Arrhythmias in Female Patients: Incidence, Presentation and Management.

There is a growing appreciation for differences in epidemiology, treatment, and outcomes of cardiovascular conditions by sex. Historically, cardiovascular clinical trials have under-represented females, but findings have nonetheless been applied to clinical care in a sex-agnostic manner. Thus, much of the collective knowledge about sex-specific cardiovascular outcomes result from post hoc and secondary analyses. In some cases, these investigations have revealed important sex-based differences with implications for optimizing care for female patients with arrhythmias. This review explores the available evidence related to cardiac arrhythmia care among females, with emphasis on areas in which important sex differences are known or suggested. Considerations related to improving female enrollment in clinical trials as a way to establish more robust clinical evidence for the treatment of females are discussed. Areas of remaining evidence gaps are provided, and recommendations for areas of future research and specific action items are suggested. The overarching goal is to improve appreciation for sex-based differences in cardiac arrhythmia care as 1 component of a comprehensive plan to optimize arrhythmia care for all patients.

Atrial Fibrillation and Dementia: A Report From the AF-SCREEN International Collaboration.

Growing evidence suggests a consistent association between atrial fibrillation (AF) and cognitive impairment and dementia that is independent of clinical stroke. This report from the AF-SCREEN International Collaboration summarizes the evidence linking AF to cognitive impairment and dementia. It provides guidance on the investigation and management of dementia in patients with AF on the basis of best available evidence. The document also addresses suspected pathophysiologic mechanisms and identifies knowledge gaps for future research. Whereas AF and dementia share numerous risk factors, the association appears to be independent of these variables. Nevertheless, the evidence remains inconclusive regarding a direct causal effect. Several pathophysiologic mechanisms have been proposed, some of which are potentially amenable to early intervention, including cerebral microinfarction, AF-related cerebral hypoperfusion, inflammation, microhemorrhage, brain atrophy, and systemic atherosclerotic vascular disease. The mitigating role of oral anticoagulation in specific subgroups (eg, low stroke risk, short duration or silent AF, after successful AF ablation, or atrial cardiopathy) and the effect of rhythm versus rate control strategies remain unknown. Likewise, screening for AF (in cognitively normal or cognitively impaired patients) and screening for cognitive impairment in patients with AF are debated. The pathophysiology of dementia and therapeutic strategies to reduce cognitive impairment warrant further investigation in individuals with AF. Cognition should be evaluated in future AF studies and integrated with patient-specific outcome priorities and patient preferences. Further large-scale prospective studies and randomized trials are needed to establish whether AF is a risk factor for cognitive impairment, to investigate strategies to prevent dementia, and to determine whether screening for unknown AF followed by targeted therapy might prevent or reduce cognitive impairment and dementia.

The Seventh Prevention of Syncope Trial (POST VII)-A randomized clinical trial of atomoxetine for the prevention of vasovagal syncope: Rationale and study design.

BACKGROUND: Vasovagal syncope (VVS) is common, recurs, and is associated with markedly reduced quality of life, anxiety, and frequent injuries. The few pharmacological therapies for VVS proven to have a moderate benefit in reducing recurrences are limited to patients without coexisting conditions such as hypertension or heart failure. Although there is some data to suggest Atomoxetine, a norepinephrine reuptake transport inhibitor (NET), may be a promising treatment option, an adequately powered randomized placebo-controlled trial is needed. STUDY DESIGN: POST VII is a multicenter, randomized, double-blind, placebo-controlled, crossover study that will randomize 180 patients with VVS and at least 2 syncopal spells in the preceding year to a target daily dose of atomoxetine 80 mg daily or to a matching placebo, with an observation period of 6 months in each phase and with a 1-week washout period between phases. The primary end point will be the proportion of patients with at least one syncope recurrence in each arm analyzed with an intention-to-treat approach. The secondary end points include total syncope burden, quality of life, cost, and cost-effectiveness. POWER CALCULATIONS: Assuming a 33% relative risk reduction in syncope recurrence with atomoxetine, and a dropout rate of 16%, the enrollment of 180 patients will give an 85% power of reaching a positive conclusion about atomoxetine, with P = .05. CONCLUSIONS: This will be the first adequately powered trial to determine whether atomoxetine is effective in preventing VVS. If proven effective, atomoxetine might become the first-line pharmacological treatment for recurrent VVS.

Atomoxetine for suppression of vasovagal syncope.

