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Background: Atrial fibrillation (AF) is associated with the development of dementia, and observational studies have shown that oral anticoagulation and catheter ablation reduce dementia risk. However, such studies did not consistently report on periprocedural anticoagulation and long-term oral anticoagulation coverage, for which reason the separate effect of AF ablation on dementia risk could not be established., Objective: We evaluated the protective effect of AF ablation in a large cohort of patients who received optimized anticoagulation and compared them with patients who were managed medically., Methods: We retrospectively included 5912 consecutive patients who underwent first-time catheter ablation for AF between 2008 and 2018 and compared them with 52,681 control individuals from the Swedish Patient Register. Propensity score matching produced 2 cohorts of equal size (n = 3940) with similar baseline characteristics. Dementia diagnosis was identified by International Classification of Diseases codes from the patient register., Results: Most propensity score-matched patients were taking an oral anticoagulant at the start (94.5%) and end (75.0%) of the study. Mean follow-up was 4.9 ± 2.8 years. Catheter ablation was associated with lower risk for the dementia diagnosis compared with the control group (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.22-0.86; P = .017). The result was similar when including patients with a stroke diagnosis before inclusion (HR, 0.50; 95% CI, 0.28-0.89; P = .019) and after adjustment for the competing risk of death (HR, 0.41; 95% CI, 0.20-0.86; P = .018)., Conclusion: Catheter ablation of AF in patients with optimized oral anticoagulation therapy was associated with a reduction in dementia diagnosis, even after adjustment for potential confounders and for competing risk of death., Competing Interests: Disclosures Nikola Drca and Astrid Paul-Nordin have received speaker fees from Johnson & Johnson. Finn Åkerström is a consultant for Johnson & Johnson and Abbott. Mats Jensen-Urstad is a consultant for Johnson & Johnson and Medtronic and has received research grants from Medtronic. Frieder Braunschweig is a consultant for Medtronic and Biotronik and has received speaker fees from Biosense Webster, Biotronik, Boston Scientific, Abbott, Pfizer, Novartis, Amgen, and Orion. For the remaining authors, no conflicts of interest are declared., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Introduction: The presence of low-voltage zones (LVZs) in the left atrium (LA) is associated with the recurrence of atrial fibrillation (AF) following pulmonary vein isolation (PVI). However, there is variability and conflict in the data regarding predictors of LVZs as reported in previous studies. The objective of this study was to identify predictors for the presence of LVZs in a cohort of patients with persistent AF., Methods: The study prospectively enrolled 439 patients with persistent AF who were scheduled for ablation. Voltage map of the LA was collected using a multipolar catheter. An LVZ was defined as an area of ≥3 cm 2 exhibiting a peak-to-peak bipolar voltage of <0.5 mV., Results: The mean age of the cohort was 65.3 ± 8.6 years and 26.4% were female. Additionally, 25.7% had significant LVZs, most frequently located in the anterior wall of the LA. Multivariable analysis identified the following independent predictors for LVZ: advanced age (OR [odds ratio] = 1.08, 95% CI [confidence interval] = 1.03-1.13, p = .002); female sex (OR = 4.83, 95% CI = 2.66-8.76, p < .001); coronary artery disease (CAD) (OR = 3.20, 95% CI = 1.32-7.77, p = .01) and enlarged LA diameter (OR = 1.10, 95% CI = 1.04-1.17, p = .001). The area under the curve (AUC) of the receiver operating characteristic (ROC) curve for the final model was 0.829., Conclusion: Approximately 25% of the patients with persistent AF had LVZs. Advanced age, female sex, CAD, and a larger LA were independent predictors for LVZs with the model demonstrating a very good AUC for the ROC curve. These findings hold the potential to be used to tailor the ablation procedure for the individual patient., (© 2024 The Authors. Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

Background: The presence of low voltage zones (LVZs) in the left atrium (LA) is associated with the recurrence of atrial fibrillation (AF) after pulmonary vein isolation. Numerous studies have posited a link between gastroesophageal reflux disease (GERD) and AF, attributing this relationship to the anatomical proximity of the esophagus to the posteroinferior wall of the LA., Objective: The objective of this study was to investigate whether GERD can predict the presence of LVZs in the posteroinferior wall of the LA., Methods: Five hundred fifty-one patients with persistent AF, scheduled for their first AF ablation procedure, were prospectively enrolled. Voltage maps were collected using a multipolar catheter, and LVZs were defined as areas measuring ≥3 cm 2 with a peak-to-peak bipolar voltage of <0.5 mV. Information on GERD symptoms was collected from the participants through a self-administered questionnaire., Results: Long-standing persistent AF was present in 22.3% of the total cohort. GERD was present in 29% of patients and LVZs in the posteroinferior wall in 12.7%. In the multivariable analysis, patients with GERD were found to have more than twice the odds (odds ratio 2.26; 95% confidence interval 1.24-4.13; P = .008) of exhibiting LVZs in the posteroinferior wall of the LA than patients without GERD. GERD was not associated with LVZs in any other region of the LA., Conclusion: GERD was found to be independently associated with LVZs in the posteroinferior LA. This association may be attributable to inflammation and may partly explain the link between GERD and AF., (© 2024 Heart Rhythm Society. Published by Elsevier Inc.)

