Pharmacotherapy Of Atrial Fibrillation Research Articles

PCR151 Adherence to Direct Oral Anticoagulants and Incidence of Stroke/Acute Coronary Syndrome/Systemic Embolism Among Patients with Atrial Fibrillation Using a Marginal Structural Model

Direct oral anticoagulants (DOACs) play an essential role in the pharmacotherapy of atrial fibrillation (AF) for preventing cardiovascular complications. However, poor adherence to DOACs is a major concern due to the elevated risk of stroke and mortality. This study aimed to investigate the association between adherence to DOACs and the risk of stroke, systemic embolism, and acute coronary syndrome (ACS) using a marginal structural model (MSM).

Abstract 15506: Optical Mapping in Atrial Engineered Heart Tissues Reveals Proarrhythmic Potential of the Anti-AF Agent Vernakalant

Pharmacotherapy for atrial fibrillation (AF) is confounded by ventricular proarrhythmia. Vernakalant (VER) belongs to a class of atrial selective channel blockers developed in attempts to convert AF safely. Yet, robust analysis of the effects of VER in human based tissues has not been performed. We hypothesized that engineered heart tissues (EHT) composed of atrial (A) or ventricular (V) human iPSCs would provide a robust platform for quantitative analysis of chamber specific electrophysiological (EP) effects of VER. Methods: iPSCs were differentiated into cardiomyocytes using biphasic Wnt signaling, insulin, and lactate purification. Atrial-like myocytes were enriched by adding 0.75 μM retinoic acid on days 4-6 to promote atrial gene expression and specification. Myocytes were seeded onto cryosectioned, laser cut and decellularized myocardial tissues and cultured under isometric conditions. EHTs were stained with high dose, water soluble di-2-ANEPEQ to enhance signal-to-noise while avoiding toxicity. Results: Staining with 25 μM di-2-ANEPEQ provided high fidelity optical AP signals that allowed comprehensive characterization of the EP substrate. A-EHT exhibited significantly shorter AP durations than V-EHT reflecting greater repolarizing drive (APD80, 180 ms vs 367 ms; p < 0.0001, n = 4-5). Consistent with its role as an atrial-selective blocker, VER increased APD80 only in A-EHTs (180 ms vs 258 ms, p = 0.0027, n = 5). This beneficial property for combatting AF was countered by marked slowing of A-EHT conduction and AP upstroke velocity (20.6 cm/s vs 11.7 cm/s, p = 0.027, n = 5). Conclusions: Optical mapping of chamber specific EHTs confirms atrial specific nature of VER as an atrial repolarization prolonging agent but raises unexpected concerns regarding potential proarrhythmic toxicity related to atrial conduction slowing.

Pharmacotherapy of atrial fibrillation in COVID-19 patients.

The coronavirus pandemic disease 2019 (COVID-19) has changed the face of contemporary medicine. However, each and every medical practitioner must be aware of potential early and late complications of COVID-19, its impact on chronic diseases - especially ones as common as atrial fibrillation (AF) - and the possible interactions between patients' chronic medications and pharmacotherapy of COVID-19. Patients with AF due to comorbidities and, often, elderly age are assumed to be at a higher risk of a severe course of COVID-19. This expert consensus summarizes the current knowledge regarding the pharmacotherapy of AF patients in the setting of the COVID-19 pandemic. In general, anticoagulation principles in quarantined or asymptomatic individuals remain unchanged. Nevertheless, it is advisable to switch from vitamin K antagonists to non-vitamin K antagonist oral anticoagulants (NOACs) whenever possible due to their consistent benefits and safety with fixed dosing and no monitoring. Additionally, in AF patients hospitalized due to mild or moderate COVID-19 pneumonia, we recommend continuing NOAC treatment or to switching to low-molecular-weight heparin (LMWH). On the other hand, in severely ill patients hospitalized in intensive care units, intravenous or subcutaneous dosing is preferable to oral, which is why the treatment of choice is either LMWH or unfractionated heparin. Finally, particularly in critical scenarios, the treatment strategy in COVID-19 patients with AF should be individualized based on possible interactions between anticoagulants, antiarrhythmics, antivirals, and antibiotics. In this consensus, we also discuss how to safely perform COVID-19 vaccination in anticoagulated AF patients.