OBJECTIVE: Vasovagal syncope (VVS) is a common clinical condition with few effective medical therapies. The study aimed to evaluate the effectiveness of atomoxetine in suppressing syncope in patients with recurrent VVS. METHODS: This was a retrospective, open-label, observational case series of 12 patients taking atomoxetine for suppression of recurrent vasovagal syncope. We compared syncope frequency in the 1 year before atomoxetine and while subjects were taking atomoxetine. We used novel applications of the Poisson distribution to describe the results as a collection of n = 1 studies. RESULTS: There were 12 subjects, eight female, with a mean age 47 ± 22 years and a mean Calgary Syncope Symptom Score of 2 (diagnostic of vasovagal syncope). The patients received a mean dose of atomoxetine of 66 ± 16 mg (1.06 ± 0.21 mg/kg). The mean follow-up period was 1.21 ± 1.01 years. While taking atomoxetine, 11/12 patients appeared to improve and 7/12 had no syncope in follow-up (p = 0.0046). The annualized syncope frequency decreased from a median 5.5 (IQR 4, 6.75) syncope per year to 0 (IQR 0, 0.88) syncope per year (p = 0.002, Wilcoxon rank-sum test). According to the Poisson distribution, 7/12 subjects significantly improved with p values of < 0.0001 to 0.0235, 3/12 did not faint but had too brief follow-up times to detect significance, and 2/12 did not improve significantly. CONCLUSIONS: In this case series, atomoxetine was a promising oral agent for the prevention of vasovagal syncope. The Poisson distribution permits individual patient-level assessment of improvement and detects insufficient follow-up despite apparent improvement.

Kidney function monitoring and trajectories in patients with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) and chronic kidney disease (CKD) frequently co-exist. The frequency of kidney monitoring and range of kidney function in patients with AF in clinical practice are uncertain. METHODS: All adult Albertans with AF between 2008 and 2017 were identified using ICD-9 and -10 codes 427.3 and I48. Kidney Disease Improving Global Outcomes (KDIGO) risk categories were defined using eGFR by the Chronic Kidney Disease Epidemiology Collaborative equation and albuminuria results within 6 months of eGFR measurement. eGFR trajectories were compared from baseline to maximum value within the following year. RESULTS: Among 105,946 patients with AF, 16.0% were KDIGO category G1 (eGFR ≥ 90), 49.0% G2 (60-89.9), 19.8% G3a (45-59.9), 11.4% G3b (30-44.9), and G4 3.8% (15-29.9). Albuminuria was normal/mild 83.4%, moderate 11.7%, and severe 4.9%. Kidney monitoring was more common among people with lower eGFR and worse albuminuria, from approximately twice annually for G1-2/A1-2 to 8 times annually in stage G4A3. Approximately 60-80% of patients received guideline-recommended monitoring, consistent across KDIGO stages. With lower baseline eGFR, annual change in eGFR decreased while the relative proportion of patients who worsened compared to improved increased: for baseline eGFR 60-89.9, 16.7% worsened vs 6.7% improved, but for eGFR 30-44.9, 8.8% worsened but only 1.0% improved. CONCLUSION: The frequency of kidney function monitoring in patients with AF increased with worsening KDIGO risk category and adhered to KDIGO guidelines in approximately three quarters of patients. A minority of patients had moderate to severe eGFR impairment, of whom most remained stable over 1 year.

Sex Differences in the Management of Oral Anticoagulation and Outcomes for Emergency Department Presentation of Incident Atrial Fibrillation.

