The Optimal Anti-Coagulation for Enhanced-Risk Patients Post-Catheter Ablation for Atrial Fibrillation (OCEAN) trial.

BACKGROUND: The optimal long-term antithrombotic regimen for patients after successful catheter-based atrial fibrillation (AF) ablation is not well defined. Presently, practice variation exists, and the benefits of oral anticoagulation over antiplatelet therapy across the entire spectrum of stroke risk profile remain undefined in the postablation population. To date, there are no randomized trials to inform clinicians on this therapeutic question. OBJECTIVE: The objective was to assess whether rivaroxaban is superior to acetylsalicylic acid (ASA) in reducing the risk of clinically overt stroke, systemic embolism, or covert stroke among patients without apparent recurrent atrial arrhythmias for at least 1 year after their most recent AF ablation procedure. METHODS/DESIGN: A prospective, multicenter, open-label, randomized trial with blinded assessment of outcomes is under way (NCT02168829). Atrial fibrillation patients with at least 1 stroke risk factor (as defined by the CHA2DS2-VASc score) and without known atrial arrhythmia recurrences for at least 12 months after ablation are randomized to rivaroxaban 15 mg or ASA 75-160 mg daily. The primary outcome is a composite of clinically overt stroke, systemic embolism, and covert stroke based on brain magnetic resonance imaging. Key secondary outcomes include major bleeding outcomes, intracranial hemorrhage, transient ischemic attack, neuropsychological testing, quality of life, and an economic analysis. Subjects will be followed for 3 years. The estimated overall sample size is 1,572 subjects (786 per arm). DISCUSSION: The OCEAN trial is a multicenter randomized controlled trial evaluating 2 antithrombotic treatment strategies for patients with risk factors for stroke after apparently successful AF ablation. We hypothesize that rivaroxaban will reduce the occurrence of clinically overt stroke, systemic embolism, and covert stroke when compared with ASA alone.

Outcomes for Emergency Department Patients With Recent-Onset Atrial Fibrillation and Flutter Treated in Canadian Hospitals.

STUDY OBJECTIVE: Recent-onset atrial fibrillation and flutter are the most common arrhythmias managed in the emergency department (ED). We evaluate the management and 30-day outcomes for recent-onset atrial fibrillation and flutter patients in Canadian EDs, where cardioversion is commonly practiced. METHODS: We conducted a prospective cohort study in 6 academic hospital EDs and enrolled patients who had atrial fibrillation and flutter onset within 48 hours. Patients were followed for 30 days by health records review and telephone. Adverse events included death, stroke, acute coronary syndrome, heart failure, subsequent admission, or ED electrocardioversion. RESULTS: We enrolled 1,091 patients with mean age 63.9 years, atrial fibrillation 84.7%, atrial flutter 15.3%, hospital admission 9.0%, and converted to sinus rhythm 80.1%. Although 10.5% of recent-onset atrial fibrillation and flutter patients had adverse events within 30 days, there were no related deaths and 1 stroke (0.1%). Adjusted odds ratios for factors associated with adverse event were hours from onset (1.03/hour; 95% confidence interval [CI] 1.01 to 1.05), history of stroke or transient ischemic attack (2.09; 95% CI 1.01 to 4.36), and pulmonary congestion on chest radiograph (7.37; 95% CI 2.40 to 22.64). Patients who left the ED in sinus rhythm were much less likely to experience an adverse event (P<.001). CONCLUSION: Although most recent-onset atrial fibrillation and flutter patients were treated aggressively in the ED, there were few 30-day serious outcomes. Physicians underprescribed oral anticoagulants. Potential risk factors for adverse events include longer duration from arrhythmia onset, previous stroke or transient ischemic attack, pulmonary congestion on chest radiograph, and not being in sinus rhythm at discharge. An ED strategy of sinus rhythm restoration and discharge in most patients is effective and safe.

ECG Features Associated With Adverse Cardiovascular Outcomes in Patients With Atrial Fibrillation: A Combined AFFIRM and AF-CHF Analysis.

