Best Evidence Topic report: Antithrombotic therapy and endovascular intervention for blunt cerebrovascular injury.

A short cut review of the literature was carried out to examine the evidence supporting antithrombotic treatment and/or endovascular therapy to reduce mortality and/or prevent future stroke following blunt cerebrovascular injury (BCVI). Five papers were identified as suitable for inclusion using the reported search strategy. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of the best papers are tabulated. It is concluded that in patients with BCVI confirmed by CT angiography, there is limited evidence to support screening for, or treating BCVI. In confirmed BCVI where the risk of stroke is felt to outweigh the risk of bleeding, antiplatelet therapy appears to be as effective as therapeutic anticoagulation.

Paced P-wave morphology templates to guide atrial tachycardia localization: A derivation and validation study.

BACKGROUND: Surface ECG is a useful tool to guide mapping of focal atrial tachycardia (AT). OBJECTIVES: We aimed to construct 12-lead ECG templates for P-wave morphology (PWM) during endocardial pacing from different sites in both atria in patients with no apparent structural heart disease (derivation cohort), with the goal of creating a localization algorithm, which could subsequently be validated in a cohort of patients undergoing catheter ablation of focal AT (validation cohort). METHODS: We prospectively enrolled consecutive patients who underwent electrophysiology study, had no structural heart disease and no atrial enlargement. Atrial pacing, at twice diastolic threshold, was carried out at different anatomical sites in both atria. Paced PWM and duration were assessed. An algorithm was generated from the constructed templates of each pacing site. The algorithm was applied on a retrospective series of successfully ablated AT patients. Overall and site-specific accuracy were determined. RESULTS: Derivation cohort included 65 patients (25 men, age 37 ± 13 years). Atrial pacing was performed in 1025 sites in 61 patients (95%) in RA and in 15 patients (23%) in LA. The validation cohort included 71 patients (28 men, age 52 ± 19 years). AT were right atrial in 66.2%. The algorithm successfully predicted AT origin in 91.5% of patients (100% in LA and 87.2% in RA). It was off by one adjacent segment in the remaining 8.5%. CONCLUSIONS: A simple ECG algorithm based on paced PWM templates was highly accurate in localizing site of origin of focal AT in patients with structurally normal hearts.

Prevalence and management of electrical lead abnormalities in cardiac implantable electronic device leads.

Background: Electrical lead abnormalities (ELAs) can result in device malfunction, leading to significant morbidity in patients with cardiac implantable electronic devices (CIEDs). Objective: We sought to determine the prevalence and management of ELAs in patients with CIEDs. Methods: This was a retrospective cohort study of patients implanted with a CIED between 2012 and 2019 at a tertiary care center. The primary outcome was ELA defined as increased capture threshold (≥2× implantation value), decreased sensing (≤0.5 implantation value), change in impedance (>50% over 3 months), or nonphysiologic potentials. A secondary outcome of device clinic utilization was also collected. Results: There were 2996 unique patients (35% female) included with 4600 leads (57% Abbott, 43% Medtronic). ELAs were observed in 135 (3%) leads, including 124 (92%) Abbott and 10 (7%) Medtronic leads (hazard ratio 9.25, P < .001). Mean follow-up was 4.5 ± 2.2 years. ELAs were associated smaller lead French size, atrial location, and Abbott leads. Lead revision was required in 28% of cases. Patients with lead abnormalities had 38% more in-clinic visits per patient year of follow-up compared with those without (P < .001). Conclusion: ELAs were more frequent in certain models, which increased rates of revision and follow-up. Identification of factors that mitigate these abnormalities to improve lead performance are required to improve care for these devices and provide efficient healthcare.

Disparities in Referral and Utilization of Implantable Cardioverter-Defibrillators for Primary Prevention of Sudden Cardiac Death.

