AF Episodes Research Articles

Early rhythm-control ablation therapy in preventing AF recurrences: insight from the CHARISMA Registry

Abstract Funding Acknowledgements Type of funding sources: None. Background An early and comprehensive rhythm-control therapy emerges as a need to treat AF in an effective way and to improve the ablation outcomes, in terms of arrhythmia-free survival. Purpose We aimed to investigate the importance of timing of ablation in preventing AF recurrences. Methods 153 consecutive patients (pts) undergoing AF ablation from the CHARISMA registry at 8 Italian centres were included. Ablations were guided by a novel radiofrequency ablation catheter with local impedance (LI)-sensing capability through a dedicated algorithm (DirectSense, Boston Scientific). Pts were grouped as early treated (ET) if the procedure was performed within 1 year after the first AF episode and as delayed treated (DT) if admitted for ablation after more than 1 year. The ablation endpoint was PVI as assessed by entrance and exit block. Post-ablation follow-up was scheduled at 3, 6 and 12 months. AF and atrial tachycardia (AT) recurrences were considered as long-term endpoint. Results Of the 153 pts enrolled (69.9% male, 59 ± 10 years, 61.4% paroxysmal AF, 38.6% persistent AF), 123 (80.4%) met Class I indications, 23 (15%) Class IIa indications and 7 (4.6%) Class IIb indications according to current ESC AF guidelines. The mean time to ablation procedure from the first AF episode was 1034 ± 1483 days. Eighty pts (52.3%) were included in ET group, whereas 73 pts (47.7%) in DT group. No differences were found between AF type in terms of ablation strategy (53.3% of the cases -52 out 94- were classified as ET for paroxysmal AF vs 47.5% of the cases -28 out 59- were ET for persistent AF, p = 0.4346). At the end of the procedures, all PVs had been successfully isolated in all study pts. During a mean follow-up of 366 ± 130 days, 18 pts (11.8%) suffered an AF/AT recurrence after the 90-day blanking period. Recurrences occurred mostly in the DT group compared to the ET one (13 out 73 -17.8%- vs 5 out 80 -6.3%-, p = 0.042) and the time to AT/AF recurrence was longer in the ET group (HR = 0.2876, 95%CI: 0.1029 to 0.8038; p = 0.0181). On multivariate logistic analysis adjusted for baseline confounders, only hypertension (HR = 4.66, 95%CI: 1.5 to 14.48, p = 0.0081) was independently associated with recurrences. An early rhythm-control therapy was associated with a low risk of recurrences beyond the hypertension risk factor, ranging from 2% (no hypertension and an ET ablation therapy) to 30.3% (with hypertension and a DT procedure) (Figure 1). Conclusion A LI-guided ablation strategy for PVI proved to be safe and effective and resulted in a very high recurrence-free rate. An early rhythm-control therapy in the absence of common risk factors was associated with the lowest rate of recurrences. Abstract Figure. AT/AF Recurrence

Antiarrhythmic Medication for Atrial Fibrillation (AIM-AF) study: A physician survey of antiarrhythmic drug (AAD) treatment practices and guideline adherence in the EU and USA

