Value of pacemaker atrial diagnostic data in patients with paroxysmal atrial fibrillation: an opportunity to improve rates of warfarin utilization

Atrial diagnostic data within implantable devices provide an opportunity to assess the frequency and quantity of atrial fibrillation (AF) episodes (AF burden) and its impact on appropriate warfarin anticoagulation. Cardiologists were given clinical scenarios to review with different types of pacemaker diagnostic data in an elderly patient with risk factors for stroke. AF specific data was associated with increased warfarin utilization, but only at intermediate rates. Potential reasons and clinical implications are discussed.     

房颤患者华法林抗凝治疗177例

目的回顾性分析心房颤动（房颤）患者的抗凝治疗与卒中情况。 方法调查2015年8月1日至2017年6月30日苏北人民医院住院房颤患者301例的病例资料,记录性别、年龄、主要诊断、合并疾病情况、CHA2DS2-VASc评分、HAS-BLED评分、INR值、华法林剂量、新型口服抗凝剂（NOAC）、阿司匹林使用情况、血栓栓塞事件、出血事件情况,分析抗凝治疗的规范性及其与临床后果的关系。 结果住院房颤患者平均年龄（72±11）岁,房颤类型以非瓣膜型房颤为主,占93.7%（282/301）,58.8%的房颤患者采用口服华法林抗凝治疗,4%接受NOAC抗凝治疗。华法林抗凝治疗组缺血性卒中发生率显著低于未抗凝治疗组差异具有统计学意义（13.0% vs 20.5%,P=0.025）。瓣膜型和非瓣膜型房颤患者华法林抗凝治疗后INR达标（INR 2.0~3.0）的比率分别为15.8%和7.1%。 结论为了达到更好的房颤患者卒中预防效果,需进一步加强华法林抗凝治疗的教育和监测。     

The increasing need for anticoagulant therapy to prevent stroke in patients with atrial fibrillation

Ischemic stroke, a major complication of atrial fibrillation (AF), is believed to result from atrial thrombus formation caused by ineffective atrial contraction. Oral anticoagulant therapy effectively reduces the risk of ischemic stroke in patients with AF; this therapy is recommended for patients with any frequency or duration of AF and other risk factors for stroke, such as increased age (>75 years), hypertension, prior stroke, left ventricular dysfunction, diabetes, or heart failure. Recently published data comparing rate-control and rhythm-control strategies in AF emphasized the importance of maintaining an international normalized ratio higher than 2.0 during warfarin therapy and the need for continuing anticoagulant therapy to prevent stroke in high-risk patients, even if the strategy is rhythm control. Hemorrhagic complications can be minimized by stringent control of the international normalized ratio (particularly in elderly patients) and appropriate therapy for comorbidities such as hypertension, gastric ulcer, and early-stage cancers. Undertreatment of patients with AF is a continuing problem, particularly in the elderly population. Patients perceived as likely to be noncompliant, such as the functionally impaired, are less likely to receive warfarin therapy. However, stroke prevention with anticoagulants is cost-effective and improves quality of life, despite the challenges of maintaining appropriate anticoagulation with monitoring and warfarin dose titration. New medications in development with more predictable dosing and fewer drug-drug interactions may reduce the complexities of achieving optimal anticoagulation and increase the practicality of long-term anticoagulant therapy for patients with AF at risk of stroke.     

ATRIAL FIBRILLATION,THROMBOEMBOLISM AND ANTITHROMBOTIC THERAPY

Atrial fibrillation is the commonest sustained disorder of cardiac rhythm and is associated with increased risk of stroke and thromboembolic events. Warfarin (dose-adjusted to a target INR of 2.0-3.0) has been well established to reduce this risk of stroke by 68% (95% CI 50-79%), while aspirin provides a risk reduction of 21% (95% CI 0-38%). Nevertheless, warfarin confers a risk of bleeding and the inconvenience of regular monitoring checks, while aspirin seems effective only for certain low-risk subgroups. Thus there have been strenuous efforts to improve thromboprophylaxis in atrial fibrillation, by using low-intensity anticoagulation regimens, combination antiplatelet therapy and refinement of risk stratification strategies. Attempts at using a low-intensity, fixed-dose warfarin regimen have, however, been disappointing. For now, a strategy of risk stratification should be adopted to identify highest risk patients with atrial fibrillation who would benefit from anticoagulation.     

