A stroke patient with an unusual electrocardiogram.

We present a case of a 70 year old man with a history of paroxysmal atrial flutter who was admitted to the hospital with symptoms and imaging consistent with an acute stroke. Physical exam was notable for a pulse rate of 50 beats per minute and right sided facial droop with mild dysarthria. Admission ECG shows a junctional bradycardia with evidence of dual AV node physiology, rarely manifested in a retrograde fashion on a standard ECG. The patient likely experienced parasympathetic sinus node slowing in the setting of acute stroke. During post-stroke monitoring, the patient demonstrated return of sinus rhythm with chronotropic competence and he had no additional arrhythmia during admission.

Real-world utilization of the pill-in-the-pocket method for terminating episodes of atrial fibrillation: data from the multinational Antiarrhythmic Interventions for Managing Atrial Fibrillation (AIM-AF) survey.

AIMS: Atrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice. Episodes may stop spontaneously (paroxysmal AF); may terminate only via intervention (persistent AF); or may persist indefinitely (permanent AF) (see European and American guidelines, referenced below, for more precise definitions). Recently, there has been renewed interest in an approach to terminate AF acutely referred to as 'pill-in-the-pocket' (PITP). The PITP is recognized in both the US and European guidelines as an effective option using an oral antiarrhythmic drug for acute conversion of acute/recent-onset AF. However, how PITP is currently used has not been systematically evaluated. METHODS AND RESULTS: The recently published Antiarrhythmic Interventions for Managing Atrial Fibrillation (AIM-AF) survey included questions regarding current PITP usage, stratified by US vs. European countries surveyed, by representative countries within Europe, and by cardiologists vs. electrophysiologists. This manuscript presents the data from this planned sub-study. Our survey revealed that clinicians in both the USA and Europe consider PITP in about a quarter of their patients, mostly for recent-onset AF with minimal or no structural heart disease (guideline appropriate). However, significant deviations exist. See the Graphical abstract for a summary of the data. CONCLUSION: Our findings highlight the frequent use of PITP and the need for further physician education about appropriate and optimal use of this strategy.

Use of the HAVOC Score to Identify Patients at Highest Risk of Developing Atrial Fibrillation.

BACKGROUND: Recent studies using insertable cardiac monitors (ICMs) show a high incidence of atrial fibrillation (AF). Further identifying subsets of patients who could benefit most from ICMs is desirable. We evaluated whether the HAVOC risk score which predicts AF in patients with cryptogenic stroke also predicts AF detection by ICMs in those without recent stroke. METHODS: Participants were included from the prospective, industry-sponsored REVEAL AF study assessing AF incidence in patients with CHADS2 scores ≥3 or =2 with 1 or more additional AF risk factors, who had ICM data and were not receiving anti-arrhythmic drugs. Ischemic stroke occurring less than 1 year prior to enrollment or documented AF were exclusion criteria. AF was defined as an adjudicated ICM-detected episode ≥6 min in duration. HAVOC scores were calculated by assigning 4 points for congestive heart failure, 2 points for each of hypertension, age ≥75 years, valvular disease, and coronary artery disease, and 1 point for each of peripheral vascular disease and obesity (body mass index >30). Scores classified risk as low (0-4), intermediate (5-9), or high (10-14); corresponding AF detection rates were compared using the log-rank test. AF incidence rates in patients with and without a history of remote stroke at baseline were also compared. RESULTS: Among 391 participants, the mean age was 71.5 ± 9.8 years and 186 (47.6%) were women. In total, 130 (33.2%) developed AF over 18 months. Stratification by HAVOC risk score was: 95 (24%) low, 241 (62%) intermediate, and 55 (14%) high. At 18 months, AF incidence in patients with low HAVOC scores (19.5%) was lower than in those with intermediate (32.1%) or high (34.2%) scores. AF incidence was similar among those with (n = 78) versus without (n = 313) remote stroke (27.3% vs. 29.8%; median time from stroke to ICM insertion was 4.2 [2.2-8.2] years). CONCLUSIONS: The HAVOC risk score identified a subset of individuals at greatest risk of developing AF, while AF incidence rates were similar among those with and without remote stroke. The use of the HAVOC score could help identify those at greatest likelihood of manifesting AF during long-term monitoring.

