Catheter ablation for persistent atrial fibrillation: patterns of recurrence and impact on quality of life and health care utilisation.

BACKGROUND AND AIMS: Patterns of atrial fibrillation (AF) recurrence post catheter ablation for persistent AF are not well described. This study aimed to describe the pattern of AF recurrence seen following catheter ablation for persistent AF (PsAF) and the implications for healthcare utilisation and quality of life. METHODS: This was a post-hoc analysis of the CAPLA study, an international, multi-centre study that randomised patients with symptomatic PsAF to pulmonary vein isolation plus posterior wall isolation or pulmonary vein isolation alone. Patients underwent twice daily single lead ECG, implantable device monitoring or three monthly Holter monitoring. RESULTS: 154 of 333 (46.2%) patients (median age 67.3 years, 28% female) experienced AF recurrence at 12-month follow-up. Recurrence was paroxysmal in 97 (63%) patients and persistent in 57 (37%). Recurrence type did not differ between randomisation groups (p=0.508). Median AF burden was 27.4% in PsAF recurrence and 0.9% in paroxysmal AF (PAF) recurrence (p<0.001). Patients with PsAF recurrence had lower baseline left ventricular ejection fraction (PsAF 50% vs PAF 60%, p<0.001) and larger left atrial volume (PsAF 54.2±19.3 ml/m² vs PAF 44.8±11.6 ml/m², p=0.008). Healthcare utilisation was significantly higher in PsAF (45 patients [78.9%]) vs PAF recurrence (45 patients [46.4%], p<0.001) and lowest in those without recurrence (17 patients [9.5%], p<0.001). Patients without AF recurrence had greater improvements in quality of life as assessed by the Atrial Fibrillation Effect on Quality-of-Life (AFEQT) questionnaire (Δ33.3±25.2 points) compared to those with PAF (Δ24.0±25.0 points, p=0.012) or PsAF (Δ13.4±22.9 points, p<0.001) recurrence. CONCLUSIONS: AF recurrence is more often paroxysmal after catheter ablation for PsAF irrespective of ablation strategy. Recurrent PsAF was associated with higher AF burden, increased healthcare utilisation and antiarrhythmic drug use. The type of AF recurrence and AF burden may be considered important endpoints in clinical trials investigating ablation of PsAF.

Sex-specific outcomes after catheter ablation for persistent AF.

BACKGROUND: Sex-specific outcomes after catheter ablation (CA) for atrial fibrillation (AF) have reported conflicting findings. OBJECTIVE: We examined the impact of female sex on outcomes in patients with persistent AF (PsAF) from the Catheter Ablation for Persistent Atrial Fibrillation: A Multicentre Randomized Trial of Pulmonary Vein Isolation vs PVI with Posterior Left Atrial Wall Isolation (CAPLA) randomized trial. METHODS: A total of 338 patients with PsAF were randomized to pulmonary vein isolation (PVI) or PVI with posterior wall isolation (PWI). The primary outcome was arrhythmia recurrence at 12 months. Clinical and electroanatomical characteristics, arrhythmia recurrence, and quality of life were compared between women and men. RESULTS: Seventy-nine women (23.4%; PVI 37; PVI + PWI 42) and 259 men (76.6%; PVI 131; PVI + PWI 128) underwent AF ablation. Women were older {median age 70.4 (interquartile range [IQR] 64.8-74.6) years vs 64.0 (IQR 56.7-69.7) years; P < .001} and had more advanced left atrial electroanatomical remodeling. At 12 months, arrhythmia-free survival was lower in women (44.3% vs 56.8% in men; hazard ratio 1.44; 95% confidence interval 1.02-2.04; log-rank, P = .036). PWI did not improve arrhythmia-free survival at 12 months (hazard ratio 1.02; 95% confidence interval 0.74-1.40; log-rank, P = .711). The median AF burden was 0% in both groups (women: IQR 0.0%-2.2% vs men: IQR 0.0%-2.8%; P = .804). Health care utilization was comparable between women (36.7%) and men (30.1%) (P = .241); however, women were more likely to undergo a repeat procedure (17.7% vs 6.9%; P = .007). Women reported more severe baseline anxiety (average Hospital Anxiety and Depression Scale [HADS] anxiety score 7.5 ± 4.9 vs 6.3 ± 4.3 in men; P = .035) and AF-related symptoms (baseline Atrial Fibrillation Effect on Quality-of-Life Questionnaire [AFEQT] score 46.7 ± 20.7 vs 55.9 ± 23.0 in men; P = .002), with comparable improvements in psychological symptoms (change in HADS anxiety score -3.8 ± 4.6 vs -3.0 ± 4.5; P = .152 (change in HADS depression score -2.9 ± 5.0 vs -2.6 ± 4.0; P = .542) and greater improvement in AFEQT score compared with men at 12 months (change in AFEQT score +45.9 ± 23.1 vs +39.2 ± 24.8; P = .048). CONCLUSION: Women undergoing CA for PsAF report more significant symptoms and poorer quality of life at baseline than men. Despite higher arrhythmia recurrence and repeat procedures in women, the AF burden was comparably low, resulting in significant improvements in quality of life and psychological well-being after CA in both sexes.

