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Background: Although catheter ablation (CA) is successful for the treatment of paroxysmal atrial fibrillation (AF), results are less satisfactory in persistent AF. Hybrid ablation (HA) results in better outcomes in patients with persistent atrial fibrillation (persAF), as it combines a thoracoscopic epicardial and transvenous endocardial approach in a single procedure., Objectives: The purpose of this study was to compare the effectiveness and safety of HA with CA in a prospective, superiority, unblinded, randomized controlled trial., Methods: Forty-one ablation-naive patients with (long-standing)-persAF were randomized to HA (n = 19) or CA (n = 22) and received pulmonary vein isolation, posterior left atrial wall isolation and, if needed, a cavotricuspid isthmus ablation. The primary efficacy endpoint was freedom from any atrial tachyarrhythmia >5 minutes off antiarrhythmic drugs after 12 months. The primary and secondary safety endpoints included major and minor complications and the total number of serious adverse events., Results: After 12 months, the freedom of atrial tachyarrhythmias off antiarrhythmic drugs was higher in the HA group compared with the CA group (89% vs 41%, P = 0.002). There was 1 pericarditis requiring pericardiocentesis and 1 femoral arteriovenous-fistula in the HA group. In the CA arm, 1 bleeding from the femoral artery occurred. There were no deaths, strokes, need for pacemaker implantation, or conversions to sternotomy, and the number of (serious) adverse events was comparable between groups (21% vs 14%, P = 0.685)., Conclusions: Hybrid AF ablation is an efficacious and safe procedure and results in better outcomes than catheter ablation for the treatment of patients with persistent AF. (Hybrid Versus Catheter Ablation in Persistent AF [HARTCAP-AF]; NCT02441738)., Competing Interests: Funding Support and Author Disclosures Dr Maesen is a consultant to AtriCure and Medtronic. Dr La Meir is a consultant to AtriCure. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: Pulmonary vein isolation (PVI) has become a cornerstone of the invasive treatment of atrial fibrillation. Severe complications are reported in 1-3% of patients. This study aims to compare complications and follow-up outcome of PVI in patients with atrial fibrillation., Methods and Results: The data were extracted from the Netherlands Heart Registration. Procedural and follow-up outcomes in patients treated with conventional radiofrequency (C-RF), multielectrode phased RF (Ph-RF), or cryoballoon (CB) ablation from 2012 to 2017 were compared. Subgroup analysis was performed to identify variables associated with complications and repeat ablations. In total, 13 823 patients (69% male) were included. The reported complication incidence was 3.6%. Patients treated with C-RF developed more cardiac tamponades (C-RF 0.8% vs. Ph-RF 0.3% vs. CB 0.3%, P ≤ 0.001) and vascular complications (C-RF 1.7% vs. Ph-RF 1.2% vs. CB 1.3%, P ≤ 0.001). Ph-RF was associated with fewer bleeding complications (C-RF: 1.0% vs. Ph-RF: 0.4% vs. CB: 0.7%, P = 0.020). Phrenic nerve palsy mainly occurred in patients treated with CB (C-RF: 0.1% vs. Ph-RF: 0.2% vs. CB: 1.5%, P ≤ 0.001). In total, 18.4% of patients were referred for repeat ablation within 1 year. Female sex, age, and CHA2DS2-VASc were independent risk factors for cardiac tamponade and bleeding complications, with an adjusted OR for female patients of 2.97 (95% CI 1.98-4.45) and 2.02 (95% CI 1.03-4.00) respectively., Conclusion: The reported complication rate during PVI was low. Patients treated with C-RF ablation were more likely to develop cardiac tamponades and vascular complications. Female sex was associated with more cardiac tamponade and bleeding complications., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

The exact frequency and clinical determinants of spontaneous conversion (SCV) in patients with symptomatic recent-onset AF are unclear. The aim of this systematic review is to provide an overview of the frequency and determinants of SCV of AF in patients presenting at the emergency department. A comprehensive literature search for studies about SCV in patients presenting to the emergency department with AF resulted in 25 articles - 12 randomised controlled trials and 13 observational studies. SCV rates range between 9-83% and determinants of SCV also varied between studies. The most important determinants of SCV included short duration of AF (<24 or <48 hours), low number of episodes, normal atrial dimensions and absence of previous heart disease. The large variation in SCV rate and determinants of SCV was related to differences in duration of the observation period, inclusion and exclusion criteria and in variables used in the prediction models., Competing Interests: Disclosure: The authors have no conflicts of interest to declare., (Copyright © 2020, Radcliffe Cardiology.)