BACKGROUND: The association between standard parameters from a simple 12-lead ECG (i.e., QRS duration and PR, JT, and QT intervals) and adverse cardiovascular outcomes (cardiovascular mortality, all-cause mortality, arrhythmic mortality, and hospitalizations) in patients with a history of atrial fibrillation (AF) has not been previously studied. METHODS AND RESULTS: A pooled analysis of patient-level data was conducted on 5,436 patients, age 68.2 ± 8.3 years, 34.8% female, with a history of non-permanent AF randomized in AFFIRM and AF-CHF trials. The predictive value of ECG parameters was assessed in AF and sinus rhythm in multivariate Cox regression models. During a follow-up of 40.8 ± 16.3 months, QRS duration >120 milliseconds was independently associated with all-cause mortality (hazard ratio [HR] 1.46, 95% confidence interval [CI; 1.21-1.76] in AF, P < 0.001), cardiovascular mortality (HR 1.75, 95% CI (1.15-2.65) in sinus rhythm, P = 0.009; HR 1.56, 95% CI [1.27-1.93] in AF, P < 0.001), arrhythmic mortality (HR 1.90, 95% CI [1.09-3.32] in sinus, P = 0.024; HR 1.84, 95% CI [1.35-2.51] in AF, P < 0.001), any hospitalization (HR 1.15, 95% CI [1.02-1.29] in AF, P = 0.027), and cardiovascular hospitalization (HR 1.21, 95% CI [1.06-1.37] in AF; P = 0.004). Increased PR interval (>200 milliseconds) was independently associated with cardiovascular (HR 1.56, 95% CI [1.11-2.21], P = 0.010) and arrhythmic (HR 1.91, 95% CI [1.14-3.18], P = 0.004) mortality. The JT and QTc intervals were not predictive of mortality. CONCLUSIONS: Simple parameters from standard ECGs are significantly and independently associated with adverse cardiovascular outcomes in patients with a history of AF.

Blood Pressure and Atrial Fibrillation: A Combined AF-CHF and AFFIRM Analysis.

BACKGROUND: Hypertension is an established risk factor for new-onset atrial fibrillation (AF). However, the relationship between blood pressure and recurrent AF is less well understood. METHODS AND RESULTS: A pooled analysis of patient-level data from AFFIRM and AF-CHF trials was conducted on all 2,715 patients with paroxysmal or persistent AF, 68 ± 8 years, 66% male, randomized to rhythm control and followed for 40.6 ± 16.5 months. We assessed the impact of a baseline systolic blood pressure (SBP; <120 mmHg [N = 1,008], 120-140 mmHg [N = 930], >140 mmHg [N = 777]) on recurrent AF and proportion of time spent in AF. In patients with LVEF >40% (N = 1,719), SBP was not associated with recurrent AF in multivariate regression analyses (P = 0.752). In contrast, in patients with LVEF ≤40% (N = 996), the AF recurrence rate was higher in those with an SBP >140 mmHg compared to 120-140 mmHg (hazard ratio 1.47; 95% CI [1.12-1.93], P = 0.005). The rate of recurrent AF was similar in patients with SBP <120 mmHg compared to 120-140 mmHg (hazard ratio 1.15; 95% CI [0.92-1.43], P = 0.225). Consistently, the proportion of time spent in AF was not influenced by SBP in patients with LVEF >40% (P = 0.645). However, in patients with LVEF ≤40%, the adjusted mean proportion of time spent in AF was 17.2% if SBP was <120 mmHg, 15.4% for SBP 120-140 mmHg, and 24.0% for SBP >140 mmHg (P = 0.025). CONCLUSION: Systolic blood pressure is an important determinant of recurrent AF and overall AF burden in patients with left ventricular dysfunction (LVEF≤40%) but not in those with preserved ventricular function.

Efficacy and safety of vernakalant in patients with atrial flutter: a randomized, double-blind, placebo-controlled trial.

