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Background: The automated NavX Ensite Precision latency-map (LM) algorithm aims to identify atrial tachycardia (AT) mechanisms. However, data on a direct comparison of this algorithm with conventional mapping are scarce., Methods: Patients scheduled for AT ablation were randomized to mapping with the LM- algorithm (LM group) or to conventional mapping (conventional only group: ConvO), using entrainment and local activation mapping techniques. Several outcomes were exploratively analyzed. Primary endpoint was intraprocedural AT Termination. If AT termination with only automated 3D-Mapping failed, additional conventional methods were applied (conversion)., Results: A total of 63 patients (mean 67 years, 34 % female) were enrolled. In the LM group (n = 31), the correct AT mechanism was identified in 14 patients (45 %) using the algorithm alone compared to 30 patients (94 %) with conventional methods. Time to termination of the first AT was not different between groups (LM group 34 ± 20 vs. ConvO 43.1 ± 28.3 min; p = 0.2). However, when AT termination did not occur with LM algorithm, time to termination prolonged significantly (65 ± 35 min; p = 0.01). After applying conventional methods (conversion), procedural termination rates did not differ between LM group (90 %) vs. ConvO (94 %) (p = 0.3). During a follow-up time of 20 ± 9 months, no differences were observed in clinical outcomes., Conclusion: In this small prospective, randomized study, the use of the LM algorithm alone may lead to AT termination, but less accurate than conventional methods., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Competing Interests: Conflict of interest: None declared.

Background: Complex ablation for persistent atrial fibrillation (AF) aims to modify the arrhythmogenic substrates to become incapable to perpetuate the arrhythmia. Ablation-associated determinants of atrial tachycardia (AT) rather than AF recurrences are unknown. The aim of the study was to evaluate the association between the type of arrhythmia recurrence and electrophysiological findings during redo procedures., Methods: A total number of 384 consecutive patients with persistent AF underwent complex ablation consisting of PV isolation (PVI), biatrial electrogram-guided ablation, and linear ablation with the desired procedural endpoint of AF termination. Electrophysiological findings during redo procedures and its relation to AR type are the subject of this study., Results: Overall, 177 (46%) patients underwent a second procedure. Patients with AT recurrences had significantly more often persistent PVI (47 vs. 25%; P = 0.002). Moreover, a higher number of recovered PVs were associated with AF recurrence (3 PVs recovered, AF = 16.1% vs. AT = 5.2%; P = 0.02; 4 PVs recovered, AF = 18.5% vs. AT = 6.3%; P = 0.01), regardless of the extent of substrate ablation during the first procedure., Conclusions: Durable PV isolation but not the extent of atrial substrate ablation determines the type of arrhythmia recurrence. Thus, the PVs may represent dominant perpetuators (and not only triggers) of persistent AF even in the presence of a significantly modified atrial substrate., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Aims: Weight management seems to be beneficial for obese atrial fibrillation (AF) patients; however, randomized data are sparse. Thus, this study aimed to investigate the influence of weight reduction on AF ablation outcomes., Methods and Results: SORT-AF is an investigator-sponsored, prospective, randomized, multicentre, and clinical trial. Patients with symptomatic AF (paroxysmal or persistent) and body mass index (BMI) 30-40 kg/m2 underwent AF ablation and were randomized to either weight-reduction (group 1) or usual care (group 2), after sleep-apnoea-screening and loop recorder (ILR) implantation. The primary endpoint was defined as AF burden between 3 and 12 months after AF ablation. Overall, 133 patients (60 ± 10 years, 57% persistent AF) were randomized to group 1 (n = 67) and group 2 (n = 66), respectively. Complications after AF-ablation were rare (one stroke and no tamponade). The intervention led to a significant reduction of BMI (34.9 ± 2.6-33.4 ± 3.6) in group 1 compared to a stable BMI in group 2 (P < 0.001). Atrial fibrillation burden after ablation decreased significantly (P < 0.001), with no significant difference regarding the primary endpoint between the groups (P = 0.815, odds ratio: 1.143, confidence interval: 0.369-3.613). Further analyses showed a significant correlation between BMI and AF recurrence for patients with persistent AF compared with paroxysmal AF patients (P = 0.032)., Conclusion: The SORT-AF study shows that AF ablation is safe and successful in obese patients using continuous monitoring via ILR. Although the primary endpoint of AF burden after ablation did not differ between the two groups, the effects of weight loss and improvement of exercise activity were beneficial for obese patients with persistent AF demonstrating the relevance of life-style management as an important adjunct to AF ablation in this setting., Trial Registration Number: NCT02064114., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Left atrial (LA) thrombus formation is the presumed origin of thromboembolic complications in patients with atrial fibrillation (AF). Beyond clinical risk factors, the factors causing formation of LA thrombi are not well known. In this case-control study, we analyzed clinical characteristics and genetic thrombophilia markers (factor V Leiden (FVL), prothrombin G20210A (FIIV), Tyr2561 variant of von Willebrand factor (VWF-V)) in 42 patients with AF and LA thrombus (LAT) and in 68 control patients with AF without LAT (CTR). Patients with LAT had more clinical conditions predisposing to stroke (mean CHA 2 DS 2 -VASc-score 3.4 ± 1.5 vs. 1.9 ± 1.4; P < 0.001), a higher LA volume (96 ± 32 vs. 76 ± 21 ml, P = 0.002) and lower LA appendage emptying velocity (0.21 ± 0.11vs. 0.43 ± 0.19 m/s, P < 0.001). Prevalence of FVL, FIIV and VWF-V mutations was not different, but in the subgroup of patients <65 years (y) there was a tendency for a higher incidence of VWF-V with a prevalence of 27% (LAT <65 y) vs. 7% (CTR <65 y, P = 0.066). These findings warrant further investigation of the VWF-V as a risk factor for LA thrombogenesis in younger patients.

Background: Catheter ablation of non-reentrant, commonly termed "idiopathic" ventricular arrhythmias (VA) is highly effective in patients without structural heart disease (SHD). Meanwhile, the outcome of catheter ablation of these arrhythmias in patients with SHD remains unclear. This study sought to characterize the outcome of patients with and without SHD undergoing catheter ablation of non-reentrant VA., Methods: In this single-centre study the acute and long-term outcome of 266 consecutive patients undergoing catheter ablation of non-reentrant VA was investigated. In 41.0% of patients a SHD was present (n = 109, 80.7% male, age 59.1 ± 14.7 years), 59.0% had no SHD (n = 157; 44.0% male, age 49.9 ± 16.5 years)., Results: Acute procedural success (absence of spontaneous or provoked VA at the end of procedure and within 48 h after the procedure) was achieved in 89.9% of patients with SHD vs. 94.3% without SHD (p = 0.238). During a mean follow-up of 34.7 ± 15.1 months a repeat catheter ablation was performed in 19.6% of patients with SHD vs. 13.0% without SHD (p = 0.179). Patients with dilated cardiomyopathy (DCM) were the most likely to require a repeat ablation procedure (32.0% of patients with DCM vs. 13.0% without SHD; p = 0.022). Periprocedural complications occurred in 5.5% of patients with SHD vs. 5.7% without SHD (p > 0.999). All complications were managed without sequelae., Conclusions: The outcome of catheter ablation of non-reentrant VA in patients with SHD appears good and is comparable to patients without SHD. A slightly higher rate of repeat ablations was observed in patients with DCM.

Introduction: Procedural atrial fibrillation (AF) termination is considered as a predictor of long-term success after catheter ablation for persistent AF (persAF). However, some patients remain free of arrhythmia recurrences despite failure to achieve AF termination. The objective of this study was to assess long-term outcome and prognostic factors in patients undergoing complex ablation without procedural AF termination., Methods and Results: This study comprised 419 patients (63.8 ± 10.2 years, 63.4% male) undergoing complex ablation for persAF. Patients without procedural AF termination (n = 137, 64.2 ± 9.7 years, 63.5% male) were categorized into patients who remained in sinus rhythm (SR) in long-term outcome (SR-group) and patients with recurrence of AF or atrial tachycardia (AT) (AR-group). During a follow-up (FU) of 19.6 ± 14.6 months, the SR-group consisted of 65 (47.5%) and the AR-group of 69 (50.4%) patients. Three patients (2.2%) were lost to FU. Left atrial appendage (LAA) flow velocity and left atrium volume index (LAVI) could be identified as predictors for long-term success. LAA flow velocity and baseline AF cycle length (AFCL) were significantly associated with the type of arrhythmia recurrence (AF vs AT), ie, higher values of both are predictive for AT rather than AF recurrences. Patients with a LAVI < 34.4 mL/m² and significant AFCL increase during the ablation procedure had rather AT than AF recurrences., Conclusion: Patients with an arrhythmia-free outcome despite failure of procedural AF termination during complex ablation for persAF are characterized by specific morphological and functional properties that are easy to obtain., (© 2019 Wiley Periodicals, Inc.)

