The Danish Atrial Fibrillation Registry: A Multidisciplinary National Pragmatic Initiative for Monitoring and Supporting Quality of Care Based on Data Retrieved from Administrative Registries.

Aim: The Danish Atrial Fibrillation (AF) Registry monitors and supports improvement of quality of care for all AF patients in Denmark. This report describes the registry's administrative and organizational structure, data sources, data flow, data analyses, annual reporting, and feedback between the registry, clinicians, and the administrative system. We also report the selection process of the quality indicators and the temporal trends in results from 2017-2021. Methods and Results: The Danish AF Registry aims for complete registration and monitoring of care for all patients diagnosed with AF in Denmark. Administrative registries provide data on contacts to general practice, contacts to private cardiology practice, hospital contacts, medication prescriptions, updated vital status information, and biochemical test results. The Danish Stroke Registry provides information on stroke events. From 2017 to 2021, the proportion with a reported echocardiography among incident AF patients increased from 39.9% (95% CI: 39.3-40.6) to 82.6% (95% CI: 82.1-83.1). The initiation of oral anticoagulant therapy among patients with incident AF and a CHA2DS2-VASc score of ≥1 in men and ≥2 in women increased from 85.3% (95% CI: 84.6-85.9) to 90.4% (95% CI: 89.9-91.0). The 1-year and 2-year persistence increased from 85.2% (95% CI: 84.5-85.9) to 88.7% (95% CI: 88.0-89.3), and from 85.4% (95% CI: 84.7-86.2) to 88.2% (95% CI: 87.5-88.8), respectively. The 1-year risk of ischemic stroke among prevalent patients with AF decreased from 0.88% (95% CI: 0.83-0.93) to 0.71% (95% CI: 0.66-0.75). Variation in clinical performance between the five administrative Danish regions was reduced. Conclusion: Continuous nationwide monitoring of quality indicators for AF originating from administrative registries is feasible and supportive of improvements of quality of care.

Atrial pacing minimization in sinus node dysfunction and risk of incident atrial fibrillation: a randomized trial.

BACKGROUND AND AIMS: High percentages of atrial pacing have been associated with an increased risk of atrial fibrillation. This study is aimed at evaluating whether atrial pacing minimization in patients with sinus node dysfunction reduces the incidence of atrial fibrillation. METHODS: In a nationwide, randomized controlled trial, 540 patients with sinus node dysfunction and an indication for first pacemaker implantation were assigned to pacing programmed to a base rate of 60 bpm and rate-adaptive pacing (DDDR-60) or pacing programmed to a base rate of 40 bpm without rate-adaptive pacing (DDD-40). Patients were followed on remote monitoring for 2 years. The primary endpoint was time to first episode of atrial fibrillation longer than 6 min. Secondary endpoints included longer episodes of atrial fibrillation, and the safety endpoint comprised a composite of syncope or presyncope. RESULTS: The median percentage of atrial pacing was 1% in patients assigned to DDD-40 and 49% in patients assigned to DDDR-60. The primary endpoint occurred in 124 patients (46%) in each treatment group (hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.76-1.25, P = .83). There were no between-group differences in atrial fibrillation exceeding 6 or 24 h, persistent atrial fibrillation, or cardioversions for atrial fibrillation. The incidence of syncope or presyncope was higher in patients assigned to DDD-40 (HR 1.71, 95% CI 1.13-2.59, P = .01). CONCLUSIONS: Atrial pacing minimization in patients with sinus node dysfunction does not reduce the incidence of atrial fibrillation. Programming a base rate of 40 bpm without rate-adaptive pacing is associated with an increased risk of syncope or presyncope.

Lenient rate control versus strict rate control for atrial fibrillation: a statistical analysis plan for the Danish Atrial Fibrillation (DanAF) randomized clinical trial.