AIMS: Vernakalant is a novel, relatively atrial-selective antiarrhythmic agent for conversion of atrial fibrillation (AF) to sinus rhythm. This study examined the safety and efficacy of vernakalant in converting atrial flutter (AFL) to sinus rhythm. METHODS AND RESULTS: This was a phase 2/3, randomized, double-blind, placebo-controlled trial. Adults with AFL received either a 10 min infusion of 3.0 mg/kg vernakalant (n = 39) or placebo (n = 15). If AFL or AF persisted at the end of a 15 min observation period, a second 10 min infusion of 2.0 mg/kg vernakalant or placebo was administered. The primary efficacy outcome was the proportion of patients who had treatment-induced conversion of AFL to sinus rhythm for a minimum duration of 1 min within 90 min after the start of the first infusion. No patient in the placebo group met the primary outcome. Only one patient receiving vernakalant (1 of 39, 3%) converted to sinus rhythm. A reduced mean absolute ventricular response rate occurred within 50 min in patients receiving vernakalant (mean change from baseline -8.2 b.p.m.) vs. patients receiving placebo (-0.2 b.p.m.) (P = 0.037). A post-hoc analysis revealed that vernakalant increased AFL cycle length by an average of 55 ms, whereas the AFL cycle length was unchanged in the placebo group (P < 0.001). There was no occurrence of 1 : 1 atrio-ventricular conduction. Dysgeusia and sneezing were the most common treatment-related adverse events, consistent with previous reports. CONCLUSION: Vernakalant did not restore sinus rhythm in patients with AFL. Vernakalant modestly slowed AFL and ventricular response rates, and was well tolerated.

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.)

Temporal Trends in Population Rates of Incident Atrial Fibrillation and Atrial Flutter Hospitalizations, Stroke Risk, and Mortality Show Decline in Hospitalizations.

BACKGROUND: Hospitalization for nonvalvular atrial fibrillation (NVAF) is common and results in substantial cost burden. Current national data trends for the incidence, stroke risk profiles, and mortality of hospitalization for NVAF and atrial flutter (AFL) are sparse. METHODS: The Canadian Institute of Health Information Discharge Abstract Database was used to identify patients ≥ 20 years with incident NVAF/AFL (NVAF, ICD-9 code 427.3 or ICD-10 I48) in any diagnosis field from 2006 to 2015 in Canada, except Québec. National and provincial trends in rate over time (rate ratio, 95% confidence interval [CI]) were calculated for age-sex standardized hospitalizations. Trends in stroke risk profiles and in-hospital mortality rates adjusted for stroke risk factors were also calculated. RESULTS: A total of 578,947 patients were hospitalized with incident NVAF/AFL. The median age was 77 years (interquartile range: 68-84), 82% were ≥ 65 years, 54% were men, 54% had a CHADS2 ≥ 2, and 69% had a CHA2DS2-Vasc ≥ 3. The overall age- and sex-standardized rate of NVAF/AFL hospitalization was 315 per 100,000 population and declined by 2% per year (P < 0.001). There was an annual rate decline in NVAF/AFL hospitalizations in every province. The majority of hospitalized patients are at high risk of stroke, and this risk remained unchanged. The average adjusted in-hospital mortality was 8.80 per 100 patients 95% CI, 8.80-8.81 with a 2% annual decline in rate (P < 0.001). CONCLUSION: Between 2006 and 2015, we found national and provincial hospitalization rates for incident NVAF/AFL are declining. The majority of patients are at high risk for stroke. In-hospital mortality has declined but remains substantial.

Surveillance for Outcomes Selected as Atrial Fibrillation Quality Indicators in Canada: 10-Year Trends in Stroke, Major Bleeding, and Heart Failure.

BACKGROUND: Whether advances in identification and management of atrial fibrillation and atrial flutter (collectively, AF) have led to improved outcomes is unclear. We sought to study trends in clinical outcomes selected as quality indicators for nonvalvular AF in Canada. METHODS: We identified hospitalized patients with a first diagnosis of nonvalvular AF between April 2006 and March 2015, in all of Canada except Quebec. We assessed trends in 1-year incidence of stroke/systemic embolism (SSE), major bleeding, and initial heart failure (HF) hospitalization. RESULTS: The cohort included 466,476 patients. The median age was 77 years (interquartile range, 68-84 years), 46% were female, and 68% had a Congestive Heart Failure, Hypertension, Age (≥75 years), Diabetes, Stroke/Transient Ischemic Attack, Vascular Disease, Age (65-74 years), Sex (Female) (CHA2DS2-VASc) score > 3. Within 1 year of discharge, 3.5% were hospitalized for stroke or SSE, 1.6% for major bleeding, and 8.6% for new HF. Over the study period, the crude rate of SSE declined from 3.6% to 3.3% (P = 0.002), whereas the rates of hospitalization for new HF and for major bleeding did not significantly change. After adjustment for CHA2DS2-VASc score, the yearly rates of incident SSE (risk ratio, 0.99; 95% confidence interval [CI], 0.98-0.99; P = 0.002) and HF (risk ratio, 0.99; 95% CI, 0.99-1.00; P = 0.001) declined ≤ 1% absolute, whereas major bleeding remained unchanged (risk ratio, 1.00; 95% CI, 0.99-1.00; P = 0.28). CONCLUSIONS: Among hospitalized patients with nonvalvular AF in Canada, the rate of SSE and new HF decreased modestly over a 10-year period, with no significant change in major bleeding. Efforts to study process-based quality indicators, with increased focus on HF prevention, are needed.

