Apixaban for Stroke Prevention in Subclinical Atrial Fibrillation.

BACKGROUND: Subclinical atrial fibrillation is short-lasting and asymptomatic and can usually be detected only by long-term continuous monitoring with pacemakers or defibrillators. Subclinical atrial fibrillation is associated with an increased risk of stroke by a factor of 2.5; however, treatment with oral anticoagulation is of uncertain benefit. METHODS: We conducted a trial involving patients with subclinical atrial fibrillation lasting 6 minutes to 24 hours. Patients were randomly assigned in a double-blind, double-dummy design to receive apixaban at a dose of 5 mg twice daily (2.5 mg twice daily when indicated) or aspirin at a dose of 81 mg daily. The trial medication was discontinued and anticoagulation started if subclinical atrial fibrillation lasting more than 24 hours or clinical atrial fibrillation developed. The primary efficacy outcome, stroke or systemic embolism, was assessed in the intention-to-treat population (all the patients who had undergone randomization); the primary safety outcome, major bleeding, was assessed in the on-treatment population (all the patients who had undergone randomization and received at least one dose of the assigned trial drug, with follow-up censored 5 days after permanent discontinuation of trial medication for any reason). RESULTS: We included 4012 patients with a mean (±SD) age of 76.8±7.6 years and a mean CHA2DS2-VASc score of 3.9±1.1 (scores range from 0 to 9, with higher scores indicating a higher risk of stroke); 36.1% of the patients were women. After a mean follow-up of 3.5±1.8 years, stroke or systemic embolism occurred in 55 patients in the apixaban group (0.78% per patient-year) and in 86 patients in the aspirin group (1.24% per patient-year) (hazard ratio, 0.63; 95% confidence interval [CI], 0.45 to 0.88; P = 0.007). In the on-treatment population, the rate of major bleeding was 1.71% per patient-year in the apixaban group and 0.94% per patient-year in the aspirin group (hazard ratio, 1.80; 95% CI, 1.26 to 2.57; P = 0.001). Fatal bleeding occurred in 5 patients in the apixaban group and 8 patients in the aspirin group. CONCLUSIONS: Among patients with subclinical atrial fibrillation, apixaban resulted in a lower risk of stroke or systemic embolism than aspirin but a higher risk of major bleeding. (Funded by the Canadian Institutes of Health Research and others; ARTESIA ClinicalTrials.gov number, NCT01938248.).

Pacing-Induced Cardiomyopathy in Leadless and Traditional Pacemakers: A Single-Center Retrospective Analysis.

BACKGROUND:  Pacing-induced cardiomyopathy (PICM) is a clinical syndrome that is characterized by a drop in the left ventricular ejection fraction (LVEF) due to chronic high-burden right ventricular (RV) pacing. It has been postulated that leadless pacemakers (LPs) cause decreased risk of PICM compared to transvenous pacemakers (TVPs), but the exact risk reduction is unknown. METHODS: We performed a single-center retrospective analysis of adults who received an LP or TVP between January 1, 2014, and April 1, 2022, and had echocardiograms before and after the pacemaker implant. This study's outcomes were the RV pacing percentage, change in EF, the need for cardiac resynchronization therapy (CRT) upgrade, and follow-up duration. A Wilcoxon rank-sum test calculated the change in EF. RV time, defined as the duration from pacemaker placement to the follow-up echocardiogram in months multiplied by the RV pacing percentage, served as a surrogate for how long the RV was paced. RESULTS: A total of 614 patients were screened, and 198 patients were included in the study, where 72 received LP and 126 received TVP. The median follow-up was 480 days. The average of the reported RV percentage pacing was 63.43% for LP and 71.30% for TVP (p=0.14). The incidence of PICM and CRT upgrade was 44% and 9.7% in the LP group and 37% and 9.5% in the TVP group (p=0.3 and p>0.9), respectively. After accounting for age, sex, LP versus TVP, atrioventricular nodal ablation, RV pacing percentage, and follow-up duration, univariate analysis showed that RV time was significantly different between the two types of pacemakers (13.54 ± 14.21 months (LP) versus 9.26 ± 13.95 months (TVP), p=0.009). The difference in RV time between patients who underwent CRT upgrade and those who did not was statistically insignificant (12.11 ± 14.47 months (no CRT) versus 9.19 ± 12.00 months (CRT), p=0.5). CONCLUSIONS: This analysis demonstrated that the incidence of PICM was high in both groups (44% (LP) versus 37% (TVP)), despite significantly more RV time in patients with LP. There was no difference in CRT upgrade between LP and TVP.

Implant efficiency and clinical performance of Aveir™ VR and Micra™ VR leadless pacemaker: A multicenter comparative analysis of 67 patients.

