF ablation, 39 patients (53%) received at least one ICD therapy when compared with 15 patients (21%) after ablation. Atrial fibrillation ablation was associated with freedom from any therapy regardless of appropriateness (odds ratio, OR, 0.366, CI 0.164-0.816, P = 0.014, adjusted for follow-up). Appropriate shocks significantly decreased from 0.3 ± 1.3 to 0.1 ± 0.5 per patient-year (P = 0.030). While heart failure medication and use of antiarrhythmic drugs were comparable during the entire follow-up, a statistically significant improvement of left ventricular ejection fraction (LVEF) from 36.9 ± 12.3% to 40.7 ± 6.7% (P = 0.008) was observed after AF ablation., Conclusions: In patients with ischaemic or dilated cardiomyopathy, catheter ablation of AF is associated with the reduction of inappropriate and appropriate ICD therapies and improvement of LVEF., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Aims: Recurrence of atrial fibrillation (AF) is frequently observed after AF catheter ablation. However, the predictive value of echocardiographic parameters associated with left ventricular diastolic dysfunction (LVDD) has not been well studied., Methods and Results: In 124 consecutive patients (mean age 61 ± 10 years, 60% male) with paroxysmal (n = 70) or persistent AF (n = 54) undergoing AF catheter ablation, mitral early diastolic peak (E-wave) and late peak (A-wave) velocities, E/A ratio, deceleration time (DT) of mitral early velocity, early diastolic mitral annulus peak velocity (e'), and E/e' ratio were determined by transthoracic echocardiography. Early (ERAF) and late AF recurrence (LRAF) were monitored with 7-day Holter electrocardiograms directly after catheter ablation and after 6 and 12 months. Early AF recurrence occurred in 34% of the patients, while LRAF was observed in 27% of the patients. Patients with ERAF had higher E-wave (0.9 ± 0.2 vs. 0.8 ± 0.2 m/s, P = 0.035) and lower A-wave velocity (0.5 ± 0.2 vs. 0.6 ± 0.2 m/s, P = 0.038), higher E/A ratio (1.8 ± 0.9 vs. 1.5 ± 0.9, P = 0.089), and slower DT (214 ± 67 vs. 243 ± 68 ms, P = 0.073), while E/e', left atrial diameter, and left ventricular ejection fraction were similar. In multivariable regression analysis, the E/A ratio was the only independent predictor of ERAF (odds ratio 2.905, 95% confidence interval 1.072-7.870, P = 0.036). None of the echocardiographic parameters influenced the late therapy outcome., Conclusion: Early results of the catheter ablation, but not the late rhythm outcome, are influenced by an impaired mitral inflow pattern, which is associated with LVDD., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Aims: The safety and efficacy of novel oral anticoagulants in patients with atrial fibrillation undergoing pacemaker or implantable cardioverter-defibrillator interventions have not been clearly defined. Therefore, we compared the incidence of bleeding and thrombo-embolic complications following cardiac rhythm device (CRD) implantations under dabigatran vs. rivaroxaban in a real-world cohort., Methods and Results: We analysed 176 consecutive procedures performed in 93 patients treated peri-interventionally with dabigatran and 83 patients with rivaroxaban, respectively. Post-operative bleeding complications and thrombo-embolic events occurring within 30 days were compared. There were no significant differences in baseline characteristics between patients in the dabigatran and the rivaroxaban group. Most of the patients in both the groups received dual chamber or cardiac resynchronization devices (71 vs. 78%) as opposed to single-chamber systems (29 vs. 22%). In the dabigatran group, two (2%) bleeding complications (two pocket haematomas) were observed in comparison with four (5%, three pocket haematomas and one pericardial effusion) in the rivaroxaban group (P = 0.330). Three complications in the rivaroxaban group necessitated surgical intervention as opposed to none in the dabigatran group (P = 0.064). One case of a transient ischaemic attack occurred in the dabigatran group (P = 0.343)., Conclusion: Bleeding and thrombo-embolic complications in patients treated with dabigatran or rivaroxban are rare. Further and larger studies are warranted to define the optimal anticoagulation management in patients with a need for oral anticoagulation and CRD interventions., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

The Grey horse phenotype, caused by a 4.6 kb duplication in Syntaxin 17, is strongly associated with high incidence of melanoma. In contrast to most human melanomas with an early onset of metastasis, the Grey horse melanomas have an extended period of benign growth, after which 50% or more eventually undergo progression and may metastasize. In efforts to define changes occurring during Grey horse melanoma progression, we established an in vitro model comprised of two cell lines, HoMel-L1 and HoMel-A1, representing a primary and a metastatic stage of the melanoma, respectively. The cell lines were examined for their growth and morphological characteristics, in vitro and in vivo oncogenic potential, chromosome numbers, and expression of melanocytic antigens and tumor suppressors. Both cell lines exhibited malignant characteristics; however, the metastatic HoMel-A1 showed a more aggressive phenotype characterized by higher proliferation rates, invasiveness, and a stronger tumorigenic potential both in vitro and in vivo. HoMel-A1 displayed a near-haploid karyotype, whereas HoMel-L1 was near-diploid. The cell lines expressed melanocytic lineage markers such as TYR, TRP1, MITF, PMEL, ASIP, MC1R, POMC, and KIT. The tumor suppressor p53 was strongly expressed in both cell lines, while the tumor suppressors p16 and PTEN were absent in HoMel-A1, potentially implicating significance of these pathways in the melanoma progression. This in vitro model system will not only aid in understanding of the Grey horse melanoma pathogenesis, but also in unraveling the steps during melanoma progression in general as well as being an invaluable tool for development of new therapeutic strategies.

Background: The interactions between atrial fibrillation (AF) and left ventricular diastolic dysfunction (LVDD) are complex and not well defined. Despite the high prevalence of LVDD in the AF population, therapies for LVDD remain limited. Previous studies have suggested that restoration of sinus rhythm with catheter ablation has a positive effect on LVDD, but the prevalence and predictors for worsened LVDD are unknown., Methods: 70 consecutive patients included in prospective AF catheter ablation registry (61±10 years, 66% male) with paroxysmal (n=40) or persistent AF (n=30) were examined by transthoracic echocardiography, before and 12 months after ablation. LVDD was classified according to current guidelines. Rhythm outcome of the ablation was verified by serial 7-day Holter ECG., Results: LVDD was present in 27 patients (38%) at baseline and in 33 patients (47%) at 12 months follow-up (p=.327). An improvement of LVDD was observed in 13 patients (19%), an aggravation was found in 19 (27%), while it was unchanged in the remaining 38 patients (54%). In uni- and multivariable regression analysis, total ablation time (OR 1.611 per 10 min ablation time, 95% CI 1.088-2.386, p=.017) was associated with LVDD progression, while neither baseline characteristics nor rhythm during follow-up influenced LVDD alterations. There was no association between echocardiographic deterioration and symptoms., Conclusions: Catheter ablation of AF can worsen LVDD in a substantial proportion of patients with more aggressive ablation leading to aggravation of LVDD. While there are no apparent negative short-term effects, long-term consequences need to be determined., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)