Frequent Premature Atrial Contractions Lead to Adverse Atrial Remodeling and Atrial Fibrillation in a Swine Model.

BACKGROUND: Frequent premature atrial complexes (PACs) are associated with future incident atrial fibrillation (AF), but whether PACs contribute to development of AF through adverse atrial remodeling has not been studied. This study aimed to explore the effect of frequent PACs from different sites on atrial remodeling in a swine model. METHODS: Forty swine underwent baseline electrophysiologic studies and echocardiography followed by pacemaker implantations and paced PACs (50% burden) at 250-ms coupling intervals for 16 weeks in 4 groups: (1) lateral left atrium (LA) PACs by the coronary sinus (Lat-PAC; n=10), (2) interatrial septal PACs (Sep-PAC; n=10), (3) regular LA pacing at 130 beats/min (Reg-130; n=10), and (4) controls without PACs (n=10). At the final study, repeat studies were performed, followed by tissue histology and molecular analyses focusing on fibrotic pathways. RESULTS: Lat-PACs were associated with a longer P-wave duration (93.0±9.0 versus 74.2±8.2 and 58.8±7.6 ms; P<0.001) and greater echocardiographic mechanical dyssynchrony (57.5±11.6 versus 35.7±13.0 and 24.4±11.1 ms; P<0.001) compared with Sep-PACs and controls, respectively. After 16 weeks, Lat-PACs led to slower LA conduction velocity (1.1±0.2 versus 1.3±0.2 [Sep-PAC] versus 1.3±0.1 [Reg-130] versus 1.5±0.2 [controls] m/s; P<0.001) without significant change in atrial ERP. The Lat-PAC group had a significantly increased percentage of LA fibrosis and upregulated levels of extracellular matrix proteins (lysyl oxidase and collagen 1 and 8), as well as TGF-ß1 (transforming growth factor-ß1) signaling proteins (latent and monomer TGF-ß1 and phosphorylation/total ratio of SMAD2/3; P<0.05). The Lat-PAC group had the longest inducible AF duration (terminal to baseline: 131 [interquartile range 30, 192] seconds versus 16 [6, 26] seconds [Sep-PAC] versus 22 [11, 64] seconds [Reg-130] versus -1 [-16, 7] seconds [controls]; P<0.001). CONCLUSIONS: In this swine model, frequent PACs resulted in adverse atrial structural remodeling with a heightened propensity to AF. PACs originating from the lateral LA produced greater atrial remodeling and longer induced AF duration than the septal-origin PACs. These data provide evidence that frequent PACs can cause adverse atrial remodeling as well as AF, and that the location of ectopic PACs may be clinically meaningful.

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.

Caudal fluoroscopic guidance for the insertion of transvenous pacing leads.

BACKGROUND: Pneumothorax is a well-recognized complication of cardiac implantable electronic device (CIED) insertion. While AP fluoroscopy alone is the most commonly imaging technique for subclavian or axillary access, caudal fluoroscopy (angle 40°) is routinely used at our institution. The caudal view provides additional separation of the first rib and clavicle and may reduce the risk of pneumothorax. We assessed outcomes at our institution of AP and caudal fluoroscopic guided pacing lead insertion. METHODS: Retrospective cohort study of consecutive patients undergoing transvenous lead insertion for pacemakers, defibrillators, and cardiac resynchronization therapy devices between 2011 and 2023. Both de novo and lead replacement/upgrade procedures were included. Data were extracted from operative, radiology, and discharge reports. All patients underwent postprocedure chest radiography. RESULTS: Three thousand two hundred fifty-two patients underwent insertion of pacing leads between February 2011 and March 2023. Mean age was 71.1 years (range 16-102) and 66.7% were male. Most (n = 2536; 78.0%) procedures used caudal guidance to obtain venous access, while 716 (22.0%) procedures used AP guidance alone. Pneumothoraxes occurred in five (0.2%) patients in the caudal group and five (0.7%) patients in the AP group (p = .03). Subclavian contrast venography was performed less frequently in the caudal group (26.2% vs. 42.7%, p < .01). CONCLUSION: Caudal fluoroscopy for axillary/subclavian access is associated with a lower rate of pneumothorax and contrast venography compared with an AP approach.

Aberrancy masquerading as ventricular tachycardia: Importance of invasive electrophysiology study for diagnosis of wide complex tachycardias.