INTRODUCTION: Leadless pacemaker (LP) is a novel pacemaker that has been proven to be effective and safe; however, the majority of LPs in previous reports were the Medtronic Micra™ VR LP. We aim to evaluate the implant efficiency and clinical performance of the Aveir™ VR LP compared to the Micra™ VR LP. METHOD: We performed a retrospective analysis in two healthcare systems (Sparrow Hospital and Ascension Health System, Michigan) in patients implanted with LPs between January 1, 2018, and April 1, 2022. The parameters were collected at implantation, 3 months and 6 months. RESULTS: A total of 67 patients were included in the study. The Micra™ VR group had shorter time in the electrophysiology lab (41 ± 12 vs. 55 ± 11.5 min, p = .008) and shorter fluoroscopic time (6.5 ± 2.2 vs. 11.5 ± 4.5 min, p < .001) compared to the Aveir™ VR group. The Aveir™ VR group had a significantly higher implant pacing threshold compared to the Micra™ VR group (0.74 ± 0.34 mA vs. 0.5 ± 0.18 mA at pulse width 0.4 ms, p < .001), but no difference was found at 3 months and 6 months. There was no significant difference in the R-wave sensing and impedance and pacing percentage at implantation, 3 months, and 6 months. Complications of the procedure were rare. The mean projected longevity of the Aveir™ VR group was longer than the Micra™ VR group (18.8 ± 4.3 vs. 7.7 ± 0.75 years, p < .001). CONCLUSION: Implantation of the Aveir™ VR required longer laboratory and fluoroscopic time, but showed longer longevity at 6 months follow-up, compare to the Micra™ VR. Complications and lead dislodgement are rare.

Reducing the electrogram review burden imposed by insertable cardiac monitors.

BACKGROUND: Insertable cardiac monitors (ICMs) are essential for ambulatory arrhythmia diagnosis. However, definitive diagnoses still require time-consuming, manual adjudication of electrograms (EGMs). OBJECTIVE: To evaluate the clinical impact of selecting only key EGMs for review. METHODS: Retrospective analyses of randomly selected Abbott Confirm Rx™ devices with ≥90 days of remote transmission history were performed, with each EGM adjudicated as true or false positive (TP, FP). For each device, up to 3 "key EGMs" per arrhythmia type per day were prioritized for review based on ventricular rate and episode duration. The reduction in EGMs and TP days (patient-days with at least one TP EGM), and any diagnostic delay (from the first TP), were calculated versus reviewing all EGMs. RESULTS: In 1000 ICMs over a median duration of 8.1 months, at least one atrial fibrillation (AF), tachycardia, bradycardia, or pause EGM was transmitted by 424, 343, 190, and 325 devices, respectively, with a total of 95 716 EGMs. Approximately 90% of episodes were contributed by 25% of patients. Key EGM selection reduced EGM review burden by 43%, 66%, 77%, and 50% (55% overall), while reducing TP days by 0.8%, 2.1%, 0.2%, and 0.0%, respectively. Despite reviewing fewer EGMs, 99% of devices with a TP EGM were ultimately diagnosed on the same day versus reviewing all EGMs. CONCLUSION: Key EGM selection reduced the EGM review substantially with no delay-to-diagnosis in 99% of patients exhibiting true arrhythmias. Implementing these rules in the Abbott patient care network may accelerate clinical workflow without compromising diagnostic timelines.

Effectiveness of SharpSense™ algorithms in reducing bradycardia and pause detection: real-world performance in Confirm Rx™ insertable cardiac monitor.

PURPOSE: SharpSense™ technology is an upgradable software enhancement introduced to the Abbott Confirm Rx™ insertable cardiac monitor (ICM). This study aims to characterize the real-world performance of SharpSense algorithms by comparing device detected pause and bradycardia episodes before and after the SharpSense upgrade. METHODS: Confirm Rx devices with at least 90 days monitoring each before and after SharpSense upgrade were included in the study. Bradycardia and pause detections and subcutaneous electrocardiograms (SECGs) within 90 days before and after the upgrade were extracted from Merlin.net™ patient care network for evaluation and adjudicated by expert adjudicators. RESULTS: A total of 197 devices were included in the analysis. Devices were implanted for syncope (35.0%), atrial fibrillation (32.5%), cryptogenic stroke (16.8%), and other indications including palpitations (15.7%). The SharpSense upgrade significantly reduced the number of bradycardia detections by 86.8% and pause detections by 93.1%. In adjudicated SECGs, the upgrade significantly reduced false positive (FP) bradycardia episodes by 91.5% and FP pause episodes by 82.8%. The percentage of devices with at least one FP episode was reduced from 39 to 20% for bradycardia and from 52 to 35% for pause. The number of devices with FP rate greater than 1 episode per week was reduced from 23 to 8% for bradycardia and from 39 to 20% for pause. CONCLUSIONS: In this real-world performance evaluation, the algorithms incorporated in SharpSense software upgrade in Confirm Rx ICMs substantially reduced false positive bradycardia and pause detections and the number of transmitted SECGs for clinic review.