Introduction: Anticoagulation therapy is pivotal in the management of stroke prevention in atrial fibrillation (AF). Prospective registries, containing longitudinal data are lacking with detailed information on anticoagulant therapy, treatment adherence and AF-related adverse events in practice-based patient cohorts, in particular for non-vitamin K oral anticoagulants (NOAC). With the creation of DUTCH-AF, a nationwide longitudinal AF registry, we aim to provide clinical data and answer questions on the (anticoagulant) management over time and of the clinical course of patients with newly diagnosed AF in routine clinical care. Within DUTCH-AF, our current aim is to assess the effect of non-adherence and non-persistence of anticoagulation therapy on clinical adverse events (eg, bleeding and stroke), to determine predictors for such inadequate anticoagulant treatment, and to validate and refine bleeding prediction models. With DUTCH-AF, we provide the basis for a continuing nationwide AF registry, which will facilitate subsequent research, including future registry-based clinical trials., Methods and Analysis: The DUTCH-AF registry is a nationwide, prospective registry of patients with newly diagnosed 'non-valvular' AF. Patients will be enrolled from primary, secondary and tertiary care practices across the Netherlands. A target of 6000 patients for this initial cohort will be followed for at least 2 years. Data on thromboembolic and bleeding events, changes in antithrombotic therapy and hospital admissions will be registered. Pharmacy-dispensing data will be obtained to calculate parameters of adherence and persistence to anticoagulant treatment, which will be linked to AF-related outcomes such as ischaemic stroke and major bleeding. In a subset of patients, anticoagulation adherence and beliefs about drugs will be assessed by questionnaire., Ethics and Dissemination: This study protocol was approved as exempt for formal review according to Dutch law by the Medical Ethics Committee of the Leiden University Medical Centre, Leiden, the Netherlands. Results will be disseminated by publications in peer-reviewed journals and presentations at scientific congresses., Trial Registration Number: Trial NL7467, NTR7706 (https://www.trialregister.nl/trial/7464)., Competing Interests: Competing interests: GC and EMT-R are supported by a research grant of ZonMW (project numbers 848050006 and 848050007). JS is supported by a grant from the Dutch Federation of Anticoagulation Clinics (FNT), outside the submitted work. FAK has received research support from Bayer, Bristol Myers Squibb, Boehringer Ingelheim, MSD, Daiichi Sankyo, Actelion, the Dutch Thrombosis Association and the Dutch Heart foundation. JRdG reports research grants from Abbott, AtriCure, Boston Scientific, Medtronic and Bayer. He received speaker/consultancy honoraria from AtriCure, Bayer, Daiichi Sankyo, Johnson & Johnson, Servier and Novartis; all outside the scope of this work. JGM received consultancy fees from BMS/Pfizer and Daiichi Sankyo. FS received consultancy fees from Daiichi Sankyo and BMS, and restricted institutional grants from Daiichi Sankyo. RGT reports grants and personal fees from Boehringer Ingelheim, Bayer, Pfizer, Bristol Meyer Squibb and Daiichi Sankyo. FHR and GJG received unrestricted institutional grants from Bayer, BMS/Pfizer, Boehringer Ingelheim and Daiichi Sankyo. MEWH received consultancy fees from Bayer, BMS/Pfizer, Boehringer Ingelheim, Daiichi Sankyo and Roche, and received a research grant from Federation of Dutch Thrombosis Services. MVH reports unrestricted grants from and personal fees from Boehringer Ingelheim, Pfizer/BMS, Bayer Health Care, Aspen and Daiichi Sankyo, outside the submitted work., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

As the mechanisms underlying persistent atrial fibrillation (AF) are still incompletely understood, a 'gold standard' strategy for ablation is lacking. The results of catheter ablation, independent of the ablation strategy applied, are disappointing. Hybrid ablation, combining a thoracoscopic epicardial and transvenous endocardial approach, has shown more favourable outcomes. To date, studies comparing both techniques are lacking. Therefore, we conducted a systematic review and meta-analysis of hybrid versus catheter ablation in patients with persistent or longstanding persistent AF. A systematic literature search of studies reporting on catheter and hybrid ablation of persistent or longstanding persistent AF was performed in the PubMed database. All identified articles were screened and checked for eligibility. A meta-analysis was performed on inter-study heterogeneity and pooled correlation between baseline characteristics, primary and secondary outcomes of hybrid and catheter studies. From the 520 articles identified by the search, 34 articles could be included in the analysis. Hybrid ablation resulted in higher freedom of atrial arrhythmias in patients with persistent and longstanding-persistent AF than catheter ablation (70.7% vs 49.9%, P < 0.001). Although hybrid ablation had a slightly higher complication rate than catheter ablation, overall morbidity and mortality were low. In conclusion, hybrid ablation is more effective than catheter ablation in maintaining the sinus rhythm in patients with persistent or longstanding persistent AF. However, data directly comparing both techniques are lacking, and small, heterogenic, single-arm studies in a random-effects model prevent definite conclusions from being drawn. Therefore, larger randomized controlled trials directly comparing both techniques are needed., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Left bundle branch block (LBBB) morphology is associated with improved outcome of cardiac resynchronisation therapy (CRT) and is an important criterion for patient selection. There are, however, multiple definitions for LBBB. Moreover, applying these definitions seems subjective. We investigated the inter- and intraobserver agreement in the determination of LBBB using available definitions, and clinicians' judgement of LBBB., Methods: Observers were provided with 12‑lead ECGs of 100 randomly selected CRT patients. Four observers judged the ECGs based on different LBBB-definitions (ESC, AHA/ACC/HRS, MADIT, and Strauss). Additionally, four implanting cardiologists scored the same 100 ECGs based on their clinical judgement. Observer agreement was summarized through the proportion of agreement (P) and kappa coefficient (k)., Results: Relative intra-observer agreement using different LBBB definitions, and within clinical judgement was moderate (range k 0.47-0.74 and k = 0.76 (0.14), respectively). The inter-observer agreement between observers using LBBB definitions as well as between clinical observers was minimal to weak (range k 0.19-0.44 and k = 0.35 (0.20), respectively). The probability of classifying an ECG as LBBB by available definitions varied considerably (range 0.20-0.76). The agreement between different definitions of LBBB ranged from good (P = 0.95 (0.07)) to weak (P = 0.40 (0.22)). Furthermore, correlation between the different LBBB definitions and clinical judgement was poor (range phi 0.30-0.55)., Conclusion: Significant variation in the probability of classifying LBBB is present in using different definitions and clinical judgement. Considerable intra- and inter-observer variability adds to this variation. Interdefinition agreement varies significantly and correlation of clinical judgement with LBBB classification by definitions is modest at best., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: In the recent ESC/EACTS guidelines, left atrial appendage (LAA) occlusion or exclusion in patients undergoing (thoracoscopic) atrial fibrillation (AF) ablation surgery is recommended. The Watchman device (WD, Boston Scientific, Minnesota) has proved to reduce the risk of thromboembolic events by closing of the LAA, yet no data exist on WD implantation during surgical AF ablation. The objective is to determine if WD implantation is safe and feasible in a hybrid AF ablation setting (i.e., combination of thoracoscopic epicardial surgical and endocardial catheter ablation) and could become subject of further testing to serve as a bail-out in cases in which surgical LAA occlusion methods cannot be applied, due to, for example, severe adhesions., Methods: In this prospective, single center, pilot study, 10 consecutive patients undergoing a hybrid ablation qualifying for LAA exclusion (CHA 2 DS 2 -VASc ≥ 1) were included. At the end of the hybrid ablation, the LAA was occluded endocardially using the WD. The feasibility endpoint was successful implantation. The safety endpoint concerned major complications., Results: One patient was excluded and replaced because the LAA was insufficiently visible on transesophageal echocardiography. In 10/11 patients, device delivery was successful (mean time: 35 minutes). No major complications occurred. Transesophageal echocardiography after 6 weeks and 6 months showed successful occlusion of the LAA without significant peridevice flow., Conclusion: Implantation of the WD seems to be feasible and safe in the setting of hybrid AF ablation and could be an alternative to epicardial occlusion in surgical AF ablation procedures. Larger studies are required to confirm these findings. This trial is registered with NCT02471131., Competing Interests: To support the research presented herein Laurent Pison reports a grant from Boston Scientific to the Cardiovascular Research Institute Maastricht (CARIM) at the University of Maastricht. Dr. La Meir reports a relationship with AtriCure and Medtronic., (Copyright © 2019 Mindy Vroomen et al.)