The Role of Posterior Wall Isolation in Catheter Ablation for Persistent Atrial Fibrillation and Systolic Heart Failure: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Catheter ablation for patients with atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF) is associated with improved left ventricular ejection fraction (LVEF) and survival compared with medical therapy. Nonrandomized studies have reported improved success with posterior wall isolation (PWI). Objective: To determine the impact of pulmonary vein isolation (PVI) with PWI vs PVI alone on outcomes in patients with HFrEF. Design, Setting, and Participants: This was an ad hoc secondary analysis of the CAPLA trial, a multicenter, prospective, randomized control trial that involved 11 centers in 3 countries (Australia, Canada, and UK). CAPLA featured 338 patients with persistent AF randomized to either PVI plusPWI or PVI alone. This substudy included patients in the original CAPLA study who had symptomatic HFrEF (LVEF <50% and New York Heart Association class ≥II). Interventions: Pulmonary vein isolation with PWI vs PVI alone. Main Outcomes and Measures: The primary end point was freedom from any documented atrial arrhythmia greater than 30 seconds, after a single ablation procedure, without the use of antiarrhythmic drug (AAD) therapy at 12 months. Results: A total of 98 patients with persistent AF and symptomatic HFrEF were identified (mean [SD] age, 62.1 [9.8] years; 79.5% men; and mean [SD] LVEF at baseline, 34.6% [7.9%]). After 12 months, 58.7% of patients with PVI plus PWI were free from recurrent atrial arrhythmia without the use of AAD therapy vs 61.5% with PVI alone (hazard ratio, 1.02; 95% CI, 0.54-1.91; P = .96). There were no significant differences in freedom from atrial arrhythmia with or without AAD therapy after multiple procedures (PVI plus PWI vs PVI alone, 60.9% vs 65.4%; P = .73) or AF burden (median, 0% in both groups; P = .78). Mean LVEF improved substantially in PVI plus PWI (∆ LVEF, 19.3% [13.0%; P < .01) and PVI alone (18.2% [14.1%; P < .01), with no difference between groups (P = .71). Normalization of LV function occurred in 65.2% of patients in the PVI plus PWI group and 50.0% of patients with PVI alone (P = .13). Conclusions and Relevance: The results of this study indicate that addition of PWI to PVI did not improve freedom from arrhythmia recurrence or recovery of LVEF in patients with persistent AF and symptomatic HFrEF. Catheter ablation was associated with significant improvements in systolic function, irrespective of ablation strategy used. These results caution against the routine inclusion of PWI in patients with HFrEF undergoing first-time catheter ablation for persistent AF. Trial Registration: http://anzctr.org.au Identifier: ACTRN12616001436460.

Impact of Posterior Left Atrial Voltage on Ablation Outcomes in Persistent Atrial Fibrillation: CAPLA Substudy.

BACKGROUND: Pulmonary vein isolation (PVI) is less effective in patients with persistent atrial fibrillation (PsAF). Adjunctive ablation targeting low voltage areas (LVAs) may improve arrhythmia outcomes. OBJECTIVES: This study aims to compare the outcomes of adding posterior wall isolation (PWI) to PVI, vs PVI alone in PsAF patients with posterior wall LVAs. METHODS: The CAPLA (Effect of Catheter Ablation Using Pulmonary Vein Isolation With vs Without Posterior Left Atrial Wall Isolation on Atrial Arrhythmia Recurrence in Patients With Persistent Atrial Fibrillation) study was a multicenter, randomized trial involving PsAF patients randomized 1:1 to either PVI alone or PVI with PWI. Voltage mapping performed during pacing pre-ablation was reviewed offline, with LVA defined as bipolar voltage of <0.5 mV. The primary endpoint was freedom from any documented atrial arrhythmia of >30 seconds off antiarrhythmic medication at 12 months after a single ablation procedure in patients with posterior LVA. RESULTS: A total of 210 patients (average 64.6 ± 9.2 years,73.3% males, median atrial fibrillation duration 4.5 months [IQR: 2 to 8 months]) underwent multipolar left atrial mapping during coronary sinus pacing with posterior LVA present in 69 (32.9%). Patients with posterior LVA were more likely to have LVA in other atrial regions (91.7% vs 57.1%; P < 0.01), larger left atrial diameter (4.8 cm vs 4.4 cm; P < 0.01), and significantly increased risk of atrial arrhythmia recurrence at 12 months (LVA: 56.5% vs no LVA: 41.4%; HR: 1.51; 95% CI: 1.01-2.27; P = 0.04) compared to no posterior LVA. However, the addition of PWI to PVI did not significantly improve freedom from atrial arrhythmia recurrence over PVI alone (PVI with PWI: 44.8% vs PVI: 41.9%; HR: 0.95; 95% CI: 0.51-1.79; P = 0.95). CONCLUSIONS: In patients with PsAF undergoing catheter ablation, posterior LVA was associated with a significant increase in atrial arrhythmia recurrence. However, the addition of PWI in those with posterior LVA did not reduce atrial arrhythmia recurrence over PVI alone.

