Review of Stereotactic Arrhythmia Radioablation Therapy for Cardiac Tachydysrhythmias.

Cardiac tachyarrhythmias are a major cause of morbidity and mortality. Treatments for these tachyarrhythmias include antiarrhythmic drugs, catheter ablation, surgical ablation, cardiac implantable electronic devices, and cardiac transplantation. Each of these treatment approaches is effective in some patients but there is considerable room for improvement, particularly with respect to the most common of the tachydysrhythmias, atrial fibrillation, and the most dangerous of the tachydysrhythmias, ventricular tachycardia (VT) or ventricular fibrillation. Noninvasive stereotactic ablative radiation therapy is emerging as an effective treatment for refractory tachyarrhythmias. Animal models have shown successful ablation of arrhythmogenic myocardial substrates with minimal short-term complications. Studies of stereotactic radioablation involving patients with refractory VT have shown a reduction in VT recurrence and promising early safety data. In this review, we provide the background for the application of stereotactic arrhythmia radioablation therapy along with promising results from early applications of the technology.

Les tachyarythmies cardiaques sont une cause importante de morbidité et de mortalité. Les traitements employés comprennent des antiarythmiques, l'ablation par cathéter, l'ablation par chirurgie, l'implantation de dispositifs cardiaques électroniques et la transplantation cardiaque. Toutes ces démarches thérapeutiques sont efficaces dans certains cas, mais les traitements peuvent encore être largement améliorés, en particulier en ce qui concerne la fibrillation auriculaire, qui est la tachyarythmie la plus fréquente, et la tachycardie ventriculaire (TV, aussi appelée fibrillation ventriculaire), qui est la tachyarythmie la plus dangereuse. La radiochirurgie stéréotaxique non invasive se démarque de plus en plus comme traitement efficace des tachyarythmies réfractaires. Des substrats myocardiques arythmogènes ont pu être réséqués avec succès sur des modèles animaux, l'intervention n'ayant entraîné que des complications minimales de courte durée. Dans le cadre d'études menées auprès de patients présentant une TV réfractaire, la radiochirurgie stéréotaxique a permis de réduire le risque de récurrence de la TV, et les premières données sur l'innocuité du traitement sont encourageantes. Dans notre revue, nous précisons le cadre d'application de la radiochirurgie stéréotaxique visant à réséquer le tissu responsable de l'arythmie, et nous présentons les résultats prometteurs des premières applications de la technologie à cette fin.

The 2020 Canadian Cardiovascular Society/Canadian Heart Rhythm Society Comprehensive Guidelines for the Management of Atrial Fibrillation.

The Canadian Cardiovascular Society (CCS) atrial fibrillation (AF) guidelines program was developed to aid clinicians in the management of these complex patients, as well as to provide direction to policy makers and health care systems regarding related issues. The most recent comprehensive CCS AF guidelines update was published in 2010. Since then, periodic updates were published dealing with rapidly changing areas. However, since 2010 a large number of developments had accumulated in a wide range of areas, motivating the committee to complete a thorough guideline review. The 2020 iteration of the CCS AF guidelines represents a comprehensive renewal that integrates, updates, and replaces the past decade of guidelines, recommendations, and practical tips. It is intended to be used by practicing clinicians across all disciplines who care for patients with AF. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system was used to evaluate recommendation strength and the quality of evidence. Areas of focus include: AF classification and definitions, epidemiology, pathophysiology, clinical evaluation, screening and opportunistic AF detection, detection and management of modifiable risk factors, integrated approach to AF management, stroke prevention, arrhythmia management, sex differences, and AF in special populations. Extensive use is made of tables and figures to synthesize important material and present key concepts. This document should be an important aid for knowledge translation and a tool to help improve clinical management of this important and challenging arrhythmia.

Periprocedural Anticoagulation for Cardioversion of Acute Onset Atrial Fibrillation and Flutter: Evidence Base for Current Guidelines.