Real-world Adoption of Smartphone-based Remote Monitoring Using the Confirm Rx™ Insertable Cardiac Monitor.

While previous generations of insertable cardiac monitors (ICMs) required a bedside monitor for remote monitoring (RM), the Confirm Rx™ ICM (Abbott, Chicago, IL, USA) utilizes Bluetooth®, Wi-Fi/cellular technology, and a smart device to connect to the RM system. We aimed to characterize compliance, connectivity, and event transmission timing with the Confirm Rx™ ICM RM system. The study cohort included American patients who received the Confirm Rx™ ICM with SharpSense™ technology within three months of release (May-July 2019). Compliance with RM was quantified as the proportion of patients registering the patient app on their smart device and transmitting at least once. Connectivity was measured as the median number of days between consecutive transmissions per patient. Event transmission time was measured from episode detection to availability on the Merlin.net™ RM system (Abbott). Time from transmission until review by a clinician was examined. Values for device connectivity, episode transmission timing, and clinician view times were reported as median [first quartile, third quartile]. Of 5,666 patients who received a Confirm Rx™ ICM, 97% registered their patient app and 92% transmitted data at least once. Among those utilizing RM (aged 66 ± 15 years; 49% female), connectivity occurred every 1.5 [1.2, 2.4] days, or 4.7 times per week. Patient-reported symptoms were transmitted to Merlin.net™ within 2.9 [2.1, 3.8] minutes of event onset and viewed by the clinician within 0.9 [0.4, 3.1] days, while device-detected episodes without symptoms were transmitted within 18.5 [11.2, 36.5] hours and then viewed within 0.8 [0.3, 2.5] days. This real-world study demonstrated excellent patient compliance with the smartphone-based RM paradigm enabled by Confirm Rx™, suggesting the suitability of this technology for future cardiac implantable devices.

Atrial Fibrillation as a Predictor of Mortality in High Risk COVID-19 Patients: A Multicentre Study of 171 Patients.

PURPOSE: Certain patient demographics and biomarkers have been suggested to predict survival in patients infected with COVID-19. However, predictors of outcome in patients who are critically ill are unclear. MATERIALS AND METHODS: We performed a multicentre analysis of 171 consecutive patients with confirmed COVID-19 who were admitted to the intensive care unit (ICU) between 1 March 2020 and 30 April 2020 and were followed until 23 May 2020. Demographic data, past medical history, laboratory values, echocardiographic and telemetry data were analysed. Patient status was classified as either alive or deceased at hospital discharge or the end of follow-up period. RESULTS: Mean patient age was 66±13 and 57% were male. Mortality rate of this ICU cohort at the end of follow-up was 46.2%. A multivariable logistic regression analysis identified the presence or history of atrial fibrillation (Odds Ratio 4.8, p=0.004) as a significant cardiovascular attribute that contributed to increased mortality. CONCLUSION: Mortality of critically ill COVID-19 patients is high. This study suggests a relationship between atrial fibrillation and increased mortality from COVID-19. Early aggressive treatment patients with high risk characteristics, such as atrial fibrillation could improve clinical outcome.

Accuracy of arrhythmia detection in implantable cardiac monitors: A prospective randomized clinical trial comparing Reveal LINQ and Confirm Rx.