Objective: Catheter ablation of atrial fibrillation effectively reduces symptomatic burden. However, its long-term effect on mortality and stroke is unclear. We investigated if patients with atrial fibrillation who undergo catheter ablation have lower risk for all-cause mortality or stroke than patients who are managed medically., Methods: We retrospectively included 5628 consecutive patients who underwent first-time catheter ablation for atrial fibrillation between 2008 and 2018 at three major Swedish electrophysiology units. Control individuals with an atrial fibrillation diagnosis but without previous stroke were selected from the Swedish National Patient Register, resulting in a control group of 48 676 patients. Propensity score matching was performed to produce two cohorts of equal size (n=3955) with similar baseline characteristics. The primary endpoint was a composite of all-cause mortality or stroke., Results: Patients who underwent catheter ablation were healthier (mean CHA 2 DS 2 -VASc score 1.4±1.4 vs 1.6±1.5, p<0.001), had a higher median income (288 vs 212 1000 Swedish krona [KSEK]/year, p<0.001) and had more frequently received university education (45.1% vs 28.9%, p<0.001). Mean follow-up was 4.5±2.8 years. After propensity score matching, catheter ablation was associated with lower risk for the combined primary endpoint (HR 0.58, 95% CI 0.48 to 0.69). The result was mainly driven by a decrease in all-cause mortality (HR 0.51, 95% CI 0.41 to 0.63), with stroke reduction showing a trend in favour of catheter ablation (HR 0.75, 95% CI 0.53 to 1.07)., Conclusions: Catheter ablation of atrial fibrillation was associated with a reduction in the primary endpoint of all-cause mortality or stroke. This result was driven by a marked reduction in all-cause mortality., Competing Interests: Competing interests: ND and AP-N have received speaker fees from Johnson & Johnson. FAk is a consultant for Johnson & Johnson and Abbott. MJ-U is a consultant for Johnson & Johnson and Medtronic and has received research grants from Medtronic. FB is a consultant for Medtronic and Biotronik and has received speaker fees from Biosense Webster, Biotronik, Boston Scientific, Abbott, Pfizer, Novartis, Amgen and Orion. ES has received institutional consulting fees from lecture fees from Bayer, Bristol-Myers Squibb-Pfizer, Boehringer Ingelheim, Johnson & Johnson and Merck Sharp & Dohme., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Atrial fibrillation (AF) haemodynamics is less well studied due to challenges explained by the nature of AF. Until now, no randomized data are available. This study evaluates haemodynamic variables after AF induction in a randomized setting., Methods and Results: Forty-two patients with AF who had been referred for ablation to the University Hospital, Linköping, Sweden, and had no arrhythmias during the 4-day screening period were randomized to AF induction vs. control (2:1). Atrial fibrillation was induced by burst pacing after baseline intracardiac pressure measurements. Pressure changes in the right and left atrium (RA and LA), right ventricle (RV), and systolic and diastolic blood pressures (SBP and DBP) were evaluated 30 min after AF induction compared with the control group. A total of 11 women and 31 men (median age 60) with similar baseline characteristics were included (intervention n = 27, control group n = 15). After 30 min in AF, the RV end-diastolic pressure (RVEDP) and RV systolic pressure (RVSP) significantly reduced compared with baseline and between randomization groups (RVEDP: P = 0.016; RVSP: P = 0.001). Atrial fibrillation induction increased DBP in the intervention group compared with the control group ( P = 0.02), unlike reactions in SBP ( P = 0.178). Right atrium and LA mean pressure (RA m and LA m ) responses did not differ significantly between the groups (RA m : P = 0.307; LA m : P = 0.784)., Conclusion: Induced AF increased DBP and decreased RVEDP and RVSP. Our results allow us to understand some paroxysmal AF haemodynamics, which provides a haemodynamic rationale to support rhythm regulatory strategies to improve symptoms and outcomes., Trial Registration Number Clinicaltrialsgov: No NCT01553045. https://clinicaltrials.gov/ct2/show/NCT01553045?term=NCT01553045&rank=1., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The strategy of cardiac implantable electronic device (CIED) implantations performed as day-case admissions has gained a wider acceptance overtime; however, data on safety are still limited. This study aims to investigate the safety of a same-day discharge protocol introduced in our hospital for the postprocedural management of patients undergoing CIED implantation., Methods: Α prospective, non-interventional, non-randomised study performed in a single high-volume implanting centre for a 16-month period (March 2020 to June 2021). At total of 821 of 965 (85.1%) patients scheduled for elective CIED implantation were considered to be eligible for inclusion in the Short-stay Device Management Protocol. These patients were compared with a historical group of 932 patients, meeting the same inclusion criteria., Results: Procedure was successful in 812 patients (98.9%), committed to same-day discharge versus 921 of 932 patients (98.8%) admitted for overnight stay (p = 0.87). Overall, 90-day complication rate was comparable in both groups (4.14% vs 4.07%, p = 0.95), as was major (1.46% vs. 1.82%, p = 0.55) and minor (2.67% vs. 2.25%, p = 0.64) complication rates. The composite early post-procedural complication rates and late post-procedural complication rates were comparable among groups (0.97 vs 1.18%, p = 0.70 and 0.73% vs 0.64%, p = 0.83, respectively). Six hundred sixty-seven patients (84%) preferred the same-day discharge strategy. Finally, a reduction of 792 bed-days was recorded, resulting in possible financial Health System benefits., Conclusions: Same-day discharge is feasible and safe in the majority of patients referred for CIED implantation. Additionally, same-day discharge is preferred by patients and may reduce procedure-related costs due to significant bed-day reductions., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aims: The recurrence rates after catheter ablation (CA) and direct current (DC) cardioversion remain high, although they have been established treatments of rhythm control of atrial fibrillation (AF). This umbrella review systematically appraises published meta-analyses of both observational and randomized controlled trials (RCTs) for the association of risk and protective factors for arrhythmia recurrence after CA and DC cardioversion of AF., Methods and Results: Three bibliographic databases were searched up to June 2021. Evidence of association was rated as convincing, highly suggestive, suggestive, weak, or not significant with respect to observational studies and as high, moderate, low, or very low with respect to RCTs, according to established criteria. Thirty-one meta-analyses were included. Of the 28 associations between CA and the risk of arrhythmia recurrence, none presented convincing evidence, and only the time from diagnosis to ablation over 1 year provided highly suggestive evidence. The association between hypertension and metabolic profile provided suggestive evidence. The associations of Class IC and III antiarrhythmic drugs use with the recurrence after DC cardioversion were supported by an intermediate level of evidence., Conclusion: Although AF is a major health issue, few risk- and protective factors for AF recurrence have been identified. None of these factors examined were supported by convincing evidence, whereas established factors such as female gender and left atrial volume showed only weak association. An early CA strategy combined with treatment of metabolic syndrome and hypertension prior to CA may reduce the risk of arrhythmia recurrence. The use of antiarrhythmics can increase the success rate of DC cardioversion., Systematic Review Registration: PROSPERO registry number: CRD42021270613., Competing Interests: Conflict of interest: None declared., (© 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.)

