Assessment of ventricular electrical heterogeneity in left bundle branch pacing and left ventricular septal pacing by using various electrophysiological methods.

INTRODUCTION: Left bundle branch area pacing (LBBAP) comprises pacing at the left ventricular septum (LVSP) or left bundle branch (LBBP). The aim of the present study was to investigate the differences in ventricular electrical heterogeneity between LVSP, LBBP, right ventricular pacing (RVP) and intrinsic conduction with different dyssynchrony measures using the ECG, vectorcardiograpy, ECG belt, and Ultrahigh frequency (UHF-)ECG. METHODS: Thirty-seven patients with a pacemaker indication for bradycardia or cardiac resynchronization therapy underwent LBBAP implantation. ECG, vectorcardiogram, ECG belt and UHF-ECG signals were recorded during RVP, LVSP and LBBP, and intrinsic activation. QRS duration (QRSd) was measured from the ECG, QRS area was calculated from the vectorcardiogram, LV activation time (LVAT) and standard deviation of activation time (SDAT) from ECG belt and electrical dyssynchrony (e-DYS16) from UHF-ECG. RESULTS: Both LVSP and LBBP significantly reduced ventricular electrical heterogeneity as compared to underlying LBBB and RV pacing in terms of QRS area (p < .001), SDAT (p < .001), LVAT (p < .001) and e-DYS16 (p < .001). QRSd was only reduced as compared to RV pacing(p < .001). QRS area was similar during LBBP and normal intrinsic conduction, e-DYS16 was similar during LVSP and normal intrinsic conduction, whereas SDAT was similar for LVSP, LBBP and normal intrinsic conduction. For all these variables there was no significant difference between LVSP and LBBP. CONCLUSION: Both LVSP and LBBP resulted in a more synchronous LV activation than LBBB and RVP. Especially LBBP resulted in levels of LV synchrony comparable to normal intrinsic conduction.

Comparison and predictors of implantable cardioverter-defibrillator therapy for primary and secondary prevention.

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) are effective in detecting and treating ventricular arrhythmias. Studies on ICD therapy for different indications (primary and secondary prevention) and possible predictors of ICD therapy are limited. In this study, the incidence and type of ICD therapy were related to the indication and the underlying cardiac pathology. METHODS: A single-centre, retrospective and observational study was performed of 482 patients who underwent ICD implantation for primary (53.3%) or secondary prevention (46.7%) between 2015 and 2020 at the Radboud University Medical Centre. RESULTS: During a median follow-up of 2.4 years (interquartile range 0.2-3.9), the occurrence of appropriate ICD therapy for primary versus secondary prevention was 9.7% and 27.6%, respectively (p < 0.001). Time to appropriate ICD therapy was significantly shorter in the secondary prevention group (p < 0.001). No difference in ICD therapy was seen for different underlying aetiologies. In the majority of cases (70%) ICD therapy was given for ventricular tachycardia (VT). The occurrence of adverse events (16.3% vs 17.3%, p = 0.772), hospitalisation for cardiovascular reasons (29.2% vs 35.1%, p = 0.559) and all-cause mortality (12.5% vs 11.6%, p = 0.763) were similar in both groups. Male gender (3.53, 95% confidence interval (CI) (1.003, 12.403), p = 0.049) and secondary prevention indication (4.90, 95% CI (1.495, 16.066), p = 0.009) were predictors of appropriate ICD therapy. CONCLUSION: The risk associated with appropriate ICD therapy is higher in secondary prevention patients, who have their first therapy within a shorter time frame after device implantation. Rates of complications, hospitalisation and all-cause mortality are comparable. Future treatment options should target the prevention of ICD therapy, mainly by preventing the recurrence of VT.

COMPARE LAAO: Rationale and design of the randomized controlled trial "COMPARing Effectiveness and safety of Left Atrial Appendage Occlusion to standard of care for atrial fibrillation patients at high stroke risk and ineligible to use oral anticoagulation therapy".

