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.

Impact of early vs. delayed atrial fibrillation catheter ablation on atrial arrhythmia recurrences.

BACKGROUND: Catheter ablation is an effective strategy in atrial fibrillation (AF). However, its timing in the course of management remains unclear. The aim of this study was to determine if an early vs. delayed AF ablation strategy is associated with differences in arrhythmia outcomes during 12-month follow-up. METHODS AND RESULTS: One hundred patients with symptomatic AF referred to a tertiary centre for management were randomized in a 1:1 ratio to either an early ablation strategy (within 1 month of recruitment) or a delayed ablation strategy (optimized medical therapy followed by catheter ablation at 12 months post recruitment). The primary endpoint was atrial arrhythmia free survival at 12 months post-ablation. Secondary outcomes included: (i) AF burden, (ii) AF burden by AF phenotype, and (iii) antiarrhythmic drug (AAD) use at 12 months. Overall, 89 patients completed the study protocol (Early vs. Delayed: 48 vs. 41). Mean age was 59 ± 12.9 years (29% women). Pulmonary vein isolation was achieved in 100% of patients. At 12 months, 56.3% of patients in the early ablation group were free from recurrent arrhythmia, compared with 58.6% in the delayed ablation group (HR 1.12, 95% CI 0.59-2.13, P = 0.7). All secondary outcomes showed no significant difference including median AF burden (Early vs. Delayed: 0% [IQR 3.2] vs. 0% [5], P = 0.66), median AF burden amongst paroxysmal AF patients (0% [IQR 1.1] vs. 0% [4.5], P = 0.78), or persistent AF patients (0% [IQR 22.8] vs. 0% [5.6], P = 0.45) or AAD use (33% vs. 37%, P = 0.8). CONCLUSION: Compared with an early ablation strategy, delaying AF ablation by 12 months for AAD management did not result in reduced ablation efficacy.

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.

Orientation of conduction velocity vectors on cardiac mapping surfaces.

AIMS: Electroanatomical maps using automated conduction velocity (CV) algorithms are now being calculated using two-dimensional (2D) mapping tools. We studied the accuracy of mapping surface 2D CV, compared to the three-dimensional (3D) vectors, and the influence of mapping resolution in non-scarred animal and human heart models. METHODS AND RESULTS: Two models were used: a healthy porcine Langendorff model with transmural needle electrodes and a computer stimulation model of the ventricles built from an MRI-segmented, excised human heart. Local activation times (LATs) within the 3D volume of the mesh were used to calculate true 3D CVs (direction and velocity) for different pixel resolutions ranging between 500 µm and 4 mm (3D CVs). CV was also calculated for endocardial surface-only LATs (2D CV). In the experimental model, surface (2D) CV was faster on the epicardium (0.509 m/s) compared to the endocardium (0.262 m/s). In stimulation models, 2D CV significantly exceeded 3D CVs across all mapping resolutions and increased as resolution decreased. Three-dimensional and 2D left ventricle CV at 500 µm resolution increased from 429.2 ± 189.3 to 527.7 ± 253.8 mm/s (P < 0.01), respectively, with modest correlation (R = 0.64). Decreasing the resolution to 4 mm significantly increased 2D CV and weakened the correlation (R = 0.46). The majority of CV vectors were not parallel (<30°) to the mapping surface providing a potential mechanistic explanation for erroneous LAT-based CV over-estimation. CONCLUSION: Ventricular CV is overestimated when using 2D LAT-based CV calculation of the mapping surface and significantly compounded by mapping resolution. Three-dimensional electric field-based approaches are needed in mapping true CV on mapping surfaces.

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.

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.

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.

Utility of cardiac imaging in patients with ventricular tachycardia.

Ventricular tachycardia (VT) is a life-threatening arrhythmia that may be idiopathic or result from structural heart disease. Cardiac imaging is critical in the diagnostic workup and risk stratification of patients with VT. Data gained from cardiac imaging provides information on likely mechanisms and sites of origin, as well as risk of intervention. Pre-procedural imaging can be used to plan access route(s) and identify patients where post-procedural intensive care may be required. Integration of cardiac imaging into electroanatomical mapping systems during catheter ablation procedures can facilitate the optimal approach, reduce radiation dose, and may improve clinical outcomes. Intraprocedural imaging helps guide catheter position, target substrate, and identify complications early. This review summarises the contemporary imaging modalities used in patients with VT, and their uses both pre-procedurally and intra-procedurally.

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.

From minimally to maximally invasive; VT ablation in the setting of mechanical aortic and mitral valves.