STUDY OBJECTIVE: To examine sex differences in oral anticoagulation management and outcomes among patients with incident nonvalvular atrial fibrillation presenting to the emergency department (ED). METHODS: We identified patients older than 20 years presenting to the ED with incident nonvalvular atrial fibrillation between April 1, 2012, and March 30, 2019, using linked administrative databases in Alberta, Canada. We assessed the use of and adherence to oral anticoagulants at 1 year using the proportion of days covered for direct oral anticoagulants and time in therapeutic range for warfarin. Outcomes included stroke, heart failure, and all-cause mortality at 1 year. RESULTS: Of the 28,886 patients with nonvalvular atrial fibrillation presenting to ED, 44% were females. After adjustment, the rate of oral anticoagulant use was 5% lower in females with a guideline indication than that in males (adjusted hazard ratio 0.95, 95% confidence interval [CI] 0.91 to 0.99) discharged home, and there was no difference among admitted patients (adjusted hazard ratio 1.00, 95% CI 0.96 to 1.05). Females had high adherence to direct oral anticoagulants (≥80% proportion of days covered) compared to males (discharged: 77.7% versus 74.0%; admitted: 80.0% versus 76.7%; adjusted odds ratio for females: 1.15, 95% CI 1.02 to 1.29). More than half of the females and males had poor warfarin control (time in therapeutic range <65%) regardless of discharge status. In multivariable analyses, there was no sex difference in outcomes except a 1.48-fold (95% CI 1.14 to 1.92) higher risk of stroke in females. CONCLUSION: Females with incident nonvalvular atrial fibrillation discharged from the ED are less likely to receive oral anticoagulants than males. When oral anticoagulant treatment is initiated, females have high adherence to direct oral anticoagulants, and both the sexes have poor warfarin control. At 1 year, females were at a significantly higher risk of developing stroke.

Validity of different dose reduction criteria for apixaban.

Reduced-dose apixaban is recommended in patients fulfilling 2 of 3 criteria: age ≥80 years, body weight ≤60 kg, and serum creatinine ≥1.5 mg/dL. However, patient weight is often not available in electronic health data. We examined the validity of alternative definitions based on age and renal function alone using an observational dataset of patients with atrial fibrillation and chronic kidney disease which included weight measurements.

Post-operative pain following cardiac implantable electronic device implantation: insights from the BRUISE CONTROL trials.

AIMS: Post-operative pain following cardiac implantable electronic device (CIED) insertion is associated with patient dissatisfaction, emotional distress, and emergency department visits. We sought to identify factors associated with post-operative pain and develop a prediction score for post-operative pain. METHODS AND RESULTS: All patients from the BRUISE CONTROL-1 and 2 trials were included in this analysis. A validated Visual Analogue Scale (VAS) was used to assess the severity of pain related to CIED implant procedures. Patients were asked to grade the most severe post-operative pain, average post-operative pain, and pain on the day of the first post-operative clinic. Multivariable regression analyses were performed to identify predictors of significant post-operative pain and to develop a pain-prediction score. A total of 1308 patients were included. Multivariable regression analysis found that the presence of post-operative clinically significant haematoma {CSH; P value < 0.001; odds ratio (OR) 3.82 [95% confidence interval (CI): 2.37-6.16]}, de novo CIED implantation [P value < 0.001; OR 1.90 (95% CI: 1.47-2.46)], female sex [P value < 0.001; OR 1.61 (95% CI: 1.22-2.12)], younger age [<65 years; P value < 0.001; OR 1.54 (95% CI: 1.14-2.10)], and lower body mass index [<20 kg/m2; P value < 0.05; OR 2.05 (95% CI: 0.98-4.28)] demonstrated strong and independent associations with increased post-operative pain. An 11-point post-operative pain prediction score was developed using the data. CONCLUSION: Our study has identified multiple predictors of post-operative pain after CIED insertion. We have developed a prediction score for post-operative pain that can be used to identify individuals at risk of experiencing significant post-operative pain.

Impact of Atrial Fibrillation Case Volume in the Emergency Department on Early and Late Outcomes of Patients With New Atrial Fibrillation.

STUDY OBJECTIVE: To define the association between atrial fibrillation case volume in the emergency department and death or all-cause hospitalization at 30 days and 1 year in patients with new atrial fibrillation. Secondary objectives examined repeat ED visits and the management of atrial fibrillation within 90 days. METHODS: We identified all adults presenting to an ED in Alberta, Canada, with a new primary diagnosis of atrial fibrillation/flutter between 2009 and 2015 using International Classification of Diseases, 10th Revision code I48. Volume was classified in tertiles weighted by annual ED number of atrial fibrillation cases. The association between volume and outcomes was evaluated using generalized linear mixed models, adjusting for prognostically important covariates as fixed effects and ED as a random effect to account for potential clustering within EDs. RESULTS: The tertiles consisted of 4 high, 9 medium, and 68 low atrial fibrillation volume EDs, with 4,217, 4,193, and 4,112 patients, respectively. Volume was not independently associated with the primary outcome or individual components. However, medium- and high-volume EDs had fewer repeat ED visits at 30 days (respective adjusted odds ratio [aOR] 0.75 [95% confidence interval {CI} 0.66 to 0.87] and 0.64 [0.52 to 0.79]) and 1 year (respective aOR 0.77 [95% CI 0.67 to 0.90] and 0.71 [0.56 to 0.90]). Fewer patients were admitted from medium- (37.1%) and high- (32.0%) compared with low-volume (39.5%) EDs. Patients attending medium- and high-volume EDs were more likely to be cardioverted (aOR 3.28 [95% CI 1.94 to 5.53] and 3.81 [1.39 to 10.48] for medium- and high-volume EDs, respectively). CONCLUSION: Treatment in higher volume EDs was associated with significantly lower admission rates and repeat ED visits but no difference in survival.