Pharmacological and Non-pharmacological Treatments for Stroke Prevention in Patients with Atrial Fibrillation

Atrial fibrillation (AF) is associated with significant risk of stroke and other thromboembolic events, which can be effectively prevented using oral anticoagulation (OAC) with either vitamin K antagonists (VKAs) or non-VKA oral anticoagulants (NOACs) dabigatran, rivaroxaban, apixaban, or edoxaban. Until recently, VKAs were the only available means for OAC treatment. NOACs had similar efficacy and were safer than or as safe as warfarin with respect to reduced rates of hemorrhagic stroke or other intracranial bleeding in the respective pivotal randomized clinical trials (RCTs) of stroke prevention in non-valvular AF patients. Increasing “real-world” evidence on NOACs broadly confirms the results of the RCTs. However, individual patient characteristics including renal function, age, or prior bleeding should be taken into account when choosing the OAC with best risk–benefit profile. In patients ineligible for OACs, surgical or interventional stroke prevention strategies should be considered. In patients undergoing cardiac surgery for other reasons, the left atrial appendage excision, ligation, or amputation may be the best option. Importantly, residual stumps or insufficient ligation may result in even higher stroke risk than without intervention. Percutaneous left atrial appendage occlusion, although requiring minimally invasive access, failed to demonstrate reduced ischemic stroke events compared to warfarin. In this review article, we summarize current treatment options and discuss the strengths and major limitations of the therapies for stroke risk reduction in patients with AF.     

Ximelagatran: a new antithrombotic option in atrial fibrillation

Treatment strategies in patients with atrial fibrillation typically involve pharmacologic or interventional invasive therapies to suppress the rhythm, control ventricular contraction rates, or prevent thromboembolic complications. Current therapies used for rhythm conversion in atrial fibrillation may have undesirable risks or side effects that limit this approach. Lifelong anticoagulation may be necessary to prevent the formation of thrombus in the left atrial chamber that can travel into the cerebral circulation to cause a stroke. Currently, warfarin is the most commonly prescribed anticoagulant for this purpose. Unfortunately, many patients with atrial fibrillation may not receive warfarin because of the difficulties in dosing and maintaining desirable target goals. The oral direct thrombin inhibitor ximelagatran has several pharmacologic properties that provide a unique and potentially desirable treatment option. Clinical studies have demonstrated that ximelagatran, administered in twice-daily doses of 36 mg, is non-inferior to warfarin for thromboprophylaxis against stroke or systemic embolism in atrial fibrillation. The pharmacology of ximelagatran and clinical trials with its use in atrial fibrillation is reviewed.     

Patterns of use of antithrombotic therapy and quality of anticoagulation among patients with non-valvular atrial fibrillation in clinical practice

We conducted a retrospective cohort study of thromboprophylaxis rates and the quality of anticoagulation control among patients with atrial fibrillation (AF) using a large, geographically diverse database of electronic medical records. The study population consisted of 13,709 AF patients treated in US outpatient physician practices. Approximately two-thirds were prescribed warfarin alone or in combination with another drug. Older patients, males, and those with congestive heart failure (CHF) or prior stroke were more likely to receive antithrombotic therapy. Among 6454 patients treated with warfarin who had at least two valid prothrombin time/international normalised ratio test results, approximately half of study days were spent in target range. Female sex, CHF and residence in the Northeast were associated with more time out of range. Our study confirms that, in routine medical practice, warfarin is not prescribed for substantial numbers of eligible patients, and anticoagulation control with warfarin is suboptimal for many of those at risk for thromboembolism.     