Double mitral and aortic mechanical valves present an access challenge when planning a ventricular tachycardia (VT) ablation. In this case report, we describe a patient who was considered for stereotactic ablative radiotherapy but was unable to proceed due to unfavorable anatomy making them at high risk of fistula formation. The patient went on to have an endocardial VT ablation via mini-thoracotomy and transapical access without complication. This case highlights the need for careful consideration when planning treatment for patients with double mechanical valves.

Clinical, electroanatomic and electrophysiologic characterization and outcomes of catheter ablation for ventricular tachycardia following valvular intervention.

INTRODUCTION: Ventricular tachycardia (VT) can occur following valvular interventions. There are limited data describing substrate and ablation approaches in such patients. We sought to describe the clinical, electrophysiologic, electroanatomic features and catheter ablation outcomes of patients with VT following aortic and/or mitral valve intervention. METHODS: Over 12-years, consecutive patients with aortic valve replacement (AVR) and/or mitral valve replacement (MVR) or repair, undergoing VT ablation, were identified from two centers. Clinical and procedural parameters and outcomes are described. RESULTS: Twenty-three patients (age 66 ± 14years, 78% male, left ventricular ejection fraction 37 ± 16%), with prior AVR (mechanical n = 6, bioprosthetic n = 2, transcatheter n = 1), MVR (mechanical n = 5, bioprosthetic n = 1), mitral valve repair (n = 6) and both mechanical AVR and MVR (n = 2), underwent VT ablation. Sixteen had concurrent ischemic cardiomyopathy, 10 with prior bypass surgery. Left ventricular access was obtained in 21/23 (91%) patients (transseptal n = 14, retrograde aortic n = 5, transapical n = 2), with perivalvular scar identified in 17/21 (81%). Re-entrant VT isthmi involved the perivalvular regions in 12/23 (52%) patients, and regions remote from the valve in the remainder; 9% had nonscar-related VT. Intramural substrate was ablated from adjacent chambers in 5/23 (22%) patients and with half-normal saline irrigation in 8/23 (35%) patients. There were no instances of catheter entrapment. Following final ablation, VA-free survival was 78% at 13-months. CONCLUSION: Only half of VT circuits following valvular interventions involve the valve regions themselves, while the remainder involves unrelated regions. Catheter ablation is safe and efficacious at treating VT following valvular intervention, but novel strategies may be required.

Why do some patients with vulval lichen sclerosus on long-term topical corticosteroid treatment experience ongoing poor quality of life?

OBJECTIVE: To identify reasons for ongoing poor quality of life (pQOL) in a subset of long-term topical corticosteroid-treated vulval lichen sclerosus (VLS) patients. METHODS: A prospective cross-sectional study of patients attending a dermato-gynaecology practice in Sydney, Australia, comparing VLS patients with good quality of life (gQOL) and pQOL, in pre-treatment and long-term treatment groups, using the Vulval Quality of Life Index (VQLI). Demographics, VQLI scores and treatment characteristics were compared between gQOL and pQOL patients. RESULTS: A total of 255 biopsy-proven VLS patients, 67 in pre-treatment and 188 in long-term treated groups were considered. There were 33 (49.3%) pQOL patients in pre-treatment and 13 (6.9%) in treatment groups (p < 0.001). The highest-scoring domain in treated pQOL patients was sexuality (1.7 [interquartile range (IQR) 1.0-2.0]), followed by anxiety [1.3 (IQR 1.0-1.5]), symptoms (1.0 [IQR 0.5-1.5]) and activities of daily living (0.7 [IQR 0.3-1.0]). Compared to treated gQOL, treated pQOL had significantly higher proportions of patients with partial treatment adherence (8 [61.5%] vs 42 [24.0%], p = 0.006), suboptimal disease control (7 [53.8%] vs 20 [11.4%], p < 0.001), scarring progression (3 [23.1%] vs 7 [4.0%], p = 0.024) and urinary incontinence (5 [38.5%] vs 27 [15.4%], p = 0.049). CONCLUSIONS: Only a minority of long-term treated VLS patients reported ongoing pQOL. Of those who did, sexuality and anxiety domains were found to be the main sources of distress. Three major areas distinguishing gQOL from pQOL patients were (1) treatment adherence and disease control, (2) psychological factors and (3) urinary incontinence.

Catheter Ablation for Ventricular Tachycardia in Ischaemic Versus Non-Ischaemic Cardiomyopathy: A Systematic Review and Meta-Analysis.