Фармакотерапия фибрилляции предсердий при субклиническом тиреотоксикозе

Фармакотерапия фибрилляции предсердий при субклиническом тиреотоксикозе

Changes in Antithrombotic Therapy of Atrial Fibrillation in the Hospital in 2011-2012 and 2016-2017 (Pharmacoepidemiological Analysis)

Aim. To study the changes that have occurred in the pharmacotherapy of atrial fibrillation (AF) in the Saratov Region for 5 years by analyzing the antithrombotic therapy of patients who were admitted in a specialized department of the multidisciplinary hospital in Saratov in 2011-2012 and in 2016-2017.Material and methods. A pharmacoepidemiological retrospective study was conducted. The object of the study was the medical records of inpatients (Form 003/y) with the diagnosis “Atrial fibrillation” (ICD-X code I48), that consecutively admitted to the cardiology department of the multidisciplinary hospital in Saratov from January 1, 2011 to December, 31, 2012 (n=211) and from January 1, 2016 to December, 31, 2017 (n=227). Criteria for inclusion in the study: patients over 18 years of age, established diagnosis of non-valvular AF of ischemic genesis. Exclusion criteria from the study: non-ischemic cardiomyopathy, thyrotoxicosis, congenital heart defects, rheumatic heart damage, acute coronary syndrome, endocarditis, myocarditis, pericarditis, pulmonary thromboembolism, the presence of prosthetic heart valve. Pharmacoepidemiological analysis was carried out for the drugs prescribed during hospitalization and given by doctors at discharge of patients from the hospital. The risk of ischemic stroke was assessed using the CHA2DS2-VASc score, and the risk of bleeding – according to the HAS-BLED score.Results. When analyzing the risk of ischemic stroke, it was found that 100% of patients in 2011-2012 years and 98.2% in 2016-2017 years had indications for the prescription of oral anticoagulants (OAСs). In 2011-2012 there were no patients with a low risk of stroke (CHA2DS2-VASc=0). High risk of bleeding (HAS-BLED≥3) occurred in 4.7% of patients in 2011-2012 and in 10.6% in 2016-2017, however, due to the high risk of stroke, the refusal to prescribe OAC in these patients was inappropriate in accordance with the recommendations for the treatment of AF. In the group of patients with CHA2DS2-VASc=0 in 2016-2017 antiplatelet therapy was prescribed in 100% at the hospital stage and at discharge, which contradicts the guidelines, according to which antithrombotic therapy is not recommended to patients with CHA2DS2-VASc=0. In patients with CHA2DS2-VASc=1, a low percentage of anticoagulants prescription was noted. In 2016-2017 OACs were prescribed only in 12.5% of patients at all stages of observation. In 2011-2012 OAC alone was prescribed only to 1 person (20%) at the hospital stage, which does not comply with modern guidelines for the treatment of patients with AF, according to which patients with a risk score CHA2DS2-VASc=1 are recommended to receive OACs in the absence of contraindications. OACs prescription in group CHA2DS2-VASc≥2 occurred only in 15% of patients in 2011-2012 and in a third of patients in 2016-2017 (p<0.05). The frequency of isolated use of OACs significantly increased in 2016-2017 compared to 2011-2012 mainly due to the increase in the spectrum of direct OACs (DOACs) (p<0.05).Conclusion. For 5 years there have been significant changes in the antithrombotic therapy of AF in the Saratov Region. The frequency of prescribing OACs according to indications has increased mainly due to the introduction of the DOACs into clinical practice. However, prevention of stroke remains insufficient.

Populations of in silico myocytes and tissues reveal synergy of multiatrial-predominant K+ -current block in atrial fibrillation.