Introduction: Long-term efficacy and safety are uncertain in patients with cardiac implantable electronic devices (CIED) and transvenous leads (TVL) undergoing radiofrequency catheter ablation of atrial fibrillation (AF). Thus, we assessed the outcome of AF ablation in those patients during long-term follow-up using continuous atrial rhythm monitoring (CARM)., Methods and Results: A total of 190 patients (71.3 ± 10.7 years; 108 (56.8% men) were included in this study. At index procedure 81 (42.6%) patients presented with paroxysmal AF and 109 (57.4%) with persistent AF. The ablation strategy included pulmonary vein isolation in all patients and biatrial ablation of complex fractionated electrograms with additional ablation lines, if appropriate. AF recurrences were assessed by CARM- and CIED-related complications by device follow-up. After a mean follow-up of 55.4 ± 38.1 months, freedom of AF was found in 86 (61.4%) and clinical success defined as an AF burden less than or equal to 1% in 101 (72.1%) patients. Freedom of AF was reported in 74.6% and 51.9% (P = 0.006) and clinical success in 89.8% and 59.3% (P < 0.001) of patients with paroxysmal and persistent AF, respectively. In 3 of 408 (0.7%) ablation procedures, a TVL malfunction occurred within 90 days after catheter ablation. During long-term follow-up 9 (4.7%) patients showed lead dislodgement, 2 (1.1%) lead fracture, and 2 (1.1%) lead insulation defect not related to the ablation procedure., Conclusion: Our findings using CARM demonstrate long-term efficacy and safety of radiofrequency catheter ablation of AF in patients with CIED and TVL., (© 2019 Wiley Periodicals, Inc.)

Background: Arterial stiffness is a strong predictor of atrial fibrillation in the community. Whether noninvasively measured conduit artery function and peripheral vascular reactivity are related to atrial fibrillation remains unknown., Methods and Results: In 15 010 individuals of the population-based Gutenberg Health Study, mean age 55 ± 11 years, 50.5% men, we determined noninvasive vascular function by flow-mediated dilation (FMD) and peripheral arterial tonometry (PAT) in relation to manifest atrial fibrillation (N = 466). Patients with atrial fibrillation exhibited a higher mean brachial artery diameter [4.81 mm (4.17, 5.33) in atrial fibrillation vs. 4.31 mm (3.67, 4.93)] and baseline pulse amplitude in arbitrary units [6.35 (5.76, 6.78) in atrial fibrillation vs. 6.09 (5.36, 6.71)] as well as a reduced FMD in arbitrary units [1.29 (1.26, 1.33) in atrial fibrillation vs. (1.31 (1.26, 1.37)] and PAT ratio [0.42 (0.19, 0.77) in atrial fibrillation vs. 0.67 (0.33, 0.94)] compared with individuals without atrial fibrillation (all PWilcoxon rank-sum test). In age-adjusted and sex-adjusted logistic regression analyses, only baseline brachial artery diameter [odds ratio (OR) per standard deviation 1.19; 95% confidence interval (CI), 1.04-1.37; P = 0.012] and PAT ratio (OR 0.83; 0.74-0.94; P = 0.0029) were associated with atrial fibrillation. In risk factor and heart rate-adjusted models, there was no statistically significant correlation of atrial fibrillation and brachial artery diameter, FMD and PAT ratio while baseline pulse amplitude was reduced in individuals with atrial fibrillation (OR 0.81; 95% CI 0.71-0.93; P = 0.0034)., Conclusion: In our large contemporary cohort, peripheral vascular function was compromised in individuals with atrial fibrillation. However, observed associations were mediated by age and classical risk factors. Noninvasive vascular function measures did not improve discriminatory ability for atrial fibrillation.

Aims: Contact force (CF) catheters provide catheter-tissue contact information to improve outcome of pulmonary vein isolation (PVI) in paroxysmal atrial fibrillation (PAF). We evaluated different target-CF values for achievement of the additional endpoint of an unexcitable ablation line., Methods: A total of 106 patients undergoing PVI were randomized into three groups (G) (G1: target-CF 15 g, G2: target-CF 10 g, G3: CF concealed from operator). The PVI encircling line was divided into predefined sections. Excitable tissue along the PVI-line identified by high output pacing (10 V, 2 ms) was targeted for further ablation., Results: Mean average CF was 17.4 ± 4.7 g (G1) vs. 12.3 ± 6.0 g (G2) vs. 11.1 ± 6.5 g (G 3) (p < 0.001). Primary unexcitable ablation lines were found in 38.6, 19.4 and 5.7% (G1, G2, G3 respectively; G1 vs. G2 p < 0.05, G1 vs. G3 p < 0.001, G2 vs. G3 ns). Additional radiofrequency (RF)-energy to achieve unexcitability was lowest in G1 (3.6 ± 3.1 kJ vs. 8.6 ± 7.2 kJ (G2) and 10.4 ± 6.7 (G3), p ≤ 0.001, G2 vs. G3 ns) with accordingly lowest additional RF applications in G1 (3.0 ± 2.6 vs. 7.0 ± 5.4 in G2 and 8.4 ± 4.0 in G3; G1 vs. G2 and G3, p < 0.001, G 2 vs. G 3 ns). Sections along ablation lines with low initial CF were most likely to reveal excitability. Single procedure success was 81.9 vs. 73.5 vs. 71.4% (G 1, 2 and 3, p = 0.6) during 437 ± 254 day follow-up., Conclusion: Higher tip-to-tissue CF during PVI facilitates the achievement of an unexcitable ablation line, requiring less additional RF-energy.

Sex differences in cardiovascular risk factors, cardiac structure and function, and disease and symptom burden in the common arrhythmia atrial fibrillation (AF) have not been investigated systematically at the population level. Cross-sectional data of 14,796 subjects (age range 35 to 74 years, 50.5% men) from the population-based Gutenberg Health Study were examined to show the distribution of cardiovascular risk factors by AF status and sex, and to determine sex-specific predictors for AF. The prevalence of AF was higher in men (4.3%) than in women (1.9%). Men had a worse cardiovascular risk factor profile, a higher prevalence of cardiovascular disease, but fewer symptoms than women. Age-adjusted Cox regressions showed sex interactions in the association of high-density lipoprotein-cholesterol, triglycerides, diabetes mellitus, coronary artery disease, myocardial infarction, generalized anxiety disorder, and heart rate with AF. After multivariable adjustment, sex interactions were seen for thickness of interventricular end-diastolic septum, odds ratio (OR) per standard deviation (SD), 95% confidence interval women: 0.9 (0.8, 1.1), men: 1.2 (1.1, 1.4), interaction p value = 0.02; left atrial diameter index, OR per SD women: 1.5 (1.3, 1.8), men: 1.9 (1.7, 2.1), interaction p value = 0.03; and myocardial infarction, OR women: 2.7 (1.3, 5.6), men: 0.7 (0.5, 1.1), interaction p value = 0.002. In conclusion, in our large cohort, we observed substantial sex differences in AF distribution and clinical characteristics including comorbidities, symptom burden, and structural cardiac changes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Slow pathway modulation is the treatment of choice in patients with atrioventricular nodal reentrant tachycardia (AVNRT). No comparative data on ablation strategies exist. Therefore, we sought to compare two common ablation approaches., Methods: We analyzed prospective ablation databases of two high-volume tertiary centers (> 1000 ablations/year) using either 30 or 50 W for slow pathway modulation from 2012 to 2013. We analyzed procedural characteristics as well as short- and long-term outcomes. Mean follow-up was 36 ± 9 months., Results: Six hundred thirty-four patients (50 W center: n = 342, 30 W center: n = 292) were ablated. Slow pathway modulation was successful in 99% in both groups (p = ns). Periprocedural AV block occurred in nine patients (2.6%) in the 50 W and five patients (1.7%) in the 30 W group (p = 0.59), respectively. We documented no permanent higher-degree AV block. The number of RF lesions and seconds of RF delivery was significantly less in the 50 W group (p = 0.04 for number of lesions; p < 0.001 for seconds). AVNRT recurrence was similar (p = 0.23). In males, significantly fewer recurrences accrued in the 50 W group (p = 0.04), while in females less transient AV blocks occurred during the procedure with 30 W (p = 0.07)., Conclusions: The 30 and 50 W target power approaches for slow pathway modulation are highly effective and safe. Significantly, fewer RF duration was necessary to modulate the slow pathway with higher power output (50 W). Our subgroup analysis suggests that males and females might benefit most from different modulation approaches.