Posterior Wall Isolation Improves Outcomes for Persistent AF With Rapid Posterior Wall Activity: CAPLA Substudy.

BACKGROUND: Pulmonary vein isolation (PVI) is less effective in persistent atrial fibrillation (PerAF) than in paroxysmal atrial fibrillation (AF). However, the CAPLA (Effect of Catheter Ablation Using Pulmonary Vein Isolation With vs Without Posterior Left Atrial Wall Isolation on Atrial Arrhythmia Recurrence in Patients With Persistent Atrial Fibrillation: The CAPLA randomized clinical trial) of PVI vs posterior wall isolation (PWI) did not support empiric PWI in PerAF. We examined pulmonary vein (PV) and posterior wall (PW) electrical characteristics to determine if select patients may benefit from additional PWI. OBJECTIVES: This study sought to determine the impact of PV and PW electrical characteristics on AF ablation outcomes in the CAPLA randomized study. METHODS: Participants in spontaneous AF at the time of ablation were included from the CAPLA study. The mean, shortest, and longest PV, PW, and left atrial (LA) appendage cycle length measurements were annotated preablation using a multipolar catheter for 100 consecutive cycles. Next, cardioversion was performed with a high-density LA voltage map completed. Cox proportional hazards regression was utilized to determine clinical and electroanatomic predictors of AF recurrence overall and according to ablation strategy. Follow-up included twice daily single-lead electrocardiograms or continuous monitoring for 12 months. RESULTS: A total of 151 patients (27% female, age 65 ± 9 years, 18% long-standing PerAF, LA volume index 52 ± 16 mL/m2, median AF duration 5 months [IQR: 2-10 months]) were in AF on the day of procedure and were randomized to PVI alone (50%) or PVI+PWI (50%) according to the CAPLA randomized clinical trial protocol. Baseline clinical, echocardiographic, and electroanatomic parameters were comparable between groups (all P > 0.05) including PV and PW characteristics. After 12 months, freedom from AF off antiarrhythmic drug therapy was 51.7% in PVI and 49.7% in PVI+PWI (log-rank P = 0.564). Rapid PW activity was defined as less than the median of the shortest PW cycle length (140 ms) and rapid PV activity was defined as less than the median of the shortest PV cycle length (126 ms). In those with rapid PW activity, the addition of PWI was associated with greater arrhythmia-free survival (56.4%) vs PVI alone (38.6%) (HR: 0.78; 95% CI: 0.67-0.94; log-rank P = 0.030). Moreover, in those undergoing PVI only, the risk of AF recurrence was higher in those with rapid PW activity (55.3% vs 46.5% in slower PW activity; HR: 1.50, 95%CI 1.11-2.26; log-rank P = 0.036). Rapid PV activity and PV cycle length (individual PVs or average of all 4 PVs) were not associated with outcome (all P > 0.05) regardless of ablation strategy. There was no correlation between PW cycle length and posterior low voltage (r = -0.06, P = 0.496). The addition of PWI did not improve arrhythmia-free survival in subgroups with LA enlargement (LA volume index >34 mL/m2) (HR: 0.69; 95% CI: 0.39-1.25; P = 0.301), posterior low-voltage zone (HR: 1.06; 95% CI: 0.68-1.66; P = 0.807), or long-standing PerAF (HR: 1.10; 95% CI: 0.71-1.72; P = 0.669). CONCLUSIONS: Rapid PW activity is associated with an increased risk of AF recurrence post-catheter ablation. The addition of PWI in this subgroup was associated with a significant improvement in freedom from AF compared with PVI alone. The presence of rapid PW activity may identify patients with PerAF likely to benefit from PWI.

Myocarditis as a trigger for the expression of biventricular arrhythmogenic cardiomyopathy in desmosomal gene mutation.

Arrhythmogenic-cardiomyopathy (ACM) is an inherited heart disease with right, left, or biventricular (BVACM) involvement based on EKG, imaging, family history, and genetic testing. We present a 64-year-old woman with prior myocarditis and diagnosis of BVACM 29 years later. We propose myocarditis as a promoter of gene expression of plakophilin-2 mutation.

Contact force and catheter stability are predictive metrics of successful pulmonary vein isolation with high-power short duration ablation in atrial fibrillation.