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) reduce mortality in patients with reduced left ventricular ejection fraction (LVEF). We investigated sex disparities in a contemporary Canadian population for utilization of primary prevention ICDs. METHODS: This was a retrospective cohort study on patients with reduced LVEF admitted to hospitals from 2010 to 2020 in Nova Scotia (population = 971,935). RESULTS: There were 4406 patients eligible for ICDs: 3108 (71%) men and 1298 (29%) women. The mean follow-up time was 3.9 ± 3.0 years. Rates of coronary disease were similar between men and women (45.8% vs 44.0%; P = 0.28), but men had lower LVEF (26.6 ± 5.9% vs 27.2 ± 5.8%; P = 0.0017). The referral rate for ICD was 11% (n = 487), with 13% of men (n = 403) and 6.5% of women (n = 84) referred (P < 0.001). The ICD implantation rate in the population was 8% (n = 358), with 9.5% of men (n = 296) and 4.8% of women (n = 62) (P < 0.001) receiving the device. Men were more likely than women to receive an ICD (odds ratio 2.08, 95% confidence interval 1.61-2.70; P < 0.0001)). There was no significant difference in mortality between men and women (P = 0.2764). There was no significant difference in device therapies between men and women (43.8% vs 31.1%; P = 0.0685). CONCLUSIONS: A significant disparity exists in the utilization of primary prevention ICDs between men and women in a contemporary Canadian population.

A virtual platform to deliver ambulatory care for patients with atrial fibrillation.

Background: There are little data on the use of virtual care for patients with arrhythmia. We evaluated a virtual clinic platform, in conjunction with specialist care, for patients with symptomatic atrial fibrillation (AF). Methods: This was a prospective, observational cohort study evaluating an online educational and treatment platform, with a randomized sub-study examining the use of an ambulatory single-lead electrocardiogram heart monitor (AHM). Follow-up was 6 months. The main outcome was patients' platform use; success was defined as 90% of patients using the platform at least once, and 75% using it at least twice. The primary outcome in the AHM sub-study was Atrial Fibrillation Symptom Severity (AFSS) score. Other outcomes included patient satisfaction questionnaires, quality of life, emergency department visits, and hospitalizations for AF. Results: We enrolled 94 patients between July 2018 and May 2019; 83% of patients logged in at least once and 54.3% more than once. Patients who were older, were male, or had new-onset AF were more likely to log in to the platform. Satisfaction scores were high; 70%-94% of patients responded favorably. Quality-of-life scores improved at 3 and 6 months. In the AHM sub-study (n = 71), those who received an AHM had lower AFSS scores (least square mean difference -2.52, 95% CI -4.48 to -0.25, P = .03). There was no difference in emergency department visits or hospitalizations. Conclusion: The online platform did not reach our feasibility target but was well received. Allocation of an AHM was associated with improved quality of life. Virtual AF care shows promise and should be evaluated in further research.

Prospective Assessment of an Automated Intraprocedural 12-Lead ECG-Based System for Localization of Early Left Ventricular Activation.

BACKGROUND: To facilitate ablation of ventricular tachycardia (VT), an automated localization system to identify the site of origin of left ventricular activation in real time using the 12-lead ECG was developed. The objective of this study was to prospectively assess its accuracy. METHODS: The automated site of origin localization system consists of 3 steps: (1) localization of ventricular segment based on population templates, (2) population-based localization within a segment, and (3) patient-specific site localization. Localization error was assessed by the distance between the known reference site and the estimated site. RESULTS: In 19 patients undergoing 21 catheter ablation procedures of scar-related VT, site of origin localization accuracy was estimated using 552 left ventricular endocardial pacing sites pooled together and 25 VT-exit sites identified by contact mapping. For the 25 VT-exit sites, localization error of the population-based localization steps was within 10 mm. Patient-specific site localization achieved accuracy of within 3.5 mm after including up to 11 pacing (training) sites. Using 3 remotes (67.8±17.0 mm from the reference VT-exit site), and then 5 close pacing sites, resulted in localization error of 7.2±4.1 mm for the 25 identified VT-exit sites. In 2 emulated clinical procedure with 2 induced VTs, the site of origin localization system achieved accuracy within 4 mm. CONCLUSIONS: In this prospective validation study, the automated localization system achieved estimated accuracy within 10 mm and could thus provide clinical utility.

