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Abstract Background Next-generation sequencing technologies yield large numbers of genetic alterations, of which a subset are missense variants that alter an amino acid in the protein product. These variants can have a potentially destabilizing effect leading to an increased risk of misfolding and aggregation. Multiple software tools exist to predict the effect of single-nucleotide variants on proteins, however, a pipeline integrating these tools while starting from an NGS data output list of variants is lacking. Results The previous version SNPeffect 4.0 (De Baets in Nucleic Acids Res 40(D1):D935–D939, 2011) provided an online database containing pre-calculated variant effects and low-throughput custom variant analysis. Here, we built an automated and parallelized pipeline that analyzes the impact of missense variants on the aggregation propensity and structural stability of proteins starting from the Variant Call Format as input. The pipeline incorporates the AlphaFold Protein Structure Database to achieve high coverage for structural stability analyses using the FoldX force field. The effect on aggregation-propensity is analyzed using the established predictors TANGO and WALTZ. The pipeline focuses solely on the human proteome and can be used to analyze proteome stability/damage in a given sample based on sequencing results. Conclusion We provide a bioinformatics pipeline that allows structural phenotyping from sequencing data using established stability and aggregation predictors including FoldX, TANGO, and WALTZ; and structural proteome coverage provided by the AlphaFold database. The pipeline and installation guide are freely available for academic users on https://github.com/vibbits/snpeffect and requires a computer cluster.

Background: Electrophysiologic characteristics, mapping strategies, and acute success rates of radiofrequency catheter ablation of atriofascicular accessory pathways are well described. However, data on long-term prognosis and predictors for freedom from arrhythmias are lacking.Objective: To report our 20-year single-center experience on ablation of atriofascicular fibers.Method: Between 1992 and 2010, 34 patients with atriofascicular accessory pathways underwent catheter ablation at our institution because of symptomatic antidromic atrioventricular reentrant tachycardias. Radiofrequency procedures were retrospectively analyzed, and patients were followed for recurrences of tachyarrhythmias. Electrocardiograms (before and after ablation and at follow-up) were analyzed for each patient.Results: Successful catheter ablation of the atriofascicular fiber was achieved in 23 (68%) patients. Mechanical block during mapping occurred in 3 (9%) patients, and in 2 of them ablation was performed at the site of mechanical block. Mere modification of conduction properties of the pathway without complete block was achieved in 5 patients (15%). Fast pathway ablation was performed in 2 (6%) of the patients ablated in the early 1990s. During follow-up of 9.3 ± 5.5 years, 24 patients (71%) remained free of tachyarrhythmias, 7 reported significant improvement, and 3 (9%) had no change in symptoms after ablation. Long-term success was identical between patients from the first (1992-1999) and second (2000-2010) decade (12 of 17 [71%] vs 12 of 17 [71%]). It was 87% in those with complete block of the atriofascicular fiber while all patients with mechanical block during mapping reported recurrences. Fast pathway ablation was complicated by complete atrioventricular block in 1 patient, who required pacemaker implantation 18 years after ablation owing to loss of conduction properties of the atriofascicular fiber over the years. On analyzing patients with preexcitation before ablation (n = 16; 47%), we found that the PR interval after ablation was significantly longer only in those without recurrence (162 ± 21 ms vs 134 ± 21 ms; P = .042). None of the other analyzed electrocardiographic parameters, including PR, QRS duration, and preexcitation, had prognostic impact.Conclusion: Acute success of complete ablation of atriofascicular pathways is associated with excellent long-term success (87%). Mere modification of conduction properties of atriofascicular fibers or ablation at the sites of mechanical block are less promising end points of ablation with high recurrence rates. Technical innovations during decades may not further improve long-term outcome in these patients. [ABSTRACT FROM AUTHOR]

Aim: COVID-19 has been associated with cardiovascular complications including ventricular arrhythmias (VA) and an increased number of out-of-hospital cardiac arrests. Nevertheless, several authors described a decrease of VA burden in patients with an implantable defibrillator (ICD) during the first wave of the COVID-19 pandemic. The objective of this study was to determine if these observations could be transferred to later periods of the pandemic as well., Methods: We retrospectively analyzed a total of 1674 patients with an ICD presenting in our outpatient clinic during the second wave of the COVID-19 pandemic and during a control period for the occurrence of VA requiring ICD interventions., Results: Seven hundred ninety-five patients with an ICD had a device interrogation in our ambulatory clinic during the second wave of the COVID-19 pandemic compared to eight hundred seventy-nine patients in the control period. There was significant higher amount of adequate ICD therapies in the course of the COVID-19 period. Thirty-six patients (4.5%) received in total eighty-five appropriate ICD interventions during COVID-19, whereas only sixteen patients (1.8%) had sustained VA in the control period (p = 0.01)., Conclusion: In contrast to the first wave of COVID-19, which was characterized by a decrease or least stable number of ICD therapies in several centers, we found a significant increase of VA in ICD patients during the second wave of COVID-19. Possible explanations for this observation include higher infectious rates, potential cardiac side effects of the vaccination as well as personal behavioral changes, or reduced utilization of medical services., (© 2023. The Author(s).)