INTRODUCTION: Preliminary data suggest that high power short duration (HPSD) ablation for pulmonary vein isolation (PVI) are safe. Limited data are available on its effectiveness. Aim was to evaluate HPSD ablation in atrial fibrillation ablation using a novel Qdot Micro catheter. METHODS AND RESULTS: Prospective multicenter study evaluating safety and efficacy of PVI with HPSD ablation. First pass isolation (FPI) and sustained PVI was assessed. If FPI was not achieved additional ablation index (AI)-guided ablation with 45 W was performed and metrics predictive of this were determined. Sixty-five patients and 260 veins were treated. Procedural and LA dwell time was 93.9 ± 30.4 and 60.5 ± 23.1 min, respectively. FPI was achieved in 47 (72.3%) patients and 231 veins (88.8%) with an ablation duration of 4.6 ± 1.0 min. Twenty-nine veins required additional AI-guided ablation to achieve initial PVI with 24 anatomical sites ablated with the right posterior carina being the most common site (37.5%). A contact force of ≥8 g (area under the curve [AUC]: 0.81; p < 0.001) and catheter position variation of ≤1.2 mm (AUC: 0.79; p < 0.001) with HPSD were strongly predictive of not requiring additional AI-guided ablation. Out of the 260 veins, only 5 (1.9%) veins showed acute reconnection. HPSD ablation was associated with shorter procedure times (93.9 vs. 159.4 min; p < 0.001), ablation times (6.1 vs. 27.7 min; p < 0.001), and lower rates of PV reconnection (9.2% vs. 30.8%; p = 0.004) compared to moderate power cohort. CONCLUSIONS: HPSD ablation is an effective ablation modality which results in effective PVI whilst maintaining a safety profile. Its superiority needs to be evaluated in randomized controlled trials.

Effect of Catheter Ablation Using Pulmonary Vein Isolation With vs Without Posterior Left Atrial Wall Isolation on Atrial Arrhythmia Recurrence in Patients With Persistent Atrial Fibrillation: The CAPLA Randomized Clinical Trial.

Importance: Pulmonary vein isolation (PVI) alone is less effective in patients with persistent atrial fibrillation (AF) compared with paroxysmal AF. The left atrial posterior wall may contribute to maintenance of persistent AF, and posterior wall isolation (PWI) is a common PVI adjunct. However, PWI has not been subjected to randomized comparison. Objective: To compare PVI with PWI vs PVI alone in patients with persistent AF undergoing first-time catheter ablation. Design, Setting, and Participants: Investigator initiated, multicenter, randomized clinical trial involving 11 centers in 3 countries (Australia, Canada, UK). Symptomatic patients with persistent AF were randomized 1:1 to either PVI with PWI or PVI alone. Patients were enrolled July 2018-March 2021, with 1-year follow-up completed March 2022. Interventions: The PVI with PWI group (n = 170) underwent wide antral pulmonary vein isolation followed by posterior wall isolation involving linear ablation at the roof and floor to achieve electrical isolation. The PVI-alone group (n = 168) underwent wide antral pulmonary vein isolation alone. Main Outcomes and Measures: Primary end point was freedom from any documented atrial arrhythmia of more than 30 seconds without antiarrhythmic medication at 12 months, after a single ablation procedure. The 23 secondary outcomes included freedom from atrial arrhythmia with/without antiarrhythmic medication after multiple procedures, freedom from symptomatic AF with/without antiarrhythmic medication after multiple procedures, AF burden between study groups at 12 months, procedural outcomes, and complications. Results: Among 338 patients randomized (median age, 65.6 [IQR, 13.1] years; 76.9% men), 330 (97.6%) completed the study. After 12 months, 89 patients (52.4%) assigned to PVI with PWI were free from recurrent atrial arrhythmia without antiarrhythmic medication after a single procedure, compared with 90 (53.6%) assigned to PVI alone (between-group difference, -1.2%; hazard ratio [HR], 0.99 [95% CI, 0.73-1.36]; P = .98). Of the secondary end points, 9 showed no significant difference, including freedom from atrial arrhythmia with/without antiarrhythmic medication after multiple procedures (58.2% for PVI with PWI vs 60.1% for PVI alone; HR, 1.10 [95% CI, 0.79-1.55]; P = .57), freedom from symptomatic AF with/without antiarrhythmic medication after multiple procedures (68.2% vs 72%; HR, 1.20 [95% CI, 0.80-1.78]; P = .36) or AF burden (0% [IQR, 0%-2.3%] vs 0% [IQR, 0%-2.8%], P = .47). Mean procedural times (142 [SD, 69] vs 121 [SD, 57] minutes, P < .001) and ablation times (34 [SD, 21] vs 28 [SD, 12] minutes, P < .001) were significantly shorter for PVI alone. There were 6 complications for PVI with PWI and 4 for PVI alone. Conclusions and Relevance: In patients undergoing first-time catheter ablation for persistent AF, the addition of PWI to PVI alone did not significantly improve freedom from atrial arrhythmia at 12 months compared with PVI alone. These findings do not support the empirical inclusion of PWI for ablation of persistent AF. Trial Registration: anzctr.org.au Identifier: ACTRN12616001436460.