BACKGROUND Recent evidence indicates that sympathetic/parasympathetic coactivation (CoA) is causally linked to changes in heart rate (HR) dynamics. Whether this is relevant for patients with atrial fibrillation (AF) is unknown. MATERIAL AND METHODS In patients with paroxysmal AF (n=26) and age-matched controls, (n=10) we investigated basal autonomic outflow and HR dynamics during separate sympathetic (cold hand immersion) and parasympathetic activation (O2-inhalation), as well as during CoA (cold face test). In an additional cohort (n=7), HR response was assessed before and after catheter-based pulmonary vein isolation (PVI). Ultra-high-density endocardial mapping was performed in patients (n=6) before and after CoA. RESULTS Sympathetic activation increased (control: 74±3 vs. 77±3 bpm, p=0.0098; AF: 60±2 vs. 64±2 bpm, p=0.0076) and parasympathetic activation decreased HR (control: 71±3 vs. 69±3 bpm, p=0.0547; AF: 60±1 vs. 58±2 bpm, p<0.0009), while CoA induced a paradoxical HR increase in patients with AF (control: 73±3 vs. 71±3 bpm, p=0.084; AF: 59±2 vs. 61±2 bpm, p=0.0006), which was abolished after PVI. Non-linear parameters of HR variability (SD1) were impaired during coactivation in patients with AF (control: 61±7 vs. 69±6 ms, p=0.042, AF: 44±32 vs. 32±5 ms, p=0.3929). CoA was associated with a shift of the earliest activation site (18±4 mm) of the sinoatrial nodal region, as documented by ultra-high-density mapping (3442±343 points per map). CONCLUSIONS CoA perturbs HR dynamics and shifts the site of earliest endocardial activation in patients with paroxysmal AF. This effect is abolished by PVI, supporting the value of emerging methods targeting the intrinsic cardiac autonomic nervous system to treat AF. CoA might be a valuable tool to assess cardiac autonomic function in a clinical setting.

Aims: To evaluate the incidence of newly diagnosed intracardiac thrombi (ICT) in respect to the mode of OAC in patients undergoing cardioversion (CV)., Methods and Results: We prospectively assessed transesophageal echocardiography (TEE) and OAC therapy prior to CV in AF patients with ≥48-hour duration scheduled for CV. A total of 60 first-time ICT (4.7%) were diagnosed in 1,286 TEE, with highest rate in patients without OAC (9.6% vs. OAC 4.1%, P  =  0.009) and an apparently lower rate in nonvitamin K antagonist anticoagulants (NOAC) therapy compared to vitamin K antagonist (VKA) (2.5% vs. 5.3%, P  =  0.02). VKA therapy control 4 weeks prior to CV was overall average (time in therapeutic range 60%) and patients showed more frequently clinical characteristics and TEE parameters associated with risk for ICT. Even among patients with effective OAC therapy (uninterrupted NOAC and VKA therapy with international normalized ratio (INR) ≥2.0 for 3 weeks), ICT occurred in 2.7%, but with no difference between both groups (P  =  0.22). There was no difference between different types of NOAC. Independent predictors for ICT were history of embolism, hypertension, BMI, absence of OAC, renal function, reduced atrial appendage flow, and presence of spontaneous echo contrast., Conclusion: NOAC therapy seems favorable in the overall prevention of ICT, although this is likely to be caused by suboptimal VKA therapy control and differences in the overall health status between VKA and NOAC patients. ICT occurred even with effective OAC therapy suggesting individual TEE-guided cardioversion in patients at risk., (© 2018 Wiley Periodicals, Inc.)

Aims: During ablation in the vicinity of the coronary arteries establishing a safe distance from the catheter tip to the relevant vessels is mandatory and usually assessed by fluoroscopy alone. The aim of the study was to investigate the feasibility of an image integration module (IIM) for continuous monitoring of the distance of the ablation catheter tip to the main coronary arteries during ablation of ventricular arrhythmias (VA) originating in the sinus of valsalva (SOV) and the left ventricular summit part of which can be reached via the great cardiac vein (GCV)., Methods and Results: Of 129 patients undergoing mapping for outflow tract arrhythmias from June 2014 till October 2015, a total of 39 patients (52.4 ± 18.1 years, 17 female) had a source of origin in the SOV or the left ventricular summit. Radiofrequency (RF) ablation was performed when a distance of at least 5 mm could be demonstrated with IIM. A safe distance in at least one angiographic plane could be demonstrated in all patients with a source of origin in the SOV, whereas this was not possible in 50% of patients with earliest activation in the summit area. However, using the IIM a safe position at an adjacent site within the GCV could be obtained in three of these cases and successful RF ablation performed safely without any complications. Ablation was successful in 100% of patients with an origin in the SOV, whereas VAs originating from the left ventricular summit could be abolished completely in only 60% of cases., Conclusion: Image integration combining electroanatomical mapping and fluoroscopy allows assessment of the safety of a potential ablation site by continuous real-time monitoring of the spatial relations of the catheter tip to the coronary vessels prior to RF application. It aids ablation in anatomically complex regions like the SOV or the ventricular summit providing biplane angiograms merged into the three-dimensional electroanatomical map., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

Introduction: Hypertrophic cardiomyopathy (HCM) is associated with an increased risk of sudden cardiac death (SCD) primarily due to ventricular arrhythmia (VA). In patients (pts.) with a high risk of SCD, the implantation of an intracardiac cardioverter defibrillator (ICD) is thus indicated. Previous studies suggest that a prolonged interval between the peak and the end of the T wave, T-peak to T-end (TpTe), is associated with an elevated risk of VA and SCD in various clinical settings. The aim of our study was to evaluate the association between TpTe and VA in HCM pts. with a previously implanted ICD., Methods: In 40 HCM pts. (51.4 ± 16.4 years; 62.5% men), TpTe was measured using the baseline digital standard resting 12-lead ECG during sinus rhythm. VA was assessed by device follow-up., Results: Within 41.8 ± 35.1 months, 7 (17.5%) pts. had VA leading to appropriate therapy (AT), 7 pts. (17.5%) had non-sustained VA, and 26 pts. (65.0%) had no VA. The maximum TpTe was significantly prolonged in pts. with VA leading to AT compared to pts. without VA (101.3 ± 19.6 vs. 79.9 ± 15.3 ms; p = 0.004). Maximum TpTe was associated with an elevated risk of VA leading to AT (hazard ratio per 10 ms increase 1.63; 95% CI 1.04-2.54; p = 0.031) and pts. with a maximum TpTe ≤ 78 ms were without any VA leading to AT during follow-up. There was no correlation of maximum TpTe to other clinical parameters in our patient cohort., Conclusion: A prolonged TpTe is associated with VA and AT in HCM. Our findings suggest that TpTe can possibly serve as a marker for ventricular arrhythmogenesis in pts. with HCM and assessment of TpTe might, therefore, optimize SCD risk stratification.