Searching for Atrial Fibrillation Poststroke: A White Paper of the AF-SCREEN International Collaboration.

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.

Rhythm monitoring strategies in patients at high risk for atrial fibrillation and stroke: A comparative analysis from the REVEAL AF study.

BACKGROUND: Reducing atrial fibrillation (AF)-related stroke requires timely AF diagnosis, but the optimal monitoring strategy is unknown. OBJECTIVE: We used insertable cardiac monitor (ICM) data from the REVEAL AF study to compare AF detection rates by various short-term continuous monitoring (STM) strategies. METHODS AND RESULTS: Patients without known AF, but with CHADS2 scores ≥3 (or = 2 with ≥1 additional AF risk factor) received an ICM for AF detection. One-time STM strategies were assessed by computing AF incidence at 1, 2, 7, 14, and 30 days post-ICM insertion. Repeated STM strategies (quarterly 24-hour, 48-hour, 7-day, or monthly 24-hour monitoring) were modeled by randomly selecting day(s) within a 30-day window around each nominal evaluation date over a 1-year period (simulated 10,000 times). Endpoints included AF ≥6 minutes, AF ≥1 hour, and daily AF burden ≥1 and ≥ 5.5 hours. The impact of compliance on AF detection was evaluated using daily compliance rates of 85%, 75%, 65% and 55% during follow-up months 1-3, 4-6, 7-9, and 9-12, respectively. Based on data from 385 patients (71.5 ±â€¯9.9 years; CHADS2 score 3.0 ±â€¯1.0) the incidence of AF ≥6 minutes via ICM at 12 months was 27.1% (95% CI, 22.5-31.5%). This exceeded the range of estimated rates from all modeled one-time and repeated STM strategies (0.8% for 24-hour Holter monitoring to 10.6% for quarterly 7-day monitoring). Findings were similar for all AF endpoints. Modeled non-compliance reduced AF detection by 4.5% to 22.9%. CONCLUSIONS: Most AF episodes detected via ICMs would go undetected via conventional STM strategies, thus preventing optimal prophylaxis for adverse consequences.

Risk of major cardiovascular and neurologic events with obstructive sleep apnea among patients with atrial fibrillation.

BACKGROUND: Obstructive sleep apnea (OSA) is a known risk factor for atrial fibrillation (AF). However, it remains unclear whether OSA is independently associated with worse cardiovascular and neurological outcomes in patients with AF. METHODS: We used the ORBIT-AF I and ORBIT-AF II to conduct a retrospective cohort study of 22,760 patients with AF with and without OSA. Adjusted multivariable Cox proportional hazards models was used to determine whether OSA was associated with increased risk for major adverse cardiac and neurologic events (MACNEs) (cardiovascular death, myocardial infarction, stroke/transient ischemic attack/non-central nervous system embolism (stroke/SE), and new-onset heart failure], combined and individually. RESULTS: A total of 4,045 (17.8%) patients had OSA at baseline. Median follow-up time was 1.5 (interquartile range: 1-2.2) years, and 1,895 patients experienced a MACNE. OSA patients were younger (median [interquartile range] 68 [61-75] years vs 74 [66-81] years), were more likely male (70.7% vs 55.3%), and had increased body mass index (median 34.6 kg/m2 [29.8-40.2] vs 28.7 kg/m2 [25.2-33.0]). Those with OSA had a higher prevalence of concomitant comorbidities such as diabetes, chronic obstructive pulmonary disease, and heart failure. OSA patients had higher use of antithrombotic therapy. After adjustment, the presence of OSA was significantly associated with MACNE (hazard ratio: 1.16 [95% CI: 1.03-1.31], P = .011). OSA was also an independent risk factor for stroke/SE beyond the CHA2DS2-VASc risk factors (HR: 1.38 [95% CI 1.12-1.70], P = .003) but not cardiovascular death, myocardial infarction, new-onset heart failure, or major bleeding. CONCLUSIONS: Among patients with AF, OSA is an independent risk factor for MACNE and, more specifically, stroke/SE.