Impact of cardiology follow-up care on treatment and outcomes of patients with new atrial fibrillation discharged from the emergency department.

AIMS: The first presentation of atrial fibrillation (AF) is often to an emergency department (ED). We evaluated the association of subsequent specialist care with morbidity and mortality. METHODS AND RESULTS: Retrospective cohort study of all adults in Alberta, Canada, with a new primary diagnosis of AF treated and released during an index ED visit between 2009 and 2015. Types of physician follow-up within 3 months of ED visit was analysed using Cox proportional hazards models with time-varying covariates. Outcomes were evaluated at 1 year. Of 7986 patients, 476 (6.0%) had no physician follow-up within 3 months, whereas 2730 (34.2%) attended a non-specialist only, 1277 (16.0%) an internal medicine specialist, and 3503 (43.9%) cardiology. An increasing gradient of cardiac investigations occurred across these groups. Cardiology compared with non-cardiologist care was associated with approximately two-fold greater electrophysiology interventions and revascularization, and increased use of beta-blockers (48.9% vs. 43.0%, P < 0.0001), statins (31.4% vs. 26.7%, P < 0.0001), and oral anticoagulation in patients with CHADS2 scores ≥1 (53.7% vs. 43.6%, P < 0.0001). In the subsequent year, cardiology care was associated with fewer deaths [adjusted hazard ratio (aHR) 0.72, 95% confidence interval (CI) 0.55-0.93], strokes (aHR 0.60, 95% CI 0.37-0.96), or major bleeds (aHR 0.69, 95% CI 0.53-0.89). No differences in the risk of hospitalization or ED visits were associated with cardiology care. CONCLUSION: Cardiology care after an ED visit for symptomatic new-onset AF is associated with better prognosis. The benefit may be mediated through more intensive investigation, identification, and treatment of cardiovascular risk factors and disease.

Estimated stroke risk, yield, and number needed to screen for atrial fibrillation detected through single time screening: a multicountry patient-level meta-analysis of 141,220 screened individuals.

BACKGROUND: The precise age distribution and calculated stroke risk of screen-detected atrial fibrillation (AF) is not known. Therefore, it is not possible to determine the number needed to screen (NNS) to identify one treatable new AF case (NNS-Rx) (i.e., Class-1 oral anticoagulation [OAC] treatment recommendation) in each age stratum. If the NNS-Rx is known for each age stratum, precise cost-effectiveness and sensitivity simulations can be performed based on the age distribution of the population/region to be screened. Such calculations are required by national authorities and organisations responsible for health system budgets to determine the best age cutoffs for screening programs and decide whether programs of screening should be funded. Therefore, we aimed to determine the exact yield and calculated stroke-risk profile of screen-detected AF and NNS-Rx in 5-year age strata. METHODS AND FINDINGS: A systematic review of Medline, Pubmed, and Embase was performed (January 2007 to February 2018), and AF-SCREEN international collaboration members were contacted to identify additional studies. Twenty-four eligible studies were identified that performed a single time point screen for AF in a general ambulant population, including people ≥65 years. Authors from eligible studies were invited to collaborate and share patient-level data. Statistical analysis was performed using random effects logistic regression for AF detection rate, and Poisson regression modelling for CHA2DS2-VASc scores. Nineteen studies (14 countries from a mix of low- to middle- and high-income countries) collaborated, with 141,220 participants screened and 1,539 new AF cases. Pooled yield of screening was greater in males across all age strata. The age/sex-adjusted detection rate for screen-detected AF in ≥65-year-olds was 1.44% (95% CI, 1.13%-1.82%) and 0.41% (95% CI, 0.31%-0.53%) for <65-year-olds. New AF detection rate increased progressively with age from 0.34% (<60 years) to 2.73% (≥85 years). Neither the choice of screening methodology or device, the geographical region, nor the screening setting influenced the detection rate of AF. Mean CHA2DS2-VASc scores (n = 1,369) increased with age from 1.1 (<60 years) to 3.9 (≥85 years); 72% of ≥65 years had ≥1 additional stroke risk factor other than age/sex. All new AF ≥75 years and 66% between 65 and 74 years had a Class-1 OAC recommendation. The NNS-Rx is 83 for ≥65 years, 926 for 60-64 years; and 1,089 for <60 years. The main limitation of this study is there are insufficient data on sociodemographic variables of the populations and possible ascertainment biases to explain the variance in the samples. CONCLUSIONS: People with screen-detected AF are at elevated calculated stroke risk: above age 65, the majority have a Class-1 OAC recommendation for stroke prevention, and >70% have ≥1 additional stroke risk factor other than age/sex. Our data, based on the largest number of screen-detected AF collected to date, show the precise relationship between yield and estimated stroke risk profile with age, and strong dependence for NNS-RX on the age distribution of the population to be screened: essential information for precise cost-effectiveness calculations.

