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.

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.

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.

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.

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.

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.

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.

Endocardial left ventricular pacing for cardiac resynchronization: systematic review and meta-analysis.

Aims: Endocardial left ventricular (LV) pacing for Cardiac Resynchronization Therapy has been proposed as an alternative to conventional LV lead placement via the coronary sinus. In order to assess the relative benefits and risks of this technique, we have performed a meta-analysis of published reports. Methods and results: A systemic search was performed using online databases to identify studies of lead-based endocardial pacing. A random-effects meta-analysis was performed, to assess the rate of complications and clinical response (defined as ≥1 decrease in NYHA class). We selected 23 studies, including 384 patients. The trans-atrial septal technique was used in 20 studies, 1 used the trans-ventricular apical technique, and 2 used the trans-ventricular septal technique. Mean age was 66 years, male 66%, EF 26%, NYHA class 3.0. Procedural success rates were over 95% in all studies. Clinical response was reported by 16 studies for 262 patients, giving a response estimate of 82% (95% CI 71-89%). There was significant heterogeneity, and response in the only large study was 59%. Thromboembolic (TE) complications were reported by all studies, over 22 ±32 months follow up. The rate of stroke was 2.5 events per 100 patient years (95% CI 1.5-4.3), and TIA 2.6 (1.1-6.1). The mortality rate was 4.5 (1.5-13.6) per 100 patient years. Conclusion: LV endocardial pacing appears to be a viable technique when conventional lead placement is not possible. Response rates were heterogeneous but comparable with conventional CRT. There is likely to be a small increase over expected rates of stroke, although included patients were high risk.

Lone Atrial Fibrillation Is Associated With Impaired Left Ventricular Energetics That Persists Despite Successful Catheter Ablation.

BACKGROUND: Lone atrial fibrillation (AF) may reflect a subclinical cardiomyopathy that persists after sinus rhythm (SR) restoration, providing a substrate for AF recurrence. To test this hypothesis, we investigated the effect of restoring SR by catheter ablation on left ventricular (LV) function and energetics in patients with AF but no significant comorbidities. METHODS: Fifty-three patients with symptomatic paroxysmal or persistent AF and without significant valvular disease, uncontrolled hypertension, coronary artery disease, uncontrolled thyroid disease, systemic inflammatory disease, diabetes mellitus, or obstructive sleep apnea (ie, lone AF) undergoing ablation and 25 matched control subjects in SR were investigated. Magnetic resonance imaging quantified LV ejection fraction (LVEF), peak systolic circumferential strain (PSCS), and left atrial volumes and function, whereas phosphorus-31 magnetic resonance spectroscopy evaluated ventricular energetics (ratio of phosphocreatine to ATP). AF burden was determined before and after ablation by 7-day Holter monitoring; intermittent ECG event monitoring was also undertaken after ablation to investigate for asymptomatic AF recurrence. RESULTS: Before ablation, both LV function and energetics were significantly impaired in patients compared with control subjects (LVEF, 61% [interquartile range (IQR), 52%-65%] versus 71% [IQR, 69%-73%], P<0.001; PSCS, -15% [IQR, -11 to -18%] versus -18% [IQR, -17% to -19%], P=0.002; ratio of phosphocreatine to ATP, 1.81±0.35 versus 2.05±0.29, P=0.004). As expected, patients also had dilated and impaired left atria compared with control subjects (all P<0.001). Early after ablation (1-4 days), LVEF and PSCS improved in patients recovering SR from AF (LVEF, 7.0±10%, P=0.005; PSCS, -3.5±4.3%, P=0.001) but were unchanged in those in SR during both assessments (both P=NS). At 6 to 9 months after ablation, AF burden reduced significantly (from 54% [IQR, 1.5%-100%] to 0% [IQR 0%-0.1%]; P<0.001). However, LVEF and PSCS did not improve further (both P=NS) and remained impaired compared with control subjects (P<0.001 and P=0.003, respectively). Similarly, there was no significant improvement in atrial function from before ablation (P=NS), and this remained lower than in control subjects (P<0.001). The ratio of phosphocreatine to ATP was unaffected by heart rhythm during assessment and AF burden before ablation (both P=NS). It was unchanged after ablation (P=0.57), remaining lower than in control subjects regardless of both recovery of SR and freedom from recurrent AF (P=0.006 and P=0.002, respectively). CONCLUSIONS: Patients with lone AF have impaired myocardial energetics and subtle LV dysfunction, which do not normalize after ablation. These findings suggest that AF may be the consequence (rather than the cause) of an occult cardiomyopathy, which persists despite a significant reduction in AF burden after ablation.

Premature termination of radiofrequency delivery during pulmonary vein isolation due to oesophageal temperature alerts: impact on acute and chronic pulmonary vein reconnection.

