Diagnosis to Ablation in Persistent AF: Any Time Can Be a Good Time to Ablate.

BACKGROUND: Nonrandomized data suggest that longer diagnosis-to-ablation time (DAT) is associated with poorer outcomes; however, a recent randomized trial found no difference in recurrences when ablation was delayed by 12 months. OBJECTIVES: This study sought to assess the impact of DAT on atrial fibrillation (AF) recurrence in patients undergoing catheter ablation for persistent AF. METHODS: 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) was a multicenter trial that randomized patients with persistent AF to pulmonary vein isolation + posterior wall isolation or pulmonary vein isolation alone. Follow-up was 12 months. Outcomes were assessed after a 3-month blanking period. RESULTS: Median DAT in the 334 patients was 28 months (Q1-Q3: 12-66 months). Patients were divided into quartile groups: Q1 was DAT 0 to 12 months (n = 84, median DAT 7 months), Q2 was DAT 13 to 28 months (n = 85, median DAT 20 months), Q3 was DAT 29 to 66 months (n = 84, median DAT 41 months), and Q4 was DAT ≥67 months (n = 81, median DAT 119 months). AF recurrence rate was 36.9% for Q1, 44.7% for Q2, 47.6% for Q3, and 56.8% for Q4 (P = 0.082). On multivariable analysis, DAT Q4 was the only factor significantly associated with risk of recurrence (HR: 1.607; 95% CI: 1.005-2.570; P = 0.048). Median AF burden was 0% (Q1-Q3: 0%-0.47%) in Q1 and 0.33% (Q1-Q3: 0%-4.6%) in Q4 (P = 0.002). Quality of life (assessed by the Atrial Fibrillation Effect on Quality-of-Life questionnaire) improved markedly in all quartiles (Q1: Δ28.8 ± 24, Q2: Δ24.4 ± 23.4, Q3: Δ21.7 ± 26.6, Q4: Δ24.6 ± 21.4; P = 0.331). CONCLUSIONS: In a cohort of patients with persistent AF undergoing ablation in a prospective trial with standardized entry criteria and intensive electrocardiogram monitoring, those with shorter DAT had lower rates of AF recurrence. However, differences were modest, and all quartiles demonstrated very low AF burden and improvements in quality of life.

Sex Differences in Outcomes of an Intensive Risk Factor Modification Program in Patients With Atrial Fibrillation.

BACKGROUND: The outcomes of atrial fibrillation (AF) seem to be variable between males and females. We therefore aimed to determine sex differences in weight loss, cardiorespiratory fitness gain, and recurrence and progression of AF following risk factor management. METHODS: Of 1415 consecutive patients referred for electrophysiology management of AF, 825 had a body mass index of ≥27 kg/m2; after exclusions, 355 (males, 234; females, 121) were offered risk factor management and participation in a tailored exercise program. RESULTS: Females were older than males (65.5±10.4 versus 62.5±10.6 years; P=0.013) with a higher body mass index (34.1±5.4 versus 32.6±4.1 kg/m2; P=0.003) and more commonly paroxysmal AF (67.8% versus 48.3%; P<0.001). There was no sex difference in clinic attendance (58.7% versus 60%; P=0.82), weight loss (P=0.86), fitness gain (P=0.44), or improvement in AF symptoms (P=0.35). Weight loss (≥10% compared with <10%) was associated with lower total AF recurrence in males (hazard ratio, 0.41 [95% CI, 0.23-0.73]) and females (hazard ratio, 0.41 [95% CI, 0.20-0.83]). Fitness gain (≥2 metabolic equivalents compared with <2 metabolic equivalents) was associated with lower total AF recurrence in females (hazard ratio, 0.13 [95% CI, 0.05-0.30]) but not in males (hazard ratio, 0.63 [95% CI, 0.38-1.04]; P=0.002). There was a trend toward more reversal from persistent to paroxysmal AF in males compared with females (21.8% versus 14.0%; P=0.079). CONCLUSIONS: Males and females with AF demonstrate a similar degree of weight loss and fitness gain through structured risk factor management. However, fitness had a much greater benefit for total arrhythmia recurrence in females compared with males, whereas there was a trend toward more AF reversal in males. REGISTRATION: URL: https://anzctr.org.au; Unique identifier: ACTRN12614001123639.