Aims: An appropriate left ventricular (LV) lead position is a pre-requisite for response to cardiac resynchronization therapy (CRT) and is highly patient-specific. The purpose of this study was to develop a non-invasive pre-procedural CRT-roadmap to guide LV lead placement to a coronary vein in late-activated myocardium remote from scar., Methods and Results: Sixteen CRT candidates were prospectively included. Electrocardiographic imaging (ECGI), computed tomography angiography (CTA), and delayed enhancement cardiac magnetic resonance imaging (DE-CMR) were integrated into a 3D cardiac model (CRT-roadmap) using anatomic landmarks from CTA and DE-CMR. Electrocardiographic imaging was performed using 184 electrodes and a CT-based heart-torso geometry. Coronary venous anatomy was visualized using a designated CTA protocol. Focal scar was assessed from DE-CMR. Cardiac resynchronization therapy-roadmaps were constructed for all 16 patients [left bundle branch block: n = 6; intraventricular conduction disturbance: n = 8; narrow-QRS (ablate and pace strategy); n = 1; right bundle branch block: n = 1]. The number of coronary veins ranged between 3 and 4 per patient. The CRT-roadmaps showed no (n = 5), 1 (n = 6), or 2 (n = 5) veins per patient located outside scar in late-activated myocardium [≥50% QRS duration (QRSd)]. Final LV lead position was outside scar in late-activated myocardium in 11 out of 14 implanted patients, while a LV lead in scar was unavoidable in the remaining three patients., Conclusion: A non-invasive pre-implantation CRT-roadmap was feasible to develop in a case series by integration of coronary venous anatomy, myocardial-scar localization, and epicardial electrical activation patterns, anticipating on clinically relevant features., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)

Background: Blood biomarkers related to AF could be useful to detect silent AF and to develop stratified strategies for AF prevention. Previous studies identified markers that predict incident AF. However, it is difficult to differentiate whether biomarkers relate to underlying cardiovascular diseases, are generated by the atria in response to an AF episode, or both. We therefore measured a panel of blood biomarkers in patients without overt CVD with and without AF to investigate the association between biomarkers and atrial fibrillation (AF) in patients without overt cardiovascular disease (CVD)., Methods: Blood samples - drawn remote from an AF episode - of 60 patients with AF but without overt forms of CVD (idiopathic AF; iAF) were compared to 120 matched patients with sinus rhythm only. A novel antibody-based method for quantification of blood biomarkers (OlinkProseek Multiplex Cardiovascular) was used to compare 92 biomarkers between the two groups., Results: N-terminal pro-B-type natriuretic peptide (NT-proBNP), Cathepsin L1, Endothelial cell-specific molecule 1, Cancer Antigen-125 (CA-125), Heat shock 27kDa protein, Galanin peptides, Proteinase-activated receptor 1, Stem cell factor, and CD40-ligand were all higher in iAF patients than in SR controls. Both NT-proBNP (OR1.55(1.07-2.25);p=0.022) and CA-125 (OR1.68(1.07-2.64);p=0.026) were independently associated with iAF., Conclusions: This exploratory study, investigating over 90 cardiovascular blood biomarkers in patients without known CVD, identified one established biomarker for paroxysmal AF, NT-proBNP, and a novel marker, CA-125. CA-125 - previously unrelated to paroxysmal AF in an otherwise healthy population - may thus be a potential indicator of remote paroxysms of AF.

Objectives: The single-step hybrid atrial fibrillation (AF) ablation procedure combines a transvenous endocardial and thoracoscopic epicardial approach in 1 procedure. Short-term results are encouraging, but long-term outcome data are not available., Methods: Hybrid AF ablation was successfully performed in 64 consecutive patients (53% with persistent AF). The mean follow-up period was 1732 ± 353 days. Perprocedural endocardial touch-up of incomplete epicardial lesions was performed in 17 (26%) patients., Results: In paroxysmal AF patients, arrhythmia-free cumulative survival rates after 1 hybrid AF ablation without Class I or III antiarrhythmic drugs procedure and without redo catheter ablation were 83%, 80% and 80% after 1, 2 and 3 years, respectively. In (long-standing) persistent AF patients, these were 82%, 79% and 79% after 1, 2 and 3 years. Thirteen (20%) patients had at least 1 recurrent episode of supraventricular arrhythmia lasting longer than 30 s: the most frequent recurrent arrhythmias were left atrial flutter and AF. No mortality or conversion to cardiopulmonary bypass, no phrenic nerve palsy and no pacemaker implantation were reported., Conclusions: Hybrid AF ablation, combining a transvenous endocardial and thoracoscopic epicardial approach in a single procedure, results in a cumulative 3-year freedom from arrhythmia without Class I or III antiarrhythmic drugs and without redo catheter ablation of 80% in paroxysmal AF (24 of 30 patients) and 79% in non-paroxysmal AF (26 of 33 patients).