Therapeutic benefits of distal ventricular pacing in mid-cavity obstructive hypertrophic cardiomyopathy.

INTRODUCTION: Hypertrophic cardiomyopathy (HCM) patients with left ventricular (LV) mid-cavity obstruction (LVMCO) often experience severe drug-refractory symptoms thought to be related to intraventricular obstruction. We tested whether ventricular pacing, guided by invasive haemodynamic assessment, reduced LVMCO and improved refractory symptoms. METHODS: Between December 2008 and December 2017, 16 HCM patients with severe refractory symptoms and LVMCO underwent device implantation with haemodynamic pacing study to assess the effect on invasively defined LVMCO gradients. The effect on the gradient of atrioventricular (AV) synchronous pacing from sites including right ventricular (RV) apex and middle cardiac vein (MCV) was retrospectively assessed. RESULTS: Invasive haemodynamic data were available in 14 of 16 patients. Mean pre-treatment intracavitary gradient was 77 ± 22 mmHg (in sinus rhythm) versus 21 ± 21 mmHg during pacing from optimal ventricular site (95% CI: -70.86 to -40.57, p < 0.0001). Optimal pacing site was distal MCV in 12/16 (86%), RV apex in 1/16 and via epicardial LV lead in 1/16. Pre-pacing Doppler-derived gradients were significantly higher than at follow-up (47 ± 15 versus 24 ± 16 mmHg, 95% CI: -37.19 to -13.73, p < 0.001). Median baseline NYHA class was 3, which had improved by ⩾1 NYHA class in 13 of 16 patients at 1-year post-procedure (p < 0.001). The mean follow-up duration was 4.6 ± 2.7 years with the following outcomes: 8/16 (50%) had continued symptomatic improvement, 4/16 had symptomatic decline and 4/16 died. Contributors to symptomatic decline included chronic atrial fibrillation (AF) (n = 5), phrenic nerve stimulation (n = 3) and ventricular ectopy (n = 1). CONCLUSION: In drug-refractory symptomatic LVMCO, distal ventricular pacing can reduce intracavitary obstruction and may provide long-term symptomatic relief in patients with limited treatment options. A haemodynamic pacing study is an effective strategy for identifying optimal pacing site and configuration.

Efficacy and safety of same-day discharge after atrial fibrillation ablation compared with post-procedural overnight stay: a systematic review and meta-analysis.

AIMS: Catheter ablation for atrial fibrillation (AF) has historically required inpatient admission post-procedure, but same-day discharge (SDD) has recently been reported. We aimed to assess the efficacy and safety of SDD compared with overnight stay (OS) post-ablation. METHODS AND RESULTS: We performed a systematic search of the PubMed database. Random-effects meta-analysis was performed to assess the efficacy (successful SDD) and safety (24 h complications, 30-day complications, 30-day re-admissions, and 30-day mortality) of a SDD AF ablation strategy. Fourteen non-randomized observational studies met criteria for inclusion, encompassing 26488 patients undergoing AF ablation, of whom 9766 were SDD. The mean age of participants was 61.9 years, and 67.9% were male. Around 61.7% underwent ablation for paroxysmal AF. The pooled success rate of SDD was 83.2% [95% confidence intervals (CIs): 61.5-97.0%, I2 100%]. The risk of bias was severe for all effect estimates due to confounding, as most cohorts were retrospectively identified without appropriately matched comparators. There was no significant difference in 30-day complications [odds ratio (OR): 0.95, 95% CI: 0.65-1.40, I2 53%] or 30-day re-admission (OR 0.96, 95% CI: 0.49-1.89, I2 82%) between groups. There were insufficient data for meta-analysis of 24 h complications and 30-day mortality. Where reported, no re-admissions occurred due to 24 h complications after SDD. Two deaths (0.04%) were reported in both SDD and OS groups. CONCLUSION: Same-day discharge after AF ablation appears to be an effective and safe strategy in selected patients. However, the available evidence is of low quality, and more robust prospective studies comparing SDD to OS are needed.

Catheter ablation for persistent atrial fibrillation: A multicenter randomized trial of pulmonary vein isolation (PVI) versus PVI with posterior left atrial wall isolation (PWI) - The CAPLA study.

BACKGROUND: The success of pulmonary vein isolation (PVI) is reduced in persistent AF (PsAF) compared to paroxysmal AF. Adjunctive ablation strategies have failed to show consistent incremental benefit over PVI alone in randomized studies. The left atrial posterior wall is a potential source of non-PV triggers and atrial substrate which may promote the initiation and maintenance of PsAF. Adding posterior wall isolation (PWI) to PVI had shown conflicting outcomes, with earlier studies confounded by methodological limitations. OBJECTIVES: To determine whether combining PWI with PVI significantly improves freedom from AF recurrence, compared to PVI alone, in patients with PsAF. METHODS: This is a multi-center, prospective, international randomized clinical trial. 338 patients with symptomatic PsAF refractory to anti-arrhythmic therapy (AAD) will be randomized to either PVI alone or PVI with PWI in a 1:1 ratio. PVI involves wide antral circumferential pulmonary vein (PV) isolation, utilizing contact force sensing ablation catheters. PWI involves the creation of a floor line connecting the inferior aspect of the PVs, and a roof line connecting the superior aspect of the PVs. Follow up is for a minimum of 12 months with rhythm monitoring via implantable cardiac device and/or loop monitor, or frequent intermittent monitoring with an ECG device. The primary outcome is freedom from any documented atrial arrhythmia of > 30 seconds off AAD at 12 months, after a single ablation procedure. CONCLUSIONS: This randomized study aims to determine the success and safety of adjunctive PWI to PVI in patients with persistent AF.