BACKGROUND: Differentiation between ventricular tachycardia (VT) and supraventricular tachycardia (SVT) with aberrancy based on the 12­lead ECG alone can be imprecise. Implantable cardiac defibrillators (ICD) may be inserted for presumed VT, particularly in patients with syncopal presentation or atypical aberrancy patterns. Accurate diagnosis of these patients facilitated by an electrophysiology study (EPS) may alter diagnosis and management. METHODS: We present a prospective collection of cases across 3 cardiac centers of consecutive patients with WCT presumed to be VT who were referred for consideration of an ICD, and in whom further evaluation including an EPS ultimately demonstrated SVT with aberrancy as the culprit arrhythmia. RESULTS: 22 patients were identified (17 male, mean age 50±13 years. Available rhythm data at the time of referral was presumptively diagnosed as monomorphic VT in 16 patients and polymorphic VT in 6 patients. Underlying structural heart disease was present in 20 (91%). EPS resulted in a diagnosis of SVT with aberrancy in all cases: comprising AV nodal re-entry tachycardia (n=10), orthodromic reciprocating tachycardia (n=3), focal atrial tachycardia (n=3), AF/AFL (n=3) and 'double fire' tachycardia (n=2). 21 (95%) patients underwent successful ablation. All patients remained free of arrhythmia recurrence at a median of 3.4 years of follow-up. ICD insertion was obviated in 18 (82%) patients, with 1 patient proceeding to ICD extraction. CONCLUSION: SVT with atypical aberrancy may mimic monomorphic or polymorphic VT. Careful examination of all available rhythm data and consideration of an EPS can confirm SVT and obviate the need for ICD therapy.

New-onset atrial fibrillation prediction: the HARMS2-AF risk score.

AIMS: Lifestyle risk factors are a modifiable target in atrial fibrillation (AF) management. The relative contribution of individual lifestyle risk factors to AF development has not been described. Development and validation of an AF lifestyle risk score to identify individuals at risk of AF in the general population are the aims of the study. METHODS AND RESULTS: The UK Biobank (UKB) and Framingham Heart Study (FHS) are large prospective cohorts with outcomes measured >10 years. Incident AF was based on International Classification of Diseases version 10 coding. Prior AF was excluded. Cox proportional hazards regression identified independent AF predictors, which were evaluated in a multivariable model. A weighted score was developed in the UKB and externally validated in the FHS. Kaplan-Meier estimates ascertained the risk of AF development. Among 314 280 UKB participants, AF incidence was 5.7%, with median time to AF 7.6 years (interquartile range 4.5-10.2). Hypertension, age, body mass index, male sex, sleep apnoea, smoking, and alcohol were predictive variables (all P < 0.001); physical inactivity [hazard ratio (HR) 1.01, 95% confidence interval (CI) 0.96-1.05, P = 0.80] and diabetes (HR 1.03, 95% CI 0.97-1.09, P = 0·38) were not significant. The HARMS2-AF score had similar predictive performance [area under the curve (AUC) 0.782] to the unweighted model (AUC 0.802) in the UKB. External validation in the FHS (AF incidence 6.0% of 7171 participants) demonstrated an AUC of 0.757 (95% CI 0.735-0.779). A higher HARMS2-AF score (≥5 points) was associated with a heightened AF risk (score 5-9: HR 12.79; score 10-14: HR 38.70). The HARMS2-AF risk model outperformed the Framingham-AF (AUC 0.568) and ARIC (AUC 0.713) risk models (both P < 0.001) and was comparable to the CHARGE-AF risk score (AUC 0.754, P = 0.73). CONCLUSION: The HARMS2-AF score is a novel lifestyle risk score which may help identify individuals at risk of AF in the general community and assist population screening.

Early Discharge to Clinic-Based Therapy of Patients Presenting With Decompensated Heart Failure (EDICT-HF): Study Protocol for a Multi-Centre Randomised Controlled Trial.