Pharmacotherapy of atrial fibrillation (AF), the most common cardiac arrhythmia, remains unsatisfactory due to low efficacy and safety concerns. New therapeutic strategies target atrial-predominant ion-channels and involve multichannel block (poly)therapy. As AF is characterized by rapid and irregular atrial activations, compounds displaying potent antiarrhythmic effects at fast and minimal effects at slow rates are desirable. We present a novel systems pharmacology framework to quantitatively evaluate synergistic anti-AF effects of combined block of multiple atrial-predominant K+ currents (ultra-rapid delayed rectifier K+ current, IKur , small conductance Ca2+ -activated K+ current, IKCa , K2P 3.1 2-pore-domain K+ current, IK2P ) in AF. We constructed experimentally calibrated populations of virtual atrial myocyte models in normal sinus rhythm and AF-remodelled conditions using two distinct, well-established atrial models. Sensitivity analyses on our atrial populations was used to investigate the rate dependence of action potential duration (APD) changes due to blocking IKur , IK2P or IKCa and interactions caused by blocking of these currents in modulating APD. Block was simulated in both single myocytes and one-dimensional tissue strands to confirm insights from the sensitivity analyses and examine anti-arrhythmic effects of multi-atrial-predominant K+ current block in single cells and coupled tissue. In both virtual atrial myocytes and tissues, multiple atrial-predominant K+ -current block promoted favourable positive rate-dependent APD prolongation and displayed positive rate-dependent synergy, that is, increasing synergistic antiarrhythmic effects at fast pacing versus slow rates. Simultaneous block of multiple atrial-predominant K+ currents may be a valuable antiarrhythmic pharmacotherapeutic strategy for AF.

СПЕКТРАЛЬНЫЙ АНАЛИЗ ВАРИАБЕЛЬНОСТИ СЕРДЕЧНОГО РИТМА У ПАЦИЕНТОВ С ФИБРИЛЛЯЦИЕЙ ПРЕДСЕРДИЙ НА ФОНЕ ПРИМЕНЕНИЯ СОТАЛОЛА И БИСОПРОЛОЛА

Background. Atrial Fibrillation is one of the most common arrhythmias. Despite the different attitude to the pharmacotherapy of Atrial Fibrillation, the problem of selection of adequate antiarrhythmic therapy for the prevention and treatment of persistent Atrial Fibrillation remains relevant and is of great interest to researchers. For the effective selection of drugs in the treatment of arrhythmia can be successfully used the method of spectral analysis of heart rhythm variability. Aims: to study the effect of antiarrhythmic drug Sotalol and β-adrenoblocker Bisoprolol on the spectral parameters of heart rhythm variability in patients with Atrial Fibrillation. Methods. 167 patients with Atrial Fibrillation of both sexes aged 46 to 94 years were examined. The study included patients with the first diagnosed Atrial Fibrillation, and with persistent Atrial Fibrillation during of 6 months to 8 years. Arterial hypertension has diagnosed in all patients. Also, patients were diagnosed with coronary heart disease with a history of myocardial infarction and without myocardial infarction. Spectral analysis of heart rhythm variability was conducted in patients with Atrial Fibrillation. Therapy in patients was performed with the antiarrhythmic drug Sotalol (80−160 mg, orally) and Bisoprolol (2.5−5 mg, orally). Results. Spectral analysis of heart rhythm variability in patients Atrial Fibrillation using Sotalol showed that the proportion of VLF in patients with the first diagnosed Atrial Fibrillation is more than half of the spectrum, whereas in patients with persistent Atrial Fibrillation this parameter is 18%, the proportion of LF is higher in patients with persistent Atrial Fibrillation. The coefficient LF/HF in patients with persistent Arial Fibrillation is two times lower than in patients with the first diagnosed Atrial Fibrillation. Spectral analysis of heart rhythm variability in patients Atrial Fibrillation using Bisoprolol, it was shown that the proportion of LF in patients with the first diagnosed Atrial Fibrillation was 2 times lower, and the proportion of HF was twice higher than in patients with persistent Atrial Fibrillation. Conclusions. In this study, a spectral analysis of heart rate variability in patients with Atrial Fibrillation, who receive antiarrhythmic drug therapy with sotalol and bisoprolol, was carried out. It was found that humoral factors play a significant role in patients with the first diagnosed Atrial Fibrillation during sotalol therapy, the role of the vagus in this group of patients is minimal, while in patients with bisoprolol therapy the vagus has a dominant effect on the activity of the heart.

Pharmacotherapy for Atrial Fibrillation in Patients With Chronic Kidney Disease: Insights From ORBIT-AF.