An active fixation quadripolar left ventricular lead for cardiac resynchronization therapy with reduced postoperative complication rates.

BACKGROUND: The rate of left ventricular (LV) lead displacement after cardiac resynchronization therapy (CRT) remains high despite improvements in lead technology. In 2017, a novel quadripolar lead with active fixation technology became available in the UK. METHODS: This was a retrospective, observational study analyzing device complications in 476 consecutive patients undergoing successful first-time implantation of a CRT device at a tertiary center from 2017 to 2020. RESULTS: Both active (n = 135) and passive fixation (n = 341) quadripolar leads had similar success rates for implantation (99.3% vs. 98.8%, p = 1.00), although the pacing threshold (0.89 [0.60-1.25] vs. 1.00 [0.70-1.60] V, p = .01) and lead impedance (632 [552-794] vs. 730 [636-862] Ohms, p < .0001) were significantly lower for the active fixation lead. Patients receiving an active fixation lead had a reduced incidence of lead displacement at 6 months (0.74% vs. 4.69%, p = .036). There was no significant difference in the rate of right atrial (RA) and right ventricular (RV) lead displacement between the two groups (RA: 1.48% vs. 1.17%, p = .68; RV: 2.22% vs. 1.76%, p = .72). Reprogramming the LV lead after displacement was unsuccessful in most cases (successful reprogramming: Active fix = 0/1, Passive fix = 1/16) therefore nearly all patients required a repeat procedure. As a result, the rate of intervention within 6 months for lead displacement was significantly lower when patients were implanted with the active fixation lead (0.74% vs. 4.40%, p = .049). CONCLUSION: The novel active fixation lead in our study has a lower incidence of lead displacement and re-intervention compared to conventional quadripolar leads for CRT.

Provocation Testing and Therapeutic Response in a Newly Described Channelopathy: RyR2 Calcium Release Deficiency Syndrome.

BACKGROUND: A novel familial arrhythmia syndrome, cardiac ryanodine receptor (RyR2) calcium release deficiency syndrome (CRDS), has recently been described. We evaluated a large and well characterized family to assess provocation testing, risk factor stratification and response to therapy in CRDS. METHODS: We present a family with multiple unheralded sudden cardiac deaths and aborted cardiac arrests, primarily in children and young adults, with no clear phenotype on standard clinical testing. RESULTS: Genetic analysis, including whole genome sequencing, firmly established that a missense mutation in RYR2, Ala4142Thr, was the underlying cause of disease in the family. Functional study of the variant in a cell model showed RyR2 loss-of-function, indicating that the family was affected by CRDS. EPS (Electrophysiological Study) was undertaken in 9 subjects known to carry the mutation, including a survivor of aborted sudden cardiac death, and the effects of flecainide alone and in combination with metoprolol were tested. There was a clear gradation in inducibility of nonsustained and sustained ventricular arrhythmia between subjects at EPS, with the survivor of aborted sudden cardiac death being the most inducible subject. Administration of flecainide substantially reduced arrhythmia inducibility in this subject and abolished arrhythmia in all others. Finally, the effects of additional metoprolol were tested; it increased inducibility in 4/9 subjects. CONCLUSIONS: The Ala4142Thr mutation of RYR2 causes the novel heritable arrhythmia syndrome CRDS, which is characterized by familial sudden death in the absence of prior symptoms or a recognizable phenotype on ambulatory monitoring or exercise stress testing. We increase the experience of a specific EPS protocol in human subjects and show that it is helpful in establishing the clinical status of gene carriers, with potential utility for risk stratification. Our data provide evidence that flecainide is protective in human subjects with CRDS, consistent with the effect previously shown in a mouse model.

INtra-procedural ultraSound Imaging for DEtermination of atrial wall thickness and acute tissue changes after isolation of the pulmonary veins with radiofrequency, cryoballoon or laser balloon energy: the INSIDE PVs study.