BACKGROUND: A key decision in the treatment of atrial fibrillation is choosing between a rhythm control strategy or a rate control strategy as the main strategy. When choosing rate control, the optimal heart rate target is uncertain. The Danish Atrial Fibrillation trial is a randomized, multicenter, two-group, superiority trial comparing strict rate control versus lenient rate control in patients with either persistent or permanent atrial fibrillation at inclusion. To prevent bias arising from selective reporting and data-driven analyses, we developed a predefined description of the statistical analysis. METHODS: The primary outcome of this trial is the physical component score of the SF-36 questionnaire. A total of 350 participants will be enrolled based on a minimal important difference of 3 points on the physical component score of the SF-36 questionnaire, a standard deviation of 10 points, a statistical power of 80% (beta of 20%), and an acceptable risk of type I error of 5%. All secondary, exploratory, and echocardiographic outcomes will be hypothesis-generating. The analyses of all outcomes will be based on the intention-to-treat principle. We will analyze continuous outcomes using linear regression adjusting for "site," type of atrial fibrillation at inclusion (persistent/ permanent), left ventricular ejection fraction (≥ 40% or < 40%), and the baseline value of the outcome (all as fixed effects). We define our threshold for statistical significance as a p-value of 0.05 and assessments of clinical significance will be based on the anticipated intervention effects defined in the sample size and power estimations. Thresholds for both statistical and clinical significance will be assessed according to the 5-step procedure proposed by Jakobsen and colleagues. DISCUSSION: This statistical analysis plan will be published prior to enrolment completion and before any data are available and is sought to increase the validity of the DANish Atrial Fibrillation trial. TRIAL REGISTRATION: Clinicaltrials.gov NCT04542785. Registered on Sept 09, 2020.

Lenient rate control versus strict rate control for atrial fibrillation: a protocol for the Danish Atrial Fibrillation (DanAF) randomised clinical trial.

INTRODUCTION: Atrial fibrillation is the most common heart arrhythmia with a prevalence of approximately 2% in the western world. Atrial fibrillation is associated with an increased risk of death and morbidity. In many patients, a rate control strategy is recommended. The optimal heart rate target is disputed despite the results of the the RAte Control Efficacy in permanent atrial fibrillation: a comparison between lenient vs strict rate control II (RACE II) trial.Our primary objective will be to investigate the effect of lenient rate control strategy (<110 beats per minute (bpm) at rest) compared with strict rate control strategy (<80 bpm at rest) on quality of life in patients with persistent or permanent atrial fibrillation. METHODS AND ANALYSIS: We plan a two-group, superiority randomised clinical trial. 350 outpatients with persistent or permanent atrial fibrillation will be recruited from four hospitals, across three regions in Denmark. Participants will be randomised 1:1 to a lenient medical rate control strategy (<110 bpm at rest) or a strict medical rate control strategy (<80 bpm at rest). The recruitment phase is planned to be 2 years with 3 years of follow-up. Recruitment is expected to start in January 2021. The primary outcome will be quality of life using the Short Form-36 (SF-36) questionnaire (physical component score). Secondary outcomes will be days alive outside hospital, symptom control using the Atrial Fibrillation Effect on Quality of Life, quality of life using the SF-36 questionnaire (mental component score) and serious adverse events. The primary assessment time point for all outcomes will be 1 year after randomisation. ETHICS AND DISSEMINATION: Ethics approval was obtained through the ethics committee in Region Zealand. The design and findings will be published in peer-reviewed journals as well as be made available on ClinicalTrials.gov. TRIAL REGISTRATION NUMBER: NCT04542785.

Association of genetic variants previously implicated in coronary artery disease with age at onset of coronary artery disease requiring revascularizations.

