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The technological evolution and widespread availability of wearables and handheld ECG devices capable of screening for atrial fibrillation (AF), and their promotion directly to consumers, has focused attention of health care professionals and patient organizations on consumer-led AF screening. In this Frontiers review, members of the AF-SCREEN International Collaboration provide a critical appraisal of this rapidly evolving field to increase awareness of the complexities and uncertainties surrounding consumer-led AF screening. Although there are numerous commercially available devices directly marketed to consumers for AF monitoring and identification of unrecognized AF, health care professional–led randomized controlled studies using multiple ECG recordings or continuous ECG monitoring to detect AF have failed to demonstrate a significant reduction in stroke. Although it remains uncertain if consumer-led AF screening reduces stroke, it could increase early diagnosis of AF and facilitate an integrated approach, including appropriate anticoagulation, rate or rhythm management, and risk factor modification to reduce complications. Companies marketing AF screening devices should report the accuracy and performance of their products in high- and low-risk populations and avoid claims about clinical outcomes unless improvement is demonstrated in randomized clinical trials. Generally, the diagnostic yield of AF screening increases with the number, duration, and temporal dispersion of screening sessions, but the prognostic importance may be less than for AF detected by single–time point screening, which is largely permanent, persistent, or high-burden paroxysmal AF. Consumer-initiated ECG recordings suggesting possible AF always require confirmation by a health care professional experienced in ECG reading, whereas suspicion of AF on the basis of photoplethysmography must be confirmed with an ECG. Consumer-led AF screening is unlikely to be cost-effective for stroke prevention in the predominantly young, early adopters of this technology. Studies in older people at higher stroke risk are required to demonstrate both effectiveness and cost-effectiveness. The direct interaction between companies and consumers creates new regulatory gaps in relation to data privacy and the registration of consumer apps and devices. Although several barriers for optimal use of consumer-led screening exist, results of large, ongoing trials, powered to detect clinical outcomes, are required before health care professionals should support widespread adoption of consumer-led AF screening.

Catheter ablation has brought major advances in the management of patients with atrial fibrillation (AF). As evidenced by multiple randomized trials, AF catheter ablation can reduce the risk of recurrent AF and improve quality of life. In some studies, AF ablation significantly reduced cardiovascular hospitalizations. Despite the existing data on AF catheter ablation, numerous knowledge gaps remain concerning this intervention. This report is based on a recent virtual workshop convened by the National Heart, Lung, and Blood Institute to identify key research opportunities in AF ablation. We outline knowledge gaps related to emerging technologies, the relationship between cardiac structure and function and the success of AF ablation in patient subgroups in whom clinical benefit from ablation varies, and potential platforms to advance clinical research in this area. This report also considers the potential value and challenges of a sham ablation randomized trial. Prioritized research opportunities are identified and highlighted to empower relevant stakeholders to collaborate in designing and conducting effective, cost-efficient, and transformative research to optimize the use and outcomes of AF ablation.

Introduction: Heart failure (HF) is the leading cause of death in patients with atrial fibrillation (AF). Although sodium-glucose co-transporter 2 inhibitors (SGLT2i) reduce HF in a broad range of populations, they have not been studied specifically in patients with AF. Objective: We aimed to determine the proportion of AF patients who are eligible for an SGLT2i based on co-morbidities, and compare their risk of cardiovascular outcomes to ineligible patients. Methods: We pooled data from two randomized controlled trials (RCTs) of AF patients (RE-LY and ACTIVE-W). Among patients assigned to the anticoagulation arms, those meeting the inclusion criteria from at least one of the large Phase 3 SGLT2i RCTs were included in the “SGLT2i-eligible” and the others in the “SGLT2i-ineligible” group. Eligibility indications were diabetes mellitus + cardiovascular disease (DM+CVD), HF with reduced ejection fraction (HFrEF), and renal disease. We examined a primary outcome of cardiovascular death and hospitalization for HF, and compared study outcomes between SGLT2i-eligible and ineligible groups. Results: A total of 21485 AF patients (mean age: 71.2±8.8, 36.1% women, Median CHA 2 DS 2 -VASc Score = 3, IQR 2-4) met inclusion. The proportion of AF patients eligible for treatment with an SGLT2i was 23.6%, with 8.9%, 22.6%, 9.1% being eligible for Empagliflozin, Dapagliflozin, and Canagliflozin, respectively. Renal disease (17.6%) was the most common eligibility indication, followed by DM+CVD (9.0%) and HFrEF (5.3%). After a median follow-up of 1.9 years, the incidence of cardiovascular death/hospitalization for HF (10.9% vs. 6.3%, p Conclusion: The majority of AF patients are not eligible for an SGLT2i. Although these patients are lower-risk than eligible patients, they still have high rates of cardiovascular events. RCTs are needed to test the efficacy of SGLT2is in AF patients.

