Importance Bleeding and thrombotic events (eg, stroke and systemic embolism) are common in patients with atrial fibrillation (AF) taking warfarin sodium despite a well-established therapeutic range. Objective To evaluate whether history of therapeutic warfarin control in patients with AF is independently associated with subsequent bleeding or thrombotic events. Design, Setting, and Participants In this multicenter cohort study of 176 primary care, cardiology, and electrophysiology clinics in the United States, data were obtained during 51 830 visits among 10 137 patients with AF in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Registry; 5545 patients treated with warfarin were included in the bleeding analysis, and 5635 patients were included in the thrombotic event analysis. Patient follow-up was performed from June 29, 2010, to November 30, 2014. Data analysis was performed from August 4, 2016, to February 15, 2019. Exposures Multiple measures of warfarin control within the preceding 6 months were analyzed: time in therapeutic range of 2.0 to 3.0, most recent international normalized ratio (INR), percentage of time that a patient had interpolated INR values less than 2.0 or greater than 3.0, INR variance, INR range, and percentage of INR values in therapeutic range. Main Outcomes and Measures Association of INR measures, alone or in combination, with clinical factors and risk for thrombotic events and bleeding during the subsequent 6 months was assessed post hoc using logistic regression models. Results A total of 5545 patients (mean [SD] age, 74.5 [9.8] years; 3184 [57.4%] male) with AF were included in the major bleeding analysis and 5635 patients (mean [SD] age, 74.5 [9.8] years; 3236 [57.4%] male) in the thrombotic event analysis. During a median follow-up of 1.5 years (interquartile range, 1.0-2.5 years), there were 339 major bleeds (6.1%) and 51 strokes (0.9%). Multiple metrics of warfarin control were individually associated with subsequent bleeding. After adjustment for clinical bleeding risk, 3 measures-time in therapeutic range (per 1-SD increase ≤55: adjusted odds ratio [aOR], 1.16; 95% CI, 1.02-1.32), variation in INR values (aOR, 1.32; 95% CI, 1.19-1.47), and maximum INR (aOR, 1.20; 95% CI, 1.10-1.31)-remained associated with bleeding risk. Adding INR variance to a clinical risk model slightly increased the C statistic from 0.68 to 0.69 and had a net reclassification improvement index of 0.028 (95% CI, -0.029 to 0.067). No INR measures were associated with subsequent stroke risk. Conclusions and Relevance Three metrics of prior warfarin control were associated with bleeding risk but only marginally more so than traditional clinical factors. This study did not identify any measures of INR control that were significantly associated with stroke risk.

BACKGROUND GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non-vitamin K antagonist oral anticoagulant (NOAC), became available.OBJECTIVES This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1.METHODS During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients' baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics.RESULTS Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA(2)DS(2)-VASc [ Congestive heart failure, Hypertension, Age >= 75 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score >= 2; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment.CONCLUSIONS The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [ GLORIA-AF]; NCT01468701) (C) 2017 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

BACKGROUND:Over a 12-month period, adolescent heart-screening programs were performed for identifying at-risk adolescents for sudden cardiac death (SCD) in our community. Novel to our study, all adolescents received an abbreviated, ultraportable echocardiography (UPE). In this report, we describe the use of UPE in this screening program.METHODS AND RESULTS:Four hundred thirty-two adolescents underwent cardiac screening with medical history questionnaire, physical examination, 12-lead electrocardiogram (ECG), and an abbreviated transthoracic echocardiographic examination. There were 11 abnormalities identified with uncertain/varying clinical risk significance. In this population, 75 adolescents had a murmur or high ECG voltage, of which only three had subsequent structural abnormalities on echocardiography that may pose risk. Conversely, UPE discovered four adolescents who had a cardiovascular structural abnormality that was not signaled by the 12-lead ECG, medical history questionnaire, and/or physical examination.CONCLUSIONS:The utilization of ultraportable, handheld echocardiography is feasible in large-scale adolescent cardiovascular screening programs. UPE appears to be useful for finding additional structural abnormalities and for risk-stratifying abnormalities of uncertain potential of adolescents' sudden death.