CONTEXTE: On ne sait pas si les avancées en matière de détection et de prise en charge de la fibrillation auriculaire et du flutter auriculaire (collectivement appelés « FA ¼ ci-après) ont permis d'améliorer les résultats pour les patients. Nous avons donc étudié les tendances à l'égard de résultats cliniques particuliers pris comme indicateurs de qualité relatifs à la FA non valvulaire au Canada. MÉTHODOLOGIE: Nous avons recensé les patients hospitalisés au Canada (sauf au Québec) entre avril 2006 et mars 2015 en raison d'une FA non valvulaire nouvellement diagnostiquée. Nous avons évalué les tendances quant à la survenue d'un accident vasculaire cérébral ou d'une embolie systémique (AVC/ES), d'une hémorragie majeure et d'une première hospitalisation pour insuffisance cardiaque. RÉSULTATS: La cohorte comprenait 466 476 patients, dont l'âge médian était de 77 ans (intervalle interquartile : 68 à 84 ans); 46 % des patients étaient des femmes, et 68 % avaient un score CHA2DS2-VASc ( C ongestive Heart Failure [insuffisance cardiaque congestive], hypertension, âge [≥ 75 ans], diabète, S troke/Transient Ischemic Attack [AVC/accident ischémique transitoire] ­ maladie vasculaire, âge [65-74 ans], sexe [femmes]) supérieur à 3. Dans l'année suivant la sortie de l'hôpital, 3,5 % des patients ont été hospitalisés en raison d'un AVC ou d'un AVC/ES, 1,6 %, en raison d'une hémorragie majeure et 8,6 %, en raison d'une nouvelle insuffisance cardiaque. Au cours de la période étudiée, le taux brut d'AVC/ES est passé de 3,6 % à 3,3 % (p = 0,002), tandis que les taux d'hospitalisation en raison d'une nouvelle insuffisance cardiaque ou d'une hémorragie majeure n'ont pas changé de manière significative. Après correction pour tenir compte du score CHA2DS2-VASc, les taux annuels de survenue d'un AVC/ES (rapport des risques de 0,99; intervalle de confiance [IC] à 95 % : de 0,98 à 0,99; p = 0,002) et d'une insuffisance cardiaque (rapport des risques de 0,99; IC à 95 % : de 0,99 à 1,00; p = 0,001) ont diminué de ≤ 1 % en valeur absolue, tandis que le taux de survenue d'une hémorragie majeure n'a pas changé (rapport des risques : 1,00; IC à 95 % : de 0,99 à 1,00; p = 0,28). CONCLUSIONS: Parmi les patients hospitalisés au Canada en raison d'une FA non valvulaire, les taux d'AVC/ES et de nouvelle insuffisance cardiaque ont affiché une réduction modeste sur une période de 10 ans, tandis que le taux d'hémorragie majeure n'a pas changé de manière significative. D'autres études évaluant les indicateurs de qualité fondés sur les procédés, notamment en matière de prévention de l'insuffisance cardiaque, s'imposent.

Prevention of atrial fibrillation: report from a national heart, lung, and blood institute workshop.

The National Heart, Lung, and Blood Institute convened an expert panel April 28 to 29, 2008, to identify gaps and recommend research strategies to prevent atrial fibrillation (AF). The panel reviewed the existing basic scientific, epidemiological, and clinical literature about AF and identified opportunities to advance AF prevention research. After discussion, the panel proposed the following recommendations: (1) enhance understanding of the epidemiology of AF in the population by systematically and longitudinally investigating symptomatic and asymptomatic AF in cohort studies; (2) improve detection of AF by evaluating the ability of existing and emerging methods and technologies to detect AF; (3) improve noninvasive modalities for identifying key components of cardiovascular remodeling that promote AF, including genetic, fibrotic, autonomic, structural, and electrical remodeling markers; (4) develop additional animal models reflective of the pathophysiology of human AF; (5) conduct secondary analyses of already-completed clinical trials to enhance knowledge of potentially effective methods to prevent AF and routinely include AF as an outcome in ongoing and future cardiovascular studies; and (6) conduct clinical studies focused on secondary prevention of AF recurrence, which would inform future primary prevention investigations.