BACKGROUND: Implantable cardiac monitors (ICMs) are increasingly used to detect arrhythmias in various clinical situations. However, the data transmission time and accuracy of detecting cardiac arrhythmias are unclear. OBJECTIVE: The objective of this study was to compare the efficiency of data transmission and arrhythmia detection accuracy of the Reveal LINQ with TruRhythm Detection with the Confirm Rx with SharpSense Technology. METHODS: In this prospective study, 142 patients were randomized 1:1 to receive Reveal LINQ or Confirm Rx ICM system. Arrhythmic events include atrial fibrillation (AF), pauses, and bradycardia. Data transmission time is defined as the time from event occurrence to physician notification. All the arrhythmic events are adjudicated for accuracy. RESULTS: A total of 3510 events were transmitted in 61 patients over 7.1 ± 3.5 months. The transmission time both for all events (448 ± 271 vs 610 ± 515 minutes, P = .02) and for patient activated triggers (24 ± 103 vs 475 ± 426 minutes, P < .0001) was significantly shorter in the Confirm Rx group. The total number of events was also higher in the Confirm Rx group (25.5 ± 45.6 vs 0.9 ± 1.1 events per patient-month, P < .01), which is likely due to event transmission setting differences between the two groups. Kaplan-Meier analysis showed that the Confirm Rx group detected true arrhythmic episodes sooner with higher percentage of diagnosed patients during 6-month follow-up (P = .006). Patient-averaged true positive detection rates were not statistically significant in the two groups (Reveal LINQ vs Confirm Rx, AF: 52% vs 38%; bradycardia: 67% vs 59%; pause: 24% vs 20%; tachycardia: 81% vs 94%). CONCLUSION: Compared to the Reveal LINQ, Confirm Rx has shorter event transmission time, more frequent event detections, shorter duration to diagnose true arrhythmic events, and higher percentage of diagnosed patients. The accuracy of arrhythmia detection in both ICMs remains suboptimal.

The learning curve associated with the implantation of the Nanostim leadless pacemaker.

PURPOSE: Use of novel medical technologies, such as leadless pacemaker (LP) therapy, may be subjected to a learning curve effect. The objective of the current study was to assess the impact of operators' experience on the occurrence of serious adverse device effects (SADE) and procedural efficiency. METHODS: Patients implanted with a Nanostim LP (Abbott, USA) within two prospective studies (i.e., LEADLESS ll IDE and Leadless Observational Study) were assessed. Patients were categorized into quartiles based on operator experience. Learning curve analysis included the comparison of SADE rates at 30 days post-implant per quartile and between patients in quartile 4 (> 10 implants) and patients in quartiles 1 through 3 (1-10 implants). Procedural efficiency was assessed based on procedure duration and repositioning attempts. RESULTS: Nanostim LP implant was performed in 1439 patients by 171 implanters at 60 centers in 10 countries. A total of 91 (6.4%) patients experienced a SADE in the first 30 days. SADE rates dropped from 7.4 to 4.5% (p = 0.038) after more than 10 implants per operator. Total procedure duration decreased from 30.9 ± 19.1 min in quartile 1 to 21.6 ± 13.2 min (p < 0.001) in quartile 4. The need for multiple repositionings during the LP procedure reduced in quartile 4 (14.8%), compared to quartiles 1 (26.8%; p < 0.001), 2 (26.6%; p < 0.001), and 3 (20.4%; p = 0.03). CONCLUSIONS: Learning curves exist for Nanostim LP implantation. Procedure efficiency improved with increased operator experience, according to a decrease in the incidence of SADE, procedure duration, and repositioning attempts.

Comparative study of acute and mid-term complications with leadless and transvenous cardiac pacemakers.

BACKGROUND: Leadless cardiac pacemakers (LCPs) aim to mitigate lead- and pocket-related complications seen with transvenous pacemakers (TVPs). OBJECTIVE: The purpose of this study was to compare complications between the LCP cohort from the LEADLESS Pacemaker IDE Study (Leadless II) trial and a propensity score-matched real-world TVP cohort. METHODS: The multicenter LEADLESS II trial evaluated the safety and efficacy of the Nanostim LCP (Abbott, Abbott Park, IL) using structured follow-up, with serious adverse device effects independently adjudicated. TVP data were obtained from Truven Health MarketScan claims databases for patients implanted with single-chamber TVPs between April 1, 2010 and March 31, 2014 and more than 1 year of preimplant enrollment data. Comorbidities and complications were identified via International Classification of Diseases, Ninth Revision and Current Procedural Terminology codes. Short-term (≤1 months) and mid-term (>1-18 months) complications were compared between the LCP cohort and a propensity score-matched subset of the TVP cohort. RESULTS: Among 718 patients with LCPs (mean age 75.6 ± 11.9 years; 62% men) and 1436 patients with TVPs (mean age 76.1 ± 12.3 years; 63% men), patients with LCPs experienced fewer complications (hazard ratio 0.44; 95% confidence interval 0.32-0.60; P < .001), including short-term (5.8% vs 9.4%; P = .01) and mid-term (0.56% vs 4.9%; P < .001) events. In the short-term time frame, patients with LCPs had more pericardial effusions (1.53% vs 0.35%; P = .005); similar rates of vascular events (1.11% vs 0.42%; P = .085), dislodgments (0.97% vs 1.39%; P = .54), and generator complications (0.70% vs 0.28%; P = .17); and no thoracic trauma compared to patients with TVPs (rate of thoracic trauma 3.27%). In short- and mid-term time frames, TVP events absent from the LCP group included lead-related, pocket-related, and infectious complications. CONCLUSION: Patients with LCPs experienced fewer overall short- and mid-term complications, including infectious and lead- and pocket-related events, but more pericardial effusions, which were uncommon but serious.