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Sanofi Introduction The 2020 European Society of Cardiology and the 2019 USA (AHA/ACC/HRS) guidelines recommend the use of AADs for rhythm control in patients with symptomatic AF. This study sought to understand AAD treatment practices and adherence to guidelines across the EU and the USA. Method An online physician survey of cardiologists, cardiac electrophysiologists and interventional electrophysiologists (N = 569) was conducted in the USA, Germany, Italy and the UK. All respondents were actively treating ≥10 AF patients who received drug therapy and/or who had received or were referred for ablation. This extensively detailed survey explored questions on physician demographics, AF types, and drug treatment and ablation practices. Results: Of the responses obtained (1) Amiodarone was used frequently across co-morbidity categories (highest use in those with heart failure with reduced left ventricular ejection fraction [LVEF] [80%]), including in those in which it is not indicated for initial therapy (minimal or no structural heart disease: 26%). Other deviations from guideline recommendations, include: class 1C drugs were used with structural heart disease, including coronary artery disease (CAD) (average class 1C use in CAD-related comorbidities: 6%); sotalol was used with renal dysfunction (22%); and drugs such as sotalol and dofetilide were initiated out of hospital (56% and 17% of respondents, respectively). (2) Nonetheless, a majority of respondents (53%) considered guidelines as the most important non-patient factor in influencing their choice of AF management. (3) Rhythm control was selected more frequently as primary therapy for paroxysmal AF (PAF) (59% of patients) while rate control was used more often for persistent AF (53%). (4) For PAF, AADs were preferred as 1st line more often than ablation, especially if PAF was infrequent and mildly symptomatic (59% of respondents) while ablation was preferred more if frequent symptomatic PAF and for recurrent persistent AF. (5) Rhythm control (AAD or ablation) was chosen in notable numbers for asymptomatic AF and subclinical AF (AADs: 36% and 37%, respectively; ablation: 9% and 14%, respectively). (6) AAD use for those with a first or recurrent episodes of symptomatic AF was 60% or 47%, respectively. (7) Efficacy and safety were chosen as the most important considerations for choice of specific rhythm control therapy (49% and 33%, respectively), and reduction of mortality and cardiovascular hospitalisation (23%) were as important as maintaining sinus rhythm (26%) for rhythm therapy goals. Conclusions Although surveyed clinicians consider guidelines important, deviations in patient types and treatments chosen that compromise safety or were not indicated were common. Findings suggest a lack of understanding of the pharmacology and safe use of AADs, highlighting an important need for further education. Abstract Figure.

Feasibility of atrial fibrillation detection from a novel wearable armband device

BackgroundAtrial fibrillation (AF) is the world’s most common heart rhythm disorder and even several minutes of AF episodes can contribute to risk for complications, including stroke. However, AF often goes undiagnosed owing to the fact that it can be paroxysmal, brief, and asymptomatic.ObjectiveTo facilitate better AF monitoring, we studied the feasibility of AF detection using a continuous electrocardiogram (ECG) signal recorded from a novel wearable armband device.MethodsIn our 2-step algorithm, we first calculate the R-R interval variability–based features to capture randomness that can indicate a segment of data possibly containing AF, and subsequently discriminate normal sinus rhythm from the possible AF episodes. Next, we use density Poincaré plot-derived image domain features along with a support vector machine to separate premature atrial/ventricular contraction episodes from any AF episodes. We trained and validated our model using the ECG data obtained from a subset of the MIMIC-III (Medical Information Mart for Intensive Care III) database containing 30 subjects.ResultsWhen we tested our model using the novel wearable armband ECG dataset containing 12 subjects, the proposed method achieved sensitivity, specificity, accuracy, and F1 score of 99.89%, 99.99%, 99.98%, and 0.9989, respectively. Moreover, when compared with several existing methods with the armband data, our proposed method outperformed the others, which shows its efficacy.ConclusionOur study suggests that the novel wearable armband device and our algorithm can be used as a potential tool for continuous AF monitoring with high accuracy.

Impact of Mobile Health Devices for the Detection of Atrial Fibrillation: Systematic Review.

BackgroundAtrial fibrillation (AF) is the most common arrhythmia, and its prevalence is increasing. Early diagnosis is important to reduce the risk of stroke. Mobile health (mHealth) devices, such as single-lead electrocardiogram (ECG) devices, have been introduced to the worldwide consumer market over the past decade. Recent studies have assessed the usability of these devices for detection of AF, but it remains unclear if the use of mHealth devices leads to a higher AF detection rate.ObjectiveThe goal of the research was to conduct a systematic review of the diagnostic detection rate of AF by mHealth devices compared with traditional outpatient follow-up. Study participants were aged 16 years or older and had an increased risk for an arrhythmia and an indication for ECG follow-up—for instance, after catheter ablation or presentation to the emergency department with palpitations or (near) syncope. The intervention was the use of an mHealth device, defined as a novel device for the diagnosis of rhythm disturbances, either a handheld electronic device or a patch-like device worn on the patient’s chest. Control was standard (traditional) outpatient care, defined as follow-up via general practitioner or regular outpatient clinic visits with a standard 12-lead ECG or Holter monitoring. The main outcome measures were the odds ratio (OR) of AF detection rates.MethodsTwo reviewers screened the search results, extracted data, and performed a risk of bias assessment. A heterogeneity analysis was performed, forest plot made to summarize the results of the individual studies, and albatross plot made to allow the P values to be interpreted in the context of the study sample size.ResultsA total of 3384 articles were identified after a database search, and 14 studies with a 4617 study participants were selected. All studies but one showed a higher AF detection rate in the mHealth group compared with the control group (OR 1.00-35.71), with all RCTs showing statistically significant increases of AF detection (OR 1.54-19.16). Statistical heterogeneity between studies was considerable, with a Q of 34.1 and an I2 of 61.9, and therefore it was decided to not pool the results into a meta-analysis.ConclusionsAlthough the results of 13 of 14 studies support the effectiveness of mHealth interventions compared with standard care, study results could not be pooled due to considerable clinical and statistical heterogeneity. However, smartphone-connectable ECG devices provide patients with the ability to document a rhythm disturbance more easily than with standard care, which may increase empowerment and engagement with regard to their illness. Clinicians must beware of overdiagnosis of AF, as it is not yet clear when an mHealth-detected episode of AF must be deemed significant.