Guideline-directed therapies for comorbidities and clinical outcomes among individuals with atrial fibrillation.

BACKGROUND: Comorbidities are common in patients with atrial fibrillation (AF) and affect prognosis, yet are often undertreated. However, contemporary rates of use of guideline-directed therapies (GDT) for non-AF comorbidities and their association with outcomes are not well described. METHODS: We used the Outcomes Registry for Better Informed Treatment of AF (ORBIT-AF) to test the association between GDT for non-AF comorbidities and major adverse cardiac or neurovascular events (MACNE; cardiovascular death, myocardial infarction, stroke/thromboembolism, or new-onset heart failure), all-cause mortality, new-onset heart failure, and AF progression. Adjustment was performed using Cox proportional hazards models and logistic regression. RESULTS: Only 6,782 (33%) of the 20,434 patients eligible for 1 or more GDT for non-AF comorbidities received all indicated therapies. Use of all comorbidity-specific GDT was highest for patients with hyperlipidemia (75.6%) and lowest for those with diabetes mellitus (43.1%). Use of "all eligible" GDT was associated with a nonsignificant trend toward lower rates of MACNE (HR 0.90 [0.79-1.02]) and all-cause mortality (HR 0.90 [0.80-1.01]). Use of GDT for heart failure was associated with a lower risk of all-cause mortality (HR 0.77 [0.67-0.89]), and treatment of obstructive sleep apnea was associated with a lower risk of AF progression (OR 0.75 [0.62-0.90]). CONCLUSIONS: In AF patients, there is underuse of GDT for non-AF comorbidities. The association between GDT use and outcomes was strongest in heart failure and obstructive sleep apnea patients where use of GDT was associated with lower mortality and less AF progression.

Patterns of amiodarone use and outcomes in clinical practice for atrial fibrillation.

BACKGROUND: Amiodarone is the most effective antiarrhythmic drug (AAD) for atrial fibrillation (AF), but it has a high incidence of adverse effects. METHODS: Using the ORBIT AF registry, patients with AF on amiodarone at enrollment, prescribed amiodarone during follow-up, or never on amiodarone were analyzed for the proportion treated with a guideline-based indication for amiodarone, the variability in amiodarone use across sites, and the outcomes (mortality, hospitalization, and stroke) among patients treated with amiodarone. Hierarchical logistic regression modeling with site-specific random intercepts compared rates of amiodarone use across 170 sites. A logistic regression model for propensity to receive amiodarone created a propensity-matched cohort. Cox proportional hazards modeling, stratified by matched pairs evaluated the association between amiodarone and outcomes. RESULTS: Among 6,987 AF patients, 867 (12%) were on amiodarone at baseline and 451 (6%) started on incident amiodarone during the 3-year follow-up. Use of amiodarone varied among sites from 3% in the lowest tertile to 21% in the highest (p<0.0001). Among those treated, 32% had documented contraindications to other AADs or had failed another AAD in the past. Mortality, cardiovascular hospitalization, and stroke were similar among matched patients on and not on amiodarone at baseline, while incident amiodarone use in matched patients was associated with higher all-cause mortality (adjusted HR 2.06, 95% CI 1.35-3.16). CONCLUSIONS: Use of amiodarone among AF patients in community practice is highly variable. More than 2 out of 3 patients treated with amiodarone appeared to be eligible for a different AAD.