BACKGROUND: Left atrial appendage occlusion (LAAO) provides an alternative to oral anticoagulation (OAC) for stroke prevention in patients with atrial fibrillation (AF). In patients with a long-term or permanent contraindication for OAC randomized controlled trial (RCT) data is lacking. STUDY OBJECTIVES: To assess the efficacy and safety of LAAO in AF patients who are ineligible to use OAC. The co-primary efficacy endpoint is (1) time to first occurrence of stroke (ischemic, hemorrhagic, or undetermined) and (2) time to first occurrence of the composite of stroke, transient ischemic attack (TIA), and systemic embolism (SE). The primary safety endpoint is the 30-day rate of peri-procedural complications. STUDY DESIGN: This is a multicenter, investigator-initiated, open-label, blinded endpoint (PROBE), superiority-driven RCT. Patients with AF, a CHA2DS2-VASc score ≥2 for men and ≥3 for women and a long-term or permanent contraindication for OAC will be randomized in a 2:1 fashion to the device- or control arm. Patients in the device arm will undergo percutaneous LAAO and will receive post-procedural dual antiplatelet therapy (DAPT) per protocol, while those in the control arm will continue their current treatment consisting of no antithrombotic therapy or (D)APT as deemed appropriate by the primary responsible physician. In this endpoint-driven trial design, assuming a 50% lower stroke risk of LAAO compared to conservative treatment, 609 patients will be followed for a minimum of 1 and a maximum of 5 years. Cost-effectiveness and budget impact analyses will be performed to allow decision-making on reimbursement of LAAO for the target population in the Netherlands. SUMMARY: The COMPARE LAAO trial will investigate the clinical superiority in preventing thromboembolic events and cost-effectiveness of LAAO in AF patients with a high thromboembolic risk and a contraindication for OAC use. NCT TRIAL NUMBER: NCT04676880.

Persistent phrenic nerve palsy after atrial fibrillation ablation: Follow-up data from The Netherlands Heart Registration.

BACKGROUND: Persistent phrenic nerve palsy (PNP) is an established complication of atrial fibrillation (AF) ablation, especially during cryoballoon and thoracoscopic ablation. Data on persistent PNP reversibility is limited because most patients recover <24 h. This study aims to investigate persistent PNP recovery, freedom of PNP-related symptoms after AF ablation and identify baseline variables associated with the occurrence and early PNP recovery in a large nationwide registry study. METHODS: In this study, we used data from the Netherlands Heart Registration, comprising data from 9549 catheter and thoracoscopic AF ablations performed in 2016 and 2017. PNP data was available of 7433 procedures, and additional follow-up data were collected for patients who developed persistent PNP. RESULTS: Overall, the mean age was 62 ± 10 years, and 67.7% were male. Fifty-four (0.7%) patients developed persistent PNP and follow-up was available in 44 (81.5%) patients. PNP incidence was 0.07%, 0.29%, 1.41%, and 1.25%, respectively for patients treated with conventional-RF, phased-RF, cryoballoon, and thoracoscopic ablation respectively. Seventy-one percent of the patients fully recovered, and 86% were free of PNP-related symptoms after a median follow-up of 203 (113-351) and 184 (82-359) days, respectively. Female sex, cryoballoon, and thoracoscopic ablation were associated with a higher risk to develop PNP. Patients with PNP recovering ≤180 days had a larger left atrium volume index than those with late or no recovery. CONCLUSION: After AF ablation, persistent PNP recovers in the majority of patients, and most are free of symptoms. Female patients and patients treated with cryoballoon or thoracoscopic ablation are more prone to develop PNP.

A VIRTUAL Sleep Apnoea management pathway For the work-up of Atrial fibrillation patients in a digital Remote Infrastructure: VIRTUAL-SAFARI.

