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While multi-level theories and frameworks have become a cornerstone in broader efforts to address HIV inequities, little is known regarding their application in adolescent and young adult (AYA) HIV research. To address this gap, we conducted a scoping review to assess the use and application of multi-level theories and frameworks in AYA HIV prevention and care and treatment empirical research. We systematically searched five databases for articles published between 2010 and May 2020, screened abstracts, and reviewed eligible full-text articles for inclusion. Of the 5890 citations identified, 1706 underwent full-text review and 88 met the inclusion criteria: 70 focused on HIV prevention, with only 14 on care and treatment, 2 on both HIV prevention and care and treatment, and 2 on HIV-affected AYA. Most authors described the theory-based multi-level framework as informing their data analysis, with only 12 describing it as informing/guiding an intervention. More than seventy different multi-level theories were described, with 38% utilizing socio-ecological models or the eco-developmental theory. Findings were used to inform the adaptation of an AYA World Health Organization multi-level framework specifically to guide AYA HIV research., (© 2024. The Author(s).)

Background: Non-pulmonary vein (PV) triggers are increasingly targeted during atrial fibrillation (AF) ablation. P-wave morphology (PWM) can be useful because point mapping of AF triggers is challenging. The impact of prior ablation on PWM is yet to be determined., Objectives: This study sought to report PWM before and after left atrial (LA) ablation and construct a P-wave algorithm of common non-PV trigger locations., Methods: This multicenter, prospective, observational study analyzed the paced PWM of 30 patients with persistent AF undergoing pulmonary vein isolation (PVI) and posterior wall isolation (PWI). Pace mapping was performed at the SVC, crista terminalis, inferior tricuspid annulus, coronary sinus ostium, left septum, left atrial appendage, Ligament of Marshall, and inferoposterior LA. The PWM was reported before PVI, then blinded comparisons were made post-PVI and post-PVI + PWI. A P-wave algorithm was constructed., Results: A total of 8,352 paced P waves were prospectively recorded. No significant changes in the PWM were seen post-PVI alone in 2,775 of 2,784 (99.7%) and post-PWI in 2,715 of 2,784 (97.5%). Changes in PWM were predominantly at the IPLA (53 P waves) with a positive P-wave in leads V 2 to V 6 before biphasic post-PWI, LA appendage (9 P waves), coronary sinus ostium (6 P waves), and ligament of Marshall (3 P waves). A PWM algorithm was created before PVI and accurately predicted the location in 93% post-PVI + PWI., Conclusions: Minimal change was observed in PWM post-PV and PWI aside from the IPLA location. A P-wave algorithm created before and applied after PVI + PWI provided an accuracy of 93%. PWM provides a reliable tool to guide the localization of common non-PV trigger sites even after PV and PWI., Competing Interests: Funding Support and Author Disclosures The following industry funding sources regarding activities outside the submitted work have been declared. Dr Lee has received consulting fees from Biosense Webster. Dr Kalman is a recipient of the Practitioner fellowship from the NHMRC; and has received fellowship support from Medtronic and Biosense Webster. Dr Kistler is a recipient of the investigator grant from the NHMRC; has received funding from Abbott Medical for consultancy and speaking engagements; and has served on the advisory board with fellowship support from Biosense Webster. All other authors have reported that they have no relationships relevant to the contents of this paper., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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/m 2 , 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/m 2 ) (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., Competing Interests: Funding Support and Author Disclosures This study received seed grant funding from the Baker Department of Cardiometabolic Health, University of Melbourne. The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. The funding source has no right to veto publication or control the decision regarding to which journal the paper was submitted. Dr Segan was supported by a cofunded National Health and Medical Research Council/National Heart Foundation postgraduate scholarship. Dr Lee has received consulting fees from Biosense Webster. Dr Pathak has served on the advisory board of Medtronic, Abbott Medical, and Boston Scientific; and received funding for research and consultancy from Medtronic, Abbott Medical, Boston Scientific, and Biotronik. Dr Ginks has received funding for speaking engagements from Abbott and Biosense Webster. Dr Kalman has received fellowship support from Medtronic and Biosense Webster. Dr Kistler has received funding from Abbott Medical for consultancy and speaking engagements; and served on the advisory board with fellowship support from Biosense Webster. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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.

Background: Pulmonary vein isolation (PVI) is less effective in patients with persistent atrial fibrillation (PsAF). Adjunctive ablation targeting low voltage areas (LVAs) may improve arrhythmia outcomes., Objectives: This study aims to compare the outcomes of adding posterior wall isolation (PWI) to PVI, vs PVI alone in PsAF patients with posterior wall LVAs., Methods: The CAPLA (Effect of Catheter Ablation Using Pulmonary Vein Isolation With vs Without Posterior Left Atrial Wall Isolation on Atrial Arrhythmia Recurrence in Patients With Persistent Atrial Fibrillation) study was a multicenter, randomized trial involving PsAF patients randomized 1:1 to either PVI alone or PVI with PWI. Voltage mapping performed during pacing pre-ablation was reviewed offline, with LVA defined as bipolar voltage of <0.5 mV. The primary endpoint was freedom from any documented atrial arrhythmia of >30 seconds off antiarrhythmic medication at 12 months after a single ablation procedure in patients with posterior LVA., Results: A total of 210 patients (average 64.6 ± 9.2 years,73.3% males, median atrial fibrillation duration 4.5 months [IQR: 2 to 8 months]) underwent multipolar left atrial mapping during coronary sinus pacing with posterior LVA present in 69 (32.9%). Patients with posterior LVA were more likely to have LVA in other atrial regions (91.7% vs 57.1%; P < 0.01), larger left atrial diameter (4.8 cm vs 4.4 cm; P < 0.01), and significantly increased risk of atrial arrhythmia recurrence at 12 months (LVA: 56.5% vs no LVA: 41.4%; HR: 1.51; 95% CI: 1.01-2.27; P = 0.04) compared to no posterior LVA. However, the addition of PWI to PVI did not significantly improve freedom from atrial arrhythmia recurrence over PVI alone (PVI with PWI: 44.8% vs PVI: 41.9%; HR: 0.95; 95% CI: 0.51-1.79; P = 0.95)., Conclusions: In patients with PsAF undergoing catheter ablation, posterior LVA was associated with a significant increase in atrial arrhythmia recurrence. However, the addition of PWI in those with posterior LVA did not reduce atrial arrhythmia recurrence over PVI alone., Competing Interests: Funding and Author Disclosures This study received seed grant funding from the Baker department of Cardiometabolic Health, University of Melbourne. Dr Lee has received consulting fees from Biosense Webster. Dr Sanders has served on advisory boards for Medtronic, Abbott Medical, Boston Scientific, CathRx, and PaceMate; and has received funding for research and consultancy from Medtronic, Abbott Medical, Boston Scientific, and Microport. Dr Kalman has received fellowship support from Medtronic and Biosense Webster. Dr Kistler has received the investigator grant from the NHMRC; has received funding from Abbott Medical for consultancy and speaking engagements; and has served on the advisory board with fellowship support from Biosense Webster. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background Transesophageal echocardiography-guided direct cardioversion is recommended in patients who are inadequately anticoagulated due to perceived risk of left atrial appendage thrombus (LAAT); however, LAAT risk factors remain poorly defined. Methods and Results We evaluated clinical and transthoracic echocardiographic parameters to predict LAAT risk in consecutive patients with atrial fibrillation (AF)/atrial flutter undergoing transesophageal echocardiography before cardioversion between 2002 and 2022. Regression analysis identified predictors of LAAT, combined to create the novel CLOTS-AF risk score (comprising clinical and echocardiographic LAAT predictors), which was developed in the derivation cohort (70%) and validated in the remaining 30%. A total of 1001 patients (mean age, 62±13 years; 25% women; left ventricular ejection fraction, 49.8±14%) underwent transesophageal echocardiography, with LAAT identified in 140 of 1001 patients (14%) and dense spontaneous echo contrast precluding cardioversion in a further 75 patients (7.5%). AF duration, AF rhythm, creatinine, stroke, diabetes, and echocardiographic parameters were univariate LAAT predictors; age, female sex, body mass index, anticoagulant type, and duration were not (all P >0.05). CHADS 2 VASc, though significant on univariate analysis ( P <0.001), was not significant after adjustment ( P =0.12). The novel CLOTS-AF risk model comprised significant multivariable predictors categorized and weighted according to clinically relevant thresholds (Creatinine >1.5 mg/dL, Left ventricular ejection fraction <50%, Overload (left atrial volume index >34 mL/m 2 ), Tricuspid Annular Plane Systolic Excursion (TAPSE) <17 mm, Stroke, and AF rhythm). The unweighted risk model had excellent predictive performance with an area under the curve of 0.820 (95% CI, 0.752-0.887). The weighted CLOTS-AF risk score maintained good predictive performance (AUC, 0.780) with an accuracy of 72%. Conclusions The incidence of LAAT or dense spontaneous echo contrast precluding cardioversion in patients with AF who are inadequately anticoagulated is 21%. Clinical and noninvasive echocardiographic parameters may identify patients at increased risk of LAAT better managed with a suitable period of anticoagulation before undertaking cardioversion.