Preliminary data in human suggest that both Intracardiac echocardiography (ICE) and Intravascular ultrasound (IVUS) can be used for real-time information on the left atrial (LA) wall thickness and on the acute tissue changes produced by energy delivery. This pilot study was conducted to compare ICE and IVUS for real-time LA wall imaging and assessment of acute tissue changes produced by radiofrequency (RF), cryo and laser catheter ablation. Patients scheduled for RF, cryoballoon or laser balloon Pulmonary Vein Isolation (PVI) catheter ablation were enrolled. Each pulmonary vein (PV) was imaged before and immediately after ablation with either ICE or IVUS. The performance of ICE and IVUS for imaging were compared. Pre- and post-ablation measurements (lumen and vessel diameters, areas and sphericity indexes, wall thickness and muscular sleeve thickness) were taken at the level of each PV ostium. A total of 48 PVs in 12 patients were imaged before and after ablation. Both ICE and IVUS showed acute tissue changes. Compared to IVUS, ICE showed higher imaging quality and inter-observer reproducibility of the PV measurements obtained. Acute wall thickening suggestive of oedema was observed after RF treatment (p = 0.003) and laser treatment (p = 0.003) but not after cryoablation (p = 0.69). Our pilot study suggests that ICE might be preferable to IVUS for LA wall thickness imaging at the LA-PV junctions during ablation. Ablation causes acute wall thickening when using RF or laser energy, but not cryoenergy delivery. Larger studies are needed to confirm these preliminary findings.

Are conflict of interest declarations appropriate to allow sufficient consideration of potential bias in presentations?

BACKGROUND: Potential conflicts of interest (CoI) are common in medical research, necessitating the use of CoI declarations. There is currently no consensus document or external authority guiding CoI declarations in conference settings, resulting in declarations of variable quality and utility. METHODS: We explored four CoI declaration parameters (sufficient slide display time; the presence of any verbal explanation pertaining to relevant CoI; the use of an adequate font size; and whether the nature and relevance of the CoI was described). Parameters were graded from one to three points, with the sum of parameters providing an overall declaration quality out of 12. We then applied this scoring system to recordings of presentations from the British Cardiovascular Society (BCS) annual conference 2018 which were available online. RESULTS: Sixty-nine presentations were suitable for inclusion, of which 47 (68%) contained a CoI statement. Thirty-six of the 47 (77%) presentations declared that they had no CoI. In the remaining 11 (23%) with reported CoI, the median time spent displaying CoI was 1 second (interquartile range (IQR) 0.7-3.3). The median quality score for presentations was 7 (IQR 6-10). CONCLUSION: This study demonstrates utility in considering aspects of CoI declarations at conferences to improve transparency.

Power, Lesion Size Index and Oesophageal Temperature Alerts During Atrial Fibrillation Ablation: A Randomized Study.

BACKGROUND: Low radiofrequency powers are commonly used on the posterior wall of the left atrium for atrial fibrillation ablation to prevent esophageal damage. Compared with higher powers, they require longer ablation durations to achieve a target lesion size index (LSI). Esophageal heating during ablation is the result of a time-dependent process of conductive heating produced by nearby radiofrequency delivery. This randomized study was conducted to compare risk of esophageal heating and acute procedure success of different LSI-guided ablation protocols combining higher or lower radiofrequency power and different target LSI values. METHODS: Eighty consecutive patients were prospectively enrolled and randomized to one of 4 combinations of radiofrequency power and target LSI for ablation on the left atrium posterior wall (20 W/LSI 4, 20 W/LSI 5, 40 W/LSI 4, and 40 W/LSI 5). The primary end point of the study was the occurrence and number of esophageal temperature alerts per patient during ablation. Acute indicators of procedure success were considered as secondary end points. Long-term follow-up data were also collected for all patients. RESULTS: Esophageal temperature alerts occurred in a similar proportion of patients in all groups. Significantly, shorter radiofrequency durations were required to achieve the target LSI in the 40 W groups. Less than 50% of the radiofrequency lesions reached the target LSI of 5 when using 20 W despite a longer radiofrequency duration. A lower rate of first-pass pulmonary vein isolation and a higher rate of acute pulmonary vein reconnection were recorded in the group 20 W/LSI 5. A lower atrial fibrillation recurrence rate was observed in the 40 W groups compared with the 20 W groups at 29 months follow-up. CONCLUSIONS: When guided by LSI, posterior wall ablation with 40 W is associated with a similar rate of esophageal temperature alerts and a lower atrial fibrillation recurrence rate at follow-up if compared with 20 W. These data will provide a basis to plan future randomized trials. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02619396.

A multicentered evaluation of ablation at higher power guided by ablation index: Establishing ablation targets for pulmonary vein isolation.

