Gender and age differences in symptoms and health-related quality of life in patients with atrial fibrillation referred for catheter ablation.

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.

Higher burden of supraventricular ectopic complexes early after catheter ablation for atrial fibrillation is associated with increased risk of recurrent atrial fibrillation.

Aims: Early identification of patients who could benefit from early re-intervention after catheter ablation is highly warranted. Our aim was to investigate the association between post-procedural burden of supraventricular ectopic complexes (SVEC) and the risk of long-term atrial fibrillation (AF) recurrence. Methods and results: A total of 125 patients undergoing catheter ablation for AF were included. Patients underwent 7-day Holter recordings immediately post-procedural. The number of SVEC in post-procedural Holter recordings was categorized into quartiles: 0-72, 73-212, 213-782 and ≥ 783 SVEC/day. Long-term AF recurrence was defined as a combined endpoint of AF ≥ 1 min during follow-up Holter recordings, cardioversion or hospitalization for AF after a 3-month blanking period and within 24 months of follow-up. High post-procedural supraventricular ectopy burden was associated with an increased risk of long-term AF recurrence in a dose-dependent manner (≥ 783 SVEC: HR 4.6 [1.9-11.5], P < 0.001) irrespective of AF recurrence during the blanking period or other risk factors. In patients with early AF recurrence < 90 days after catheter ablation ectopy burden was also highly predictive of long-term AF recurrence (SVEC ≥ 213: HR 3.0 [1.3-6.7], P = 0.007). Correspondingly, patients with early AF recurrence but low ectopy burden remained at low risk of long-term AF recurrence after the blanking period. Conclusion: Our results indicate that post-procedural ectopy burden is highly associated with long-term AF recurrence and could be a potent risk marker for selection of patients for early re-ablation. Development of future ablation risk stratification and strategies should include focus on post-procedural ectopy burden.

Radiofrequency ablation as initial therapy in paroxysmal atrial fibrillation.

BACKGROUND: There are limited data comparing radiofrequency catheter ablation with antiarrhythmic drug therapy as first-line treatment in patients with paroxysmal atrial fibrillation. METHODS: We randomly assigned 294 patients with paroxysmal atrial fibrillation and no history of antiarrhythmic drug use to an initial treatment strategy of either radiofrequency catheter ablation (146 patients) or therapy with class IC or class III antiarrhythmic agents (148 patients). Follow-up included 7-day Holter-monitor recording at 3, 6, 12, 18, and 24 months. Primary end points were the cumulative and per-visit burden of atrial fibrillation (i.e., percentage of time in atrial fibrillation on Holter-monitor recordings). Analyses were performed on an intention-to-treat basis. RESULTS: There was no significant difference between the ablation and drug-therapy groups in the cumulative burden of atrial fibrillation (90th percentile of arrhythmia burden, 13% and 19%, respectively; P=0.10) or the burden at 3, 6, 12, or 18 months. At 24 months, the burden of atrial fibrillation was significantly lower in the ablation group than in the drug-therapy group (90th percentile, 9% vs. 18%; P=0.007), and more patients in the ablation group were free from any atrial fibrillation (85% vs. 71%, P=0.004) and from symptomatic atrial fibrillation (93% vs. 84%, P=0.01). One death in the ablation group was due to a procedure-related stroke; there were three cases of cardiac tamponade in the ablation group. In the drug-therapy group, 54 patients (36%) underwent supplementary ablation. CONCLUSIONS: In comparing radiofrequency ablation with antiarrhythmic drug therapy as first-line treatment in patients with paroxysmal atrial fibrillation, we found no significant difference between the treatment groups in the cumulative burden of atrial fibrillation over a period of 2 years. (Funded by the Danish Heart Foundation and others; MANTRA-PAF ClinicalTrials.gov number, NCT00133211.).

Is the acetylcholine-regulated inwardly rectifying potassium current a viable antiarrhythmic target? Translational discrepancies of AZD2927 and A7071 in dogs and humans.