Dronedarone treatment following cardioversion in patients with atrial fibrillation/flutter: A post hoc analysis of the EURIDIS and ADONIS trials.

INTRODUCTION: The phase 3 EURIDIS and ADONIS studies evaluated dronedarone for atrial fibrillation (AF)/atrial flutter (AFL) recurrence in patients with nonpermanent AF. Here we assessed whether patient characteristics and/or treatment outcomes in these studies differed based on the need for cardioversion before randomization. METHODS: Time to adjudicated first AF/AFL recurrence, symptomatic recurrence, cardiovascular hospitalization/death, and AF hospitalization, and safety were assessed by cardioversion status. RESULTS: Of 1237 patients randomized (2:1 dronedarone:placebo), 364 required baseline cardioversion (dronedarone 243, placebo 121). Patients requiring cardioversion had a greater prevalence of cardiovascular comorbidities and shorter times to first AF/AFL recurrence compared with those not requiring cardioversion. Dronedarone was associated with longer median time to first AF/AFL recurrence vs placebo regardless of cardioversion status (cardioversion: 50 vs 15 days, hazard ratio [HR] 0.76; 95% confidence interval [CI], 0.59-0.97; P = .02; non-cardioversion: 150 vs 77 days, HR 0.76; 95% CI, 0.64-0.90; P < .01). Dronedarone was similarly associated with prolonged median time to symptomatic recurrence vs placebo in the cardioversion (347 vs 87 days, HR 0.65; 95% CI, 0.49-0.87) and non-cardioversion (288 vs 120 days, HR 0.74; 95% CI, 0.62-0.90) populations. Risk of cardiovascular hospitalization/death and first AF hospitalization was lower with dronedarone vs placebo regardless of cardioversion status, but differences were not statistically significant. The safety of dronedarone was similar in both groups. CONCLUSION: Patients requiring baseline cardioversion represent a distinct population, having more underlying cardiovascular disease and experiencing a shorter time to AF/AFL recurrences. Dronedarone was associated with improved efficacy vs placebo regardless of cardioversion status.

Sinus node depolarization - Present during all sinus rhythms but never seen on the 12-lead ECG: An illustrative case-report that provides its recording.

Because it is not visible on the 12-lead ECG, few if any electrocardiographers have seen the waveform of sinus node (SN) depolarization. Yet, SN depolarization is present before every P wave during all sinus rhythms. Herein, a case is presented in which a recorded SN depolarization waveform is observed.

The high road, the low road, and no road: She took them all.

A 42-year old female with no significant past medical history, normal physical exam, and normal routine lab studies presents with "thumps" in her chest. A Holter monitor evaluation revealed normal sinus rhythm with two different PR intervals suggesting "dual AV nodal pathways" and occasional blocked P waves with junctional escape complexes. The behavior was most suggestive that no conduction through either pathway reached the His bundle, suggesting distal block must be beyond each pathway, but still within the AV node. These strips are shown. Their interpretation is discussed, along with the underlying explanation and significance.

Prognostic Significance of Nuisance Bleeding in Anticoagulated Patients With Atrial Fibrillation.