Automated intraprocedural localization of origin of ventricular activation using patient-specific computed tomographic imaging.

BACKGROUND: To facilitate catheter ablation of ventricular tachycardia (VT), we previously developed an automated method to identify sources of left ventricular (LV) activation in real time using 12-lead electrocardiography (ECG), the accuracy of which depends on acquisition of a complete electroanatomic (EA) map. OBJECTIVE: The purpose of this study was to assess the feasibility of using a registered cardiac computed tomogram (CT) rather than an EA map to permit real-time localization and avoid errors introduced by incomplete maps. METHODS: Before LV VT ablation, 10 patients underwent CT imaging and 3-dimensional reconstruction of the cardiac surface to create a triangle mesh surface, which was registered to the EA map during the procedure and imported into custom localization software. The software uses QRS integrals from leads III, V2, and V6; derives personalized regression coefficients from pacing at ≥5 sites with known locations; and estimates the location of unknown activation sites on the 3-dimensional patient-specific LV endocardial surface. Localization accuracy was quantified for VT exit sites in millimeters by comparing the calculated against the known locations. RESULTS: The VT exit site was identified for 20 VTs using activation and entrainment mapping, supplemented by pace-mapping at the scar margin. The automated localization software achieved incremental accuracy with additional pacing sites and had a mean localization error of 6.9 ± 5.7 mm for the 20 VTs. CONCLUSION: Patient-specific CT geometry is feasible for use in real-time automated localization of ventricular activation and may avoid reliance on a complete EA map.

New toxicity testing of PQ grass allergy immunotherapy to support product development.

PQ Grass represents an allergen-specific immunotherapy for pre-seasonal treatment of patients with seasonal allergic rhinitis (or rhinoconjunctivitis) with or without mild-to-moderate bronchial asthma. It consists of a native pollen extract for 13 grass species, chemically modified with glutaraldehyde, and adsorbed to l-tyrosine in a microcrystalline form with addition of the adjuvant Monophosphoryl Lipid A (MPL® ). Previous non-clinical safety testing, including rat repeat dose toxicity in adult and juvenile animals, rat reproductive toxicity and rabbit local tolerance studies showed no safety findings of concern. A new Good Laboratory Practice compliant rat subcutaneous repeat dose toxicity study to evaluate a higher clinical dose and modified posology (once every 2 weeks for 13 weeks) showed no signs of toxicity. As seen in previous studies, relatively minor, immunostimulatory effects were seen such as reversible increased white cell count (notably neutrophils), increased globulin level (resulting in decreased A/G ratio) and increased fibrinogen as well as minor dose site reaction in the form of inflammatory cell infiltrate. These findings are likely due to the immunostimulatory nature of MPL and/or the presence of l-tyrosine within the adjuvanted vaccine. This new toxicity study with PQ Grass therefore supports longer posology with higher dose levels.

The Effect of Cardiac Rehabilitation and a Specialized Clinic on Outcomes of Patients With Atrial Fibrillation.

BACKGROUND: Cardiac rehabilitation (CR) intervention programs are currently not part of management in patients with atrial fibrillation (AF). We sought to determine the effect of CR compared with a specialized AF clinic (AFC) and usual care on outcomes in patients with AF. METHODS: This was a single-centre retrospective cohort study that was carried out using 3 databases: the Hearts in Motion database (2010-2014), prospectively collected data in an AFC (2011-2014), and a retrospective chart review for patients in usual care (2009-2012). Three care pathways were compared: (1) CR; (2) AFC; and (3) usual specialist-based care. The main outcome was AF-related emergency department visits and cardiovascular hospitalizations. RESULTS: Of 566 patients with newly diagnosed AF, 133 (23.5%) patients underwent CR, 197 patients (34.8%) attended the AFC, whereas the remaining 236 (41.7%) were followed in a usual specialist-based care clinic. At 1 year, AF-related emergency department visits and cardiovascular hospitalization rates occurred in 7.5% in the CR group, 16.8% in the AFC group, and 29.2% in usual care. After a propensity matched analysis, usual care was associated with the highest rate of the main outcome (odds ratio, 4.91; 95% confidence interval, 2.09-11.53) compared with CR, as did the AFC compared with CR (odds ratio, 2.75; 95% confidence interval, 1.14-6.6). CONCLUSIONS: Among patients with AF, CR was associated with a lower risk of AF-related outcomes. These findings support further study of the use of CR in the management of these patients to determine the optimal model of care for AF patients.