Background: New-onset atrial fibrillation (NOAF) is a common complication after transcatheter aortic valve replacement (TAVR), though estimates of the precise incidence are variable. We sought to quantify the incidence of NOAF after TAVR, explore the associated outcomes and identify predictors for this complication. Methods: Using a broad strategy, we searched Medline, EMBASE and the Cochrane database from 2015-2020 for articles that reported any outcomes of TAVR. We extracted data for studies published prior to 2015 from a previous systematic review (22 studies in total). Reviewers performed screening and data extraction in duplicate. We pooled data using a random effects model with Mantel-Haenszel weighting. Results: We identified 183 studies with 296,986 total participants that reported NOAF from 2008 to 2020. The pooled incidence of NOAF after TAVR was 9.9% (95%CI 8.1-12%). NOAF after TAVR was associated with longer index hospitalization (MD 2.66 days, 95% CI 1.05-4.27), higher risk of stroke (RR 1.65, 95% CI 1.09-2.5) and 30-day mortality (RR 1.76, 95%CI 1.12-2.76). NOAF after TAVR was also associated with increased risk of major or life-threatening bleeding (RR 1.60, 95%CI 1.39-1.84) and new permanent pacemaker implantation (RR 1.12, 95%CI 1.05-1.18). Risk factors for the development of NOAF after TAVR included trans-apical access, pulmonary hypertension, chronic kidney disease, peripheral vascular disease, and severe mitral regurgitation. Conclusions: NOAF is common after TAVR and associated with a longer hospital stay, a higher risk of stroke, major bleeding, mortality and permanent pacemaker implantation. Whether this risk is modifiable requires further study.

Cardiac thromboembolism attributed to atrial fibrillation (AF) is responsible for up to one-third of ischemic strokes. Stroke may be the first manifestation of previously undetected AF. Given the efficacy of oral anticoagulants in preventing AF-related ischemic strokes, strategies of searching for AF after a stroke using ECG monitoring followed by oral anticoagulation (OAC) treatment have been proposed to prevent recurrent cardioembolic strokes. This white paper by experts from the AF-SCREEN International Collaboration summarizes existing evidence and knowledge gaps on searching for AF after a stroke by using ECG monitoring. New AF can be detected by routine plus intensive ECG monitoring in approximately one-quarter of patients with ischemic stroke. It may be causal, a bystander, or neurogenically induced by the stroke. AF after a stroke is a risk factor for thromboembolism and a strong marker for atrial myopathy. After acute ischemic stroke, patients should undergo 72 hours of electrocardiographic monitoring to detect AF. The diagnosis requires an ECG of sufficient quality for confirmation by a health professional with ECG rhythm expertise. AF detection rate is a function of monitoring duration and quality of analysis, AF episode definition, interval from stroke to monitoring commencement, and patient characteristics including old age, certain ECG alterations, and stroke type. Markers of atrial myopathy (eg, imaging, atrial ectopy, natriuretic peptides) may increase AF yield from monitoring and could be used to guide patient selection for more intensive/prolonged poststroke ECG monitoring. Atrial myopathy without detected AF is not currently sufficient to initiate OAC. The concept of embolic stroke of unknown source is not proven to identify patients who have had a stroke benefitting from empiric OAC treatment. However, some embolic stroke of unknown source subgroups (eg, advanced age, atrial enlargement) might benefit more from non–vitamin K-dependent OAC therapy than aspirin. Fulfilling embolic stroke of unknown source criteria is an indication neither for empiric non–vitamin K-dependent OAC treatment nor for withholding prolonged ECG monitoring for AF. Clinically diagnosed AF after a stroke or a transient ischemic attack is associated with significantly increased risk of recurrent stroke or systemic embolism, in particular, with additional stroke risk factors, and requires OAC rather than antiplatelet therapy. The minimum subclinical AF duration required on ECG monitoring poststroke/transient ischemic attack to recommend OAC therapy is debated.

Ischemic strokes related to atrial fibrillation are highly prevalent, presenting with severe neurologic syndromes and associated with high risk of recurrence. Although advances have been made in both primary and secondary stroke prevention for patients with atrial fibrillation, the long-term risks for stroke recurrence and bleeding complications from antithrombotic treatment remain substantial. We summarize the major advances in stroke prevention for patients with atrial fibrillation during the past 30 years and focus on novel diagnostic and treatment approaches currently under investigation in ongoing clinical trials. Non–vitamin K antagonist oral anticoagulants have been proven to be safer and equally effective compared with warfarin in stroke prevention for patients with nonvalvular atrial fibrillation. Non–vitamin K antagonist oral anticoagulants are being investigated for the treatment of patients with atrial fibrillation and rheumatic heart disease, for the treatment of patients with recent embolic stroke of undetermined source and indirect evidence of cardiac embolism, and in the prevention of vascular-mediated cognitive decline in patients with atrial fibrillation. Multiple clinical trials are assessing the optimal timing of non–vitamin K antagonist oral anticoagulant initiation after a recent ischemic stroke and the benefit:harm ratio of non–vitamin K antagonist oral anticoagulant treatment in patients with atrial fibrillation and history of previous intracranial bleeding. Ongoing trials are addressing the usefulness of left atrial appendage occlusion in both primary and secondary stroke prevention for patients with atrial fibrillation, including those with high risk of bleeding. The additive value of prolonged cardiac monitoring for subclinical atrial fibrillation detection through smartphone applications or implantable cardiac devices, together with the optimal medical management of individuals with covert paroxysmal atrial fibrillation, is a topic of intensive research interest. Colchicine treatment and factor XIa inhibition constitute 2 novel pharmacologic approaches that might provide future treatment options in the secondary prevention of cardioembolic stroke attributable to atrial fibrillation.