Background: Patients with heart failure with preserved ejection fraction (HFpEF) frequently develop atrial fibrillation (AF). There are no randomized trials examining the effects of AF ablation on HFpEF outcomes., Objectives: The aim of this study is to compare the effects of AF ablation vs usual medical therapy on markers of HFpEF severity, including exercise hemodynamics, natriuretic peptide levels, and patient symptoms., Methods: Patients with concomitant AF and HFpEF underwent exercise right heart catheterization and cardiopulmonary exercise testing. HFpEF was confirmed with pulmonary capillary wedge pressure (PCWP) of 15 mm Hg at rest or ≥25 mm Hg on exercise. Patients were randomized to AF ablation vs medical therapy, with investigations repeated at 6 months. The primary outcome was change in peak exercise PCWP on follow-up., Results: A total of 31 patients (mean age: 66.1 years; 51.6% females, 80.6% persistent AF) were randomized to AF ablation (n = 16) vs medical therapy (n = 15). Baseline characteristics were comparable across both groups. At 6 months, ablation reduced the primary outcome of peak PCWP from baseline (30.4 ± 4.2 to 25.4 ± 4.5 mm Hg; P < 0.01). Improvements were also seen in peak relative VO 2 (20.2 ± 5.9 to 23.1 ± 7.2 mL/kg/min; P < 0.01), N-terminal pro-B-type natriuretic peptide levels (794 ± 698 to 141 ± 60 ng/L; P = 0.04), and MLHF (Minnesota Living with Heart Failure) score (51 ± -21.9 to 16.6 ± 17.5; P < 0.01). No differences were detected in the medical arm. Following ablation, 50% no longer met exercise right heart catheterization-based criteria for HFpEF vs 7% in the medical arm (P = 0.02)., Conclusions: AF ablation improves invasive exercise hemodynamic parameters, exercise capacity, and quality of life in patients with concomitant AF and HFpEF., Competing Interests: Funding Support and Author Disclosures Dr Chieng is supported by co-funded NHMRC/NHF post-graduate scholarship. Dr Prabhu has received an NHMRC Post-Doctoral Research Fellowship. Dr Voskoboinik has received a National Heart Foundation Early Career Fellowship. Dr Lee has received consulting fees from Biosense Webster. Dr Kistler has received funding from Abbott Medical for consultancy and speaking engagements; and has served on the advisory board with fellowship support from Biosense Webster. Dr Kalman has received fellowship support from Medtronic and Biosense Webster. Dr Kaye has received an NHMRC Investigator Grant. Dr Ling has received funding from Abbott Medical for project funding, consultancy, and speaking engagements; and has received funding from Abbott Medical for project funding, consultancy, and speaking engagements. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Atrial fibrillation (AF) is an irregular heart rhythm, characterised by chaotic atrial activation, which is promoted by remodelling. Once initiated, AF can also propagate the progression of itself in the so-called ''AF begets AF''. Several lines of investigation have shown that signalling molecules, including reactive oxygen species, angiotensin II, and phosphoinositide 3-kinases (PI3Ks), in presence or absence of cardiovascular disease risk factors, stabilise and promote AF maintenance. In particular, reduced cardiac-specific PI3K activity that is not associated with oncology is cardiotoxic and increases susceptibility to AF. Atrial-specific PI3K(p110α) transgene can cause pathological atrial enlargement. Highlighting the crucial importance of the p110α protein in a clinical problem that currently challenges the professional health care practice, in over forty (40) transgenic mouse models of AF (Table1), currently existing, of which some of the models are models of human genetic disorders, including PI3K(p110α) transgenic mouse model, over 70% of them reporting atrial size showed enlarged, greater atrial size. Individuals with minimal to severely dilated atria develop AF more likely. Left atrial diameter and volume stratification are an assessment for follow-up surveillance to detect AF. Gene therapy to reduce atrial size will be associated with a reduction in AF burden. In this overview, PI3K(p110α), a master regulator of organ size, was investigated in atrial enlargement and in physiological determinants that promote AF., (© 2022. The Author(s).)