BACKGROUND: The relation between burden of risk factors, familial coronary artery disease (CAD), and known genetic variants underlying CAD and low-density lipoprotein cholesterol (LDL-C) levels is not well-explored in clinical samples. We aimed to investigate the association of these measures with age at onset of CAD requiring revascularizations in a clinical sample of patients undergoing first-time coronary angiography. METHODS: 1599 individuals (mean age 64 years [min-max 29-96 years], 28% women) were genotyped (from blood drawn as part of usual clinical care) in the Copenhagen area (2010-2014). The burden of common genetic variants was measured as aggregated genetic risk scores (GRS) of single nucleotide polymorphisms (SNPs) discovered in genome-wide association studies. RESULTS: Self-reported familial CAD (prevalent in 41% of the sample) was associated with -3.2 years (95% confidence interval -4.5, -2.2, p<0.0001) earlier need of revascularization in sex-adjusted models. Patients with and without familial CAD had similar mean values of CAD-GRS (unweighted scores 68.4 vs. 68.0, p = 0.10, weighted scores 67.7 vs. 67.5, p = 0.49) and LDL-C-GRS (unweighted scores 58.5 vs. 58.3, p = 0.34, weighted scores 63.3 vs. 61.1, p = 0.41). The correlation between the CAD-GRS and LDL-C-GRS was low (r = 0.14, p<0.001). In multivariable adjusted regression models, each 1 standard deviation higher values of LDL-C-GRS and CAD-GRS were associated with -0.70 years (95% confidence interval -1.25, -0.14, p = 0.014) and -0.51 years (-1.07, 0.04, p = 0.07) earlier need for revascularization, respectively. CONCLUSIONS: Young individuals presenting with CAD requiring surgical interventions had a higher genetic burden of SNPs relating to LDL-C and CAD (although the latter was statistically non-significant), compared with older individuals. However, the absolute difference was modest, suggesting that genetic screening can currently not be used as an effective prediction tool of when in life a person will develop CAD. Whether undiscovered genetic variants can still explain a "missing heritability" in early-onset CAD warrants more research.

Subclinical and overt thyroid dysfunction and risk of all-cause mortality and cardiovascular events: a large population study.

CONTEXT: Thyroid dysfunction has been associated with both increased all-cause and cardiovascular mortality, but limited data are available on mild thyroid dysfunction and cause-specific mortality. OBJECTIVE: The objective of the study was to examine the risk of all-cause mortality, major adverse cardiovascular events (MACEs), and cause-specific events in subjects with overt and subclinical thyroid dysfunction. DESIGN: This was a retrospective cohort study. SETTING AND PARTICIPANTS: Participants in the study were subjects who underwent thyroid blood tests, without prior thyroid disease, consulting their general practitioner in 2000-2009 in Copenhagen, Denmark. MAIN OUTCOME MEASURE: All-cause mortality, MACEs, and cause-specific events identified in nationwide registries were measured. RESULTS: A total of 47 327 (8.4%) deaths occurred among 563 700 included subjects [mean age 48.6 (SD ± 18.2) y; 39% males]. All-cause mortality was increased in overt and subclinical hyperthyroidism [age adjusted incidence rates of 16 and 15 per 1000 person-years, respectively; incidence rate ratios (IRRs) 1.25 [95% confidence interval (CI) 1.15-1.36] and 1.23 (95% CI 1.16-1.30)] compared with euthyroid (incidence rate of 12 per 1000 person-years). Risk of MACEs was elevated in overt and subclinical hyperthyroidism [IRRs 1.16 (95% CI 1.05-1.27) and 1.09 (95% CI 1.02-1.16)] driven by heart failure [IRRs 1.14 (95% CI 0.99-1.32) and 1.20 (95% CI 1.10-1.31)]. A reduction of all-cause mortality was observed in subclinical hypothyroidism with TSH of 5-10 mIU/L [IRR 0.92 (95% CI 0.86-0.98)]. CONCLUSIONS: Heart failure is the leading cause of an increased cardiovascular mortality in both overt and subclinical hyperthyroidism. Subclinical hypothyroidism with TSH 5-10 mIU/L might be associated with a lower risk of all-cause mortality.

Diagnostic value of exercise-induced changes in circulating high sensitive troponin T in stable chest pain patients.