Background: Atrial fibrillation (AF) significantly increases risk for heart failure (HF) and independently increases mortality and adverse in-hospital outcomes in HF patients. Validated clinical risk scores (ARC2H) can predict HF in patients with AF, but are limited in application as AF is frequently clinically silent or undetected. However, AF may be preceded by significant preclinical remodeling (left atrial enlargement (LAE) or excessive atrial ectopy (EAE)). Whether LAE and EAE are associated with HF prior to AF is unclear. Method(s): We analyzed consecutive adults >65 years with outpatient echocardiography or Holter at 11 Ontario community cardiology clinics (2010-2017). Exclusions were history of AF, anticoagulation, pacemaker/ICD/ILR, and prosthetic valve. Using linked administrative databases, we assessed 5-year rates of HF (primary) and incident AF and death (secondary) associated with LAE and EAE and among subgroups (M vs. F; 75; CHADS-VASC 0-2 vs. 3-6). Competing risks cox proportional hazards estimated adjusted hazard of HF for severe LAE: >47mm (M);>52mm (F)) or increased APBs/hour (EAE: >30) or both LAE and EAE, adjusting for age, vascular comorbidities and left ventricular (LV) dysfunction. Results: In 28,261 adults (mean 73+/-6 years), direct age-adjusted survival was reduced for those with severe LAE and EAE. 5-year rates of HF were increased for severe (8.8%) vs. moderate (3.5%) and mild (1.4%) LAE and for those with excessive (3.8%) vs. normal (2.5%) ectopy. For both LAE and EAE, those >75 and with a CHADS score 3-6 showed marked increases in HF at 5 years compared to both LAE and EAE showed an over 3-fold increased hazard of HF (HR=3.28; p Conclusions: Severe LAE and EAE without known AF are associated with increased risk of HF and AF after adjusting for LV dysfunction, particularly for those >75 and with high vascular burden. These data have implications for risk stratification, AF screening, and trials for HF prevention in individuals with left atrial remodeling.

The left atrial appendage (LAA) has been deemed by some to be our “most lethal attachment,” and the concept of excluding it from systemic circulation has been thought to hold great promise. This concept has been around since 1948, when John Madden1 proclaimed it a plausible therapy for recurrent emboli in atrial fibrillation. Despite this, higher-quality evidence in the field is only just emerging. In 2009, we were asked to debate on the topic “Does left atrial appendage occlusion eliminate the need for warfarin?” Dr Holmes represented the protagonist viewpoint,2 while Dr Whitlock represented the antagonist viewpoint.3 The protagonist viewpoint was based on 3 key points to support the position that LAA occlusion can replace warfarin. First, the dominant source of stroke in patients with nonvalvular atrial fibrillation (AF) is cardioemboli, of which >90% are from the LAA.4 Second, oral anticoagulation (OAC) therapy requires long-term use, good control, and ongoing compliance to be effective. Warfarin is underused, is difficult to maintain in therapeutic range, and increases bleeding risk. On the contrary, LAA occlusion is a 1-time procedure that requires no long-term compliance. Third, the imbalance of safety that favored warfarin over the Watchman device in the Watchman LAA Closure Technology for Embolic Protection in Patients With Atrial Fibrillation (PROTECT AF) clinical trial was driven by periprocedural events, which were thought to be decreasing with experience.5 The antagonist viewpoint raised 3 key points to support the position that LAA occlusion could not yet replace warfarin therapy. First, the success and safety of LAA occlusion were as yet incompletely understood. Second, the longer-term protection from stroke related to leaks around occlusion devices had not been shown, and the surgical literature suggests that these leaks may contribute to recurrent events.6 This has important implications for LAA occlusion …

We thank Jin-shan and Xue-bin, Kosiuk et al, and Ye et al for their interest in our study1 and for raising some important points. The intent of the SMAC-AF study (Substrate Modification with Aggressive Blood Pressure Control) was to focus on both the initiating triggers and maintaining substrate for atrial fibrillation (AF) that result from hypertension, testing whether aggressive blood pressure control could modify the outcomes of catheter ablation. There are 3 potential mechanisms by which blood pressure treatment may affect the substrate involved in the maintenance of AF: (1) reduction in left ventricular diastolic pressure, leading to improved left ventricular hemodynamics, thereby decreasing atrial stretch; (2) reduction of fibrosis; and (3) effects on ion channel function.2 Chronically elevated blood pressure (BP) has been demonstrated in animal models to result in significant conduction abnormalities, shortening of atrial wavelength, and increased AF.2 Further studies demonstrated functional changes in the atrium as quickly as 15 weeks by using magnetic resonance …

Background— Atrial fibrillation (AF) is the most common sustained arrhythmia; however, little is known about patients in a primary care setting from high-, middle-, and low-income countries. Methods and Results— This prospective registry enrolled patients presenting to an emergency department with AF at 164 sites in 46 countries representing all inhabited continents. Patient characteristics were compared among 9 major geographic regions. Between September 2008 and April 2011, 15 400 patients were enrolled. The average age was 65.9, standard deviation 14.8 years, ranging from 57.2, standard deviation 18.8 years in Africa, to 70.1, standard deviation 13.4 years in North America, P P P 2 score of ≥2 was greatest in North America (65.7%) but was only 11.2% in China, P P Conclusions— There is a large global variation in age, risk factors, concomitant diseases, and treatment of AF among regions. Improving outcomes globally requires an understanding of this variation and the conduct of research focused on AF associated with different underlying conditions and treatment of AF and predisposing conditions in different socioeconomic settings.