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., Competing Interests: Conflict of interest: D.C. is supported by co-funded NHMRC/NHF post-graduate scholarship. The following industry funding sources regarding activities outside the submitted work have been declared in accordance with ICMJE guidelines. P.M.K. has received funding from Abbott Medical for consultancy and speaking engagements and fellowship support from Biosense Webster. J.M.K. holds a Practitioner Fellowship of the NHMRC and has research and fellowship support from Medtronic, Abbott and Biosense Webster. S.P. has a NHMRC Post Doctoral Research Fellowship. A.V. has a National Heart Foundation Early Career Fellowship. The remaining authors have nothing to disclose., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Accurate annotation of local activation time is crucial in the functional assessment of ventricular tachycardia (VT) substrate. A major limitation of modern mapping systems is the standard prospective window of interest (sWOI) is limited to 490 to 500 milliseconds, preventing annotation of very late potentials (LPs). A novel retrospective window of interest (rWOI), which allows annotation of all diastolic potentials, was used to assess the functional VT substrate., Objectives: This study sought to investigate the utility of a novel rWOI, which allows accurate visualization and annotation of all LPs during VT substrate mapping., Methods: Patients with high-density VT substrate maps and a defined isthmus were included. All electrograms were manually annotated to latest activation using a novel rWOI. Reannotated substrate maps were correlated to critical sites, with areas of late activation examined. Propagation patterns were examined to assess the functional aspects of the VT substrate., Results: Forty-eight cases were identified with 1,820 ± 826 points per map. Using the novel rWOI, 31 maps (65%) demonstrated LPs beyond the sWOI limit. Two distinct patterns of channel activation were seen during substrate mapping: 1) functional block with unidirectional conduction into the channel (76%); and 2) wave front collision within the channel (24%). In addition, a novel marker termed the zone of early and late crowding was studied in the rWOI substrate maps and found to have a higher positive predictive value (85%) than traditional deceleration zones (69%) for detecting critical sites of re-entry., Conclusions: The standard WOI of contemporary mapping systems is arbitrarily limited and results in important very late potentials being excluded from annotation. Future versions of electroanatomical mapping systems should provide longer WOIs for accurate local activation time annotation., Competing Interests: Funding Support and Author Disclosures Dr Kistler has received fellowship support from Biosense Webster. Dr Kalman is supported by a National Health and Medical Research Council of Australia practitioner fellowship and by fellowship support from Biosense Webster. Dr Hsia has received honoraria from Biosense Webster. Dr Kalman has received research support from Biosense Webster. Dr Lee has received speaker honoraria from Biosense Webster. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Epidemiological studies report the beneficial effects of habitual coffee consumption on incident arrhythmia, cardiovascular disease (CVD), and mortality. However, the impact of different coffee preparations on cardiovascular outcomes and survival is largely unknown. The aim of this study was to evaluate associations between coffee subtypes on incident outcomes, utilizing the UK Biobank., Methods and Results: Coffee subtypes were defined as decaffeinated, ground, and instant, then divided into 0, <1, 1, 2-3, 4-5, and >5 cups/day, and compared with non-drinkers. Cardiovascular disease included coronary heart disease, cardiac failure, and ischaemic stroke. Cox regression modelling with hazard ratios (HRs) assessed associations with incident arrhythmia, CVD, and mortality. Outcomes were determined through ICD codes and death records. A total of 449 563 participants (median 58 years, 55.3% females) were followed over 12.5 ± 0.7 years. Ground and instant coffee consumption was associated with a significant reduction in arrhythmia at 1-5 cups/day but not for decaffeinated coffee. The lowest risk was 4-5 cups/day for ground coffee [HR 0.83, confidence interval (CI) 0.76-0.91, P < 0.0001] and 2-3 cups/day for instant coffee (HR 0.88, CI 0.85-0.92, P < 0.0001). All coffee subtypes were associated with a reduction in incident CVD (the lowest risk was 2-3 cups/day for decaffeinated, P = 0.0093; ground, P < 0.0001; and instant coffee, P < 0.0001) vs. non-drinkers. All-cause mortality was significantly reduced for all coffee subtypes, with the greatest risk reduction seen with 2-3 cups/day for decaffeinated (HR 0.86, CI 0.81-0.91, P < 0.0001); ground (HR 0.73, CI 0.69-0.78, P < 0.0001); and instant coffee (HR 0.89, CI 0.86-0.93, P < 0.0001)., Conclusion: Decaffeinated, ground, and instant coffee, particularly at 2-3 cups/day, were associated with significant reductions in incident CVD and mortality. Ground and instant but not decaffeinated coffee was associated with reduced arrhythmia., Competing Interests: Conflict of interest: D.C. is supported by cofunded NHMRC/NHF post-graduate scholarship. The following industry funding sources regarding activities outside the submitted work have been declared in accordance with ICMJE guidelines. P.M.K. has received funding from Abbott Medical for consultancy and speaking engagements and fellowship support from Biosense Webster. J.M.K. holds a Practitioner Fellowship of the NHMRC and has research and fellowship support from Medtronic, Abbott, and Biosense Webster. D.M.K. is the recipient of an NHMRC Research Fellowship. S.P. has an NHMRC Post-Doctoral Research Fellowship. A.V. has a National Heart Foundation Early Career Fellowship. The remaining authors have nothing to disclose., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Class I phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases. They are super elevated in many human cancer types and exert their main cellular functions by activating Akt to trigger an array of distinct responses, affecting metabolism and cell polarity. The signal equally plays important roles in cardiovascular pathophysiology. PI3K is required for cardiogenesis and regulation of cardiac structure and function. Overexpression of PI3K governs the development of cardiac pressure overload adaptation and compensatory hypertrophy. Therefore, inhibition of PI3K shortens life span, enhances cardiac dysfunction and pathological hypertrophy. The inverse inhibition effect, however, desirably destroys many cancer cells by blocking several aspects of the tumorigenesis phenotype. Given the contrasting effects in cardio-oncology; the best therapeutic strategy to target PI3K in cancer, while maintaining or rather increasing cardiac safety is under intense investigational scrutiny. To improve our molecular understanding towards identifying cardiac safety signalling of PI3K and/or better therapeutic strategy for cancer treatment, this article reviews PI3K signalling in cardio-oncology. PI3K signalling at the interface of metabolism, inflammation and immunity, and autonomic innervation networks were examined. Examples were then given of cardiovascular drugs that target the networks, being repurposed for cancer treatment. This was followed by an intersection scheme of the networks that can be functionalised with machine learning for safety and risk prediction, diagnoses, and defining new novel encouraging leads and targets for clinical translation. This will hopefully overcome the challenges of the one-signalling-one-health-outcome alliance, and expand our knowledge of the totality of PI3K signalling in cardio-oncology., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The accumulating literature linking stress with negative health outcomes, including cardiovascular disease (CVD), is extensively reported yet poorly defined. Stress is associated with a higher risk of hypertension, acute myocardial infarction, arrhythmogenesis, and heart failure. Stress mediates its effect through direct neuronal, endocrine, autonomic, and immune processes and indirectly by modifying lifestyle behaviors that promote CVD progression. Stress occurs when an individual perceives that internal or external demands exceed the capacity for an adaptive response. Psychologic stress is increasingly recognized in the atrial fibrillation (AF) population, although the pathophysiology remains unclear. There appears to be a bidirectional relationship between AF and stress with a complex interplay between the 2 entities. Stress modulates the immune and autonomic nervous systems, key drivers in AF initiation and potentiation. AF leads to increasing anxiety, psychologic distress, and suicidal ideation. Recently, lifestyle modification has emerged as the fourth pillar of AF management, with stress reduction a potential reversible risk factor and future target for intervention. This review examines proposed mechanisms linking AF and stress and explores stress reduction as an adjunct to the AF management armamentarium., Competing Interests: Funding Support and Author Disclosures