Objective: Postoperative atrial fibrillation (POAF) is a common complication affecting approximately one-third of patients after cardiac surgery and valvular interventions. This umbrella review systematically appraises the epidemiological credibility of published meta-analyses of both observational and randomised controlled trials (RCT) to assess the risk and protective factors of POAF., Methods: Three databases were searched up to June 2021. According to established criteria, evidence of association was rated as convincing, highly suggestive, suggestive, weak or not significant concerning observational studies and as high, moderate, low or very low regarding RCTs., Results: We identified 47 studies (reporting 61 associations), 13 referring to observational studies and 34 to RCTs. Only the transfemoral transcatheter aortic valve replacement (TAVR) approach was associated with the prevention of POAF and was supported by convincing evidence from meta-analyses of observational data. Two other associations provided highly suggestive evidence, including preoperative hypertension and neutrophil/lymphocyte ratio. Three associations between protective factors and POAF presented a high level of evidence in meta-analyses, including RCTs. These associations included atrial and biatrial pacing and performing a posterior pericardiotomy. Nineteen associations were supported by moderate evidence, including use of drugs such as amiodarone, b-blockers, glucocorticoids and statins and the performance of TAVR compared with surgical aortic valve replacement., Conclusions: Our study provides evidence confirming the protective role of amiodarone, b-blockers, atrial pacing and posterior pericardiotomy against POAF as well as highlights the risk of untreated hypertension. Further research is needed to assess the potential role of statins, glucocorticoids and colchicine in the prevention of POAF., Prospero Registration Number: CRD42021268268., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There is no consensus on the most efficient catheter ablation (CA) strategy for patients with atrial fibrillation (AF). The objective of this study was to compare the efficacy and safety of different CA strategies for AF ablation through network meta-analysis (NMA)., Methods: A systematic search of PubMed, Web of Science, and CENTRAL was performed up to October 5th, 2020. Randomized controlled trials (RCT) comparing different CA approaches were included. Efficacy was defined as arrhythmia recurrence after CA and safety as any reported complication related to the procedure during a minimum follow-up time of 6 months., Results: In total, 67 RCTs (n = 9871) comparing 19 different CA strategies were included. The risk of recurrence was significantly decreased compared to pulmonary vein isolation (PVI) alone for PVI with renal denervation (RR: 0.60, CI: 0.38-0.94), PVI with ganglia-plexi ablation (RR: 0.62, CI: 0.41-0.94), PVI with additional ablation lines (RR: 0.8, CI: 0.68-0.95) and PVI in combination with bi-atrial modification (RR: 0.32, CI: 0.11-0.88). Strategies including PVI appeared superior to non-PVI strategies such as electrogram-based approaches. No significant differences in safety were observed., Conclusions: This NMA showed that PVI in combination with additional CA strategies, such as autonomic modulation and additional lines, seem to increase the efficacy of PVI alone. These strategies can be considered in treating patients with AF, since, additionally, no differences in safety were observed. This study provides decision-makers with comprehensive and comparative evidence about the efficacy and safety of different CA strategies., Systematic Review Registration: PROSPERO registry number: CRD42020169494 ., (© 2022. The Author(s).)