In a Clinician Update, Dr Lip seems to recommend oral anticoagulation for all patients with device-detected atrial high-rate episodes (AHREs) and a CHA2DS2-VASc score of at least 1.1 Unfortunately, this recommendation is not evidence based. Although the TRENDS study (The Relationship Between Daily Atrial Tachyarrhythmia Burden From Implantable Device Diagnostics and Stroke Risk)2 and ASSERT (Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and Atrial Fibrillation Reduction Atrial Pacing Trial) …

Background— Approximately 268 000 Fidelis leads were implanted worldwide until distribution was suspended because of a high rate of early failure. Careful analyses of predictors of increased lead failure hazard are required to help direct future lead design and also to inform decision making on lead replacement. We sought to perform a comprehensive analysis of all potential predictors in a multicenter study. Methods and Results— A total of 3169 Sprint Fidelis leads were implanted in 11 centers with a total of 251 failures. Lead failure rates at 3, 4, and 5 years were 5.3%, 10.6%, and 16.8%, respectively. The rate of lead failure continues to accelerate ( P P =0.005). Both axillary and subclavian access increased the hazard of failure ( P =0.007); hazard ratio for axillary was 1.94, (95% confidence interval, 1.23–3.04) and for subclavian 1.63 (95% confidence interval, 1.08–2.46). Previous lead failure increased the hazard of a subsequent Fidelis failure with a hazard ratio of 3.12 (95% confidence interval, 1.80–5.41; P Conclusions— The rate of Fidelis failure continues to increase over time, with failures approaching 17% at 5 years. Women, patients with leads inserted via the subclavian or axillary vein, and those with a previous lead fracture were at greatest risk of Fidelis failure. Our data suggest that Fidelis replacement should be strongly considered at the time of generator replacement.

Background— Genetic testing can diagnose long-QT syndrome (LQTS) in asymptomatic relatives of patients with an identified mutation; however, it is costly and subject to availability. The accuracy of a simple algorithm that incorporates resting and exercise ECG parameters for screening LQTS in asymptomatic relatives was evaluated, with genetic testing as the gold standard. Methods and Results— Asymptomatic first-degree relatives of genetically characterized probands were recruited from 5 centers. QT intervals were measured at rest, during exercise, and during recovery. Receiver operating characteristics were used to establish optimal cutoffs. An algorithm for identifying LQTS carriers was developed in a derivation cohort and validated in an independent cohort. The derivation cohort consisted of 69 relatives (28 with LQT1, 20 with LQT2, and 21 noncarriers). Mean age was 35±18 years, and resting corrected QT interval (QTc) was 466±39 ms. Abnormal resting QTc (females ≥480 ms; males ≥470 ms) was 100% specific for gene carrier status, but was observed in only 48% of patients; however, mutations were observed in 68% and 42% of patients with a borderline or normal resting QTc, respectively. Among these patients, 4-minute recovery QTc ≥445 ms correctly restratified 22 of 25 patients as having LQTS and 19 of 21 patients as being noncarriers. The combination of resting and 4-minute recovery QTc in a screening algorithm yielded a sensitivity of 0.94 and specificity of 0.90 for detecting LQTS carriers. When applied to the validation cohort (n=152; 58 with LQT1, 61 with LQT2, and 33 noncarriers; QTc=443±47 ms), sensitivity was 0.92 and specificity was 0.82. Conclusions— A simple algorithm that incorporates resting and exercise-recovery QTc is useful in identifying LQTS in asymptomatic relatives.

Background— Dabigatran 150 and 110 mg twice a day and warfarin are effective for stroke prevention in atrial fibrillation. The purpose of this study was to compare their risks of bleeding in the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) trial. Methods and Results— The RE-LY trial randomized 18 113 patients to receive dabigatran 110 or 150 mg twice a day or warfarin dose adjusted to an international normalized ratio of 2.0 to 3.0 for a median follow-up of 2.0 years. Compared with warfarin, dabigatran 110 mg twice a day was associated with a lower risk of major bleeding (2.87% versus 3.57%; P =0.002), whereas dabigatran 150 mg twice a day was associated with a similar risk of major bleeding (3.31% versus 3.57%; P =0.32). There was a significant treatment-by-age interaction, such that dabigatran 110 mg twice a day compared with warfarin was associated with a lower risk of major bleeding in patients aged P P =0.89; P for interaction P P =0.07; P for interaction Conclusions— In patients with atrial fibrillation at risk for stroke, both doses of dabigatran compared with warfarin have lower risks of both intracranial and extracranial bleeding in patients aged Clinical Trial Registration— http://www.clinicaltrials.gov . Unique identifier: NCT00262600.

Background— Oral anticoagulation (OAC) therapy is effective in atrial fibrillation but requires vigilance to maintain the international normalized ratio in the therapeutic range. This report examines how differences in time in therapeutic range (TTR) between centers and between countries affect the outcomes of OAC therapy. Methods and Results— In a posthoc analysis, the TTRs of patients on OAC in a randomized trial of OAC versus clopidogrel plus aspirin (Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events [ACTIVE W]) were used to calculate the mean TTR for each of 526 centers and 15 countries. Proportional-hazards analysis, with and without adjustment for baseline variables, was performed, with patients stratified by TTR quartile and country. A wide variation in TTRs was found between centers, with mean TTRs for centers in the 4 quartiles of 44%, 60%, 69%, and 78%. For patients at centers below the median TTR (65%), no treatment benefit was demonstrated as measured by relative risk for vascular events of clopidogrel plus aspirin versus OAC (relative risk, 0.93; 95% confidence interval, 0.70 to 1.24; P =0.61). However, for patients at centers with a TTR above the study median, OAC had a marked benefit, reducing vascular events by >2-fold (relative risk, 2.14; 95% confidence interval, 1.61 to 2.85; P Conclusions— A wide variation exists in international normalized ratio control, as measured by TTR, between clinical centers and between countries, which has a major impact on the treatment benefit of OAC therapy. For centers and countries, a target threshold TTR exists (estimated between 58% and 65%) below which there appears to be little benefit of OAC over antiplatelet therapy.