A worldwide experience of the management of battery failures and chronic device retrieval of the Nanostim leadless pacemaker.

BACKGROUND: The Nanostim leadless pacemaker (LP) met the primary endpoints in an investigational device exemption trial, and was shown to be fully retrievable percutaneously. In October 2016, St Jude Medical issued a worldwide alert of a battery malfunction that caused lost pacing output and LP communication. OBJECTIVE: To report the battery failure mechanism and incidence and the worldwide patient management, including device retrieval experiences. METHODS: The affected LP battery is a custom lithium-carbon monofluoride cell. These were returned after failure and underwent analysis assessing electronics and battery performance. Data were collected in ongoing clinical studies when LPs were abandoned or retrieved. RESULTS: Of 1423 LPs implanted worldwide, there were 34 battery failures, occurring at 2.9 ± 0.4 years with no instances of associated patient injury. Analysis of returned batteries revealed an increase in battery resistance caused by insufficient electrolyte availability at the cathode/anode interface. A total of 66 of 73 retrieval attempts were successful (90.4%; implant duration range: 0.2-4.0 years). The LP docking button was inaccessible in 6 patients, and the docking button detached from the LP during retrieval in 1 patient. There was 1 case of arteriovenous fistula and another case of the LP docking button migrating into the pulmonary artery. There were also 115 non-LP retrieval patients after the advisory who received an additional pacemaker, with no adverse device-to-device interactions reported. CONCLUSION: As with standard pacers, LPs can have critical battery failures. Chronic retrieval of LPs is safe and efficacious.

Determinants of Time in Therapeutic Range in Patients Receiving Oral Anticoagulants (A Substudy of IMPACT).

Implanted cardiac arrhythmia devices can detect atrial tachyarrhythmias (atrial high-rate episodes [AHREs]) that are considered to correlate with atrial fibrillation and risk of stroke. In the IMPACT trial, oral anticoagulation was initiated when AHREs were detected by implanted cardioverter-defibrillators and withdrawn when they abated, according to a protocol accounting both for AHRE duration as detected by remote device monitoring and stroke risk assessment. In this analysis, we ascertained determinants of time in therapeutic range (TTR) among protocol-determined vitamin K antagonist-treated patients during the trial. We enrolled 2,718 patients with at least 1 additional stroke risk factor (CHADS2 score ≥1) at 104 arrhythmia centers. The sex, age <60, medical history, treatments interacting with VKA, tobacco use (2 points) and race (2 points for non-Caucasian) (SAMe-TT2R2) score is a simple clinical-derived score designed to aid decision-making on whether a patient is likely to achieve good anticoagulation control on vitamin K antagonist (e.g., warfarin), which was calculated and related to TTR achieved using the Rosendaal method. We analyzed 229 patients (mean age 66.7 years; mean CHADS2 score 2.85 [SD 1.1]) with mean TTR of 0.536 (SD 0.23) overall. Univariate analysis identified 5 variables associated with differences in mean TTR. Mean TTR was lower in those who were women (p = 0.031), of black race (p = 0.005) and in New York Heart Association class IV (p = 0.014), whereas hemoglobin >13.5 g/dl (p = 0.010) and New York Heart Association class I (p = 0.037) were associated with higher mean TTR. There was a significant difference in mean TTR value between US and non-US sites (Canada and Germany) (mean TTR for US: 0.513 vs non-US: 0.686; p <0.0001). Mean TTR was significantly lower (Δ = 0.1382, 95% CI 0.0382 to 0.2382) for patients with SAMe-TT2R2 scores of 4 (p = 0.007) and higher (Δ = 0.0612, 95% CI 0.0005 to 0.1219) for patients with SAMe-TT2R2 scores of 1 (p = 0.048). Linear regression confirmed a significant association between lower SAMe-TT2R2 score and improved anticoagulation control (p = 0.0021) with a 1-unit decrease in SAMe-TT2R2 score associated with an increase in TTR of 0.0404 (95% CI 0.0149 to 0.0659). In conclusion, clinical, geographical, and demographic factors were associated with the quality of anticoagulation control as reflected by TTR. Although overall TTR in this population was poor, lower SAMe-TT2R2 scores were associated with better TTR.

Percutaneous Implantation of an Entirely Intracardiac Leadless Pacemaker.