2023 Cardiac Society of Australia and New Zealand Expert Position Statement on Catheter and Surgical Ablation for Atrial Fibrillation.

Catheter ablation for atrial fibrillation (AF) has increased exponentially in many developed countries, including Australia and New Zealand. This Expert Position Statement on Catheter and Surgical Ablation for Atrial Fibrillation from the Cardiac Society of Australia and New Zealand (CSANZ) recognises healthcare factors, expertise and expenditure relevant to the Australian and New Zealand healthcare environments including considerations of potential implications for First Nations Peoples. The statement is cognisant of international advice but tailored to local conditions and populations, and is intended to be used by electrophysiologists, cardiologists and general physicians across all disciplines caring for patients with AF. They are also intended to provide guidance to healthcare facilities seeking to establish or maintain catheter ablation for AF.

Global LEADR pivotal trial results.

BACKGROUND: Implantable cardioverter-defibrillators last longer, and interest in reliable leads with targeted lead placement is growing. The OmniaSecure™ defibrillation lead is a novel small-diameter, catheter-delivered lead designed for targeted placement, based on the established SelectSecure SureScan MRI Model 3830 lumenless pacing lead platform. OBJECTIVE: This trial assessed safety and efficacy of the OmniaSecure defibrillation lead. METHODS: The worldwide LEADR pivotal clinical trial enrolled patients indicated for de novo implantation of a primary or secondary prevention implantable cardioverter-defibrillator/cardiac resynchronization therapy defibrillator, all of whom received the study lead. The primary efficacy end point was successful defibrillation at implantation per protocol. The primary safety end point was freedom from study lead-related major complications at 6 months. The primary efficacy and safety objectives were met if the lower bound of the 2-sided 95% credible interval was >88% and >90%, respectively. RESULTS: In total, 643 patients successfully received the study lead, and 505 patients have completed 12-month follow-up. The lead was placed in the desired right ventricular location in 99.5% of patients. Defibrillation testing at implantation was completed in 119 patients, with success in 97.5%. The Kaplan-Meier estimated freedom from study lead-related major complications was 97.1% at 6 and 12 months. The trial exceeded the primary efficacy and safety objective thresholds. There were zero study lead fractures and electrical performance was stable throughout the mean follow-up of 12.7 ± 4.8 months (mean ± SD). CONCLUSION: The OmniaSecure lead exceeded prespecified primary end point performance goals for safety and efficacy, demonstrating high defibrillation success and a low occurrence of lead-related major complications with zero lead fractures.

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

BACKGROUND AND AIMS: Patterns of atrial fibrillation (AF) recurrence post-catheter ablation for persistent AF (PsAF) are not well described. This study aimed to describe the pattern of AF recurrence seen following catheter ablation for PsAF and the implications for healthcare utilization and quality of life (QoL). METHODS: This was a post-hoc analysis of the CAPLA study, an international, multicentre study that randomized 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 randomization groups (P = .508). Median AF burden was 27.4% in PsAF recurrence and .9% in paroxysmal AF (PAF) recurrence (P < .001). Patients with PsAF recurrence had lower baseline left ventricular ejection fraction (PsAF 50% vs. PAF 60%, P < .001) and larger left atrial volume (PsAF 54.2 ± 19.3 mL/m² vs. PAF 44.8 ± 11.6 mL/m², P = .008). Healthcare utilization was significantly higher in PsAF (45 patients [78.9%]) vs. PAF recurrence (45 patients [46.4%], P < .001) and lowest in those without recurrence (17 patients [9.5%], P < .001). Patients without AF recurrence had greater improvements in QoL 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 = .012) or PsAF (Δ13.4 ± 22.9 points, P < .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 utilization and antiarrhythmic drug use. The type of AF recurrence and AF burden may be considered important endpoints in clinical trials investigating ablation of PsAF.

Efficacy of left bundle branch area pacing versus biventricular pacing in patients treated with cardiac resynchronization therapy: Select site - cohort study.