OBJECTIVE: We investigated the diagnostic value of exercise-induced increase in cardiac Troponin T (cTnT) in stable chest pain subjects. METHODS: CTnT was measured before and 20 h after an exercise test in 157 subjects suspected of coronary artery disease (CAD). RESULTS: CAD subjects (n = 41) had higher baseline cTnT levels compared to non-CAD subjects (n = 116), 6.39 ng/l and 3.00 ng/l, respectively, p < 0.0001, and were more likely to increase in cTnT (70.7% versus 27.6%, p < 0.0001). Net Reclassification Index for the combined variable was 19%, p = 0.02. CONCLUSIONS: Exercise-induced increase in cTnT was found to be associated with CAD and cTnT measurements improved the diagnostic evaluation.

New-onset atrial fibrillation is a predictor of subsequent hyperthyroidism: a nationwide cohort study.

AIMS: To examine the long-term risk of hyperthyroidism in patients admitted to hospital with new-onset AF. Hyperthyroidism is a well-known risk factor for atrial fibrillation (AF), but it is unknown whether new-onset AF predicts later-occurring hyperthyroidism. METHODS AND RESULTS: All patients admitted with new-onset AF in Denmark from 1997-2009, and their present and subsequent use of anti-thyroid medication was identified by individual-level linkage of nationwide registries. Patients with previous thyroid diagnosis or thyroid medication use were excluded. Development of hyperthyroidism was assessed as initiation of methimazole or propylthiouracil up to a 13-year period. Risk of hyperthyroidism was analysed by Poisson regression models adjusted for important confounders such as amiodarone treatment. Non-AF individuals from the general population served as reference. A total of 145,623 patients with new-onset AF were included (mean age 66.4 years [SD ±13.2] and 55.3% males) of whom 3% (4,620 events; 62.2% women) developed hyperthyroidism in the post-hospitalization period compared to 1% (48,609 events; 82% women) in the general population (n = 3,866,889). In both women and men we found a significantly increased risk of hyperthyroidism associated with new-onset AF compared to individuals in the general population. The highest risk was found in middle-aged men and was consistently increased throughout the 13-year period of observation. The results were confirmed in a substudy analysis of 527,352 patients who had thyroid screening done. CONCLUSION: New-onset AF seems to be a predictor of hyperthyroidism. Increased focus on subsequent risk of hyperthyroidism in patients with new-onset AF is warranted.

The spectrum of thyroid disease and risk of new onset atrial fibrillation: a large population cohort study.

OBJECTIVES: To examine the risk of atrial fibrillation in relation to the whole spectrum of thyroid function in a large cohort of patients. DESIGN: Population based cohort study of general practice patients identified by linkage of nationwide registries at the individual level. SETTING: Primary care patients in the city of Copenhagen. SUBJECTS: Registry data for 586,460 adults who had their thyroid function evaluated for the first time by their general practitioner during 2000-10 and who were without previously recorded thyroid disease or atrial fibrillation. MAIN OUTCOME MEASURE: Poisson regression models used to estimate risk of atrial fibrillation by thyroid function. RESULTS: Of the 586,460 individuals in the study population (mean (SD) age 50.2 (16.9) years, 39% men), 562,461 (96.0%) were euthyroid, 1670 (0.3%) had overt hypothyroidism, 12,087 (2.0%) had subclinical hypothyroidism, 3966 (0.7%) had overt hyperthyroidism, and 6276 (1.0%) had subclinical hyperthyroidism. Compared with the euthyroid individuals, the risk of atrial fibrillation increased with decreasing levels of thyroid stimulating hormone (TSH) from high normal euthyroidism (incidence rate ratio 1.12 (95% CI 1.03 to 1.21)) to subclinical hyperthyroidism with reduced TSH (1.16 (0.99 to 1.36)) and subclinical hyperthyroidism with supressed TSH (1.41 (1.25 to 1.59)). Both overt and subclinical hypothyroidism were associated with a lower risk of atrial fibrillation. CONCLUSION: The risk of atrial fibrillation was closely associated with thyroid activity, with a low risk in overt hypothyroidism, high risk in hyperthyroidism, and a TSH level dependent association with risk of atrial fibrillation across the spectrum of subclinical thyroid disease.

Atrial fibrillation in heart failure is associated with an increased risk of death only in patients with ischaemic heart disease.