BACKGROUND: Acute decompensated heart failure involves a high rate of mortality and complications. Management typically involves a multi-day hospital admission. However, patients often lose part of their function with each successive admission, and are at a high risk for hospital-associated complications such as nosocomial infection. This study aims to determine the safety and efficacy of the management of patients presenting with acute decompensated heart failure to clinic-based therapy vs usual inpatient care using a reproducible management pathway. METHOD: An investigator-initiated, prospective, non-inferiority, 1:1 randomised-controlled trial, stratified by left ventricular ejection fraction including 460 patients with a minimum follow-up of 7 days. This is a multi-centre study to be performed in centres across Victoria, Australia. Participants will be patients with either heart failure with reduced ejection fraction (HFrEF) or heart failure with preserved ejection fraction (HFpEF), admitted for acute decompensation of heart failure. INTERVENTION: Early discharge to an outpatient-based Heart Failure Rapid Access Clinical Review (RACER) in addition to frequent medical/nursing at-home review for patients admitted with decompensated heart failure. RESULTS: The primary endpoint will be a non-inferiority assessment of re-hospitalisation at 30 days. Secondary outcomes include superiority assessment of hospitalisation at 30 days, a composite clinical endpoint of major adverse cardiac and cerebrovascular event (MACCE), hospital re-admission or mortality at 3 months, achievement of guideline-directed medical therapy, patient assessment of symptoms (visual-analogue scale quantified as area under curve and Kansas City Cardiomyopathy Questionnaire-12 [KCCQ-12]), attendance at 3-month outpatient follow-up, number of bed stays/clinics attended, proportion of patients free from congestion, change in serum creatinine level, treatment for electrolyte disturbances, time to transition from intravenous to oral diuretics, and health economics analysis (cost-benefit analysis, cost-utility analysis, incremental cost-effectiveness ratio). CONCLUSIONS: The Early Discharge to Clinic-Based Therapy of Patients Presenting with Decompensated Heart Failure (EDICT-HF) trial will help determine whether earlier discharge to out-of-hospital care is non-inferior to the usual practice of inpatient care, in patients with heart failure admitted to hospital for acute decompensation, as an alternative model of care.

Alcohol Abstinence in Drinkers with Atrial Fibrillation.

BACKGROUND: Excessive alcohol consumption is associated with incident atrial fibrillation and adverse atrial remodeling; however, the effect of abstinence from alcohol on secondary prevention of atrial fibrillation is unclear. METHODS: We conducted a multicenter, prospective, open-label, randomized, controlled trial at six hospitals in Australia. Adults who consumed 10 or more standard drinks (with 1 standard drink containing approximately 12 g of pure alcohol) per week and who had paroxysmal or persistent atrial fibrillation in sinus rhythm at baseline were randomly assigned in a 1:1 ratio to either abstain from alcohol or continue their usual alcohol consumption. The two primary end points were freedom from recurrence of atrial fibrillation (after a 2-week "blanking period") and total atrial fibrillation burden (proportion of time in atrial fibrillation) during 6 months of follow-up. RESULTS: Of 140 patients who underwent randomization (85% men; mean [±SD] age, 62±9 years), 70 were assigned to the abstinence group and 70 to the control group. Patients in the abstinence group reduced their alcohol intake from 16.8±7.7 to 2.1±3.7 standard drinks per week (a reduction of 87.5%), and patients in the control group reduced their alcohol intake from 16.4±6.9 to 13.2±6.5 drinks per week (a reduction of 19.5%). After a 2-week blanking period, atrial fibrillation recurred in 37 of 70 patients (53%) in the abstinence group and in 51 of 70 patients (73%) in the control group. The abstinence group had a longer period before recurrence of atrial fibrillation than the control group (hazard ratio, 0.55; 95% confidence interval, 0.36 to 0.84; P = 0.005). The atrial fibrillation burden over 6 months of follow-up was significantly lower in the abstinence group than in the control group (median percentage of time in atrial fibrillation, 0.5% [interquartile range, 0.0 to 3.0] vs. 1.2% [interquartile range, 0.0 to 10.3]; P = 0.01). CONCLUSIONS: Abstinence from alcohol reduced arrhythmia recurrences in regular drinkers with atrial fibrillation. (Funded by the Government of Victoria Operational Infrastructure Support Program and others; Australian New Zealand Clinical Trials Registry number, ACTRN12616000256471.).

Diagnostic evaluation of unexplained ventricular tachyarrhythmias in younger adults.