AIMS: We aimed at examining the acetylcholine-dependent inward-rectifier current (IKAch) as a target for the management of atrial fibrillation (AF). METHODS AND RESULTS: The investigative agents AZD2927 and A7071 concentration-dependently blocked IKACh in vitro with minimal off-target activity. In anaesthetized dogs (n = 17) subjected to 8 weeks of rapid atrial pacing (RAP), the left atrial effective refractory period (LAERP) was maximally increased by 50 ± 7.4 and 50 ± 4.8 ms following infusion of AZD2927 and A7071. Ventricular refractoriness and the QT interval were unaltered. During sustained AF, both drugs significantly reduced AF frequency and effectively restored sinus rhythm. AZD2927 successfully restored sinus rhythm at 10/10 conversion attempts and A7071 at 14/14 attempts, whereas saline converted 4/17 episodes only (P<0.001 vs. AZD2927 and A7071). In atrial flutter patients (n = 18) undergoing an invasive investigation, AZD2927 did not change LAERP, the paced QT interval, or ventricular refractoriness when compared with placebo. To address the discrepancy on LAERP by IKACh blockade in man and dog and the hypothesis that atrial electrical remodelling is a prerequisite for IKACh blockade being efficient, six dogs were studied after 8 weeks of RAP followed by sinus rhythm for 4 weeks to reverse electrical remodelling. In these dogs, both AZD2927 and A7071 were as effective in increasing LAERP as in the dogs studied immediately after the 8-week RAP period. CONCLUSION: Based on the present series of experiments, an important role of IKACh in human atrial electrophysiology, as well as its potential as a viable target for effective management of AF, may be questioned.

The cost-effectiveness of radiofrequency catheter ablation as first-line treatment for paroxysmal atrial fibrillation: results from a MANTRA-PAF substudy.

AIM: The aim of this prospective substudy was to estimate the cost-effectiveness of treating paroxysmal atrial fibrillation (AF) with radiofrequency catheter ablation (RFA) compared with antiarrhythmic drugs (AADs) as first-line treatment. METHODS AND RESULTS: A decision-analytic Markov model, based on MANTRA-PAF (Medical Antiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation) study data, was developed to study long-term effects and costs of RFA compared with AADs as first-line treatment. Positive clinical effects were found in the overall population, a gain of an average 0.06 quality-adjusted life years (QALYs) to an incremental cost of €3033, resulting in an incremental cost-effectiveness ratio of €50 570/QALY. However, the result of the subgroup analyses showed that RFA was less costly and more effective in younger patients. This implied an incremental cost-effectiveness ratio of €3434/QALY in ≤50-year-old patients respectively €108 937/QALY in >50-year-old patients. CONCLUSION: Radiofrequency catheter ablation as first-line treatment is a cost-effective strategy for younger patients with paroxysmal AF. However, the cost-effectiveness of using RFA as first-line therapy in older patients is uncertain, and in most of these AADs should be attempted before RFA (MANTRA-PAF ClinicalTrials.gov number; NCT00133211).

Validation of the English version of the arrhythmia-specific questionnaire in tachycardia and arrhythmia (ASTA): a Rasch evaluation study.