AIMS: The prognostic importance of atrial fibrillation (AF) in heart failure (HF) populations is controversial and may depend on patient selection. In the present study, we investigated the prognostic impact of AF in a large population with HF of various aetiologies. METHODS AND RESULTS: We included 2881 patients admitted to hospital with symptoms of worsening HF over a 4-year period (2001-2004), all patients were participants in the Echocardiography and Heart Outcome Study (ECHOS). Patients were followed for up to 7 years for all-cause mortality stratified according to heart rhythm (sinus rhythm, paroxysmal, or chronic AF) and according to the presence of ischaemic heart disease (IHD). During follow-up, 1934 patients (67%) died. In HF patients with a history of IHD, chronic AF was associated with an increased risk of death [hazard ratio (HR) 1.44; 95% confidence interval (CI): 1.18-1.77; P < 0.001). In contrast, in patients without IHD, chronic AF was not associated with an increased mortality risk (HR 0.88; 95% CI: 0.71-1.09; P = 0.25). There was significant interaction between the aetiology of HF and the prognostic importance of chronic AF (P(interaction) = 0.003). CONCLUSION: In patients with HF, AF is associated with an increased risk of death only in patients with underlying IHD.

Rhythm control versus rate control for atrial fibrillation and heart failure.

BACKGROUND: It is common practice to restore and maintain sinus rhythm in patients with atrial fibrillation and heart failure. This approach is based in part on data indicating that atrial fibrillation is a predictor of death in patients with heart failure and suggesting that the suppression of atrial fibrillation may favorably affect the outcome. However, the benefits and risks of this approach have not been adequately studied. METHODS: We conducted a multicenter, randomized trial comparing the maintenance of sinus rhythm (rhythm control) with control of the ventricular rate (rate control) in patients with a left ventricular ejection fraction of 35% or less, symptoms of congestive heart failure, and a history of atrial fibrillation. The primary outcome was the time to death from cardiovascular causes. RESULTS: A total of 1376 patients were enrolled (682 in the rhythm-control group and 694 in the rate-control group) and were followed for a mean of 37 months. Of these patients, 182 (27%) in the rhythm-control group died from cardiovascular causes, as compared with 175 (25%) in the rate-control group (hazard ratio in the rhythm-control group, 1.06; 95% confidence interval, 0.86 to 1.30; P=0.59 by the log-rank test). Secondary outcomes were similar in the two groups, including death from any cause (32% in the rhythm-control group and 33% in the rate-control group), stroke (3% and 4%, respectively), worsening heart failure (28% and 31%), and the composite of death from cardiovascular causes, stroke, or worsening heart failure (43% and 46%). There were also no significant differences favoring either strategy in any predefined subgroup. CONCLUSIONS: In patients with atrial fibrillation and congestive heart failure, a routine strategy of rhythm control does not reduce the rate of death from cardiovascular causes, as compared with a rate-control strategy. (ClinicalTrials.gov number, NCT00597077.)

Atrial fibrillation, ischaemic heart disease, and the risk of death in patients with heart failure.

AIMS: Atrial fibrillation (AF) is a risk factor for death in patients with a myocardial infarction, but highly variable results are reported in patients with heart failure. We studied the prognostic impact of AF in heart failure patients with and without ischaemic heart disease. METHODS AND RESULTS: During a period of 2 years, 3587 patients admitted to hospital because of heart failure were included in this study. All patients were examined by echocardiography and the presence of AF was recorded. Follow-up was available for 8 years. Twenty four percent of those discharged alive from hospital had AF. After 4 and 8 years of follow-up, mortality was higher in patients with AF than in patients without, 56 vs. 52% and 77 vs. 73%, respectively. Cox multivariable regression analysis showed a small but significant importance of AF for long-term mortality [hazard ratio (HR) 1.12, 95% confidence limits (CI), 1.02-1.23, P=0.018]. There was a significant interaction between the importance of AF and the presence of ischaemic heart disease (P=0.034). In patients with AF at the time of discharge and ischaemic heart disease, HR was 1.25 (95% CI: 1.09-1.42) and P<0.001; in patients with AF at discharge and without ischaemic heart disease, HR was 1.01 (95% CI: 0.88-1.16) and P=0.88. CONCLUSION: AF is associated with increased risk of death only in patients with ischaemic heart disease. This finding may explain the variable results of studies of the prognosis associated with AF in heart failure.