BackgroundChronic kidney disease (CKD) is a common comorbidity in patients with atrial fibrillation. The presence of CKD complicates drug selection for stroke prevention and rhythm control.Methods and ResultsPatients enrolled in ORBIT AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) with baseline renal function and follow‐up data were included (N=9019). CKD was defined as an estimated creatinine clearance <60 mL/min. Patient characteristics were compared by CKD status, and Cox proportional hazards modeling was used to examine the association between oral anticoagulant (OAC) use and outcomes and antiarrhythmic drug use and outcomes stratified by CKD stages. At enrollment, 3490 (39%) patients had an estimated creatinine clearance <60 mL/min. Patients with CKD were older and had higher CHA 2 DS 2 VASc and Anticoagulant and Risk Factors in Atrial Fibrillation (ATRIA) scores. A rhythm control strategy was selected less frequently in patients with CKD, while OAC use was lower among Stage IV and V CKD patients. After adjustment, no significant interaction was noted for OAC and CKD on all‐cause mortality (P=0.5442) or cardiovascular death (P=0.1233), although a trend for increased major bleeding (P=0.0608) and stroke, systemic embolism or transient ischemic attack (P=0.0671) was observed. No interaction was noted for antiarrhythmic drug use and CKD status on all‐cause mortality (P=0.9706), or stroke, systemic embolism or transient ischemic attack (P=0.4218).ConclusionsPatients with atrial fibrillation and CKD are less likely to be treated with rhythm control. Patients with advanced CKD are less likely to receive OAC. Finally, outcomes with OAC in patients with advanced CKD may be materially different with higher rates of both bleeding and stroke.

Computational Modeling of Electrophysiology and Pharmacotherapy of Atrial Fibrillation: Recent Advances and Future Challenges.

The pathophysiology of atrial fibrillation (AF) is broad, with components related to the unique and diverse cellular electrophysiology of atrial myocytes, structural complexity, and heterogeneity of atrial tissue, and pronounced disease-associated remodeling of both cells and tissue. A major challenge for rational design of AF therapy, particularly pharmacotherapy, is integrating these multiscale characteristics to identify approaches that are both efficacious and independent of ventricular contraindications. Computational modeling has long been touted as a basis for achieving such integration in a rapid, economical, and scalable manner. However, computational pipelines for AF-specific drug screening are in their infancy, and while the field is progressing quite rapidly, major challenges remain before computational approaches can fill the role of workhorse in rational design of AF pharmacotherapies. In this review, we briefly detail the unique aspects of AF pathophysiology that determine requirements for compounds targeting AF rhythm control, with emphasis on delimiting mechanisms that promote AF triggers from those providing substrate or supporting reentry. We then describe modeling approaches that have been used to assess the outcomes of drugs acting on established AF targets, as well as on novel promising targets including the ultra-rapidly activating delayed rectifier potassium current, the acetylcholine-activated potassium current and the small conductance calcium-activated potassium channel. Finally, we describe how heterogeneity and variability are being incorporated into AF-specific models, and how these approaches are yielding novel insights into the basic physiology of disease, as well as aiding identification of the important molecular players in the complex AF etiology.

Differences and time trends in drug treatment of atrial fibrillation in men and women and doctors’ adherence to warfarin therapy recommendations

Little is known about prescription trends in atrial fibrillation (AF) in primary health care in Sweden. The aim was to study time trends in pharmacotherapy, in men and women with AF. We also aimed at studying doctors' adherence to CHADS2 for prescribing warfarin. CHADS2 assesses stroke risk by presence of known risk factors, i.e., congestive heart failure, hypertension, age >75 years, diabetes, previous stroke and transient ischemic attack. Data were obtained from primary health care records that contained individual clinical data. In total, 371,036 patients were included in the sample from 2002, and 424,329 patients were included in the sample from 2007. The study population consisted of individuals aged 45+ years who were diagnosed with AF in 2002 (1,330 men and 1,096 women) and 2007 (2,748 men and 2,234 women). The pharmacotherapies prescribed in 2002 and 2007 were analyzed separately in men and women. Logistic regression was used to calculate the association between the CHADS2 score and prescribed warfarin treatment. Selective beta-blockers, anti-coagulant therapy and lipid-lowering drugs were prescribed more frequently in 2007 than in 2002. In 2007, antithrombotic and RAS-blocking agents were prescribed more frequently to men, whereas beta-1 selective beta-blockers were prescribed more frequently to women. There was no consistent association between the CHADS2 score and prescribed warfarin treatment. Pharmacotherapy of AF has improved over time, though CHADS2 guidelines need to be implemented systematically in primary health care in Sweden to decrease the risk of stroke and improve quality of life in patients with AF.