Use of Administrative Data to Monitor Cardiac Implantable Electronic Device Complications.

Cardiac implantable electronic devices (CIEDs) are increasingly used in the Canadian population, because of expanding indications and an aging population. Device-related complications are a source of morbidity and mortality. There is currently no comprehensive monitoring strategy of CIED-related complications in Canada. The objective of this study was to determine the utility of administrative data in tracking CIED complications. This was a retrospective observational study in patients with newly implanted pacemakers, pacemaker system revisions, and implantable cardioverter defibrillators (ICDs) from 2011 to 2014. The study was performed at a single academic centre in Nova Scotia. A comprehensive chart review was used as the gold standard for device-related complications. This was compared with the reporting of complications identified in the Canadian Institute for Health Information Discharge Abstract Database and the National Ambulatory Care Reporting System Database (NACRS). Sensitivity and specificity of Canadian Institute for Health Information/NACRS was reported. There were 1327 patients included in the study (742 pacemakers, 585 ICDs). The rate of complications in the pacemaker population was 8.0%; the sensitivity of Discharge Abstract Database/NACRS for detection of these was 83.1%, and specificity 100%. The rate of complications in the ICD population was 12.0%, with a sensitivity of 92.1%, and specificity 100%. Thirty-day mortality was 1.8% in the pacemaker population, and 0.3% in the ICD population. This study provides feasibility for use of administrative data for detection of device-related complications, showing reasonable sensitivity and excellent specificity. Further work to determine generalizability of these data across Canada is required to ensure accurate monitoring of device-related complications.

The Effect of Shock Burden on Heart Failure and Mortality.

BACKGROUND: Prior studies have demonstrated an association between appropriate implantable cardioverter defibrillator (ICD) shocks and mortality in clinical trials. The effect of shock burden on heart failure and mortality has not been previously studied in a large population-based cohort. METHODS: The cohort was derived using a comprehensive prospective ICD registry in the province of Nova Scotia with a mean follow-up of 4 ± 2.3 years. With the use of time-varying analysis, the relationship among shock burden, mortality, and heart failure hospitalization was determined. RESULTS: A total of 776 patients (mean age of 64.8 years) were included in the study, of whom 37% received appropriate therapy during follow-up. A single ICD shock did not confer an increased mortality risk compared with no therapy (hazard ratio [HR], 1.23; 95% confidence interval [CI], 0.84-1.79; P = 0.3), but mortality risk was significantly increased with ≥ 2 shocks (HR, 3.23; 95% CI, 2.04-5.09; P < 0.0001). There was a significant increase in heart failure hospitalization associated with receiving 1 ICD shock (HR, 2.05; 95% CI, 1.46-2.89; P < 0.0001) or more than 1 ICD shock (HR, 4.36; CI, 2.53-7.52; P < 0.0001) compared with patients receiving no ICD therapy. Patients who received antitachycardia pacing alone showed no difference in heart failure hospitalization (HR, 0.93; CI, 0.67-1.29; P = 0.7) and improved survival (HR, 0.69; CI, 0.5-0.96; P = 0.03) compared with those receiving no ICD therapy. CONCLUSION: Ventricular arrhythmia treated with appropriate ICD shocks is associated with an increased risk of heart failure hospitalization, whereas recurrent episodes of ventricular arrhythmia requiring shocks are associated with both higher mortality and higher heart failure hospitalization rates.