Background: Placing the left ventricular (LV) lead at a site of late electrical activation remote from scar is desired to improve cardiac resynchronization therapy (CRT) response., Objective: The purpose of this study was to integrate coronary venous electroanatomic mapping (EAM) with delayed enhancement cardiac magnetic resonance (DE-CMR) enabling LV lead guidance to the latest activated vein remote from scar., Methods: Eighteen CRT candidates with focal scar on DE-CMR were prospectively included. DE-CMR images were semi-automatically analyzed. Coronary venous EAM was performed intraprocedurally and integrated with DE-CMR to guide LV lead placement in real time. Image integration accuracy and electrogram parameters were evaluated offline., Results: Integration of EAM and DE-CMR was achieved using 8.9 ± 2.8 anatomic landmarks and with accuracy of 4.7 ± 1.1 mm (mean ± SD). Maximal electrical delay ranged between 72 and 197ms (57%-113% of QRS duration) and was heterogeneously located among individuals. In 12 patients, the latest activated vein was located outside scar, and placing the LV lead in the latest activated vein remote from scar was accomplished in 10 patients and prohibited in 2 patients. In the other 6 patients, the latest activated vein was located in scar, and targeting alternative veins was considered. Unipolar voltages were on average lower in scar compared to nonscar (6.71 ± 3.45 mV vs 8.18 ± 4.02 mV [median ± interquartile range), P <.001) but correlated weakly with DE-CMR scar extent (R -0.161, P <.001) and varied widely among individual patients., Conclusion: Integration of coronary venous EAM with DE-CMR can be used during CRT implantation to guide LV lead placement to the latest activated vein remote from scar, possibly improving CRT., (Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: A patent foramen ovale (PFO) with atrial septal aneurysm (ASA) has been identified as a risk factor for cryptogenic stroke. Patients with migraine with aura (MA) appear to be at risk for silent brain infarction, which might be related to the presence of a PFO. However, the association between MA and PFO with ASA has never been reported. We examined this association in a large observational study., Methods and Results: Patients (>18 years) who underwent an agitated saline transesophageal echocardiography (cTEE) at our outpatient clinics within a timeframe of 4 years were eligible to be included. Before cTEE they received a validated headache questionnaire. Two neurologists diagnosed migraine with or without aura according to the International Headache Criteria. A total of 889 patients (mean age 56.4±14.3 years, 41.7% women) were included. A PFO was present in 23.2%, an isolated ASA in 2.7%, and a PFO with ASA in 6.9%. The occurrence of migraine was 18.9%; the occurrence of MA was 8.1%. The prevalence of PFO with ASA was significantly higher in patients with MA compared to patients without migraine (18.1% vs 6.1%; OR 3.72, 95% CI 1.86-7.44, P<0.001). However, a PFO without ASA was not significantly associated with MA (OR 1.50, 95% CI 0.79-2.82, P=0.21). Interestingly, a PFO with ASA was strongly associated with MA (OR 2.71, 95% CI 1.23-5.95, P=0.01)., Conclusion: In this large observational study, PFO with ASA was significantly associated with MA only. PFO closure studies should focus on this specific intra-atrial anomaly., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: Left ventricular septal (LVS) pacing reduces ventricular dyssynchrony and improves cardiac function relative to right ventricular apex (RVA) pacing in animals. We aimed to establish permanent placement of an LVS pacing lead in patients using a transvenous approach through the interventricular septum., Methods and Results: Ten patients with sinus node dysfunction scheduled for dual-chamber pacemaker implantation were prospectively enrolled. A custom pacing lead with extended helix was introduced via the left subclavian vein and, after positioning against the right ventricular septum (RVS) using a preshaped guiding catheter, driven through the interventricular septum to the LVS. The acute hemodynamic effect of RVA, RVS, and LVS pacing was evaluated by invasive LVdP/dtmax measurements. The lead was successfully delivered to the LVS in all patients. Procedure time and fluoroscopy time shortened with experience. QRS duration was shorter during LVS pacing (144 ± 20 ms) than during RVA (172 ± 33 ms; P = 0.02 versus LVS) and RVS pacing (165 ± 17 ms; P = 0.004 versus LVS). RVA and RVS pacing reduced LVdP/dtmax compared with baseline atrial pacing (-7.1 ± 4.1% and -6.9 ± 4.3%, respectively), whereas LVS pacing maintained LVdP/dtmax at baseline level (1.0 ± 4.3%; P = 0.001 versus RVA and RVS). R-wave amplitude and pacing threshold were 12.2 ± 6.7 mV and 0.5 ± 0.2 V at implant and remained stable during 6-month follow-up without lead-related complications., Conclusions: Permanent placement of an LVS pacing lead by transvenous approach through the interventricular septum is feasible in patients. LVS pacing preserves acute left ventricular pump function. This new pacing method could serve as an alternative and hemodynamically preferable approach for antibradycardia pacing., (© 2016 American Heart Association, Inc.)

A 53-year-old female patient with hypertrophic obstructive cardiomyopathy (HOCM) was admitted for alcohol septal ablation (ASA). A subcutaneous internal cardioverter defibrillator (S-ICD) was implanted for primary prevention. After ASA, the patient developed a right bundle branch block, and the S-ICD delivered a total of five inappropriate shocks due to T-wave oversensing (TWOS). TWOS is a relatively frequent cause of inappropriate shocks in S-ICD patients. After invasive treatment for HOCM, there is a risk of developing intraventricular conduction delay and subsequent changes in QRS and T-wave morphology. This should be taken into consideration when ICD indication is evaluated in HOCM patients., (©2015 Wiley Periodicals, Inc.)