ガイドラインから見たベプリジルの位置づけ

心房細動（AF）に対する包括的アプローチが求められるなか，本邦でもJ-RHYTHM，J-BAF試験などのエビデンスが集積され，それを受けた新しいガイドラインが示された．そこではまず抗血栓療法を重視し，孤立性発作性AFではNa+チャネル遮断薬によるリズム治療を推奨した．この点は基本的に海外のガイドラインと変わりないが，持続性AFや病的心に伴うAFに対する治療薬については海外でも混乱をきたしている．ドロネダロンが一時期，有力な選択肢となっていたが，その危険性が指摘され，心不全例においては急速にその支持を失いつつある．病的心に伴うAFに対しては，アミオダロン，ソタロール，ドフェチリドなどのK+チャネル遮断薬もリズム治療薬として推奨されているが，本邦ではK+チャネル遮断作用に加え，リモデリングを逆転させる作用などによって高い抗AF効果をもつベプリジルが，新たな選択肢として注目されている．しかしながら，K+チャネル遮断作用は心室筋にも影響を与え，QT延長を促進させるため，torsade de pointesなど致死性催不整脈作用をもたらすことがある．特に器質的心疾患例ではその危険性が増すことが知られており，細心の注意を払いながらその高い効果の発現を促す工夫が求められる．

Instructions and methods for clinical testing of drugs for the treatment of atrial fibrillation

Instructions and methods for clinical testing of drugs for the treatment of atrial fibrillation are the subject of this paper. Certain criteria must be considered to demonstrate the effectiveness and benefit/risk ratio of pharmacotherapy of atrial fibrillation for the planning and performance of clinical trials. These criteria include the various forms of atrial fibrillation, the corresponding definition of endpoints, the appropriate study design, randomization and blinding, and also the adequate dose, investigation methods, sample size determination, analysis, and early termination. Only the consideration of these criteria may allow an appropriate treatment decision.

Pharmacotherapy of Atrial Fibrillation: A Pathophysiological Perspective and Review

Atrial fibrillation (AF) is one of the most common arrhythmia encountered in clinical practice. Although AF is due to the structural and electrophysiological alterations in the atria, its sustainability is multifactorial, and the actual mechanisms are still not clear. Despite the recent advances in catheter ablation technology and techniques, pharmacotherapy still remains the first-line therapy for the management of AF. Current pharmacotherapy targets ion channel alterations that in fact represent only one aspect of the management of this complex arrhythmia. Successful pharmacological treatment of AF and restoration of sinus rhythm is limited and is in part due to its potential deleterious side effects. Newer agents having diverse mechanisms acting on the recently uncovered pathophysiological processes are on the horizon. These include atrial repolarization delaying agents, newer class III agents, Na(+)-Ca(2+) channel blockers, stretch receptor blockers, I(KACH) blockers, gap junction modifiers, upstream therapies, and agents targeting ischemia-induced AF. Gene- and cell-specific therapies including 'tailored nanopharmacy,' newer rate control medications with minimal side effects and the emergence of novel drugs targeting multiple areas of AF arrhythmogenesis in tandem with electrical therapy may be the future direction in the management of AF.

Recent advances in pharmacotherapy of atrial fibrillation

Atrial fibrillation (AF) is the most common sustained arrhythmia associated with increased morbidity and mortality. Efficacy and safety of currently employed antiarrhythmic drugs (AADs) continue to be less optimal in AF. Development of newer AADs has recently been made possible through a greater understanding of electro-pathophysiology of AF. Highly specific drugs acting on atria are currently being explored, although there is little data available on effectiveness of atrial specific agents in maintaining sinus rhythm. Combining AADs and non-AADs such as angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may increase effectiveness of AADs in patients with AF. Controlled clinical trials are required to precisely define the efficacy of single agents versus various combinations in maintaining sinus rhythm in patients with AF. This review describes some of the most promising therapeutic approaches that may overcome some of the limitations of drugs used at present for the management of AF.