Incidence of newly detected atrial arrhythmias via implantable devices in patients with a history of thromboembolic events.

BACKGROUND AND PURPOSE: Evidence of atrial tachycardia/atrial fibrillation (AT/AF) is often sought in patients with ischemic stroke or transient ischemic attack. We studied patients with previous thromboembolic events (TE) who were implanted with devices capable of continuous arrhythmia monitoring to comprehensively quantify the incidence and duration of newly detected AT/AF. METHODS: This study represents a subgroup analysis of the TRENDS trial, which included patients with clinical indications for pacemakers or defibrillators and >or=1 stroke risk factors (heart failure, hypertension, age 65 or older, diabetes, or previous TE). A history of AF was not required. All implanted devices were capable of continuously monitoring the cumulative time spent in AT/AF each day. This analysis focuses primarily on the incidence and duration of newly detected AT/AF (defined as >or=5 minutes of AT/AF on any day) in patients with previous TE, no documented history of AF, and no warfarin or antiarrhythmic drug use. RESULTS: A total of 319 patients had a history of TE and >or=1 day of device data. Patients with a documented history of AF (n=80), warfarin use (n=56), or antiarrhythmic drug use (n=20) were excluded from analysis. Of the remaining 163 patients, newly detected AT/AF was identified via the device in 45 patients (28%) over a mean follow-up of 1.1+/-0.7 years. AT/AF recurred infrequently, with only 12 patients experiencing AT/AF on >10% of follow-up days. CONCLUSIONS: Newly detected episodes of AT/AF were found via continuous monitoring in 28% of patients with previous TE. Most episodes would not have been detected by standard intermittent monitoring techniques.

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.

Vernakalant hydrochloride for rapid conversion of atrial fibrillation: a phase 3, randomized, placebo-controlled trial.

BACKGROUND: The present study assessed the efficacy and safety of vernakalant hydrochloride (RSD1235), a novel compound, for the conversion of atrial fibrillation (AF). METHODS AND RESULTS: Patients were randomized in a 2:1 ratio to receive vernakalant or placebo and were stratified by AF duration of 3 hours to 7 days (short duration) and 8 to 45 days (long duration). A first infusion of placebo or vernakalant (3 mg/kg) was given for 10 minutes, followed by a second infusion of placebo or vernakalant (2 mg/kg) 15 minutes later if AF was not terminated. The primary end point was conversion of AF to sinus rhythm for at least 1 minute within 90 minutes of the start of drug infusion in the short-duration AF group. A total of 336 patients were randomized and received treatment (short duration, n=220; long duration, n=116). Of the 145 vernakalant patients, 75 (51.7%) in the short-duration AF group converted to sinus rhythm (median time, 11 minutes) compared with 3 of the 75 placebo patients (4.0%; P<0.001). Overall, in the short- and long-duration AF groups, 83 of the 221 vernakalant patients (37.6%) experienced termination of AF compared with 3 of the 115 placebo patients (2.6%; P<0.001). Transient dysgeusia and sneezing were the most common side effects in vernakalant-treated patients. Four vernakalant-related serious adverse events (hypotension [2 events], complete atrioventricular block, and cardiogenic shock) occurred in 3 patients. CONCLUSIONS: Vernakalant demonstrated rapid conversion of short-duration AF and was well tolerated.

Beneficial effects of statin therapy for prevention of atrial fibrillation following DDDR pacemaker implantation.