AIMS: In atrial fibrillation (AF) patients, untreated sleep-disordered breathing (SDB) is associated with lower success rates of rhythm control strategies and as such structured SDB testing is recommended. Herein, we describe the implementation of a virtual SDB management pathway in an AF outpatient clinic and examine the utility and feasibility of this new approach. METHODS AND RESULTS: Prospectively, consecutive AF patients accepted for AF catheter ablation procedures without previous diagnosis of SDB were digitally referred to a virtual SDB management pathway and instructed to use WatchPAT-ONE (ITAMAR) for one night. Results were automatically transferred to a virtual sleep laboratory, upon which a teleconsultation with a sleep physician was planned. Patient experience was measured using surveys. SDB testing was performed in 119 consecutive patients scheduled for AF catheter ablation procedures. The median time from digital referral to finalization of the sleep study report was 18 [11-24] days. In total, 65 patients (55%) were diagnosed with moderate-to-severe SDB. Patients with SDB were prescribed more cardiovascular drugs and had higher body mass indices (BMI, 29 ± 3.3 vs. 27 ± 4.4kg/m2, P < 0.01). Patients agreed that WatchPAT-ONE was easy to use (91%) and recommended future use of this virtual pathway in AF outpatient clinics (86%). Based on this remote SDB testing, SDB treatment was recommended in the majority of patients. CONCLUSION: This novel virtual AF management pathway allowed remote SDB testing in AF outpatient clinics with a short time to diagnosis and high patient satisfaction. Structured SDB testing results in a high detection of previously unknown SDB in AF patients scheduled for AF ablation.

Meta-analysis of controlled studies on minimally interrupted vs. continuous use of non-vitamin K antagonist oral anticoagulants in catheter ablation for atrial fibrillation.

AIMS: At present, there are no guideline recommendations for minimally interrupted use of non-vitamin K antagonist oral anticoagulants (mi-NOAC) during catheter ablation (CA) for atrial fibrillation (AF). Current evidence is predominantly based on observational studies, with continuous use of vitamin K antagonist in the control arm. This quantitative summary reflects the first high-level evidence on contemporary regimens, with continuous NOAC use (c-NOAC) as the current gold standard. METHODS AND RESULTS: Meta-analysis (Pubmed, Embase, and Web of Science) on prospective, controlled studies comparing contemporary mi-NOAC (without bridging) with c-NOAC. Net adverse clinical events (major bleeding, thrombo-embolic events) were the primary outcome. In addition, we analysed total bleeding, minor bleeding, and silent cerebral embolism. Eight studies (six randomized, two observational) with 2168 patients were summarized. The primary endpoint occurred in 1.0% (18/1835): 1.1% (11/1005) vs. 0.8% (7/830) for the mi-NOAC and c-NOAC groups, respectively; odds ratio (OR) 1.20 [95% confidence interval (CI) 0.49-2.92, P = 0.64]. The OR for total bleeding on mi-NOAC was 1.26 (95% CI 0.97-1.63, P = 0.07). ORs for minor bleeding and silent cerebral embolism were 1.17 (95% CI 0.80-1.70, P = 0.34) and 2.62 (95% CI 0.54-12.61, P = 0.12), respectively. CONCLUSION: This synopsis provides a quantitative synthesis of high-level evidence on a contemporary strategy of mi-NOAC in CA for AF, and overall clinical outcomes were not different from continuous NOAC use. Despite preprocedural interruption, there was no sign of lower bleeding rates. Additional higher volume datasets are warranted for more precise treatment effect estimations of this everyday alternative anticoagulation strategy in AF ablation.

Complications in pulmonary vein isolation in the Netherlands Heart Registration differ with sex and ablation technique.

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.

Risk Factors for Inadequate Defibrillation Safety Margins Vary With the Underlying Cardiac Disease: Implications for Selective Testing Strategies.