CONTEXTE: Des études menées antérieurement ont révélé l'existence d'un lien entre l'administration appropriée de décharges électriques au moyen d'un défibrillateur cardioverteur implantable (DCI) et la mortalité au cours des essais cliniques. L'effet de telles décharges sur l'insuffisance cardiaque et la mortalité n'avait encore jamais été étudié au sein d'une cohorte d'envergure représentative de la population. MÉTHODOLOGIE: La cohorte a été établie au moyen d'un registre prospectif exhaustif des DCI implantés chez des patients de la Nouvelle-Écosse ayant fait l'objet d'un suivi moyen de 4 ± 2,3 ans. La relation entre le fardeau imposé par les décharges, la mortalité et l'hospitalisation pour insuffisance cardiaque a été déterminée au moyen d'une analyse en fonction du temps. RÉSULTATS: Au total, 776 patients (âge moyen : 64,8 ans) ont été admis dans l'étude; 37 % d'entre eux avaient reçu un traitement approprié au cours de la période de suivi. Une seule décharge délivrée par un DCI n'augmentait pas le risque de mortalité par rapport à l'absence de traitement (rapport des risques instantanés [RRI] de 1,23; intervalle de confiance [IC] à 95 %, de 0,84 à 1,79; p = 0,3), mais le risque de mortalité était significativement accru chez les patients ayant reçu ≥ 2 décharges (RRI de 3,23; IC à 95 %, de 2,04 à 5,09; p < 0,0001). Le risque d'hospitalisation pour insuffisance cardiaque s'est révélé significativement supérieur chez les sujets ayant reçu 1 décharge par DCI (RRI de 2,05; IC à 95 %, de 1,46 à 2,89; p < 0,0001) ou plus de 1 décharge par DCI (RRI de 4,36; IC à 95 %, de 2,53-7,52; p < 0,0001), comparativement à ceux n'ayant reçu aucun traitement par DCI. On n'a observé aucune différence quant à l'hospitalisation pour insuffisance cardiaque (RRI de 0,93; IC à 95 %, de 0,67 à 1,29; p = 0,7) et à l'amélioration de la survie (RRI de 0,69; IC à 95 %, de 0,5 à 0,96; p = 0,03) chez les patients qui ont reçu uniquement une stimulation antitachycardie comparativement à ceux qui n'ont reçu aucun traitement par DCI. CONCLUSION: L'arythmie ventriculaire traitée de façon appropriée au moyen de décharges électriques délivrées par un DCI est associée à un risque accru d'hospitalisation pour insuffisance cardiaque, tandis que des épisodes récurrents d'arythmie ventriculaire exigeant un traitement par décharge électrique sont associés à des taux supérieurs de mortalité et d'hospitalisation pour insuffisance cardiaque.

Effect of coronary revascularization on long-term clinical outcomes in patients with ischemic cardiomyopathy and recurrent ventricular arrhythmia.

BACKGROUND: Patients with ventricular tachycardia (VT) postmyocardial infarction (MI) are a higher risk group with significant morbidity and mortality. We examined the impact of prior coronary revascularization on clinical outcomes in patients with ischemic cardiomyopathy and VT. METHODS: The VANISH trial randomized 259 patients with prior MI and antiarrhythmic drug-refractory VT to receive escalated medical therapy or catheter ablation. Clinical outcomes were compared according to whether patients have undergone prior revascularization procedures. The primary outcome was a composite of death, appropriate implantable cardiac defibrillator (ICD) shock, or VT storm. The secondary outcomes included elements of the primary outcome, hospitalization, and any ventricular arrhythmia. RESULTS: 190 patients (73%) had prior coronary revascularization. Revascularization group had more men (97% vs 83%; P  =  0.0003) and patients in that group were older (mean age 69.3 ± 7.6 vs 66.7 ± 9.2; P  =  0.04), had more renal insufficiency (22.6% vs 8.7%; P  =  0.01), and were more likely to have an implanted cardiac resynchronization device (23% vs 10%, P  =  0.03) as compared with the nonrevascularized patients. There were no significant differences in baseline medication use. There was a trend toward fewer hospitalizations in the revascularization group (64% vs 77%; P  =  0.07); there were no differences in the individual outcomes of mortality, VT storm, ICD shocks, recurrent MI, or cardiac failure. CONCLUSIONS: In this cohort of patients with an ischemic cause for VT, a history of prior coronary revascularization was not associated with a reduction in ventricular arrhythmia or mortality.