AIMS: Oesophageal temperature monitoring is currently used during atrial fibrillation (AF) ablation to prevent atrio-oesophageal fistula. The aim of our study was to investigate if oesophageal temperature alerts, leading to early termination of radiofrequency (RF) energy and/or reduction in power during pulmonary vein isolation, can promote pulmonary vein reconnection (PVR). METHODS AND RESULTS: Patients undergone two consecutive AF ablation procedures with a three-dimensional electro-anatomical mapping system and oesophageal temperature monitoring were studied. Any lesions causing oesophageal temperature rises >39°C during the index procedure, leading to premature cessation of RF and/or reduction in power, were labelled on the left atrial geometry in a different colour from standard uninterrupted RF lesions. Acute (at the time of the index procedure) and chronic (at the time of there-do procedure) PVR and the site of subsequent re-isolation were compared with the lesion markers for temperature alerts from the index procedure. Fifty-four patients were included (36 male, mean age 68 ± 8, 59% persistent AF). Forty-six PVs (21% of the total) in 30 patients (56%) had been subject to at least one temperature alert during the index procedure. In 12 patients, 23 PVs had acute PVR requiring further ablation. At the re-do procedure, 103 PVs were found to be reconnected in 44 patients. No correlation was found between the occurrence of temperature alerts at the index procedure and acute or chronic PVR in the associated PV. CONCLUSION: Just over half of patients undergoing PV isolation will have an oesophageal temperature alert, however, precautionary oesophageal temperature monitoring does not compromise ablation efficacy.

The relative role of patient physiology and device optimisation in cardiac resynchronisation therapy: A computational modelling study.

Cardiac resynchronisation therapy (CRT) is an established treatment for heart failure, however the effective selection of patients and optimisation of therapy remain controversial. While extensive research is ongoing, it remains unclear whether improvements in patient selection or therapy planning offers a greater opportunity for the improvement of clinical outcomes. This computational study investigates the impact of both physiological conditions that guide patient selection and the optimisation of pacing lead placement on CRT outcomes. A multi-scale biophysical model of cardiac electromechanics was developed and personalised to patient data in three patients. These models were separated into components representing cardiac anatomy, pacing lead location, myocardial conductivity and stiffness, afterload, active contraction and conduction block for each individual, and recombined to generate a cohort of 648 virtual patients. The effect of these components on the change in total activation time of the ventricles (ΔTAT) and acute haemodynamic response (AHR) was analysed. The pacing site location was found to have the largest effect on ΔTAT and AHR. Secondary effects on ΔTAT and AHR were found for functional conduction block and cardiac anatomy. The simulation results highlight a need for a greater emphasis on therapy optimisation in order to achieve the best outcomes for patients.

Analysis of lead placement optimization metrics in cardiac resynchronization therapy with computational modelling.

AIMS: The efficacy of cardiac resynchronization therapy (CRT) is known to vary considerably with pacing location, however the most effective set of metrics by which to select the optimal pacing site is not yet well understood. Computational modelling offers a powerful methodology to comprehensively test the effect of pacing location in silico and investigate how to best optimize therapy using clinically available metrics for the individual patient. METHODS AND RESULTS: Personalized computational models of cardiac electromechanics were used to perform an in silico left ventricle (LV) pacing site optimization study as part of biventricular CRT in three patient cases. Maps of response to therapy according to changes in total activation time (ΔTAT) and acute haemodynamic response (AHR) were generated and compared with preclinical metrics of electrical function, strain, stress, and mechanical work to assess their suitability for selecting the optimal pacing site. In all three patients, response to therapy was highly sensitive to pacing location, with laterobasal locations being optimal. ΔTAT and AHR were found to be correlated (ρ < -0.80), as were AHR and the preclinical activation time at the pacing site (ρ ≥ 0.73), however pacing in the last activated site did not result in the optimal response to therapy in all cases. CONCLUSION: This computational modelling study supports pacing in laterobasal locations, optimizing pacing site by minimizing paced QRS duration and pacing in regions activated late at sinus rhythm. Results demonstrate information content is redundant using multiple preclinical metrics. Of significance, the correlation of AHR with ΔTAT indicates that minimization of QRSd is a promising metric for optimization of lead placement.

Point-by-Point Radiofrequency Ablation Versus the Cryoballoon or a Novel Combined Approach: A Randomized Trial Comparing 3 Methods of Pulmonary Vein Isolation for Paroxysmal Atrial Fibrillation (The Cryo Versus RF Trial).