BACKGROUND: Bleeding is commonly cited as a reason for stopping oral anticoagulants (OACs). Whether minor bleeding events (nuisance bleeding, NB) in patients with atrial fibrillation on OACs are associated with OAC discontinuation, major bleeding, and stroke/systemic embolism (SSE) is unknown. METHODS: Within the ORBIT-AF prospective, outpatient registry (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation), we identified 6771 patients ≥18 years of age at 172 sites with atrial fibrillation and eligible follow-up visits. NB was ascertained from the medical record and was defined as minor bleeding that did not require medical attention (eg, bruising, hemorrhoidal bleeding). We used multivariable pooled logistic regression modeling to evaluate the associations between NB and major bleeding and SSE in the 180 days after documentation of NB. Our unit of analysis was the patient visit, occurring at ≈6-month intervals for a median of 1.5 years following enrollment. Changes in anticoagulation treatment satisfaction after NB were examined descriptively in a subset of patients. RESULTS: The median age of the overall population was 75.0 (interquartile range, 67.0-81.0); 90.0% were white and 42.5% were female. Among 6771 patients (18 560 visits), n=1357 (20.0%) had documented NB, for an incidence rate of 14.8 events per 100 person-years. Over 96.4% of patients remained on OAC therapy after the NB event. Overall, 287 (4.3%) patients experienced major bleeding and 64 (0.96%) had a SSE event during follow-up. NB was not associated with a significant increased risk of major bleeding over 6 months in models adjusting for the ATRIA bleeding score (Anticoagulation and Risk Factors in Atrial Fibrillation) (odds ratio, 1.04; 95% confidence interval, 0.68-1.60; P=0.86). NB was also not associated with increased SSE risk over 6 months in models adjusting for the CHA2DS2-VASc risk score (odds ratio, 1.24; 95% confidence interval, 0.53-2.91; P=0.62). CONCLUSIONS: NB is common among patients with atrial fibrillation on OACs. However, NB was not associated with a higher risk of major bleeding or SSE over the next 6 months, suggesting its occurrence should not lead to changes in anticoagulation treatment strategies in OAC-treated patients. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01165710.

Treatment of atrial fibrillation with concomitant coronary or peripheral artery disease: Results from the outcomes registry for better informed treatment of atrial fibrillation II.

BACKGROUND: Treatment patterns and outcomes of individuals with vascular disease who have new-onset atrial fibrillation (AF) are not well characterized. METHODS: Among patients with new-onset AF, we analyzed treatment and outcomes in those with or without vascular disease in the ORBIT-AF II registry. Vascular disease was defined as coronary disease with or without myocardial infarction (MI) or revascularization, or peripheral artery disease. The primary outcomes included major adverse cardiovascular or neurological events (MACNE) and major bleeding. Cox proportional hazard models were used to adjust the difference in patient characteristics. RESULTS: Overall 1920 of 6203 (31.0%) of new-onset AF had vascular disease. In patients with vascular disease, 62.2% of those were treated with direct oral anticoagulants (DOACs) and 23.4% with warfarin. Dual therapy and triple therapy were used in 36.9% and 4.9%, respectively. Vascular disease patients had increased risk of MACNE (adjusted hazard ratio [aHR] 1.83 [95%CIs 1.32-2.55]), but not major bleeding (aHR 1.24 [0.95-1.63]). Among patients with vascular disease, relative to those on warfarin, those treated with DOACs had similar risk for MACNE (aHR 1.20 [0.77-1.87]) but lower risks for bleeding, although it did not reach statistical significance (aHR 0.70 [0.43-1.15]). Concomitant antiplatelet therapy was associated with higher bleeding (aHR 2.27 [1.38-3.73]) with no apparent reduction in MACNE (aHR 1.50 [1.00-2.25]). CONCLUSIONS: Most patients with AF and vascular disease were managed with oral anticoagulation. About half of them were also treated with concomitant antiplatelet therapy, which was associated with increased risk of bleeding, without evidence of improved cardiovascular outcomes.

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

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

Long-term electrocardiographic safety monitoring in clinical drug development: A report from the Cardiac Safety Research Consortium.

This white paper, prepared by members of the Cardiac Safety Research Consortium (CSRC), discusses important issues regarding scientific and clinical aspects of long-term electrocardiographic safety monitoring during clinical drug development. To promote multistakeholder discussion of this topic, a Cardiac Safety Research Consortium-sponsored Think Tank was held on 2 December 2015 at the American College of Cardiology's Heart House in Washington, DC. The goal of the Think Tank was to explore how and under what circumstances new and evolving ambulatory monitoring technologies could be used to improve and streamline drug development. This paper provides a detailed summary of discussions at the Think Tank: it does not represent regulatory guidance.