Background: Delayed left ventricular (LV) lateral wall (LVLW) activation is considered the electrical substrate underlying LV dysfunction amenable to cardiac resynchronization therapy (CRT)., Objective: The purpose of this study was to assess LVLW activation in CRT candidates using coronary venous electroanatomic mapping (EAM) and to investigate whether the QRS area (QRSAREA) on the vectorcardiogram (VCG) can identify delayed LVLW activation., Methods: Fifty-one consecutive CRT candidates (29 left bundle branch block [LBBB], 15 intraventricular conduction delay [IVCD], 7 right bundle branch block [RBBB]) underwent intraprocedural coronary venous EAM using EnSite NavX. VCGs were constructed from preprocedural digital 12-lead ECGs using the Kors method. QRSAREA was assessed and compared to QRS duration and 5 different LBBB definitions., Results: Delayed LVLW activation (activation time >75% of QRS duration) occurred in 38 of 51 patients (29/29 LBBB, 8/15 IVCD, 1/7 RBBB). QRSAREA was larger in patients with than in patients without delayed LVLW activation (108 ± 42 µVs vs 51 ± 27 µVs, P < .001), and identified delayed LVLW activation better than QRS duration (area under the curve 0.89 [95% confidence interval 0.79-0.99] vs 0.49 [95% confidence interval 0.33-0.65]). QRSAREA >69 µVs diagnosed delayed LVLW activation with a higher sum of sensitivity (87%) and specificity (92%) than any of the LBBB definitions. Of the different LBBB definitions, the European Society of Cardiology textbook definition performed best with sensitivity of 76% and specificity of 100%., Conclusion: Coronary venous EAM can be used during CRT implantation to determine the presence of delayed LVLW activation. QRSAREA is a noninvasive alternative for intracardiac measurements of electrical activation, which identifies delayed LVLW activation better than QRS duration and LBBB morphology., (Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Delayed left ventricular (LV) lateral wall activation is considered the electrical substrate that characterises patients suitable for cardiac resynchronisation therapy (CRT). Although typically associated with left bundle branch block, delayed LV lateral wall activation may also be present in patients with non-specific intraventricular conduction delay (IVCD). We assessed LV lateral wall activation in a cohort of CRT candidates with IVCD using coronary venous electroanatomical mapping, and investigated whether baseline QRS characteristics on the ECG can identify delayed LV lateral wall activation in this group of patients., Methods: Twenty-three consecutive CRT candidates with IVCD underwent intra-procedural coronary venous electroanatomical mapping using EnSite NavX. Electrical activation time was measured in milliseconds from QRS onset and expressed as percentage of QRS duration. LV lateral wall activation was considered delayed if maximal activation time measured at the LV lateral wall (LVLW-AT) exceeded 75 % of the QRS duration. QRS morphology, duration, fragmentation, axis deviation, and left anterior/posterior fascicular block were assessed on baseline ECGs., Results: Delayed LV lateral wall activation occurred in 12/23 patients (maximal LVLW-AT = 133 ± 20 ms [83 ± 5 % of QRS duration]). In these patients, the latest activated region was consistently located on the basal lateral wall. QRS duration, and prevalence of QRS fragmentation and left/right axis deviation, and left anterior/posterior fascicular block did not differ between patients with and without delayed LV lateral wall activation., Conclusion: Coronary venous electroanatomical mapping can be used at the time of CRT implantation to determine the presence of delayed LV lateral wall activation in patients with IVCD. QRS characteristics on the ECG seem unable to identify delayed LV lateral wall activation in this subgroup of patients.

Introduction: The pulmonary vein ablation catheter (PVAC) is designed for pulmonary vein isolation (PVI). Electrical reconnection of pulmonary veins is believed to result in AF recurrence. The purpose of this study was to establish the location and extent of PV reconnection after PVI with the PVAC catheter., Methods and Results: Eighty-two patients (79 % male, age 60 ± 9 years) that underwent a redo procedure for recurrent AF after PVAC ablation were assessed for prevalence and location of reconnection. The number of reconnected PV's was 0, 1, 2, 3, or 4 in 2 (2.4 %), 14 (17 %), 23 (28 %), 28 (34 %), and 15 (18 %) patients, respectively. Reconnection of left superior, left inferior, left common, right superior, and right inferior PV's was found in 66, 63, 83, 57, and 67 %, respectively (p = 0.48). In the left PV's, reconnection was located significantly more anterior than posterior; LSPV anterior 32/70 vs posterior 13/70 (p < 0.01), LIPV anterior 26/70 vs posterior 9/70 (p < 0.01). In the right PV's reconnection was distributed equally in all quadrants. Different modes of RF delivery during PVAC ablation (bipolar/unipolar 2:1 [n = 35] vs. 4:1 [n = 47]) yielded comparable rates of PV reconnection. During follow-up (median 296 days) no AF/AT was documented in 57 patients (70 %)., Conclusion: Almost all patients (98 %) with AF after PVAC ablation show reconnection of at least one PV. All PV's are equally likely to show reconnection. In the left PV's, reconnection was found more often anteriorly than posteriorly. During pulmonary vein isolation with the PVAC catheter, prevalent sites of reconnection deserve close attention to increase success.