Nonchannel drug targets in atrial fibrillation

Atrial fibrillation (AF) is the most common clinical arrhythmia and one of the most important factors for ischemic stroke. In general, AF is treated with "channel-blocking drugs" to restore sinus rhythm and warfarin is recommended in the majority of patients to prevent atrial thrombus formation and thromboembolic events. In the recent years, a tremendous amount has been learned about the pathophysiology and molecular biology of AF. Thus, pharmacologic interference with specific signal transduction pathways with "non-channel-blocking drugs" appears promising as a novel antiarrhythmic approach to maintain sinus rhythm and to prevent atrial clot formation. Therefore, this review will highlight some novel "nonchannel drug targets" for AF therapy.     

ATRIAL FIBRILLATION IN A GENERAL HOSPITAL: HOW WELL ARE WE DOING?

Atrial fibrillation (AF) is an important risk factor for ischaemic stroke, and anticoagulation is now indicated in many patients, particularly those with congestive cardiac failure, hypertension, a history of transient ischaemic attacks or embolic stroke. In a retrospective study (and audit), we examined 280 cases of AF (acute, paroxysmal non-sustained and chronic sustained) admitted to a general hospital in the UK. The commonest underlying medical condition was ischaemic heart disease (57%), while the commonest presenting feature was congestive cardiac failure (60%). Pharmacological cardioversion was preferred against electrical cardioversion for reverting to sinus rhythm. Fifty-six patients (20%) received warfarin, 55 patients (20%) were on aspirin, and the remaining 169 (60%) received neither warfarin nor aspirin. More awareness is needed among physicians managing AF particularly in relation to anticoagulation.     

Personalizing oral anticoagulant treatment in patients with atrial fibrillation

For decades, warfarin has remained the standard oral anticoagulation for stroke prevention in atrial fibrillation (AF). Three novel oral anticoagulants (NOACs) have been recently approved for stroke prevention in non-valvular AF: dabigatran, rivaroxaban and apixaban. Better pharmacological and clinical profiles make these newcomers a preferable alternative over warfarin. Current AF guidelines do not endorse NOACs over warfarin, or one NOAC over another. Indeed, choice of the anticoagulation regimen should be personalized based on the relative efficacy and safety of different agents across subgroups stratified by thrombotic and bleeding risk, as well as on other clinical factors, including anticoagulation control on warfarin, drug interactions, compliance and need for coagulation monitoring. This review appraises i) the randomized evidence on approved NOACs versus warfarin in AF across subgroups stratified by risk factors of stroke and bleeding and by the anticoagulation level reached on warfarin; and ii) clinical factors impacting on the anticoagulation regimen selection.     

Management of Recent-onset Sustained Atrial Fibrillation: Pharmacologic and Nonpharmacologic Strategies

Purpose

Recent studies have highlighted significant variations in the management of recent-onset sustained atrial fibrillation (AF). We aim to provide a succinct and clear management algorithm for physicians treating patients with recent-onset sustained AF.

Methods

We performed a comprehensive search of the literature on the management of recent-onset sustained AF with focus on studies reporting cardioversion of AF, antiarrhythmic agents, and anticoagulation. We also reviewed recent practice guidelines on AF management.

Findings

This review provides a guide on a tailored management approach of patients with recent-onset sustained AF. After initial detailed clinical assessment, optimal rate and rhythm control options can be provided, depending on hemodynamic stability, duration of AF episode, and AF stroke risk. Issues surrounding electrical and pharmacologic cardioversion are discussed in detail. We emphasize the importance of thromboembolic risk assessment and appropriate anticoagulation surrounding the point of cardioversion. Last, we highlighted the need for appropriate specialized follow-up care after acute AF management.

Implications

Despite the highly heterogeneous clinical presentations, management of recent-onset sustained AF must include stroke risk assessment, appropriate anticoagulation, and follow-up care in all patients beyond optimum rate and rhythm control strategies.     