Mapping of Idiopathic Ventricular Arrhythmias. Background: Termination of ventricular tachycardia (VT) by mechanical pressure has been described for fascicular and postinfarction VT. Mechanical interruption of idiopathic ventricular arrhythmias (VT/premature ventricular complexes [PVCs]) arising in the right ventricular outflow tract (RVOT) has not been described in systematic fashion. Methods: Eighteen consecutive patients (13 females, age 49 ± 13 years, ejection fraction 0.55 ± 0.12) underwent mapping and ablation of RVOT VT or PVCs. In 7 patients, 9 distinct VTs (mean cycle length 440 ± 127 ms), and in 11 patients, 11 distinct PVCs originating in the RVOT were targeted. Mechanical termination was considered present if a reproducibly inducible VT was no longer inducible or if frequent PVCs suddenly ceased with the mapping catheter at a particular location. Endocardial activation time, electrogram characteristics, and pace‐mapping morphology were assessed at this location. Radiofrequency energy was delivered if mechanical termination was observed. Results: All targeted arrhythmias were successfully ablated. In 7 of 18 patients (39%), catheter manipulation terminated the arrhythmia with the mapping catheter located at a particular site. Local endocardial activation time was earlier at sites of mechanical termination (−31 ± 7 ms) compared with effective sites without termination (−25 ± 3 ms, P = 0.04). The 10‐ms isochronal area was smaller in patients with mechanical interruption (0.35 ± 0.2 cm2) than in patients without mechanical termination (1.33 ± 0.9 cm2, P = 0.01). At all sites susceptible to mechanical trauma, the pace map displayed a match with the targeted VT/PVC. All sites where mechanical termination of VT or PVCs occurred were effective ablation sites. Conclusions: Mechanical suppression at the site of origin of idiopathic RVOT arrhythmias frequently occurs during the mapping procedure and is a reliable indicator of effective ablation sites. Mechanical termination of RVOT arrhythmias may be indicative of a more localized arrhythmogenic substrate. (J Cardiovasc Electrophysiol, Vol. 21, pp. 42–46, January 2010)

BACKGROUND Premature ventricular complexes (PVCs) and ventricular tachycardia (VT) with origin in the left ventricular papillary muscle have recently been described. There are no prior studies describing the characteristics of the ventricular arrhythmias (VAs) arising from the right ventricular papillary muscles (RV PAPs).METHODS Among 169 consecutive patients who underwent a catheter ablation of a VA, eight patients with RV PAPs were identified (seven men, mean PVC burden 17.0% +/- 20%). A control group consisted of 10 consecutive patients with arrhythmias originating from the right ventricle (10 women, mean PVC burden 13.9% +/- 12.8%). All patients underwent cardiac magnetic resonance imaging (MRI). Intracardiac echocardiography was used to identify the site of origin of the RV PAP arrhythmias. The site of origin of a total of 15 distinct PAP arrhythmias was mapped to the following papillary muscles: posterior (n = 3), anterior (n = 4), or septal (n = 8).RESULTS Postablation echocardiograms did not reveal new tricuspid regurgitation. During a mean follow-up of 8 +/- 9 months, there were no adverse outcomes. The PVC burden was reduced from 17% +/- 20% preablation to 0.6% +/- 0.8% postablation in the RV PAP group and from 13.9% +/- 12.8% to 0.3% +/- 0.4% in the control group. The QRS complex was broader in the RV PAP group compared with in the control group (163 +/- 21 ms vs. 141 +/- 22 ms; P = .02). RV PAP arrhythmias originating from the posterior or anterior RV PAPs more often had a superior axis with late R-wave transition (>V4) compared with septal RV RAP arrhythmias, which more often had an inferior axis with an earlier R-wave transition in the precordial leads (<= V4; P < .05).CONCLUSION PVCs and VT may originate in the RV PAPs. Radiofrequency ablation is effective in eliminating these arrhythmias.

BACKGROUND Left atrial appendage (LAA) isolation is rare and may be associated with impaired transport function and thromboembolism.OBJECTIVE The purpose of this study was to determine the mechanisms of inadvertent isolation of the LAA during atrial fibrillation (AF) ablation.METHODS This study consisted of 11 patients (ejection fraction 0.43 +/- 0.18, left atrial diameter 51 +/- 8 mm) with persistent AF who had LAA conduction block during a procedure for AF (n = 8) or atrial tachycardia (AT) (n = 3).RESULTS LAA conduction block occurred during ablation at the Bachmann bundle region in 6 patients, mitral isthmus in 3, LAA base in 2, and coronary sinus in 1. The mean distance from the ablation site to the LAA base was 5.0 +/- 1.9 cm. LAA isolation was transient in all 6 patients in whom LAA conduction was monitored and was permanent in the 4 patients in whom conduction was not monitored during energy delivery. The remaining patient was noted to have LAA isolation during a redo procedure before any ablation. Nine of (82%) the 11 patients have remained arrhythmia-free without antiarrhythmic drugs at mean follow-up of 6 +/- 7 months, and all have continued taking warfarin.CONCLUSION Electrical isolation of the LAA may occur during ablation of persistent AF and AT even when the ablation site is remote from the LAA. This likely is due to disruption of the Bachmann bundle and its leftward extension, which courses along the anterior left atrium and bifurcates to surround the LAA. Monitoring of LAA conduction during ablation of persistent AF or AT is important in avoiding permanent LAA isolation.