The practice of electrical or pharmacological cardioversion (CV) to restore sinus rhythm in patents with symptomatic atrial fibrillation (AF) or atrial flutter has been a part of clinical practice for more than 100 years. For almost as long as CV has been performed, it has been recognized that the act of restoring sinus rhythm is associated with an increased risk of stroke and systemic embolism, and that oral anticoagulant (OAC) therapy can be used to prevent peri-CV thromboembolism. Although it has been widely accepted that OAC therapy is necessary to prevent thromboembolism in patients with chronic AF/atrial flutter who undergo CV, previous clinical practice recommendations have suggested that OAC therapy may be omitted in patients at low risk of stroke. However, in recent years, evidence has emerged from several sources challenging these historical conventions. In 2018 the Canadian Cardiovascular Society AF guidelines updated the previous recommendations regarding CV of acute onset AF, and the use of peri-CV anticoagulation. In this article we present an extensive review of the evidence informing the previous recommendations, as well as the novel evidence that informed the change in recommendations. In addition, the current Canadian Cardiovascular Society AF guideline recommendations are examined within the context of contemporary international major society guidelines.

Effect of Catheter Ablation vs Antiarrhythmic Drug Therapy on Mortality, Stroke, Bleeding, and Cardiac Arrest Among Patients With Atrial Fibrillation: The CABANA Randomized Clinical Trial.

Importance: Catheter ablation is effective in restoring sinus rhythm in atrial fibrillation (AF), but its effects on long-term mortality and stroke risk are uncertain. Objective: To determine whether catheter ablation is more effective than conventional medical therapy for improving outcomes in AF. Design, Setting, and Participants: The Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation trial is an investigator-initiated, open-label, multicenter, randomized trial involving 126 centers in 10 countries. A total of 2204 symptomatic patients with AF aged 65 years and older or younger than 65 years with 1 or more risk factors for stroke were enrolled from November 2009 to April 2016, with follow-up through December 31, 2017. Interventions: The catheter ablation group (n = 1108) underwent pulmonary vein isolation, with additional ablative procedures at the discretion of site investigators. The drug therapy group (n = 1096) received standard rhythm and/or rate control drugs guided by contemporaneous guidelines. Main Outcomes and Measures: The primary end point was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. Among 13 prespecified secondary end points, 3 are included in this report: all-cause mortality; total mortality or cardiovascular hospitalization; and AF recurrence. Results: Of the 2204 patients randomized (median age, 68 years; 37.2% female; 42.9% had paroxysmal AF and 57.1% had persistent AF), 89.3% completed the trial. Of the patients assigned to catheter ablation, 1006 (90.8%) underwent the procedure. Of the patients assigned to drug therapy, 301 (27.5%) ultimately received catheter ablation. In the intention-to-treat analysis, over a median follow-up of 48.5 months, the primary end point occurred in 8.0% (n = 89) of patients in the ablation group vs 9.2% (n = 101) of patients in the drug therapy group (hazard ratio [HR], 0.86 [95% CI, 0.65-1.15]; P = .30). Among the secondary end points, outcomes in the ablation group vs the drug therapy group, respectively, were 5.2% vs 6.1% for all-cause mortality (HR, 0.85 [95% CI, 0.60-1.21]; P = .38), 51.7% vs 58.1% for death or cardiovascular hospitalization (HR, 0.83 [95% CI, 0.74-0.93]; P = .001), and 49.9% vs 69.5% for AF recurrence (HR, 0.52 [95% CI, 0.45-0.60]; P < .001). Conclusions and Relevance: Among patients with AF, the strategy of catheter ablation, compared with medical therapy, did not significantly reduce the primary composite end point of death, disabling stroke, serious bleeding, or cardiac arrest. However, the estimated treatment effect of catheter ablation was affected by lower-than-expected event rates and treatment crossovers, which should be considered in interpreting the results of the trial. Trial Registration: ClinicalTrials.gov Identifier: NCT00911508.

Association Between Patient and Physician Sex and Physician-Estimated Stroke and Bleeding Risks in Atrial Fibrillation.