Background: Familial hypercholesterolemia (FH) is an underdiagnosed and undertreated genetic disorder with high risk of premature atherosclerotic cardiovascular disease and death. Clinical decision support (CDS) systems have the potential to aid in the identification and management of patients with FH. Prior studies using computer-based systems to screen patients for FH have shown promising results, but there has been no randomized controlled trial conducted. The aim of the current cluster randomized study is to evaluate if a CDS can increase the identification of FH., Methods: We have developed a CDS integrated in the electronic health records that will be activated in patients with elevated cholesterol levels (total cholesterol >8 mmol/L or low-density lipoprotein-cholesterol >5.5 mmol/L, adjusted for age, ongoing lipid lowering therapy and presence of premature coronary artery disease) at increased risk for FH. When activated, the CDS will urge the physician to send an automatically generated referral to the local lipid clinic for further evaluation. To evaluate the effects of the CDS, all primary care clinics will be cluster randomized 1:1 to either CDS intervention or standard care in a Swedish region with almost 500,000 inhabitants. The primary endpoint will be the number of patients diagnosed with FH at 30 months. Resource use and long-term health consequences will be estimated to assess the cost-effectiveness of the intervention., Conclusion: Despite increasing awareness of FH, the condition remains underdiagnosed and undertreated. The present study will investigate whether a CDS can increase the number of patients being diagnosed with FH., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Although catheter ablation (CA) is an established treatment for paroxysmal atrial fibrillation (PAF), there is no consensus regarding the most efficient CA strategy. The objective of this network meta-analysis (NMA) was to compare the efficacy and safety of different CA strategies for PAF. A systematic search was performed in PubMed, Web of Science, and CENTRAL until the final search date, 5 October 2020. Randomised controlled trials (RCT) comparing different CA strategies and methods for pulmonary vein isolation (PVI) were included. Efficacy was defined as lack of arrhythmia recurrence after CA and safety as any reported complication related to the procedure during a minimum follow-up time of six months. In total, 43 RCTs comparing 11 different CA strategies involving 6701 patients were included. The risk of recurrence was significantly decreased in comparison with PVI with radiofrequency only for the following treatments: PVI with adjuvant ablation (RR: 0.79, CI: 0.65-0.97) and PVI with sympathetic modulation (RR: 0.64, CI: 0.46-0.88). However, PVI with radiofrequency was superior to non-PVI strategies (RR: 1.65, CI: 1.2-2.26). No statistically significant difference was found in safety between different CA strategies. Concerning different PVI strategies, no difference was observed either in efficacy or in safety between tested strategies. This NMA suggests that different PVI strategies are generally similar in terms of efficacy, while PVI with additional ablation or sympathetic modulation may be more effective than PVI alone. This study provides decision-makers with insights into the efficacy and safety of different CA strategies.

Objectives: To investigate the effect of catheter ablation (CA) on symptoms and health-related quality of life (HRQoL) after 5 years, and analyze predictors of recurrence of symptoms., Background: The primary indication for CA of atrial fibrillation (AF) is to reduce symptoms and improve HRQoL where long-term follow-up are sparse., Methods: In this observational, long-term, single-center study, patients were recruited from Linköping University Hospital, Sweden. They were aged ≥18 years and had been referred for CA from November 2011 until June 2019. Arrhythmia-specific symptoms and HRQoL were assessed by patient-reported outcome measures (PROMs) with the Arrhythmia-Specific questionnaire in Tachycardia and Arrhythmia (ASTA)., Results: In the study were 1521 patients, 69% men, mean age 62 years. At baseline, 87% of the patients and at the 5-year follow-up 80% of those eligible filled out the ASTA questionnaire. At follow-up, 50% reported freedom from symptoms, 18% had >50% symptom reduction, 14% had a minor reduction, while 18% reported no effect or a worsening of symptoms. Factors predicting symptoms were female gender (hazard ratio [HR]: 1.8; 1.2-2.8), body mass index ≥ 35 (HR: 3.9; 1.6-9.8), and ischemic heart disease (IHD) (HR: 2.6; 1.2-5.9). After 5 years, breathlessness during activity, weakness/fatigue, and tiredness were still the most common symptoms; regarding HRQoL they were impaired physical ability and deteriorated life situation., Conclusions and Clinical Implications: This clinical cohort of patients with AF evaluated through PROMs showed that CA had long-lasting effects on symptoms and HRQoL and that the use of PROMs in clinical routines was feasible. Factors predicting symptoms after CA were female gender, IHD, and obesity, an important reminder to encourage lifestyle management., (© 2021 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)

Background: Radiofrequency ablation (RFA)is an important treatment option for patients with atrial fibrillation (AF). During RFA, a significant amount of energy is delivered into the left atrium (LA), resulting in considerable LA-injury. The impact of this damage on mechanical and endocrine LA-function, however, is often disregarded.We therefore aimed to evaluate the endocrine- and mechanical function of the heart 4-months after RFA of AF., Methods: In total 189 patients eligible for RFA of AF were studied. The levels of the N-terminal pro-B-natriuretic peptide (NT-proBNP) and the mid-regional fragment of the N-terminal pro-atrial natriuretic peptide (MR-proANP)were measured. The maximum LAvolume (LAVmax),the LAejection fraction (LAEF) and the LA peak longitudinal strain (PALS), were measured usingtransthoracic echocardiography. The measurements were performed before and 4-months after the intervention., Results: 87 patients had a recurrence during a mean follow-up of 143±36 days.NT-proBNPand MR-proANPdecreased significantly at follow-up. This reduction was greater in patients who did not suffer any recurrence after RFA.The LAVmax decreased significantly, whereasthe PALS only improved in patients who did not suffer from any recurrence. On the other hand, LAEF did not change significantly after RFA of AF., Conclusions: Despite extensiveablation during RFA of AF, the endocrine function of the heart improved 4-months after the index procedure. Patients with no arrhythmia recurrence showed a more pronounced improvement in their endocrinal function. Mechanically, the LAVmax was reduced, and the LA strain improved significantly.