BACKGROUND:Inappropriate implantable cardioverter-defibrillator (ICD) therapy of atrial tachycardia (AT) with 1:1 atrioventricular (AV) conduction is common because it is difficult to discriminate from ventricular tachycardia (VT) with 1:1 retrograde conduction. Tachycardia cycle length (CL) variability and the relationship between atrial and ventricular CLs may be useful in discriminating AT from VT with 1:1 retrograde conduction.OBJECTIVE:The purpose of this study was to evaluate the usefulness of the relationship between the atrial and ventricular CLs in differentiating AT with 1:1 conduction from VT with 1:1 retrograde conduction.METHODS:We studied 71 patients who had a tachycardia with a 1:1 AV relationship and significant CL variability. Thirty-nine patients had AT (21 inducible and 18 simulated), and 32 patients had VT (11 inducible and 21 simulated). The relationship between atrial and ventricular CLs was examined.RESULTS:A change in atrial CL predicted the change in subsequent ventricular CL in 37 (95%) of 39 patients with AT and in none of the patients with VT. A change in preceding ventricular CL predicted the change in atrial CL in 31 (97%) of 32 patients with VT and in only one (3%) of 39 patients with AT. The sensitivity, specificity, and positive and negative predictive values of a change in atrial CL predicting the change in ventricular CL for AT with significant CL variability were 95%, 100%, 100%, and 94%, respectively. The corresponding values for the change in preceding ventricular CL predicting the change in atrial CL for AT with significant CL variability were 97%.CONCLUSION:The relationship between atrial and ventricular CL is useful in differentiating AT from VT with retrograde conduction. A change in atrial CL that predicts the change in subsequent ventricular CL rules in AT and excludes VT.

Nonischemic Cardiomyopathy and Ventricular Tachycardia.  Background: In patients with prior infarction, isolated potentials (IPs) during sinus rhythm reflect fixed scar and often indicate sites critical for ventricular tachycardia (VT). The purpose of this study was to determine the value of IPs in conjunction with pace‐mapping to guide VT ablation in patients with various types of nonischemic cardiomyopathy.

Background—The prevalence of epicardial idiopathic ventricular arrhythmias that can be ablated from within the coronary venous system (CVS) has not been described. Methods and Results—In a consecutive group of 189 patients with idiopathic ventricular arrhythmias referred for ablation, the site of origin (SOO) of ventricular tachycardia and/or premature ventricular contractions was determined by activation mapping and pace mapping. Mapping was performed within the CVS if endocardial mapping did not reveal an SOO. Venography of the CVS and coronary angiography were performed before ablation in the CVS. In 27 of 189 patients (14%±5%; 95% confidence interval), the SOO of the ventricular arrhythmia was identified from within the coronary venous system, either in the great cardiac vein (n=26) or the middle cardiac vein (n=1). The mean activation time at the SOO was −29±8 ms. Twenty of 27 patients (74%) underwent successful ablation within the CVS. Epicardial ventricular arrhythmias displayed a broader R wave in V1 compared with arrhythmias in the control group (85 ms [interquartile range, 40] versus 65 ms [interquartile range, 95]; P<0.01). Two patients had recurrent premature ventricular contractions within 2 weeks after ablation, and no recurrences occurred in the remaining patients during a median follow-up of 13 months (range, 25). In the 7 patients with unsuccessful ablation, failure was because the ablation catheter could not be advanced to the SOO within the great cardiac vein (n=4), inadequate power delivery at the SOO (n=1), proximity to the phrenic nerve (n=1), or proximity of the SOO to a major coronary artery (n=1). Transcutaneous epicardial ablation was effective in 1 of 2 patients in whom it was attempted. Conclusions—Almost 15% of idiopathic ventricular arrhythmias have an epicardial origin. ECG characteristics help to differentiate epicardial arrhythmias from endocardial ventricular arrhythmias. The SOO of epicardial arrhythmias can be ablated from within the CVS in approximately 70% of patients.