Paradoxical undersensing at a high sensitivity in dual chamber pacemakers

In view of the evolving indications for device therapy in atrial arrhythmia the accurate detection of high rate atrial events is a necessity. In a sheep model of atrial fibrillation (AF) we observed a contradictory behavior of the Thera DR pacemaker. The pacemakers were programmed to deliver burst pacing on detection of sinus rhythm (SR). Paradoxically, progressively more inappropriate bursts were delivered during AF, at a higher sensitivity. This implied that the pacemaker interpreted AF as SR. We assessed the atrial detection of the Thera DR, Diamond, Saphir, and Marathon pacemakers during AF, in a sheep model and in vitro using a waveform generator. By counting the annotated atrial-sensed events reported by the pacemaker we charted the behavior of the pacemakers at different sensitivities. At a higher sensitivity both the Thera DR and the Diamond paradoxically reported fewer atrial events during AF. This behavior led to inappropriate mode switching and incorrect diagnostic data collection. It could be reproduced in vitro. The Marathon did not show this paradoxical undersensing in vivo or in vitro. This paradoxical undersensing at a high sensitivity is dependent on the amplitude of the input signal and could not be explained by an overlap of programmable timing parameters. It is caused by ringing of the atrial sensing amplifier. At high atrial rates and a high sensitivity the ringing of the repetitive atrial signal input results in blanking of the atrial amplifier. This observation may be relevant in the device management of patients with paroxysmal AF.     

Left atrial appendage occlusion for stroke prevention in patients with atrial fibrillation

The most severe consequence of atrial fibrillation (AF) is a cardioembolic stroke. The incidence of cardioembolic stroke increases significantly in patients with AF. Although warfarin has been the mainstay of the prevention of cardioembolic stroke, there are several limitations to the use of warfarin that hinder its effectiveness. This article provides the historical development of devices that exclude the left atrial appendage, their effectiveness and potential patient selection, as an alternative to warfarin and the novel oral anticoagulation therapy for the prevention of cardioembolic stroke in patients with AF.     

Atrial Fibrillation and Embolic Complications in Paced Patients

Atrial fibrillation (AF) and thromboembolism are discussed to he complications of the WI mode. We reinvestigated the spontaneous ECG and the anamnesis of 246 pacemaker patients with the indications second and third degree atrioventricular block (AV block, n = III), sick sinus syndrome (SSS, n - 101) and other indications (n = 34), all had shown sinus rhythm at implantation. The mean implantation time was 63 ± 45 months (203 VVI and 43 dual chamber pacemkers). The results: (1) Atrial fibrillation was found in 63 patients (26%). Only one of them had a DDD pacemaker inserted, the implantation time of dual chamber devices being shorter, however, (2) The incidence of AF in patients with SSS (37%) was significantly higher (P < 0.01) than in patients with AV block (19%). (3) Three patients suffered from strokes or transitory ischemic attacks in the follow-up, only one of them had AF at control. Conclusions: Our results confirm that VVI stimulation favors AF long-term which is most likely due to irritation of the atrial rhythm by retrograde conduction. In our patients the incidence of thromboembolic complications was not higher in the group of patients with AF. However, from this study in surviving patients, we cannot exclude that we Jost some patients due to severe stroke.     

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.     

Novel antithrombotic agents for atrial fibrillation

Atrial fibrillation (AF) is the most common cardiac arrhythmia. It is estimated that 1 in 4 individuals aged 40 years or above will develop at least 1 episode of AF during their lifetime. Stroke is a leading cause of serious, long-term disability and death, and a major socioeconomic burden in developed countries. The major risk factor for thromboembolic stroke is AF. Oral antithrombotic treatment for AF patients has been limited to vitamin K antagonists for more than 60 years. Treatment with warfarin can reduce, but fails to abolish thromboembolic stroke associated with AF. Despite anticoagulation, patients with AF are at increased stroke risk. Furthermore, warfarin has important limitations namely, the limited time in therapeutic range, the need for INR monitoring, risk of major bleeding including stroke, and drug interactions. Recently there have been very exciting and important new advances in thromboprophylaxis for AF. Novel oral agents have been developed and evaluated clinically. These include direct thrombin inhibitors (dabigatran etexilate), oral selective factor Xa inhibitors (rivaroxaban, apixaban and edoxaban) and PAR-1 inhibitors (vorapaxar and atopaxar). Some of the new drugs have demonstrated promising results in the clinical studies, they are convenient in use and do not require monitoring. The downsides are lack of antidotes or specific blood assays to monitor the anticoagulant effect. This review evaluates traditional and novel approaches to thromboprophylaxis in patients with AF.     