Increased risk of sudden and non-sudden cardiovascular death in patients with atrial fibrillation/flutter following acute myocardial infarction.

AIMS: Atrial fibrillation (AF) is a common complication in patients with acute myocardial infarction and is associated with an increase in the risk of death. The excess mortality associated with AF complicating acute myocardial infarction has not been studied in detail. Observations indicate that AF facilitates induction of ventricular arrhythmias, which may increase the risk of sudden cardiovascular death (SCD). A close examination of the mode of death could potentially provide useful knowledge to guide further investigations and treatments. METHODS AND RESULTS: We analysed the relation between AF/atrial flutter (AFL) and modes of death in 5983 consecutive patients discharged alive after an acute myocardial infarction screened in the TRAndolapril Cardiac Evaluation registry. This cohort of patients with an enzyme-verified acute myocardial infarction was admitted to 27 centres in 1990-92. Survival status was obtained 2 years after screening of the last patient. An independent endpoint committee assessed the modes of death. Left ventricular ejection fraction was determined in all the screened patients and information about presence or absence of AF/AFL was prospectively collected. Sustained or paroxysmal AF/AFL was observed in 1149 patients (19%) during hospitalization. During follow-up, 1659 patients (34%) died: 482 (50%) patients with AF/AFL and 1177 (30%) patients without AF/AFL, P<0.001. SCD occurred in 536, non-SCD occurred in 725, and 398 died of non-cardiovascular causes (includes 142 unclassifiable cases). The adjusted risk ratio of AF/AFL for total mortality was 1.33 (95% CI: 1.19-1.49; P<0.0001) and the risk ratio for SCD was 1.31 (95% CI: 1.07-1.60; P<0.009). The adjusted risk ratio of AF/AFL for non-SCD was 1.43 (95% CI: 1.21-1.70; P<0.0001). CONCLUSION: The excess mortality observed in patients with AF/AFL following acute myocardial infarction is due to a significant increase in both SCD and non-SCD.

New antiarrhythmic agents for atrial fibrillation and atrial flutter.

Atrial fibrillation is the most common sustained cardiac arrhythmia and is a frequent reason for antiarrhythmic therapy. Existing antiarrhythmic drugs have important side effects and presently the therapy to maintain sinus rhythm is not superior to a strategy of controlling excessive heart rate. This review summarises current strategies to improve antiarrhythmic therapy for atrial fibrillation. The most important strategies are: i) to develop drugs without proarrhythmic effects--development of drugs devoid of QT prolonging potential is the main strategy; ii) multiple channel-blocking drugs--inspired by the efficacy of amiodarone, several drugs are being developed that have similar electrophysiological properties as amiodarone, but without the extracardiac side effects; iii) drugs that act exclusively in the atria--the atria contain specific potassium channels, and several drugs that act only on these channels are in development; and iv) antiarrhythmic therapy without effects on ion channels--inhibition of the renin-angiotensin system and steroid therapy has been shown to have some effect in the treatment of atrial fibrillation. Many drugs are in development and the therapeutic scenario for treatment of atrial fibrillation may change quickly.

Impact of congestive heart failure and left ventricular systolic function on the prognostic significance of atrial fibrillation and atrial flutter following acute myocardial infarction.