BACKGROUND: The diagnostic work-up for cardiac arrest from ventricular tachyarrhythmias occurring in younger adults and structurally normal hearts is variable and often incomplete. METHODS: We reviewed records for all recipients of a secondary prevention implantable cardiac defibrillator (ICD) younger than 60 years at a single quaternary referral hospital from 2010 to 2021. Patients with unexplained ventricular arrhythmias (UVA) were identified as those with no structural heart disease on echocardiogram, no obstructive coronary disease, and no clear diagnostic features on ECG. We specifically evaluated the adoption rate of five modalities of "second-line" cardiac investigations: cardiac magnetic resonance imaging (CMR), exercise ECG, flecainide challenge, electrophysiology study (EPS), and genetic testing. We also evaluated patterns of antiarrhythmic drug therapy and device-detected arrhythmias and compared them with secondary prevention ICD recipients with a clear etiology found on initial assessment. RESULTS: One hundred and two recipients of a secondary prevention ICD under the age of 60 were analyzed. Thirty-nine patients (38.2%) were identified with UVA and were compared with the remaining 63 patients with VA of clear etiology (61.8%). UVA patients were younger (35.6 ± 13.0 vs. 46.0 ± 8.6 years, p < .001) and were more often female (48.7% vs. 28.6%, p = .04). CMR was performed in 32 patients with UVA (82.1%), whereas flecainide challenge, stress ECG, genetic testing, and EPS were only performed in a minority of patients. Overall, the use of a second-line investigation suggested an etiology in 17 patients with UVA (43.5%). Compared to patients with VA of clear etiology, UVA patients had lower rates of antiarrhythmic drug prescription (64.1% vs. 88.9%, p = .003) and had a higher rate of device-delivered tachy-therapies (30.8% vs. 14.3%, p = .045). CONCLUSION: In this real-world analysis of patients with UVA, the diagnostic work-up is often incomplete. While CMR was increasingly utilized at our institution, investigations for channelopathies and genetic causes appear to be underutilized. Implementation of a systematic protocol for work-up of these patients requires further study.

The impact of age on ablation outcomes in AF-mediated cardiomyopathy.

INTRODUCTION: The absence of ventricular scar in patients with atrial fibrillation (AF) and systolic heart failure (HF) predicts left ventricular (LV) recovery following AF ablation. It is unknown whether age impacts the degree of LV recovery, reverse remodeling, or AF recurrence following catheter ablation (CA) among this population. OBJECTIVES: To evaluate the impact of age on LV recovery and AF recurrence in a population with AF and systolic HF without fibrosis (termed AF-mediated cardiomyopathy) following CA. METHODS: Consecutive patients undergoing CA between 2013 and 2021 with LV ejection fraction (LVEF) < 45% and absence of cardiac magnetic resonance imaging (CMR) detected LV myocardial fibrosis were stratified by age (<65 vs. ≥65 years). Following CA, participants underwent remote rhythm monitoring for 12 months with repeat CMR for HF surveillance. RESULTS: The study population consisted of 70 patients (10% female, mean LVEF 33 ± 9%), stratified into younger (age < 65 years, 63%) and older (age ≥ 65 years, 37%) cohorts. Baseline comorbidities, LVEF (34 ± 9 vs. 33 ± 8 ≥65 years, p = .686), atrial and ventricular dimensions (left atrial volume index: 55 ± 21 vs. 56 ± 14 mL/m2 age ≥ 65, p = .834; indexed left ventricular end-diastolic volume: 108 ± 40 vs. 104 ± 28 mL/m2 age ≥ 65, p = .681), pharmacotherapy and ablation strategy (pulmonary vein isolation in all; posterior wall isolation in 27% vs. 19% age ≥ 65, p = .448; cavotricuspid isthmus in 9% vs. 11.5% age ≥ 65) were comparable (all p > .05) albeit a higher CHADS2 VASc score in the older cohort (2.7 ± 0.9 vs. 1.6 ± 0.6 age < 65, p < .001).   Freedom from AF was comparable (hazard ratio: 0.65, 95% confidence interval: 0.38-1.48, LogRank p = .283) as was AF burden [0% (interquartile range, IQR: 0.0-2.1) vs. age ≥ 65: [0% (IQR 0.0-1.7), p = .516], irrespective of age. There was a significant improvement in LV systolic function in both groups (ΔLVEF + 21 ± 14% vs. +21 ± 12% age ≥ 65, p = .913), with LV recovery in the vast majority (73% vs. 69%, respectively, p = .759) at 13 (IQR: 12-16) months. This was accompanied by comparable improvements in functional status (New York Heart Association class p = .851; 6-min walk distance 50 ± 61 vs. 93 ± 134 m in age ≥ 65, p = .066), biomarkers (ΔN-terminal-pro brain natriuretic peptide -139 ± 246 vs. -168 ± 181 age ≥ 65,p = .629) and HF symptoms (Short Form-36 survey Δphysical component summary p = .483/Δmental component summary, p = .841). CONCLUSION: In patients undergoing CA for AF with systolic HF in the absence of ventricular scar, comparable improvements in ventricular function, symptoms, and freedom from AF are achieved irrespective of age.