INTRODUCTION: In view of the shift from routine toward no or selective defibrillation testing, optimization of the current risk stratification for inadequate defibrillation safety margins (DSMs) could improve individualized testing decisions. Given the pathophysiological differences in myocardial substrate between ischemic and nonischemic heart disease (IHD/non-IHD) and the accompanying differences in clinical characteristics, we studied inadequate DSMs and their predictors in relation to the underlying etiology. METHODS AND RESULTS: Cohort of routine defibrillation tests (n = 785) after first implantable cardioverter defibrillator (ICD)-implantations at the Radboud UMC (2005-2014). A defibrillation threshold >25 J was regarded as an inadequate DSM. In total, 4.3% of patients had an inadequate DSM; in IHD 2.5% versus 7.3% in non-IHD (P = 0.002). We identified a group of non-IHD patients at high risk (13-42% inadequate DSM); the remainder of the cohort (>70%) had a risk of only 2% (C-statistic entire cohort 0.74; C-statistic non-IHD 0.82). This was based upon two identified interaction terms: (1) non-IHD and age (aOR 0.94 [95% CI 0.91-0.97]); (2) non-IHD and the indexed left ventricular (LV) internal diastolic diameter (aOR 3.50 [95% CI 2.10-5.82]). CONCLUSION: The present study on risk stratification for an inadequate DSM not only confirms the importance of making a distinction between IHD and non-IHD, but also shows that risk factors in an entire cohort (LV dilatation, age) may only apply to a subgroup (non-IHD). Appreciation of this concept could favorably affect current risk stratification. If confirmed, our approach may be used to optimize individualized testing decisions in an upcoming era of non-routine testing.

The pharmacokinetics and pharmacodynamics of ibogaine in opioid use disorder patients.

OBJECTIVE: Ibogaine is a hallucinogenic drug that may be used to treat opioid use disorder (OUD). The relationships between pharmacokinetics (PKs) of ibogaine and its metabolites and their clinical effects on side effects and opioid withdrawal severity are unknown. We aimed to study these relationships in patients with OUD undergoing detoxification supported by ibogaine. METHODS: The study was performed in 14 subjects with OUD. They received a single dose of 10mg/kg ibogaine hydrochloride. Plasma PKs of ibogaine, noribogaine, and noribogaine glucuronide were obtained during 24 h. Cytochrome P450 isoenzyme 2D6 (CYP2D6) genotyping was performed. The PKs were analyzed by means of nonlinear mixed effects modeling and related with corrected QT interval (QTc) prolongation, cerebellar ataxia, and opioid withdrawal severity. RESULTS: The PK of ibogaine were highly variable and significantly correlated to CYP2D6 genotype (p < 0.001). The basic clearance of ibogaine (at a CYP2D6 activity score (AS) of 0) was 0.82 L/h. This increased with 30.7 L/h for every point of AS. The relation between ibogaine plasma concentrations and QTc was best described by a sigmoid Emax model. Spearman correlations were significant (p < 0.03) for ibogaine but not noribogaine with QTc (p = 0.109) and cerebellar effects (p = 0.668); neither correlated with the severity of opioid withdrawal symptoms. CONCLUSIONS: The clearance of ibogaine is strongly related to CYPD2D6 genotype. Ibogaine cardiac side effects (QTc time) and cerebellar effects are most likely more driven by ibogaine rather than noribogaine. Future studies should aim at exploring lower doses and/or applying individualized dosing based on CYP2D6 genotype.

A new efficient and integrated pathway for patient evaluation prior to atrial fibrillation ablation.

AIMS: In this quality improvement project, a care pathway for patients considered for atrial fibrillation (AF) ablation was optimized with the goals to improve the patient journey and simultaneously integrate prospective data collection into the clinical process. METHODS AND RESULTS: The Lean Six Sigma approach was used to map the pre-existing process, identify constraints, and formulate countermeasures. The percentage of patients going through the full pre-ablation preparation that eventually underwent AF ablation, number of hospital visits and consultations, pathway compliance, and completeness of scientific data were measured before and after pathway optimization. Constraints in the process were (i) lack of standardized processes, (ii) inefficient use of resources, (iii) lack of multidisciplinary integration, (iv) lack of research integration, and (v) suboptimal communication. The impact of the corresponding countermeasures (defining a uniform process, incorporating 'go/no-go' moment, introducing a 'one-stop-shop', integrating prospective data collection, and improving communication) was studied for 33 patients before and 26 patients after pathway optimization. After optimization, the percentage of patients receiving a full pre-ablation preparation that eventually underwent AF ablation increased from 59% to 94% (P < 0.01). Fewer hospital visits (3.2 ± 1.2 vs. 2.3 ± 0.8, P = 0.01) and electrophysiologist consultations (1.8 ± 0.7 vs. 1.0 ± 0.3, P < 0.01) were required after pathway optimization. Pathway compliance and complete collection of scientific data increased significantly (3% vs. 73%, P < 0.01 and 15% vs. 73%, P < 0.01, respectively). CONCLUSION: The optimization project resulted in a more efficient evaluation of patients considered for AF ablation. The new more efficient process includes prospective data collection and facilitates easy conduct of research studies focused on improvements of patient outcomes.