Objectives: This study sought to compare interrupted and uninterrupted oral anticoagulant therapy (I-OAC vs. U-OAC) in patients on OAC undergoing percutaneous coronary intervention., Background: There is a paucity of data regarding the optimal peri-procedural management of OAC-treated patients., Methods: In the SWEDEHEART registry, all patients on OAC who were admitted acutely and underwent percutaneous coronary intervention or coronary angiography with a diagnostic procedure, from 2005 to 2017, were included. Outcomes were major adverse cardiac and cerebrovascular events (MACCE; death, myocardial infarction, or stroke) and bleeds at 120 days. Propensity score was used to adjust for the nonrandomized treatment selection., Results: The study included 6,485 patients: 3,322 in the I-OAC group and 3,163 in the U-OAC group. The cumulative incidence of MACCE was 8.2% (269 events) versus 8.2% (254 events) in the I-OAC and the U-OAC groups, respectively. The adjusted risk for MACCE did not differ between the groups (I-OAC vs. U-OAC hazard ratio: 0.89; 95% confidence interval: 0.71 to 1.12). Similarly, no difference was found in the risk for MACCE or bleeds (12.6% vs. 12.9%, adjusted hazard ratio: 0.87; 95% confidence interval: 0.70 to 1.07). The risk for major or minor in-hospital bleeds did not differ between the groups. However, U-OAC was associated with a significantly shorter duration of hospitalization: 4 (3 to 7) days versus 5 (3 to 8) days; p < 0.01., Conclusions: I-OAC and U-OAC were associated with equivalent risk for MACCE and bleeding complications. An U-OAC strategy was associated with shorter length of hospitalization. These data support U-OAC as the preferable strategy in patients on OAC undergoing coronary intervention., Competing Interests: Funding Support and Author Disclosures Dr. Venetsanos has received a grant from Boston Scientific. Dr. Janzon has received lecture fees from AstraZeneca and Pfizer. Dr. Böhm has received research grants and lecture fees from Abbott, Boston Scientific, AstraZeneca, and Bayer. Dr. Karlson has served on an advisory board for Biosense Webster. Dr. Simonsson has received lecture fees from AstraZeneca, Pfizer, and Bayer. Dr. Erlinge has received speaker fees from AstraZeneca and Bayer; and has served on advisory boards for Bayer and Boehringer Ingelheim. Dr. Omerovic has received an institutional research grant from AstraZeneca; and has received consulting fees from Novartis, Merck Sharp & Dohme, AstraZeneca, and Bayer. Dr. Alfredsson has received grants from AstraZeneca; has received lecture fees from AstraZeneca, Lilly, Pfizer, Bayer, Novartis, and Boehringer Ingelheim; and has served on advisory boards for AstraZeneca, Novartis, and Merck Sharp & Dohme. 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.)

Introduction: Atrial fibrillation (AF) is the most common sustained arrhythmia. Catheter ablation (CA) of AF is an increasingly offered therapeutic approach, primary to relieve AF-related symptoms. Despite the development of new ablation approaches, there is no consensus regarding the most efficient ablation strategy. The objective of this network meta-analysis (NMA) is to compare the efficacy and safety of all different CA approaches for the treatment of patients with paroxysmal (PAF) and non-PAF (non-PAF)., Methods and Analysis: We will perform a systematic search to identify randomised controlled trials of different CA approaches for the treatment of PAF and non-PAF, through the final search date of 1 March 2020. Information sources will include major bibliographic databases (MEDLINE, Web of Science and CENTRAL) and clinical trial registries. Our primary outcomes will be the efficacy (recurrence-free survival) and safety of different CA approaches for the treatment of AF. Secondary outcomes will be all-cause mortality and procedural time. An NMA will be performed to determine the relative effects of different catheter ablation approaches (such as pulmonary vein isolation alone or in combination with ablation lines, ablation of complex fractionated atrial electrograms, etc). In PAF, a separate analysis will be performed including different energy sources (such as radiofrequency, cryogenic and laser energy). Risk of bias assessment and sensitivity analyses will be conducted to assess the robustness of the findings to potential bias., Ethics and Dissemination: No ethical approval will be needed because data are collected from previous studies. The results will be presented through peer-review journals and conference presentation., Prospero Registration Number: CRD42020169494., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Premature ventricular complex (PVC) is common in the general population. Symptoms vary from none to pronounced. The prognostic significance of PVC's depends on the presence of underlying structural heart disease. The clinical evaluation in patients with PVC aims at excluding structural heart disease and usually involves transthoracic echocardiogram and Holter. Patients without structural heart disease usually have a good prognosis. Frequent PVC's may cause impaired left ventricular function, which usually is reversible after treatment with drugs or ablation. A 12-lead ECG provides important information about PVC localization, however anatomical factors such as the heart's localization in the thorax as well as electrode placement and pharmacological treatment may affect the ECG appearance. In symptomatic patients with or without left ventricular impairment, pharmacological treatment or catheter ablation is indicated. However, in most cases the main goal is to reasure the patient of the good prognosis. To summarize, treatment of choice depends on symptoms, comorbidities, left ventricular function and patient's choice.

Background: Primary indication for catheter ablation of atrial fibrillation (AF) is to reduce symptoms and improve health-related quality of life (HRQoL). There are data showing differences between the genders and between younger and older patients. To evaluate this, we studied a large Scandinavian cohort of patients referred for catheter ablation of AF., Methods: Consecutive patients filled out the ASTA questionnaire, assessing symptoms, HRQoL, and perception of arrhythmia, prior to ablation. Patients were recruited from four Swedish and one Danish tertiary center., Results: A total of 2493 patients (72% men) filled out the ASTA questionnaire. Women experienced eight of the nine ASTA scale symptoms more often than men. Patients <65 years reported four symptoms more often, only tiredness was more frequent in those ≥65 years (P = .007). Women and patients <65 years experienced more often palpitations and regarding close to fainting and this was more common among women, no age differences were seen. Women and men scored differently in 10 of the 13 HRQoL items. Only negative impact on sexual life was more common in men (P < .001). Older patients reported more negative influence in four of the HRQoL items and the younger in one; ability to concentrate., Conclusions: Women experienced a more pronounced symptom burden and were more negatively affected in all HRQoL concerns, except for the negative impact on sexual life, where men reported more influence of AF. Differences between age groups were less pronounced. Disease-specific patient-reported outcomes measures (PROMs) add important information where gender differences should be considered in the care., (© 2019 Wiley Periodicals, Inc.)