Dr Segan is supported by a NHMRC/NHF co-funded postgraduate scholarship. Prof Kalman is the recipient of a Practitioner Fellowship of the NHMRC and has received research and fellowship support from Medtronic, Abbott, Itamar Medical, and Biosense Webster. Prof Kistler has received funding from Abbott Medical for consultancy and speaking engagements and fellowship support from Biosense Webster. Dr Prabhu has reported that he has no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Observational studies report that obstructive sleep apnea (OSA) is associated with an increasingly remodeled atrial substrate in atrial fibrillation (AF). However, the impact of OSA management on the electrophysiologic substrate has not been evaluated., Objectives: In this study, the authors sought to determine the impact of OSA management on the atrial substrate in AF., Methods: We recruited 24 consecutive patients referred for AF management with at least moderate OSA (apnea-hypopnea index [AHI] ≥15). Participants were randomized in a 1:1 ratio to commence continuous positive airway pressure (CPAP) or no therapy (n = 12 CPAP; n = 12 no CPAP). All participants underwent invasive electrophysiologic study (high-density right atrial mapping) at baseline and after a minimum of 6 months. Outcome variables were atrial voltage (mV), conduction velocity (m/s), atrial surface area <0.5 mV (%), proportion of complex points (%), and atrial effective refractory periods (ms). Change between groups over time was compared., Results: Clinical characteristics and electrophysiologic parameters were similar between groups at baseline. Compliance with CPAP therapy was high (device usage: 79% ± 19%; mean usage/day: 268 ± 91 min) and resulted in significant AHI reduction (mean reduction: 31 ± 23 events/h). There were no differences in blood pressure or body mass index between groups over time. At follow-up, the CPAP group had faster conduction velocity (0.86 ± 0.16 m/s vs 0.69 ± 0.12 m/s; P (time × group) = 0.034), significantly higher voltages (2.30 ± 0.57 mV vs 1.94 ± 0.72 mV; P < 0.05), and lower proportion of complex points (8.87% ± 3.61% vs 11.93% ± 4.94%; P = 0.011) compared with the control group. CPAP therapy also resulted in a trend toward lower proportion of atrial surface area <0.5 mV (1.04% ± 1.41% vs 4.80% ± 5.12%; P = 0.065)., Conclusions: CPAP therapy results in reversal of atrial remodeling in AF and provides mechanistic evidence advocating for management of OSA in AF., Competing Interests: Funding Support and Author Disclosures For this work, Dr Nalliah received the Eric Prystowsky Fellows Clinical Research Award, Heart Rhythm Society, May 2020, and the Ralph Reader Young Investigator Prize of the Cardiac Society of Australia and New Zealand, December 2020; and he is supported also by the National Heart Foundation and a Viertel Charitable Foundation Clinical Investigator Award. Dr Voskoboinik is supported by an NHMRC EL1 Investigator Grant and an NHF Early Career Fellowship. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Men who have sex with men (MSM) bear a disproportionately high burden of new HIV infections while lagging behind other populations with respect to engagement across the HIV care continuum. General risk factors for condomless anal intercourse (CAI) among MSM are well studied but there is a paucity of partner-level data, where emerging evidence suggests that much of the variation in condom use occurs., Methods: MSM were recruited across 10 cities in India using respondent-driven sampling (RDS) from 2016-17. Among the individuals who reported sexual intercourse in the prior 6 months, condom use and partner characteristics of the last 4 partners were captured. Correlates of CAI at the individual and partner level were determined using Poisson regression models using generalized estimating equations and incorporating RDS-II weights, which weights estimates for the participant's network size., Results: Among the 8,086 individuals, 21,723 sexual partnerships were analyzed. The prevalence of CAI was 46.9% and most partners were casual or one-time (70.7%) with partner HIV status reported as unknown in 42.6% of the sexual encounters. In multivariable analyses, partner-level characteristics associated with higher likelihood of CAI included unknown partner HIV status (aPR vs. known HIV negative partner: 1.34; 95% confidence interval (CI): 1.27-1.43) and use of alcohol/ drugs prior to intercourse either sometimes (aPR 1.42; 95% CI: 1.33-1.51) or always (aPR 1.31; 95% CI: 1.23-1.41). At an individual level, any HIV treatment literacy was associated with a lower likelihood of CAI (aPR 0.80; 95% CI: 0.74-0.86)., Conclusions: To reduce HIV transmission among this population of MSM across India, combination interventions are likely needed. Interventions targeting substance use and education as well as initiatives to increase self-testing are urgently needed among MSM in India and have the potential to reduce HIV transmission in this high-risk population. Trial registration ClinicalTrials.gov Identifier: NCT01686750. Date of Registration: September 18, 2012., (© 2022. The Author(s).)

Objectives: This study sought to assess the association between electrocardiographic imaging (ECGI) parameters and voltage from simultaneous electroanatomic mapping (EAM)., Background: ECGI offers noninvasive assessment of electrophysiologic features relevant for mapping ventricular arrhythmia and its substrate, but the accuracy of ECGI in the delineation of scar is unclear., Methods: Sixteen patients with structural heart disease underwent simultaneous ECGI (CardioInsight, Medtronic) and contact EAM (CARTO, Biosense-Webster) during ventricular tachycardia catheter ablation, with 7 mapped epicardially. ECGI and EAM geometries were coregistered using anatomic landmarks. ECGI points were paired to the closest site on the EAM within 10 mm. The association between EAM voltage and ECGI features from reconstructed epicardial unipolar electrograms was assessed by mixed-effects regression models. The classification of low-voltage regions was performed using receiver-operating characteristic analysis., Results: A total of 9,541 ECGI points (median: 596; interquartile range: 377-737 across patients) were paired to an EAM site. Epicardial EAM voltage was associated with ECGI features of signal fractionation and local repolarization dispersion (N = 7; P < 0.05), but they poorly classified sites with bipolar voltage of <1.5 mV or <0.5 mV thresholds (median area under the curve across patients: 0.50-0.62). No association was found between bipolar EAM voltage and low-amplitude reconstructed epicardial unipolar electrograms or ECGI-derived bipolar electrograms. Similar results were found in the combined cohort (n = 16), including endocardial EAM voltage compared to epicardial ECGI features (n = 9)., Conclusions: Despite a statistically significant association between ECGI features and EAM voltage, the accuracy of the delineation of low-voltage zones was modest. This may limit ECGI use for pr-procedural substrate analysis in ventricular tachycardia ablation, but it could provide value in risk assessment for ventricular arrhythmias., Competing Interests: Funding Support and Author Disclosures Dr Graham was supported by a Barts Charity grant. Dr Lambiase was supported by University College London Hospital Biomedicine National Institute for Health Research and Barts Biomedical Research Centre; has received research grants from Boston Scientific, Medtronic, and Abbott; and has received speaker fees from Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The number of older women living with HIV in Africa is growing, and their health outcomes may be adversely impacted by social frailty, which reflects deficits in social resources that accumulate over the lifespan. Our objective was to adapt a Social Vulnerability Index (SVI) originally developed in Canada for use in a study of older women living with or without HIV infection in Mombasa, Kenya., Methods: We adapted the SVI using a five-step process: formative qualitative work, translation into Kiswahili, a Delphi procedure, exploration of potential SVI items in qualitative work, and a rating and ranking exercise. Four focus group discussions (FGD) were conducted (three with women living with HIV and one with HIV-negative women), and two expert panels were constituted for this process., Results: Themes that emerged in the qualitative work were physical impairment with aging, decreased family support, a turn to religion and social groups, lack of a financial safety net, mixed support from healthcare providers, and stigma as an added burden for women living with HIV. Based on the formative FGD, the expert panel expanded the original 19-item SVI to include 34 items. The exploratory FGD and rating and ranking exercise led to a final 16-item Kenyan version of the SVI (SVI-Kenya) with six domains: physical safety, support from family, group participation, instrumental support, emotional support, and financial security., Conclusions: The SVI-Kenya is a holistic index to measure social frailty among older women in Kenya, incorporating questions in multiple domains. Further research is needed to validate this adapted instrument., (© 2022. The Author(s).)