Atrial fibrillation-specific refinement of the STOP-Bang sleep apnoea screening questionnaire: insights from the Virtual-SAFARI study.

BACKGROUND: Sleep-disordered breathing (SDB) is prevalent in up to 50% of patients referred for atrial fibrillation (AF) catheter ablation (CA). Currently, it remains unclear how to improve pre-selection for SDB screening in patients with AF. AIM: We aimed to (1) assess the accuracy of the STOP-Bang screening questionnaire for detection of SDB within an AF population referred for CA; (2) derive a refined, AF-specific SDB score to improve pre-selection. METHODS: Consecutive AF patients referred for CA without a history of SDB and/or SDB screening were included. Patients were digitally referred to the previously implemented Virtual-SAFARI SDB screening and management pathway including a home sleep test. An apnoea-hypopnoea index (AHI) of  ≥ 15 was interpreted as moderate-to-severe SDB. Logistic regression analysis was used to assess characteristics associated with moderate-to-severe SDB to refine pre-selection for SDB screening. RESULTS: Of 206 included patients, 51% were diagnosed with moderate-to-severe SDB. The STOP-Bang questionnaire performed poorly in detecting SDB, with an area under the receiver operating characteristic curve (AUROC) of 0.647 (95% Confidence-Interval (CI) 0.573-0.721). AF-specific refinement resulted in the BOSS-GAP score. Therein, BMI with cut-off point ≥ 27 kg/m2 and previous stroke or transient ischaemic attack (TIA) were added, while tiredness and neck circumference were removed. The BOSS-GAP score performed better with an AUROC of 0.738 (95% CI 0.672-0.805) in the overall population. CONCLUSION: AF-specific refinement of the STOP-Bang questionnaire moderately improved detection of SDB in AF patients referred for CA. Whether questionnaires bring benefits for pre-selection of SDB compared to structural screening in patients with AF requires further studies. TRIAL REGISTRATION NUMBER: ISOLATION was registered NCT04342312, 13-04-2020.

Isolating the pulmonary veins as first-line therapy in patients with lone paroxysmal atrial fibrillation using the cryoballoon.

AIMS: Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. Nowadays, catheter-based ablative approaches are mainly reserved for drug-refractory patients. However, the value of an ablative therapy as a first-line alternative remains elusive. The aim of our study was to analyse the acute procedural success and clinical outcome of patients with lone paroxysmal AF undergoing cryoballoon ablation (CBA) as first-line treatment. METHODS AND RESULTS: Eighteen individuals (mean age 44 ± 9 years, range 23-61 years, 15 males) with lone paroxysmal AF preferring a catheter-based treatment to drug treatment as first-line therapy were consecutively enrolled in our study. Mean left atrial size was 39 ± 4 mm and mean left ventricular ejection fraction 58 ± 3%. After a mean of 2.4 CBA (range 2-4) applications pulmonary vein (PV) isolation could be demonstrated in 70 (97%) PVs. Additional lesions with a focal ablation catheter were needed to isolate one right inferior pulmonary vein and one left superior pulmonary vein in two different patients. At the end of the procedure, all (100%) PVs were isolated. After a 2-month blanking period, 16 patients (89%) were free of symptomatic AF recurrence at a mean follow-up of 14 ± 9 months and without antiarrhythmic drugs (AADs). CONCLUSION: Cryoballoon ablation in patients with lone paroxysmal AF yields a high acute efficacy rate with a great chance of being free of symptomatic AF recurrence without antiarrhythmic drugs on a mid-term follow-up period, when offered as a first-line treatment.