Pharmacotherapy for atrial fibrillation in elderly hospitalized patients with comorbid congestive heart failure in australia: A retrospective study

Background: Despite the proven effectiveness of antiplatelet and anticoagulation treatment for atrial fibrillation (AF), their use has been suboptimal in practice, particularly in rural areas of Australia. Objective: The aim of this study was to describe medication use in the management of AF in elderly hospitalized patients with comorbid congestive heart failure (CHF). Methods: The hospital records of patients with a diagnosis of AF and CHF were reviewed in a rural Australian medical center. All the patients were hospitalized because of significant systolic ventricular dysfunction. The collected data included age, sex, weight, presenting symptoms of AF, and principle diagnosis on admission; medical history; and history of smoking and alcohol consumption. Electrocardiogram before hospital discharge was also retrieved from patient's medical records and was analyzed by the investigators. Cardiovascular and noncardiovascular drugs administered during the hospital stay and at discharge were also documented. Comparison of antiarrhythmic and anticoagulant drugs was made between patients who had AF while hospitalized and those who had a history of AF but were in sinus rhythm while hospitalized. When patients had ≥2 moderate risk factors (eg, age ≥75 years, hypertension, CHF, left ventricular ejection fraction ≤35%, diabetes mellitus) or ≥1 high risk factor (eg, previous stroke, transient ischemic attack or embolism, mitral valve stenosis, or prosthetic heart valve), they were defined as being eligible for anticoagulation treatment. Results: One hundred forty patients (74 men, 66 women; mean [SD] age, 77.1 [6.9] years; all were white) had a diagnosis of AF and were selected for the study. Of these, 92 patients (65.7%) (47 women, 45 men; mean [SD] age, 77.4 [9–2] years) had continuous AF and 48 patients (34.3%) (29 men, 19 women; mean [SD] age, 76.3 [12.4] years) had a history of AF but were in sinus rhythm at admission and discharge. The most commonly used antiarrhythmic drug was digoxin, which was prescribed significantly more frequently in the AF group than in the history of AF group (50 (54.3%] vs 14 [29.2%]; P < 0.01). Amiodarone was prescribed significantly less frequently in the continuous AF group than in the group with a history of AF (7 [7.6%] vs 19 [39−6%]; P < 0.01). There was no significant between-group difference in the use of β-blockers (26 [28.3%] vs 19 [39−6%]), verapamil/diltiazem (9 [9–8%] vs 3 [6.3%]), or Sotalol (2 [2.2%] vs 4 [8.3%]). The mean (SD) resting heart rate for the 140 study patients was 91 (27) bpm. The mean resting heart rate for the patients with AF was significantly higher at admission than at discharge (97 [28] vs 79 [19] bpm; P < 0.01). Of the 110 patients who were eligible for anticoagulation treatment, 64 (58.2%) were prescribed warfarin at discharge. Eligible patients not receiving oral warfarin were significantly older than those who did receive warfarin (79−7 [9−0] vs 75.8 [9.0] years; P = 0.02). Conclusions: In these elderly hospitalized Australian patients with AF and CHF, digoxin, β-blockers, and amiodarone were the most commonly used antiarrhythmic drugs. Anticoagulation treatment was prescribed in ~60% of these patients.

Rate versus Rhythm Control Pharmacotherapy for Atrial Fibrillation: Where are We in 2008?

Rate versus Rhythm Control Pharmacotherapy for Atrial Fibrillation: Where are We in 2008?

Pharmacotherapy of atrial fibrillation: an old option with new possibilities

Background: Atrial fibrillation is the most common sustained arrhythmia observed worldwide. Despite modern ablative treatment options, pharmacotherapy remains the first-line therapy in patients with atrial fibrillation. Objective: Based on recently published guidelines for the management of atrial fibrillation, the present paper reviews the current and emerging concepts of pharmacotherapy in atrial fibrillation. Methods: A MEDLINE search was conducted using the keyword ‘atrial fibrillation’ and ‘drug therapy’. The reviewed literature included clinical trials and published reviews as well as clinical guidelines. Results: The mainstay of atrial fibrillation therapy is the prevention of thromboembolic events. With growing knowledge of the pathophysiology of atrial fibrillation new drug targets have been identified that promise improved outcomes in atrial fibrillation management and this will allow individual drug treatment in the near future.

