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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., Funding Agencies|Swedish Research Council; Swedish Heart- Lung Foundation [20190301, 20200537, 202110302]; Center for Innovative Medicine [FoUI- 954510, FoUI- 954075]

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., Funding Agencies|Swedish Research Council [2019-0097, 2021-00202]; Swedish Heart Lung Foundation [20190301, 20200537, 20210302]; Center for Innovative Medicine [20190797]; ALF Region Stockholm [FoUI-954075]; Wibergs Stiftelse [M19-0424]

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 (RAm and LAm) responses did not differ significantly between the groups (RAm: P = 0.307; LAm: 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.

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.

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.

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 coronar y arter y 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.

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., Funding Agencies|ALF grants (County Council of Ostergotland) [RO818141]

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 Linkoping 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.

Background: Sudden cardiac death (SCD) is a global public health issue, accounting for 10-20% of deaths in industrialized countries. Identification of modifiable risk factors may reduce SCD incidence. Methods: This umbrella review systematically evaluates published meta-analyses of observational and randomized controlled trials (RCT) for the association of modifiable risk and protective factors of SCD. Results: Fifty-five meta-analyses were included in the final analysis, of which 31 analyzed observational studies and 24 analyzed RCTs. Five associations of meta-analyses of observational studies presented convincing evidence, including three risk factors [diabetes mellitus (DM), smoking, and early repolarization pattern (ERP)] and two protective factors [implanted cardiac defibrillator (ICD) and physical activity]. Meta-analyses of RCTs identified five protective factors with a high level of evidence: ICDs, mineralocorticoid receptor antagonist (MRA), beta-blockers, and sodium-glucose cotransporter-2 (SGLT-2) inhibitors in patients with HF. On the contrary, other established, significant protective agents [i.e., amiodarone and statins along with angiotensin-converting enzyme (ACE) inhibitors in heart failure (HF)], did not show credibility. Likewise, risk factors as left ventricular ejection fraction in HF, and left ventricular hypertrophy, non-sustain ventricular tachycardia, history of syncope or aborted SCD in pediatric patients with hypertrophic cardiomyopathy, presented weak or no evidence. Conclusions: Lifestyle risk factors (physical activity, smoking), comorbidities like DM, and electrocardiographic features like ERP constitute modifiable risk factors of SCD. Alternatively, the use of MRA, beta-blockers, SGLT-2 inhibitors, and ICD in patients with HF are credible protective factors. Further investigation targeted in specific populations will be important for reducing the burden of SCD.

Premature ventricular complex (PVC) is common in the general population. Symptoms vary from none to pronounced. The prognostic significance of PVCs 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 PVCs 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 hearts 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 patients choice., Ventrikulära extraslag (VES) är vanliga och förekommer hos patienter med eller utan strukturell hjärtsjukdom. Deras prognostiska betydelse är kopplad till eventuellunderliggande hjärtsjukdom. En basal utredning inbegriper ekokardiografi samt Holter-EKG för kvantifieringav VES-börda och symtomkorrelation. Prognosen är god i frånvaro av strukturell hjärtsjukdom. Vid förekomst av kardiell påverkan eller symtomföreligger indikation för behandling med läkemedel ellerkateterablation. 12-avlednings-EKG ger bra informationom var i hjärtat extraslagen har sitt ursprung. För dets tora flertalet gäller exspektans med information om eni regel god prognos.

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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, Funding agencies: County Council of Ostergotland [LIO-280731, LIO-445511]; Carldavid Jonsson Research Foundation; Linkoping University; Biosense Webster; Johnson Johnson; Heart Foundation

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 amp;gt; 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 amp;lt; 0.001). In the ASTA HRQoL scale score, the presence of heart failure and amp;gt; 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 amp;lt; 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., Funding Agencies|Biosense Webster; Carldavid Jonsson Research Foundation; County Council of Ostergotland [LIO-280731LIO-445511]; Heart Foundation, Linkoping University

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., Funding Agencies:Carl David Jonsson Research Foundation County Council of Östergötland

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, Funding Agencies|ALF grants, Region Ostergotland [LIO 608011]

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., Funding agencies: ALF grants (County Council of Ostergotland); Carldavid Jonsson Research Foundation; Heart Foundation; Linkoping University; Biosense Webster; Johnson Johnson

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, Link_ oping, 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-fvamp;lt;0.001, P-CSamp;lt;0.001, P-LAamp;lt;0.001; NT-proBNP: P-LAamp;lt;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., Funding Agencies|ALF (County Council of Ostergotland); Carldavid Jonsson Research Foundation; Heart Foundation; Linkoping University; Biosense Webster; ALF (Linkoping University); Johnson Johnson