Objectives: To develop a quantitative event-free prediction model of late atrial arrhythmia after atrial septal defect (ASD) repair., Background: The clinical management of ASD is driven by risk factors that determine the occurrence of late atrial arrhythmia., Methods: Data from ASD type secundum patients, included in the Belgian Congenital Heart Disease Registry, were analyzed. Based on review of the literature, age at repair, gender, pulmonary hypertension, atrial arrhythmia before and within one month after repair were included in the model. Using Cox-regression analysis, a weighted risk score was derived, which was validated using the Brier score., Results: A total of 155 patients (117 women; median age at follow-up 53.9 years, range 18.0-78.8) having 349 follow-up years was included. Thirty-nine patients (25.2%) presented with late atrial arrhythmia. Multivariate analysis showed that a mPAP ≥ 25 mmHg (HR 4.39; 95%CI 2.17-9.09; P<0.0001), the presence of atrial arrhythmia before (HR 3.52; 95%CI 1.75-7.14; P=0.002) and ≤ 1month after repair (HR 6.62; 95%CI 2.38-20.00; P<0.0001) and gender (HR 2.18 95%CI 1.11-4.35) were associated with late atrial arrhythmia. A risk score (0 to 28 points) to predict atrial arrhythmia free survival was derived for follow-up times ranging from one to 5 years. Mean Brier score for the model was 0.10., Conclusions: We formulated a well validated risk model to predict arrhythmia-free survival in ASD patients undergoing ASD repair. Further research is needed whether this model can be used for individual clinical risk stratification and whether the model can be adapted for application in other congenital heart defects., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Aims: Percutaneous patent foramen ovale (PFO) closure seems to be effective for secondary prevention of cryptogenic stroke in patients younger than 55 years of age. The efficacy in older patients remains uncertain. We compared the efficacy of PFO closure between patients younger and older than 55 years., Methods and Results: All 335 patients (mean age 50.2 ± 12.6 years; 205 men) with cryptogenic thromboembolism who underwent PFO closure in our centres between 1998 and 2008 were included. Mean follow-up period was 4.2 ± 1.9 years in the elderly (n=120) and 3.8 ± 2.4 years in the younger patients (n=215) (p=0.15). Prevalence of hypertension, diabetes, hyperlipidaemia and coronary and peripheral artery disease was higher in the elderly (p<0.05 for all). Re-occurrence of stroke or TIA was higher in the elderly compared to the younger (annual event rate 2.4% versus 0.6%; log rank, p=0.005). Re-occurrence of stroke alone was higher in the elderly (annual event rate 1.2% versus 0.1%; log rank, p=0.01). Multivariate analysis showed that an age of >55 years was an independent predictor of recurrent stroke or TIA (HR 3.2, p=0.03)., Conclusions: Percutaneous PFO closure appears to be effective for secondary prevention of cryptogenic stroke in younger patients but seems to be related with less beneficial outcome in elderly. Randomised controlled trials are needed to confirm our findings.

Aims: Transcatheter closure of the secundum-type atrial septal defect (ASD) is widely practised. We report complications and efficacy of percutaneous ASD closure in adults using the Amplatzer ASD occluder and the Cardioseal/Starflex device during long-term follow-up., Methods and Results: Between 1996 and 2008 percutaneous ASD closure was performed in 133 patients (mean age 46.8 ± 16.9 years; 36 men) by using the Amplatzer(r) device in 104 patients and the Cardioseal/Starflex device in 29. During a mean follow-up of 3.4 ± 2.8 years the occurrence of major complications was higher in patients with the Cardioseal/Starflex compared to patients with the Amplatzer(r) devices (17.2 vs. 2.9%, log rank, P=0.005), due to a higher embolisation rate (13.8 vs. 1.0%, log rank, P=0.002). In univariable analysis, the implantation of a Cardioseal/Starflex device (OR 6.0 (CI 1.4-25.2); P=0.01) and a larger device diameter (OR 1.1 (CI 1.0-1.2); P=0.04) were found to be predictors of the occurrence of major complications. Minor complications occurred in 10.5%, recurrent thrombo-embolism in 2.3% and residual shunting at six months was 13.9% without differences between devices. NYHA class improved from 1.8 ± 0.6 before to 1.2 ± 0.4 after closure (P<0.001) without differences between devices., Conclusions: During long-term follow-up, percutaneous ASD closure in adults is safe and effective when using the Amplatzer(r) device. Larger Cardioseal/Starflex devices are related to a higher embolisation rate. Randomised trials are needed.

Aims: To compare the mid-term efficacy and safety of the bioabsorbable BioSTAR(r) device with the non-bioabsorbable CardioSEAL(r) device for percutaneous patent foramen ovale (PFO) closure., Methods and Results: All 81 consecutive patients who underwent PFO closure with the CardioSEAL(r) or BioSTAR(r) device between June 2003 and July 2008 were included. The presence of a residual shunt (minimal, moderate or large) was measured in both groups at six months follow-up, using contrast transthoracic echocardiography. Forty-four patients (48.4±11.4 years) received the CardioSEAL(r) device and 37 patients the BioSTAR(r) device (47.9±10.7 years). There were no significant differences in short-term complications. Two patients who received the BioSTAR(r) device developed a recurrent transient cerebral ischaemic event. Overall, atrial arrhythmias occurred in 19%, with no difference between both groups. At six months, a residual shunt was present in 29% (27% minimal, 2% moderate) using the CardioSEAL(r) device compared to 28% (17% minimal, 11% moderate) using the BioSTAR(r) device (p=0.18). A predictor for residual shunt could not be found., Conclusions: There is no difference in safety and efficacy at six months between the CardioSEAL(r) and BioSTAR(r) device used for PFO closure. However, using the BioSTAR(r) device tends to be associated with a higher percentage of moderate shunting.