BACKGROUND: Patient-reported outcome measures are important in person-centered care, providing valuable information about patients' experiences. Disease-specific questionnaires add important information about a certain disease in comparison to generic questionnaires. Questionnaires need to be validated in the targeted population to achieve reliable data. The purpose with the study was to use Rasch measurement theory to evaluate the English version of the ASTA questionnaire. METHODS: The Rasch model theory was used to evaluate global and item fit, targeting, response category functioning, local independency, unidimensionality, differential item functioning (DIF) for gender and age, and reliability. RESULTS: The study included 202 patients undergoing DC conversion or catheter ablation at the Centre for Heart Rhythm Disorders at the University of Adelaide, Australia. The mean age was 67 years and 30% were women. Most patients had atrial fibrillation (n = 179), others had atrial flutter or had a combination. One of nine items demonstrated unsatisfactory model fit in the ASTA Symptom scale and two of 13 in the ASTA Health-Related Quality of Life (HRQoL) scale. Unidimensionality was supported for both scales. The targeting was acceptable except for the lower end of the scales. Both scales showed reversed thresholds for the response categories "quite a lot" and "a lot" (eight of ASTA symptoms and 12 of ASTA HRQoL items). Some problems with local dependency were detected in both scales. The reliability (person separation index) was satisfactory: 0.75 for the ASTA symptom scale and 0.77 for the ASTA HRQoL scale. No DIF for gender and age were detected. CONCLUSIONS: The English version of the ASTA questionnaire demonstrated satisfactory measurement properties according to the Rasch model. However, it needs to be evaluated in patients with other arrhythmias. The response categories should be considered as well as DIF in further validation. The ASTA questionnaire can be used for assessments of symptoms and HRQoL between groups of different ages and genders in patients with arrhythmia.

Symptoms and health-related quality of life 5 years after catheter ablation of atrial fibrillation.

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.

Risk and protective factors for atrial fibrillation after cardiac surgery and valvular interventions: an umbrella review of meta-analyses.

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.

Endocrine and Mechanical Cardiacfunction Four Months after Radiofrequency Ablation of Atrialfibrillation.

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.

A randomized invasive cardiac electrophysiology study of the combined ion channel blocker AZD1305 in patients after catheter ablation of atrial flutter.

BACKGROUND: This study assessed the cardiac electrophysiological and hemodynamic effects of an intravenous infusion of the combined ion channel blocker AZD1305. METHODS: After successful ablation of atrial flutter, patients were randomized to receive placebo (n = 12) or AZD1305 (n = 38) in 4 ascending dose groups. Electrophysiological and hemodynamic measurements were performed before and commencing 20 minutes after start of infusion. RESULTS: Left atrial effective refractory period increased dose and the primary outcome measure increased dose and plasma concentration dependently, with a mean increase of 55 milliseconds in dose group 3. There was a corresponding increase in right atrial effective refractory period of 84 milliseconds. The right ventricular effective refractory period and the paced QT interval also increased dose and concentration dependently, by 59 and 70 milliseconds, respectively, in dose group 3. There were indications of moderate increases of atrial, atrioventricular nodal, and ventricular conduction times. No consistent changes in intracardiac pressures were observed, but there was a small transient decrease in systolic blood pressure. Adverse events were consistent with the study population and procedure, and there were no signs of proarrhythmia despite marked delay in ventricular repolarization in some individuals. CONCLUSIONS: AZD1305 shows electrophysiological characteristics indicative of potential antiarrhythmic efficacy in atrial fibrillation.

Effects of AZD0837, a novel direct thrombin inhibitor, on the electrophysiological properties of the human heart: a randomized, double-blind, parallel-group, placebo-controlled study.