Objective and Background:  Data on incidence of in-hospital pulmonary embolisms (PE) after catheter ablation (CA) are scarce. To gain further insights, we sought to provide new findings through case-based analyses of administrative data., Methods:  Incidences of PE after CA of supraventricular tachycardias (SVT), atrial fibrillation (AF), atrial flutter (AFlu), and ventricular tachycardias (VT) in three German tertiary centers between 2005 and 2020 were determined and coded by the G-DRG (German Diagnosis Related Groups System) and OPS (German Operation and Procedure Classification) systems. An administrative search was performed with a consecutive case-based analysis., Results:  Overall, 47,344 ablations were analyzed (10,037 SVT; 28,048 AF; 6,252 AFlu; 3,007 VT). PE occurred in 14 (0.03%) predominantly female ( n  = 9; 64.3%) patients with a mean age of 55.3 ± 16.9 years, body mass index 26.2 ± 5.1 kg/m 2 , and left ventricular ejection fraction of 56 ± 13.6%. PE incidences were 0.05% ( n  = 5) for SVT, 0.02% ( n  = 5) for AF, and 0.13% ( n  = 4) for VT ablations. No patient suffered PE after AFlu ablation. Five patients (35.7%) with PE after CA had no prior indication for oral anticoagulation (OAC). Preprocedural international normalized ratio in PE patients was 1.2 ± 0.5. Most patients with PE following CA presented with symptoms the day after the procedure ( n  = 9) after intraprocedural heparin application of 12,943.2 ± 5,415.5 IU. PE treatment included anticoagulation with either phenprocoumon ( n  = 5) or non-vitamin K-dependent OAC ( n  = 9). Two patients with PE died after VT/AF ablation, respectively. The remaining patients were discharged without sequels., Conclusion:  Over a 15-year period, incidence of PE after ablation is low, particularly low in patients with ablation for AF/AFlu. This is most likely due to stricter anticoagulation management in these patients compared with those receiving SVT/VT ablation procedures and could argue for continuation of OAC prior to ablation. Optimizing periprocedural anticoagulation management should be subject of further prospective trials., Competing Interests: None declared., (Thieme. All rights reserved.)

Despite impressive developments in the field of ventricular arrhythmias, there is still a relevant number of patients with ventricular arrhythmias who require antiarrhythmic drug therapy and may, e.g., in otherwise drug and/or ablation refractory situations, benefit from agents known for decades, such as mexiletine. Through its capability of blocking fast sodium channels in cardiomyocytes, it has played a minor to moderate antiarrhythmic role throughout the recent decades. Nevertheless, certain patients with structural heart disease suffering from drug-refractory, i.e., mainly amiodarone refractory ventricular arrhythmias, as well as those with selected forms of congenital long QT syndrome (LQTS) may nowadays still benefit from mexiletine. Here, we outline mexiletine's cellular and clinical electrophysiological properties. In addition, the application of mexiletine may be accompanied by various potential side effects, e.g., nausea and tremor, and is limited by several drug-drug interactions. Thus, we shed light on the current therapeutic role of mexiletine for therapy of ventricular arrhythmias and discuss clinically relevant aspects of its indications based on current evidence., (© 2024. The Author(s).)

Background: Atrial fibrillation (AF) is a cardiac arrhythmia frequently documented in patients requiring implantable cardioverter defibrillators (ICDs) and/or cardiac resynchronization therapy with defibrillator (CRT-D). Patients with diagnosed AF at the point of ICD or CRT-D implantation may have an impaired follow-up outcome., Methods: The German DEVICE I-II registry is a nationwide prospective multicentre database of patients implanted with ICD and CRT-D with clinical follow-up data. We analysed a 1-year follow up of implanted patients with AF and with sinus rhythm (SR)., Results: A total of 4,929 ICD/CRT patients are included in the present analysis: 946 (19.2%) were in AF and 3,983 (80.8%) were SR at time of device implantation. AF patients had a significantly more comorbid profile including older age {72 [interquartile range (IQR), 66-77] vs. 66 (IQR, 56-73) years; P<0.001}, and higher rate of patients with left ventricular ejection fraction <30% (68.2% vs. 61.0%; P<0.001), peripheral artery disease (4.5% vs. 2.7%; P=0.002), diabetes (33.6% vs. 25.5%; P<0.001), hypertension (58.4% vs. 51.1%; P<0.001) and renal failure (22.6% vs. 15.3%; P<0.001). The intra-hospital complication rate was 4.3% in the AF and 3.6% in the SR group (P=0.38). In 1-year follow-up AF patients experienced a significantly higher rate of defibrillator shocks (25% vs. 15.3%; P<0.001). One-year estimated mortality was 10.8% in the AF and 5.9% in the SR group (P<0.001), while estimated 1-year major adverse cardiac and cerebrovascular events (MACCE) rate was 11.2% vs. 7.0% (P<0.001). The effects of AF on electrical shocks and mortality persisted after adjusting for age, sex, advanced New York Heart Association (NYHA) class, severely impaired left ventricular ejection fraction (LVEF), coronary artery disease (CAD), chronic obstructive pulmonary disease (COPD), diabetes mellitus (DM), chronic renal failure (CRF), QRS duration, and type of indication for electronic device implantation., Conclusions: Our clinical data on an extended cohort of contemporary patients confirm the significant impact of AF, and its associated comorbidities, upon mortality and major adverse events after implantation of ICD/CRT., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-274/coif). G.D. serves as an unpaid editorial board member of Journal of Thoracic Disease from February 2023 to January 2025. H.I. received an institutional research grant from Boston Scientific. J.K. received honoraria for lectures and travel grants from Abbott, Boston Scientific and Biotronik. The other authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Aims: In-hospital complications of catheter ablation for atrial fibrillation (AF), atrial flutter (AFL), and ventricular tachycardia (VT) may be overestimated by analyses of administrative data., Methods and Results: We determined the incidences of in-hospital mortality, major bleeding, and stroke around AF, AFL, and VT ablations in four German tertiary centres between 2005 and 2020. All cases were coded by the G-DRG- and OPS-systems. Uniform code search terms were applied defining both the types of ablations for AF, AFL, and VT and the occurrence of major adverse events including femoral vascular complications, iatrogenic tamponade, stroke, and in-hospital death. Importantly, all complications were individually reviewed based on patient-level source records. Overall, 43 031 ablations were analysed (30 361 AF; 9364 AFL; 3306 VT). The number of ablations/year more than doubled from 2005 (n = 1569) to 2020 (n = 3317) with 3 times and 2.5 times more AF and VT ablations in 2020 (n = 2404 and n = 301, respectively) as compared to 2005 (n = 817 and n = 120, respectively), but a rather stable number of AFL ablations (n = 554 vs. n = 612). Major peri-procedural complications occurred in 594 (1.4%) patients. Complication rates were 1.1% (n = 325) for AF, 1.0% (n = 95) for AFL, and 5.3% (n = 175) for VT. With an increase in complex AF/VT procedures, the overall complication rate significantly increased (0.76% in 2005 vs. 1.81% in 2020; P = 0.004); but remained low over time. Following patient-adjudication, all in-hospital cardiac tamponades (0.7%) and strokes (0.2%) were related to ablation. Major femoral vascular complications requiring surgical intervention occurred in 0.4% of all patients. The in-hospital mortality rate adjudicated to be ablation-related was lower than the coded mortality rate: AF: 0.03% vs. 0.04%; AFL: 0.04% vs. 0.14%; VT: 0.42% vs. 1.48%., Conclusion: Major adverse events are low and comparable after catheter ablation for AFL and AF (∼1.0%), whereas they are five times higher for VT ablations. In the presence of an increase in complex ablation procedures, a moderate but significant increase in overall complications from 2005-20 was observed. Individual case analysis demonstrated a lower than coded ablation-related in-hospital mortality. This highlights the importance of individual case adjudication when analysing administrative data., Competing Interests: Conflict of interest: L.E. discloses consultant fees, speaking honoraria, and travel expenses from Abbott, Bayer Healthcare, Biosense Webster, Biotronik, Boehringer, Boston Scientific, Bristol-Myers Squibb, Daiichi Sankyo, Medtronic, Pfizer, and Sanofi Aventis. Research has been supported by German Research Foundation (DFG) and German Heart Foundation outside the submitted work. The other authors declared no conflicts of interest regarding this study., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Cryoballoon ablation is a widely used single-shot technique for pulmonary vein isolation (PVI) in the treatment of paroxysmal atrial fibrillation (AF). Procedural endpoints ensuring maximal PVI durability are important., Objective: To assess the performance of cryoablation procedural markers to predict long-term PVI., Methods: In a single center, consecutive patients who underwent redo ablation with high-density mapping for symptomatic AF recurrence after cryoballoon ablation were included and cryoballoon procedural data were collected, including temperature values at 30 and 60 s, time to isolation, nadir temperature and the velocity of temperature decline estimated with the temperature/time catch-up point (T2T-Catch-Up) defined as positive when the freeze temperature in minus degree equals the time in seconds after cryoablation initiation (e.g. - 15 °C in the first 15 s of the ablation impulse)., Results: 47 patients (62% male; 58.3 ± 11.2 years) were included. Overall, 38 (80.9%) patients had ≥ 1 reconnected PV. Among 186 PVs, 56 (30.1%; 1.2 per patient on average) were reconnected. Univariate analysis revealed T2T-Catch-Up in 103 (56%) and more frequent in durably isolated than in reconnected PVs (93 [72%] vs 10 [19%], p < 0.0001). Among binary endpoints, T2T-Catch-Up had the highest specificity (82%) and predictive value for durable PVI at redo ablation (90%). In multivariable analyses, absence of T2T-Catch-Up (Odds-ratio 0.12, 95% CI [0.05-0.31], p < 0.0001) and right superior PV (Odds-ratio 3.14, 95% CI [1.27-7.74], p = 0.01) were the only variables independently associated with PV reconnection., Conclusion: T2T-Catch-Up, a new and simple cryoballoon procedural endpoint demonstrated excellent predictive value and strong statistical association with durable PVI., (© 2023. The Author(s).)