Introduction: Patient decision aids (PtDA) support quality decision making and improve patient reported outcomes. This pilot randomized controlled trial aimed to evaluate the use of an ICD specific PtDA on patient’s decisional conflict and ICD knowledge. Methods: In accordance with the International Patient Decision Aid Standards (IPDAS), a PtDA was developed. We conducted a single-centre non-blinded RCT with concealed allocation to evaluate the effect of a PtDA in patients offered an ICD for primary prevention. Exclusions: 1) inability to read English and complete a PtDA, 2) ICD for secondary prevention, 3) biventricular devices. Consented patients were randomized to 1) usual care, 2) PtDA intervention. Prior to specialist consultation the PtDA intervention group received the PtDA. The primary outcome of decisional conflict was measured before consultation and post-ICD implantation. The decisional conflict scale measures patient’s perception of difficultly making a decision, uncertainty regarding the decision and factors contributing to uncertainty. Higher scores are indicative of greater decisional conflict. Knowledge was measured as a secondary outcome using 5 questions related to ICD treatment, benefits and risks. Results: Eighty-two patients were randomized to usual care (n=41) or PtDA intervention (n=41). Mean age (SD) was 66.76 (11.05), 27% female. Baseline characteristics between groups were balanced. Patients receiving the PtDA intervention scored significantly lower on the DCS scale with a total mean score of 27.32 (18.37) when compared to usual care, scoring 49.53 (18.62) (p Conclusion: The results of this pilot study suggest that use of an ICD-specific PtDA reduced patient’s decisional conflict both pre and post implantation and improved knowledge. In the context of making decisions regarding life prolonging interventions, our findings suggest evidence based decision support results in improved patient decision quality.

Introduction: Sub-clinical AF has been reported in 10% of pacemaker patients (≥ 6 minutes, with 3 months of monitoring) and 16% of patients following cryptogenic stroke (≥ 30 seconds, with 1 month of monitoring). It is unknown how common sub-clinical AF is among other patient groups, including the elderly. These data are needed to give context to the detection of sub-clinical AF in clinical practice. Methods: We prospectively investigated the prevalence of sub-clinical AF among individuals ≥ 80 years, without known AF or symptoms of arrhythmia, attending primary care clinics. Subjects had a history of hypertension and at least one of the following: diabetes, BMI ≥ 30, sleep apnea, smoking, coronary disease, heart failure or left ventricular hypertrophy. Patients were recruited from 7 Ontario family practice clinics (n=119) and one general medicine clinic (n=10). Patients underwent 30 days of continuous, non-invasive ambulatory ECG monitoring using a device with automatic AF detection (Vitaphone 3100). The primary outcome was a composite of atrial flutter (AFL) or AF ≥ 6 minutes in duration. Those without AF were invited to complete an additional 30 days of monitoring. Results: Of 129 patients screened and consented, 100 patients initiated monitoring for an average monitoring duration of 36± 21 days. The mean (SD) age was 84 ± 3 years and systolic blood pressure was 138 ± 17 mmHg; 50% had coronary disease, 28% had diabetes and 6% had heart failure. Only 4% had a history of prior stroke. Thirty days of monitoring was completed by 57% of patients and 31% completed an additional 30 days. AFL or AF ≥ 30 seconds duration was documented in 19/100 patients; ≥ 6 minutes in 15; ≥ 30 minutes in 12; ≥ 6 hours in 8 and ≥ 24 hours in 2. Shorter episodes of atrial tachycardia lasting less than 30 seconds were observed in 47 patients. Conclusions: In this prospective, outpatient study, using non-invasive ECG monitoring, we found AFL or AF ≥ 6 minutes in 15% of elderly individuals with stroke risk factors. This high background prevalence of AFL/AF among elderly patients suggests a possible role for AF screening in this population; but also should be taken into consideration when interpreting the prevalence of AFL/AF in other populations.

There is a “buzz” around the field of left atrial appendage (LAA) occlusion. Although it is an area of emerging evidence,1 that evidence and our understanding of thrombus formation in the LAA in atrial fibrillation is as yet incomplete. We agree with Drs Salzberg and Emmert that a Heart Team approach must be taken in assessing patients for potential LAA occlusion. However, we do caution extrapolating the results of 1 device to another; ie, assuming that there is a device class effect. Currently, the surgical occlusion devices do …

Introduction: Ablation of ventricular tachycardia (VT) substrate in patient at risk for VT in the setting of ischemic heart disease is a technically challenging procedure. We thought to evaluate a novel algorithm used to automatically identify target electrograms. Methods: 16 consecutive patients (70±10 years of age, 90% male, 34±18% LV EF) had 20 ablations for ischemic VT using CARTO 3 mapping system over 2 years. Left ventricular (LV) substrate was mapped during right ventricular (RV) apical stimulation. Navistar Thermocool 3.5 mm irrigated tip catheters were used in all patients. A novel algorithm counting the number of electrogram deflections (NOD) crossing the 0.05mV noise threshold and duration of time from first to last such deflection during the window of interest (total fractionation time, TFT) was applied to all acquired maps after ablation was complete. Snapshots of 200 electrograms representing the high and low end of TFT and NOD values were presented to a group of 8 electrophysiologists experienced in VT ablation who were asked to select electrograms they would target for substrate ablation. The diagnostic accuracy of TFT and NOD values was then analysed. Results: Across the range of TFT values (0.0-281.0 ms), a cut-off value of 49.0 ms (81.6% sensitivity, 57% specificity) was established as an optimal indicator of an ablation target. Area under the curve for TFT was 0.675 (95% CI: 0.59-0.75, p=0.001). For NOD values (0.0-70.0 deflections), a cut off of 4.5 deflections (88.0% Sensitivity, 57 % specificity) was established as an optimal indicator of an ablation target. The area under the curve for NOD yielded an area of 0.75 (95% CI: 0.68-0.82, P=0.001). For TFT-NOD product as a variable, a cut-off value of 64 (91.0% Sensitivity, 52.4 % specificity) an optimal indicator of an ablation target. The Area under the curve for NOD and TFT multiple was 0.72 (95% CI: 0.65-0.80, P=0.001). Conclusion: A novel algorithm may be able to automatically classify LV substrate during mapping and ablation of ischemic VT with high sensitivity and acceptable specificity.