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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: This study sought to report P-wave morphology (PWM) from a series of paraseptal (PS) atrial tachycardia (AT), revise then prospectively evaluate a simplified PWM algorithm against a contemporary consecutive cohort with focal AT., Background: The 2006 PWM algorithm was useful in predicting the origin of focal AT. An updated algorithm was developed given advances in multipolar 3-dimensional mapping, potential limitations of PWM in separating PS sites, and a renewed interest in the P-wave in mapping non-pulmonary vein triggers., Methods: The PWM from a consecutive series of 67 patients with PS AT were analyzed. PS sites included were coronary sinus ostium, perinodal, left and right septum, septal tricuspid annulus, superior mitral annulus, and noncoronary cusp. Next the P-wave algorithm was revised and prospectively evaluated by 3 blinded assessors., Results: The P-wave for PS sites was neg/pos (n = 50), iso/pos (n = 10), or isoelectric (n = 4) in lead V 1 (96%). The P-wave algorithm was modified and prospectively applied to 30 consecutive patients with focal AT who underwent successful ablation. Foci (n = 30) originated from the right atrium (33.3%), left atrium (30%), and PS (36.7%). Using the PW algorithm, the correct anatomic location was identified in 93%. Incorrect interpretation of the terminal positive P-wave component (n = 3) and initial negative P-wave deflection (n = 1) in lead V 1 misidentified 4 paraseptal cases., Conclusions: The revised PWM algorithm offers a simplified and accurate method of localizing the responsible site for focal AT. The P-wave remains an important first step in mapping atrial arrhythmias., Competing Interests: Funding Support and Author Disclosures Dr Chieng has been supported by a co-funded National Health and Medical Research Council (NHMRC)/National Heart Foundation postgraduate scholarship. The following industry funding sources regarding activities outside the submitted work have been declared in accordance with ICMJE guidelines. Prof Kistler has received funding from Abbott Medical for consultancy and speaking engagements and fellowship support from Biosense Webster. Prof Kalman has had an NHMRC practitioner fellowship, and research and fellowship support from Medtronic and Biosense Webster. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to describe expected changes in a mirror-image prone electrocardiogram (ECG) compared with normal supine, including a range of cardiac conditions., Background: Unwell COVID-19 patients are at risk of cardiac complications. Prone ventilation is recommended but poses practical challenges to acquisition of a 12-lead ECG. The effects of prone positioning on the ECG remain unknown., Methods: 100 patients each underwent 3 ECGs: standard supine front (SF); prone position with precordial leads attached to front (PF); and prone with precordial leads attached to back in a mirror image to front (PB)., Results: Prone positioning was associated with QTc prolongation (PF 437 ± 32 ms vs. SF 432 ± 31 ms; p < 0.01; PB 436 ± 34 ms vs. SF 432 ± 31 ms; p = 0.02). In leads V 1 to V 3 on PB ECG, a qR morphology was present in 90% and changes in T-wave polarity in 84%. In patients with anterior ischemia, ST-segment changes in V 1 to V 3 on supine ECG were no longer visible on PB in 100% and replaced by an R-wave in V 1 . Bundle branch block (BBB) remained detectable in 100% on PB, with left BBB appearing as right BBB on PB in 71% and QRS narrowing with qR in V 1 for right BBB. ST-segment/T-wave changes in limb leads and arrhythmia detection were largely unaffected in PB., Conclusions: As expected, the PB ECG is unreliable for the detection of anterior myocardial injury but remains useful for ST-segment/T-wave abnormalities in limb leads, BBB detection, and rhythm monitoring. The prone ECG is a useful screening tool with diagnostic utility in COVID-19 patients who require prone ventilation., Competing Interests: Funding Support and Author Disclosures Dr. Chieng is supported by a cofunded National Health and Medical Research Council/ National Heart Foundation post-graduate scholarship. Dr. Kalman has received research and fellowship support from Medtronic and Biosense Webster. Prof. Kistler has received funding from Abbott Medical; and fellowship support from Biosense Webster. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aim: Immediate implant in the esthetic zone is a treatment of choice. However, much research regarding immediate implant provisionalization lacked in the literature. Hence, our study was conducted with an aim to assess the changes in the soft tissue, hard tissue, and esthetic outcomes following immediate implants with provisionalization with or without bone grafting., Materials and Methods: Twenty patients with a mean age between 18 and 55 years referred to the department of periodontology, for immediate implant placement in maxillary anterior region were included in the study. Patients were enrolled into two groups. Group I (test group) included patients with immediate implant placement with provisionalization with bone grafting. Group II (control group) included patients with immediate implant placement with provisionalization without bone grafting. Cement-retained provisional restoration was fitted over temporary abutment for 6 months of healing period. After 6 months of implant placement, definite crown was delivered., Results: The results of our study showed the least resorption of buccal cortical plate and good amount of bone gain in both the groups in terms of horizontal alveolar dimensional changes. The mean amount of horizontal alveolar gain in group I was 1.12 mm at 2 mm, 1.08 mm at 4 mm, and 0.85 mm at 6 mm; in group II, it was 0.97 mm at 2 mm, 1.4 mm at 4 mm, and 0.93 mm at 6 mm., Conclusion: This study showed a significantly better outcome in both the groups in terms of all the parameters when compared from baseline but the mean differences between the two groups were not very significant. The study concluded that immediate implant with provisionalization with or without bone grafting has maintained stability of soft tissues as well as hard tissues and has also given better esthetic outcomes., Clinical Significance: The findings of this study proved that immediate implant placement with provisionalization with bone grafting is a predictable treatment modality that maintains the three-dimensional stability of alveolar bone and integrity of soft tissue and gives acceptable esthetics. Hence, this technique promises to fulfill both functional and esthetic concerns of the patient.