Background: Early repolarization pattern (ERP) has been associated with idiopathic ventricular fibrillation (IVF) and with cardiovascular mortality in the general population. As there is limited data about long- term outcome of IVF, the aim of our study was to observe ventricular arrhythmia (VA) recurrences in these patients and to identify a possible correlation of VA with ECG markers of early repolarization., Methods and Results: We investigated 56 consecutive IVF patients who received an implantable cardioverter-defibrillator for secondary prevention. ERP was defined as a J-point elevation ≥ 0.1 mV in two or more contiguous inferior or lateral leads. Markers of early repolarization were present in 32.1% of cases with a preponderance of QRS slurring (77.8%). During a mean follow-up of 41.2 months, 11 patients (19.6%) received in total 18 adequate ICD-therapies. VF was most the common cause for ICDtherapy (61.1%) but monomorphic VT also occurred in four patients. Presence of ERP was associated with a significant trend towards arrhythmia recurrences. 38.9% patients with ERP received appropriate ICD-therapies whereas only 10.5% of patients without ERP had arrhythmia recurrence (p = 0.05). Inappropriate ICD-therapies occurred in seven patients (12.5%) with a non-significant trend towards a higher incidence in patients with a transvenous ICD (p = 0.15)., Conclusion: A significant correlation between ERP and VA recurrences in patients with IVF could be observed. Though monomorphic VA also play a role in the studied IVF-population, our data support the use of the S-ICD in this collective., (© 2022. The Author(s).)