Atrial fibrillation (AF) is the most common cardiac arrhythmia1 and a leading cause of stroke.2 AF-related strokes are associated with significant morbidity, mortality, and healthcare costs,2–5 yet they are highly preventable.6,7 Unfortunately, AF is often undiagnosed or untreated when stroke occurs.8 Given the availability of effective oral anticoagulant (OAC) medications and evidence-based guidelines for their use,9–11 population-based AF screening has the potential to become an important public health program. Article see p 2176 There is considerable interest in developing AF screening programs for 3 reasons: (1) The prevalence of AF is increasing as a result of our aging population; (2) new OAC medications offer safe, effective, and convenient therapy for patients once AF is identified; and (3) a variety of portable, wearable, and implantable technologies have been developed to detect AF, which may facilitate AF screening in a variety of clinical settings.12–14 Although there is great optimism for AF screening, high-quality studies examining optimal AF screening methods, settings, and target populations are only starting to emerge.12,13,15 In this issue of Circulation , Svennberg and colleagues16 report the results of the STROKESTOP study, a prospective, population-based study of systematic AF screening with intermittent ambulatory …

Background— Several randomized trials have compared atrial-based (dual-chamber or atrial) pacing with ventricular pacing in patients with bradycardia. No trial has shown a mortality reduction, and only 1 small trial suggested a reduction in stroke. The goal of this review was to determine whether atrial-based pacing prevents major cardiovascular events. Methods and Results— A systematic review was performed of publications since 1980. For inclusion, trials had to compare an atrial-based with a ventricular-based pacing mode; use a randomized, controlled, parallel design; and have data on mortality, stroke, heart failure, or atrial fibrillation. Individual patient data were obtained from 5 of the 8 identified studies, representing 95% of patients in the 8 trials, and a total of 35 000 patient-years of follow-up. There was no significant heterogeneity among the results of the individual trials. There was no significant reduction in mortality (hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.87 to 1.03; P =0.19) or heart failure (HR, 0.89; 95% CI, 0.77 to 1.03; P =0.15) with atrial-based pacing. There was a significant reduction in atrial fibrillation (HR, 0.80; 95% CI, 0.72 to 0.89; P =0.00003) and a reduction in stroke that was of borderline significance (HR, 0.81; 95% CI, 0.67 to 0.99; P =0.035). There was no convincing evidence that any patient subgroup received special benefit from atrial-based pacing. Conclusions— Compared with ventricular pacing, the use of atrial-based pacing does not improve survival or reduce heart failure or cardiovascular death. However, atrial-based pacing reduces the incidence of atrial fibrillation and may modestly reduce stroke.

Background— The relative contribution of the atrial septum and interatrial connections to biatrial activation is a fundamental concept of human cardiac electrophysiology that has yet to be fully characterized. The purpose of the present study was to determine how both atria are coupled electrically. Methods and Results— Twenty patients (16 men; mean age 54±11years) with a history of symptomatic atrial fibrillation (AF) underwent simultaneous biatrial noncontact mapping before catheter ablation of AF. The multiple electrode array catheters were positioned, respectively, in the left atrium (LA; transseptally) and the right atrium (RA). In all but 2 patients, isopotential maps revealed that endocardial septal activations of the RA and LA were separate, independent, and asynchronous of each other. Interatrial conduction was related to the site of initial atrial depolarization, revealing conduction over Bachmann’s bundle in all patients during sinus rhythm, high RA pacing, and pacing from the LA appendage. Pacing from the coronary sinus was associated with conduction over the interatrial connection at the level of the coronary sinus in all patients, and conduction over Bachmann’s bundle also occurred in 5 (26%) of 19 patients. Interatrial conduction over the fossa ovalis occurred in only 2 (2%) of the 116 segments analyzed. Conclusions— Electrical coupling of the RA and LA in humans is predominantly provided by muscular connections at the level of Bachmann’s bundle and the coronary sinus. The true septum (the fossa ovalis and its limbus) of the RA and LA is asynchronous and discordant, usually without contralateral conduction during sinus rhythm or atrial pacing.

