Search

Purpose: Reflex syncope is a burdensome disease with considerable repercussions on the quality of life. Tilt training is a therapeutic option, but evidence on this topic is scarce and outdated. Hyperventilation is oftentimes associated with reflex syncope. This study aimed to evaluate the effectiveness of tilt training in patients with reflex syncope and study the association between reflex syncope and hyperventilation., Methods: Patients referred for tilt training after a positive tilt test from July 2014 to March 2021 were included in a single-center, retrospective registry. Demographic characteristics and outcomes of the program were collected. The response of tilt training on (pre)syncope recurrence and the association with hyperventilation were studied., Results: A total of 173 patients were included. The median age was 27 [17-48] years. Patients needed 2 [1-3] sessions to reach the first negative tilt training. The tilt training program was successfully completed by 65% of patients. An additional 3% reported no complaints in daily life, despite remaining symptomatic during tilt training. Another therapy was initiated in 10% of patients, while 21% dropped out of the tilt training. Presyncope recurred in 21% of patients during a follow-up period of 21 months [16-23]. Concomitant hyperventilation was suspected in 24%. Among these patients, 74% were referred for a hyperventilation provocation test, which confirmed the diagnosis in 82%., Conclusion: We report a reasonable success of tilt training in a contemporary cohort of patients. In patients completing the tilt training program, presyncope, and syncope recurrence was low. Concomitant hyperventilation seems prevalent in patients with reflex syncope and warrants specific attention and treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hornikx, Haemers, Stans, Robyns, Garweg, Ector, Vandenberk and Willems.)

Aims: In cardiac device implantation, having both surgical skills and ability to manipulate catheter/lead/wire is crucial. Few cardiologists, however, receive formal surgical training prior to implanting. Skills are mostly acquired directly on-the-job and surgical technique varies across institutions; suboptimal approaches may increase complications. We investigated how novel proficiency-based progression (PBP) simulation training impacts the surgical quality of implantations, compared to traditional simulation (SIM) training., Methods and Results: In this international prospective study, novice implanters were randomized (blinded) 1:1 to participate in a simulation-based procedure training curriculum, with proficiency demonstration requirements for advancing (PBP approach) or without (SIM). Ultimately, trainees performed the surgical tasks of an implant on a porcine tissue that was video-recorded and then scored by two independent assessors (blinded to group), using previously validated performance metrics. Primary outcomes were the number of procedural Steps Completed, Critical Errors, Errors (non-critical), and All Errors Combined. Thirty novice implanters from 10 countries participated. Baseline experiences were similar between groups. Compared to SIM-trained, the PBP-trained group completed on average 11% more procedural Steps (P < 0.001) and made 61.2% fewer Critical Errors (P < 0.001), 57.1% fewer Errors (P = 0.140), and 60.7% fewer All Errors Combined (P = 0.001); 11/15 (73%) PBP trainees demonstrated the predefined target performance level vs. 3/15 SIM trainees (20%) in the video-recorded performance., Conclusion: Proficiency-based progression training produces superior objectively assessed novice operators' surgical performance in device implantation compared with traditional (simulation) training. Systematic PBP incorporation into formal academic surgical skills training is recommended before in vivo device practice. Future studies will quantify PBP training's effect on surgery-related device complications., Competing Interests: Conflict of interest: J.M. conducted the present research project as part of his PhD studies at KU Leuven, Belgium. J.M. is also an employee of Medtronic. M.S. reports personal fees (honoraria for educational activity) from Medtronic during the conduct of the project and personal fees from Biotronik outside the submitted work; A.P. reports personal fees (honoraria for educational activity) from Medtronic during the conduct of the project; L.M. reports grants and personal fees (support for Fellowship programme, research grants, consulting honoraria) from Medtronic, Abbott, and Boston Scientific during the conduct of the project; A.R. reports teaching honoraria from Medtronic outside the submitted work; H.R. reports personal fees (honoraria for educational activity) from Medtronic during the conduct of the project and outside the submitted work; C.G. reports research funding from Abbott, Biotronik, and Medtronic, and speaker/consultancy fees from Medtronic, Biotronik, and Abbott outside the submitted work; A.G.G. reports personal fees (consulting) from Medtronic during the conduct of the project; T.V. reports personal fees (lectures honoraria) from Medtronic outside the submitted work., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The second generation of transcatheter pacing systems, called Micra AV, can provide atrioventricular (AV) synchronous pacing via a new pacing algorithm relying on sensing mechanical atrial contraction. Several novel programming parameters were introduced to enable AV synchronous pacing, including an A3 window and A4 window as well as a conduction mode switch and an activity mode switch. In addition to several automated features, manual programming optimization of some of the novel parameters is key to improving AV synchrony. A solid knowledge of the features and their programming is essential for electrophysiologists implanting or following patients with Micra AV devices. Differences in programming optimization might partially explain the high variability of AV synchrony published in real-world data reports. This article reviews the key programming parameters of Micra AV. Subsequently, optimal programming recommendations for defined patient profiles are presented. Those were established by consensus within an expert panel comprised of 11 European electrophysiologists from high-volume Micra AV centres. The patient profiles were (1) high degree AV block and slow sinus rhythm; (2) high degree AV block and fast sinus rhythm; and (3) intermittent AV block. The panel recommended to evaluate the mechanical atrial activity on transthoracic echocardiography prior to implant. It was also agreed that Auto