Pulmonary vein isolation during cryoballoon ablation using the novel Achieve inner lumen mapping catheter: a feasibility study.

AIMS: Cryoballoon (CB) ablation has proven very effective in achieving pulmonary vein isolation (PVI). The Achieve catheter (AC) is a novel inner lumen catheter designed to be used in conjunction with the CB, which serves the double purpose of a guidewire and a mapping catheter. We aimed to evaluate the feasibility of CB ablation in conjunction with the novel AC, in terms of PVI and safety in a series of patients affected by drug resistant paroxysmal atrial fibrillation (AF). METHODS AND RESULTS: Seventy patients (49 male) affected by paroxysmal AF were assigned to CB PVI using the AC as a mapping catheter. Patients underwent loop-Holter monitoring 1, 3 and 6 months after ablation. Isolation occurred in 98% of PVs with the CB-AC association without having switching to a regular guidewire. Pulmonary vein isolation could be documented by real-time (RT) recordings in 47% (132) of veins. Time to isolation was significantly longer in PVs exhibiting early left atrium-PV reconnection if compared with veins with sustained isolation (117 ± 25 s vs. 59 ± 25 s; P< 0,005). No serious complications occurred; four transient phrenic nerve palsies occurred all resolving completely before the end of the procedure. CONCLUSION: Cryoballoon ablation in conjunction with the novel AC is feasible, safe, and most importantly affords PVI in nearly all veins without having to switch to a regular guidewire. However, RT recordings could be documented in only 47% of pulmonary veins.

Single procedural outcomes in the setting of percutaneous ablation for persistent atrial fibrillation: a propensity-matched score comparison between different strategies.

BACKGROUND: Catheter ablation for persistent atrial fibrillation (persAF) is associated with less favorable outcomes than for paroxysmal AF. To improve success rates, left atrial (LA) substrate modification is frequently performed in addition to pulmonary vein isolation (PVI). The purpose of the study was to compare 4 different ablation approaches using radiofrequency catheter ablation (RFCA) or cryoballoon ablation (CB-A) for persAF and to evaluate the respective outcomes on a midterm follow-up of 12 months. METHODS: We did a propensity score-matched comparison of 30 patients undergoing PVI + LA posterior wall isolation (LAPWI) with CB-A, 30 patients who underwent PVI + linear ablation (roof and mitral lines) using RFCA, 60 patients with PVI alone using CB-A, and 60 patients who had PVI alone using RFCA. The endpoint was recurrence of documented atrial tachyarrhythmias (ATas) > 30 s at 1-year follow-up. RESULTS: After 12 months, freedom from ATas after a single procedure was 83.3% in the PVI + LAPWI group, 46.7% in the PVI + linear ablation group, 58.3% in the PVI-alone CB-A group, and 61.6% PVI-alone RFCA (p = 0.03). Moreover, freedom from ATas was significantly higher comparing the PVI + LAPWI group with each of the other groups. CONCLUSIONS: In this propensity-matched comparison of strategies for persAF, LAPW ablation in addition to PVI with CB-A seems to improve 1-year outcome in comparison to PVI + linear ablation using RFCA and to PVI alone using RFCA or CB-A. Randomized comparisons are eagerly awaited.

Rationale and Design of the ISOLATION Study: A Multicenter Prospective Cohort Study Identifying Predictors for Successful Atrial Fibrillation Ablation in an Integrated Clinical Care and Research Pathway.