Atrial fibrillation pharmacotherapy after hospital discharge between 1995 and 2004: a shift towards beta-blockers

To study evolvement in pharmacotherapy of atrial fibrillation from 1995 to 2004. All Danish patients were discharged following first-time atrial fibrillation and their pharmacotherapy was identified by individual-level-linkage of nationwide registers of hospitalization and drug dispensing from pharmacies. A total of 108 791 patients survived 30 days after discharge and were included. In 1995-1996, 7.4% of the patients received beta-blockers, increasing to 44.3% in 2003-2004. The corresponding figures for amiodarone were 2.9 and 5.4%. In contrast, use of nondihydropyridine calcium-channel blockers, digoxin, sotalol, and class 1C antiarrhythmics decreased from 20.6, 63.9, 21.3, and 4.0% in 1995-1996 to 12.6, 43.8, 4.2, and 1.3% in 2003-2004, respectively. Notably, patients receiving anticoagulants increased from 29.8 to 43.5%. Multivariate logistic regression analysis revealed females to be associated with more use of digoxin, but less use of amiodarone and oral anticoagulants than males. Patients above 80 years received less pharmacotherapy, apart from digoxin treatment that was more commonly used in elderly. Pharmacotherapy of atrial fibrillation has changed towards increased beta-blocker use with a coincident decrease in the use of other rate-limiting drugs and sotalol. Treatment with amiodarone or class 1C antiarrhythmics remained very low. Oral anticoagulant therapy increased considerably, but women and elderly were apparently undertreated.

Mounting Evidence That Fibrosis Generates a Major Mechanism for Atrial Fibrillation

See related article, pages 839–847 It is widely known that atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, with the problem magnified by the clinical sequelae; eg, thromboembolic events. It is pertinent that the incidence of AF is expected to increase in the future,1 especially in aging patients. Thus, finding preventive measures for this arrhythmia has become an increasingly important goal. In addition to considering clinical risk factors, focusing on prevention necessitates knowledge of the associated pathophysiology of AF,2 which involves the initiation of AF and the wavefront dynamics that sustain it. In recent years considerable new information has appeared concerning AF mechanisms that occur in different regions of the atria in different cardiac states.3 This point is highlighted by the report of Tanaka et al4 in this issue of Circulation Research . These authors used high-resolution electrophysiological and microstructural techniques, along with computer model simulations, to study wavefront dynamics during acetylcholine (ACh)-induced AF in heart failure sheep hearts. The heart failure hearts had developed prominent fibrotic patches in the posterior left atrium near the pulmonary veins, whereas in the control (normal) hearts patches of fibrosis were smaller, diffusely distributed, and more centrally located with respect to the 4 pulmonary vein ostia. In the heart failure hearts, during AF variable wavefront breakthroughs to the endocardium occurred in the area of fibrotic patches adjacent to the pulmonary veins. The authors concluded that scroll waves within the posterior left atrial wall produced a microreentry source for the endocardial breakthroughs in the region of the larger collagen patches, thus providing the underlying mechanism of AF.4 A myriad of reports provide varied information about substrates and mechanisms of AF as a background for the study of Tanaka et al …

Pharmacotherapy for atrial fibrillation: is rhythm control achievable?

As the most common sustained cardiac arrhythmia, the health burden presented by atrial fibrillation (AF) continues to grow. One of the current dilemmas in managing AF lies in the decision of whether to pursue a rate or rhythm control strategy. Current antiarrhythmic drugs have many limitations in terms of efficacy and adverse effects, and the availability of better antiarrhythmic drugs that are effective and safe would probably improve outcomes in AF. Enthusiasm for pulmonary vein ablation procedures has been tempered by the relatively high frequency of recurrences of AF, which are often asymptomatic. Ablation also frequently converts symptomatic episodes to asymptomatic recurrences. Irrespective of whether a rate control or a rhythm control strategy is adopted in patients with persistent AF, appropriate antithrombotic therapy should be used.