Lidocaine is classified as a class Ib anti-arrhythmic that blocks voltage- and pH-dependent sodium channels. It exhibits well investigated anti-arrhythmic effects and has been the anti-arrhythmic of choice for the treatment of ventricular arrhythmias for several decades. Lidocaine binds primarily to inactivated sodium channels, decreases the action potential duration, and increases the refractory period. It increases the ventricular fibrillatory threshold and can interrupt life-threatening tachycardias caused by re-entrant mechanisms, especially in ischemic tissue. Its use was pushed into the background in the era of amiodarone and modern electric device therapy. Recently, lidocaine has come back into focus for the treatment of acute sustained ventricular tachyarrhythmias. In this brief overview, we review the clinical pharmacology including possible side effects, the historical course, possible indications, and current Guideline recommendations for the use of lidocaine., (© 2023 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Objective and Background: Catheter-based treatment of patients with ventricular arrhythmias (VA) reduces VA and mortality in selected patients. With regard to potential risks of catheter ablation, a benefit-risk assessment should be carried out. This can be performed with risk scores such as the recently published "Risk in Ventricular Ablation (RIVA) Score". We sought to validate this score and to test for possible additional predictors in a large database of VT ablations., Methods and Results: We analyzed 1964 catheter ablations for VA in patients with (1069; 54.4%) and without (893, 45.6%) structural heart disease (SHD) and observed an overall major adverse event rate of 4.0% with an in-hospital mortality of 1.3% with significantly less complications occurring in patients without structural heart disease (6.5% vs. 1.1%; p ≤ 0.01). The RIVA Score demonstrated to be a valid predictive tool for major in-hospital complications (OR 1.18; 95% CI 1.12, 1.25; p ≤ 0.001). NYHA Class ≥ III (OR 2.5; 95% CI 1.5, 4.2; p < 0.001) and age (OR 1.04; 95% CI 1.02, 1.07; p ≤ 0.001) proved to be additional predictive parameters. Hence, a modified RIVA Score (mRIVA) model was analyzed with a subset of established predictors (SHD, eGFR, epicardial puncture) as well as new predictive parameters (age, NYHA Class ≥ III), that achieved a higher predictive value for major complications compared with the model based on all RIVA variables., Conclusion: Adding age and functional heart failure status (NYHA class) as simple clinical parameters to the recently published RIVA Score increases the predictive value for ablation-associated complications in a large VT ablations registry., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Aims: The incidence of in-hospital post-interventional complications and mortality after ablation of supraventricular tachycardia (SVT) vary among the type of procedure and most likely the experience of the centre. As ablation therapy of SVT is progressively being established as first-line therapy, further assessment of post-procedural complication rates is crucial for health care quality., Methods and Results: We aimed at determining the incidence of in-hospital mortality and bleeding complications from SVT ablations in German high-volume electrophysiological centres between 2005 and 2020. All cases were registered by the German Diagnosis Related Groups-and the German Operation and Procedure Classification (OPS) system. A uniform search for SVT ablations from 2005 to 2020 with the same OPS codes defining the type of ablation/arrhythmia as well as the presence of a vascular complication, cardiac tamponade, and/or in-hospital death was performed. An overall of 47 610 ablations with 10 037 SVT ablations were registered from 2005 to 2020 among three high-volume centres. An overall complication rate of 0.5% (n = 38) was found [median age, 64; ±15 years; female n = 26 (68%)]. All-cause mortality was 0.02% (n = 2) and both patients had major prior co-morbidities precipitating a lethal outcome irrespective of the ablation procedure. Vascular complications occurred in 10 patients (0.1%), and cardiac tamponade was detected in 26 cases (0.3%)., Conclusion: The present case-based analysis shows an overall low incidence of in-hospital complications after SVT ablation highlighting the overall very good safety profile of SVT ablations in high-volume centres. Further prospective analysis is still warranted to guarantee continuous quality control and optimal patient care., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The subcutaneous ICD (S-ICD) has developed as a valuable alternative to transvenous implantable cardioverter defibrillator (ICD) systems. However there are certain peculiarities which are immanent to the S-ICD and may limit its use. Besides oversensing the main issue is the missing option for antibradycardia pacing. To evaluate the actual need for pacing during follow-up and changes to transvenous ICD we analyzed our large tertiary centre registry and compared it with data from other large cohorts and trials., Methods and Results: We found out that in the 398 patients from our centre, there was a need for changing to a transvenous ICD in only 2 patients (0.5%) during a follow-up duration of almost 3 years. This rate was comparable to data obtained from other large data sets so that in the pooled analysis of almost 4000 patients the rate of bradycardia-associated complications was only 0.3%., Conclusions: The use of the S-ICD is safe in a variety of heart diseases and the need for antibradycardia stimulation is a very rare complication throughout many different large studies. Clinicians may take these results into account when opting for a certain ICD system and the S-ICD may be chosen more often also in elderly patients, in whom the risk for bradycardia is deemed higher., Competing Interests: LE, FR, CE, JW, GF, PSL, BR, JK, PL and KW received travel or research grants from Boston Scientific. All other authors declare no conflict of interest., (Copyright: © 2022 The Author(s). Published by IMR Press.)

Catheter-based ablation is nowadays a safe and widespread procedure for the treatment of cardiac arrhythmia. This requires exact anatomical knowledge both before and during the examination and is an important prerequisite for targeted treatment. At the beginning of the era of interventional catheter-based treatment, fluoroscopy was the only and usual means of visualization, whereas in the middle of the 1990s continuous 3D-mapping systems were developed for the non-fluoroscopic examination of patients. The correct use of these 3‑D systems, which non-fluoroscopically visualize the catheter and mostly identify mechanisms of arrhythmia in great detail, nowadays makes an important contribution to successful interventional catheter treatment of arrhythmia; however, it is not uncommon for patients with ventricular arrhythmia to also carry implanted electronic devices, such as pacemakers, defibrillators or less frequently left ventricular hemodynamic support systems. All implantable devices lead to electromagnetic interferences, which can complicate the diagnostics and treatment during electrophysiological examinations and ablation. This article addresses the adversities and experiences associated with magnet-based 3D systems and implantable electromagnetically active cardiac devices., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

1. Introduction: Pulmonary vein isolation (PVI) is an established procedure used to achieve rhythm control in atrial fibrillation (AF). In obese patients (pts), in whom AF occurs more frequently, a reduced effectiveness of PVI has been observed. Therefore, this study’s aim was to compare the long-term efficacy of PVI between obese and non-obese patients. 2. Methods: We enrolled 111 consecutive pts with a body mass index (BMI) of >30 kg/m2 undergoing PVI from our large registry. Procedural data and outcomes were compared with a matched group of 115 non-obese PVI pts and the long-term outcomes were analyzed. 3. Results: Overall follow-up duration was 314 patient-years in the obese and 378 patient-years in the non-obese group. The follow-up rate was 71% in the obese and 76% in the non-obese group. In both groups, their AF-characteristics did not differ significantly, while known risk factors were significantly more prevalent in the obese group. Procedural characteristics were similar in both groups. During follow-up, the obese pts demonstrated significant weight loss compared to the non-obese pts, while at the same time, the overall recurrence rate during follow-up did not differ significantly between both groups (obese: 39.2% and non-obese: 43.7%). PVI related and long-term complications were comparable between both groups. In the univariate analysis, obesity was not found to be associated with an increased AF recurrence risk. 4. Conclusion: These real-life data demonstrate that obese pts may not show higher AF recurrence rates after PVI compared to pts with normal body weight. Furthermore, PVI was found to be safe and effective in obese patients; thus, a BMI alone may not be a criterion for refusal of PVI.