Introduction: Continuous progress in atrial fibrillation (AF) ablation techniques has led to an increasing number of procedures with improved outcome. However, about 30-50% of patients still experience recurrences within 1 year after their ablation. Comprehensive translational research approaches integrated in clinical care pathways may improve our understanding of the complex pathophysiology of AF and improve patient selection for AF ablation. Objectives: Within the "IntenSive mOlecular and eLectropathological chAracterization of patienTs undergoIng atrial fibrillatiOn ablatioN" (ISOLATION) study, we aim to identify predictors of successful AF ablation in the following domains: (1) clinical factors, (2) AF patterns, (3) anatomical characteristics, (4) electrophysiological characteristics, (5) circulating biomarkers, and (6) genetic background. Herein, the design of the ISOLATION study and the integration of all study procedures into a standardized pathway for patients undergoing AF ablation are described. Methods: ISOLATION (NCT04342312) is a two-center prospective cohort study including 650 patients undergoing AF ablation. Clinical characteristics and routine clinical test results will be collected, as well as results from the following additional diagnostics: determination of body composition, pre-procedural rhythm monitoring, extended surface electrocardiogram, biomarker testing, genetic analysis, and questionnaires. A multimodality model including a combination of established predictors and novel techniques will be developed to predict ablation success. Discussion: In this study, several domains will be examined to identify predictors of successful AF ablation. The results may be used to improve patient selection for invasive AF management and to tailor treatment decisions to individual patients.

Left Ventricular Lead Placement Guided by Reduction in QRS Area.

Background: Reduction in QRS area after cardiac resynchronization therapy (CRT) is associated with improved long-term clinical outcome. The aim of this study was to investigate whether the reduction in QRS area is associated with hemodynamic improvement by pacing different LV sites and can be used to guide LV lead placement. Methods: Patients with a class Ia/IIa CRT indication were prospectively included from three hospitals. Acute hemodynamic response was assessed as the relative change in maximum rate of rise of left ventricular (LV) pressure (%∆LVdP/dtmax). Change in QRS area (∆QRS area), in QRS duration (∆QRS duration), and %∆LVdP/dtmax were studied in relation to different LV pacing locations within a patient. Results: Data from 52 patients paced at 188 different LV pacing sites were investigated. Lateral LV pacing resulted in a larger %∆LVdP/dtmax than anterior or posterior pacing (p = 0.0007). A similar trend was found for ∆QRS area (p = 0.001) but not for ∆QRS duration (p = 0.23). Pacing from the proximal electrode pair resulted in a larger %∆LVdP/dtmax (p = 0.004), and ∆QRS area (p = 0.003) but not ∆QRS duration (p = 0.77). Within patients, correlation between ∆QRS area and %∆LVdP/dtmax was 0.76 (median, IQR 0.35; 0,89). Conclusion: Within patients, ∆QRS area is associated with %∆LVdP/dtmax at different LV pacing locations. Therefore, QRS area, which is an easily, noninvasively obtainable and objective parameter, may be useful to guide LV lead placement in CRT.

Comparing Ventricular Synchrony in Left Bundle Branch and Left Ventricular Septal Pacing in Pacemaker Patients.

BACKGROUND: Left bundle branch area pacing (LBBAP) has recently been introduced as a novel physiological pacing strategy. Within LBBAP, distinction is made between left bundle branch pacing (LBBP) and left ventricular septal pacing (LVSP, no left bundle capture). OBJECTIVE: To investigate acute electrophysiological effects of LBBP and LVSP as compared to intrinsic ventricular conduction. METHODS: Fifty patients with normal cardiac function and pacemaker indication for bradycardia underwent LBBAP. Electrocardiography (ECG) characteristics were evaluated during pacing at various depths within the septum: starting at the right ventricular (RV) side of the septum: the last position with QS morphology, the first position with r' morphology, LVSP and-in patients where left bundle branch (LBB) capture was achieved-LBBP. From the ECG's QRS duration and QRS morphology in lead V1, the stimulus- left ventricular activation time left ventricular activation time (LVAT) interval were measured. After conversion of the ECG into vectorcardiogram (VCG) (Kors conversion matrix), QRS area and QRS vector in transverse plane (Azimuth) were determined. RESULTS: QRS area significantly decreased from 82 ± 29 µVs during RV septal pacing (RVSP) to 46 ± 12 µVs during LVSP. In the subgroup where LBB capture was achieved (n = 31), QRS area significantly decreased from 46 ± 17 µVs during LVSP to 38 ± 15 µVs during LBBP, while LVAT was not significantly different between LVSP and LBBP. In patients with normal ventricular activation and narrow QRS, QRS area during LBBP was not significantly different from that during intrinsic activation (37 ± 16 vs. 35 ± 19 µVs, respectively). The Azimuth significantly changed from RVSP (-46 ± 33°) to LVSP (19 ± 16°) and LBBP (-22 ± 14°). The Azimuth during both LVSP and LBBP were not significantly different from normal ventricular activation. QRS area and LVAT correlated moderately (Spearman's R = 0.58). CONCLUSIONS: ECG and VCG indices demonstrate that both LVSP and LBBP improve ventricular dyssynchrony considerably as compared to RVSP, to values close to normal ventricular activation. LBBP seems to result in a small, but significant, improvement in ventricular synchrony as compared to LVSP.