Mexiletine or catheter ablation after amiodarone failure in the VANISH trial.

INTRODUCTION: In patients with ischemic heart disease and ventricular tachycardia (VT) refractory to high dose amiodarone, the two most common therapeutic options are adjunctive mexiletine therapy or catheter ablation. There are little existing data on the efficacy of these strategies. We examined the relative efficacy of adjunctive mexiletine and catheter ablation among patients enrolled in the VANISH trial. METHODS: All subjects enrolled in the VANISH trial who had VT refractory to high dose (≥ 300 mg daily) amiodarone at baseline were included. Per protocol, subjects randomized to escalated drug therapy received adjunctive mexiletine. RESULTS: Nineteen of the 259 patients were receiving high-dose amiodarone at baseline and 11 were randomized to escalated therapy with mexiletine and 8 to ablation. The adjunctive mexiletine group had a higher rate of the primary composite outcome (death, VT storm, or appropriate shock) in comparison to catheter ablation (HR 6.87 [2.08-22.8]). Over 90% of the patients in the adjunctive mexiletine/group experienced a primary endpoint during a median 9.2 months' follow-up. There was no difference in the rate of adverse events between the two groups. CONCLUSIONS: Mexiletine has limited efficacy in the treatment of recurrent VT despite high-dose amiodarone therapy, in patients with ischemic heart disease. Catheter ablation is a superior strategy in this population.

Social-media-enabled learning in emergency medicine: a case study of the growth, engagement and impact of a free open access medical education blog.

BACKGROUND: Clinicians are increasingly using social media for professional development and education. In 2012, we developed the St.Emlyn's blog, an open access resource dedicated to providing free education in the field of emergency medicine. OBJECTIVE: To describe the development and growth of this international emergency medicine blog. METHOD: We present a narrative description of the development of St.Emlyn's blog. Data on scope, impact and engagement were extracted from WordPress, Twitter and Google Analytics. RESULTS: The St.Emlyn's blog demonstrates a sustained growth in size and user engagement. Since inception in 2012, the site has been viewed over 1.25 million times with a linear year-on-year growth. We have published over 500 blog posts, each of which attracts a mean of 2466 views (range 382-69 671). The site has been viewed in nearly every country in the world, although the majority (>75%) of visitors come from the USA, UK and Australia. SUMMARY: This case study of an emergency medicine blog quantifies the reach and engagement of social-media-enabled learning in emergency medicine.

Primary Prevention of Sudden Cardiac Death With Device Therapy in Urban and Rural Populations.

BACKGROUND: Implantable cardioverter defibrillators (ICDs) have shown benefit in reducing mortality in patients with heart failure, after myocardial infarction, and those with reduced ejection fraction. We sought to explore the use of this therapy in specialized heart function clinics, in rural and urban locations. METHODS: This was a retrospective cohort study performed in 3 specialized heart function clinics in Nova Scotia, 2 of which were in rural locations. All patients with an initial left ventricular ejection fraction ≤ 35% were included from 2006 to 2011. Rates of referral, ICD implantation, and mortality were compared between urban and rural groups. RESULTS: There were 922 patients included in the study; 636 patients in the urban clinic, 286 in the rural locations. Referral rates were higher in the urban clinic compared with the rural locations (80.4% vs 68.3%; P = 0.024). Refusal rates for referral were higher in the rural locations (13.7% vs 2.1%; P < 0.0001). Higher referral rates were associated with urban location (odds ratio [OR], 1.81; 95% confidence interval [CI], 1.01-3.26; P = 0.047), and younger age (OR, 0.96; 95% CI, 0.93-0.99; P = 0.003); lower referral rates for women was observed (OR, 2.29; 95% CI, 1.13-4.63; P = 0.021). Mortality was significantly associated with older age, lack of referral, presence of comorbidities (renal failure, diabetes, peripheral vascular disease) and a rural location. CONCLUSIONS: Specialized heart function clinics have a high rate of appropriate referral for primary prevention ICDs, but referral rates for this life-saving therapy remain lower in rural jurisdictions. This disparity in access to care is associated with increased mortality and might require particular attention to prevent unnecessary deaths.