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., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Objectives: This study sought to determine the long-term outcomes of restoring sinus rhythm with catheter ablation (CA)., Background: The CAMERA-MRI (Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Heart Failure-An MRI-Guided Multicenter Randomized Controlled Trial) study demonstrated that restoration of sinus rhythm with CA significantly improved left ventricular ejection fraction (LVEF) compared with medical rate control (MRC) at 6 months in persistent atrial fibrillation and otherwise unexplained systolic heart failure. However, the long-term outcomes have not been reported., Methods: Patients enrolled in the CAMERA-MRI study were followed for 4 years with echocardiogram and cardiac magnetic resonance. CA involved pulmonary vein isolation and posterior left atrial wall isolation in 94%. Patients crossed over to CA after 6-month study duration. Arrhythmia burden was determined with implanted cardiac monitors or cardiac devices., Results: Sixty-six patients (age 62 ± 10 years, atrial fibrillation duration of 22 ± 16 months, and LVEF 33 ± 9%) were randomized 1:1 to CA versus MRC. Eighteen of 33 patients crossed over from MRC group to CA group. At 4.0 ± 0.9 years, atrial fibrillation recurred in 27 patients (57%) in the CA group with a mean burden of 10.6 ± 21.2% after 1.4 ± 0.6 procedures. There was an absolute increase in LVEF with CA of 16.4 ± 13.3% compared with 8.6 ± 7.6% in MRC (p = 0.001). In the CA group, the absence of ventricular late gadolinium enhancement was associated with a greater improvement in absolute LVEF (19 ± 13% vs. 10 ± 11% in the late gadolinium enhancement-positive group; p = 0.04) and LVEF normalization in 19 patients (58%) versus 4 patients (18%) in the late gadolinium enhancement-positive group (p = 0.008) at 4.0 ± 0.9 years follow-up., Conclusions: CA is superior to MRC in improving LVEF in the long term in patients with atrial fibrillation and systolic heart failure. The greatest recovery in systolic function was demonstrated in the absence of ventricular fibrosis on cardiac magnetic resonance., Competing Interests: Author Disclosures Dr. Sugumar has received support from a co-funded National Health and Medical Research Committee/National Health Foundation post-graduate scholarships and Royal Australian College of Physicians J.J. Billings and Centre of Research Excellence in Cardiovascular Outcomes Improvement scholarships. Prof. Jonathan M. Kalman has received a National Health and Medical Research Committee practitioner fellowship; and research and fellowship support from Medtronic and Biosense Webster, all outside the submitted work. Prof. Kistler has received funding from Abbott Medical for consultancy and speaking engagements, outside the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to assess the atrial electrophysiological properties and post-ablation outcomes in patients with atrial fibrillation (AF) with and without the rs2200733 single nucleotide variant., Background: The phenotype associated with chromosome 4q25 of the AF-susceptibility locus remains unknown., Methods: In this study, 102 consecutive patients (ages 61 ± 9 years, 64% male) with paroxysmal or persistent AF were prospectively recruited prior to ablation. Patients were genotyped for rs2200733 and high-density left atrial (LA) electroanatomic maps were created using a multipolar catheter during distal coronary sinus (CS) pacing at 600 ms. Voltage, conduction velocity (CV), CV heterogeneity, and fractionated signals of 6 LA segments were determined. Arrhythmia recurrence was assessed by continuous device (51%) and Holter monitoring., Results: Overall, 41 patients (40%) were single nucleotide variant carriers (38 heterozygous, 3 homozygous). A mean of 2,239 ± 852 points per patient were collected. Carriers had relatively increased CV heterogeneity (45.7 ± 7.5% vs. 35.9 ± 2.3%; p < 0.001), complex signals (9.4 ± 2.9% vs 6.0 ± 1.2%; p = 0.008), regional LA slowing, or conduction block (31.7 ± 8.2% vs. 17.9 ± 1.9%; p = 0.013) particularly in the posterior and lateral walls. There were no differences in CV, voltage, atrial refractoriness, or sinus node function. At follow-up (median: 27 months; range 19 to 31 months), carriers had lower arrhythmia-free survival (51% vs. 80%; p = 0.003). On multivariable analysis, carrier status was independently associated with CV heterogeneity (p = 0.001), complex signals (p = 0.002), and arrhythmia recurrence (p = 0.019)., Conclusions: These data provide the first evidence that the rs2200733-tagged haplotype alters LA electrical remodeling and is a determinant of long-term outcome following AF ablation. The molecular mechanisms underpinning these changes warrant further investigation., Competing Interests: Author Relationship With Industry Dr. Wong has received support from co-funded National Health and Medical Research Council (NHMRC)/Heart Foundation post-graduate scholarships. Dr. Fatkin has received support from the NHMRC, Victor Chang Cardiac Research Institute, Estate of the Late RT Hall, and Simon Lee Foundation. Prof. Kalman has received support from an NHMRC practitioner fellowship; and has received research and fellowship support from Biosense Webster, Boston Scientific, St. Jude Medical, and Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020. Published by Elsevier Inc.)

Background: Female gender is associated with an increased recurrence of atrial fibrillation (AF) after catheter ablation (CA). Although AF is more common in men, women constitute a significant proportion with persistent atrial fibrillation (PsAF)., Objective: The purpose of this study was to determine whether multiple ablation procedures improves arrhythmia outcomes in females with PsAF compared to men., Methods: We performed a multicenter observational study to determine long-term arrhythmia outcomes in patients undergoing >1 CA for PsAF. CA involved pulmonary vein (PV) isolation with additional ablation including linear, posterior wall isolation, electrogram-guided, or a combination of these., Results: A total of 281 patients had >1 ablation procedure for PsAF and were included in this analysis (mean age 58.7 ± 9.3 years; 86 [30.6%] female; left atrial [LA] area 27.0 ± 5.3 cm 2 ; PsAF duration 1.7 ± 1.7 years). At mean follow-up of 45.5 ± 31.8 months, freedom from recurrent AF was present in 148 patients(52.7%) after 2.2 ± 0.5 procedures. After multivariate analysis, female gender (hazard ratio [HR] 2.10; P <.001) and enduring PV isolation (HR 1.64; P = .01) were independently associated with AF recurrence. Enduring PV isolation was significantly higher in women than in men (33.7% vs 19.5%; P = .01)., Conclusion: Female gender was independently and strongly associated with arrhythmia recurrence in patients undergoing multiple procedures for PsAF. PV reconnection was less likely, and fewer reconnected PVs occurred in women. Further studies are required to better understand the mechanisms responsible for AF in females to assist in closing the gender gap in the success of CA., (Copyright © 2019 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to determine the impact of rate and direction on left atrial (LA) substrate., Background: The extent to which substrate mapped in sinus rhythm varies according to cycle length and direction of wave front propagation is unknown., Methods: A total of 73 consecutive patients with atrial fibrillation (AF) underwent electroanatomic LA mapping before pulmonary vein isolation using multipolar catheter during distal coronary sinus (CS) pacing at 600 ms and 300 ms. Additional maps were created during left superior pulmonary vein pacing at 300 ms. Bipolar voltage, conduction velocity (CV), and complex signals were determined., Results: Mean age was 61 ± 9 years, 67% were men, and 53% had persistent AF. Global mean voltage was lower with CS pacing at 300 ms compared with 600 ms (1.56 ± 0.47 mV vs. 1.74 ± 0.48 mV; p < 0.001). This was seen in all LA segments. Global CV was reduced (30.4 ± 13.0 cm/s vs. 38.6 ± 14.0 cm/s; p < 0.001) with greater complex signals at 300 ms (8.9% vs. 5.3%; p < 0.005). Compared with CS pacing, left superior pulmonary vein pacing demonstrated highly regional changes with decreased voltage (1.04 ± 0.43 mV vs. 1.47 ± 0.53 mV; p = 0.01) and CV (24.4 ± 13.0 cm/s vs. 39.9 ± 16.6 cm/s; p = 0.008), and greater complex signals posteriorly. Longer AF duration in paroxysmal AF (p = 0.02) and shorter duration in persistent AF (p = 0.015) and left ventricular ejection fraction (p = 0.016) were independent predictors of voltage change., Conclusions: In patients with AF, variation in cycle length and direction of wave front activation produce both generalized and regional changes in voltage, CV, and complex fractionation, resulting in significant changes in substrate maps. This study highlights the potential limitations of static low-voltage maps to identify the AF ablation target zone., (Copyright © 2019. Published by Elsevier Inc.)