The implantation of cardiac devices significantly reduces morbidity and mortality in patients with cardiac arrhythmias. Arrhythmias as well as therapy delivered by the device may impact quality of life of patients concerned considerably. Therefore we aimed at conducting a systematic search and meta-analysis of trials examining the impact of the implantation of cardiac devices, namely implantable cardioverter-defibrillators (ICD), pacemakers and left-ventricular assist devices (LVAD) on quality of life. After pre-registering the trial with the PROSPERO database, we searched Medline, PsycINFO, Web of Science and the Cochrane databases for relevant publications. Study quality was assessed by two independent reviewers using standardized protocols. A total of 37 trials met our inclusion criteria. Of these, 31 trials were cohort trials while 6 trials used a randomized controlled design. We found large pre-post effect sizes for positive associations between quality of life and all types of devices. The effect sizes for LVAD, pacemaker and ICD patients were g = 1.64, g = 1.32 and g = 0.64, respectively. There was a lack of trials examining the effect of implantation on quality of life relative to control conditions. Trials assessing quality of life in patients with cardiac devices are still scarce. Yet, the existing data suggest beneficial effects of cardiac devices on quality of life. We recommend that clinical trials on cardiac devices routinely assess quality of life or other parameters of psychological well-being as a decisive study endpoint. Furthermore, improvements in psychological well-being should influence decisions about implantations of cardiac devices and be part of patient education and may impact shared decision-making.

Background: Decision-making in primary prevention is not always trivial and many clinical scenarios are not reflected in current guidelines. To help evaluate a patient’s individual risk, a new score to predict the benefit of an implantable defibrillator (ICD) for primary prevention, the MADIT-ICD benefit score, has recently been proposed. The score tries to predict occurrence of ventricular arrhythmias and non-arrhythmic death based on data from four previous MADIT trials. We aimed at examining its usefulness in a large single-center register of S-ICD patients with various underlying cardiomyopathies. Methods and results: All S-ICD patients with a primary preventive indication for ICD implantation from our large single-center database were included in the analysis (n = 173). During a follow-up of 1227 ± 978 days, 27 patients developed sustained ventricular arrhythmias, while 6 patients died for non-arrhythmic reasons. There was a significant correlation for patients with ischemic cardiomyopathy (ICM) (n = 29, p = 0.04) to the occurrence of ventricular arrhythmia. However, the occurrence of ventricular arrhythmias could not sufficiently be predicted by the MADIT-ICD VT/VF score (p = 0.3) in patients with (n = 142, p = 0.19) as well as patients without structural heart disease (n = 31, p = 0.88) and patients with LV-EF < 35%. Of the risk factors included in the risk score calculation, only non-sustained ventricular tachycardias were significantly associated with sustained ventricular arrhythmias (p = 0.02). Of note, non-arrhythmic death could effectively be predicted by the proposed non-arrhythmic mortality score as part of the benefit score (p = 0.001, r = 0.3) also mainly driven by ICM patients. Age, diabetes mellitus, and a BMI < 23 kg/m2 were key predictors of non-arrhythmic death implemented in the score. Conclusion: The MADIT-ICD benefit score adds a new option to evaluate expected benefit of ICD implantation for primary prevention. In a large S-ICD cohort of primary prevention, the value of the score was limited to patients with ischemic cardiomyopathy. Future research should evaluate the performance of the score in different subgroups and compare it to other risk scores to assess its value for daily clinical practice.

Syncopes are a very common phenomenon and have a high recurrence rate. The differentiation between the psychogenic and physical, especially of arrhythmic origin, remains difficult. In many cases, an implantable loop recorder is used for the detection of possible arrhythmias, leading to syncopes. Yet, the existing literature suggests that psychological factors may play a significant role in recurrent syncopes. We aimed at analyzing the potential role of several psychological factors on the recurrence of arrhythmic or non-arrhythmic syncopes. Methods and results: A total of 119 patients, who had received an implantable loop recorder for recurrent syncopes at our center between 01/2018 and 12/2021, participated in this retrospective cohort study. Anxiety, depression and quality of life were assessed using extensively validated questionnaires (GAD-7, PHQ-9 and SF-12). The mean follow-up after loop recorder implantation was 710 ± 430 days and 50% of patients were female. The mean patient age was 54.8 ± 18.6 years. Most patients had no evidence of structural heart disease (84%), and normal LV function (92%). A statistical analysis revealed that the presence of structural heart disease was the strongest predictor for arrhythmic syncope during follow-up. In patients with non-arrhythmic syncopes, we found significantly higher levels of anxiety (GAD-7 score: 2.5 ± 2.6 vs. 4.8 ± 4.3) and depression (PHQ-9 score: 3.9 ± 3.6 vs. 6.8 ± 5.1), and a lower quality of life (SF-12 score: 33.7 ± 6.4 vs. 29.6 ± 7.8). Discussion: We identified factors as contributors to a better identification of patients at risk for arrhythmic as well as non-arrhythmic syncopes. Especially anxious or depressive symptoms may hinted at non-arrhythmic causes of syncope. However, the study was limited by its retrospective design and low patient number. Further trials should likewise combine the diagnostic yield of loop recorders with psychometric evaluations before implantation and combine it with additional diagnostic measures, such as video monitoring, to further examine the role of psychological factors in the pathomechanism and treatment of syncope.