A3 Threshold and Tracking Check should be turned off in all patients, AV conduction mode switch should be turned off in all patients with high degree AV block, and the lower rate should be programmed to 50 bpm with exceptions based on individual clinical assessment. Future studies will be useful to evaluate the strength of those recommendations to improve the AV synchrony., Competing Interests: Conflict of interest: C.G. receives consultant and/or speaker fees and research grants from Abbot, Biotronik, and Medtronic. A.B. has received consultant and/or speaker fees from Abbott, Bayer Healthcare, Biosense Webster, Biotronik, Boston Scientific, Bristol-Myers Squibb, Cook Medical, Daiichi Sankyo, Medtronic, Pfizer, and Spectranetics/Philips. N.C. receives consulting fees from Medtronic. C.D.A. received research grants from Biotronik, Medtronic, Abbott, LivaNova, Boston Scientific, AtriCure, Philips, and Acutus; and received compensation for teaching purposes and proctoring from Medtronic, Abbott, Biotronik, Livanova, Boston Scientific, Atricure, Acutus Medical, and Daiichi Sankyo. J.B.J. receives consulting fees from Medtronic. T.R. receives research grants from the Swiss National Science Foundation, the Swiss Heart Foundation, and the Sitem Insel support fund; speaker/consulting honoraria or travel support from Abbott/SJM, Bayer, Biosense Webster, Biotronik, Boston Scientific, Daiichi Sankyo, Farapulse, Medtronic, and Pfizer-BMS; support for the institution’s fellowship programme from Abbott/SJM, Biosense Webster, Biotronik, Boston Scientific, and Medtronic. All remaining authors have declared no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Left bundle branch pacing (LBBP) has been shown to better maintain electrical synchrony compared with right ventricular pacing (RVP), but little is known about its impact on mechanical synchrony. This study investigates whether LBBP better preserves left ventricular (LV) mechanical synchronicity and function compared with RVP., Methods and Results: Sixty patients with pacing indication for bradycardia were included: LBBP (n = 31) and RVP (n = 29). Echocardiography was performed before and shortly after pacemaker implantation and at 1-year follow-up. The lateral wall-septal wall (LW-SW) work difference was used as a measure of mechanical dyssynchrony. Septal flash, apical rocking, and septal strain patterns were also assessed. At baseline, LW-SW work difference was small and similar in two groups. SW was markedly decreased, while LW work remained mostly unchanged in RVP, resulting in a larger LW-SW work difference compared with LBBP (1253 ± 687 mmHg·% vs. 439 ± 408 mmHg·%, P < 0.01) at last follow-up. In addition, RVP more often induced septal flash or apical rocking and resulted in more advanced strain patterns compared with LBBP. At 1 year follow-up, LV ejection fraction (EF) and global longitudinal strain (GLS) were more decreased in RVP compared with LBBP (ΔLVEF: -7.4 ± 7.0% vs. 0.3 ± 4.1%; ΔLVGLS: -4.8 ± 4.0% vs. -1.4 ± 2.5%, both P < 0.01). In addition, ΔLW-SW work difference was independently correlated with LV adverse remodelling (r = 0.42, P < 0.01) and LV dysfunction (ΔLVEF: r = -0.61, P < 0.01 and ΔLVGLS: r = -0.38, P = 0.02)., Conclusion: LBBP causes less LV mechanical dyssynchrony than RVP as it preserves a more physiologic electrical conduction. As a consequence, LBBP appears to preserve LV function better than RVP., Competing Interests: Conflict of interests: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Importance: In cardiac device implant training, there is no common system to objectively assess trainees' ability to perform tasks at predetermined performance levels before in vivo practice; therefore, patients are potentially exposed to risks related to operators' early learning curve., Objective: To assess the effect on implant performance quality of novel metrics-based simulation training to proficiency (proficiency-based progression [PBP]) vs traditional simulation-based training (SBT)., Design, Setting, and Participants: In this prospective randomized trial, conducted between March 8, 2022 and November 24, 2022, novice implanters were randomized (blinded) 1:1 to participate in an SBT curriculum (procedural knowledge e-learning and in-person simulation training) at an international skills training center, with proficiency demonstration requirements at each training stage for advancing (PBP approach) or without the requirements. Ultimately, trainees performed a cardiac resynchronization therapy (CRT) implant using virtual reality simulation. The procedure was video-recorded and subsequently scored using previously validated metrics by 2 independent assessors blinded to group. Physicians who had already implanted more than 20 pacemakers or defibrillators and fewer than 200 CRT systems as the first operator were eligible. Thirty-two implanters from 10 countries voluntarily enrolled in the training program and were randomized; 30 (15 per group) started and completed training. Data analysis was performed from November 27 to December 22, 2022., Intervention: Training with PBP vs SBT., Main Outcome and Measures: The primary outcome comprised 4 objectively assessed performance metrics derived from the video-recordings: number of procedural steps completed, errors, critical errors, and all errors combined., Results: Baseline experience of the 30 participants (19 [63%] male; mean [SD] number of years in implant practice, 2.0 [1.8]; median [IQR] number of implanted pacemakers or defibrillators, 47.5 [30.0-115.0]; median [IQR] number of implanted CRT systems, 3.0 [1.25-10.0]) was similar between study groups. Compared with the SBT group, the PBP group completed 27% more procedural steps (median [IQR], 31 [30-32] vs 24 [22-27]; P < .001) and made 73% fewer errors (median [IQR], 2 [1-3] vs 7 [5-8]; P < .001), 84% fewer critical errors (median [IQR], 1 [0-1] vs 3 [3-5]; P < .001), and 77% fewer all errors combined (errors plus critical errors) (median [IQR], 3 [1-3] vs 11 [8-12]; P < .001); 14 of the 15 PBP trainees (93%) demonstrated the predefined target performance level vs 0 of the 15 SBT trainees., Conclusions and Relevance: In this randomized trial, the PBP approach to novice implanter training generated superior objectively assessed performance vs SBT. If implemented broadly and systematically, PBP training may ensure safe and effective performance standards before trainees proceed to (supervised) in vivo practice. Future studies are needed to verify implications on procedure-related patient complications., Trial Registration: ClinicalTrials.gov Identifier: NCT05952908.