Background: Fingolimod can lead to increased risk of cardiac events such as bradycardia or atrioventricular (AV) block., Objective: Evaluate acute and long-term effects of fingolimod on heart rhythm (HR), heart rate variability (HRV) and development of AV-blocks., Methods: In 64 patients with relapsing-remitting multiple sclerosis Holter ECG monitoring (HEM) and HRV analysis were performed 24h before, six h during and 72h after initiation of fingolimod. We additionally analyzed a 24h HEM after a follow up of ≥ three months., Results: Heart rate (HR) decreased significantly (p < 0.001) under fingolimod treatment with nadir at five hours after starting and maintained decreased for 72h. Five (7.8%) patients suffered from new-onset AV-block requiring cessation of treatment. In four of five patients (80%), the AV-block could only be documented in the 72h-HEM with a median time of occurrence at 14h. The mean heart rate was still significant lower after a mean follow up time of 14.1 ± 9.6 months (85.0 ± 9.8 vs. 75.3 ± 16.2 bpm; p = 0.002) in comparison to baseline., Conclusion: The treatment with fingolimod leads to an increase of vagal activation which persists even after 14 months of treatment. These changes did not return to baseline levels on treatment with fingolimod. Based on our data an additional at least 24h hour-HEM after the initiation of fingolimod therapy should be considered., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Introduction: Comparative data of early recurrence rates of atrial fibrillation (ERAF) following second-generation cryoballoon (CB-G2) and radiofrequency current (RFC) ablation for pulmonary vein isolation (PVI) in paroxysmal AF (PAF) are rare. We randomized PAF patients into either PVI with CB-G2 (group 1) or PVI with a combined RFC-approach applying contact force (CF) with the endpoint of unexcitability (group 2) to investigate ERAF., Methods and Results: In group 1 (n = 30), CB-G2-PVI was performed. After CF-PVI in group 2 (n = 30), bipolar pacing on the ablation line and additional ablation until unexcitability was conducted. Follow-up included 48 h of in-hospital monitoring followed by 5-day Holter ECGs 1, 2, 3, 6, 12 months postablation to evaluate ERAF. Acute PVI was reached in 100% of group 2 and in 99% of group 1. Shorter procedure durations (98.0 ± 21.9 vs. 114.3 ± 18.7 min, P < 0.05) but extended fluoroscopy times (15.4 ± 3.9 vs. 10.0 ± 4.3 min, P < 0.05) were found in the CB-G2 group. Ten non-severe complications occurred (6 vs. 4 in group 1 and 2, P = 0.73). In group 2, five patients suffered from ERAF vs. seven patients in group 1 (P = 0.67). The time until the occurrence of ERAF was shorter in group 2 (1 day (q1-q3: 1-4.5)) when compared with group 1 (22 (q1-q3: 6-54) days, P = 0.025)., Conclusion: ERAF rates were equal among groups; however, they occurred earlier in the initial phase after RFC ablation when compared with CB-G2. PVI utilizing cryoablation is associated with shorter procedure durations but extended fluoroscopy time while being similarly secure., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Objectives: This study sought to compare long-term arrhythmia-free survival between electrical circumferential pulmonary vein isolation (PVI) and PVI with the endpoint of unexcitability along the ablation line., Background: PVI is the standard ablation strategy of paroxysmal atrial fibrillation, although arrhythmia recurrence in long-term follow-up (FU) is high. The endpoint of unexcitability along the ablation line results in decreased arrhythmia recurrence compared to electrical PVI in 1-year FU., Methods: Seventy-four consecutive patients (age 62.5 ± 10.6 years; 70.3% male) with de novo paroxysmal atrial fibrillation who were initially included in our randomized trial and underwent catheter ablation at our institution were analyzed. Patients who were randomized to either a conventional group (PVI, guided by circumferential catheter signals) or a pace-guided group (PG, anatomical ablation line encircling, ablation until loss of pace capture at 10 V, 2-ms pulse width on the ablation line) underwent long-term FU. The primary endpoint was recurrence of any atrial fibrillation or atrial tachycardia after a blanking period of 3 months., Results: Sixty-nine patients completed a mean FU period of 5.14 ± 0.98 years. Arrhythmia-free survival without antiarrhythmic drug therapy was significantly higher in the PG group (71.05% vs. 25.81%, p = 0.002). Furthermore, multiple procedure success (1.29 ± 0.61 procedures in PG vs. 1.97 ± 1.06 procedures in conventional group, p < 0.001) was higher in the PG group compared to the conventional group (89.47% vs. 58.06%, p = 0.005)., Conclusions: The endpoint of unexcitability along the PVI line improves success rates, resulting in a significant reduction of exposure to invasive procedures in 5-year FU., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: The need for transesophageal echocardiography (TEE) before catheter ablation of atrial fibrillation (CA-AF) is still being questioned. The aim of this study is to analyze patients' (patients) risk factors of left atrial appendage thrombus (LAAT) prior to CA-AF in daily clinical practice, according to oral anticoagulation (OAC) strategies recommended by current guidelines., Methods and Results: All patients scheduled for CA-AF from 01/2015 to 12/2016 in our center were included and either treated with NOACs (novel-OAC; paused 24-hours preablation) or continuous vitamin K antagonists (INR 2.0-3.0). All patients received a preprocedural TEE at the day of ablation. Two groups were defined: (1) patients without LAAT, (2) patients with LAAT. The incidence of LAAT was 0.78% (13 of 1,658 patients). No LAAT was detected in patients with a CHA 2 DS 2 -VASc score of ≤1 (n = 640 patients) irrespective of the underlying AF type. Independent predictors for LAAT are: higher CHA 2 DS 2 -VASc scores (odds ratio [OR] 1.54, 95%-confidence interval [CI]: 1.07-2.23, P = 0.0019), a history of nonparoxysmal AF (OR 7.96, 95%-CI: 1.52-146.64, P = 0.049), hypertrophic cardiomyopathy (HCM; OR 9.63, 95% CI: 1.36-43.05, P = 0.007), and a left ventricular ejection fraction (LVEF) < 30% (OR 8.32, 95% CI: 1.18-36.29, P = 0.011). The type of OAC was not predictive (P = 0.70)., Conclusions: The incidence of LAAT in patients scheduled for CA-AF is low. Therefore, periprocedural OAC strategies recommended by current guidelines seem feasible. Preprocedural TEE may be dispensed in patients with a CHA 2 DS 2 -VASc score ≤1. However, a CHA 2 DS 2 -VASc score ≥2, reduced LVEF, HCM, or history of nonparoxysmal AF are independently associated with an increased risk for LAAT., (© 2017 Wiley Periodicals, Inc.)

Introduction: Despite a rising demand for catheter ablation (CA) of atrial fibrillation (AF) in an elderly population, complication and success rates are not fully elucidated. We sought to compare complication rates of CA of AF in patients ≥75 versus <75 years of age., Methods and Results: Patients with symptomatic, drug-refractory AF were prospectively enrolled from January 2007 to 2010 in this multicenter study. A total of 4,449 patients, group 1 ≥75 years and group 2 <75 years (n = 227, age 77.3 ± 2.2 vs. 59.7 ± 9.8 years, 52.0% vs. n = 4,222, 68.9% male, CHA 2 DS 2 -VASc-Score 3.7 ± 1.0 vs. 1.7 ± 1.2; P < 0.001, respectively), with paroxysmal AF (59.9% in group 1 vs. 63.3% in group 2, P = 0.30), and persistent AF (34.8% in group 1 vs. 29.4% in group 2, P = 0.082) underwent CA of AF. A centralized follow-up was obtained in 4,347 patients by the Institute for Myocardial Infarction Research (IHF, Ludwigshafen). There was a significant difference between periprocedural stroke rates in the elderly versus the younger cohort (1.3% vs. 0.1%, P < 0.01). In-hospital severe nonfatal complications did not differ significantly between the groups (4.4% vs. 2.7%, P = 0.14). Other procedure-related, in-hospital complications were not significantly different. After a mean follow-up of 472 ± 99 days (group 1) and 477 ± 94 days (group 2), no differences were found in complication rates., Conclusion: CA of AF in patients ≥75 years is associated with higher in-hospital stroke rates. In a 1-year follow-up, complication rates do not differ between the groups., (© 2016 Wiley Periodicals, Inc.)

Background: The implantable cardioverter-defibrillator (ICD) is the standard therapy to prevent sudden cardiac death in patients with coronary artery disease and unstable ventricular tachyarrhythmias. The prospective multinational SMS (Substrate Modification Study) was designed to assess whether prophylactic ablation of the arrhythmogenic substrate reduces or prevents the recurrence of ventricular tachycardia/ventricular fibrillation in such patients., Methods and Results: Of 111 patients included in an intention-to-treat analysis, 54 were randomly assigned catheter ablation plus ICD implantation (ablation group: 68±8 years; 47 men), whereas 57 were assigned ICD implantation without catheter ablation (ICD-only group: 66±8 years; 46 men). Primary study end point was the time to first recurrence of ventricular tachycardia/ventricular fibrillation. ICD episodes were assessed and verified by an independent board. Patients were followed up for 2.3±1.1 years. The primary end point was reached by 25 ablation patients and 26 ICD-only patients. Two-year event-free survival was estimated at 49.0% (95% confidence interval, 33.3%-62.9%) in the former and 52.4% (36.7%-65.9%) in the latter groups. Comparison of episode incidence revealed no significant difference in the primary end point ( P =0.84). In an Andersen-Gill regression model with multiple end point recurrences, the difference between the study arms significantly favored catheter ablation for both the primary end point and all but one of the predefined subgroups of detected arrhythmia events., Conclusions: SMS failed to meet the primary end point of time to first ventricular tachycardia/ventricular fibrillation recurrence. However, catheter ablation did reduce the total number of ICD interventions during the duration of follow-up., Clinical Trial Registration: https://clinicaltrials.gov. Unique identifier: NCT00170287., (© 2017 American Heart Association, Inc.)

Background: Extensive and repeated substrate modification (SM) is frequently performed as an ablation strategy in persistent atrial fibrillation (persAF). The effect of these extended ablation strategies on atrial function has not been investigated sufficiently so far. The purpose was to assess atrial function by cardiac magnetic resonance (CMR) and its association with left atrial (LA) scar burden by electroanatomical voltage-mapping after multiple persAF ablation procedures., Methods: We included 16 persAF patients who had ≥2 SM procedures and a control group (CG) of 21 persAF patients without prior ablation. CMR was performed in sinus rhythm at least 4 weeks after the last cardioversion. Active left and right (RA) atrial emptying fractions (AEF) as well as peak active left atrial appendage (LAA) emptying velocities were obtained by CMR flow measurements. Furthermore, LA scar burden was quantified on electroanatomical voltage maps by the portion of points with local voltage amplitude <0.2 mV., Results: We found median LA-AEF to be lower (13 [9-22] vs 32 [26-36] %, P < 0.001) and median LA scar burden to be higher (40 [20-68] vs nine [3-18] %, P < 0.05) in the SM group compared with the CG. Furthermore, a significant correlation was found between mean LA voltage and LA-AEF (r 2 = 0.62, P < 0.001). No significant differences were detected with respect to median RA-AEF (41 [28-48] vs 47 [35-50] %, P = 0.43) and median peak LAA emptying velocities (30 [16-40] vs 17 [13-28] cm/s, P = 0.07)., Conclusions: Active LA function is preserved but significantly impaired and associated with ablation-related LA scar burden after multiple extensive persAF ablations., (©2016 Wiley Periodicals, Inc.)