As with all cardiac interventions, performing left ventricular ablation requires profound knowledge of cardiac anatomy. The aim of this article is to provide an overview of left ventricular anatomy and to characterize complex and clinically relevant structures from an electrophysiologist-centered perspective. In addition to the different access routes, the trabecular network, the left ventricular outflow tract, and the left ventricular conduction system, complex anatomical structures such as the aortomitral continuity and the left ventricular summit are also explained. In addition, this article offers multiple clinical examples that combine ECG, anatomy, and electrophysiologic study., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Amiodarone has a profound adverse toxicity profile. Large population-based analyses quantifying the risk of thyroid dysfunction (TD) in adults with and without congenital heart disease (ACHD) are lacking. Methods: All adults registered with a major German health insurer (≈9.2 million members) with amiodarone prescriptions were analyzed. Occurrence of amiodarone-associated TD was assessed. Results: Overall, 48,891 non-ACHD (37% female; median 73 years) and 886 ACHD (34% female; median 66 years) received amiodarone. Over 184,787 patient-years, 10,875 cases of TD occurred. The 10-year risk for TD was 38% in non-ACHD (35% ACHD). Within ACHD, compared to amiodarone-naïve patients, the hazard ratio (HR) for TD was 3.9 at 4 years after any amiodarone exposure. TD was associated with female gender (HR 1.42, p < 0.001) and younger age (HR 0.97 per 10 years, p = 0.009). Patients with congenital heart disease were not at increased risk (HR 0.98, p = 0.80). Diagnosis of complex congenital heart disease, however, was a predictor for TD (HR 1.56, p = 0.02). Amiodarone was continued in 47% of non-ACHD (38% ACHD), and 2.3% of non-ACHD (3.5% ACHD) underwent thyroid surgery/radiotherapy. Conclusions: Amiodarone-associated TD is common and comparable in non-ACHD and ACHD. While female gender and younger age are predictors for TD, congenital heart disease is not necessarily associated with an elevated risk.

Background: Registry data add important information to randomized controlled trials (RCT) on real-life aspects of implantable cardioverter-defibrillator (ICD) patients with and without cardiac resynchronization therapy (CRT-D). This analysis of the prospectively conducted German Device Registry aims at comparing mortality rates, comorbidities, complication rates to results from RCT., Methods: The German Device registry (DEVICE) prospectively collected data on ICD and CRT-D first implantations from 50 German centres. Demographic data, details on cardiac disease, electrocardiogram (ECG), medication, and data about procedure, complications, and hospital stay were stored in electronic case report forms. One year after device implantation patients were contacted for follow-up., Results: DEVICE included n = 4384 first ICD/CRT-D implantations (29.3% CRT-D devices). We found a strong adherence to guidelines with over 90% of patients being on ß-blocker and ACE-inhibitor medication and adequate QRS width in the majority of CRT-D patients. Patients receiving a CRT-D were older (67.6 ± 11.0 years vs. 63.9 ± 13.4 years, p < .001) and had lower ejection fractions (mean 25% vs. 30%, p < .001) compared to ICD patients. Dilated cardiomyopathy was the predominant underlying heart disease in CRT-D (53.3%), coronary artery disease in ICD patients (64.7%). Compared to RCT our DEVICE patients had more comorbidities (17.9% chronic kidney disease [CKD]) and higher 1-year mortality rates (10.7% ICD group, 12.3% CRT group). In multivariate analysis, CKD patients had an almost 2-fold higher risk of 1-year mortality., Conclusion: Despite relevant limitations of registry data, DEVICE highlights important differences between RCT and real-world registry data and the impact of comorbidities on mortality of ICD and CRT-D recipients., (© 2022 The Authors. Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

Background: Left atrial tachycardias (LAT) are a well-known outcome of pulmonary vein isolation (PVI). Few data are available on whether the catheter used to perform PVI influences the incidence, as well as the characteristics of post PVI LAT. We present data on LAT following PVI by the following three ablation technologies: (1) phased multi-electrode radiofrequency catheter (PVAC), (2) irrigated single-tip catheter (iRF), and (3) cryoballoon ablation., Methods: Using a prospectively designed single-center database, we analyzed 650 patients (300 iRF, 150 PVAC, and 200 cryoballoon) with paroxysmal ( n = 401) and persistent atrial fibrillation (AF), who underwent their first PVI at our center., Results: The three populations were comparable in their baseline characteristics; however, the cryoballoon group comprised a higher percentage of patients with persistent AF ( p = 0.05). The LAT rates were 3.7% in the iRF group (mean follow-up 22 ± 14 months), 0.7% in the PVAC group (mean follow-up 21 ± 14 months), and 4% in the cryoballoon group (mean follow-up 15 ± 8 months). The predominant mechanism of LAT was macro-reentrant tachycardia. Reconnection of at least one pulmonary vein was observed in 87% of the patients who underwent 3D mapping. No predictors for LAT occurrence were identified., Conclusion: The occurrence of LAT post PVI is rare; the predominant mechanism was macro-reentrant tachycardia. Reconnection of at least one pulmonary vein was observed in nearly all the LAT patients. In our retrospective analysis, the lowest rate of LAT was observed with the PVAC. No predictors for LAT occurrence were identified.

Background: Different electrocardiogram (ECG) findings are known to be independent predictors of clinical response to cardiac resynchronization therapy (CRT). It remains unknown how these findings influence very long-term prognosis., Methods and Results: A total of 102 consecutive patients (75 males, mean age 65 ± 10 years) referred to our center for CRT implantation had previously been included in this prospective observational study. The same patient group was now re-evaluated for death from all causes over a prolonged median follow-up of 10.3 years (interquartile range 9.4-12.5 years). During follow-up, 55 patients died, and 82% of the clinical non-responders ( n = 23) and 44% of the responders ( n = 79) were deceased. We screened for univariate associations and found QRS width during biventricular (BIV) pacing ( p = 0.02), left ventricular (LV) pacing ( p < 0.01), Δ LV paced-right ventricular (RV) paced ( p = 0.03), age ( p = 0.03), New York Heart Association (NYHA) class ( p < 0.01), CHA 2 DS 2 -Vasc score ( p < 0.01), glomerular filtration rate ( p < 0.01), coronary artery disease ( p < 0.01), non-ischemic cardiomyopathy (NICM) ( p = 0.01), arterial hypertension ( p < 0.01), NT-proBNP ( p < 0.01), and clinical response to CRT ( p < 0.01) to be significantly associated with mortality. In the multivariate analysis, NICM, the lower NYHA class, and smaller QRS width during BIV pacing were independent predictors of better outcomes., Conclusion: Our data show that QRS width duration during biventricular pacing, an ECG parameter easily obtainable during LV lead placement, is an independent predictor of mortality in a long-term follow-up. Our data add further evidence that NICM and lower NYHA class are independent predictors for better outcome after CRT implantation.