BACKGROUND: Physicians treating nonvalvular atrial fibrillation (AF) assess stroke and bleeding risks when deciding on anticoagulation. The agreement between empirical and physician-estimated risks is unclear. Furthermore, the association between patient and physician sex and anticoagulation decision-making is uncertain. METHODS: We pooled data from 2 national primary care physician chart audit databases of patients with AF (Facilitating Review and Education to Optimize Stroke Prevention in Atrial Fibrillation and Coordinated National Network to Engage Physicians in the Care and Treatment of Patients with Atrial Fibrillation Chart Audit) with a combined 1035 physicians (133 female, 902 male) and 10,927 patients (4567 female and 6360 male). RESULTS: Male physicians underestimated stroke risk in female patients and overestimated risk in male patients. Female physicians estimated stroke risk well in female patients but underestimated the risk in male patients. Risk of bleeding was underestimated in all. Despite differences in risk assessment by physician and patient sex, > 90% of patients received anticoagulation across all subgroups. There was modest agreement between physician estimated and calculated (ie, CHADS2 score) stroke risk: Kappa scores were 0.41 (0.35-0.47) for female physicians and 0.34 (0.32-0.36) for male physicians. CONCLUSIONS: Our study is the first to examine the association between patient and physician sex influences and stroke and bleeding risk estimation in AF. Although there were differences in agreement between physician estimated stroke risk and calculated CHADS2 scores, these differences were small and unlikely to affect clinical practice; further, despite any perceived differences in the accuracy of risk assessment by sex, most patients received anticoagulation.

2018 Focused Update of the Canadian Cardiovascular Society Guidelines for the Management of Atrial Fibrillation.

The Canadian Cardiovascular Society (CCS) Atrial Fibrillation Guidelines Committee provides periodic reviews of new data to produce focused updates that address clinically important advances in atrial fibrillation (AF) management. This 2018 Focused Update addresses: (1) anticoagulation in the context of cardioversion of AF; (2) the management of antithrombotic therapy for patients with AF in the context of coronary artery disease; (3) investigation and management of subclinical AF; (4) the use of antidotes for the reversal of non-vitamin K antagonist oral anticoagulants; (5) acute pharmacological cardioversion of AF; (6) catheter ablation for AF, including patients with concomitant AF and heart failure; and (7) an integrated approach to the patient with AF and modifiable cardiovascular risk factors. The recommendations were developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) standards. Individual studies and literature were reviewed for quality and bias; the literature review process and evidence tables are included as Supplementary Material and are available on the CCS Web site. Details of the updated recommendations are presented, along with their background and rationale. This document is linked to an updated summary of all CCS AF guidelines recommendations, from 2010 to the present 2018 Focused Update, which is provided in the Supplementary Material.

Ranolazine in High-Risk Patients With Implanted Cardioverter-Defibrillators: The RAID Trial.

BACKGROUND: Ventricular tachycardia (VT) and ventricular fibrillation (VF) remain a challenging problem in patients with implantable cardioverter-defibrillators (ICDs). OBJECTIVES: This study aimed to determine whether ranolazine administration decreases the likelihood of VT, VF, or death in patients with an ICD. METHODS: This was double-blind, placebo-controlled clinical trial in which high-risk ICD patients with ischemic or nonischemic cardiomyopathy were randomized to 1,000 mg ranolazine twice a day or placebo. The primary endpoint was VT or VF requiring appropriate ICD therapy or death, whichever occurred first. Pre-specified secondary endpoints included ICD shock for VT, VF, or death and recurrent VT or VF requiring ICD therapy. RESULTS: Among 1,012 ICD patients (510 randomized to ranolazine and 502 to placebo) the mean age was 64 ± 10 years and 18% were women. During 28 ± 16 months of follow-up there were 372 (37%) patients with primary endpoint, 270 (27%) patients with VT or VF, and 148 (15%) deaths. The blinded study drug was discontinued in 199 (39.6%) patients receiving placebo and in 253 (49.6%) patients receiving ranolazine (p = 0.001). The hazard ratio for ranolazine versus placebo was 0.84 (95% confidence interval: 0.67 to 1.05; p = 0.117) for VT, VF, or death. In a pre-specified secondary analysis, patients randomized to ranolazine had a marginally significant lower risk of ICD therapies for recurrent VT or VF (hazard ratio: 0.70; 95% confidence interval: 0.51 to 0.96; p = 0.028). There were no other significant treatment effects in other pre-specified secondary analyses, which included individual components of the primary endpoint, inappropriate shocks, cardiac hospitalizations, and quality of life. CONCLUSIONS: In high-risk ICD patients, treatment with ranolazine did not significantly reduce the incidence of the first VT or VF, or death. However, the study was underpowered to detect a difference in the primary endpoint. In prespecified secondary endpoint analyses, ranolazine administration was associated with a significant reduction in recurrent VT or VF requiring ICD therapy without evidence for increased mortality. (Ranolazine Implantable Cardioverter-Defibrillator Trial [RAID]; NCT01215253).