Marfan syndrome (MFS) is a rare, severe, chronic, life-threatening disease with multiorgan involvement that requires optimal multidisciplinary care to normalize both prognosis and quality of life. In this article, each key team member of all the medical disciplines of a multidisciplinary health care team at the Hamburg Marfan center gives a personal account of his or her contribution in the management of patients with MFS. The authors show how, with the support of health care managers, key team members organize themselves in an organizational structure to create a common meaning, to maximize therapeutic success for patients with MFS. First, we show how the initiative and collaboration of patient representatives, scientists, and physicians resulted in the foundation of Marfan centers, initially in the US and later in Germany, and how and why such centers evolved over time. Then, we elucidate the three main structural elements; a team of coordinators, core disciplines, and auxiliary disciplines of health care. Moreover, we explain how a multidisciplinary health care team integrates into many other health care structures of a university medical center, including external quality assurance; quality management system; clinical risk management; center for rare diseases; aorta center; health care teams for pregnancy, for neonates, and for rehabilitation; and in structures for patient centeredness. We provide accounts of medical goals and standards for each core discipline, including pediatricians, pediatric cardiologists, cardiologists, human geneticists, heart surgeons, vascular surgeons, vascular interventionists, orthopedic surgeons, ophthalmologists, and nurses; and of auxiliary disciplines including forensic pathologists, radiologists, rhythmologists, pulmonologists, sleep specialists, orthodontists, dentists, neurologists, obstetric surgeons, psychiatrist/psychologist, and rehabilitation specialists. We conclude that a multidisciplinary health care team is a means to maximize therapeutic success., Competing Interests: The authors report no conflicts of interest in this work.

Background: Electrogram-based identification of the regions maintaining persistent Atrial Fibrillation (AF) is a subject of ongoing debate. Here, we explore the concept of local electrical dyssynchrony to identify AF drivers., Methods and Results: Local electrical dyssynchrony was calculated using mean phase coherence. High-density epicardial mapping along with mathematical model were used to explore the link between local dyssynchrony and properties of wave conduction. High-density mapping showed a positive correlation between the dyssynchrony and number of fibrillatory waves (R2 = 0.68, p<0.001). In the mathematical model, virtual ablation at high dyssynchrony regions resulted in conduction regularization. The clinical study consisted of eighteen patients undergoing catheter ablation of persistent AF. High-density maps of left atrial (LA) were constructed using a circular mapping catheter. After pulmonary vein isolation, regions with the top 10% of the highest dyssynchrony in LA were targeted during ablation and followed with ablation of complex atrial electrograms. Catheter ablation resulted in termination during ablation at high dyssynchrony regions in 7 (41%) patients. In another 4 (24%) patients, transient organization was observed. In 6 (35%) there was no clear effect. Long-term follow-up showed 65% AF freedom at 1 year and 22% at 2 years., Conclusions: Local electrical dyssynchrony provides a reasonable estimator of regional AF complexity defined as the number of fibrillatory waves. Additionally, it points to regions of dynamical instability related with action potential alternans. However, despite those characteristics, its utility in guiding catheter ablation of AF is limited suggesting other factors are responsible for AF persistence., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Conventional mapping of complex atrial tachycardias (ATs) can be challenging. Thus, we evaluated feasibility and utility of a novel, ultra high-density 3D mapping approach to characterize and map AT in these cases., Methods and Results: Overall, 21 patients (67.4 ± 7.6 years; male: 52.4%, 1.9 ± 1.4 previous ablation procedures) with documented AT referred to our center underwent catheter ablation including ultra high-density mapping using a novel 64-electrode mini-basket catheter and an adjunctive 3D mapping system. A total of 24 AT (20 left atrial, 4 right atrial AT) were analyzed in 19 cases. In 2 patients, map acquisition failed due to scarce local electrograms and unstable AT cycle length, respectively. Underlying mechanisms were focal (n = 3), as well as local (n = 8) and macro (n = 13) reentry tachycardias with a mean cycle length of 311.8 ± 67.7 milliseconds. The analysis of propagation waves, activation and voltage revealed complex activation patterns and allowed for the identification of critical sites of AT initiation or maintenance without the need for further mapping techniques. In all cases critical sites could be verified by successful consecutive ablation. Mean mapping time was 19.4 ± 7.6 minutes, mean number of mapping points was 19,217 ± 10,270. Radiofrequency application until first effect was 165.1 ± 374.2 seconds; total procedure time was 157.6 ± 51.4 minutes, fluoroscopy time 21.7 ± 13.8 minutes, and total radiofrequency duration 1,016 ± 951.9 seconds, respectively. No severe complications occurred., Conclusion: Ultra high-density mapping of complex AT is safe and feasible. Further, it enables detailed insight into AT mechanisms. Critical AT sites can be identified precisely in order to guide successful catheter ablation., (© 2016 Wiley Periodicals, Inc.)

Introduction: Ventricular arrhythmias (VAs) in patients with chronic heart failure (CHF) are sometimes refractory to antiarrhythmic drugs and cardiac ablation. This study aimed to investigate catheter-based renal sympathetic denervation (RDN) as antiarrhythmic strategy in refractory VA., Methods: These are the first data from a pooled analysis of 13 cases from five large international centers (age 59.2 ± 14.4 years, all male) with CHF (ejection fraction 25.8 ± 10.1 %, NYHA class 2.6 ± 1) presented with refractory VA who underwent RDN. Ventricular arrhythmias, ICD therapies, clinical status, and blood pressure (BP) were evaluated before and 1-12 months after RDN., Results: Within 4 weeks prior RDN, a median of 21 (interquartile range 10-30) ventricular tachycardia (VT) or fibrillation (VF) episodes occurred despite antiarrhythmic drugs and prior cardiac ablation. RDN was performed bilaterally with a total number of 12.5 ± 3.5 ablations and without peri-procedural complications. One and 3 months after RDN, VT/VF episodes were reduced to 2 (0-7) (p = 0.004) and 0 (p = 0.006), respectively. Four (31 %) and 11 (85 %) patients of these 13 patients were free from VA at 1 and 3 months. Although BP was low at baseline (116 ± 18/73 ± 13 mmHg), no significant changes of BP or NYHA class were observed after RDN. During follow-up, three patients died from non-rhythm-related causes., Conclusions: In patients with CHF and refractory VA, RDN appears to be safe concerning peri-procedural complications and blood pressure changes, and is associated with a reduced arrhythmic burden.

Catheter ablation of complex fractionated atrial electrograms (CFAE), also known as defragmentation ablation, may be considered for the treatment of persistent atrial fibrillation (AF) beyond pulmonary vein isolation (PVI). Concomitant antiarrhythmic drug (AAD) therapy is common, but the relevance of AAD administration and its optimal timing during ablation remain unclear. Therefore, we investigated the use and timing of AADs during defragmentation ablation and their possible implications for AF termination and ablation success in a large cohort of patients. Retrospectively, we included 200 consecutive patients (age: 61 ± 12 years, LA diameter: 47 ± 8 mm) with persistent AF (episode duration 47 ± 72 weeks) who underwent de novo ablation including CFAE ablation. In all patients, PVI was performed prior to CFAE ablation. The use and timing of AADs were registered. The follow-ups consisted of Holter ECGs and clinical visits. Termination of AF was achieved in 132 patients (66 %). Intraprocedural AADs were administered in 168/200 patients (84 %) 45 ± 27 min after completion of PVI. Amiodarone was used in the majority of the patients (160/168). The timing of AAD administration was predicted by the atrial fibrillation cycle length (AFCL). At follow-up, 88 patients (46 %) were free from atrial arrhythmia. Multivariate logistic regression analysis revealed that administration of AAD early after PVI, LA size, duration of AF history, sex and AFCL were predictors of AF termination. The administration of AAD and its timing were not predictive of outcome, and age was the sole independent predictor of AF recurrence. The administration of AAD during ablation was common in this large cohort of persistent AF patients. The choice to administer AAD therapy and the timing of the administration during ablation were influenced by AFCL, and these factors did not significantly influence the moderate single procedure success rate in this retrospective analysis.

Introduction: Diagnosis of infrequent cardiac arrhythmias (CA) is often unsuccessful using resting or Holter ECG. As early detection and treatment of CA, especially atrial fibrillation (AF), has implications on patients' treatment and outcome, we investigated, whether self-guided, trans-telephonic event-recorder monitoring (Tele-ECG) improves diagnosis and influences treatment options., Methods: Between 2009 and 2014, 790 patients (54 ± 18 years, 40% male; no history of CA: 582, known AF: 179, other CA: 29) presented with recurrent symptoms suggestive of CA and were screened by Tele-ECG (17.3 ± 26.9 days). A total of 11,775 ECGs were transmitted via a 24-hour telephone hotline including documentation of the respective symptoms., Results: In 73% of patients, CA was documented at the time of symptoms: sinus tachycardia 23%, premature ventricular beats 19%, AF 14%, supraventricular tachycardia 9%, sinus bradycardia 5%, sinus arrhythmia 2%, and AV block II 1%. The mean time until the first symptomatic episode occurred was 6.9 ± 15.3 days (median 2.5 days). The first documented arrhythmia occurred on average after 7.7 ± 14.1 days (median 3 days). In patients with AF (n = 110), 44% was newly diagnosed. According to the Tele-ECG diagnosis, AF ablation was performed in 27% of these patients, 7% electrical cardioversion, and in 30% antiarrhythmic therapy was initiated. In 65% of the patients with recurrence of known AF, (re-)ablation was performed or recommended and in 16% antiarrhythmic therapy was modified., Conclusions: Tele-ECG monitoring is effective in the diagnosis of suspected symptomatic CA. A diagnosis can usually be achieved within 1 week and has implications on patients' care., (© 2016 Wiley Periodicals, Inc.)