BACKGROUND: Cardiac pacemakers are limited by device-related complications, notably infection and problems related to pacemaker leads. We studied a miniaturized, fully self-contained leadless pacemaker that is nonsurgically implanted in the right ventricle with the use of a catheter. METHODS: In this multicenter study, we implanted an active-fixation leadless cardiac pacemaker in patients who required permanent single-chamber ventricular pacing. The primary efficacy end point was both an acceptable pacing threshold (≤2.0 V at 0.4 msec) and an acceptable sensing amplitude (R wave ≥5.0 mV, or a value equal to or greater than the value at implantation) through 6 months. The primary safety end point was freedom from device-related serious adverse events through 6 months. In this ongoing study, the prespecified analysis of the primary end points was performed on data from the first 300 patients who completed 6 months of follow-up (primary cohort). The rates of the efficacy end point and safety end point were compared with performance goals (based on historical data) of 85% and 86%, respectively. Additional outcomes were assessed in all 526 patients who were enrolled as of June 2015 (the total cohort). RESULTS: The leadless pacemaker was successfully implanted in 504 of the 526 patients in the total cohort (95.8%). The intention-to-treat primary efficacy end point was met in 270 of the 300 patients in the primary cohort (90.0%; 95% confidence interval [CI], 86.0 to 93.2, P=0.007), and the primary safety end point was met in 280 of the 300 patients (93.3%; 95% CI, 89.9 to 95.9; P<0.001). At 6 months, device-related serious adverse events were observed in 6.7% of the patients; events included device dislodgement with percutaneous retrieval (in 1.7%), cardiac perforation (in 1.3%), and pacing-threshold elevation requiring percutaneous retrieval and device replacement (in 1.3%). CONCLUSIONS: The leadless cardiac pacemaker met prespecified pacing and sensing requirements in the large majority of patients. Device-related serious adverse events occurred in approximately 1 in 15 patients. (Funded by St. Jude Medical; LEADLESS II ClinicalTrials.gov number, NCT02030418.).

Randomized trial of atrial arrhythmia monitoring to guide anticoagulation in patients with implanted defibrillator and cardiac resynchronization devices.

AIMS: Atrial tachyarrhythmias (ATs) detected by implanted devices are often atrial fibrillation or flutter (AF) associated with stroke. We hypothesized that introduction and termination of anticoagulation based upon AT monitoring would reduce both stroke and bleeding. METHODS AND RESULTS: We randomized 2718 patients with dual-chamber and biventricular defibrillators to start and stop anticoagulation based on remote rhythm monitoring vs. usual office-based follow-up with anticoagulation determined by standard clinical criteria. The primary analysis compared the composite endpoint of stroke, systemic embolism, and major bleeding with the two strategies. The trial was stopped after 2 years median follow-up based on futility of finding a difference in primary endpoints between groups. A total of 945 patients (34.8%) developed AT, 264 meeting study anticoagulation criteria. Adjudicated atrial electrograms confirmed AF in 91%; median time to initiate anticoagulation was 3 vs. 54 days in the intervention and control groups, respectively (P < 0.001). Primary events (2.4 vs. 2.3 per 100 patient-years) did not differ between groups (HR 1.06; 95% CI 0.75-1.51; P = 0.732). Major bleeding occurred at 1.6 vs. 1.2 per 100 patient-years (HR 1.39; 95% CI 0.89-2.17; P = 0.145). In patients with AT, thromboembolism rates were 1.0 vs. 1.6 per 100 patient-years (relative risk -35.3%; 95% CI -70.8 to 35.3%; P = 0.251). Although AT burden was associated with thromboembolism, there was no temporal relationship between AT and stroke. CONCLUSION: In patients with implanted defibrillators, the strategy of early initiation and interruption of anticoagulation based on remotely detected AT did not prevent thromboembolism and bleeding. CLINICAL TRIAL REGISTRATION: IMPACT ClinicalTrials.gov identifier: NCT00559988 ( http://clinicaltrials.gov/ct2/show/NCT00559988?term=NCT00559988&rank=1 ).

Efficacy and safety of vernakalant in patients with atrial flutter: a randomized, double-blind, placebo-controlled trial.