Background: Real‐time esophageal imaging is critical in avoiding esophageal injury. However, the safety of esophageal imaging with barium has not been specifically explored. Methods: Three hundred seventy consecutive patients underwent left atrial (LA) ablation of atrial fibrillation (AF) under conscious sedation. One hundred eighty‐five patients (50%) underwent the ablation procedure with, and 185 patients (50%) underwent the procedure without administration of barium. Fever, as a surrogate for aspiration, was defined as a maximal temperature ≥100°F within the first 24 hours following the ablation procedure. Results: Thirty of the 370 patients (8%) developed fever within 24 hours after LA ablation. The prevalence of fever was 9% (17/185) among patients who received barium and 7% (13/185) among those who did not receive barium (P = 0.6). Evaluation revealed the following causes of fever in 14 of the 30 patients (47%) with no difference in prevalence between the 2 groups: pericarditis, venous thromboembolism, hematoma, and infiltrate on chest radiography. Multivariate analysis failed to reveal any factors associated with development of fever. None of the patients experienced serious complications such as respiratory failure or atrioesophageal fistula. Conclusions: Fever may occur in approximately 10% of patients undergoing LA ablation of AF. Administration of barium is not associated with fever or other complications such as aspiration pneumonia. Real‐time imaging of the esophagus with barium administration in conjunction with conscious sedation appears to be safe.

BACKGROUND Termination of persistent atrial fibrillation (AF) by radiofrequency ablation (RFA) is associated with a high probability of freedom from AF but requires extensive ablation and long procedure times.OBJECTIVE The purpose of this study was to determine whether a critical decrease in the dominant frequency (DF) of AF is a sufficient endpoint for RFA of persistent AF.METHODS Antral pulmonary vein isolation (APVI) followed by RFA of complex fractionated atrial electrograms (CFAEs) in the atria and coronary sinus was performed in 100 consecutive patients with persistent AF. The DF of AF in lead V1 and in the coronary sinus was determined by fast Fourier transform (FFT) analysis at baseline and before termination of AF to identify a critical decrease in DF predictive of sinus rhythm after RFA.RESULTS A >= 11% decrease in DF had the highest accuracy in predicting freedom from atrial arrhythmias, with a sensitivity of 0.71 and a specificity of 0.82 (P <.001). At a mean follow-up of 14 +/- 3 months after one ablation procedure, sinus rhythm was maintained off antiarrhythmic drugs in 8/35 (23%) and 20/26 (77%) of patients with a <11% and >= 11% decrease in DF, respectively (P <.001). Sinus rhythm was maintained in 24/39 patients (62%) in whom RFA terminated AF. The duration of RFA and total procedure time were longer in patients with AF termination (95 +/- 23 and 358 +/- 87 minutes) than in patients with a >= 11% decrease in the DF (77 +/- 16 and 293 +/- 70 minutes) or >= 11% decrease in DF (80 +/- 17 and 289 +/- 73 minutes), respectively (P <.01). Among the variables of age, gender, left atrial diameter, duration of AF, left ventricular ejection fraction, duration of RFA, a >= 11% decrease in DF, and termination of AF, a >= 11% decrease in DF (odds ratio = 9.89, 95% confidence interval [CI] 2.84-34.47) and termination during RFA (OR = 4.38, 95% CI 1.50-12.80) were the only independent predictors of freedom from recurrent atrial arrhythmias.CONCLUSION In a retrospective analysis of consecutive patients with persistent AF, a decrease in the DF of AF by 11% in response to APVI and ablation of CFAEs was associated with a probability of maintaining sinus rhythm that was similar to that when RFA terminates AF.