BACKGROUND: AZD0837 is an investigational oral anticoagulant that is bioconverted to its active form, AR-H067637, a selective direct thrombin inhibitor. OBJECTIVES: The objectives of the present study were to investigate if there are any clinically relevant adverse effects of intravenous AZD0837 on cardiac conduction, refractoriness and repolarization, and to study its safety and tolerability. METHODS: In this randomized, double-blind, parallel-group, placebo-controlled study (study code D1250C00026), invasive electrophysiological measurements were performed twice in 30 subjects with a history of, or ongoing, atrial flutter, starting 30 minutes after successful ablation of atrial flutter and then 60 minutes after start of an intravenous infusion of AZD0837. Pre-study warfarin therapy was not an exclusion criterion. The stimulation protocol was performed mainly at 500 and 400 ms drive cycle length. A 12-lead ECG was also recorded before and during AZD0837 infusion. Plasma concentrations of AZD0837 and its metabolites were obtained at predefined timepoints. RESULTS: Measurements were made at baseline and during stable plasma concentrations of the prodrug AZD0837 (mean +/- standard deviation 7.96 +/- 2.38 micromol/L, approximate target of 10 micromol/L), the intermediate metabolite AR-H69927 (1.26 +/- 0.39 micromol/L, target 1-2 micromol/L) and the active direct thrombin inhibitor AR-H067637 (0.35 +/- 0.14 micromol/L, target 0.5-1.0 micromol/L). There were no clinically relevant effects on cardiac conduction (QRS duration, PR interval, His bundle electrogram, Wenckebach point), refractoriness (atrial, atrioventricular and ventricular effective refractory periods) or repolarization (QT, QT interval corrected for heart rate using Fridericia's formula, QRS onset to the top of the T wave [QT(top)], QRS onset to the end of the T wave [QT(end)] or QT(top) - QT(end)). CONCLUSIONS: AZD0837 was well tolerated, and had no clinically relevant effects on cardiac electrophysiology of the target population, either in subjects previously treated with warfarin or in those without previous treatment.

ASK FOR IT: An Internet-based educational program for patients with atrial fibrillation - Results from a pilot study and design of the randomized, controlled, multicenter ASK FOR IT study.

Background: In the structured care of patients with atrial fibrillation (AF), education is compulsory. Patients search for information but sources of reliable information are sparse. ASK FOR IT, an internet- and guideline-based educational program, offers such information. Objective: To describe the development of ASK FOR IT, report on a pilot study, and present the design of a randomized controlled trial evaluating the benefits of ASK FOR IT in addition to standard care on symptoms, health-related quality of life (HRQoL), and health economy. Methods: ASK FOR IT was developed by healthcare providers, patients, and a psychologist. ASK FOR IT contains 6 parts: basic mechanisms, symptoms, treatment options, diagnostic possibilities, lifestyle management, and a mental support section. The following questionnaires were used: SF-36, EQ-5D, the disease-specific ASTA (symptoms and HRQoL), and HADS (depression and anxiety). Interviews regarding usability and understanding were conducted. Results: Pilot study: Fifteen patients (mean age 65 years), 4 women and 11 men, took part in the study. During follow-up, the patients improved regarding symptoms in ASTA (P = .038) and the HRQoL mental domain (P = .011), while no differences were seen in SF-36, EQ-5D, or HADS. Interviews indicated that the program was easy to use and the content easy to understand. Conclusion: The ASK FOR IT program functioned as intended. It was easy to use and the information was easy to understand. The significant reduction in symptoms and improvement in HRQoL (mental domain) after only 3 months are encouraging. In the main study, 200 patients will be randomized.

[Evaluation and treatment of PVC's]. / Utredning och behandling av ventrikulära extraslag.

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.

The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) trial: clinical rationale, study design, and implementation.

AIMS: No large randomized multicentre trial has evaluated the efficacy of radiofrequency ablation (RFA) vs. anti-arrhythmic drug (AAD) therapy as a first-line treatment of paroxysmal atrial fibrillation (AF). METHODS AND RESULTS: The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation (MANTRA-PAF) trial is a randomized, controlled, parallel group, multicentre study designed to test whether catheter-based RFA is superior to optimized AAD therapy in suppressing relapse within 24 months of symptomatic and/or asymptomatic AF in patients with paroxysmal AF without prior AAD therapy. The primary endpoint is cumulative AF burden on repeated 7 days Holter monitoring. Secondary endpoints are: thromboembolic events, hospitalization due to arrhythmia, pro-arrhythmic events, procedure/treatment-related side effects, health economics, quality of life, and change in left ventricular function. Ten centres in Scandinavia and Germany are participating in the study. Enrolment was started in 2005 and as of November 2008, 260 patients have been enrolled into the study. It is expected that enrolment will end by March 2009, when 300 patients have been included. CONCLUSION: The MANTRA-PAF trial will determine whether catheter-based RFA is superior to optimized AAD therapy as a first-line treatment in suppressing long-term relapse of symptomatic and/or asymptomatic AF.