Rationale and design of a large population study to validate software for the assessment of atrial fibrillation from data acquired by a consumer tracker or smartwatch: The Fitbit heart study

Early detection of atrial fibrillation or flutter (AF) may enable prevention of downstream morbidity. Consumer wrist-worn wearable technology is capable of detecting AF by identifying irregular pulse waveforms using photoplethysmography (PPG). The validity of PPG-based software algorithms for AF detection requires prospective assessment. The Fitbit Heart Study (NCT04380415) is a single-arm remote clinical trial examining the validity of a novel PPG-based software algorithm for detecting AF. The proprietary Fitbit algorithm examines pulse waveform intervals during analyzable periods in which participants are sufficiently stationary. Fitbit consumers with compatible wrist-worn trackers or smartwatches were invited to participate. Enrollment began May 6, 2020 and as of October 1, 2020, 455,699 participants enrolled. Participants in whom an irregular heart rhythm was detected were invited to attend a telehealth visit and eligible participants were then mailed a one-week single lead electrocardiographic (ECG) patch monitor. The primary study objective is to assess the positive predictive value of an irregular heart rhythm detection for AF during the ECG patch monitor period. Additional objectives will examine the validity of irregular pulse tachograms during subsequent heart rhythm detections, self-reported AF diagnoses and treatments, and relations between irregular heart rhythm detections and AF episode duration and time spent in AF. The Fitbit Heart Study is a large-scale remote clinical trial comprising a unique software algorithm for detection of AF. The study results will provide critical insights into the use of consumer wearable technology for AF detection, and for characterizing the nature of AF episodes detected using consumer-based PPG technology.

IS TAILORED ANTICOAGULATION MANAGEMENT FEASIBLE IN PATIENTS WITH ARTERIAL HYPERTENSION AFTER THEIR FIRST CLINICAL ECG-DOCUMENTED PAROXYSMAL ATRIAL FIBRILLATION EPISODE?

Objective: Long-term anticoagulation therapy is usually recommended for most of the patients with hypertension as the CHA2DS2-VASc score is at least 1. However, this is to some extent arbitrary, because it is not known if these patients will continue to present AF episodes. Furthermore, recent data showed that only AF episodes with a duration >24 hours increased significantly the risk of ischemic stroke. We tested the hypothesis whether the identification of the exact natural course of AF would have a favorable impact on AF-personalized anticoagulation, by facilitating the selection of patients in need of antithrombotic treatment on the basis of their AF recurrence profile. Design and method: Consecutive patients who received an implantable loop recorder-ILR (Reveal XT 9529; Medtronic, Minneapolis, Minnesota, USA) after their first ECG-documented symptomatic episode of paroxysmal AF were enrolled. Low recurrence rate and short durations episodes of the arrhythmia was defined as <5 AF episodes/year and </=24 h AF episodes respectively. Results: Thirty (30) consecutive patients (mean age 66.9 +/− 10 years; 14 men); 25/30 (83.3%) with arterial hypertension, were included in the study. The follow-up period lasted for 34,63 +/− 2,96 months after the implantation of the ILR. The mean CHA2DS2-VASc score was 2.83 ± 1.66. Three patients (10%) had no AF recurrence, while 4 patients (13.3%) presented only one episode during the three-year follow-up period. Almost half of the patients (46.7%) had a low recurrence rate (<5 episodes/year), while the majority of patients (19/30) suffered from episodes with maximum duration of </=24 h. Eleven patients (36.7%) presented either no episode or a low recurrence rate with episodes lasting </=24 h. Conclusions: A significant percentage of patients either suffer 0–1 AF recurrence (23.3%) after their first episode or show a low recurrence rate (46.7%). Most patients present episodes of short duration (<24 h). If these findings are confirmed by larger studies, they could have an impact in the strategy towards a more personalized approach, in the long-term AF anticoagulation management, especially in the era of non-Vitamin K antagonists and devices that provide long-term cardiac rhythm monitoring.