Aims: Diagnosis of Long QT syndrome (LQTS) is based on prolongation of the QT interval corrected for heart rate (QTc) on surface ECG and genotyping. However, up to 25% of genotype positive patients have a normal QTc interval. We recently showed that individualized QT interval (QTi) derived from 24 h holter data and defined as the QT value at the intersection of an RR interval of 1,000 ms with the linear regression line fitted through QT-RR data points of each individual patient was superior over QTc to predict mutation status in LQTS families. This study aimed to confirm the diagnostic value of QTi, fine-tune its cut-off value and evaluate intra-individual variability in patients with LQTS., Methods: From the Telemetric and Holter ECG Warehouse, 201 recordings from control individuals and 393 recordings from 254 LQTS patients were analysed. Cut-off values were obtained from ROC curves and validated against an in house LQTS and control cohort., Results: ROC curves indicated very good discrimination between controls and LQTS patients with QTi, both in females (AUC 0.96) and males (AUC 0.97). Using a gender dependent cut-off of 445 ms in females and 430 ms in males, a sensitivity of 88% and specificity of 96% were achieved, which was confirmed in the validation cohort. No significant intra-individual variability in QTi was observed in 76 LQTS patients for whom at least two holter recordings were available (483 ± 36 ms vs. 489 ± 42 ms, p  = 0.11)., Conclusions: This study confirms our initial findings and supports the use of QTi in the evaluation of LQTS families. Using the novel gender dependent cut-off values, a high diagnostic accuracy was achieved., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor JE is currently organizing a Research Topic with the author BV., (© 2023 Robyns, Nuyens, Vandenberk, Haemers, Breckpot, Garweg, Ector and Willems.)

Background: While prior Micra trials demonstrated a high implant success rate and favorable safety and efficacy results, changes in implant populations and safety over time is not well studied. The objective of this analysis was to report the performance of Micra in European and Middle Eastern patients and compare to the Micra Investigational Device Exemption (IDE) and Micra Post Approval Registry (PAR) studies., Methods: The prospective, single-arm Micra Acute Performance European and Middle Eastern (MAP EMEA) registry was designed to further study the performance of Micra in patients from EMEA. The primary endpoint was to characterize acute (30-day) major complications. Electrical performance was analyzed. The major complication rate through 12 months was compared with the IDE and PAR studies., Results: The MAP EMEA cohort ( n  = 928 patients) had an implant success rate of 99.9% and were followed for an average of 9.7 ± 6.5 months. Compared to prior studies, MAP EMEA patients were more likely to have undergone dialysis and have a condition which precluded the use of a transvenous pacemaker ( p  < .001). Within 30 days of implantation, the MAP EMEA cohort had a major complication rate of 2.59%. Mean pacing thresholds were low and stable through 12 months (0.61 ± 0.40 V at 0.24 ms at implant and 12 months). Through 12 months post-implantation, the major complication rate for MAP EMEA was not significantly different from IDE ( p  = .56) or PAR ( p  = .79)., Conclusion: Despite patient differences over time, the Micra leadless pacemaker was implanted with a high success rate and low complication rate, in-line with prior reports., Competing Interests: Dr. Roberts reports having received honoraria from Medtronic, Inc and Boston Scientific. Dr. Clémenty reports having received consulting fees from Medtronic, Inc; Dr. Winter reports having received lecture fees from ZOLL‐CMS Germany, Medtronic, Inc. and Biotronik. Mr. Anderson, Mrs. Pol and Dr. Butler report being employees and shareholders of Medtronic, Inc. Dr. Garweg reports receiving consultant fees from Medtronic, Inc. The remaining authors have nothing to disclose., (© 2023 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of Japanese Heart Rhythm Society.)

Aims: There is limited information on what clinical factors are associated with the development of pericardial effusion after leadless pacemaker implantation. We sought to determine predictors of and to develop a risk score for pericardial effusion in patients undergoing Micra leadless pacemaker implantation attempt., Methods and Results: Patients (n = 2817) undergoing implant attempt from the Micra global trials were analysed. Characteristics were compared between patients with and without pericardial effusion (including cardiac perforation and tamponade). A risk score for pericardial effusion was developed from 18 pre-procedural clinical variables using lasso logistic regression. Internal validation and future prediction performance were estimated using bootstrap resampling. The scoring system was also externally validated using data from the Micra Acute Performance European and Middle East (MAP EMEA) registry. There were 32 patients with a pericardial effusion [1.1%, 95% confidence interval (CI): 0.8-1.6%]. Following lasso logistic regression, 11 of 18 variables remained in the model from which point values were assigned. The C-index was 0.79 (95% CI: 0.71-0.88). Patient risk score profile ranged from -4 (lowest risk) to 5 (highest risk) with 71.8% patients considered low risk (risk score ≤0), 16.6% considered medium risk (risk score = 1), and 11.7% considered high risk (risk score ≥2) for effusion. The median C-index following bootstrap validation was 0.73 (interquartile range: 0.70-0.75). The C-index based on 9 pericardial effusions from the 928 patients in the MAP EMEA registry was 0.68 (95% CI: 0.52-0.83). The pericardial effusion rate increased significantly with additional Micra deployments in medium-risk (P = 0.034) and high-risk (P < 0.001) patients., Conclusion: The overall rate of pericardial effusion following Micra implantation attempt is 1.1% and has decreased over time. The risk of pericardial effusion after Micra implant attempt can be predicted using pre-procedural clinical characteristics with reasonable discrimination., Clinical Trial Registration: The Micra Post-Approval Registry (ClinicalTrials.gov identifier: NCT02536118), Micra Continued Access Study (ClinicalTrials.gov identifier: NCT02488681), and Micra Transcatheter Pacing Study (ClinicalTrials.gov identifier: NCT02004873)., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Mitral valve prolapse (MVP) causes left ventricular (LV) remodelling even in the absence of significant mitral regurgitation. To evaluate whether apical insertion of the papillary muscle (PM) influences the pattern and severity of MVP-related LV remodelling., Methods and Results: All MVP patients who underwent CMR at our institution between December 2008 and December 2019 were included, thoroughly reviewed and grouped according to apical/non-apical PM insertion. Apical PM insertion was found in 53/92 patients (58%) and associated with mitral leaflet thickening (P < 0.01) and a trend towards higher prevalence of mitral annular disjunction (P = 0.05). Whereas no differences in ventricular volumes or ejection fraction were found, patients with apical PM insertion showed more lateral wall remodelling with mid lateral wall thinning [2.1 (1.8-2.5) vs. 4.0 (3.5-5.0) mm, P < 0.01], increased LV eccentricity