Use of Evidence-Based Therapy for Cardiovascular Risk Factors in Canadian Outpatients With Atrial Fibrillation: From the Facilitating Review and Education to Optimize Stroke Prevention in Atrial Fibrillation (FREEDOM AF) and Co-ordinated National Network to Engage Physicians in the Care and Treatment of Patients With Atrial Fibrillation (CONNECT AF).

Using data collected from 2 national atrial fibrillation (AF) primary care physician chart audits (Facilitating Review and Education to Optimize Stroke Prevention in Atrial Fibrillation [FREEDOM AF] and Co-ordinated National Network to Engage Physicians in the Care and Treatment of Patients With Atrial Fibrillation [CONNECT AF]), we evaluated the frequency of, and factors associated with, the use of cardiovascular (CV) evidence-based therapies in Canadian AF outpatients with at least 1 CV risk factor or co-morbidity. Of the 11,264 patients enrolled, 9,495 (84.3%) were eligible for one or more CV evidence-based therapies. The proportions of patients with AF receiving all eligible guideline-recommended therapies were 40.8% of patients with coronary artery disease, 48.9% of patients with diabetes mellitus, 40.2% of patients with heart failure, 96.7% of patients with hypertension, and 55.1% of patients with peripheral arterial disease. Factors that were independently associated with nonreceipt of all indicated evidence-based therapies included sinus rhythm rather than AF at baseline and liver disease. In conclusion, although most Canadian outpatients with AF have CV risk factors or co-morbidities, a substantial portion of these patients did not receive all guideline-recommended therapies. These findings suggest that there is an opportunity to improve the quality of care for patients with AF in Canada.

2016 Focused Update of the Canadian Cardiovascular Society Guidelines for the Management of Atrial Fibrillation.

The Canadian Cardiovascular Society (CCS) Atrial Fibrillation (AF) Guidelines Committee provides periodic reviews of new data to produce focused updates that address clinically important advances in AF management. This 2016 Focused Update deals with: (1) the management of antithrombotic therapy for AF patients in the context of the various clinical presentations of coronary artery disease; (2) real-life data with non-vitamin K antagonist oral anticoagulants; (3) the use of antidotes for the reversal of non-vitamin K antagonist oral anticoagulants; (4) digoxin as a rate control agent; (5) perioperative anticoagulation management; and (6) AF surgical therapy including the prevention and treatment of AF after cardiac surgery. The recommendations were developed with the same methodology used for the initial 2010 guidelines and the 2012 and 2014 Focused Updates. Using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) standards, individual studies and literature were reviewed for quality and bias; the literature review process and evidence tables are included in the Supplementary Material, and on the CCS Web site. The section on concomitant AF and coronary artery disease was developed in collaboration with the CCS Antiplatelet Guidelines Committee. Details of the updated recommendations are presented, along with their background and rationale. This document is linked to an updated summary of all CCS AF Guidelines recommendations, from 2010 to the present 2016 Focused Update.

The Risk Stratification and Stroke Prevention Therapy Care Gap in Canadian Atrial Fibrillation Patients.

BACKGROUND: Canadian atrial fibrillation (AF) guidelines recommend that all AF patients be risk stratified with respect to stroke and bleeding, and that most should receive antithrombotic therapy. METHODS: As part of the Canadian Facilitating Review and Education to Optimize Stroke Prevention in Atrial Fibrillation (FREEDOM AF) chart audit, data were collected on 4670 patients ≥ 18 years old without significant valvular heart disease from the primary care practices of 474 physicians (February to September, 2011). RESULTS: Physicians did not provide an estimate of stroke and bleeding risk in 15% and 25% of patients, respectively. When risks were provided, they were on the basis of a predictive stroke and bleeding risk index in only 50% and 26% of patients, respectively. There were over- and underestimation of stroke and bleeding risk in a large proportion of patients. Antithrombotic therapy included warfarin (90%); 24% of patients had a time in the therapeutic range (TTR) < 50%, 9% between 50% and 60%, 11% between 60% and 70%, and 56% had a TTR ≥ 70%. CONCLUSIONS: In a large Canadian AF population, primary care physicians did not provide a stroke or bleeding risk in a substantial proportion of their AF patients. When estimates were provided, they were on the basis of a predictive stroke and bleeding risk index in less than half of the patients. Furthermore, there was under- and overestimation of stroke and bleeding risk in a substantial proportion of patients. As many as 1 in 3 patients receiving warfarin have their TTR < 60%. These findings suggest an opportunity to enhance knowledge translation to primary care physicians.