Higher power short duration vs. lower power longer duration posterior wall ablation for atrial fibrillation and oesophageal injury outcomes: a prospective multi-centre randomized controlled study (Hi-Lo HEAT trial).

AIMS: Radiofrequency (RF) ablation for pulmonary vein isolation (PVI) in atrial fibrillation (AF) is associated with the risk of oesophageal thermal injury (ETI). Higher power short duration (HPSD) ablation results in preferential local resistive heating over distal conductive heating. Although HPSD has become increasingly common, no randomized study has compared ETI risk with conventional lower power longer duration (LPLD) ablation. This study aims to compare HPSD vs. LPLD ablation on ETI risk. METHODS AND RESULTS: Eighty-eight patients were randomized 1:1 to HPSD or LPLD posterior wall (PW) ablation. Posterior wall ablation was 40 W (HPSD group) or 25 W (LPLD group), with target AI (ablation index) 400/LSI (lesion size index) 4. Anterior wall ablation was 40-50 W, with a target AI 500-550/LSI 5-5.5. Endoscopy was performed on Day 1. The primary endpoint was ETI incidence. The mean age was 61 ± 9 years (31% females). The incidence of ETI (superficial ulcers n = 4) was 4.5%, with equal occurrence in HPSD and LPLD (P = 1.0). There was no difference in the median value of maximal oesophageal temperature (HPSD 38.6°C vs. LPLD 38.7°C, P = 0.43), or the median number of lesions per patient with temperature rise above 39°C (HPSD 1.5 vs. LPLD 2, P = 0.93). Radiofrequency ablation time (23.8 vs. 29.7 min, P < 0.01), PVI duration (46.5 vs. 59 min, P = 0.01), and procedure duration (133 vs. 150 min, P = 0.05) were reduced in HPSD. After a median follow-up of 12 months, AF recurrence was lower in HPSD (15.9% vs. LPLD 34.1%; hazard ratio 0.42, log-rank P = 0.04). CONCLUSION: Higher power short duration ablation was associated with similarly low rates of ETI and shorter total/PVI RF ablation times when compared with LPLD ablation. Higher power short duration ablation is a safe and efficacious approach to PVI.

Transvenous versus subcutaneous implantable cardioverter defibrillators in young cardiac arrest survivors.

Secondary prevention implantable cardioverter defibrillators (ICDs) are indicated in young patients presenting with aborted sudden cardiac death (SCD) because of ventricular arrhythmias. Transvenous-ICDs (TV-ICDs) are effective, established therapies supported by evidence. The significant morbidity associated with transvenous leads led to the development of the newer subcutaneous-ICD (S-ICD). This review discusses the clinical considerations when selecting an ICD for the young patient presenting with out-of-hospital cardiac arrest. The major benefits of TV-ICDs are their ability to pace (antitachycardia pacing [ATP], bradycardia support and cardiac resynchronisation therapy [CRT]) and the robust evidence base supporting their use. Other benefits include a longer battery life. Significant complications associated with transvenous leads include pneumothorax and tamponade during insertion and infection and lead failure in the long term. Comparatively, S-ICDs, by virtue of having no intravascular leads, prevent these complications. S-ICDs have been associated with a higher incidence of inappropriate shocks. Patients with an indication for bradycardia pacing, CRT or ATP (documented ventricular tachycardia) are seen as unsuitable for a S-ICD. If venous access is unsuitable or undesirable, S-ICDs should be considered given the patient is appropriately screened. There is a need for further randomised controlled trials to directly compare the two devices. TV-ICDs are an effective therapy for preventing SCD limited by significant lead-related complications. S-ICDs are an important development hindered largely by an inability to pace. Young patients stand to gain the most from a S-ICD as the cumulative risk of lead-related complications is high. A clinical framework to aid decision-making is presented.

Atrial Fibrillation Catheter Ablation vs Medical Therapy and Psychological Distress: A Randomized Clinical Trial.