AIMS: Data suggest that atrial pacing, statins, angiotensin-converting enzyme-inhibitors and angiotensin receptor blocking drugs prevent atrial tachycardia/atrial fibrillation (AT/AF) in some patients. The clinical predictors of at/af recurrence following dual-chamber pacemaker insertion were examined in 185 consecutive patients with paroxysmal AF. METHODS AND RESULTS: Predictors of AT/AF recurrence were evaluated in this observational cohort study. The time to first AT/AF recurrence and AT/AF burden (h/day) was retrieved at each follow-up visit by interrogating the pacemaker. AT/AF recurred following pacemaker implantation in 157 (85%) patients. At 1 year of follow-up, patients without recurrence were more likely to be on statin therapy (54%) when compared with patients without statin therapy (25%, chi = 12.31, P = 0.0004). Statin therapy was the only significant predictor of AT/AF recurrence in a multivariate logistic regression model (adjusted odds ratio 0.33, 95% confidence interval 0.14-0.74, P = 0.007). AT/AF burden was significantly lower in the group on statin therapy (median 0.10 h/day) when compared with the group not on statin therapy (median 0.39 h/day, P = 0.0059). CONCLUSION: AT/AF recurs frequently following pacemaker implantation in patients with sinus node disease. The progression to permanent AF remains low over time. Statin therapy was significantly associated with AT/AF suppression.

An Update on the Development and Feasibility Assessment of Canadian Quality Indicators for Atrial Fibrillation and Atrial Flutter.

BACKGROUND: In 2010, the Canadian Cardiovascular Society Atrial Fibrillation/Atrial Flutter (AF/AFL) quality indicator (QI) working group was established to develop QIs and assess feasibility of measurement. After extensive review, 3 priority QIs were selected. However, none were measurable at a national level. METHODS: The working group reconvened in 2017 to review the relevance of previously proposed QIs, identify opportunities to develop new QIs, and propose an initial strategy for measuring and reporting. RESULTS: Two additional priority QIs were added to the previous 3: proportion of patients with nonvalvular (NV) AF/AFL sorted by stroke risk stratum and annual rate of hospitalization for a new heart failure diagnosis. An environmental scan was undertaken to determine the potential of existing databases to provide national and provincial estimates. On the basis of validated administrative codes, the Canadian Institute for Health Information discharge abstract database can be used for inpatients. In collaboration with the Canadian Primary Care Sentinel Surveillance Network, 2 of the 5 QIs can be assessed in outpatients (patients with NVAF/AFL sorted by stroke risk stratum and high risk for stroke NVAF/AFL receiving oral anticoagulation). Stroke prevention therapy can be further measured in selected provinces with linked databases including prescriptions. CONCLUSIONS: This first step could provide a better initial understanding of the quality of AF/AFL care in Canada, but important gaps in the meaningful measurement of QIs remain. The AF/AFL QI working group has limited capacity to make progress without national level leadership and the resources to support data aggregation, data analysis, and pan-Canadian reporting.

CONTEXTE: En 2010, le groupe de travail des indicateurs de qualité (IQ) de la Société canadienne de cardiologie sur la fibrillation auriculaire (FA) et le flutter auriculaire (FLA) a été mis sur pied pour élaborer des IQ et évaluer la faisabilité d'utiliser ces IQ comme outils de mesure. Après un examen approfondi, trois IQ prioritaires ont été sélectionnés, mais aucun n'a pu être mesuré à l'échelle nationale. MÉTHODOLOGIE: Le groupe de travail s'est réuni à nouveau en 2017 afin d'examiner la pertinence des IQ proposés au départ, de recenser des occasions d'élaborer de nouveau IQ et de proposer une stratégie initiale de mesure et de production de rapports à cet égard. RÉSULTATS: Deux IQ prioritaires supplémentaires ont été ajoutés aux trois premiers : la proportion de patients atteints de FA non valvulaire (FANV) ou de FLA ayant fait l'objet d'un tri selon la strate de risque d'AVC et le taux annuel d'hospitalisations attribuables à un nouveau diagnostic d'insuffisance cardiaque. Une analyse de l'environnement a été réalisée afin de déterminer si les bases de données existantes pouvaient fournir des estimations nationales et provinciales. Dans le cas de patients hospitalisés, on peut utiliser la Base de données sur les congés des patients de l'Institut canadien d'information sur la santé en se servant de codes administratifs validés. Dans le cas de patients non hospitalisés (patients atteints de FANV/FLA, triés par strate de risque, exposés à un risque élevé d'AVC en raison d'une FANV ou d'un FLA et recevant une anticoagulation orale), on peut mesurer deux des cinq IQ, en collaboration avec le Réseau canadien de surveillance sentinelle en soins primaires. Le traitement préventif de l'AVC peut continuer à faire l'objet de mesures dans certaines provinces grâce aux bases de données interreliées, comme les bases de données sur les ordonnances. CONCLUSIONS: Cette première étape a permis d'obtenir une meilleure compréhension initiale de la qualité de la prise en charge de la FA et du FLA au Canada, mais d'importantes lacunes restent à combler pour rendre pertinente la mesure des IQ. Le groupe de travail des IQ sur de la FA et le FLA n'a pas toutes les capacités requises pour réaliser des progrès en l'absence de leadership national et de ressources permettant de soutenir le regroupement et l'analyse des données, ainsi que la production de rapports à l'échelle pancanadienne.