BACKGROUND: Cardiac resynchronization therapy (CRT) is typically attempted with biventricular (BiV) pacing. One-third of patients are nonresponders. Left bundle branch area pacing (LBBAP) has been evaluated as an alternative means. OBJECTIVE: The purpose of this study was to assess the feasibility and clinical response of permanent LBBAP as an alternative to BiV pacing. METHODS: Of 479 consecutive patients referred with heart failure, 50 with BiV-CRT and 51 with LBBAP-CRT were included in this analysis after study exclusions. Quality-of-Life (QoL) assessments, echocardiographic measurements, and New York Heart Association (NYHA) class were obtained at baseline and at 6-monthly intervals. RESULTS: There were no differences in baseline characteristics between groups (all P > .05). Clinical outcomes such as left ventricular ejection fraction, left ventricular end-systolic volume, QoL, and NYHA class were significantly improved for both pacing groups compared to baseline. The LBBAP-CRT group showed greater improvement in left ventricular ejection fraction at 6 months (P = .001) and 12 months (P = .021), accompanied by greater reduction in left ventricular end-systolic volume (P = .007). QRS duration < 120 ms (baseline 160.82 ± 21.35 ms vs 161.08 ± 24.48 ms) was achieved in 30% in the BiV-CRT group vs 71% in the LBBAP-CRT group (P ≤ .001). Improvement in NYHA class (P = .031) and QoL index was greater (P = .014). Reduced heart failure admissions (P = .003) and health care utilization (P < .05) and improved lead performance (P < .001) were observed in the LBBAP-CRT group. CONCLUSION: LBBAP-CRT is feasible and effective CRT. It results into a meaningful improvement in QoL and reduction in health care utilization. This can be offered as an alternative to BiV-CRT or potentially as first-line therapy.

Utility of a guiding catheter for conduction system pacing: An early multicenter experience.

Background: Conduction system pacing (CSP), either as His bundle pacing (HBP) or as left bundle branch area pacing (LBBAP), may be superior to right ventricular apical or septal pacing. Objective: The study sought to present acute results for a new guiding catheter (Biotronik Selectra 3D) designed for CSP implantations of a retractable screw-in lead (Biotronik Solia S). Methods: The primary endpoint of the prospective, international nonrandomized BIO|MASTER.Selectra 3D study was freedom from catheter-related serious adverse device effects (SADEs) within 1 week of lead implantation. Results: Of 157 enrolled patients, CSP was achieved in 147 (93.6%) patients. No SADEs occurred within 7 days. LBBAP was achieved in 82 patients (45 as crossover from an HBP attempt) and HBP in 65 (44.2%) patients. In centers considering both HBP and LBBAP, the CSP implantation success approached 99%. Successful CSP implantations lasted on average ∼50 minutes (fluoroscopy ∼6 minutes). Most procedures (87.9%) needed only 1 catheter, even after switch from HBP to LBBAP. The catheter's handling was rated largely positive. In patients without bundle branch block, mean QRS duration increased from 106 ms (intrinsic) to 122 ms (CSP) (P = .001). In patients with bundle branch block, mean QRS duration decreased from 151 ms (intrinsic) to 137 ms (CSP) (P = .004). Conclusion: The Selectra 3D catheter is a valuable tool for HBP and LBBAP implantations of the stylet-supported pacemaker leads. When implanters considered both HBP and LBBAP, the success rate was ∼99%. Flexibility to change between different approaches may be advisable in heterogeneous and challenging areas, such as CSP implantations.

Characteristics of the phenotype of mixed cardiomyopathy in patients with implantable cardioverter-defibrillators.