Wolff-Parkinson-White syndrome and atrioventricular nodal re-entry tachycardia in a Swedish population: consequences on health-related quality of life.

BACKGROUND: Living with paroxysmal supraventricular tachycardia affects a patient's whole life situation, but few studies have addressed health-related quality of life (HRQOL) aspects in these patients. The aim was therefore to describe HRQOL in patients with atrioventricular nodal re-entry tachycardia (AVNRT) or Wolff-Parkinson-White (WPW) syndrome, referred for radiofrequency ablation (RF-ablation), compared to age- and gender-matched Swedish reference groups. METHODS: HRQOL was assessed with SF-36 and EuroQol (EQ-5D and EQ-VAS) and the patients were asked disease-specific questions. RESULTS: The 97 patients with AVNRT [53 +/- 16 years of age/65 women] and 79 patients with WPW [42 +/- 15 years of age/26 women] exhibited significantly lower HRQOL scores in SF-36 in the same seven of the eight scales: Physical functioning (PF), role-physical (RP), social functioning (SF), role-emotional (RE), general health (GH), vitality (VT), and mental health (MH) while there was no difference in bodily pain (BP) compared to their respective age- and gender matched Swedish reference group. HRQOL scores were lower for patients with AVNRT compared to WPW in the areas of PF (P < 0.001), BP (P < 0.05), and GH (P < 0.01) in SF-36, and the same was found in EQ-VAS (64.8 vs. 71.2, P < 0.05). Occurrence of episodes of tachycardia more often than once a month compared to less frequently than once a month was associated with significantly lower HRQOL in all eight scales in SF-36 (GH, RE, MH: P < 0.01 and PF, RP, BP, VT, SF: P < 0.001) and EQ-5D index (P < 0.001) and EQ-VAS (P < 0.05) Arrhythmia duration longer than one hour compared to patients with shorter duration of the tachycardia-affected GH in SF-36 negatively (P < 0.05). Patients who experienced symptoms not only during activity but also at rest scored lower in SF-36 GH (P < 0.01) and SF (P < 0.05). CONCLUSION: Measuring HRQOL in patients with WPW or AVNRT is an important way to evaluate and describe these patients' life situation. These conditions were found to have a pronounced negative impact on HRQOL. The frequency of arrhythmia occurrence is one important factor to consider when setting priorities for treatment with RF-ablation.

Predictors of improvement in arrhythmia-specific symptoms and health-related quality of life after catheter ablation of atrial fibrillation.

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 (R2 = 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 (R2 = 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.

The association between alcohol consumption, cardiac biomarkers, left atrial size and re-ablation in patients with atrial fibrillation referred for catheter ablation.

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.

Focal atrial tachycardia: increased electrogram fractionation in the vicinity of the earliest activation site.