Continued vs. interrupted direct oral anticoagulants at the time of device surgery, in patients with moderate to high risk of arterial thrombo-embolic events (BRUISE CONTROL-2).

Aims: Guidelines recommend warfarin continuation rather than heparin bridging for pacemaker and defibrillator surgery, after the BRUISE CONTROL trial demonstrated an 80% reduction in device pocket haematoma with this approach. However, direct oral anticoagulants (DOACs) are now used to treat the majority of patients with atrial fibrillation. We sought to understand the best strategy to manage the DOACs at the time of device surgery and specifically hypothesized that performing device surgery without DOAC interruption would result in a reduced haematoma rate. Methods and results: We randomly assigned patients with atrial fibrillation and CHA2DS2-VASc score ≥2, to continued vs. interrupted DOAC (dabigatran, rivaroxaban, or apixaban). The primary outcome was blindly evaluated, clinically significant device pocket haematoma: resulting in re-operation, interruption of anticoagulation, or prolonging hospital stay. In the continued arm, the median time between pre- and post-operative DOAC doses was 12 h; in the interrupted arm the median time was 72 h. Clinically significant haematoma occurred in of 7 of 328 (2.1%; 95% CI 0.9-4.3) patients in the continued DOAC arm and 7 of 334 (2.1%; 95% CI 0.9-4.3) patients in the interrupted DOAC arm (P = 0.97). Complications were uncommon, and included one stroke and one symptomatic pericardial effusion in each arm. Conclusions: These results suggest that, dependent on the clinical scenario, either management strategy (continued DOAC or interrupted DOAC) might be reasonable, at least for patients similar to those enrolled in our trial.

Screening for Atrial Fibrillation: A Report of the AF-SCREEN International Collaboration.

Approximately 10% of ischemic strokes are associated with atrial fibrillation (AF) first diagnosed at the time of stroke. Detecting asymptomatic AF would provide an opportunity to prevent these strokes by instituting appropriate anticoagulation. The AF-SCREEN international collaboration was formed in September 2015 to promote discussion and research about AF screening as a strategy to reduce stroke and death and to provide advocacy for implementation of country-specific AF screening programs. During 2016, 60 expert members of AF-SCREEN, including physicians, nurses, allied health professionals, health economists, and patient advocates, were invited to prepare sections of a draft document. In August 2016, 51 members met in Rome to discuss the draft document and consider the key points arising from it using a Delphi process. These key points emphasize that screen-detected AF found at a single timepoint or by intermittent ECG recordings over 2 weeks is not a benign condition and, with additional stroke factors, carries sufficient risk of stroke to justify consideration of anticoagulation. With regard to the methods of mass screening, handheld ECG devices have the advantage of providing a verifiable ECG trace that guidelines require for AF diagnosis and would therefore be preferred as screening tools. Certain patient groups, such as those with recent embolic stroke of uncertain source (ESUS), require more intensive monitoring for AF. Settings for screening include various venues in both the community and the clinic, but they must be linked to a pathway for appropriate diagnosis and management for screening to be effective. It is recognized that health resources vary widely between countries and health systems, so the setting for AF screening should be both country- and health system-specific. Based on current knowledge, this white paper provides a strong case for AF screening now while recognizing that large randomized outcomes studies would be helpful to strengthen the evidence base.

Sedation strategies for defibrillation threshold testing: safety outcomes with anaesthesiologist compared to proceduralist-directed sedation: an analysis from the SIMPLE study.