Monitoring the ACTIVE-W trial: some issues in monitoring a noninferiority trial.

Noninferiority comparisons of new to current therapies and the use of composite outcomes represent significant advances in the design of clinical trials. They increasingly characterize trials of new cardiovascular agents, posing new challenges to Data Safety Monitoring Boards (DSMB) and principal investigators. The ACTIVE-W study was a noninferiority comparison of the combination of clopidogrel and acetylsalicylic acid versus oral anticoagulant among patients with atrial fibrillation. When unexpectedly high rates of stroke and then of the composite outcome of stroke, non-central nervous system systemic embolism, myocardial infarction, and vascular death emerged, the DSMB modified its monitoring plan and conducted its first formal interim analysis much earlier than had been planned in the DSMB charter. The study was terminated when only 27% of the anticipated outcomes had occurred. This paper discusses issues of appropriate stopping guidelines for noninferiority trials and the early emergence of significant harm in relation to one component (stroke) of a composite outcome. Conditional power was not determined concurrently with the HRs during the monitoring of ACTIVE-W; however, the members of the DSMB now believe that such calculations should be considered as useful adjuncts to the calculation of HRs and could lead to earlier termination of noninferiority trials whose interim results suggest futility, without the need for convincing proof of harm.

Therapeutic considerations in applying rate control therapy for atrial fibrillation.

The therapeutic strategy of heart rate control for atrial fibrillation (AF) is undergoing a renaissance since several recent randomized trials demonstrated clear advantages over the rhythm control for many patients. Heart rate control for AF is hampered, however, by a dearth of information relating target heart rates to physiological measures or clinical outcomes. In this review, the rather sparse rationale behind the data elements for heart rate control - resting heart rate, activity heart rate, and regularity of the heart rate, is outlined. Beat-to-beat stroke volume is probably a key variable for calibrating heart rate targets. Presently it seems reasonable to propose targets for resting and activity heart rates but not for regularity. It also seems plausible but remains unproven that there should be a range (upper and lower) of heart rate targets rather than a simple upper limit. Nevertheless, it remains to be demonstrated through randomized clinical trials how to apply various heart rate control targets in patients with AF and whether complexity offers any advantage over simplicity.

Clinical criteria for predicting benefit of ICD/PM in post myocardial infarction patients: an AVID and CAST analysis.

BACKGROUND: Three clinical factors from the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial-heart failure, left ventricular dysfunction and certain historical features defined a subgroup in which an implantable cardioverter defibrillator (ICD/PM) has a mortality advantage over amiodarone. METHODS: These three factors were jointly evaluated in the AVID cohort with ischemic heart disease (IHD) and the results applied in placebo-treated post-infarction patients in the cardiac arrhythmia suppression trial (CAST). RESULTS: Similar predictive power was noted in AVID patients with IHD. In CAST the factors defined three groups; one group (5.8%), corresponding to AVID patients that had high risk and benefited from an ICD/PM and another group (17.2%) corresponding to patients in AVID where the risk was moderate and ICD/PM and amiodarone had equal efficacy, demonstrated a two-fold higher risk of sudden arrhythmic than non-arrhythmic death and hence would be expected to benefit from antiarrhythmia therapy. The third group, corresponding to AVID patients with low risk of arrhythmia, demonstrated similar and low risks of sudden arrhythmic and non-arrhythmic death. Thus this group (77%) is unlikely to benefit from indiscriminate antiarrhythmia therapy. Onset of risk of death in CAST patients was offset from randomization by 3 to 6 months. CONCLUSIONS: Readily available clinical criteria identify a small group likely to benefit from an ICD/PM after recent myocardial infarction (MI) and the remainder unlikely to benefit from nonselective ICD/PM therapy. Additional risk stratification should focus on the latter patients and be timed to allow ICD/PM implantation between 2 and 6 months after MI.