Cryoballoon ablation for paroxysmal atrial fibrillation: mid‐term outcome evaluated by ECG monitoring with an implantable loop recorder

The success rate after cryoballoon ablation (CB-A) performed for paroxysmal atrial fibrillation (PAF) might be overestimated by traditional noninvasive monitoring techniques. The purpose of this study was to evaluate the mid-term outcome of CB-A in patients with PAF implanted with an implantable loop recorder (ILR) after the procedure. Between January 2017 and March 2019, all patients who underwent CB-A for PAF and who were subsequently implanted with an ILR were retrospectively included. All devices were equipped with remote monitoring. All ILR-documented atrial tachycardia (AT) or AF episodes ≥ 6 min were considered as recurrence; both true and false episodes were collected. A 3-month post-procedural blanking period (BP) was applied. A total of 102 patients (77 men, mean age 60.6 ± 9.6 years) who underwent pulmonary vein isolation (PVI) by CB-A were included; mean time from first diagnosis of AF to PVI was 51.5 ± 46.9 months. Mean follow-up was 29.3 ± 8.1 months; at 12-month follow-up, the success rate was 65.7%, while at 2-year follow-up, freedom from AT/AF recurrences was achieved in 59.3% of the patients. In the follow-up, a total of 4987 ECG strips were analyzed; true-positive episodes were confirmed in 2026 cases (40.6%), whereas 2961 episodes (59.4%) were considered false-positive. In patients with PAF implanted with an ILR, CB-A results in freedom from any AT/AF recurrence in 65.7% of patients at 12-month follow-up and in 59.3% of patients when evaluated at 2-year. Careful adjudication of all ILR-documented AF episodes is required to avoid misdiagnosis.

Usefulness of transesophageal echocardiography before cardioversion in atrial arrhythmias.

Although many thromboembolism risk factors are well defined, formation of thrombus or dense spontaneous contrast (sludge) in the left atrium remains enigmatic and confounding. Exclusion of the thrombus is extremely important with respect to planned reversal of sinus rhythm. Data regarding the routine transesophagal echocardiography (TEE) before cardioversion are inconclusive. The authors focused on analyzing the usefulness of TEE before cardioversion by assessment of factors influencing the risk of thrombus and/or dense spontaneous echo contrast with the intention of extending indications for TEE in the group with a high risk of thrombus or to forgo TEE in the low risk group. Two hundred sixty-nine consecutive patients with persistent (> 48 h) atrial fibrillation or atrial flutter, in whom a direct current cardioversion was planned, were undergoing TEE for the detection of the left atrial thrombus or dense spontaneous echo contrast. Additional clinical and echocardiographic data were collected. The relationship between both thrombus and dense spontaneous echo contrast and covariates was analyzed with the use of binary logistic regression. Left atrium (LA) appendage (LAA) thrombus and/or sludge were detected in 79 (29%) patients. Signs of dementia in mini-mental state examination (hazard ratio [HR]: 1.16; p = 0.005), low velocities in LAA (HR: 3.38; p = 0.032); presence of spontaneous echo contrast in LA (HR: 3.38; p = 0,003) consecutive episode of AF (HR: 2.27; p = 0,046); longer duration of atrial fibrillation (HR: 1.009; p = 0.022); were significant predictors of thrombus and/or dense spontaneous echo contrast. None of the patients with a CHA2DS2VASc score ≤ 1 had thrombus or sludge in the LAA. Among patients with a CHA2DS2VASc score > 1, the prevalence of thrombus or sludge in LAA was independent of the CHA2DS2VASc score value. Amongst many factors, including an established as risk for thromboembolism only a few of them increased the risk for the presence of thrombus in LAA: low velocities in LAA, presence of spontaneous echo contrast, longer duration of arrhythmia, consecutive (not first) arrhythmia episode and signs of dementia from a mini-mental state examination questionnaire. It was believed that there could be a need for an extension of indications of TEE in vast majority of the patients with atrial arrhythmias, due most often to an unpredictable occurrence of thrombus and potentially disastrous thromboembolism. The only exception could have been the group of the patients with a CHA2DS2VASc score ≤ 1.