BACKGROUND: There are differences in substrate and ablation approaches for ventricular tachycardia (VT) in ischaemic (ICM) and non-ischaemic cardiomyopathy (NICM). OBJECTIVE: To perform a systematic review and meta-analysis comparing clinical and procedural characteristics/outcomes of VT ablation in ICM versus NICM. METHODS: Electronic databases were searched for comparative studies reporting outcomes of VT ablation in patients with ICM and NICM. Primary outcomes were acute procedural success, VT recurrence and long-term mortality. Meta-analyses were performed using random-effects modelling. RESULTS: Thirty-one (31) studies (7,473 patients; 4,418 ICM and 3,055 NICM) were included. Patients with ICM were significantly older (67.0 vs 55.3 yrs), more commonly male (89% vs 79%), had lower left ventricular ejection fraction (29% vs 38%) were less likely to undergo epicardial access (11% vs 36%) and were more likely to require haemodynamic support during ablation (relative risk [RR] 1.30; 95% CI 1.01-1.69). Acute procedural success (i.e. non-inducibility of VT) was higher in the ICM cohort (RR 1.10, 95% CI 1.05-1.15). Recurrence of VT at follow-up was significantly lower in the ICM cohort (RR 0.77; 95% CI 0.70-0.84). Peri-procedural mortality, incidence of procedural complications and long-term mortality were not significantly different between the cohorts. CONCLUSIONS: NICM and ICM patients undergoing VT ablation are fundamentally different in their clinical characteristics, ablation approaches, acute procedural outcomes and likelihood of VA recurrence. VT ablation in NICM has a lower likelihood of procedural success with increased risk of VA recurrence, consistent with known challenging arrhythmia substrate.

Substrate-based approaches in ventricular tachycardia ablation.

Catheter ablation for ventricular tachycardia (VT) in patients with structural heart disease is now part of standard care. Mapping and ablation of the clinical VT is often limited when the VT is noninducible, nonsustained or not haemodynamically tolerated. Substrate-based ablation strategies have been developed in an aim to treat VT in this setting and, subsequently, have been shown to improve outcomes in VT ablation when compared to focused ablation of mapped VTs. Since the initial description of linear ablation lines targeting ventricular scar, many different approaches to substrate-based VT ablation have been developed. Strategies can broadly be divided into three categories: 1) targeting abnormal electrograms, 2) anatomical targeting of conduction channels between areas of myocardial scar, and 3) targeting areas of slow and/or decremental conduction, identified with "functional" substrate mapping techniques. This review summarises contemporary substrate-based ablation strategies, along with their strengths and weaknesses.

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.

Sleep apnoea has a dose-dependent effect on atrial remodelling in paroxysmal but not persistent atrial fibrillation: a high-density mapping study.

AIMS: Obstructive sleep apnoea (OSA) associates with atrial fibrillation (AF), but the relationship of OSA severity and AF phenotype with the atrial substrate remains poorly defined. We sought to define the atrial substrate across the spectrum of OSA severity utilizing high-density mapping. METHODS AND RESULTS: Sixty-six consecutive patients (male 71%, age 61 ± 9) having AF ablation (paroxysmal AF 36, persistent AF 30) were recruited. All patents underwent formal overnight polysomnography and high-density left atrial (LA) mapping (mean 2351 ± 1244 points) in paced rhythm. Apnoea-hypopnoea index (AHI) (mean 21 ± 18) associated with lower voltage (-0.34, P = 0.005), increased complex points (r = 0.43, P < 0.001), more low-voltage areas (r = 0.42, P < 0.001), and greater voltage heterogeneity (r = 0.39, P = 0.001), and persisted after multivariable adjustment. Atrial conduction heterogeneity (r = 0.24, P = 0.025) but not conduction velocity (r = -0.09, P = 0.50) associated with AHI. Patchy regions of low voltage that co-localized with slowed conduction defined the atrial substrate in paroxysmal AF, while a diffuse atrial substrate predominated in persistent AF. The association of AHI with remodelling was most apparent among paroxysmal AF [LA voltage: paroxysmal AF -0.015 (-0.025, -0.005), P = 0.004 vs. persistent AF -0.006 (-0.017, 0.005), P = 0.30]. Furthermore, in paroxysmal AF an AHI ≥ 30 defined a threshold at which atrial remodelling became most evident (nil-mild vs. moderate vs. severe: 1.92 ± 0.42 mV vs. 1.84 ± 0.28 mV vs. 1.34 ± 0.41 mV, P = 0.006). In contrast, significant remodelling was observed across all OSA categories in persistent AF (1.67 ± 0.55 mV vs. 1.50 ± 0.66 mV vs. 1.55 ± 0.67 mV, P = 0.82). CONCLUSION: High-density mapping observed that OSA associates with marked atrial remodelling, predominantly among paroxysmal AF cohorts with severe OSA. This may facilitate the identification of AF patients that stand to derive the greatest benefit from OSA management.