and a lower GCS at this level (15 ± 3% vs. 20 ± 3%, P < 0.01). In long-axis direction, increased end-diastolic mid lateral wall angulation was found (i.e. angle <155° measured in the thinnest point of the mid lateral wall in four-chamber view) with a higher angle variation during systole (25 ± 11° vs. 17 ± 8°, P < 0.01). Remarkably, PM fibrosis was significantly more frequent in patients with apical PM insertion (i.e. 66% vs. 28%, P < 0.01). Finally, a higher burden of premature ventricular complexes (>5%) and non-sustained ventricular tachyarrhythmias was found in patients with apical PM insertion: 53% vs. 25% (P = 0.04) and 38% vs. 18% (P = 0.04), respectively., Conclusion: Apical PM insertion is part of the phenotypic spectrum of MVP, impacts significantly LV remodelling, and potentially may be related to increased ventricular arrhythmogenicity., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Objectives: This study sought to formulate a predictive model for describing the long-term electrical performance of Micra (Medtronic, Mounds View, Minnesota)., Background: The Micra leadless pacemaker is an alternative ventricular pacing option that avoids the pitfalls of transvenous leads. However, well-defined metrics to predict the long-term electrical performance of the device are lacking., Methods: We identified all patients who underwent successful Micra implantation enrolled in the investigational device exemption study, continued access study, or post-approval registry with complete 1-year post-implantation data or system revision due to elevated thresholds (N = 1,843). The analysis endpoint was an elevated pacing capture threshold (PCT) at ≥12 months post-implantation, defined as ≥2.0 V at 0.24 ms or an increase of ≥1.5 V from implantation or need for system revision due to elevated thresholds at ≤12 months post-implantation. We evaluated for univariate and multivariate associations between patient and device characteristics at implantation and for elevated thresholds at 12 months., Results: Among the total cohort, 75 patients (4.1%) had elevated thresholds at 12 months; of these, 13 required system revisions. Predictors associated with elevated thresholds in univariate analysis included the total number of deployments (excluded from the multivariable model), impedance and PCT at implantation, male sex, history of diabetes, and ischemic cardiomyopathy. Multivariable regression modeling found that male sex, history of diabetes, implantation PCT of ≥2 V, and impedance of <800 Ω were independent predictors of elevated PCT at 12 months (all p < 0.05)., Conclusion: A history of diabetes, male sex, elevated PCT, and low impedance at implantation were independent predictors of elevated thresholds at 12 months. These metrics represent the foundation of a simple tool to aid in procedural decision making., Competing Interests: Funding Support and Author Disclosures Ms. Wallace is an employee and shareholder of Medtronic. Mr. Stromberg is an employee and shareholder of Medtronic. Dr. Piccini is supported by R01HL128595 from the National Heart, Lung, and Blood Institute; receives grants for clinical research from Abbott, the American Heart Association, Association for the Advancement of Medical Instrumentation, Bayer, Boston Scientific, and Philips; and serves as a consultant to Abbott, Allergan, ARCA Biopharma, Biotronik, Boston Scientific, LivaNova, Medtronic, Milestone, Myokardia, Sanofi, Philips, and UpToDate. Dr. Roberts has received honoraria from Medtronic. Dr. El-Chami has served as a consultant for Medtronic and Boston Scientific. Dr. Soejima has received honoraria for lecturing with Medtronic, Japan and Abbott, Japan. Dr. Garweg has received research funding from Biotronik, Boston Scientific, and Medtronic; and has received speaker fees and consultancy fees from Medtronic; Boston Scientific, and Biotronik. Dr. Fagan is an employee and shareholder of Medtronic. Dr. Lloyd has provided consulting and research support to Medtronic; and has provided research support to Boston Scientific. Dr. Kiani has reported that he has no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Permanent pacing is common after valve intervention. The presence of a conventional pacemaker in this population is recognized as a risk factor for infectious events. Therefore, a leadless pacing system could be the preferred strategy when permanent pacing is required after valve intervention., Aim: To report periprocedural outcomes and follow-up of patients undergoing implantation of a leadless pacing system after valve intervention., Methods: Patients with previous valve intervention at the time of attempted implantation of a leadless pacemaker (Micra™, Medtronic, Minneapolis, MN, USA) were included, and were compared with a control group (patients also implanted with Micra™ without valve intervention)., Results: Among a total of 170 Micra™ implantation procedures, 54 patients (31.8%) had a history of valve intervention: 28 after aortic valve replacement; 10 after mitral valve replacement; one after single tricuspid valvuloplasty; and 15 after multiple valve surgery. Median age of the patients was 82.5 (77.0-86.0) years and 53.7% were male. Patients with previous valve intervention had a higher incidence of arterial hypertension (P=0.014) and ischaemic heart disease (P=0.040). The primary indications for permanent pacing after valve intervention were high-degree atrioventricular block (59.3%) and atrial fibrillation with bradycardia (27.8%). Micra™ was successfully implanted in all patients (n=170) without any procedure-related major complications. During a median follow-up of 12 months, electrical performance was excellent and similar in both groups. Also, a similar reduction in left ventricular ejection fraction was observed at 12 months in both groups, which was correlated with the percentage of right ventricular pacing., Conclusion: A leadless pacemaker is safe and efficient after valve intervention, and therefore represents an effective pacing option in patients after valve intervention., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background: Atrioventricular nodal reentrant tachycardia (AVNRT) is a common supraventricular arrhythmia that is frequently encountered in an otherwise healthy patient population. Recent guidelines of the European Society of Cardiology underline the role of catheter ablation in the long-term management of these patients., Case Summary: This case describes the clinical presentation and treatment options in a patient with typical slow/fast AVNRT, the most common subform of AVNRT, where antegrade conduction occurs over the slow pathway and retrograde conduction over the fast pathway. The ablation strategy in these patients is illustrated based on intracardiac recordings in combination with per-procedural three-dimensional imaging., Discussion: Atrioventricular nodal reentrant tachycardia is a common arrhythmia with good prognosis but significant impact on quality of life of affected patients. Catheter ablation should be considered early as it can be performed safely and with a very high success rate., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: This study reports on the performance of a leadless ventricular pacemaker with automated, enhanced accelerometer-based algorithms that provide atrioventricular (AV) synchronous pacing., Background: Despite many advantages, leadless pacemakers