BACKGROUND OR PURPOSE: The prognosis of m ixed cardiomyopathy (CMP) in patients with implanted cardioverter-defibrillators (ICDs) has not been investigated. We aim to study the demographic, clinical, device therapies and survival characteristics of mixed CMP in a cohort of patients implanted with a defibrillator. METHODS: The term mixed CMP was used to categorise patients with impaired left ventricular ejection fraction attributed to documented non-ischemic triggers with concomitant moderate coronary artery disease. This is a single center observational cohort of 526 patients with a mean follow-up of 8.7 ± 3.5 years. RESULTS: There were 42.5% patients with ischemic cardiomyopathy (ICM), 26.9% with non-ischemic cardiomyopathy (NICM) and 30.6% with mixed CMP. Mixed CMP, compared to NICM, was associated with higher mean age (69.1 ± 9.6 years), atrial fibrillation (55.3%) and greater incidence of comorbidities. The proportion of patients with mixed CMP receiving device shocks was 23.6%, compared to 18.4% in NICM and 27% in ICM. The VT cycle length recorded in mixed CMP (281.6 ± 43.1 ms) was comparable with ICM (282.5 ± 44 ms; p = 0.9) and lesser than NICM (297.7 ± 48.7 ms; p = 0.1). All-cause mortality in mixed CMP (21.1%) was similar to ICM (20.1%; p = 0.8) and higher than NICM (15.6%; p = 0.2). The Kaplan-Meier curves revealed hazards of 1.57 (95% CI: 0.91, 2.68) for mixed CMP compared to NICM. CONCLUSION: In a cohort of patients with ICD, the group with mixed CMP represents a phenotype predominantly comprised of the elderly with a higher incidence of comorbidities. Mixed CMP resembles ICM in terms of number of device shocks and VT cycle length. Trends of long-term prognosis of patients with mixed CMP are worse than NICM and similar to ICM.

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.

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.

Theoretical Appraisal of Cyclopropenone: Aggregation and Complexes with Water.

Cyclopropenone (HCCOCH, "CPN") is an exotic quasi-aromatic cyclic carbene that abounds in the interstellar medium (ISM). Astronomical observations suggest that (i) stagnate CPN exhibits a tendency to polymerize and that (ii) interactions may occur between CPN and water that is also ubiquitous in the ISM. In this light, density functional theory investigations reveal cooperative hydrogen bonding, which leads to stable polymeric conformations of (CPN)n, tracked up to n = 14. Stable agglomerations with water, however, constitute at best only two CPN and two water molecules, signifying that while CPN exhibits remarkable cooperativity for "cohesive" clustering via hydrogen bonding, this tendency is markedly diminished for "hetero"-interactions. Multifaceted data are employed to probe cogent molecular descriptors, such as structure and energetics of various conformers, vibrational spectroscopic response, molecular electrostatic potential (MESP), effective atomic charges: all these, in unison, describe the evolution of the characteristics upon cluster formation. Salient stretching frequency shifts, as well as charge redistribution gleaned from MESP morphology, have a direct bearing on variegated hydrogen bonding patterns: linear, nonlinear, as well as bifurcated. In particular, characteristic C-H, C═O stretching, and O-H vibrations in the water complexes reveal a "softening" (downshift) of frequencies. While small conformers have markedly distinct MESP variations, the differences become less pronounced with incremental clustering, an effect substantiated by corresponding emergent atomic charges.

Correlation of myocardial strain by CMR-feature tracking with substrate abnormalities detected by electro-anatomical mapping in patients with nonischemic cardiomyopathy.

BACKGROUND: Late gadolinium enhancement (LGE) detected by cardiac MRI (CMR) has low correlation with low voltage zones (LVZs) detected by electroanatomical mapping (EAM). We aim to study correlation of myocardial strain by CMR- Feature Tracking (FT) alongside LGE with LVZs detected by EAM. METHODS: Nineteen consecutive CMRs of patients with EAM were analyzed offline by CMR-FT. Peak value of circumferential strain (CS), longitudinal strain (LS), and LGE was measured in each segment of the left ventricle (17-segment model). The percentage of myocardial segments with CS and LS > -17% was determined. Percentage area of LGE-scar was calculated. Global and segment-wise bipolar and unipolar voltage was collected. Percentage area of bipolar LVZ (<1.5 mV) and unipolar LVZ (<8.3 mV) was calculated. RESULTS: Mean age was 62±11 years. Mean LVEF was 37±13%. Mean global CS was -11.8±5%. Mean global LS was -11.2±4%. LGE-scar was noted in 74% of the patients. Mean percentage area of LGE-scar was 5%. There was significant correlation between percentage abnormality detected by LS with percentage bipolar LVZ (r = +0.5, p = 0.03) and combined percentage CS+LS abnormality with percentage unipolar LVZ (r = +0.5, p = 0.02). Per-unit increase in CS increased the percentage area of unipolar LVZ by 2.09 (p = 0.07) and per-unit increase in LS increased the percentage area of unipolar LVZ by 2.49 (p = 0.06). The concordance rates between CS and LS to localize segments with bipolar/unipolar LVZ were 79% and 95% compared to 63% with LGE. CONCLUSIONS: Myocardial strain detected by CMR-FT has a better correlation with electrical low voltage zones than the conventional LGE.