Bundle Branch Re-Entrant Ventricular Tachycardia: Novel Genetic Mechanisms in a Life-Threatening Arrhythmia.

OBJECTIVES: This study sought to investigate for an underlying genetic etiology in cases of apparent idiopathic bundle branch re-entrant ventricular tachycardia (BBRVT). BACKGROUND: BBRVT is a life-threatening arrhythmia occurring secondary to macro-re-entry within the His-Purkinje system. Although classically associated with dilated cardiomyopathy, BBRVT may also occur in the setting of isolated, unexplained conduction system disease. METHODS: Cases of BBRVT with normal biventricular size and function were recruited from 6 North American centers. Enrollment required a clinically documented wide complex tachycardia and BBRVT proven during invasive electrophysiology study. Study participants were screened for mutations within genes associated with cardiac conduction system disease. Pathogenicity of identified mutations was evaluated using in silico phylogenetic and physicochemical analyses and in vitro biophysical studies. RESULTS: Among 6 cases of idiopathic BBRVT, each presented with hemodynamic compromise and 2 suffered cardiac arrests requiring resuscitation. Putative culprit mutations were identified in 3 of 6 cases, including 2 in SCN5A (Ala1905Gly [novel] and c.4719C>T [splice site mutation]) and 1 in LMNA (Leu327Val [novel]). Biophysical analysis of mutant Ala1905Gly Nav1.5 channels in tsA201 cells revealed significantly reduced peak current density and positive shifts in the voltage-dependence of activation, consistent with a loss-of-function. The SCN5A c.4719C>T splice site mutation has previously been reported as disease-causing in 3 cases of Brugada syndrome, whereas the novel LMNA Leu327Val mutation was associated with a classic laminopathy phenotype. Following catheter ablation, BBRVT was noninducible in all cases and none experienced a clinical recurrence during follow-up. CONCLUSIONS: Our investigation into apparent idiopathic BBRVT has identified the first genetic culprits for this life-threatening arrhythmia, providing further insight into its underlying pathophysiology and emphasizing a potential role for genetic testing in this condition. Our findings also highlight BBRVT as a novel genetic etiology of unexplained sudden cardiac death that can be cured with catheter ablation.

An Integrated Management Approach to Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia resulting in mortality and morbidity. Gaps in oral anticoagulation and education of patients regarding AF have been identified as areas that require improvement. METHODS AND RESULTS: A before-and-after study of 433 patients with newly diagnosed AF in the 3 emergency departments in Nova Scotia from January 1, 2011 until January 31, 2014 was performed. The "before" phase underwent the usual-care pathway for AF management; the "after" phase was enrolled in a nurse-run, physician-supervised AF clinic. The primary outcome was a composite of death, cardiovascular hospitalization, and AF-related emergency department visits. A propensity analysis was performed to account for differences in baseline characteristics. RESULTS: A total of 185 patients were enrolled into the usual-care group, and 228 patients were enrolled in the AF clinic group. The mean age was 64±15 years and 44% were women. In a propensity-matched analysis, the primary outcome occurred in 44 (26.2%) patients in the usual-care group and 29 (17.3%) patients in the AF clinic group (odds ratio 0.71; 95% CI [0.59, 1]; P=0.049) at 12 months. Prescription of oral anticoagulation was increased in the CHADS2 ≥2 group (88.4% in the AF clinic versus 58.5% in the usual-care group, P<0.01). CONCLUSIONS: Adoption of this integrated management approach for the burgeoning population of AF may provide an overall benefit to cardiovascular morbidity and mortality.