Comparison of 24 h ECG Holter Monitoring with Real-time Long-term ECG Monitoring System using ECGalert Software and Savvy Single-Lead Patch

AIM: The aim of the study was to show non-inferiority of the single-channel ECGalert system to the gold standard (ECG Holter) in the detection of arrhythmias over the total wear time of both devices.
 METHODS: A prospective study enrolled a total of 165 patients hospitalized at the University Clinic of Cardiology, who underwent simultaneous single-channel ECG recording with ECGAlert system and a conventional 24 h Holter monitor on the 1st day and continued ECGAlert monitoring for few more days, under assignment of the doctor or at the wish of the patient.
 RESULTS: A total of 165 patients were included in the study, 61.2% male, mean age of 58.4 ± 12.7 years. Mean duration of ECG Holter monitoring was 23.2 ± 0.5 h and mean duration of ECGalert/Savvy monitoring was 64.6 ± 31.2. During the first 24 h of simultaneous ECG monitoring with both methods, no statistically significant difference was found in arrhythmia detection. Over the total wear time of both devices, the ECGalert system detected significantly more AF episodes as compared to Holter (p < 0.000). ECGalert demonstrated significantly lower detection rate of false pauses (0.001). However, false detection of episodes of VT or AF was significantly higher in ECGalert system versus Holter (p < 0.000 and p < 0.000 respectively). Patients were more satisfied with ECGalert system, due to lesser interference in daily activities.
 CONCLUSION: The ECGalert system demonstrated superiority over traditional Holter monitoring in arrhythmia detection in the total monitoring period, but not in the first 24 h.

Continuous ECG Monitoring V. Mobile Telemetry: A Comparison of Arrhythmia Diagnostics

Introduction: A myriad of long-term (>48 hr) cardiac rhythm monitors are available for use. Clinicians rarely scrutinize the full disclosure and thus rely on manufacturers to detect and report relevant rhythm abnormalities using processes that are opaque to most providers. This study compares the diagnostic accuracy between mobile cardiac telemetry (MCT) and long term continuous ECG monitoring. Methods: In an outpatient arrhythmia clinic, 50 sequential patients ordered to wear a 30-day MCT were enrolled to simultaneously wear a continuous ECG monitor. Periods of concomitant wear of both devices were examined. Studies were reviewed by two electrophysiologists and categorized according to whether significant clinical arrhythmias were identified and correctly diagnosed. Results: Of the 50 patients enrolled, 46 wore both monitors simultaneously for an average time of simultaneous recording of 10.3 ± 4.4 days. During simultaneous recording, significant arrhythmias were diagnosed by the MCT in 11/46 patients (24%) compared with 23/46 (50%) patients p=0.018, by continuous ECG monitoring. Thus, in 12 of 46 patients (26%), a significant arrhythmia finding was captured by the long-term ECG and missed by the MCT. Long term continuous ECG captured several rhythms which were misreported or unreported by MCT including AV node re-entry in two patients, second degree AV block in three patients, VT in 6 patients, and captured 4 additional AF episodes missed by MCT. Conclusions: In a time-controlled, paired analysis of two disparate rhythm monitors worn simultaneously, human review of long-term continuous ECG recordings significantly outperformed algorithm-dependent MCT monitor's ability to detect significant arrhythmias.

Surgical factors associated with new-onset postoperative atrial fibrillation after lung resection: the EPAFT multicentre study

Purpose of the studyPostoperative atrial fibrillation (POAF) is a recognised complication in approximately 10% of major lung resections. In order to best target preoperative treatment, this study aimed at determining...