Aims: No standard practice exists with respect to anaesthesiologist-directed sedation (ADS) vs. sedation by proceduralist (PDS) for defibrillation threshold (DT) testing. We aimed to evaluate adverse events and safety outcomes with ADS vs. PDS for DT testing. Methods and results: A post hoc analysis of the Shockless Implant Evaluation (SIMPLE) study was performed among the 1242 patients who had DT testing (624 ADS and 618 PDS). We evaluated both intraoperative and in-hospital adverse composite events and two safety composite outcomes at 30-days of the main trial. Propensity score adjusted models were used to compute odds ratio (OR) and 95% confidence interval (CI) to evaluate the association between adverse and safety outcomes with method of sedation and independent predictors for use of ADS. Compared to PDS, patients who received ADS were younger (62 ± 12 years vs. 64 ± 12 years, P = 0.01), had lower ejection fraction (left ventricular ejection fraction 0.31 ± 13 vs. 0.33 ± 13, P = 0.03), were more likely to receive inhalational anaesthesia, propofol, or narcotics (P < 0.001, respectively) and receive an arterial line (43% vs. 8%, P = <0.0001). Independent predictors for ADS sedation were presence of coronary artery disease (OR 1.69, 95% CI 1.0-2.72; P = 0.03) and hypertrophic cardiomyopathy (OR 2.64, 95% CI 1.19-5.85; P = 0.02). Anaesthesiologist directed sedation had higher intraoperative adverse events (2.2% vs. 0.5%; OR 4.47, 95% CI 1.25-16.0; P = 0.02) and higher primary safety outcomes at 30 days (8.2% vs. 4.9%; OR 1.72 95% CI 1.06-2.80; P = 0.03) and no difference in other outcomes compared to PDS. Conclusion: Proceduralist-directed sedation is safe, however, this could be result of selection bias. Further research is needed.

Evaluating the potential for pharmacists to prescribe oral anticoagulants for atrial fibrillation.

BACKGROUND: Oral anticoagulant therapy (OAC) to prevent atrial fibrillation (AF)-related strokes remains poorly used. Alternate strategies, such as community pharmacist prescribing of OAC, should be explored. METHODS: Approximately 400 pharmacists, half with additional prescribing authority (APA), randomly selected from the Alberta College of Pharmacists, were invited to participate in an online survey over a 6-week period. The survey consisted of demographics, case scenarios assessing appropriateness of OAC (based on the 2014 Canadian Cardiovascular Society AF guidelines) and perceived barriers to prescribing. Regression analysis was performed to determine predictors of knowledge. RESULTS: A total of 35% (139/397) of pharmacists responded to the survey, and 57% of these had APA. Depending on the case scenario, 55% to 92% of pharmacists correctly identified patients eligible for stroke prevention therapy, but only about a half selected the appropriate antithrombotic agent; there was no difference in the knowledge according to APA status. In multivariable analysis, predictors significantly associated with guideline-concordant prescribing were having the pharmacist interact as part of an interprofessional team (p = 0.04) and direct OAC (DOAC) self-efficacy (confidence in ability to extend, adapt, initiate or alter prescriptions; p = 0.02). Barriers to prescribing OAC for APA pharmacists included a lack of AF and DOAC knowledge and preference for consulting the physician first, but these same pharmacists also identified difficulty in contacting the physician as a major barrier. INTERPRETATION AND CONCLUSION: Community pharmacists can identify patients who would benefit from stroke prevention therapy in AF. However, physician collaboration and further training on AF and guidelines for prescribing OAC are needed.

Assessing physician knowledge regarding indications for a primary prevention implantable defibrillator and potential barriers for referral.