Substantial progress has been made this century in bringing millions of people living with HIV into care, but progress for early HIV diagnosis has stalled. Individuals first diagnosed with advanced HIV have higher rates of mortality than those diagnosed at an earlier stage even after starting antiretroviral therapy (ART), resulting in substantial costs to health systems. Diagnosis of these individuals is hindered because many patients are asymptomatic, despite being severely immunosuppressed. Baseline CD4 counts and screening for opportunistic infections, such as tuberculosis and cryptococcus, is crucial because of the high mortality associated with these co-infections. Individuals with advanced HIV should have rapid ART initiation (except when found to have symptoms, signs, or a diagnosis of cryptococcal meningitis) and those in treatment failure should switch treatment. Overcoming barriers to testing and adherence through the development of differentiated care models and providing psychosocial support will be key in reaching populations at high risk of presenting with advanced HIV., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objectives: This study sought to determine the long-term right atrial (RA) electrical and structural changes in a subgroup from the CAMERA-MRI (Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction-Magnetic Resonance Imaging) study., Background: Catheter ablation (CA) is successful in restoring ventricular function in patients with atrial fibrillation (AF) and otherwise unexplained cardiomyopathy, as demonstrated in the randomized study of CA versus rate control (CAMERA-MRI). It is unknown if this is associated with atrial remodeling., Methods: Detailed electroanatomical (EA) mapping of the RA using CARTO3 and a force sensing catheter was performed at initial CA and electively at least 12 months after CA in patients with >90% reduction in AF burden following ablation. Bipolar voltage, fractionation, and conduction velocity were collected in 4 segments together with echo and cardiac magnetic resonance imaging., Results: Fifteen patients (mean age 59.1 ± 6.8 years) underwent repeat RA EA mapping. At a mean follow-up of 23.4 ± 11.9 months, left ventricular (LV) ejection fraction improved from 33.6 ± 3.2% to 54.1 ± 3.2% (p = 0.001), RA area decreased from 28.4 ± 2.0 cm 2 to 20.8 ± 1.2 cm 2 (p < 0.001), and left atrial area decreased from 32.9 ± 2.3 cm 2 to 26.8 ± 1.4 cm 2 (p = 0.007). On EA mapping, RA bipolar voltage increased from 1.6 ± 0.1 mV to 1.9 ± 0.1 mV (p = 0.04). Tissue voltage increased across all regions, which achieved statistical significance at the posterior (p = 0.002) and septal (p = 0.01) segments. There was a significant decrease in complex fractionated electrograms from 21.7 ± 3.5% to 8.3 ± 1.8% (p = 0.002); however, no significant change occurred in global or regional conduction velocities (p = 0.5)., Conclusions: Recovery of atrial electrical and structural changes was observed following restoration of sinus rhythm and recovery of LV function in patients who underwent CA for persistent AF and LV systolic dysfunction. The randomized CAMERA MRI study demonstrated significant improvement in LV systolic function with AF ablation compared with rate control. The present study demonstrated reverse electrical and structural atrial recovery in concert with recovery of LV systolic function at 2 years post-AF ablation. This may partially explain the long-term success of CA in patients with AF and otherwise unexplained cardiomyopathy., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Atrial fibrillation and heart failure (HF) frequently coexist and are associated with a significant increase in morbidity and mortality. Despite the shared common risk factors atrial fibrillation and HF subtypes exacerbate each other. This review provides an overview of the pathophysiologic relationship between atrial fibrillation and the two most common types of heart failure syndromes: HF with reduced ejection fraction and HF with preserved ejection fraction., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Light-to-moderate regular alcohol consumption has been associated with reduced mortality, heart failure, and sudden death, with a well described "U-shaped" relationship. We sought to determine whether markers of diffuse ventricular fibrosis as assessed by cardiac magnetic resonance imaging (CMR) T 1 mapping differ between nondrinkers and regular drinkers. We prospectively recruited 165 participants to undergo 3T CMR ventricular T1 mapping which included 120 regular light-to-moderate drinkers (7 to 28 standard drinks per week for >12 months) and 45 age and gender-matched nondrinking controls (1 standard drink ∼12 g alcohol). Diffuse ventricular fibrosis was assessed using ShMOLLI T1 mapping sequences performed in mid-short axis. Native T1, postcontrast T1 times and extracellular volume were compared in the left ventricle between regular drinkers and lifelong nondrinkers. In total 165 participants (mean age 59 ± 12 years, 70% male, 36% hypertension, mean LVEF 58 ± 11%) underwent CMR. Moderate alcohol intake (mean alcohol intake 16 ± 6 SDs/week) was associated with lower markers of diffuse ventricular fibrosis: native T1 time 1140 ± 47 vs 1173 ± 39 ms, p < 0.001; postcontrast T1 time 470 ± 47 vs 445 ± 43 ms, p = 0.01; extracellular volume 25.0 ± 2.7% vs 27.0 ± 2.8%, p = 0.003 despite similar LV size (p = 0.55) and mass compared with nondrinkers (p = 0.78). Quantity of alcohol intake and beverage type did not predict lower native T1 times. In conclusion, light-to-moderate or "social" alcohol consumption is associated with T1 changes on CMR suggestive of a reduction in diffuse ventricular fibrosis. These preliminary findings may provide some insights into the association between modest alcohol intake and reduction in sudden death and heart failure., (Copyright © 2018. Published by Elsevier Inc.)