are currently only capable of single-chamber ventricular pacing., Methods: The prospective MARVEL 2 (Micra Atrial tRacking using a Ventricular accELerometer 2) study assessed the performance of an automated, enhanced accelerometer-based algorithm downloaded to the Micra leadless pacemaker for up to 5 h in patients with AV block. The primary efficacy objective was to demonstrate the superiority of the algorithm to provide AV synchronous (VDD) pacing versus VVI-50 pacing in patients with sinus rhythm and complete AV block. The primary safety objective was to demonstrate that the algorithm did not result in pauses or heart rates of >100 beats/min., Results: Overall, 75 patients from 12 centers were enrolled; an accelerometer-based algorithm was downloaded to their leadless pacemakers. Among the 40 patients with sinus rhythm and complete AV block included in the primary efficacy objective analysis, the proportion of patients with ≥70% AV synchrony at rest was significantly greater with VDD pacing than with VVI pacing (95% vs. 0%; p < 0.001). The mean percentage of AV synchrony increased from 26.8% (median: 26.9%) during VVI pacing to 89.2% (median: 94.3%) during VDD pacing. There were no pauses or episodes of oversensing-induced tachycardia reported during VDD pacing in all 75 patients., Conclusions: Accelerometer-based atrial sensing with an automated, enhanced algorithm significantly improved AV synchrony in patients with sinus rhythm and AV block who were implanted with a leadless ventricular pacemaker. (Micra Atrial Tracking Using a Ventricular Accelerometer 2 [MARVEL 2]; NCT03752151)., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: Prolonged participation in exercise results in structural and electrical cardiac remodelling. The development of an athlete's heart is recognized as a risk factor for atrial arrhythmias. This study aims to evaluate the impact of athlete heart remodelling on the presentation of atrioventricular nodal re-entrant tachycardia (AVNRT)., Methods and Results: A retrospective analysis of an ablation database selecting all patients with an electrophysiologically confirmed diagnosis of AVNRT. Athletes (individuals participating in moderate to intensive sports for ≥3 h per week having done so for ≥5 years) were compared with healthy non-athletes. Atrioventricular nodal re-entrant tachycardia subforms were classified according the methods described by Katritsis and Josephson in 2013 and by Heidbuchel and Jackman in 2014. A total of 504 AVNRT patients were fully characterized, of whom 85 (17%) were athletes. Almost half of the athletes presented with atypical forms of AVNRT, where in non-athletes this frequency was about 20%. There was no difference in acute procedural success among the two groups, but the procedures in athletes were more complex, as reflected by an almost two-fold increase in the use of a long sheath to reach the slow pathway ablation area and a higher recurrence rate in athletes (10% vs. 4%)., Conclusion: Athletes present more frequently with atypical subforms of AVNRT. This is possibly related to cardiac remodelling with dilatation of the cardiac cavities leading to changed conduction properties in the septal area. Ablation outcome is equally safe in athletes as in non-athletes with similar acute success rates. Athletes experience a higher longer-term recurrence rate., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Objectives: This study sought to report periprocedural outcomes and intermediate-term follow-up of hemodialysis patients undergoing Micra implantation., Background: Leadless pacemakers may be preferred in patients with limited vascular access and high-infection risk, such as patients on hemodialysis., Methods: Patients on hemodialysis at the time of Micra implantation attempt (n = 201 of 2,819; 7%) from the Micra Transcatheter Pacing Study investigational device exemption trial, Micra Transcatheter Pacing System Continued Access Study Protocol, and Micra Transcatheter Pacing System Post-Approval Registry were included in the analysis. Baseline characteristics, periprocedural outcomes, and intermediate-term follow-up were summarized., Results: Patients on hemodialysis at the time of Micra implantation attempt were on average 70.5 ± 13.5 years of age and 59.2% were male. The dialysis patients commonly had hypertension (80%), diabetes (61%), coronary artery disease (39%), and congestive heart failure (27%), and 72% had a condition that the implanting physician felt precluded the use of a transvenous pacemaker. Micra was successfully implanted in 197 patients (98.0%). Reasons for unsuccessful implantation included inadequate thresholds (n = 2) and pericardial effusion (n = 2). The median implantation time was 27 min (interquartile range: 20 to 39 min). There were 3 procedure-related deaths: 1 due to metabolic acidosis following a prolonged procedure duration in a patient undergoing concomitant atrioventricular nodal ablation and 2 deaths occurred in patients who needed surgical repair after perforation. Average follow-up was 6.2 months (range 0 to 26.7 months). No patients had a device-related infection or required device removal because of bacteremia., Conclusions: Leadless pacemakers represent an effective pacing option in this challenging patient population on chronic hemodialysis. The risk of infection appears low with an acceptable safety profile. (Micra Transcatheter Pacing Study; NCT02004873; Micra Transcatheter Pacing System Continued Access Study Protocol; NCT02488681; Micra Transcatheter Pacing System Post-Approval Registry; NCT02536118)., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Sudden cardiac death (SCD) results from a complex interplay of abnormalities in autonomic function, myocardial substrate and vulnerability. We studied whether a combination of noninvasive risk stratification tests reflecting these key players could improve risk stratification., Methods: Patients implanted with an ICD in whom 24-hr holter recordings were available prior to implant were included. QRS fragmentation (fQRS) was selected as measure of myocardial substrate and a high ventricular premature beat count (VPB >10/hr) for arrhythmic vulnerability. From receiver operating characteristics analysis, detrended fluctuation analysis (DFA), turbulence slope, and deceleration capacity were selected for autonomic function. Adjusted Cox regression analysis with comparison of C-statistics was performed to predict first appropriate shock (AS) and total mortality., Results: A total of 220 patients were included in the analysis with an overall follow-up of 4.3 ± 3.1 years. A model including VPB >10/hr, inferior fQRS, and abnormal nonedited DFA was the best for prediction of AS after 1 year of follow-up with a trends toward improvement of the C-statistics compared to baseline (p = 0.055). The risk increased significantly with every abnormal test (HR 1.793, 95%CI 1.255-2.564). A model including fQRS in any region and abnormal edited DFA was the best for prediction of mortality after 3 years of follow-up with significant improvement of the C-statistics (p = 0.023). Each abnormal test was associated with a significant increase in mortality (HR 5.069, 95%CI 1.978-12.994)., Conclusion: Combining noninvasive risk stratification tests according to their physiological background can improve the risk prediction of SCD and mortality., (© 2018 Wiley Periodicals, Inc.)