A 68-year-old woman with well-controlled hypertension is having 3 to 4 episodes of paroxysmal atrial fibrillation (AF) each month. Despite a ventricular rate of 80 to 100/min while in AF, she complains of palpitations, chest discomfort, and light-headedness. Oral flecainide failed to improve her symptoms, and she refuses to take amiodarone because of concerns about its potential toxicity. She was started on dabigatran (150 mg twice daily) for stroke prevention; her creatinine clearance was calculated at 92 ml/min. AF ablation has been scheduled, and advice is needed regarding periprocedural dabigatran management. AF, the most common cardiac arrhythmia, is a major cause of stroke.1 Although many AF patients are asymptomatic or have adequate symptom palliation with rate-controlling medications, some require treatment strategies aimed at maintaining sinus rhythm. In the United States, it is estimated that >150 000 AF patients undergo catheter ablation each year in an attempt to achieve rhythm control.2 Originally targeted to younger AF patients without structural heart disease, catheter ablation is performed in a broader population now that outcomes have improved. Consequently, the number of ablation procedures performed is expected to increase exponentially over the next decade. Current guidelines recommend anticoagulant prophylaxis in all but the lowest risk AF patients. Until recently, vitamin K antagonists, such as warfarin, were the only option for stroke prevention in such patients. This situation changed with the introduction of new oral anticoagulants (NOACs), which target thrombin or factor Xa. With a more predictable anticoagulant response and shorter half-lives than warfarin, NOACs have the potential to streamline periprocedural management in AF patients undergoing ablation. However, data with NOACs in this setting are limited, and at times contradictory, which complicates their integration into routine practice in patients undergoing catheter ablation. ### Comparison of the Pharmacological Properties of the NOACs With Those of Warfarin NOACs have pharmacological properties that distinguish them from warfarin. These are summarized …

We thank Barra and Agarwal for their interest in our examination of implantable cardioverter-defibrillator (ICD) outcomes and therapies in different age groups, focusing on the elderly.1 We agree that rates of device therapies with conventional programming may overestimate the potential benefit of ICD implantation. Barra and Agarwal suggest that device programming approaches that were used in the Primary Prevention Parameters Evaluation (PREPARE),2 Multicenter Automatic Defibrillator Implantation Trial - Reduce Inappropriate Therapy (MADIT-RIT),3 and Avoid Delivering Therapies for Non-sustained Arrhythmias in ICD Patients III (ADVANCE III)4 trials would lead to rates of appropriate shock and therapy that better reflect the occurrence of ventricular tachyarrhythmia episodes that would more likely have been associated with an arrhythmic death. Early after the initiation of the Ontario ICD Database, the PREPARE study was published, the potential benefits of delaying ICD-delivered therapies were recognized, and participating sites adapted …

Background— The benefit of implantable cardioverter-defibrillators (ICDs) among elderly patients is controversial and may be attenuated by nonarrhythmic death. We examined the impact of age on device-delivered therapies and outcomes after primary or secondary prevention ICD. Methods and Results— In a prospective, inclusive registry of 5399 ICD recipients in Ontario, Canada (February 2007 to September 2010), device-delivered therapies and complications were determined at routine clinic visits. Among primary prevention ICD recipients aged 18 to 49 (n=317), 50 to 59 (n=769), 60 to 69 (n=1336), 70 to 79 (n=1242), and ≥80 (n=275) years, mortality increased with age, as follows: 2.1, 3.0, 5.4, 6.9, and 10.2 deaths per 100 person-years, respectively ( P P P =0.139) and from 11.4 (18–49 years) to 11.9 (≥80 years) per 100 person-years after secondary prevention ICDs ( P =0.993). Covariate-adjusted competing risk analysis demonstrated higher risk of death ( P trend P =0.130) or secondary ( P =0.810) prevention ICD implantation. Conclusions— Whereas elderly patients exhibited increased mortality after ICD implantation, rates of appropriate device shocks were similar across age groups. Decisions regarding ICD candidacy should not be based on age alone but should consider factors that predispose to mortality despite defibrillator implantation.

RE-LY is the largest randomized experience reporting outcomes after interruption of anticoagulant therapy.1 There was no excess of bleeding in patients taking dabigatran, including those having major or urgent surgery.1 David and colleagues correctly state that the majority of procedures performed during the RE-LY trial were minor. Nonetheless, our analysis included 1482 major procedures that had a 6% to 8% rate of major bleeding,1 which was numerically lower among dabigatran-treated patients.1 Hjemdahl et al opine that the high rate of major bleeding in RE-LY patients assigned to dabigatran 150 mg twice daily who had interruption for >72 hours before surgery suggests accumulation of dabigatran in patients with renal impairment. However, data from RE-LY do not support this interpretation, because the same pattern …

Background— Dabigatran reduces ischemic stroke in comparison with warfarin; however, given the lack of antidote, there is concern that it might increase bleeding when surgery or invasive procedures are required. Methods and Results— The current analysis was undertaken to compare the periprocedural bleeding risk of patients in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial treated with dabigatran and warfarin. Bleeding rates were evaluated from 7 days before until 30 days after invasive procedures, considering only the first procedure for each patient. A total of 4591 patients underwent at least 1 invasive procedure: 24.7% of patients received dabigatran 110 mg, 25.4% received dabigatran 150 mg, and 25.9% received warfarin, P =0.34. Procedures included: pacemaker/defibrillator insertion (10.3%), dental procedures (10.0%), diagnostic procedures (10.0%), cataract removal (9.3%), colonoscopy (8.6%), and joint replacement (6.2%). Among patients assigned to either dabigatran dose, the last dose of study drug was given 49 (35–85) hours before the procedure on comparison with 114 (87–144) hours in patients receiving warfarin, P P =0.28; dabigatran 150 mg versus warfarin: relative risk, 1.09; 95% CI, 0.80 to 1.49; P =0.58. Among patients having urgent surgery, major bleeding occurred in 17.8% with dabigatran 110 mg, 17.7% with dabigatran 150 mg, and 21.6% with warfarin: dabigatran 110 mg; relative risk, 0.82; 95% CI, 0.48 to 1.41; P =0.47; dabigatran 150 mg: relative risk, 0.82; 95% CI, 0.50 to 1.35; P =0.44. Conclusions— Dabigatran and warfarin were associated with similar rates of periprocedural bleeding, including patients having urgent surgery. Dabigatran facilitated a shorter interruption of oral anticoagulation. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00262600.