Aims: Propofol sedation has been shown to be safe for atrial fibrillation ablation and internal cardioverter-defibrillator implantation but its use for catheter ablation (CA) of ventricular tachycardia (VT) has yet to be evaluated. Here, we tested the hypothesis that VT ablation can be performed using propofol sedation administered by trained nurses under a cardiologist's supervision., Methods and Results: Data of 205 procedures (157 patients, 1.3 procedures/patient) undergoing CA for sustained VT under propofol sedation were analysed. The primary endpoint was change of sedation and/or discontinuation of propofol sedation due to side effects and/or haemodynamic instability. Propofol cessation was necessary in 24 of 205 procedures. These procedures (Group A; n = 24, 11.7%) were compared with those with continued propofol sedation (Group B; n = 181, 88.3%). Propofol sedation was discontinued due to hypotension (n = 22; 10.7%), insufficient oxygenation (n = 1, 0.5%), or hypersalivation (n = 1, 0.5%). Procedures in Group A were significantly longer (210 [180-260] vs. 180 [125-220] min, P = 0.005), had a lower per hour propofol rate (3.0 ± 1.2 vs. 3.8 ± 1.2 mg/kg of body weight/h, P = 0.004), and higher cumulative dose of fentanyl administered (0.15 [0.13-0.25] vs. 0.1 [0.05-0.13] mg, P < 0.001), compared with patients in Group B. Five (2.4%) adverse events occurred., Conclusion: Sedation using propofol can be safely performed for VT ablation under the supervision of cardiologists. Close haemodynamic monitoring is required, especially in elderly patients and during lengthy procedures, which carrying a higher risk for systolic blood pressure decline., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Background: Early recurrences (ERs) of atrial tachyarrhythmia are common after catheter ablation of atrial fibrillation. A 3-month blanking period is recommended by current guidelines. This study sought to investigate the significance of ER during the first 3 months post ablation in predicting late recurrences and determine whether it varies according to timing., Methods and Results: A total of 401 patients with paroxysmal atrial fibrillation undergoing pulmonary vein isolation were followed for 12 months with transtelephonic monitoring in the ADVICE (Adenosine Following Pulmonary Vein Isolation to Target Dormant Conduction Elimination) trial. Patients with atrial tachyarrhythmia ≥30 s within the 3-month blanking period were stratified according to the timing of ER. A total of 179 patients (44.6%) experienced their last episode of ER during the first (n=53), second (n=44), or third (n=82) month of the 3-month blanking period. One-year freedom from symptomatic atrial tachyarrhythmia was 77.2% in patients without ER compared with 62.6%, 36.4%, and 7.8% in patients with ER 1, 2, and 3 months post ablation, respectively (P<0.0001). Receiver operating curve analyses revealed a strong correlation between the timing of ER and late recurrence (area under the curve 0.82, P<0.0001). Corresponding hazard ratios for ER during the first, second, and third months were 1.84, 4.45, and 9.64, respectively., Conclusions: This study validates the use of a blanking period after catheter ablation for paroxysmal atrial fibrillation but calls into question the 90-day cut-off value. In particular, >90% of patients with ER during the third month post ablation experience late recurrence by 1 year. However, pending further study, repeat ablation before 90 days cannot be routinely advocated., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01058980., (© 2016 American Heart Association, Inc.)

Different follow-up methods have been used to report success rates after AF ablation. Recent studies have shown that intermittent rhythm monitoring underestimates the actual AF recurrence rate. We therefore report our experience with continuous rhythm monitoring by implantable loop recorder (ILR) in a large patient cohort. Between 09/2008 and 12/2012, 343 cardiac surgical patients underwent concomitant surgical AF ablation. ILR implantation was performed in 206 patients. ILR interrogation was accomplished at 3, 6 and 12 months postoperatively. Successful ablation was defined as AF Burden <0.5 %. Primary outcome of the study was freedom from AF at 12-month follow-up. Mean patient's age was 70.5 ± 7.4 years. No major ablation- or ILR-related complications occurred. In 4 patients (1.9 %) ILR had to be explanted due to ILR-related wound infection (n = 2) or chronic pain (n = 2). Survival rate at 1-year follow-up was 96.6 %. Freedom from AF rate after 1-year follow-up was 68.5 and 63.6 % off antiarrhythmic drugs, respectively. Statistically significant predictors for successful ablation at 1-year follow-up were smaller LA diameter, shorter duration of AF and preoperative paroxysmal AF. Demographic data, indication for surgery, lesion set and used energy source had no impact on freedom from AF after 1 year. Continuous ILR monitoring after concomitant surgical AF ablation was safe and feasible, with registered freedom from AF rate of 68.5 % at 1-year follow-up. Thus continuous rhythm monitoring provides reliable outcome data and helps to guide antiarrhythmic therapy.

Aims: Pulmonary vein isolation (PVI) is an effective treatment option for paroxysmal atrial fibrillation (PAF). Reconnection of pulmonary veins (PVs) is the predominant cause for recurrence of PAF. However, treatment of patients with recurrence of PAF despite isolated PV in the absence of extra-PV foci remains challenging., Methods and Results: Of 265 patients undergoing repeat catheter ablation (CA) for recurrence of PAF 21 (8%) patients (14 men, age 58 ± 14 years) showed no reconnection of PV. Therefore, inducibility of sustained atrial arrhythmias was tested. If sustained atrial fibrillation (AF) or sustained atrial tachycardia (AT) was induced, patients underwent CA. During follow-up (FU), Holter- and Tele-electrocardiogram were performed. In 19 (91%) of 21 patients, sustained atrial arrhythmias [16 (84%) AF; 3 (15%) patients AT] were induced. One patient showed PAF. Eighteen patients underwent CA aiming for termination of induced arrhythmia. In 14 (77%) patients, termination into sinus rhythm was achieved. Despite extensive CA, three (16%) patients were externally cardioverted. No periprocedural complications occurred. During 21.2 ± 6.8-month FU, 10 (53%) patients were free of any arrhythmia. Paroxysmal atrial fibrillation recurred in 4 (21%) and AT in 5 (26%) patients. One patient showed persistent AF. Repeat CA was scheduled and successfully performed for these patients., Conclusion: In patients with recurrence of PAF despite isolated PV, termination of induced atrial arrhythmias can be achieved in most patients by defragmentation and AT ablation. Moreover, this ablation strategy results in favourable mid-term outcome results., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Background: Regional cardiac sympathetic denervation causes electrophysiological heterogeneity and has been found to be a predictor of potentially lethal VT., Case Report: We present the case of 69-year-old patient admitted with recurrent ventricular tachycardia and a history of anterior myocardial infarction. In line with Tc-99m-MIBI-SPECT perfusion imaging, electroanatomical mapping revealed extensive LV anterior scarring as detected by low-voltage areas. Surprisingly, I-123-MIBG-SPECT showed an extensive deficit of sympathetic innervation inferior (mismatch) and anterolateral (match)., Conclusions: Combination of electroanatomical mapping with tomographic imaging of innervation and perfusion might improve our understanding of the neural trigger of VT after myocardial infarction or substrate-based catheter ablation.

Electrical cardiac pacing today is the standard therapy for symptomatic bradycardia. Importantly, despite technical advantages, complications associated with conventional transvenous pacing leads and pockets are still challenging in a relevant number of patients. Beyond cosmetic benefits, miniaturized leadless pacemaker may partly overcome these limitations and beneficially influence implantation-related physical restrictions. Initial findings with single-chamber pacemakers for right ventricular pacing, which are completely implanted via a femoral venous vascular access, are promizing. In summary, leadless pacing offers novel perspectives regarding cardiac implantable electronic devices although acute safety and the long-term performance of these systems needs to be determined in more detail., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: The success rate of catheter ablation for persistent atrial fibrillation (AF) is still far from satisfactory. Identification of patients who will benefit from ablation is highly desirable. We investigated the predictive value of noninvasive AF complexity parameters derived from standard 12-lead ECGs for AF termination and long-term success of catheter ablation and compared them with clinical predictors., Methods and Results: The study included a training (93 patients) and a validation set (81 patients) of patients with persistent AF undergoing stepwise radiofrequency ablation. In the training set AF terminated in 81% during catheter ablation, 77% were in sinus rhythm after 6 years and multiple ablations. ECG-derived complexity parameters were determined from a baseline 10-s 12-lead ECG. Prediction of AF termination was similar using only ECG (cross-validated mean area under the curve [AUC], 0.76±0.15) or only clinical parameters (mean AUC, 0.75±0.16). The combination improved prediction to a mean AUC of 0.79±0.13. Using a combined model of ECG and clinical parameters, sinus rhythm at long-term follow-up could be predicted with a mean AUC of 0.71±0.12. In the validation set AF terminated in 57%, 61% were in sinus rhythm after 4.6 years. The combined models predicted termination with an AUC of 0.70 and sinus rhythm at long-term follow-up with an AUC of 0.61. Overall, fibrillation-wave amplitude provided the best rhythm prediction., Conclusions: The predictive performance of ECG-derived AF complexity parameters for AF termination and long-term success of catheter ablation in patients with persistent AF is at least as good as known clinical predictive parameters, with fibrillation-wave amplitude as the best predictor., (© 2016 American Heart Association, Inc.)