BACKGROUND: Reports on the prognostic importance of atrial fibrillation following myocardial infarction have provided considerable variation in results. Thus, this study examined the impact of left ventricular systolic function and congestive heart failure on the prognostic importance of atrial fibrillation in acute myocardial infarction patients that might explain previous discrepancies. METHODS: The study population was 6676 patients consecutively admitted to hospital with acute myocardial infarction. Information on the presence of atrial fibrillation/flutter, left ventricular systolic function and congestive heart failure were prospectively collected. Mortality was followed for 5 years. RESULTS: In patients with left ventricular ejection fraction<0.25, atrial fibrillation/atrial flutter was associated with an increased in-hospital mortality (OR=1.8 (1.1-3.2); p<0.05) but not an increased 30-day mortality. In patients with 0.250.35. In patients with congestive heart failure, atrial fibrillation/atrial flutter was associated with an increased in-hospital mortality (OR=1.5 (1.2-1.9); p<0.001) and increased 30-day mortality (OR=1.4 (1.1-1.7); p<0.001) but not in patients without congestive heart failure. In hospital survivors, atrial fibrillation/atrial flutter was associated with an increased long-term mortality in all subgroups except those with left ventricular ejection fraction<0.25. CONCLUSIONS: Atrial fibrillation/atrial flutter is primarily associated with increased in-hospital mortality in heart failure patients. Long-term mortality is increased in all subgroups except those with left ventricular ejection fraction<25%.

A benefit-risk assessment of class III antiarrhythmic agents.

The prevalence of arrhythmia in the population is increasing as more people survive for longer with cardiovascular disease. It was once thought that antiarrhythmic therapy could save life, however, it is now evident that antiarrhythmic therapy should be administrated with the purpose of symptomatic relief. Since many patients experience a decrease in physical performance as well as a diminished quality of life during arrhythmia there is still a need for antiarrhythmic drug therapy. The development of new antiarrhythmic agents has changed the focus from class I to class III agents since it became evident that with class I drug therapy the prevalence of mortality is considerably higher. This review focuses on the benefits and risks of known and newer class III antiarrhythmic agents. The benefits discussed include the ability to maintain sinus rhythm in persistent atrial fibrillation patients, and reducing the need for implantable cardioverter defibrillator shock/antitachycardia therapy, since no class III antiarrhythmic agents have proven survival benefit. The risks discussed mainly focus on pro-arrhythmia as torsade de pointes ventricular tachycardia.

Prevalence, prognostic significance, and treatment of atrial fibrillation in congestive heart failure with particular reference to the DIAMOND-CHF study.

Atrial fibrillation is a growing health problem and the most common cardiac arrhythmia, affecting 5% of persons above the age of 65 years. The number of hospital discharges for atrial fibrillation has more than doubled in the past decade. It occurs very often in patients with congestive heart failure and the prevalence increases with the severity of the disease. These two conditions seem to be linked together, and congestive heart failure may either be the cause or the consequence of atrial fibrillation. The prognosis of atrial fibrillation is controversial, but studies indicate that atrial fibrillation is a risk factor in congestive heart failure patients. In the last 10-15 years, significant advances in the treatment of heart failure have improved survival, whereas effective management of atrial fibrillation in heart failure patients still awaits similar progress. Empirically, two strategies have evolved for treatment of atrial fibrillation: 1) rhythm control, which means conversion to sinus rhythm and maintenance of sinus rhythm; and 2) rate control, which means reduction of heart rate to an acceptable frequency. It is unknown whether one of these strategies is better than the other. In this review the authors discuss the prevalence, impact, and treatment of atrial fibrillation in heart failure patients.

Dofetilide: a new drug to control cardiac arrhythmia.

Atrial fibrillation (AF) is the most common cardiac arrhythmia. Mortality, and especially morbidity caused by AF, are major and growing health problems in the western world. AF is strongly associated with arterial hypertension, congestive heart failure, valvular heart disease, ischaemic heart disease, and with prevalence increasing with age. A variety of drugs have been used to terminate or prevent AF but, as many antiarrhythmic agents have the potential life-threatening pro-arrhythmia, safety problems remain. Dofetilide (Tikosyn, Pfizer), a new Vaughan Williams class III antiarrhythmic agent, has been developed and approved for the treatment of AF. In contrast to most antiarrhythmic agents, the development programme included two safety studies in high-risk patients. Dofetilide is effective and safe when an elaborate procedure for dosing is implemented. Along with amiodarone and betablockers, dofetilide is the only antiarrhythmic drug, which is recommended by guidelines for the treatment of AF in a wide range of patients.