Background: RFA is a well-established treatment for symptomatic patients with AF. However, the success rate of a single procedure is low. We aimed to investigate the association between the risk of recurrence of atrial fibrillation (AF) after a single radiofrequency ablation (RFA) procedure and cardiac neurohormonal function, left atrial (LA) mechanical function as well as proteins related to inflammation, fibrosis, and apoptosis. Methods and Results: We studied 189 patients undergoing RFA between January 2012 and April 2014, with a follow-up period of 12 months. A logistic regression analysis was performed to investigate the association between pre-ablation LA emptying fraction (LAEF), MR-proANP, Caspase-8 (CASP8), Neurotrophin-3 (NT3), and the risk for recurrence of AF after a single RFA procedure. 119 (63.0%) patients had a recurrence during a mean follow-up of 402 ± 73 days. An increased risk of recurrence was associated with: Elevated MR-proANP (fourth quartile vs. first quartile: HR, 2.80 (95% CI, 1.14-6.90]; P = 0.025); Low LAEF (fourth quartile vs. first quartile: hazard ratio [HR], 2.41 [95% CI, 1.01-5.79]; P = 0.045); Elevated CASP8 (fourth quartile vs. first quartile: HR 12.198 95% CI 2.216-67.129; P = 0.004); Elevated NT-3 (fourth quartile vs. first quartile: HR 7.485 95% CI 1.353-41.402; P = 0.021). In a receiver operating characteristic curve analysis, the combination of MR-proANP, CASP8, and NT3 produced an area under the curve of 0.819; CI 95% (0.710-0.928). Conclusions: Patients with better LA mechanical function and lower levels of atrial neurohormones as well as of proteins related to fibrosis and apoptosis, have a better outcome after an RFA procedure. Unique identifier: No. NCT01553045 (https://clinicaltrials.gov/ct2/show/NCT01553045?term=NCT01553045&rank=1)., (Copyright © 2019 Charitakis, Karlsson, Papageorgiou, Walfridsson and Carlhäll.)

Background: Information on alcohol consumption in patients undergoing radiofrequency ablation (RFA) of atrial fibrillation (AF) is often limited by the reliance on self-reports. The aim of this study was to describe the long-term alcohol consumption, measured as ethyl glucuronide in hair (hEtG), in patients undergoing RFA due to AF, and to examine potential associations with cardiac biomarkers, left atrial size and re-ablation within one year after the initial RFA., Methods: The amount of hEtG was measured in patients referred for RFA, and a cut-off of 7 pg/mg was used. N-terminal pro B-type natriuretic peptide (NT-proBNP) and the mid-regional fragment of pro atrial natriuretic peptide (MR-proANP) were examined and maximum left atrium volume index (LAVI) was measured. The number of re-ablations was examined up to one year after the initial RFA. Analyses were stratified by gender, and adjusted for age, systolic blood pressure, body mass index, presence of heart failure and heart rhythm for analyses regarding NT-proBNP, MR-proANP and LAVI and heart rhythm being replaced by type of AF for analyses regarding re-ablation., Results: In total, 192 patients were included in the study. Median (25th- 75th percentile) NT-proBNP in men with hEtG ≥ 7 vs. < 7 pg/mg was 250 (96-695) vs. 130 (49-346) pg/ml (p = 0.010), and in women it was 230 (125-480) vs. 230 (125-910) pg/ml (p = 0.810). Median MR-proANP in men with hEtG ≥ 7 vs. < 7 pg/mg was 142 (100-224) vs. 117 (83-179) pmol/l (p = 0.120) and in women it was 139 (112-206) vs. 153 (93-249) pmol/l (p = 0.965). The median of maximum LAVI was 30.1 (26.7-33.9) vs. 25.8 (21.4-32.0) ml/m2 (p = 0.017) in men, and 25.0 (18.9-29.6) vs. 25.7 (21.7-34.6) ml/m2 (p = 0.438) in women, with hEtG ≥ 7 vs. < 7 pg/ml, respectively. Adjusted analyses showed similar results, except for MR-proANP turning out significant in men with hEtG ≥ 7 vs. < 7 pg/mg (p = 0.047). The odds ratio of having a re-ablation was 3.5 (95% CI 1.3-9.6, p = 0.017) in men with hEtG ≥ 7 vs. < 7 pg/mg, while there was no significant difference in women., Conclusions: In male patients with AF and hEtG ≥ 7 pg/mg, NT-proBNP and MR-proANP were higher, LA volumes larger, and there was a higher rate of re-ablations, as compared to men with hEtG < 7 pg/mg. This implies that men with an alcohol consumption corresponding to an hEtG-value ≥ 7, have a higher risk for LA remodelling that could potentially lead to a deterioration of the AF situation., Competing Interests: HW received unrestricted grants from Biosense Webster, Johnson & Johnson (www.biosensewebster.com). This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products to declare.