Prospective multicentric validation of a novel prediction model for paroxysmal atrial fibrillation

BackgroundThe early recognition of paroxysmal atrial fibrillation (pAF) is a major clinical challenge for preventing thromboembolic events. In this prospective and multicentric study we evaluated prediction scores for the presence of pAF, calculated from non-invasive medical history and echocardiographic parameters, in patients with unknown AF status.MethodsThe 12-parameter score with parameters age, LA diameter, aortic root diameter, LV,ESD, TDI Aʹ, heart frequency, sleep apnea, hyperlipidemia, type II diabetes, smoker, ß-blocker, catheter ablation, and the 4-parameter score with parameters age, LA diameter, aortic root diameter and TDI A’ were tested. Presence of pAF was verified by continuous electrocardiogram (ECG) monitoring for up to 21 days in 305 patients.ResultsThe 12-parameter score correctly predicted pAF in all 34 patients, in which pAF was newly detected by ECG monitoring. The 12- and 4-parameter scores showed sensitivities of 100% and 82% (95%-CI 65%, 93%), specificities of 75% (95%-CI 70%, 80%) and 67% (95%-CI 61%, 73%), and areas under the receiver operating characteristic (ROC) curves of 0.84 (95%-CI 0.80, 0.88) and 0.81 (95%-CI 0.74, 0.87). Furthermore, properties of AF episodes and durations of ECG monitoring necessary to detect pAF were analysed.ConclusionsThe prediction scores adequately detected pAF using variables readily available during routine cardiac assessment and echocardiography. The model scores, denoted as ECHO-AF scores, represent simple, highly sensitive and non-invasive tools for detecting pAF that can be easily implemented in the clinical practice and might serve as screening test to initiate further diagnostic investigations for validating the presence of pAF.Graphic abstractProspective validation of a novel prediction model for paroxysmal atrial fibrillation based on echocardiography and medical history parameters by long-term Holter ECG

Abstract 14514: The Incidence and Natural Progression of New Onset Post-Operative Atrial Fibrillation

Introduction: New onset postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery that is associated with an increased risk for stroke and all-cause mortality. Long term data on POAF recurrence and anticoagulation remains sparse. We aimed to characterize the natural progression and recurrence of new onset POAF during a long-term follow up post cardiac surgery utilizing continuous event monitoring. Methods: This is a single-center, prospective observational study evaluating 42 patients undergoing cardiac surgery and diagnosed during indexed admission with new onset, transient POAF who were discharged in sinus rhythm between May 2015 and December 2019. Prior to discharge, all patients received implantable loop recorders (ILR) for continuous monitoring. Study outcomes were the presence and timing of AF recurrence (first and repeated AF recurrence), all-cause mortality and cerebrovascular accidents (CVA). Results: Forty-two patients [mean age 67.6± 9.6 years, 74% male, mean CHADS 2- VASc 3.5±1.5] were evaluated during a mean follow-up of 1.7 ± 1.2 years. AF recurrence after discharge occurred in 30 patients (71%). Twenty-four of these 30 patients (80%) had their first AF recurrence within the first month, 3 (10%) patients during months 1-12, and 3 (10%) patients beyond 1 year. Repeated AF recurrence occurred in 13 (43%) patients between 1 and 12-months. Beyond one year of follow-up, 5 (17%) patients had either their first AF recurrence (3) or repeated AF recurrence (2). During follow-up, there was one death ((-) AF recurrence) and two CVAs ((+) AF recurrence). Conclusions: In this study of continuous monitoring with ILR , the recurrence of AF in patients who develop transient POAF is common. Seventy percent of patients had either their first AF recurrence 6 (20%) or repeated episodes of recurrent AF 15 (50%) after 1-month post-operative follow-up.

Abstract 14523: N-acetylcysteine for the Prevention of Atrial Fibrillation After Noncardiac Thoracic Surgery: A Double-blind, Randomized, Placebo-controlled Trial