Background: Deranged energy metabolism contributes to the pathophysiology of heart failure (HF). Recent studies showed diminished free fatty acid (FFA) oxidation in experimental HF models with a shift towards oxidation of ketone bodies. However, conflicting clinical data on FFA metabolism and limited knowledge on ketone body metabolism in human HF mandate additional metabolic profiling studies. We, therefore, investigated cardiac uptake of FFAs and ketone bodies (β-hydroxybutyrate and acetoacetate) in patients with HF with reduced ejection fraction (HFrEF) or with aortic stenosis (AS)-induced left ventricular hypertrophy. We hypothesized that FFA oxidation is impaired in HFrEF and in AS and results in decreased concentrations of free carnitine, the necessary carrier for mitochondrial entry of activated FFAs, and in accumulation of metabolic intermediates., Methods and Results: We collected arterial and coronary sinus blood samples in patients with HFrEF (n=15), in AS patients with preserved systolic function (n=15), and in control patients (n=15). Plasma concentration gradients across the heart show significantly greater uptake of ketone bodies in patients with HFrEF than in controls. Patients with AS show significantly increased uptake of β-hydroxybutyrate and FFAs. Free carnitine concentration and concentration gradients of intermediates of FFA oxidation were comparable between groups., Conclusions: In conclusion, our results show significantly increased cardiac uptake of ketone bodies in patients with stable HFrEF and AS and increased uptake of FFAs in AS compared with control patients. The lack of myocardial release of acyl-carnitine species or change in free carnitine uptake suggests no impairment of FFA oxidation.

Introduction: Loss-of-function (LoF) mutations in the SCN5A gene cause multiple phenotypes including Brugada Syndrome (BrS) and a diffuse cardiac conduction defect. Markers of increased risk for sudden cardiac death (SCD) in LoF SCN5A mutation carriers are ill defined. We hypothesized that late potentials and fragmented QRS would be more prevalent in SCN5A mutation carriers compared to SCN5A-negative BrS patients and evaluated risk markers for SCD in SCN5A mutation carriers., Methods: We included all SCN5A loss-of-function mutation carriers and SCN5A-negative BrS patients from our center. A combined arrhythmic endpoint was defined as appropriate ICD shock or SCD., Results: Late potentials were more prevalent in 79 SCN5A mutation carriers compared to 39 SCN5A-negative BrS patients (66% versus 44%, p = .021), while there was no difference in the prevalence of fragmented QRS. PR interval prolongation was the only parameter that predicted the presence of a SCN5A mutation in BrS (OR 1.08; p < .001). Four SCN5A mutation carriers, of whom three did not have a diagnostic type 1 ECG either spontaneously or after provocation with a sodium channel blocker, reached the combined arrhythmic endpoint during a follow-up of 44 ± 52 months resulting in an annual incidence rate of 1.37%., Conclusion: LP were more frequently observed in SCN5A mutation carriers, while fQRS was not. In SCN5A mutation carriers, the annual incidence rate of SCD was non-negligible, even in the absence of a spontaneous or induced type 1 ECG. Therefore, proper follow-up of SCN5A mutation carriers without Brugada syndrome phenotype is warranted., (© 2018 Wiley Periodicals, Inc.)

Aims: The latest 2015 ESC Guidelines on the prevention of sudden cardiac death make a Class IIa recommendation for ICD implantation in patients listed for heart transplantation. This recommendation was based on expert consensus in view of the sparsity of data., Methods and Results: All patients listed for heart transplantation at the University Hospitals of Leuven from 2002 until 2014 were studied retrospectively. Exclusion criteria were age <16 years, cardiac disease other than ischaemic or dilated cardiomyopathy and re-transplantation. A total of 286 patients were included, of which 140 (49.0%) received an ICD. There was a historical increase of the time on the waiting list before transplantation (P < 0.001) together with an increase of the use of ICDs (P < 0.001) and left ventricular assist devices (LVADs) (P < 0.001). The proportion of patients reaching heart transplant remained unchanged (P = 0.700). The annual appropriate shock rate in patients with ICD was 28.0%/y on the active waiting list. Patients with ICD showed a trend to improved survival (P = 0.070). Independent predictors of mortality or removal from the transplant list because of clinical deterioration were the need for LVAD (HR 4.38, 95%CI 2.11-9.01), a history of stroke (HR 2.95, 95%CI 1.61-5.40), older age (HR 1.03, 95%CI 1.01-1.05) and a worse renal function (HR 1.15, 95%CI 1.00-1.33)., Conclusion: The time on the waiting list for heart transplantation significantly increased together with an increased use of device therapy in this population. The proportion of patients reaching transplant remained unchanged. This patient group is prone to life-threatening arrhythmias and the use of an ICD may improve survival.