AIMS: Vernakalant is a novel, relatively atrial-selective antiarrhythmic agent for conversion of atrial fibrillation (AF) to sinus rhythm. This study examined the safety and efficacy of vernakalant in converting atrial flutter (AFL) to sinus rhythm. METHODS AND RESULTS: This was a phase 2/3, randomized, double-blind, placebo-controlled trial. Adults with AFL received either a 10 min infusion of 3.0 mg/kg vernakalant (n = 39) or placebo (n = 15). If AFL or AF persisted at the end of a 15 min observation period, a second 10 min infusion of 2.0 mg/kg vernakalant or placebo was administered. The primary efficacy outcome was the proportion of patients who had treatment-induced conversion of AFL to sinus rhythm for a minimum duration of 1 min within 90 min after the start of the first infusion. No patient in the placebo group met the primary outcome. Only one patient receiving vernakalant (1 of 39, 3%) converted to sinus rhythm. A reduced mean absolute ventricular response rate occurred within 50 min in patients receiving vernakalant (mean change from baseline -8.2 b.p.m.) vs. patients receiving placebo (-0.2 b.p.m.) (P = 0.037). A post-hoc analysis revealed that vernakalant increased AFL cycle length by an average of 55 ms, whereas the AFL cycle length was unchanged in the placebo group (P < 0.001). There was no occurrence of 1 : 1 atrio-ventricular conduction. Dysgeusia and sneezing were the most common treatment-related adverse events, consistent with previous reports. CONCLUSION: Vernakalant did not restore sinus rhythm in patients with AFL. Vernakalant modestly slowed AFL and ventricular response rates, and was well tolerated.

Surveillance of AF recurrence post-surgical AF ablation using implantable cardiac monitor.

BACKGROUND: Although pulmonary vein isolation is an effective treatment for recurrent atrial fibrillation (AF), there is no consensus on the definition of success or follow-up strategies. Existing data are limited to intermittent Holter or transtelephonic monitoring with reliance on patient symptoms. OBJECTIVE: We sought to determine the outcomes of surgical ablation and post-ablation AF surveillance with a leadless implantable cardiac monitor (ICM). METHODS: Forty-five patients with drug-refractory paroxysmal or persistent AF underwent video-assisted epicardial ablation using a bipolar radiofrequency clamp. An ICM was implanted subcutaneously post-ablation to assess AF recurrence. AF recurrence was defined as ≥1 AF episode with a duration of ≥30 s. The device-stored data was downloaded weekly over the internet, and all transmitted events were reviewed. RESULTS: A total of 1,220 AF automatic and patient-activated AF episodes were analyzed over a follow-up of 12 ± 3 months. Of these episodes, 46% were asymptomatic. Furthermore, only 66% of the patient-activated episodes were AF. AF recurrence was highest in first 4 weeks and substantially decreased 6 months post-ablation. The overall freedom from AF recurrence at the end of follow-up was 60%. When 48-h Holter recordings were compared with the device-stored episodes, the sensitivity of the device to detect AF was 98%, and the specificity was 71%. CONCLUSIONS: The ICM provides an objective measure of AF ablation success and may be useful in making clinical decisions. This device may be used in future ablation studies to develop a more rigorous definition of procedural success.

Programming antitachycardia pacing for primary prevention in patients with implantable cardioverter defibrillators: results from the PROVE trial.

OBJECTIVES: the PROVE trial was designed to determine if antitachycardia pacing (ATP) is clinically beneficial for primary prevention in patients who have implantable cardioverter defibrillators (ICDs) or cardiac resynchronization therapy defibrillators (CRT-Ds). BACKGROUND: use of ICDs and CRT-Ds reduces mortality in patients with ventricular dysfunction and mild to moderate heart failure. However, in studies of the primary prevention population, shock-only ICDs are predominantly used, without ATP programming for less painful termination of ventricular tachycardia (VT). METHODS: we conducted a prospective, nonrandomized, multicenter study using market-released ICDs and CRT-Ds. Patients received devices programmed to deliver ATP for VT cycle lengths of 270-330 ms. Follow-up evaluation was performed at 3, 6, and 12 months. The incidence of VT and the rate of successful termination by ATP were analyzed. RESULTS: of 830 patients in the study population (men, 73%; mean age, 67.3 ± 12 years), 32% received single-chamber ICDs, 44% dual-chamber ICDs, and 24% CRT-Ds. ATP was attempted for 112 VT episodes in 71 patients, and 103 (92%) of the VT episodes were successfully terminated. Three VT episodes were accelerated by ATP and required termination by ICD shock; 6 episodes terminated spontaneously or by ICD shock. CONCLUSIONS: VT is common in patients without a history of this arrhythmia who have received ICDs or CRT-Ds for primary prevention indications. Programming ICDs for ATP therapy at the time of implantation could potentially terminate most VT episodes and reduce the number of painful shocks for these patients.

Multicenter randomized study of anticoagulation guided by remote rhythm monitoring in patients with implantable cardioverter-defibrillator and CRT-D devices: Rationale, design, and clinical characteristics of the initially enrolled cohort The IMPACT study.