Summary Objectives: We investigated the haemodynamic effect of percutaneous closure of an intra-atrial shunt, using non-invasive finger pressure measurements., Background: Percutaneous closure of both patent foramen ovale (PFO) and atrial septal defect (ASD) is widely practised. Currently no data are available on short-term haemodynamic changes induced by closure., Methods: Twenty-five consecutive patients (mean age 49 +/- 17 years, 10 men) who underwent a percutaneous closure of a PFO (n = 15) or ASD (n = 10) were included in this study. During the procedure blood pressure and heart rate (HR) were monitored continuously with a Finometer. Changes in systolic, mean, and diastolic pressure, stroke volume (SV), cardiac output (CO) and total peripheral resistance (TPR) were computed from the pressure registrations using Modelflow methodology., Results: Baseline characteristics were similar for the PFO and ASD patients. After PFO closure none of the haemodynamic parameters changed significantly. After ASD closure the systolic, mean, and diastolic pressures increased 7.1 +/- 5.4 (P = 0.003), 3.8 +/- 3.5 (P = 0.007) and 2.0 +/- 3.0 mmHg (P = ns) respectively. HR decreased 5.1 +/- 5.3 beats per minute (P = 0.01). SV, CO and TPR increased 8.5 +/- 6.4 ml (13.5%; P = 0.002), 0.21 +/- 0.45 l min(-1) (5.6%; P = ns) and 0.02 +/- 0.14 dynes (4.1%; P = ns) respectively. The changes in SV differ between the PFO and ASD patients (P = 0.009)., Conclusions: Using non-invasive finger pressure measurements, we found that SV, mean and systolic blood pressure increased immediately after percutaneous closure of an ASD in adults, whereas the percutaneous PFO closure had no effect on haemodynamic characteristics.

Background: A right-to-left shunt, as seen in patients with a patent foramen ovale, seems to be associated with migraine. An atrial septal defect (ASD), however, is characterized by a predominant left-to-right shunt (LRS). We prospectively evaluated the effect of percutaneous ASD closure on migraine, Methods: All 70 consecutive patients (>16 years) who underwent a percutaneous ASD closure between November 2003 and December 2005 in one of the two participating centers were included in the study. On the basis of standardized headache questionnaire, two independent neurologists diagnosed migraine with or without aura (MA+ and MA-, respectively) according to the International Headache Society criteria, before, 6 and 12 months after closure., Results: Sixty-eight patients (97%; mean age 47.3 + or - 16.4 years; 22% men) agreed to participate in the study and completed the questionnaire. Before ASD closure, the overall prevalence of migraine was 34%, MA+ 22% and MA- 12%. At 6 months follow-up, the headache questionnaire was completed by 63 patients (93%) and the prevalence of overall migraine decreased to 19%, MA+ to 8% and MA- to 11% (Mc Nemar test, P = 0.08, P = 0.07, and P = 1.0, respectively). At 12 months, the prevalence of migraine decreased further to 12%, MA+ to 5% and MA- to 7% (McNemar test, P = 0.003, P = 0.04, and P = 0.29 versus at inclusion, respectively) based on a completed headache questionnaire of 57 patients (84%)., Conclusion: We found a high prevalence of migraine in patients with an ASD, and observed prospectively a reduction in the occurrence of migraine, especially migraine with aura, 1 year after percutaneous closure.

Background: A low serum total IGF1 is considered as a diagnostic indicator of GH deficiency (GHD) in the presence of hypopituitarism. Introduction of IRMA and chemiluminescent immunometric assay (CLIA) IGF1 immunoassays has introduced endogenous antibodies as a new source of interference. In general, this goes unnoticed and might lead to unnecessary diagnostic and therapeutic interventions., Case: A 56-year-old man was referred with a decline in physical performance, unexplained osteopenia, and weight loss of 3 kg over the past 8 months. Although clinical signs and symptoms were unremarkable, laboratory results pointed to secondary hypothyroidism and secondary hypogonadism. In addition, the serum total IGF1 level (CLIA; Siemens Medical Solutions Diagnostics) was in the low normal range. Two GH stimulation tests were performed, but these tests did not support the diagnosis GHD. Moreover, IGF1 bioactivity measured by the kinase receptor activation assay was normal. Interference of heterophilic antibodies was considered. After pretreatment with specific heterophilic blocking tubes that contain blocking reagents to eliminate heterophilic antibodies, serum-free thyroxine, testosterone, and IGF1 levels turned out to be normal., Conclusion: To the best of our knowledge, we here describe the first case in the literature of a patient with low serum total IGF1 levels due to interference from heterophilic antibodies in the used IGF1 immunoassay. When confronted with low-IGF1 levels that do not fit the clinical picture, interference of heterophilic antibodies should be considered in the differential diagnosis.

Pulmonary arteriovenous malformations (PAVMs) are associated with severe neurological complications in patients with hereditary haemorrhagic telangiectasia (HHT). The objective of the present study was to prospectively establish the diagnostic value of transthoracic contrast echocardiography (TTCE) as a screening technique for PAVM using chest high-resolution computed tomography (HRCT) as the gold standard for PAVMs. All consecutive adult patients referred for HHT screening underwent a chest HRCT (n = 299), TTCE (n = 281), arterial blood gas analysis (n = 291), shunt fraction measurement (n = 111) and chest radiography (n = 296). TTCE was positive in 87 (58.8%), 12 (16.7%) and four (6.7%) patients, and chest HRCT was positive in 54 (36.5%), three (4.2%) and zero (0%) patients with a definite, possible and negative clinical diagnosis of HHT, respectively. Two patients with a negative TTCE were diagnosed with PAVMs after computed tomography; in both cases the PAVMs were too small to be treated by embolotherapy. The sensitivity of TTCE was 97% (95% confidence interval (CI) 93.6-98.3) and negative predictive value 99% (95% CI 96.9-99.8). The other diagnostic tests showed a considerable lower diagnostic value. The present prospective study shows that transthoracic contrast echocardiography has an excellent diagnostic value and can be used as an initial screening procedure for pulmonary arteriovenous malformations. The high false-positive rate of transthoracic contrast echocardiography possibly represents microscopic pulmonary arteriovenous malformations.