BACKGROUND: Although there is clear evidence to demonstrate that primary prevention implantable defibrillators (ICDs) reduce mortality in high-risk patients, ICDs are underutilized. Limited data exist assessing referring physicians' knowledge about guideline indications and attitudes towards ICDs, which may influence decision for referral. METHODS AND RESULTS: The Arrhythmia Working Group from the Alberta Cardiovascular and Stroke Strategic Clinical Network developed a web-based survey consisting of case scenarios regarding primary prevention ICD indications and a list of barriers for referral to aid in the design of a complex device care pathway. We invited referring physicians to participate in the survey including internists and cardiologists and cardiology residents. The survey was completed by 109 of 799 (response rate = 14%) of physicians. Of those, 55% were internists, 32% cardiologists, and 13% cardiology residents. The majority of physicians were male (62%), practicing in a university hospital (66%). Overall, complete guideline-concordant answers were provided by 34% of physicians. In multivariable analysis, predictors of complete guideline concordance were being a cardiologist (odd ratio [OR] 5.9, confidence interval [CI] 2.1-16.4, P = 0.001) and cardiology resident (OR 6.7, CI 1.7-27.3, P = 0.007). The most common barrier for referral for internists was lack of confidence in knowledge of guideline recommendations; while cardiologists reported concerns about cost-effectiveness and cardiology residents were most concerned with inappropriate shocks. CONCLUSION: Knowledge regarding indications for primary prevention ICD is limited and varies significantly among referring physicians. The barriers for referral differ among physician groups and addressing these identified barriers may help to improve appropriate ICD utilization.

The 'obesity paradox' in atrial fibrillation: observations from the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial.

AIMS: The prognostic implication of adiposity on clinical outcomes in atrial fibrillation (AF) patients treated with oral anticoagulation is unclear. METHODS AND RESULTS: A total of 17 913 patients in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial had body mass index (BMI) measured at baseline. For the primary analysis, BMI was categorized as normal (18.5 to <25 kg/m2), overweight (25 to <30 kg/m2), and obese (≥30 kg/m2). Waist circumference (WC) was defined as high if >102 cm for men and >88 cm in women. Outcomes were stroke or systemic embolism, a composite endpoint (stroke, systemic embolism, myocardial infarction, or all-cause mortality), all-cause mortality, and major bleeding. Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) across categories of BMI and WC adjusting for established risk factors and treatment allocation. At baseline, 4052 (22.6%) patients had a normal BMI, 6702 (37.4%) were overweight, and 7159 (40.0%) were obese. In multivariable analyses, higher BMI was associated with a lower risk of all-cause mortality [overweight: HR 0.67 (95% CI 0.59-0.78); obese: HR 0.63 (95% CI 0.54-0.74), P < 0.0001] and the composite endpoint [overweight: HR 0.74 (95% CI 0.65-0.84); obese: HR 0.68 (95% CI 0.60-0.78), P < 0.0001] compared with normal BMI. In women, high WC was associated with a 31% lower risk of all-cause mortality (P = 0.001), 27% lower risk of the composite endpoint (P = 0.001), and 28% lower risk of stroke or systemic embolism (P = 0.048) but not in men. There was no significant association between adiposity and major bleeding. CONCLUSION: In patients with AF treated with oral anticoagulants, higher BMI and WC are associated with a more favourable prognosis.

Strategy of continued vs interrupted novel oral anticoagulant at time of device surgery in patients with moderate to high risk of arterial thromboembolic events: The BRUISE CONTROL-2 trial.

BACKGROUND: Patients who require perioperative anticoagulation during cardiac implantable electronic device surgery are at increased risk for bleeding complications. The BRUISE CONTROL trial demonstrated that continuing warfarin was safer than heparin bridging, reducing the incidence of clinically significant pocket hematoma. Novel oral anticoagulants are being increasingly prescribed in place of warfarin. The best perioperative management of these new anticoagulants is unknown. METHODS/DESIGN: A randomized controlled trial to investigate whether a strategy of continued vs interrupted novel oral anticoagulant (dabigatran, rivaroxaban, or apixaban) at the time of device surgery, in patients with moderate to high risk of arterial thromboembolic events, reduces the incidence of clinically significant hematoma (defined as a hematoma requiring reoperation and/or resulting in prolongation of hospitalization, and/or requiring interruption of anticoagulation). The secondary outcomes include components of the primary outcome, composite of all other major perioperative bleeding events, thromboembolic events, all-cause mortality, cost-effectiveness, patient quality of life, perioperative pain, and satisfaction. Planned analyses include descriptive statistics of all baseline variables. For the primary outcome, interrupted vs continued novel oral anticoagulant arms will be compared using the χ(2) test. If any clinically significant differences are identified, a logistic regression analysis will be conducted. Quality of life will be assessed using EuroQol-5D, and perioperative pain using a visual analog scale. DISCUSSION: BRUISE CONTROL-2 is a randomized trial evaluating the best strategy to manage novel oral anticoagulants at the time of device surgery. We hypothesize that device surgery can be performed safely without interruption of these medications.