Atrial fibrillation and atrial flutter are common cardiac arrhythmias associated with an increased risk of stroke in patients with additional risk factors. Anticoagulation ameliorates stroke risk, but because these arrhythmias may occur intermittently without symptoms, initiation of prophylactic therapy is often delayed until electrocardiographic documentation is obtained. The IMPACT study is a multicenter, randomized trial of remote surveillance technology in patients with implanted dual-chamber cardiac resynchronization therapy defibrillator (CRT-D) devices designed to test the hypothesis that initiation and withdrawal of oral anticoagulant therapy guided by continuous ambulatory monitoring of the atrial electrogram improve clinical outcomes by reducing the combined rate of stroke, systemic embolism, and major bleeding compared with conventional clinical management. For those in the intervention group, early detection of atrial high-rate episodes (AHRE) generates an automatic alert to initiate anticoagulation based on patient-specific stroke risk stratification. Subsequently, freedom from AHRE for predefined periods prompts withdrawal of anticoagulation to avoid bleeding. Patients in the control arm are managed conventionally, the anticoagulation decision prompted by incidental detection of atrial fibrillation or atrial flutter during routine clinical follow-up. The results will help define the clinical utility of wireless remote cardiac rhythm surveillance and help establish the critical threshold of AHRE burden warranting anticoagulant therapy in patients at risk of stroke. In this report, we describe the study design and baseline demographic and clinical features of the initial cohort (227 patients).

Impact of atrial prevention pacing on atrial fibrillation burden: primary results of the Study of Atrial Fibrillation Reduction (SAFARI) trial.

BACKGROUND: The role of atrial-based pacing algorithms in preventing atrial fibrillation (AF) remains controversial. The inconsistent results noted in previous trials may be due in part to differences in endpoints, pacing algorithms, and study design. SAFARI, a worldwide, prospective, randomized clinical trial, was designed to address these issues and to evaluate the safety and efficacy of a suite of prevention pacing therapies (PPTs) among patients with paroxysmal AF. METHODS AND RESULTS: Patients who met standard pacemaker indications and documented symptomatic AF were implanted with a pacemaker (Vitatron Selection 9000). At 4 months, only patients with documented AF despite dual-chamber pacing were randomized to PPTs ON or PPTs OFF and followed for 6 months. Incidence of permanent AF and change in AF burden were compared between the two groups. Among the 555 patients enrolled, 240 had AF burden at 4 months and were randomized. The risk of developing permanent AF was similar in both groups (0 in the PPTs ON group vs. 3 in the OFF group). However, there was a significant reduction in AF burden between baseline and 10-month follow-up in the ON group compared with the OFF group (median decrease of 0.08 hours/day vs no change, P = .03). CONCLUSION: Among patients with paroxysmal AF and standard bradycardia indications, PPTs are safe and associated with less AF burden compared with conventional pacing.

Role of microvolt T-wave alternans in assessment of arrhythmia vulnerability among patients with heart failure and systolic dysfunction: primary results from the T-wave alternans sudden cardiac death in heart failure trial substudy.

BACKGROUND: Sudden cardiac death remains a leading cause of mortality despite advances in medical treatment for the prevention of ischemic heart disease and heart failure. Recent studies showed a benefit of implantable cardioverter defibrillator implantation, but appropriate shocks for ventricular tachyarrhythmias were noted only in a minority of patients during 4 to 5 years of follow-up. Accordingly, better risk stratification is needed to optimize patient selection. In this regard, microvolt T-wave alternans (TWA) has emerged as a potentially useful measure of arrhythmia vulnerability, but it has not been evaluated previously in a prospective, randomized trial of implantable cardioverter defibrillator therapy. METHODS AND RESULTS: This investigation was a prospective substudy of the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) that included 490 patients at 37 clinical sites. TWA tests were classified by blinded readers as positive (37%), negative (22%), or indeterminate (41%) by standard criteria. The composite primary end point was the first occurrence of any of the following events: sudden cardiac death, sustained ventricular tachycardia/fibrillation, or appropriate implantable cardioverter defibrillator discharge. During a median follow-up of 30 months, no significant differences in event rates were found between TWA-positive or -negative patients (hazard ratio 1.24, 95% confidence interval 0.60 to 2.59, P=0.56) or TWA-negative and nonnegative (positive and indeterminate) subjects (hazard ratio 1.28, 95% confidence interval 0.65 to 2.53, P=0.46). Similar results were obtained with the inclusion or exclusion of patients randomized to amiodarone in the analyses. CONCLUSIONS: TWA testing did not predict arrhythmic events or mortality in SCD-HeFT, although a small reduction in events (20% to 25%) among TWA-negative patients cannot be excluded given the sample size of this study. Accordingly, these results suggest that TWA is not useful as an aid in clinical decision making on implantable cardioverter defibrillator therapy among patients with heart failure and left ventricular systolic dysfunction.