Background: Drug safety precautions recommend monitoring of the corrected QT interval. To determine which QT correction formula to use in an automated QT-monitoring algorithm in our electronic medical record, we studied rate correction performance of different QT correction formulae and their impact on risk assessment for mortality., Methods and Results: All electrocardiograms (ECGs) in patients >18 years with sinus rhythm, normal QRS duration and rate <90 beats per minute (bpm) in the University Hospitals of Leuven (Leuven, Belgium) during a 2-month period were included. QT correction was performed with Bazett, Fridericia, Framingham, Hodges, and Rautaharju formulae. In total, 6609 patients were included (age, 59.8±16.2 years; 53.6% male and heart rate 68.8±10.6 bpm). Optimal rate correction was observed using Fridericia and Framingham; Bazett performed worst. A healthy subset showed 99% upper limits of normal for Bazett above current clinical standards: men 472 ms (95% CI, 464-478 ms) and women 482 ms (95% CI 474-490 ms). Multivariate Cox regression, including age, heart rate, and prolonged QTc, identified Framingham (hazard ratio [HR], 7.31; 95% CI, 4.10-13.05) and Fridericia (HR, 5.95; 95% CI, 3.34-10.60) as significantly better predictors of 30-day all-cause mortality than Bazett (HR, 4.49; 95% CI, 2.31-8.74). In a point-prevalence study with haloperidol, the number of patients classified to be at risk for possibly harmful QT prolongation could be reduced by 50% using optimal QT rate correction., Conclusions: Fridericia and Framingham correction formulae showed the best rate correction and significantly improved prediction of 30-day and 1-year mortality. With current clinical standards, Bazett overestimated the number of patients with potential dangerous QTc prolongation, which could lead to unnecessary safety measurements as withholding the patient of first-choice medication., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: Recently a new risk marker for drug-induced arrhythmias called index of cardio-electrophysiological balance (iCEB), measured as QT interval divided by QRS duration, was evaluated in an animal model. It was hypothesized that iCEB is equivalent to the cardiac wavelength λ (λ = effective refractory period (ERP) x conduction velocity) and that an increased or decreased value of iCEB would potentially predict an increased susceptibility to TdP or non-TdP mediated VT/VF, respectively., Methods: First, the correlation between QT interval and ERP was evaluated by invasively measuring ERP during a ventricular stimulation protocol in humans (N = 40). Then the effect of administration of sotalol and flecainide on iCEB was measured in 40 patients with supraventricular tachycardias. Finally iCEB was assessed in carriers of a long QT syndrome (LQTS, N = 70) or Brugada syndrome (BrS, N = 57) mutation and compared them with genotype negative family members (N = 65)., Results: The correlation between QT interval and ERP was established (Pearson R(2) = 0.25) which suggests that iCEB≈ERPxCV≈QT/QRS. Sotalol administration increased iCEB (+ 0.23; P = 0.01), while it decreased with the administration of flecainide (-0.21, P = 0.03). In the LQTS group iCEB was increased (5.22 ± 0.93, P < 0.0001) compared to genotype negative family members (4.24 ± 0.5), while it was decreased in the BrS group (3.52 ± 0.43, P < 0.0001)., Conclusions: Our data suggest that iCEB (QT/QRS) is a simple but effective ECG surrogate of cardiac wavelength. iCEB is increased in situations that predispose to TdP and is decreased in situations that predispose to non-TdP mediated VT/VF. Therefore, iCEB might serve as a noninvasive and readily measurable marker to detect increased arrhythmic risk., (© 2015 Wiley Periodicals, Inc.)

Aims: Interventional left ventricular (LV) procedures integrating static 3D anatomy visualization are subject to mismatch with dynamic catheter movements due to prominent LV motion. We aimed to evaluate the accuracy of a recently developed acquisition and post-processing protocol for low radiation dose LV multi-phase rotational angiography (4DRA) in patients., Methods and Results: 4DRA image acquisition of the LV was performed as investigational acquisition in patients undergoing left-sided ablation (11 men; BMI = 24.7 ± 2.5 kg/m²). Iodine contrast was injected in the LA, while pacing from the RA at a cycle length of 700 ms. 4DRA acquisition and reconstruction were possible in all 11 studies. Reconstructed images were post-processed using streak artefact reduction algorithms and an interphase registration-based filtering method, increasing contrast-to-noise ratio by a factor 8.2 ± 2.1. This enabled semi-automatic segmentation, yielding LV models of five equidistant phases per cardiac cycle. For evaluation, off-line 4DRA fluoroscopy registration was performed, and the 4DRA LV contours of the different phases were compared with the contours of five corresponding phases of biplane LV angiography, acquired in identical circumstances. Of the distances between these contours, 95% were <4 mm in both incidences. Effective radiation dose for 4DRA, calculated by patient-specific Monte-Carlo simulation, was 5.1 ± 1.1 mSv., Conclusion: Creation of 4DRA LV models in man is feasible at near-physiological heart rate and with clinically acceptable radiation dose. They showed high accuracy with respect to LV angiography in RAO and LAO. The presented technology not only opens perspectives for full cardiac cycle dynamic anatomical guidance during interventional procedures, but also for 3DRA without need for very rapid pacing., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Aims: The effective radiation dose (ED) of three-dimensional rotational angiography (3DRA) is 5-8 mSv, leading to reticence on its use. We evaluated the potential of 3DRA with a reduced number of frames (RNF) and a reduced dose per frame., Methods and Results: Three-dimensional rotational angiography was performed in 60 patients (52.5 ± 9.6 years, 16 females) referred for ablation in the right (RA; n = 10) and left atrium (LA; n = 50). In a simulation group (n = 20), the effect of dropping frames from a conventional 248 frames 3DRA LA acquisition was simulated. In a prospective group (n = 40), RNF 3DRA were acquired of LA (n = 30) and RA (n = 10) with 67 frames (0.24 Gy/frame) and 45 frames (0.12 μGy/frame), respectively. Accuracy was evaluated qualitatively and quantitatively. Effective radiation dose was determined by Monte Carlo simulation on every frame. In the simulation group, surface errors increased minimally and non-significantly when reducing frames from 248 to 124, 83, 62, 50, 42, and 31: 0.49 ± 0.51, 0.52 ± 0.46, 0.61 ± 0.49, 0.62 ± 0.47, 0.71 ± 0.48, and 0.81 ± 0.47 mm, respectively (Pearson coefficient 0.20). All 3D LA images were clinically useful, even with only 31 frames. In the prospective group, good or optimal 3D image quality was achieved in 80% of LA and all of RA reconstructions. These accurate models were obtained with ED of 2.6 ± 0.4 mSv for LA and 1.2 ± 0.5 mSv for RA., Conclusion: Three-dimensional rotational angiography is possible with a significant reduction in ED (to the level of prospectively gated cardiac computed X-ray tomography) without compromising image quality. Low-dose 3DRA could become the preferred online 3D imaging modality for pulmonary vein isolation and other anatomy-dependent ablations.