An Exercise and Physical Activity Program in Patients With Atrial Fibrillation: The ACTIVE-AF Randomized Controlled Trial.

BACKGROUND: There are limited data on the effect of exercise interventions on atrial fibrillation (AF) recurrence and symptoms. OBJECTIVES: The aim of this study was to determine the efficacy of an exercise and physical activity intervention on AF burden and symptoms among patients with symptomatic AF. METHODS: This prospective, randomized controlled trial included 120 patients with paroxysmal or persistent, symptomatic AF, randomized 1:1 to receive an exercise intervention, combining home and supervised aerobic exercise over 6 months, or to receive usual care. The coprimary outcomes were: 1) AF recurrence, off antiarrhythmic medications and without catheter ablation; and 2) symptom severity assessed by using a validated questionnaire. RESULTS: By 12 months, freedom from AF was achieved in 24 (40%) of 60 patients in the exercise group and 12 (20%) of 60 patients in the control group (HR: 0.50: 95% CI: 0.33 to 0.78). At 6 months, AF symptom severity was lower in the exercise group compared with the control group (mean difference -2.3; 95% CI: -4.3 to -0.2; P = 0.033). This difference persisted at 12 months (-2.3; 95% CI: -4.5 to -0.1; P = 0.041). Total symptom burden was lower at 6 months in the exercise group but not at 12 months. Peak oxygen consumption was increased in the exercise group at both 6 and 12 months. There were no between-group differences in cardiac structure or function, body mass index, or blood pressure. CONCLUSIONS: Participation in an exercise-based intervention over 6 months reduced arrhythmia recurrence and improved symptom severity among patients with AF. (A Lifestyle-based, PhysiCal AcTIVity IntErvention for Patients With Symptomatic Atrial Fibrillation [the ACTIVE-AF Study]; ACTRN12615000734561).

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.

Cyclopropenylidene: Clustering and Interaction with Water Molecules.

Cyclopropenylidene (c-C3H2, abbreviated CPD) is a highly reactive, planar, partially aromatic carbene discovered in the interstellar medium, and, also recently, in the outer solar system. It is demonstrated herein on cogent quantum chemical grounds that CPD which possesses an electric dipole moment of 3.4 D is capable of forming stable dimer and trimer clusters through hydrogen-bonding. These attributes of CPD are conducive to the formation of stable hydrogen-bonded conformations with one- and two-water molecules. Having determined its consistency with the second-order Møller-Plesset perturbation theory MP2, we employ the ωB97xD hybrid density functional theory in conjunction with a 6-311++G(2d,2p) basis set for a credible description of noncovalent interactions involved in clustering. Molecular electrostatic potential (MESP) and characteristic vibrational frequency shifts upon clustering are presented.

Long-term mortality in heart failure with mid-range ejection fraction: systematic review and meta-analysis.