Importance: The impact of atrial fibrillation (AF) catheter ablation on mental health outcomes is not well understood. Objective: To determine whether AF catheter ablation is associated with greater improvements in markers of psychological distress compared with medical therapy alone. Design, Setting, and Participants: The Randomized Evaluation of the Impact of Catheter Ablation on Psychological Distress in Atrial Fibrillation (REMEDIAL) study was a randomized trial of symptomatic participants conducted in 2 AF centers in Australia between June 2018 and March 2021. Interventions: Participants were randomized to receive AF catheter ablation (n = 52) or medical therapy (n = 48). Main Outcomes and Measures: The primary outcome was Hospital Anxiety and Depression Scale (HADS) score at 12 months. Secondary outcomes included follow-up assessments of prevalence of severe psychological distress (HADS score >15), anxiety HADS score, depression HADS score, and Beck Depression Inventory-II (BDI-II) score. Arrhythmia recurrence and AF burden data were also analyzed. Results: A total of 100 participants were randomized (mean age, 59 [12] years; 31 [32%] women; 54% with paroxysmal AF). Successful pulmonary vein isolation was achieved in all participants in the ablation group. The combined HADS score was lower in the ablation group vs the medical group at 6 months (8.2 [5.4] vs 11.9 [7.2]; P = .006) and at 12 months (7.6 [5.3] vs 11.8 [8.6]; between-group difference, -4.17 [95% CI, -7.04 to -1.31]; P = .005). Similarly, the prevalence of severe psychological distress was lower in the ablation group vs the medical therapy group at 6 months (14.2% vs 34%; P = .02) and at 12 months (10.2% vs 31.9%; P = .01), as was the anxiety HADS score at 6 months (4.7 [3.2] vs 6.4 [3.9]; P = .02) and 12 months (4.5 [3.3] vs 6.6 [4.8]; P = .02); the depression HADS score at 3 months (3.7 [2.6] vs 5.2 [4.0]; P = .047), 6 months (3.4 [2.7] vs 5.5 [3.9]; P = .004), and 12 months (3.1 [2.6] vs 5.2 [3.9]; P = .004); and the BDI-II score at 6 months (7.2 [6.1] vs 11.5 [9.0]; P = .01) and 12 months (6.6 [7.2] vs 10.9 [8.2]; P = .01). The median (IQR) AF burden in the ablation group was lower than in the medical therapy group (0% [0%-3.22%] vs 15.5% [1.0%-45.9%]; P < .001). Conclusion and Relevance: In this trial of participants with symptomatic AF, improvement in psychological symptoms of anxiety and depression was observed with catheter ablation, but not medical therapy. Trial Registration: ANZCTR Identifier: ACTRN12618000062224.

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.

Polymorphic Ventricular Tachycardia Storm After Coronary Artery Bypass Graft Surgery: A Form of 'Angry Purkinje Syndrome'.

BACKGROUND: Polymorphic ventricular tachycardia (PMVT) is a highly lethal arrhythmia which is commonly caused by acute myocardial ischaemia. PMVT mediated by short-coupled ventricular ectopy patients with ischaemic heart disease but in the absence of acute ischaemia may relate to transient peri-infarct Purkinje fibre irritability and has been termed 'Angry Purkinje Syndrome'. METHODS: We present a case series of three patients with PMVT storm 3-5 days following coronary artery bypass graft surgery (CABG). In all three cases, recurrent episodes of PMVT were initiated by monomorphic ventricular ectopy with a short coupling interval. Acute coronary ischaemia was excluded in all three patients with a coronary angiogram and graft study. Two out of three of the patients commenced oral quinidine sulphate with subsequent rapid suppression of arrhythmia. Implantable cardiac defibrillators were implanted in all three patients and revealed no recurrence of PMVT following hospital discharge. CONCLUSION: The Angry Purkinje Syndrome is a rare but important cause of ventricular tachycardia storm after CABG surgery and is mediated by short-coupled ventricular ectopy in the absence of acute myocardial ischaemia. This arrhythmia may be highly responsive to quinidine.

A Prospective, Multicentre Randomised Controlled Trial Comparing Catheter Ablation Versus Antiarrhythmic Drugs in Patients With Structural Heart Disease Related Ventricular Tachycardia: The CAAD-VT Trial Protocol.