Background: The primary goal of radiofrequency ablation (RFA) of atrial fibrillation (AF) is to improve symptoms and health-related quality of life (HRQoL). However, most studies have focused on predictors of AF recurrence rather than on predictors of improvement in symptoms and HRQoL., Hypothesis: We sought to explore predictors of improvement in arrhythmia-specific symptoms and HRQoL after RFA of AF, and to evaluate the effects on symptoms, HRQoL, anxiety, and depression., Methods: We studied 192 patients undergoing their first RFA of AF. The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), arrhythmia-specific questionnaire in tachycardia and arrhythmia (ASTA), and hospital anxiety and depression scale (HADS) questionnaires were filled out at baseline, at 4 months, and at a 1-year follow-up., Results: All questionnaire scale scores improved significantly over time. In the ASTA symptom scale score, female gender and > 10 AF episodes the month before RFA were significant positive predictors of improvement, while diabetes and AF recurrence within 12 months after RFA were significant negative predictors (R 2 = 0.18; P < 0.001). In the ASTA HRQoL scale score, the presence of heart failure and > 10 AF episodes the month before RFA were significant positive predictors of improvement, while diabetes, maximum left atrial volume and AF recurrence were significant negative predictors (R 2 = 0.20; P < 0.001)., Conclusion: Left atrial volume, gender, diabetes, heart failure, the frequency of AF attacks prior to RFA, and recurrence of AF after RFA were significant factors affecting improvement in symptoms and HRQoL after RFA of AF. Future studies are warranted to confirm these findings., (© 2018 Wiley Periodicals, Inc.)

Background: Atrial fibrillation (AF) is associated with substantial morbidity, in particular stroke. Despite good evidence for the reduction of stroke risk with anticoagulant therapy, there remains significant undertreatment. The main aim of the current study was to investigate whether a clinical decision support tool (CDS) for stroke prevention integrated in the electronic health record could improve adherence to guidelines for stroke prevention in patients with AF., Methods and Findings: We conducted a cluster-randomized trial where all 43 primary care clinics in the county of Östergötland, Sweden (population 444,347), were randomized to be part of the CDS intervention or to serve as controls. The CDS produced an alert for physicians responsible for patients with AF and at increased risk for thromboembolism (according to the CHA2DS2-VASc algorithm) without anticoagulant therapy. The primary endpoint was adherence to guidelines after 1 year. After randomization, there were 22 and 21 primary care clinics in the CDS and control groups, respectively. There were no significant differences in baseline adherence to guidelines regarding anticoagulant therapy between the 2 groups (CDS group 70.3% [5,186/7,370; 95% CI 62.9%-77.7%], control group 70.0% [4,187/6,009; 95% CI 60.4%-79.6%], p = 0.83). After 12 months, analysis with linear regression with adjustment for primary care clinic size and adherence to guidelines at baseline revealed a significant increase in guideline adherence in the CDS (73.0%, 95% CI 64.6%-81.4%) versus the control group (71.2%, 95% CI 60.8%-81.6%, p = 0.013, with a treatment effect estimate of 0.016 [95% CI 0.003-0.028]; number of patients with AF included in the final analysis 8,292 and 6,508 in the CDS and control group, respectively). Over the study period, there was no difference in the incidence of stroke, transient ischemic attack, or systemic thromboembolism in the CDS group versus the control group (49 [95% CI 43-55] per 1,000 patients with AF in the CDS group compared to 47 [95% CI 39-55] per 1,000 patients with AF in the control group, p = 0.64). Regarding safety, the CDS group had a lower incidence of significant bleeding, with events in 12 (95% CI 9-15) per 1,000 patients with AF compared to 16 (95% CI 12-20) per 1,000 patients with AF in the control group (p = 0.04). Limitations of the study design include that the analysis was carried out in a catchment area with a high baseline adherence rate, and issues regarding reproducibility to other regions., Conclusions: The present study demonstrates that a CDS can increase guideline adherence for anticoagulant therapy in patients with AF. Even though the observed difference was small, this is the first randomized study to our knowledge indicating beneficial effects with a CDS in patients with AF., Trial Registration: ClinicalTrials.gov NCT02635685.

Objectives: The purpose of this study was to correlate the arrhythmia-related symptoms and health-related quality of life (HRQoL) in patients with atrial fibrillation (AF) who are eligible for radiofrequency ablation (RFA) with a number of objective indicators., Background: Although the clinical consequences of AF have been studied extensively, the variation in the symptoms of patients with AF and HRQoL remains under-researched., Methods: We studied 192 patients eligible for RFA of AF referred to the University Hospital, Linköping, Sweden, between January 2012 and April 2014. The ASTA (Arrhythmia-Specific questionnaire in Tachycardia and Arrhythmia) symptom scale was used to assess arrhythmia-related symptoms in the patients. The ASTA HRQoL scale and the short-form 36 (SF-36) physical and mental components summaries (PCS and MCS) were used to express disease-specific and overall HRQoL of the patients, respectively., Results: Anxiety, low-grade inflammation, and left atrial dilatation significantly predicted arrhythmia-related symptoms (R 2  = 0.313; p < 0.001). Depression was the most important predictor of arrhythmia-specific HRQoL (standardized beta: 0 .406), and the produced model explained a significant proportion of the variation in arrhythmia-specific HRQoL (R 2  = 0.513; p < 0.001). The most important predictor of PCS was obesity (body mass index >30 kg/m 2 ) (standardized beta: -0.301), whereas the most important predictor of MCS was anxiety (standardized beta: -0.437)., Conclusions: Anxiety, depression, and low-grade inflammation were the factors that predicted both arrhythmia-related symptoms and HRQoL in patients with AF. Obesity was the most significant predictor of patient general physical status. These factors need to be addressed in patients with AF to improve management of their disease. Intensive risk factor modification can be of great importance. (Reasons for Variations in Health Related Quality of Life and Symptom Burden in Patients With Atrial Fibrillation [SMURF]; NCT01553045)., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Atrial fibrillation (AF) is associated with substantial morbidity, in