Background: Regular alcohol intake is an important modifiable risk factor associated with atrial fibrillation (AF) and left atrial (LA) dilation., Objective: The purpose of this study was to determine the impact of different degrees of alcohol consumption on atrial remodeling using high-density electroanatomic mapping., Methods: We enrolled 75 patients before AF ablation to undergo high-density LA mapping (CARTO, Biosense Webster) using a multipolar catheter. The Confidense algorithm was used to create maps during distal coronary sinus pacing at 600 ms. Bipolar voltage and complex atrial activity were assessed, and isochronal activation maps were created to determine global conduction velocity (CV). Patients were classified as lifelong nondrinkers, mild drinkers (2-7 drinks/week), or moderate drinkers (8-21 drinks/week)., Results: High-density electroanatomic mapping (mean 1016 ± 445 points per patient) was performed on 25 lifelong nondrinkers, 25 mild drinkers (4.4 ± 2.3 drinks/week), and 25 moderate drinkers (14.0 ± 4.2 drinks/week). Moderate drinkers had significantly lower mean global bipolar voltages (1.53 ± 0.62 mV vs 1.89 ± 0.45 mV; P = .02), slower CV (33.5 ± 14.4 cm/s vs 41.7 ± 12.1 cm/s; P = .04), and a higher proportion of complex atrial potentials (7.8% ± 4.7% vs 4.5% ± 2.7%; P = .004) compared to nondrinkers. Global voltage and CV did not differ significantly in mild drinkers, but there was a significant increase in global complex potentials (6.6% ± 4.6%; P = .04) and regional low-voltage zones (<0.5 mV) in the septum and lateral wall (P <.05) compared with nondrinkers., Conclusion: Regular moderate alcohol consumption, but not mild consumption, is an important modifiable risk factor for AF associated with lower atrial voltage and conduction slowing. These electrical and structural changes may explain the propensity to AF in regular drinkers., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to determine the impact of regular alcohol consumption on left atrial (LA) mechanical and reservoir function., Background: Earlier studies suggest that regular alcohol intake is associated with increased atrial fibrillation (AF) and LA dilatation., Methods: This study prospectively enrolled 160 patients with paroxysmal or persistent AF to undergo 3-T cardiac magnetic resonance (CMR) imaging in sinus rhythm. Patients self-reported alcohol consumption in standard drinks (∼12 g alcohol) per week over the preceding 12 months and were categorized into 4 groups: 1) lifelong nondrinkers; 2) mild drinkers (3 to 10 standard drinks/week); 3) moderate drinkers (11 to 20 standard drinks/week); 4) heavy drinkers (>20 standard drinks/week). Permanent AF and cardiomyopathy were excluded. On CMR, maximum LA volume (LA max ) and minimum LA volume (LA min ), global LA emptying fraction (LAEF) as (LA max  - LA min ) / LA max , and LA reservoir function as (LA max  - LA min ) / LA min were calculated., Results: Regular alcohol consumption (mean 15.8 ± 6.9 standard drinks/week, n = 120) was associated with larger LA size (LA volume index 50 ± 13 ml/m 2 vs. 43 ± 12 ml/m 2 ; p = 0.005), reduction in LAEF (40 ± 14% vs. 52 ± 15%; p < 0.001), and reduction in reservoir function (77 ± 48% vs. 119 ± 63%; p < 0.001) compared with lifelong nondrinkers (n = 40). There were progressive dose-related impairments in LAEF (mild 45.4 ± 13.5% vs. moderate 39.1 ± 14.7% vs. heavy drinkers 35.6 ± 12.6%; p < 0.01) and reservoir function (mild 95.8 ± 55.6% vs. moderate 74.8 ± 47.1% vs. heavy drinkers 61.7 ± 34.4%; p < 0.01). Predictors of atrial mechanical dysfunction included weekly alcohol intake (p = 0.001), older age (p = 0.018), and persistent AF (p = 0.016), but not binge drinking or beverage type., Conclusions: In patients with AF, habitual alcohol consumption is associated with significantly increased LA size and atrial mechanical dysfunction compared with nondrinkers., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The interaction between arrhythmias and certain lifestyle factors such as obesity and alcohol consumption is well-established. There is significant public and professional interest in the role of various diets, vitamins, and minerals in cardiovascular health. However, many widely held beliefs are not supported by the literature. There is limited evidence for routine magnesium and omega-3 poly-unsaturated fatty acids supplementation, while coffee, tea, nuts, antioxidant vitamins, and even chocolate may have some antiarrhythmic properties. Saturated fat, added salt, and excessive energy drink consumption appear to be harmful for patients with rhythm disorders. However most recommendations are based on observation studies, and this remains a fertile area for further research., (Copyright © 2018. Published by Elsevier Inc.)

Aims: Catheter ablation to achieve posterior left atrial wall (PW) isolation may be performed as an adjunct to pulmonary vein isolation (PVI) in patients with persistent atrial fibrillation (AF). We aimed to determine whether routine adenosine challenge for dormant posterior wall conduction improved long-term outcome., Methods and Results: A total of 161 patients with persistent AF (mean age 59 ± 9 years, AF duration 6 ± 5 years) underwent catheter ablation involving circumferential PVI followed by PW isolation. Posterior left atrial wall isolation was performed with a roof and inferior wall line with the endpoint of bidirectional block. In 54 patients, adenosine 15 mg was sequentially administered to assess reconnection of the pulmonary veins and PW. Sites of transient reconnection were ablated and adenosine was repeated until no further reconnection was present. Holter monitoring was performed at 6 and 12 months to assess for arrhythmia recurrence. Posterior left atrial wall isolation was successfully achieved in 91% of 161 patients (procedure duration 191 ± 49 min, mean RF time 40 ± 19 min). Adenosine-induced reconnection of the PW was demonstrated in 17%. The single procedure freedom from recurrent atrial arrhythmia was superior in the adenosine challenge group (65%) vs. no adenosine challenge (40%, P < 0.01) at a mean follow-up of 19 ± 8 months. After multiple procedures, there was significantly improved freedom from AF between patients with vs. without adenosine PW challenge (85 vs. 65%, P = 0.01)., Conclusion: Posterior left atrial wall isolation in addition to PVI is a readily achievable ablation strategy in patients with persistent AF. Routine adenosine challenge for dormant posterior wall conduction was associated with an improvement in the success of catheter ablation for persistent AF., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions please email: journals.permissions@oup.com.)

Aims: Catheter ablation of atrial fibrillation (AF) in patients with heart failure (HF) can improve left ventricular (LV) function and HF symptoms. We aimed to investigate whether long-term maintenance of sinus rhythm impacts on hard outcomes such as stroke and death., Methods and Results: An international multicentre registry was compiled from seven centres for consecutive patients undergoing catheter ablation of AF. Long-term freedom from AF was examined in patients with and without HF. The impact of maintaining sinus rhythm on rates of stroke and death was also examined. A total of 1273 patients were included: 171 with HF and 1102 without. Median follow-up was 3.1 years (IQR 2.0-4.3). The final procedure success rate was no different for paroxysmal AF (PAF) (78.7 vs. 85.7%, P = 0.186), but significantly different for persistent AF (57.3 vs. 75.8%, P < 0.001). Multivariate analysis showed that HF independently predicted recurrent arrhythmia [hazard ratio (HR) 1.7, 95% confidence interval (CI) 1.2-2.4, P = 0.002]. New York Heart Association class decreased from 2.3 ± 0.7 at baseline to 1.5 ± 0.8 at follow-up (P < 0.001). Left ventricular ejection fraction (LVEF) increased from 34.3 ± 9.0 to 45.8 ± 12.8% (P < 0.001). Recurrent AF was strongly predictive of stroke or death in HF patients (HR 8.33, 95% CI 1.86-37.7, P = 0.001)., Conclusion: Long-term success rates for persistent (but not paroxysmal) AF ablation are significantly lower in HF patients. Left ventricular function and HF symptoms were improved following ablation. In HF patients, recurrent arrhythmia strongly predicted stroke and death during follow-up., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)