Fully reduced HMGB1 accelerates the regeneration of multiple tissues by transitioning stem cells to GAlert.

A major discovery of recent decades has been the existence of stem cells and their potential to repair many, if not most, tissues. With the aging population, many attempts have been made to use exogenous stem cells to promote tissue repair, so far with limited success. An alternative approach, which may be more effective and far less costly, is to promote tissue regeneration by targeting endogenous stem cells. However, ways of enhancing endogenous stem cell function remain poorly defined. Injury leads to the release of danger signals which are known to modulate the immune response, but their role in stem cell-mediated repair in vivo remains to be clarified. Here we show that high mobility group box 1 (HMGB1) is released following fracture in both humans and mice, forms a heterocomplex with CXCL12, and acts via CXCR4 to accelerate skeletal, hematopoietic, and muscle regeneration in vivo. Pretreatment with HMGB1 2 wk before injury also accelerated tissue regeneration, indicating an acquired proregenerative signature. HMGB1 led to sustained increase in cell cycling in vivo, and using Hmgb1-/- mice we identified the underlying mechanism as the transition of multiple quiescent stem cells from G0 to GAlert HMGB1 also transitions human stem and progenitor cells to GAlert Therefore, exogenous HMGB1 may benefit patients in many clinical scenarios, including trauma, chemotherapy, and elective surgery.

Quality of life of women with untreated vulval lichen sclerosus assessed with vulval quality of life index (VQLI).

BACKGROUND/OBJECTIVE: The diagnosis of vulval lichen sclerosus (VLS) is often delayed, and little is known about quality of life (QoL) of women with it prior to receiving diagnosis and treatment. This study aimed to investigate the impact on QoL on patients with previously untreated VLS using the Vulval Quality of Life Index (VQLI). METHODS: A prospective cross-sectional survey of patients attending a dermato-gynaecology practice in Sydney, Australia from March 2018 to November 2019. Patients with a new biopsy-proven diagnosis of VLS not previously commenced on topical corticosteroid treatment were invited to complete the VQLI. RESULTS: A total of 68 participants with median age of 58 (interquartile range, IQR 48-67) years. Median symptom duration was 24 (IQR 11-60) months. Scarring was present in 53% of participants. The median total score was 13.5 (IQR 7.5-22.0), global score 1.0 (IQR 1.0-2.0). Twelve per cent had nil to minimal effect on QoL, 38% had a mild effect on QoL, 28% had a moderate effect on QoL, 22% had a severe effect on QoL, and none had a very severe effect on QoL. The highest-scoring domains were symptoms, followed by sexuality, anxiety and activities of daily living. CONCLUSION: There was significant impairment in all QoL areas of women with untreated VLS. Most experienced moderate-to-severe impairment as a result of the disease and approximately half had already developed scarring at the time of diagnosis. The findings emphasise the importance of improved awareness, early diagnosis and early commencement of treatment in VLS.

Use of narrowband ultraviolet B (NBUVB) in paediatric psoriasis: A systematic literature review and meta-analysis.

BACKGROUND/ OBJECTIVES: Phototherapy is used commonly in adult psoriasis; however, there is little data on its use in the paediatric population. We performed a systematic review and meta-analysis on current available literature to review the safety and efficacy of NBUVB in paediatric psoriasis. METHODS: A systematic review and meta-analysis according to PRISMA guidelines. Meta-analysis of proportions was used to obtain efficacy, and meta-regression was used to explore the impact of treatment variables on efficacy. RESULTS: We identified 10 prospective and retrospective studies for inclusion. From pooled data, we determined the efficacy of NBUVB in paediatric psoriasis to be 80% (CI 70%-88%). There was a positive association between the number of treatments and efficacy of NBUVB. There was no association between the cumulative dose and efficacy. Erythema was the most commonly described side effect. There were no studies of long-term safety of NBUVB in paediatric psoriasis. Limitations included that studies had small patient numbers and were observational in nature. CONCLUSIONS: NBUVB is effective in the treatment of paediatric psoriasis with a good short-term safety profile. More studies are required to assess the influence of variables on efficacy and to elucidate the long-term safety profile of NBUVB in paediatric psoriasis.