Computerized Analysis of the Ventricular Fibrillation Waveform Allows Identification of Myocardial Infarction: A Proof-of-Concept Study for Smart Defibrillator Applications in Cardiac Arrest.

Background In cardiac arrest, computerized analysis of the ventricular fibrillation (VF) waveform provides prognostic information, while its diagnostic potential is subject of study. Animal studies suggest that VF morphology is affected by prior myocardial infarction (MI), and even more by acute MI. This experimental in-human study reports on the discriminative value of VF waveform analysis to identify a prior MI. Outcomes may provide support for in-field studies on acute MI. Methods and Results We conducted a prospective registry of implantable cardioverter defibrillator recipients with defibrillation testing (2010-2014). From 12-lead surface ECG VF recordings, we calculated 10 VF waveform characteristics. First, we studied detection of prior MI with lead II, using one key VF characteristic (amplitude spectrum area [AMSA]). Subsequently, we constructed diagnostic machine learning models: model A, lead II, all VF characteristics; model B, 12-lead, AMSA only; and model C, 12-lead, all VF characteristics. Prior MI was present in 58% (119/206) of patients. The approach using the AMSA of lead II demonstrated a C-statistic of 0.61 (95% CI, 0.54-0.68). Model A performance was not significantly better: 0.66 (95% CI, 0.59-0.73), P=0.09 versus AMSA lead II. Model B yielded a higher C-statistic: 0.75 (95% CI, 0.68-0.81), P<0.001 versus AMSA lead II. Model C did not improve this further: 0.74 (95% CI, 0.67-0.80), P=0.66 versus model B. Conclusions This proof-of-concept study provides the first in-human evidence that MI detection seems feasible using VF waveform analysis. Information from multiple ECG leads rather than from multiple VF characteristics may improve diagnostic accuracy. These results require additional experimental studies and may serve as pilot data for in-field smart defibrillator studies, to try and identify acute MI in the earliest stages of cardiac arrest.

Atrial fibrillation in patients with an atrial septal defect in a single centre cohort during a long clinical follow-up: its association with closure and outcome of therapy.

OBJECTIVE: Currently, consensus is lacking on the relation between closure of atrial septal defect (ASD) and the incidence of atrial fibrillation (AF), which is a known complication in ASD patients. More importantly, studies reporting on the treatment applied for AF in ASD patients are scarce. The aims of this study were (1) to assess the incidence of AF in ASD patients, (2) to study the relation between closure and AF and (3) to evaluate applied treatment strategies. METHODS: A single-centre retrospective study in 173 patients with an ASD was performed. We analysed the incidence of AF, the relation of AF with closure, method of closure and the treatment success of therapies applied. RESULTS: Almost 20% of patients with an ASD developed AF, with a mean age of 59 (±14) years at first presentation of AF during a median clinical follow-up of 43 (29-59) years. Older age (OR 1.072; p<0.001) and a dilated left atrium (OR 3.727; p=0.009) were independently associated with new-onset AF. Closure itself was not independently associated with AF. First applied treatment strategy was rhythm control in 77%. Of the 18 patients treated with antiarrhythmic drugs 50% had at least 1 recurrence of AF. CONCLUSION: No clear relation between closure of the ASD and AF could be assessed. This is the first study describing applied therapy for AF in ASD patients of which medical rhythm control was the most applied strategy with a disappointing efficacy.