The 2014 Atrial Fibrillation Guidelines Companion: A Practical Approach to the Use of the Canadian Cardiovascular Society Guidelines.

The Canadian Cardiovascular Society (CCS) Atrial Fibrillation Guidelines Program has generated a comprehensive series of documents regarding the management of atrial fibrillation (AF) between 2010 and 2014. The guidelines provide evidence-based consensus management recommendations in a broad range of areas. These guidelines have proven useful in informing clinical practice, but often lack detail in specifications related to practical application, particularly for areas in which the evidence base is limited or conflicting. Based on feedback from the community, the CCS Atrial Fibrillation Guidelines Committee has identified a number of areas that require clarification to address commonly asked practical questions related to guidelines application. In the present article a number of such questions are presented and suggestions about how they can be answered are suggested. Among the issues considered are: (1) What duration of AF is clinically significant? (2) How are the risk factors in the CCS Algorithm for selecting anticoagulation therapy derived and defined? (3) How is valvular heart disease defined and how do different forms of valve disease affect the choice of anticoagulant therapy for AF patients? (4) How should we quantify renal dysfunction and how does it affect therapeutic choices? The response to these questions and the underlying logic are provided, along with an indication of future research needed where no specific approach can presently be recommended based on the literature.

Sudden cardiac death.

Sudden death accounts for 300,000-400,000 deaths annually in the United States. Most sudden deaths are cardiac, and most sudden cardiac deaths are related to arrhythmias secondary to structural heart disease or primary electrical abnormalities of the heart. The most common structural disease leading to sudden death is ischemic heart disease. Nonischemic cardiomyopathy and other structural abnormalities such as arrhythmogenic ventricular dysplasia and hypertrophic cardiomyopathy may also be causative. Patients without structural disease have a primary electrical abnormality, such as long-QT syndrome or Brugada syndrome. Severe left ventricular systolic dysfunction is the main marker for sudden death in patients with ischemic or nonischemic cardiomyopathy. In other conditions, other markers for structural heart disease and electrical abnormalities need to be considered. It is seen that ß-blocker therapy is associated with a reduction in sudden cardiac death across a broad range of disorders. Nevertheless, the implantable cardioverter defibrillator remains the most effective treatment strategy in selected patients.

2014 focused update of the Canadian Cardiovascular Society Guidelines for the management of atrial fibrillation.

Atrial fibrillation (AF) is an extremely common clinical problem with an important population morbidity and mortality burden. The management of AF is complex and fraught with many uncertain and contentious issues, which are being addressed by extensive ongoing basic and clinical research. The Canadian Cardiovascular Society AF Guidelines Committee produced an extensive set of evidence-based AF management guidelines in 2010 and updated them in the areas of anticoagulation and rate/rhythm control in 2012. In late 2013, the committee judged that sufficient new information regarding AF management had become available since 2012 to warrant an update to the Canadian Cardiovascular Society AF Guidelines. After extensive evaluation of the new evidence, the committee has updated the guidelines for: (1) stroke prevention principles; (2) anticoagulation of AF patients with chronic kidney disease; (3) detection of AF in patients with stroke; (4) investigation and management of subclinical AF; (5) left atrial appendage closure in stroke prevention; (6) emergency department management of AF; (7) periprocedural anticoagulation management; and (8) rate and rhythm control including catheter ablation. This report presents the details of the updated recommendations, along with their background and rationale. In addition, a complete set of presently applicable recommendations, those that have been updated and those that remain in force from previous guideline versions, is provided in the Supplementary Material.