IMPORTANCE: Randomised trials have shown that catheter ablation (CA) is superior to medical therapy for ventricular tachycardia (VT) largely in patients with ischaemic heart disease. Whether this translates to patients with all forms and stages of structural heart disease (SHD-e.g., non-ischaemic heart disease) is unclear. This trial will help clarify whether catheter ablation offers superior outcomes compared to medical therapy for VT in all patients with SHD. OBJECTIVE: To determine in patients with SHD and spontaneous or inducible VT, if catheter ablation is more efficacious than medical therapy in control of VT during follow-up. DESIGN: Randomised controlled trial including 162 patients, with an allocation ratio of 1:1, stratified by left ventricular ejection fraction (LVEF) and geographical region of site, with a median follow-up of 18-months and a minimum follow-up of 1 year. SETTING: Multicentre study performed in centres across Australia. PARTICIPANTS: Structural heart disease patients with sustained VT or inducible VT (n=162). INTERVENTION: Early treatment, within 30 days of randomisation, with catheter ablation (intervention) or initial treatment with antiarrhythmic drugs only (control). MAIN OUTCOMES, MEASURES, AND RESULTS: Primary endpoint will be a composite of recurrent VT, VT storm (≥3 VT episodes in 24 hrs or incessant VT), or death. Secondary outcomes will include each of the individual primary endpoints, VT burden (number of VT episodes in the 6 months preceding intervention compared to the 6 months after intervention), cardiovascular hospitalisation, mortality (including all-cause mortality, cardiac death, and non-cardiac death) and LVEF (assessed by transthoracic echocardiography from baseline to 6-, 12-, 24- and 36-months post intervention). CONCLUSIONS AND RELEVANCE: The Catheter Ablation versus Anti-arrhythmic Drugs for Ventricular Tachycardia (CAAD-VT) trial will help determine whether catheter ablation is superior to antiarrhythmic drug therapy alone, in patients with SHD-related VT. TRIAL REGISTRY: Australian New Zealand Clinical Trials Registry (ANZCTR) TRIAL REGISTRATION ID: ACTRN12620000045910 TRIAL REGISTRATION URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377617&isReview=true.

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.

Long-Term Implications of Pacemaker Insertion in Younger Adults: A Single Centre Experience.

BACKGROUND: The long-term implications of pacemaker insertion in younger adults are poorly described in the literature. METHODS: We performed a retrospective analysis of consecutive younger adult patients (18-50 yrs) undergoing pacemaker implantation at a quaternary hospital between 1986-2020. Defibrillators and cardiac resynchronisation therapy devices were excluded. All clinical records, pacemaker checks and echocardiograms were reviewed. RESULTS: Eighty-one (81) patients (median age 41.0 yrs IQR=35-47.0, 53% male) underwent pacemaker implantation. Indications were complete heart block (41%), sinus node dysfunction (33%), high grade AV block (11%) and tachycardia-bradycardia syndrome (7%). During a median 7.9 (IQR=1.1-14.9) years follow-up, nine patients (11%) developed 13 late device-related complications (generator or lead malfunction requiring reoperation [n=11], device infection [n=1] and pocket revision [n=1]). Five (5) of these patients were <40 years old at time of pacemaker insertion. At long-term follow-up, a further nine patients (11%) experienced pacemaker-related morbidity from inadequate lead performance managed with device reprogramming. Sustained ventricular tachycardia was detected in two patients (2%). Deterioration in ventricular function (LVEF decline >10%) was observed in 14 patients (17%) and seven of these patients required subsequent biventricular upgrade. Furthermore, four patients (5%) developed new tricuspid regurgitation (>moderate-severe). Of 69 patients with available long-term pacing data, minimal pacemaker utilisation (pacing <5% at all checks) was observed in 13 (19%) patients. CONCLUSIONS: Pacemaker insertion in younger adults has significant long-term implications. Clinicians should carefully consider pacemaker insertion in this cohort given risk of device-related complications, potential for device under-utilisation and issues related to lead longevity. In addition, patients require close follow-up for development of structural abnormalities and arrhythmias.

Prediction of Pacemaker Requirement in Patients With Unexplained Syncope: The DROP Score.

BACKGROUND: Implantable loop recorders (ILR) are increasingly utilised in the evaluation of unexplained syncope. However, they are expensive and do not protect against future syncope. OBJECTIVES: To compare patients requiring permanent pacemaker (PPM) implantation during ILR follow-up with those without abnormalities detected on ILR in order to identify potential predictors of benefit from upfront pacing. METHODS: We analysed 100 consecutive patients receiving ILR: Group 1 (n=50) underwent PPM insertion due to bradyarrhythmias detected on ILR; Group 2 (n=50) had no arrhythmias detected on ILR over >3 years follow-up. Baseline clinical characteristics, syncope history, electrocardiographic and echocardiographic parameters were assessed to identify predictors of ultimate requirement for pacing. RESULTS: Group 1 (64% male, median age 70.8 years; IQR 65.5-78.8) were older than Group 2 (58% male, median 60.2 years; IQR 44.0-73.0 p=0.001) and were less likely to have related historical factors such as overheating, posture and exercise (98% vs 70% p<0.001). PR interval was also longer in Group 1 (192±51 vs 169±23 p=0.006) with greater prevalence of distal conduction system disease (30% vs 4.3% p=0.002). Significant univariate predictors for PPM insertion were distal conduction disease (p=0.007), first degree atrioventricular (AV) block (p=0.003), absence of precipitating factors (p=0.004), and age >65 years (p=0.001). Injury sustained, recurrent syncope, history of atrial fibrillation (AF) or heart failure, left atrial (LA) size and left ventricular ejection fraction (LVEF) were not predictive. These significant predictors were incorporated into the DROP score1 (0-4). Using time-to-event analysis, no patients with a score of 0 progressed to pacing, while higher scores (3-4) strongly predicted pacing requirement (log-rank p<0.001). CONCLUSION: The DROP score may be helpful in identifying patients likely to benefit from upfront permanent pacemaker (PPM) insertion following unexplained syncope. Larger prospective studies are required to validate this tool.