Background: Pathways of oxidative stress, nitric oxide bioavailability and L-arginine derivatives are hypothesized to be related to atrial fibrillation (AF). Circulating methylated L-arginine metabolites can be assessed in the general population and may show an association with AF., Methods: We determined L-arginine and its metabolites asymmetric dimethylarginine (ADMA), L-N(ω)-monomethylarginine (NMMA) and symmetric dimethylarginine (SDMA) in the population-based Gutenberg Health Study (n=5000), mean age 55 ± 11 years, 51% men, in association with clinical variables of AF such as electrocardiographic and echocardiographic measures and manifest AF., Results: Individuals with AF (N=161), 71% men, were older, mean age 64.9 ± 8.3 years. In Bonferroni-corrected multivariable-adjusted regression analyses we observed moderate inverse associations for L-arginine, SDMA, and L-arginine/ADMA ratio with ventricular heart rate, and for L-arginine and L-arginine/ADMA ratio with QTc interval. L-arginine was correlated with QRS duration. In echocardiographic analyses, SDMA was related to left atrial diameter and deceleration time, ADMA and NMMA were correlated with left ventricular mass. ADMA (odds ratio [OR] 1.21, 95% confidence interval [CI] 1.11-1-32; p=0.013) and NMMA (OR 1.17, 95% CI 1.09-1.26, p=0.014) were related to prevalent AF. L-arginine/ADMA ratio was inversely associated (OR 0.8, 95% CI 0.71-0.90, p=0.0082). Results were similar after adjustment for creatinine., Conclusions: In our large, population-based cohort, we observed moderate associations of l-arginine metabolites and intermediate electrocardiographic and echocardiographic variables and AF. Our findings support further investigations to define the role of L-arginine derivatives in AF and their clinical utility., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Ablation of atrial fibrillation (AF) is an established treatment option for symptomatic patients. It is not known whether complete pulmonary vein isolation (PVI) is superior to incomplete PVI with regard to the patients' clinical outcome., Methods and Results: Patients with drug-refractory, symptomatic paroxysmal AF were randomly assigned to either incomplete (group A) or complete PVI (group B). In group A, a persistent gap was intentionally left within the circumferential ablation line, whereas in group B, complete PVI without any gaps was intended. At 3 months, all patients underwent invasive reevaluation to assess the rate of persistent PVI. Clinical follow-up was based on daily 30-s transtelephonic ECG transmissions. Primary study end point was the time to first recurrence of (symptomatic or asymptomatic) AF. A total of 233 patients were enrolled (116 in group A and 117 in group B). AF recurrence within 3 months was observed in a total of 161 patients (136 [84.5%] with symptomatic and 25 [15.5%] with asymptomatic AF); AF recurred in 62.2% of group B patients and 79.2% of group A patients (P<0.001), for a difference in favor of complete PVI of 17.1% (95% confidence interval, 5.3%-28.9%). Invasive restudy in 103 group A patients and 93 group B patients revealed conduction gaps in 92 (89.3%) and 65 (69.9%) patients, respectively., Conclusions: This study proves the superiority of complete PVI over incomplete PVI with respect to AF recurrence within 3 months. However, the rate of electric reconduction 3 months after PVI is high in patients with initially isolated PVs., Clinical Trial Registration: URL: http://clinicaltrials.gov; Unique identifier: NCT00293943., (© 2016 American Heart Association, Inc.)

Vascular reflex mechanisms contribute to vasovagal syncope. However, the alterations in central haemodynamics in patients with vasovagal syncope are unknown. 30 consecutive patients (36.5 ± 15 years, 14 females) with recurrent vasovagal syncope (VVS) and a positive tilt table test were compared to 39 age- and sex-matched controls (36.9 ± 16 years, 15 females) with a negative tilt table result and no history of syncope. Central aortic pressure parameters including augmentation index and central pulse pressure as markers of aortic stiffness were generated non-invasively by applanation tonometry of the radial artery and use of a validated mathematical transfer function. No difference in aortic augmentation index was observed between groups. (VVS 9 ± 2.6 vs. Control 11 ± 2.4, p = 0.8). However, in patients with vasovagal syncope the aortic pressure waveform significantly differed from healthy controls. A prolonged time to the peak of aortic pressure wave (aortic T2) was observed in patients with vasovagal syncope (226 ± 24 vs. 208 ± 21 ms, p = 0.001). Furthermore time to the first shoulder of the aortic pressure wave (aortic T1) was slightly shorter compared to healthy controls, but did not reach statistical significance (106 ± 22 vs. 110 ± 12 ms, p = 0.33). Patients with vasovagal syncope have an altered aortic pressure waveform at rest, but no signs of elevated aortic stiffness. The underlying mechanisms for these findings may potentially result from a complex imbalance of the autonomic nervous system with a continuous deregulation of the sympathetic and parasympathetic reflex arcs.

Background: Long-term success rates using ablation for persistent atrial fibrillation (AF) are disappointing and usually do not exceed 60%., Objectives: This study sought to compare arrhythmia-free survival between pulmonary vein isolation (PVI) and a stepwise approach (full defrag) consisting of PVI, ablation of complex fractionated electrograms, and additional linear ablation lines in the setting of atrial tachycardias (AT) in patients with persistent AF after PVI., Methods: From November 2010 to February 2013, 205 patients (151 men; 61.7 ± 10.2 years of age) underwent de novo ablation for persistent AF. Subsequently, patients were prospectively randomized to either PVI alone (n = 78) or full defrag (n = 75), with 52 patients not randomized due to AF termination with the original PVI. The primary endpoint was recurrence of any AT after a blanking period of 3 months., Results: During the entire study, 241 ablations were performed (mean: 1.59 in the PVI-alone group, 1.55 in the full-defrag group). With the stepwise approach, termination of AF occurred in 45 (60%) patients. However, arrhythmia-free survival did not differ whether patients underwent single or multiple procedures (p = 0.468). Procedure duration, fluoroscopy time, and radiofrequency duration were significantly longer in the full-defrag group (all p < 0.001)., Conclusions: A stepwise approach aimed at AF termination does not seem to provide additional benefit over PVI alone in patients with persistent AF, but it is associated with significantly longer procedural and fluoroscopic duration as well as radiofrequency application time. (The Randomized Catheter Ablation of Persist End Atrial Fibrillation Study [CHASE-AF]; NCT01580124)., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: Marfan syndrome (MFS) is associated with a substantial risk for ventricular arrhythmia and sudden cardiac death (SCD). We used heart rate turbulence (HRT) and deceleration capacity (DC), to evaluate the risk stratification for these patients., Methods: We enrolled 102 patients [45 male (44.1 %), age 40.5 ± 14.6 years] with MFS. Blood samples were obtained to determine N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Transthoracic echocardiography studies were conducted to evaluate heart function parameters and a 24-h holter ECG was performed. An analysis of two HRT parameters, turbulence onset (TO) and turbulence slope (TS), and DC was performed. Therefore, optimal cut-off values were calculated. Primary endpoint was the combination of SCD, ventricular arrhythmia and arrhythmogenic syncope. Secondary endpoint was total mortality., Results: During a follow-up of 1145 ± 491 days, 12 (11.7 %) patients reached the primary and 8 (7.8 %) patients the secondary endpoint. Patients reaching the primary were significantly older, had a higher burden of premature ventricular complexes and NT-proBNP levels and lower values of LVEF, DC and HRT TS. Multivariate analysis identified NT-proBNP (HR 1.25, 95 % CI 1.01-1.56, p = .04) and the abnormal HRT (abnormal TS and/or TO (HR 7.04, 95 % CI 1.07-46.27, p = .04) as independent risk predictor of arrhythmogenic events., Conclusion: Patients with Marfan syndrome are at risk for severe ventricular arrhythmias and SCD. Abnormal HRT parameters and NT-proBNP values are independent risk factors for arrhythmogenic events and SCD. The assessment of these tools may help predicting SCD patients with MFS.