AIMS: Heart failure patients with mid-range ejection fraction (HFmrEF) have overlapping clinical features, compared with patients with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). We aim to perform a meta-analysis of studies reporting long-term outcomes in HFmrEF compared with HFrEF and HFpEF. METHODS AND RESULTS: Data from 18 eligible large-scale studies including 126 239 patients were pooled. Patients with HFmrEF had a lower risk of all-cause death than those with HFrEF [risk ratio (RR) = 0.92; 95% CI = 0.85-0.98; P < 0.001]. This significant difference was seen in the follow-up at 1, 2, and 3 years. Patients with HFmrEF had significantly lower risk of cardiovascular (CV) deaths than HFrEF (RR = 0.77; 95% CI = 0.65-0.92; P < 0.001). Subgroup analysis showed that studies recruiting >50% of males had higher risk of deaths with HFrEF (RR = 1.15; 95% CI = 1.04-1.26; P = 0.006). When compared with HFpEF, patients with HFmrEF had comparable risk of all-cause death (RR = 1.02; 95% CI = 0.96-1.09; P = 0.53). Similarly, there were no differences in the 1, 2, and 3 year deaths; CV and non-CV deaths were insignificant between HFmrEF and HFpEF. CONCLUSIONS: The results of the study support that HFmrEF has better prognosis than HFrEF but similar prognosis when compared with HFpEF. Gender disparity between studies seems to influence the results between HFmrEF and HFrEF. Transition in left ventricular ejection fraction (LVEF), which could not be addressed in the study, may play a decisive role in determining outcomes. PROSPERO review registration number CRD42021277107.

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.

HRS White Paper on Clinical Utilization of Digital Health Technology.

This collaborative statement from the Digital Health Committee of the Heart Rhythm Society provides everyday clinical scenarios in which wearables may be utilized by patients for cardiovascular health and arrhythmia management. We describe herein the spectrum of wearables that are commercially available for patients, and their benefits, shortcomings and areas for technological improvement. Although wearables for rhythm diagnosis and management have not been examined in large randomized clinical trials, undoubtedly the usage of wearables has quickly escalated in clinical practice. This document is the first of a planned series in which we will update information on wearables as they are revised and released to consumers.

Position Statement on the Management of Cardiac Electrophysiology and Cardiac Implantable Electronic Devices in Australia During the COVID-19 Pandemic: A Living Document.

The COVID-19 pandemic poses a significant stress on health resources in Australia. The Heart Rhythm Council of the Cardiac Society of Australia and New Zealand aims to provide a framework for efficient resource utilisation balanced with competing risks when appropriately treating patients with cardiac arrhythmias. This document provides practical recommendations for the electrophysiology (EP) and cardiac implantable electronic devices (CIED) services in Australia. The document will be updated regularly as new evidence and knowledge is gained with time.

Miniaturized implantable cardiac monitor with a long sensing vector (BIOMONITOR III): Insertion procedure assessment, sensing performance, and home monitoring transmission success.

BACKGROUND: Implantable Cardiac Monitors (ICMs) are used for long-term monitoring of arrhythmias. BIOMONITOR III is a novel ICM with a miniaturized profile, long sensing vector due to a flexible antenna, simplified implantation with a dedicated insertion tool for pocket formation and ICM placement in a single step, and daily automatic Home Monitoring (HM) function. METHODS: In 47 patients undergoing BIOMONITOR III insertion for any ICM indication, 16 investigators at 10 Australian sites assessed handling characteristics of the insertion tool, R-wave amplitudes, noise burden, P-wave visibility, and HM transmission success. Patients were followed for 1 month. RESULTS: All 47 attempted insertions were successful. Median time from skin incision to removal of the insertion tool after ICM insertion was 39 s (IQR 19-65) and to wound closure and cleaning was 4.7 min (IQR 3.5-7.8). All aspects of the insertion tool were rated as "good" or "excellent" in ≥97.9% and "fair" in ≤2.1% of patients, except for "force needed for tunnelling" (91.5% good/excellent, 8.5% fair). Based on HM data, R-waves in the first month were stable at 0.70 ± 0.37 mV. Median noise burden (disabling automatic rhythm evaluation) was 0.19% (IQR 0.00-0.93), equivalent to 2.7 min (IQR 0.0-13.4) per day. In HM-transmitted ECG strips with regular sinus rhythm, P-waves were visible in 89 ± 24% of heart cycles. Patient-individual automatic Home Monitoring transmission success was 98.0% ± 5.5%. CONCLUSIONS: The novel ICM performed well in all aspects studied, including fast insertion, reliable R-wave sensing, good P-wave visibility, and highly successful HM transmissions.