Predictors of long-term success after catheter ablation of premature ventricular complexes.

INTRODUCTION: Some patients have late recurrence after acutely successful radiofrequency catheter ablation (RFCA) of premature ventricular complexes (PVCs). The aim of this study was to evaluate predictors of long-term success following acutely successful PVC RFCA. METHODS: We identified consecutive patients at our institution with frequent PVCs undergoing RFCA and reviewed procedural data and medical records. Acute success was defined as elimination of targeted PVCs for at least 30-min after RFCA. Long-term success was defined as absence of targeted PVCs during all follow-up visits and PVC-burden <5% on follow-up monitoring. RESULTS: Among 241 patients (mean age 57 ± 15 years, 58% male), 161 (66.8%) had long-term success with median follow-up of 17.7 (IQR, 12.2-29.8) months. Unadjusted predictors of late PVC recurrence were increasing age, diabetes mellitus and alcohol use, while female-sex, shorter ablation-time, right ventricular PVC-origin, single PVC morphology, and earliest bipolar activation ≥24 ms pre-QRS were predictors of long-term success. In multivariate-analysis, female-sex, single-PVC morphology and earliest-onset of PVC ≥ 24 ms pre-QRS were independent predictors for long-term success. The positive-predictive value of earliest-bipolar onset of PVC ≥ 24 ms pre-QRS for long-term success was 0.77 (p < .001). Negative-predictive value of PVC < 15 ms pre-QRS for long-term success was 0.86 (p = .003), suggesting that RFCA when the bipolar electrogram preceded QRS by <15 ms was unlikely to result in long-term success. CONCLUSIONS: Female-sex, single-PVC morphology, and earliest-onset of bipolar electrogram ≥24 ms pre-QRS were multivariable predictors of long-term success in patients with PVCs undergoing RFCA. RFCA at sites with local onset <15 ms pre-QRS are unlikely to be successful.

A prospective evaluation of the impact of individual RF applications for slow pathway ablation for AVNRT: Markers of acute success.

BACKGROUND: Catheter ablation is highly effective for atrioventricular nodal re-entrant tachycardia (AVNRT). Generally junctional rhythm (JR) is an accepted requirement for successful ablation however there is a lack of detailed prospective studies to determine the characteristics of JR and the impact on slow pathway conduction. METHODS: Multicentre prospective observational study evaluating the impact of individual radiofrequency (RF) applications in typical AVNRT (slow/fast). Characteristics of JR during ablation were documented and detailed testing was performed after every RF application to determine outcome. Procedural success was defined as ≤1 AV nodal echo. RESULTS: Sixty-seven patients were included (mean age 53 ± 18years, 57% female and a history of SVT 2.9 ± 4.7 years). RF (50w, 60°) ablation for AVNRT was applied in 301 locations with JR in 178 (59%). Successful slow pathway modification was achieved in 66 (99%) patients with slow pathway block in 30 (46%). Success was associated with JR in all patients. Success was achieved in six patients with RF < 10 s. There was no significant difference in the CL of JR during RF between effective (587 ± 150 ms) versus ineffective (611 ± 193 ms, p = .4) applications. Inadvertent junctional beat-atrial (JA) block with immediate termination of RF was observed in 19 (28%) patients with AVNRT no longer inducible in 14 (74%). Freedom from SVT was achieved in 66 (99%) patients at a mean follow up of 15 ± 6 months. CONCLUSION: In this prospective study, JR was required during RF for acute success in AVNRT. Cycle length of JR during RF was not predictive of success. Although unintended JA block during faster JR was associated with slow pathway block, this is a precursor to fast pathway block and should not be intentionally targeted.