Aims: Current fluoroscopic and 3D image-guided treatment of atrial fibrillation (AF) by radiofrequency ablation is characterized by a substantial amount of X-ray radiation. We investigated the potential of an asymmetric collimation technique to reduce dose., Methods and Results: For 30 patients, referred for AF ablation, we determined the received fluoroscopy dose for various collimation scenarios: a single collimation window encompassing all veins as used in most labs (Sc 1), an optimal adjusted symmetric collimation window encompassing each two ipsilateral veins (Sc 2) or each individual vein (Sc 3) and an optimal asymmetric collimation window encompassing each two ipsilateral veins (Sc 4) or each individual vein (Sc 5). Twenty patients were studied retrospectively and 10 were studied prospectively. Total fluoroscopy effective dose for all collimation strategies amounted to 45 ± 31 mSv for a single collimation field (Sc 1), 36 ± 25 mSv (Sc 2), and 24 ± 14 mSv (Sc 3) for a symmetrically adjusted collimation window and 15 ± 10 (Sc 4) and 5 ± 3 mSv (Sc 5) for an asymmetrically adjusted collimation approach. Validation of symmetric (Sc 2) and asymmetric (Sc 4) collimation in 10 patients confirmed the retrospective analysis., Conclusions: Implementation and effective application of an optimal asymmetric collimation approach would yield an average three- to nine-fold reduction of fluoroscopy dose during AF ablation procedures. This reduction exceeds what has been previously reported by implementing an electromagnetic catheter tracking approach. Furthermore, it can be easily integrated in the clinical workflow with limited additional one-time cost. Manufacturers of imaging systems should consider its implementation a priority, and physicians should adopt it in their workflow.

Aims: Endurance sports activities have been associated with the development of atrial fibrillation (AF). Pulmonary vein isolation (PVI) by means of radiofrequency catheter ablation has been established as an effective treatment for AF. The aim of the present study was to analyse the efficacy of AF ablation in athletes., Methods and Results: We compared procedural outcome and median term follow-up in 94 consecutive athletes (>3 h of sports/week for ≥ 10 years or ≥ 1500 h lifetime) who underwent PVI (94% men, 51 ± 8 years, 87% paroxysmal AF, left atrial (LA) diameter 40 ± 8 mm, mean follow-up 41 months), and 41 contemporary controls. Sixty-three per cent of athletes performed endurance sports (running, cycling, swimming, and rowing). Documented focal induction of AF and failed treatment with ≥ 1 anti-arrhythmic drug were pre-requisites for selection of ablation treatment. Patients with long-standing persistent or permanent AF or an LA diameter ≥ 55 mm were not considered for ablation. Median lifetime cumulative hours of sports was 8638 (4175-13 688) in athletes vs. 450 (280-600) in controls (P < 0.001). Other baseline characteristics except for gender (94 vs. 66% men, respectively, P < 0.001) were comparable between both groups, as was the total number of ablation procedures per patient (1.2 ± 0.5, P = 0.62). Survival analysis showed similar AF recurrence rate after a first ablation for controls and endurance athletes, though non-endurance athletes had a significantly higher AF recurrence rate (48 vs. 46 vs. 34% freedom from AF at 3 year follow-up after a single ablation, P= 0.04). Final outcome after all ablations was similar (87 vs. 84 vs. 85% freedom from AF at 3-year follow-up, P = 0.88). No other independent predictor for AF recurrence was identified., Conclusion: In patients with documented focal induction of non-permanent AF and absence of structural heart disease, PVI is as effective in endurance athletes as in other patients.

Recent studies on spontaneous fluctuations in the functional MRI blood oxygen level-dependent (BOLD) signal in awake healthy subjects showed the presence of coherent fluctuations among functionally defined neuroanatomical networks. However, the functional significance of these spontaneous BOLD fluctuations remains poorly understood. By means of 3 T functional MRI, we demonstrate absent cortico-thalamic BOLD functional connectivity (i.e. between posterior cingulate/precuneal cortex and medial thalamus), but preserved cortico-cortical connectivity within the default network in a case of vegetative state (VS) studied 2.5 years following cardio-respiratory arrest, as documented by extensive behavioral and paraclinical assessments. In the VS patient, as in age-matched controls, anticorrelations could also be observed between posterior cingulate/precuneus and a previously identified task-positive cortical network. Both correlations and anticorrelations were significantly reduced in VS as compared to controls. A similar approach in a brain dead patient did not show any such long-distance functional connectivity. We conclude that some slow coherent BOLD fluctuations previously identified in healthy awake human brain can be found in alive but unaware patients, and are thus unlikely to be uniquely due to ongoing modifications of conscious thoughts. Future studies are needed to give a full characterization of default network connectivity in the VS patients population., ((c) 2009 Wiley-Liss, Inc.)

Introduction: Combination antibiotic therapy for ventilator associated pneumonia (VAP) is often used to broaden the spectrum of activity of empirical treatment. The relevance of such synergy is commonly supposed but poorly supported. The aim of the present study was to compare the clinical outcome and the course of biological variables in patients treated for a VAP, using a monotherapy with a beta-lactam versus a combination therapy., Methods: Patients with VAP were prospectively randomised to receive either cefepime alone or cefepime in association with amikacin or levofloxacin. Clinical and inflammatory parameters were measured on the day of inclusion and thereafter., Results: Seventy-four mechanically ventilated patients meeting clinical criteria for VAP were enrolled in the study. VAP was microbiologically confirmed in 59 patients (84%). Patients were randomised to receive cefepime (C group, 20 patients), cefepime with amikacin (C-A group, 19 patients) or cefepime with levofloxacin (C-L group, 20 patients). No significant difference was observed regarding the time course of temperature, leukocytosis or C-reactive protein level. There were no differences between length of stay in the intensive care unit after infection, nor in ventilator free days within 28 days after infection. No difference in mortality was observed., Conclusion: Antibiotic combination using a fourth generation cephalosporin with either an aminoside or a fluoroquinolone is not associated with a clinical or biological benefit when compared to cephalosporin monotherapy against common susceptible pathogens causing VAP.