AIMS: Fractionated electrograms are often noted during mapping of focal atrial tachycardia (FAT). This finding suggests poor cell-to-cell coupling, which is thought to be an important prerequisite in the process of ectopic impulse initiation and propagation. The purpose of the present study was to assess the electrogram fractionation in the vicinity of the earliest activation site and in the remaining atrium in these patients. METHODS AND RESULTS: Thirteen patients with FAT (age 48 +/- 17 years) who underwent catheter ablation were investigated. Mapping was performed with the CARTO system. Electrogram fractionation was assessed on the basis of the number of negative deflections, both in the region surrounding the earliest activation site and in the remaining atrium. Unipolar and bipolar peak-to-peak voltage and bipolar electrogram duration were also studied. All patients underwent successful radiofrequency ablation. A higher degree of electrogram fractionation existed in the region surrounding the earliest activation site and activated within the first 15 ms when compared with the remaining atrium (incidence of bipolar electrograms with multiple negative deflections: 88 vs. 79%, P < 0.0001; incidence of unipolar electrograms with multiple negative deflections: 56 vs. 43%, P = 0.0001). The peak-to-peak voltage in the region activated within the first 15 ms was less than that in the remaining atrium (bipolar voltage: 1.33 +/- 0.99 vs. 1.61 +/- 1.11 mV, P < 0.001; unipolar voltage: 1.75 +/- 0.92 vs. 1.95 +/- 1.11 mV, P = 0.0188). There were no significant differences in bipolar electrogram duration. Within the region activated during the first 15 ms, from the periphery to the earliest activation site, there was a gradual increase in electrogram fractionation (incidence of bipolar electrograms with multiple negative deflections gradually increasing from 82 to 100% and incidence of unipolar electrograms with multiple negative deflections increasing from 56 to 90%), as well as a gradual decrease in peak-to-peak voltage (bipolar voltage gradually decreasing from 1.47 +/- 1.06 to 0.89 +/- 0.54 mV, P < 0.0001; unipolar voltage gradually decreasing from 1.89 +/- 0.94 to 1.30 +/- 0.63 mV, P < 0.0001). Irregular, closely spaced isochrones were also noted in the region activated during the first 15 ms. The area of this region was 4.88 +/- 3.59 cm(2). CONCLUSION: Increased electrogram fractionation exists within a relatively wide region around the tachycardia origin when compared with the remaining atrium. Moreover, this region is electrically heterogeneous, as suggested by the fact that the degree of electrogram fractionation increases gradually whereas the electrogram voltage decreases gradually towards the earliest activation site. These findings suggest that a non-discrete atrial region with gradually changing electrophysiological properties may underlie the substrate of FAT.

Source of inflammatory markers in patients with atrial fibrillation.

AIMS: Elevated levels of C-reactive protein and other inflammatory markers have been reported in some patients with atrial fibrillation (AF). Whether this finding is related to AF per se or to other conditions remains unclear. In addition, the source of inflammatory markers is unknown. Therefore, in the present study, we sought to assess the extent and the source of inflammation in patients with AF and no other concomitant heart or inflammatory conditions. METHODS AND RESULTS: The study group consisted of 29 patients referred for radiofrequency catheter ablation: 10 patients with paroxysmal AF, 8 patients with permanent AF, and 10 control patients with Wolf-Parkinson-White (WPW) syndrome and no evidence of AF (mean age 54 +/- 11 vs. 57 +/- 13 vs. 43 +/- 16). No patient had structural heart diseases or inflammatory conditions. High-sensitive C-reactive protein, interleukin-6 (IL-6), and interleukin-8 (IL-8) were assessed in blood samples from the femoral vein, right atrium, coronary sinus, and the left and right upper pulmonary veins. All samples were collected before ablation. Compared with controls and patients with paroxysmal AF, patients with permanent AF had higher plasma levels of IL-8 in the samples from the femoral vein, right atrium, and coronary sinus, but not in the samples from the pulmonary veins (median values in the femoral vein: 2.58 vs. 2.97 vs. 4.66 pg/mL, P = 0.003; right atrium: 2.30 vs. 3.06 vs. 3.93 pg/mL, P = 0.013; coronary sinus: 2.85 vs. 3.15 vs. 4.07, P = 0.016). A high-degree correlation existed between the IL-8 levels in these samples (correlation coefficient between 0.929 and 0.976, P < 0.05). No differences in the C-reactive protein and IL-6 levels were noted between the three groups of patients. CONCLUSION: The normal levels of C-reactive protein and IL-6, along with the elevated levels of IL-8 in patients with permanent AF but not in those with paroxysmal AF, suggest a link between a low-grade inflammatory reaction and long-lasting AF. The elevated IL-8 levels in the peripheral blood, right atrium, and coronary sinus but not in the pulmonary veins suggest a possible source of inflammation in the systemic circulation.