INTRODUCTION: Catheter ablation of paroxysmal AF using the Cryoballoon (CRYO) has yielded similar success rates to conventional wide encirclement using radiofrequency catheter ablation (RFCA), but randomized data are lacking. Pilot data suggested a high success rate with a combined approach (COMBINED) using wide encirclement with RFCA followed by 2 CRYO applications to each vein. We compared these 3 strategies in a randomized controlled trial. METHODS AND RESULTS: Patients undergoing first time paroxysmal AF ablation were randomized to RFCA, CRYO, or COMBINED. Patients were followed up at 3, 6, and 12 months with 7 days of ambulatory ECG monitoring. Success was defined as freedom from arrhythmia without antiarrhythmic drugs after a single procedure. A total of 237 patients were randomized. Success at 1 year was achieved in 47% in the RFCA group, 67% in the CRYO group, and 76% in the COMBINED group (P < 0.001 for RFCA vs. CRYO, P<0.001 for RFCA vs. COMBINED, and P = 0.220 for CRYO vs. COMBINED). Procedure time was 211 (IQR 174-256) minutes for RFCA compared to 167 (136-202) minutes for CRYO and 278 (243-327) minutes for COMBINED (P < 0.001 for RFCA vs. COMBINED, RFCA vs. CRYO, and CRYO vs. COMBINED groups). CONCLUSIONS: Pulmonary vein isolation for paroxysmal AF is faster with CRYO and results in a higher single procedure success rate than conventional point by point RFCA. The COMBINED approach was not superior to CRYO alone.

A prospective evaluation of cardiovascular magnetic resonance measures of dyssynchrony in the prediction of response to cardiac resynchronization therapy.

BACKGROUND: Many patients with electrical dyssynchrony who undergo cardiac resynchronization therapy (CRT) do not obtain substantial benefit. Assessing mechanical dyssynchrony may improve patient selection. Results from studies using echocardiographic imaging to measure dyssynchrony have ultimately proved disappointing. We sought to evaluate cardiac motion in patients with heart failure and electrical dyssynchrony using cardiovascular magnetic resonance (CMR). We developed a framework for comparing measures of myocardial mechanics and evaluated how well they predicted response to CRT. METHODS: CMR was performed at 1.5 Tesla prior to CRT. Steady-state free precession (SSFP) cine images and complementary modulation of magnetization (CSPAMM) tagged cine images were acquired. Images were processed using a novel framework to extract regional ventricular volume-change, thickening and deformation fields (strain). A systolic dyssynchrony index (SDI) for all parameters within a 16-segment model of the ventricle was computed with high SDI denoting more dyssynchrony. Once identified, the optimal measure was applied to a second patient population to determine its utility as a predictor of CRT response compared to current accepted predictors (QRS duration, LBBB morphology and scar burden). RESULTS: Forty-four patients were recruited in the first phase (91% male, 63.3 ± 14.1 years; 80% NYHA class III) with mean QRSd 154 ± 24 ms. Twenty-one out of 44 (48%) patients showed reverse remodelling (RR) with a decrease in end systolic volume (ESV) ≥ 15% at 6 months. Volume-change SDI was the strongest predictor of RR (PR 5.67; 95% CI 1.95-16.5; P = 0.003). SDI derived from myocardial strain was least predictive. Volume-change SDI was applied as a predictor of RR to a second population of 50 patients (70% male, mean age 68.6 ± 12.2 years, 76% NYHA class III) with mean QRSd 146 ± 21 ms. When compared to QRSd, LBBB morphology and scar burden, volume-change SDI was the only statistically significant predictor of RR in this group. CONCLUSION: A systolic dyssynchrony index derived from volume-change is a highly reproducible measurement that can be derived from routinely acquired SSFP cine images and predicts RR following CRT whilst an SDI of regional strain does not.

A comparison of left ventricular endocardial, multisite, and multipolar epicardial cardiac resynchronization: an acute haemodynamic and electroanatomical study.

AIMS: Alternative forms of cardiac resynchronization therapy (CRT), including biventricular endocardial (BV-Endo) and multisite epicardial pacing (MSP), have been developed to improve response. It is unclear which form of stimulation is optimal. We aimed to compare the acute haemodynamic response (AHR) and electrophysiological effects of BV-Endo with MSP via two separate coronary sinus (CS) leads or a single-quadripolar CS lead. METHODS AND RESULTS: Fifteen patients with a previously implanted CRT system received a second temporary CS lead and left ventricular (LV) endocardial catheter. A pressure wire and non-contact mapping array were placed into the LV cavity to measure LVdP/dtmax and perform electroanatomical mapping. Conventional CRT, BV-Endo, and MSP were then performed (MSP-1 via two epicardial leads and MSP-2 via a single-quadripolar lead). The best overall AHR was found using BV-Endo pacing with a 19.6 ± 13.6% increase in AHR at the optimal endocardial site over baseline (P < 0.001). There was an increase in LVdP/dtmax with MSP-1 and MSP-2 compared with conventional CRT, but this was not statistically significant. Biventricular endocardial pacing from the optimal site was significantly superior to conventional CRT (P = 0.039). The AHR achieved when BV-Endo pacing was highly site specific. Within individuals, the best pacing modality varied and was affected by the underlying substrate. Left ventricular activation times did not predict the optimal haemodynamic configuration. CONCLUSION: Biventricular endocardial pacing and not MSP was superior to conventional CRT, but was highly site specific. Within individuals, however, different methods of stimulation are optimal and may need to be tailored to the underlying substrate.

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.

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.