Introduction: Multiple studies have shown that left atrial (LA) enlargement is a strong predictor of poor outcome after catheter ablation of atrial fibrillation (AF). LA size is commonly approximated as the diameter in the parasternal long axis. It remains unknown whether more precise echocardiographic measurements of LA size allow for better correlation with outcome after pulmonary vein isolation (PVI)., Methods and Results: We performed a retrospective study of 131 consecutive patients (43 females, 60% paroxysmal AF, mean CHA2DS2-Vasc score 1.6, mean age 61 ± 12 years) referred for PVI. Measurements of the LA were carried out by a single observer in transthoracic echocardiograms (TTE) performed prior to ablation. We calculated diameter of the LA in the parasternal long axis (PLAX), LA area in the 2- as well as 4-Chamber (CH) view. LA volume was computed using the disc summation technique (LAV) and indexed to body surface area (LAVI). Procedural and follow-up data were gathered from a prospective AF database. Ablation was performed exclusively using the second generation cryoballoon by the same operators. Follow-up visits at 3, 6 and 12 months showed freedom from AF in 76%, 73% and 73% respectively. Mean values of LA calculations were LAPLAX: 37.9 mm ± 6.3 mm, 2CH area: 22.5 cm 2 ± 6.7 cm 2 , 4CH area: 21.4 cm 2 ± 5.5 cm 2 , LAV: 73.7 mL ± 26.1 mL and LAVI: 36.2 mL/m 2 ± 12.7 mL/m 2 , respectively. C statistic revealed the best concordance of LAVI with outcome after 12 months (C = 0.67), LAV also exhibited a satisfactory value (C = 0.61) in comparison to surfaces in 2CH (C = 0.59) and 4CH (C = 0.57). PLAX showed the worst correlation (C = 0.51). Additionally, different binary logistic regression models identified three independent predictors of AF outcome after cryoballoon PVI: gender (OR = 0.95 per year; p = 0.01); LAV (OR = 1.3/10mL; p = 0.02) and LAVI (OR = 1.58/10 mL/m 2 ; p = 0.02). In all models, PLAX and area measurements were not predictive., Conclusions: Our data add further to evidence that LA size lends itself well as a predictor of PVI outcome. LAVI and LAV were independently predictive of rhythm outcome after PVI. This did not hold true for more commonly used measurements, such as PLAX diameter and surfaces of the LA, irrespective of the view chosen.

Aims: The present study aims at analyzing the role of a preimplantation 12-lead electrocardiogram (ECG) on the prediction of inappropriate S-ICD® episodes., Methods: N=116 screened patients (pts) with an S-ICD® and a follow-up of at least 6 months were included. A preimplantation 12-lead ECG (50 mm/s, 10 mm/mV) was analyzed with regard to QRS and T-wave amplitude, T wave concordance or discordance and QRS/T wave ratio in all 12 leads. To ensure an exact determination of parameters Datinf® Measure software was used. Results were correlated to the occurrence of oversensing of cardiac signals during follow-up., Results: N = 116 pts. (63,8% male, mean age 40,9 ± 15,5 years) were included (primary prevention in 47.4% of pts). The most frequent cardiac diseases were hypertrophic cardiomyopathy (HCM) in n = 25 (21,6%), electrical heart disease in n = 20 (17,2%), and dilated cardiomyopathy in n = 17 (14,7%). Mean follow-up was 740 ± 549 days. During follow- up n = 17 (14.7%) pts. experienced n = 27 inappropriate episodes due to T-wave oversensing. Besides HCM (OR 6.16, CI 1.79-21.15, p = 0.004) a discordance of QRS to T-wave in lead I (OR 6.5, CI 1.86-22.67, p = 0.003) was found to be a strong predictor for inappropriate shocks. In multivariate analysis the pts. with a combination of both had an 8.4-fold higher risk of misclassification of intracardiac signals (p = 0.003) with consecutive inappropriate therapy., Conclusion: A discordance of QRS to T-wave in lead I turned out to be a strong predictor for future inappropriate shocks in a typical S-ICD® cohort with special impact on HCM pts., Competing Interests: Declaration of Competing Interest J.W.: no conflicts of interest. B.R., K.W., N.B. G.F. DG.D., F.R., J.K.: received lecture honoraria and travel grants from Astra/Zeneca, Biosense Webster, Biotronik, Boehringer Ingelheim, Boston Scientific, Medtronic, Abbott. L.E.: has received research grants from Biotronik, St. Jude Medical, Sanofi and Osypka. He holds the Peter-Osypka-professorship for experimental and clinical electrophysiology of the University of Muenster, Germany., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Supraventricular tachycardias (SVT) are often difficult to document due to their intermittent, short-lasting nature. Smartphone-based one-lead ECG monitors (sECG) were initially developed for the diagnosis of atrial fibrillation. No data have been published regarding their potential role in differentiating inappropiate sinus tachycardia (IST) from regular SVT. If cardiologists could distinguish IST from SVT in sECG, economic health care burden might be significantly reduced., Methods: We prospectively recruited 75 consecutive patients with known SVT undergoing an EP study. In all patients, four ECG were recorded: a sECG during SVT and during sinus tachycardia and respective 12-lead ECG. Two experienced electrophysiologists were blinded to the diagnoses and separately evaluated all ECG., Results: Three hundred individual ECG were recorded in 75 patients (47 female, age 50 ± 18 years, BMI 26 ± 5 kg/m 2 , 60 AVNRT, 15 AVRT). The electrophysiologists' blinded interpretation of sECG recordings showed a sensitivity of 89% and a specificity of 91% for the detection of SVT (interobserver agreement κ = 0.76). In high-quality sECG recordings (68%), sensitivity rose to 95% with a specificity of 92% (interobserver agreement of κ = 0.91). Specificity increased to 96% when both electrophysiologists agreed on the diagnosis. Respective 12-lead ECG had a sensitivity of 100% and specificity of 98% for the detection of SVT., Conclusion: A smartphone-based one-lead ECG monitor allows for differentiation of SVT from IST in about 90% of cases. These results should encourage cardiologists to integrate wearables into clinical practice, possibly reducing time to definitive diagnosis of an arrhythmia and unnecessary EP procedures. A smartphone-based one lead ECG device (panel A) can be used reliably to differentiate supraventricular tachycardia (panel B) from inappropriate sinus tachycardia when compared to a simultaneously conducted gold-standard electrophysiology study (panels C, D).