Noninducibility by High‐Dose Isoproterenol. Objective: To determine the relative clinical value of noninducibility of atrial fibrillation (AF) by isoproterenol (ISO) and by rapid atrial pacing (RAP) in patients with paroxysmal AF (PAF). Background: AF can be induced by RAP or ISO in >85% of patients with PAF. Methods: ISO was administered in escalating doses of 5, 10, 15, and 20 μg/min in 112 patients (age = 56 ± 13 years) with PAF before radiofrequency catheter ablation. AF was inducible in 97 of 112 patients (87%) at a mean dose of 15 ± 5 μg/min. RAP induced AF in the remaining 14 of 15 patients. Antral pulmonary vein (PV) isolation (APVI) was followed by ablation of complex fractionated atrial electrograms (CFAEs) as necessary to terminate AF and render AF noninducible in response to ISO. Results: AF terminated during APVI in 72 of 111 patients (65%) and after APVI plus ablation of CFAEs in 11 of 111 patients (10%). In the remaining 28 patients (25%), sinus rhythm was restored by transthoracic cardioversion. RAP was performed in the last 61 consecutive patients who were rendered noninducible by ISO. RAP initiated AF in 20 of 61 patients (33%) and atrial flutter in 6 patients (10%). No additional ablation was performed if AF was induced with RAP; however, atrial flutter was targeted. At 12 ± 5 months, 63/75 patients (84%) who were noninducible by ISO and 2 of 8 (25%) who still were reinducible by ISO were free from recurrent AF after a single ablation procedure without antiarrhythmic drugs (P = 0.001). AF recurred in 20 of 36 patients (56%) who required cardioversion for persistent AF after ablation (P < 0.001). Among the 61 patients who also underwent RAP, 12 of 20 (60%) who were, and 31 of 41 (76%) who were not inducible by RAP were free from recurrent AF (P = 0.21). The accuracy of noninducibility as a predictor of clinical outcome was 83% with ISO and 64% by RAP (P = 0.03). Conclusions: The response to isoproterenol after catheter ablation of PAF more accurately predicts clinical outcome than the response to RAP. (J Cardiovasc Electrophysiol, Vol. 21, pp. 13–20, January 2010)

BACKGROUND:The papillary muscles (PAP) have been implicated in arrhythmogenesis, largely based on theoretical considerations and experimental studies. Few clinical studies have described papillary muscle arrhythmias. OBJECTIVE:This study sought to describe ventricular arrhythmias arising from the left ventricular PAPs in a consecutive series of patients without prior myocardial infarction and to compare these arrhythmias with fascicular arrhythmias. METHODS:Nine of 122 consecutive patients (7%) presenting with symptomatic premature ventricular complexes (PVCs) or nonsustained ventricular tachycardia (VT) were found to have a site of origin in the anterolateral or posteromedial left ventricular PAP. Their mean age was 57 +/- 9 years, and the mean ejection fraction was 0.49 +/- 13. Four of 9 patients had idiopathic cardiomyopathy. The PAP involvement was established by intracardiac echocardiography. Eight of the 122 patients (6.5%) had idiopathic VT originating in the left anterior or posterior fascicle, and these patients served as a control group. RESULTS:Compared with patients with fascicular arrhythmias, the QRS width was significantly greater in patients with PAP arrhythmias (150 +/- 15 ms vs. 127 +/- 11 ms; P = .001). Presystolic Purkinje potentials were identified at all effective ablation sites for fascicular arrhythmias, but in arrhythmias originating from PAPs, more distal Purkinje potentials often were recorded from the Purkinje-myocardial interface located at the PAP. All arrhythmias originating from the PAPs and the fascicles were effectively ablated. Echocardiography before and after radiofrequency ablation did not show new or worsened mitral insufficiency. CONCLUSION:The PAPs can give rise to ventricular arrhythmias in normal and structurally abnormal hearts without prior infarcts. Intracardiac echocardiography seems helpful in recognizing and guiding radiofrequency ablation of PAP arrhythmias.

BACKGROUND:Left atrial (LA) ablation of atrial fibrillation (AF) may rarely be complicated by an atrio-esophageal fistula.OBJECTIVE:The purpose of this study was to determine the feasibility of mechanical displacement of the esophagus in patients undergoing LA ablation.METHODS:Twelve patients underwent mechanical displacement of the esophagus performed by an endoscopist during an LA ablation procedure under conscious sedation.RESULTS:The intrinsic course of the esophagus was near the left pulmonary veins (PVs) in 6 patients, the right PVs in 5 patients, and the mid-LA in 1 patient. In 10 (83%) of the 12 patients, the esophagus could be displaced with the endoscope. The maximal displacement toward the left-sided and right-sided PVs was 2.4 and 2.1 cm, respectively. In 2 (22%) of the 9 patients in whom a prior procedure was unsuccessful because of an unfavorable esophageal course, the esophagus remained at the same location to which it was displaced after removal of the endoscope, facilitating energy delivery at the target site. In the remaining 7 patients, the esophagus returned to its original location after the endoscope was removed. There were no complications related to the endoscopic procedure.CONCLUSION:The esophagus can be mechanically displaced with an endoscope during an LA ablation procedure under conscious sedation. However, in most patients, the esophagus assumes its original course after removal of the endoscope. In some patients in whom PV isolation is problematic because of an unfavorable esophageal course, endoscopic displacement may facilitate safe energy delivery over the posterior LA.