We would like to thank Dr Maytin and colleagues for highlighting some important issues with regard to the Fidelis lead and its appropriate management. The experience that we reported is the only comprehensive experience regarding the Fidelis lead and complications related to its revision.1 The complication classification that we used is based on prior reports on complications due to device advisories or replacements.2,3 Our study was not designed specifically to examine complications due to transvenous lead extraction, so the system of classification suggested by Maytin et al would not be applicable. If traction was attempted, but the lead was abandoned, the patient was classified as lead abandoned. The data reported by Maytin et al4 have significant potential referral bias, as patients with a higher degree of comorbid illness may not have been referred. In …

Background— It has been observed that replacement of an implantable cardioverter-defibrillator generator in response to a device advisory may be associated with a substantial rate of complications, including death. The risk of lead revision in response to a lead advisory has not been determined previously. Methods and Results— Twenty-five implantable cardioverter-defibrillator implantation and follow-up centers from the Canadian Heart Rhythm Society Device Advisory Committee were surveyed to assess complication rates as a result of lead revisions due to the Sprint Fidelis advisory issued in October 2007. As of June 1, 2009, there had been 310 lead failures found in 6237 Sprint Fidelis leads in Canada (4.97%) over a follow-up of 40 months. There were 469 leads to be revised, 66% for confirmed fracture. Of the patients who underwent revision, 95% had a new lead inserted, whereas 4% had a pace/sense lead added. The lead was removed in 248 cases (53%), by simple traction in 61% and by laser lead extraction in 33%. Complications were encountered in 14.5% of the lead revisions; 7.25% of these were major, whereas 7.25% were minor. There were 2 deaths (0.43%). The overall risk of complications (19.8%) was greater in those who underwent lead removal at the time of revision than in those whose leads were abandoned (8.6%; P =0.0008). Conclusions— The overall rate of major complications that arose from lead revision due to the Sprint Fidelis advisory was significant. This must be taken into account when lead revision is planned in those patients who have not yet demonstrated an abnormality in lead performance.

A trial fibrillation (AF) is the most common sustained heart rhythm disorder. It is increasing in incidence, which has major societal implications for our aging population.1–3 It is estimated to affect 1% to 1.5% of the developed world, and the incidence increases with age to a rate of 19.2 per 1000 patient-years in those 65 years of age and older. The most important aspect of the treatment of patients with AF is the prevention of stroke. The average annual stroke rate across risk groups is 5%, and AF-associated strokes confer worse outcomes than those occurring in the absence of AF.1,4 Furthermore, Stroke Prevention in Nonrheumatic Atrial Fibrillation (SPINAF) data suggest that 15% of patients with AF suffer silent cerebral infarctions on computed tomography, the implications of which are unknown.5 Response by Holmes and Schwartz on p 1932 Oral anticoagulant (OAC) therapy with warfarin has been established as the standard for stroke prevention in patients with AF and more than 1 risk factor for stroke.6 Hart et al have summarized this literature in meta-analyses that include 29 trials and 28 044 patients.7,8 Compared with placebo, warfarin reduced the rate of stroke by 64% (95% confidence interval [CI], 49% to 74%), and in trials of warfarin versus antiplatelet, warfarin reduced the rate of stroke by 37% (95% CI, 23% to 48%). This is a large treatment effect when compared with other drug therapies in cardiovascular medicine. Further, even with an absolute risk increase in intracerebral hemorrhage and major hemorrhage of 0.2% per year over antiplatelet therapy, warfarin still produces a statistically significant 26% reduction in overall mortality compared with placebo.7 Despite its demonstrated benefit, warfarin therapy is administered to as few as 25% of patients with AF and only to 70% of patients who are considered …

Background— Cardiac arrest without evident cardiac disease may be caused by subclinical genetic conditions. Provocative testing to unmask a phenotype is often necessary to detect primary electrical disease, direct genetic testing, and perform family screening. Methods and Results— Patients with apparently unexplained cardiac arrest and no evident cardiac disease (normal cardiac function on echocardiogram, no evidence of coronary artery disease, and a normal ECG) underwent systematic evaluation that included cardiac magnetic resonance imaging, signal-averaged ECG, exercise testing, drug challenge, and selective electrophysiological testing. Diagnostic criteria were based on accepted criteria or provocation of the characteristic clinical features for long-QT syndrome, catecholaminergic polymorphic ventricular tachycardia, Brugada syndrome, early repolarization, arrhythmogenic right ventricular cardiomyopathy, coronary spasm, and myocarditis. Sixty-three patients in 9 centers were enrolled (age 43.0±13.4 years, 29 women). A diagnosis was obtained in 35 patients (56%): Long-QT syndrome in 8, catecholaminergic polymorphic ventricular tachycardia in 8, arrhythmogenic right ventricular cardiomyopathy in 6, early repolarization in 5, coronary spasm in 4, Brugada syndrome in 3, and myocarditis in 1. Targeted genetic testing demonstrated evidence of causative mutations in 9 (47%) of 19 patients. Screening of 64 family members of these patients identified 15 affected individuals who were treated (24%). The remaining 28 patients (44%) were considered to have idiopathic ventricular fibrillation. Conclusions— Systematic clinical testing, including drug provocation and advanced imaging, results in unmasking of the cause of apparently unexplained cardiac arrest in >50% of patients. This approach assists in directing genetic testing to diagnose genetically mediated arrhythmia syndromes, which results in successful family screening.