particular stroke. Despite good evidence for the reduction of stroke risk with anticoagulant therapy, there remains a significant undertreatment. The main aim of the current study is to investigate whether a clinical decision support tool for stroke prevention (CDS) integrated in the electronic health record can improve adherence to guidelines for stroke prevention in patients with AF., Methods: We will conduct a cluster randomized trial where 43 primary care clinics in the county of Östergötland, Sweden (population 444,347), will be randomized to be part of the CDS intervention or serve as controls. The CDS will alert responsible physicians of patients with AF and increased risk for thromboembolism according to the CHA 2 DS 2 VASc (Congestive heart failure, Hypertension, Age ≥ 74 years, Diabetes mellitus, previous Stroke/TIA/thromboembolism, Vascular disease, Age 65-74 years, Sex category (i.e. female sex)) algorithm without anticoagulant therapy. The primary end point will be adherence to guidelines after 1 year., Conclusion: The present study will investigate whether a clinical decision support system integrated in an electronic health record can increase adherence to guidelines regarding anticoagulant therapy in patients with AF., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Biomarker activation in atrial fibrillation (AF) has been widely studied, but the immediate effect of AF initiation remains unclear. We studied the effect of AF initiation on 2 cardiac biomarkers: the N-terminal fragment of the proB-type natriuretic peptide (NT-proBNP), the midregional fragment of the N-terminal of pro-atrial natriuretic peptide (MR-proANP), and 2 extracardiac biomarkers-the copeptin and the midregional portion of proadrenomedullin (MR-proADM)., Methods and Results: This was a randomized controlled study, including 45 patients with AF who had been referred for radiofrequency ablation to the University Hospital, Linköping, Sweden, between February 2012 and April 2014. Freedom from AF during the 4 days prior to radiofrequency ablation was confirmed by transtelephonic ECGs. Biomarkers were collected from the femoral vein (fv), coronary sinus (CS), and left atrium (LA) prior to AF initiation (baseline) and 30 minutes later. The MR-proANP and NT-proBNP concentrations increased in the intervention group compared with the control group 30 minutes after the initiation of AF (MR-proANP: P fv <0.001, P CS <0.001, P LA <0.001; NT-proBNP: P LA <0.001). Copeptin levels in patients without ischemic heart disease were decreased after the initiation of AF (P fv =0.003, P CS =0.015, P LA =0.011)., Conclusions: AF is a strong stimulus that results in immediate activation of different biomarkers., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01553045., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: There is limited knowledge on the short-term influence of radiofrequency ablation (RFA) of atrial fibrillation (AF) on 2 cardiac biomarkers; the N-terminal pro-B-type natriuretic peptide (NT-proBNP) and the midregional fragment of the N-terminal of pro-ANP (MR-proANP) and 2 extracardiac biomarkers; the c-terminal provasopressin (copeptin) and the midregional portion of proadrenomedullin (MR-proADM). There are also limited data concerning cardiac production of the latter two., Methods and Results: We studied 192 consecutive patients eligible for RFA of AF referred to the University Hospital, Linköping, Sweden. NT-proBNP, MR-proANP, copeptin, and MR-proADM levels were measured in peripheral blood, the coronary sinus (CS), and the left atrium before ablation, and in peripheral blood immediately and the day after RFA. The level of NT-proBNP decreased the day after RFA in participants in AF at the time of RFA, compared to the participants in sinus rhythm who showed a slight increase (P<0.001). Furthermore, regardless of the actual rhythm, the level of MR-proANP showed an increase immediately after RFA (P<0.001), followed by a decrease the day after ablation (P<0.001). Copeptin level showed a 6-fold increase immediately after RFA compared to baseline (P<0.001), whereas MR-proADM level increased the day after RFA (P<0.001). Levels of copeptin and MR-proADM were not higher in the CS compared to peripheral blood., Conclusions: RFA of AF is a strong stimulus with a significant and direct impact on different neurohormonal systems. We found no sign of a cardiac release of MR-proADM or copeptin., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique Identifier: NCT01553045., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Introduction: Atrial fibrillation (AF) is the most common cardiac arrhythmia, with an estimated prevalence of 1.5-2%. It is an independent risk factor for ischaemic stroke and is estimated to cause about 20-25% of all stroke cases. AF has a great impact on health-related quality of life (HRQoL); however, one unresolved issue related to AF is the wide variation in its symptoms., Methods and Analysis: The symptom burden, metabolic profile, ultrasound findings, rhythm, neurohormonal activation, haemodynamics and HRQoL in patients with AF (Symptom burden, Metabolic profile, Ultrasound findings, Rhythm, neurohormonal activation, haemodynamics and health-related quality of life in patients with atrial Fibrillation, SMURF) study is a prospective observational, cohort study, with a randomised interventional part. The aim of the study is to investigate, in patients with AF, the relationship between symptom burden and metabolic aspects, atrial function and different neurohormones, and the effect of radiofrequency ablation (RFA). The interventional part of the study will give an insight into the neurohormonal and intracardiac pressure changes directly after initiation of AF. Consecutive patients with symptomatic AF accepted for treatment with RFA for the first time at Linköping University Hospital are eligible for participation. The enrolment started in January 2012, and a total of 200 patients are to be included into the study, with 45 of them being enrolled into the interventional study with initiation of AF. The sample size of the interventional study is based on a small pilot study with 5 patients induced to AF while 2 served as controls. The results indicated that, in order to find a statistically significant difference, there was a need to include 28 patients; for safety reasons, 45 patients will be included., Ethics and Dissemination: The SMURF study is approved by the Regional Ethical Review Board at the Faculty of Health Sciences, Linköping, Sweden. The results will be presented through peer-review journals and conference presentation., Trial Registration Number: NCT01553045; Pre-results., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)