Aim: The subcutaneous ICD (S-ICD) has evolved to a potential first option for many patients who have to be protected from sudden cardiac death. Many trials have underlined a similar performance regarding its effectiveness in relation to transvenous ICDs and have shown the expected benefits concerning infective endocarditis and lead failure. However, there have also been problems due to the peculiarities of the device, such as oversensing and myopotentials. In this study, we present patients from a large tertiary centre suffering from complications with an S-ICD and propose possible solutions., Methods and Results: All S-ICD patients who experienced complications related to the device (n = 40) of our large-scale single-centre S-ICD registry (n = 351 patients) were included in this study. Baseline characteristics, complications occurring and solutions to these problems were documented over a mean follow-up of 50 months. In most cases (n = 23), patients suffered from oversensing (18 cases with T wave or P wave oversensing, 5 due to myopotentials). Re-programming successfully prevented further oversensing episode in 13/23 patients. In 9 patients, generator or lead-related complications, mostly due to infectious reasons (5/9), occurred. Further problems consisted of ineffective shocks in one patient and need for antibradycardia stimulation in 2 patients and indication for CRT in 2 other patients. In total, the S-ICD had to be extracted in 10 patients. 7 of them received a tv-ICD subsequently, 3 patients refused re-implantation of any ICD. One other patient kept the ICD but had antitachycardic therapy deactivated due to inappropriate shocks for myopotential oversensing., Conclusion: The S-ICD is a valuable option for many patients for the prevention of sudden cardiac death. Nonetheless, certain problems are immanent to the S-ICD (limited re-programming options, size of the generator) and should be addressed in future generations of the S-ICD.

Background: The benefits of de novo cardiac resynchronization therapy (CRT) in patients with QRS-prolongation and impaired left-ventricular function (LVEF) are well established. Current guidelines also recommend CRT-upgrade in patients requiring permanent or frequent right ventricular pacing (RVP) with symptomatic heart failure and reduced LVEF. Whereas several predictors of response to de novo CRT-implantation such as female gender, QRS-duration, non-ischemic cardiomyopathy (NICM) are known due to large prospective trials, similar factors regarding CRT-upgrade are currently lacking., Methods and Results: We examine 114 patients 3-6 months after CRT-upgrade due to frequent RVP (> 50%) and symptomatic heart failure. Response to CRT was evaluated by improvement in NYHA class referring to the Minnesota Living With Heart Failure Questionnaire. Only cardiomyopathy type and use of Angiotensin-converting-enzyme (ACE) inhibitor had an impact on response to CRT-upgrade in a linear regression model. Patients with NICM presented a greater responder rate than patients with ischemic cardiomyopathy (ICM) (80.4 vs. 60.3%, p < 0.05). Other traditional response predictors in de novo CRT recipients (e.g. QRS-width, female gender) showed no effect on CRT-response in this cohort., Conclusion: Only underlying heart disease (NICM vs. ICM) and the use of ACE inhibitor were significant predictors of response to CRT-upgrade. In contrast to de novo CRT-recipients, where pre-implant QRS-duration is a key predictor, QRS-duration during RV-pacing has no significant impact on CRT-response in this cohort.

Fortunately, the population of adults with congenital heart disease (ACHD) is growing due to improved operation techniques. Life expectancy is continuously rising, nevertheless, sudden cardiac death is one of the leading causes of mortality in ACHD late after initial diagnosis. Risk stratification in ACHD remains challenging as large study results are missing, congenital defects and operation methods differ considerably between individual patients and results from acquired heart diseases are often not conferrable. The purpose of this narrative review is to objectively summarize the current knowledge on arrhythmogenic risk of ACHD and to give an overview on implantable cardioverter-defibrillator (ICD) therapy in this collective. Remarkable progress has been made in electrophysiological understanding of critical areas of slow conduction especially in patients with Tetralogy of Fallot (ToF). In patients with transposition of the great arteries after atrial baffling (Mustard/Senning procedure) atrial arrhythmias play a crucial role in sudden cardiac death. ICD therapy in ACHD may pose special technical challenges due to limited access for intracardiac leads. The introduction of the totally subcutaneous ICD improved therapeutic options for ACHD especially when contraindications for transvenous leads are present. Risk stratification in ACHD has to be seen as a team approach, requires thorough understanding of congenital heart defects and the operation techniques and needs unconventional technical approaches in some cases., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/cdt-20-633). The series “Current Management Aspects in Adult Congenital Heart Disease (ACHD): Part III” was commissioned by the editorial office without any funding or sponsorship. Dr. HB reports other from Edwards Lifesciences, other from Actelion, outside the submitted work. The authors have no other conflicts of interest to declare., (2021 Cardiovascular Diagnosis and Therapy. All rights reserved.)