Introduction: Permanent pulmonary vein isolation (PVI) remains an essential goal of ablation therapy in patients with atrial fibrillation. Aim of this study was the intraindividual comparison of unexcitability to pacing along the ablation line versus dormant conduction (DC) as additional procedural endpoints., Methods: A total of 58 patients with paroxysmal atrial fibrillation (PAF) underwent PVI by circumferential ablation of ipsilateral pulmonary veins (PVs), followed by testing for DC by adenosine administration. Irrespective of the presence of DC, pacing along the ablation line for left atrium capture was performed and additional radio frequency energy applied if necessary. PVs with initial DC were retested after achieving unexcitability., Results: PVI was achieved in 224 of 224 PVs. In 33 of 224 PVs (15%) DC was revealed. At 92 of 112 ablation lines (82%) sites of excitability were found. Three (9%) of the initial 33 PVs with DC showed further DC after achieving unexcitability at repeated testing. Thirty-two of 33 assumed areas of unmasked PV-LA reconduction as revealed by DC-testing showed a corresponding site of excitability on the ablation line. After a follow-up of 11.6 ± 3.4 months 79% of patients were free of arrhythmia., Conclusions: Pacing for unexcitability can safely identify potential sites of DC and even sites that would have not been detected by testing for DC. Unexcitability, therefore, serves as a suitable and safe procedural endpoint not only for patients with contraindications to adenosine administration. Our data suggest that adenosine may be expendable when achieving unexcitability along the ablation line., (© 2015 Wiley Periodicals, Inc.)

Introduction: Recently, a new image integration module (IIM, CartoUnivu™ Module) has been introduced to combine and merge fluoroscopy images with 3-dimensional-(3D)-electroanatomical maps (Carto® 3 System) into an accurate 3D view. The aim of the study was to investigate the influence of IIM on the fluoroscopy exposure during pulmonary vein isolation (PVI) for paroxysmal atrial fibrillation (PAF) in a prospective randomized trial., Methods and Results: Between June and November 2014, a total of 60 patients with PAF (73.3% male, 64.0 ± 9.2 years), who underwent PVI with the endpoint of unexcitability of the ablation line, were randomized to either a conventional 3D mapping system (Carto® 3 System) or to an additional IIM on the basis of an assumed reduction of fluoroscopy exposure by the use of IIM. There were no significant differences in baseline characteristics. The median ablation procedure time was identical in both groups (140.7 ± 27.8 minutes vs. 140.8 ± 39.5 minutes; P = 0.851). A significant decrease of mean fluoroscopy time from 11.9 ± 2.1 to 7.4 ± 2.6 minutes (P < 0.0006) and median fluoroscopy dose from 882.9 to 476.5 cGycm(2) (P < 0.001) was achieved. The main reduction of radiation could be realized during creation of the 3D-map. No major complications occurred during the procedures. After a median follow-up of 125.7 ± 45.6 days 80% of the patients were free from any atrial arrhythmias., Conclusion: CartoUnivu™ module easily integrates into the workflow of PVI with the endpoint of unexcitability of the ablation line without prolonging the procedure time. It is associated with a marked reduction in fluoroscopic dose when compared to a conventional 3D mapping system., (© 2015 Wiley Periodicals, Inc.)

Aims: Atrial fibrillation (AF) is the most common cause of ischemic stroke. Recent data suggest that AF patients after successful ablation have the same risk for thromboembolic events (TE) as patients without AF. Despite current guideline recommendations it is still under debate if oral anticoagulation (OAC) can be safely discontinued after ablation. We analyzed follow-up (FU) after ablation of paroxysmal AF (PAF) in a high- (previous stroke; group 1) and a low-risk group (no previous stroke; group 2) based on data from the German Ablation Registry to reveal real-life prescription behavior., Methods: Overall 29 centers in Germany participated by performing AF-ablation. Between April 2008 and April 2011, 83 patients in group 1 and 377 patients in group 2 with a first ablation of PAF were included in the registry., Results: Mean CHA2DS2-VASc-Score was 4.2 ± 1.4 (group 1) vs. 1.6 ± 1.2 (group 2) (p < 0.0001). No peri-interventional TE was observed. Arrhythmia recurrence was seen in 47.4 vs. 48.4% (p = 0.79) during a median FU of 489 (453-782) days, resulting in a repeat procedure in 20.0 vs. 20.7% (p = 0.88), respectively. OAC was discontinued in 38.6% in group 1 vs. 66.3% in group 2 (p < 0.0001) during FU. TE during FU occurred more often in group 1 than in group 2 (4.3 vs. 0.3%, p < 0.05)., Conclusion: Even in patients with previous stroke, OAC was frequently discontinued during FU after PAF ablation in this observational study. However, TE occurred significantly more frequent in these high-risk patients. These data argue against OAC discontinuation after ablation in patients with previous stroke.

Background: Atrial arrhythmias lower the biventricular pacing percentage in cardiac resynchronization therapy (CRT) treated patients (pts) and have a high prevalence in this population. External electrical cardioversion (ECV) is commonly performed to restore sinus rhythm. There is a paucity of data on the safety and efficacy of ECV in pts with CRT devices., Methods: Forty-three pts with CRT devices undergoing ECV at two centers were included prospectively. Devices were interrogated immediately prior to and after ECV, as well as after 4 weeks., Results: Devices (CRT-D in 38 and CRT-P in 5) were all implanted in left pectoral position, with predominantly bipolar left ventricular (LV) leads. Sixty-one shocks were delivered, all biphasic. Arrhythmia had recurred in 36 % of pts at follow-up (FU). There was a significant increase in LV lead threshold voltage and drop in bipolar LV lead impedance after ECV, which returned to normal at FU. An at least twofold increase in pacing threshold voltage at FU was seen in 2 LV leads and a 0.5 V increase in threshold in 3 LV leads. Overall, biventricular pacing significantly increased during FU., Conclusion: ECV in CRT pts was safe and effective in this two-center study. A transient increase in LV lead pacing threshold was observed. Relevant changes in pacing threshold at FU occurred in five LV leads-identification and regular FU of these pts are necessary. Restoring SR through ECV significantly increased the biventricular pacing percentage but arrhythmia recurrence was frequent. CRT pts with atrial arrhythmias require close FU after ECV.

Background: In the meantime, catheter ablation is widely used for the treatment of persistent atrial fibrillation (AF). There is a paucity of data about long-term outcomes. This study evaluates (1) 5-year single and multiple procedure success and (2) prognostic factors for arrhythmia recurrences after catheter ablation of persistent AF using the stepwise approach aiming at AF termination., Methods and Results: A total of 549 patients with persistent AF underwent de novo catheter ablation using the stepwise approach (2007-2009). A total of 493 patients were included (Holter ECGs ≥ every 6 months). Mean follow-up was 59 ± 16 months with 2.1 ± 1.1 procedures per patient. Single and multiple procedure success rates were 20.1% and 55.9%, respectively (80% off antiarrhythmic drug). Antiarrhythmic drug-free multiple procedure success was 46%. Long-term recurrences (n=171) were paroxysmal AF in 48 patients (28%) and persistent AF/atrial tachycardia in 123 patients (72%). Multivariable recurrent event analysis revealed the following factors favoring arrhythmia recurrence: failure to terminate AF during index procedure (hazard ratio [HR], 1.279; 95% confidence interval [CI], 1.093-1.497; P = 0.002), number of procedures (HR, 1.154; 95% CI, 1.051-1.267; P = 0.003), female sex (HR, 1.263; 95% CI, 1.027-1.553; P = 0.027), and the presence of structural heart disease (HR, 1.236; 95% CI, 1.003-1.524; P = 0.047). AF termination was correlated with a higher rate of consecutive procedures because of atrial tachycardia recurrences (P = 0.003; HR, 1.71; 95% CI, 1.20-2.43)., Conclusions: Catheter ablation of persistent AF using the stepwise approach provides limited long-term freedom of arrhythmias often requiring multiple procedures. AF termination, the number of procedures, sex, and the presence of structural heart disease correlate with outcome success. AF termination is associated with consecutive atrial tachycardia procedures., (© 2015 American Heart Association, Inc.)

Background: Catheter ablation (CA) of ventricular tachycardia (VT) is an important treatment option in patients with structural heart disease (SHD) and implantable cardioverter defibrillator (ICD). A subset of patients requires epicardial CA for VT., Objective: The purpose of the study was to assess the significance of epicardial CA in these patients after a systematic sequential endocardial approach., Methods: Between January 2009 and October 2012 CA for VT was analyzed. A sequential CA approach guided by earliest ventricular activation, pacemap, entrainment and stimulus to QRS-interval analysis was used. Acute CA success was assessed by programmed ventricular stimulation. ICD interrogation and 24h-Holter ECG were used to evaluate long-term success., Results: One hundred sixty VT ablation procedures in 126 consecutive patients (114 men; age 65±12years) were performed. Endocardial CA succeeded in 250 (94%) out of 265 treated VT. For 15 (6%) VT an additional epicardial CA was performed and succeeded in 9 of these 15 VT. Long-term FU (25±18.2month) showed freedom of VT in 104 pts (82%) after 1.2±0.5 procedures, 11 (9%) suffered from repeated ICD shocks and 11 (9%) died due to worsening of heart failure., Conclusions: Despite a heterogenic substrate for VT in SHD, endocardial CA alone results in high acute success rates. In this study additional epicardial CA following a sequential endocardial mapping and CA approach was performed in 6% of VT. Thus, due to possible complications epicardial CA should only be considered if endocardial CA fails., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)