Background: A causal relationship between migraine and a right-to-left shunt, due to a patent foramen ovale (PFO), has been suggested. In mainly retrospective studies, percutaneous closure of a PFO has been associated with a decrease in the prevalence of migraine., Objective: In this prospective observational study we evaluated whether percutaneous closure of a PFO is associated with a decrease in the prevalence of migraine., Methods: Between November 2003 and August 2005, we included 92 patients (age >16 years) who underwent a percutaneous closure of a symptomatic PFO, which was considered to be related to a paradoxical embolism.They received a headache questionnaire before and six months after closure.Two neurologists diagnosed migraine, according to the International Headache Criteria., Results: Eighty-nine of 92 patients (97%, mean age 51.6 +/- 12.3 years, 63 men) completed the questionnaire immediately before PFO closure.The overall prevalence of migraine was 27.0%, for migraine without aura (MA-) 15.7%, and for migraine with aura (MA+) 11.2%. After more than six months of follow-up 84 of 89 patients (94%, mean age 52.1 +/- 12.0 years, 60 men) returned the questionnaire. The overall prevalence of migraine in this group decreased from 28.6% to 10.7% (P = 0.001), for MA-from 16.7% to 8.3% (P = 0.07), and for MA+ from 11.9% to 2.4% (P = 0.02)., Conclusions: Percutaneous PFO closure is related to a decrease in the prevalence of migraine in this prospective observational study. However, randomized placebo controlled trials have to confirm these findings.

Background: Percutaneous patent foramen ovale (PFO) closure seems to reduce the risk of recurrent thromboembolism. We report the safety and efficacy of percutaneous PFO closure in our centre., Methods: All patients, >16 years of age, who underwent a percutaneous PFO closure in our centre were included. Reoccurrence of stroke, transient ischaemic attack (TIA) and peripheral thromboembolism were assessed. Periprocedural and midterm complications are reported., Results: Eighty-three consecutive patients (mean age 49+/-13 years) were included. Indications for PFO closure were cryptogenic stroke (59.0%), TIA (33.7%), peripheral embolism (2.4%) and other (4.8%). For PFO closure, a Cardioseal/Starflex device was used in 63 patients and an Amplatzer PFO occluder device in 20 patients. Stroke recurred in 1.2%, TIA in 3.6%, peripheral embolism in 0% during a mean follow-up of 1.9+/-1.2 years. Major periprocedural complications occurred in 1.2%. The mid-term complication rate was 2.4% and only consisted of minor complications. During follow-up, a residual right-to-left shunt was present in 5.7% of the patients. No significant difference in outcome, complications or residual shunting could be documented between the two device types., Conclusion: In our centre, the percutaneous closure of a PFO seems to be a safe and effective procedure to prevent recurrence of paradoxical thrombo-embolic events. (Neth Heart J 2008;16:332-6.).

Aims: Recently we reported that percutaneous atrial septal defect (ASD) closure had no influence on the prevalence of migraine during a short followup period. 12 % of patients however developed a new-onset migraine after the ASD closure. As it has been suggested that the closing device might induce or maintain migraine temporarily, we were interested in the prevalence of migraine at longer follow-up., Methods: All 75 patients included in the previous study, received the same structured headache questionnaire. A neurologist, blinded to previous data, diagnosed migraine with or without aura (MA+ or MA-) according to the International Headache Criteria. McNemar paired X2 test was used to evaluate changes in the occurrence of migraine., Results: Seventy-one patients (94.7%) answer the questionnaire (55 women, mean age at closure 51 +/- 18 years). Mean follow-up time was 52 +/- 13 months. The overall migraine prevalence decreased from 30.7% before to 22.5% after closure (P=0.21). A significant reduction was noted in patients with new-onset migraine early after closure (n=7), where migraine disappeared in 6 patients (P=0.031). In the group with persistent migraine early after closure (n=13), another 6 patients became migraine-free (P=0.031)., Conclusion: Percutaneous ASD closure was not related to a significant decrease in overall migraine prevalence. However, new-onset and persistent migraine early after closure disappeared.

Objectives: This multi-centre study reports safety and efficacy of percutaneous patent foramen ovale (PFO) closure, using the fourth generation Intrasept device., Background: PFO has been associated with paradoxical embolism and cryptogenic stroke. Percutaneous PFO closure seems to reduce the risk for recurrent paradoxical thrombo-embolism. Currently, different devices are used for PFO closure., Methods: Patients, who underwent a PFO closure with the Intrasept device (Cardia, Eagan, MN) between July 2002 and September 2006, were included in the study. The primary endpoint was defined as reoccurrence of stroke, transient ischemic attack (TIA), or peripheral thrombo-embolism. Peri-procedural and mid-term complications were reported., Results: Four-hundred thirty patients (mean age 50.7 +/- 13.0 years, 231 men) underwent closure. The indications were cryptogenic stroke (69.8%), TIA (23.5%), peripheral embolism (3.3%), and other (3.5%). The median follow-up time was 0.8 years, range 3.9 years. The primary endpoint occurred in 0.5% for stroke, in 2.5% for TIA, and in none for peripheral embolism. Peri-procedural complications were reported in 11.5% of cases, from which 0.2% was defined as major. No severe complications occurred during mid-term follow-up. A residual shunt was present in 12.5% of patients who did not suffer from a recurrent event, compared to 36.4% of patients who reached the primary endpoint (P = 0.04)., Conclusion: This multi-centre study suggests that percutaneous closure of a symptomatic PFO with the fourth generation Intrasept device is safe and might be effective to prevent the recurrence of paradoxical thrombo-embolic events., (2008 Wiley-Liss, Inc.)

Migraine is a common neurological disorder with a great impact on the quality of life and social activities. The patent foramen ovale (PFO) is an intra-atrial right-to-left shunt with a prevalence of 25% in the general population. An increased prevalence is found in patients with migraine, especially in migraine with aura. Percutaneous PFO closure might decrease the prevalence of migraine. However, most of these observational studies were retrospective without a randomized design and the results need to be interpreted with caution. In this review we describe the association between PFO and migraine and the different pathophysiological hypotheses, which have been proposed to explain this relationship., (Copyright (c) 2006 Wiley-Liss, Inc.)