BACKGROUND: Pulmonary vein isolation (PVI) using high power delivered by SmartTouch Surround Flow (STSF) catheters guided by ablation index (AI) was evaluated in a multicenter registry. METHODS: Patients with paroxysmal AF underwent PVI with STSF catheters using 30 W on the posterior wall and 40 W elsewhere. AI targets were 350 posterior walls and 450 elsewhere. Procedures were compared with controls using conventionally irrigated contact force-sensing catheters using conventional powers (25 W posterior wall and 30 W elsewhere) guided by force-time integral (no agreed targets). The waiting period of 30 minutes was observed before adenosine administration to assess acute pulmonary vein (PV) reconnection. RESULTS: One hundred patients from four centers were included: 50 patients in the high power ablation index (HPAI) group and 50 controls. Procedure time was 22% shorter in the HPAI group (156 [133.8-179] vs 199 [178.5-227] minutes; P < 0.001). Duration of the radiofrequency application was 37% shorter in the HPAI group (27.2 [21.5-35.8] vs 43.2 [35.1-52.1] minutes; P < 0.001). Acute PV reconnection was reduced (28 of 200 [14%] vs 48 of 200 [24%] veins; P = 0.015). Reconnection was predicted by a largest interlesion distance greater than 6 mm, a lesion with impedance drop less than 2.5 Ω, contact force less than 6 g, or less than 68% of the regional AI target (all P < 0.001). Freedom from atrial arrhythmia at 1 year off antiarrhythmic drugs after a single procedure was 78% in the HPAI group vs 64% in the control group ( P = 0.186). CONCLUSION: High-powered ablation guided by AI was safe and led to shorter procedure times with reduced acute PV reconnection compared with conventional ablation.

Myocardial Perfusion Is Impaired and Relates to Cardiac Dysfunction in Patients With Atrial Fibrillation Both Before and After Successful Catheter Ablation.

Background Atrial fibrillation ( AF ) is associated with myocardial infarction, and patients with AF and no obstructive coronary artery disease can present with symptoms and evidence of cardiac ischemia. We hypothesized that microvascular coronary dysfunction underlies these observations. Methods and Results Myocardial blood flow ( MBF ) at baseline and during adenosine stress and left ventricular and left atrial function were evaluated by magnetic resonance in 49 patients with AF (25 paroxysmal, 24 persistent) with no history of epicardial coronary artery disease or diabetes mellitus, before and 6 to 9 months after ablation. Findings were compared with those obtained in matched controls in sinus rhythm (n=25). Before ablation, patients with AF had impaired left atrial function and left ventricular ejection fraction and strain indices (all P<0.05 versus controls). MBF was impaired in patients both under baseline conditions (1.21±0.24 mL/min per g·[mm Hg·bpm/104]-1 versus 1.34±0.28 mL/min per g·[mm Hg·bpm/104]-1 in controls, P=0.044) and during adenosine stress (2.29±0.48 mL/min per g versus 2.73±0.37 mL/min per g in controls, P<0.001). Under baseline conditions, MBF correlated with left ventricular strain and left atrial function (all P≤0.001), so that cardiac function was most impaired in patients with the lowest MBF . Baseline and stress MBF remained unchanged postablation (both P=ns), and baseline MBF showed similar correlations with functional indices to those present preablation (all P≤0.001). Conclusions Baseline and stress MBF are significantly impaired in patients with AF but no epicardial coronary artery disease. Reduction in MBF is proportional to severity of left ventricular and left atrial dysfunction, even after successful ablation. Coronary microvascular dysfunction may be a relevant pathophysiological mechanism in patients with a history of AF .

Endocardial left ventricular pacing across the interventricular septum for cardiac resynchronization therapy: Clinical results of a pilot study.

BACKGROUND: Cardiac resynchronization therapy (CRT) is an effective treatment for selected patients with heart failure, but it can be limited by the inability to place the left ventricular (LV) lead via the coronary sinus. OBJECTIVE: The purpose of this study was to develop an alternative approach, placing the LV lead endocardially via an interventricular septal puncture, and to assess the feasibility and safety of this technique. METHODS: All patients were anticoagulated with warfarin (international normalized ratio 2.5-3.5). A superior approach ventricular transseptal puncture using radiofrequency energy was performed. An active fixation pacing lead was delivered to the mapped site of latest electrical activation on the endocardial LV. RESULTS: Twenty patients were recruited, 15 with failed transvenous LV lead placement and 5 nonresponders to CRT. Mean (± SD) age was 67 ± 12, with 80% male, QRS duration 157 ± 14 ms, ischemic etiology 45%, New York Heart Association functional class 2.9 ± 0.4, and LV ejection fraction 28% ± 7%. The procedure was successful in all, with no serious complications. Clinical composite score improved at 6 months in 65% and worsened in 35%. LV ejection fraction improved >5% in 88%, from 28% ± 7% to 41% ± 9%. Six-minute walking distance improved >10% in 64%, from 248 ± 125 m to 316 ± 109 m. One patient suffered a lacunar ischemic stroke after 5 months with partial neurological recovery, associated with labile international normalized ratios. After 2.0 ± 1.0 years of follow-up, 3 patients died (2 pneumonia, 1 heart failure), and 2 patients suffered transient ischemic attacks. CONCLUSION: LV endocardial pacing via interventricular septal puncture in patients for whom standard CRT is not possible is similarly effective and durable, with significant but potentially acceptable risks.