Anticoagulation for stroke prevention in elderly patients with atrial fibrillation,including those with falls and/or early-stage dementia: A single-center,retrospective, observational study

Background: Anticoagulation for stroke prevention is underused in elderly patients with nonvalvular atrial fibrillation (AF). Those with falls and/or early dementia may be at particular risk for stroke and hemorrhage.Objective: The aim of this study was to determine the prescribing patterns, risks, and benefits of anticoagulation with warfarin or acetylsalicylic acid (ASA) in elderly patients with AF at risk for stroke and hemorrhage, including those with falls and/or dementia.Methods: In this single-center, retrospective, observational study, data from patients aged ≥65 years with chronic nonvalvular AF treated at an urban academic geriatrics practice over a 1-year period were included. Eligible patients were receiving noninvasive management of AF with warfarin or ASA. Data were assessed to determine the prevalences of stroke, hemorrhage, falls, and the possible effects of anticoagulation with dementia. Outcomes events at 12 months, including time-in-therapeutic range (TTR), stroke, hemorrhage, and death, were determined. The stroke risk in each patient was estimated using the CHADS₂ (congestive heart failure, hypertension, age ≥75 years, diabetes, history of stroke or transient ischemic attack) score, and the risk for hemorrhage was estimated using the Outpatient Bleeding Risk Index.Results: A total of 112 patients (mean age, 82 years) were identified; 106 were included in the present analysis (80 women, 26 men); 6 were not receiving antithrombotic therapy and thus were excluded from the analysis. Warfarin was prescribed in 85% (90 patients); ASA, 15% (16). International normalized ratio testing was done frequently, with a median interval of 13.7 days between tests (92% within 28 days). No association was found between an improved TTR and the number of tests per unit of time or the number of patients per clinician. The distributions of both the CHADS₂ and Outpatient Bleeding Risk Index scores were not significantly different between the warfarin and ASA groups. The proportions of patients treated with warfarin were not significantly different between the groups with a high risk for hemorrhage and the groups at lower risk. At 12 months in the 90 patients initially treated with warfarin, the rate of stroke was 2% (2 patients); major hemorrhage, 6% (5); and death, 20% (18). Mortality was greater in patients with falls (45% [5/11]) and/or dementia (47% [8/17]) compared with those without either falls or dementia (12% [8/65]).Conclusions: In this well-monitored geriatric population with chronic AF, including patients with falls and/or dementia, a high percentage were prescribed warfarin (85%), with low rates of stroke, hemorrhage, and death at 12 months despite a low TTR. Patients with falls and/or dementia had a high mortality rate (~45%).     

Atrial fibrillation and stroke

Atrial fibrillation (AF) is the most common cardiac arrhythmia. The prevalence of AF is 0.4% in the general population and increases with age up to 6-8% in octogenarians. In Switzerland, approximately 68,000 persons are in atrial fibrillation, and in the EU countries 3.5 millions. Atrial fibrillation disturbs synchronous mechanical atrial activity and impairs the haemodynamics. This can give rise to thrombus formation, mostly in the left atrial appendage, and embolism to the systemic circulation. Clinical manifestations are most often neurological such as transient ischaemic attacks or ischaemic strokes, on average 5% per year. Of all strokes, one in every six occurs in patients with AF. Antiarrhythmic therapy is useful to improve cardiac rate and function in AF. However, to reduce first or recurrent emboli, antithrombotic therapy is of paramount importance. Adjusted-dose warfarin reduces first or recurrent strokes by about 60%. When patients with non-valvular AF are anticoagulated, the odds against ischaemic stroke and intracranial bleeding favour an INR between 2.0 and 3.0. Acetylsalicylic acid is less efficacious than warfarin in AF patients, reducing the risk of stroke by about 20%. Therefore, anticoagulation is the current treatment modality in AF patients at high or intermediate risk, i.e. patients with history of transient ischaemic attack or stroke, those aged > 65 years, those with a history of hypertension, diabetes, heart failure or structural heart disease, valvular disease or significant systolic dysfunction. Antiplatelet agents should be used only for young (< 65 years) AF patients at low risk.