Introduction: Adding N-acetylcysteine (NAC) to amiodarone may mitigate inflammation and oxidative stress, preventing postoperative atrial fibrillation (POAF). NAC, reported to reduce cardiac surgery POAF, has not been tested in major thoracic surgery. Methods: Patients at high risk for POAF (BNP≥25pg/ml, male, age≥75, or history of AF) who underwent major thoracic surgery (n=154) were randomized to amiodarone + NAC (n=78) or amiodarone + placebo (n=76). Begun on arrival to the PACU were amiodarone 150 mg iv then 1 g/24 h iv x 48 h, and NAC or placebo bolus 50 mg/kg iv then 50 mg/kg/24 h iv x 48 h. The primary endpoint was sustained AF >30 s by telemetry (first 72 h) or symptoms within 7 days of surgery; patients with the primary endpoint underwent home ECG monitoring. Secondary endpoints were AF up to 1-year post discharge and systemic markers of inflammation. Results: Baseline characteristics were similar between arms (Table). POAF occurred in 15/78 NAC patients (19%) and 13/76 placebo patients (17%) (p=0.8). The trial was stopped at the interim analysis for futility. Regardless of treatment, of 28 patients with POAF, 3/28 (11%) were discharged in AF, and 1/28 (4%) met the primary endpoint after discharge. At 1-year, 7/28 patients with POAF (25%) had recurrent episodes of AF, and 1 developed persistent AF—none developed stroke. Inflammatory markers were similar between treatment arms; however, regardless of NAC, on postoperative day 2, patients with POAF (n=28) had higher CRP (p=0.008) and IL-6 (p=0.001) than patients without POAF (n=126). Conclusions: Compared to amiodarone alone, NAC + amiodarone did not reduce the incidence of POAF nor markers of inflammation early after major thoracic surgery. Recurrent AF episodes are common among patients with POAF within 1-year of surgery.

Abstract 15403: New-onset Atrial Fibrillation is Infrequent in Acute COVID-19 but Maybe Associated With Worse Outcomes

Introduction: The COVID-19 has reached pandemic status with significant morbidity and mortality including cardiovascular complications. Systemic inflammation caused by the COVID-19 infection has been associated with an intense release of multiple cytokines which directly cause myocardial injury. New-onset atrial fibrillation (noAF) is a common consequence of systemic inflammation in bacterial pneumonia as well as influenza and has been shown to have independently poorer outcomes. Hypothesis: We sought to determine the incidence and significance of noAF in patients with confirmed COVID-19 infection. Methods: We prospectively studied patients with acute COVID-19 infection admitted to our referral center between March and May 2020. Data of demographics, clinical features, comorbidities and complications were collected. Cardiac rhythms were observed using 12-lead electrocardiogram and continuous telemetry. Results: Total 62 patients were followed. The end-point included incidence of any episode of AF, cardiovascular death and total mortality. Mean age was 66 ±17 years, 56% were males, 37 patients without history of cardiac disease, 25 patients with documented cardiac disease including 31% of coronary artery disease (CAD), 28% of congestive heart failure (CHF), 11% of history of prior atrial fibrillation (hoAF). Four (6.5%) patients manifested noAF during hospitalization (95% CI, 1.8, 16). There was a significant difference in mortality between patients with and without cardiac diseases (P = 0.02) (Table). All patients with noAF required ventilation support and had significantly higher mortality compared to patients without cardiac disease (P < 0.05) (Figure). Conclusions: New-onset AF was infrequently observed, however was associated with a poorer prognosis for hospitalized patients with acute COVID-19 infection. Larger studies are needed to confirm these findings as well as identify measures of AF prevention in this population.

Atrial fibrillation up to 50 days after cardiac surgery should be considered postoperative atrial fibrillation

Abstract Introduction Postoperative atrial fibrillation (POAF) occurs in up to 45% of patients following cardiothoracic surgery and is defined as any atrial tachyarrhythmia occurring ≤30 days after surgery. Consequently, atrial arrhythmias after 30 days are regarded as new-onset AF. However, biological and clinical data on the association between POAF and new-onset AF, or empirical data supporting the cut-off of 30 days, are lacking. Purpose We hypothesize that patients with POAF are biologically different with respect to atrial fibrosis compared to patients who develop new-onset AF. Methods PREDICT AF is a prospective, multicenter, observational trial that included patients with a CHA2DS2VAsc score≥2 without a history of AF. Patients underwent CABG or valve surgery and the left atrial appendage (LAA) was removed during surgery. The LAA was obtained for expression analysis of extracellular matrix (ECM) genes such as collagen 1 (COL1A1), collagen 3 (COL3A1) and fibronectin (FN1) by qPCR. Patients were monitored during hospitalisation and followed-up at 1, 6, 12 and 24 months with 24-h Holters and ECGs. The primary endpoint was any recorded atrial tachyarrhythmia lasting >30 seconds. We documented all new-onset arrhythmias over time in order to determine potential cut-offs for POAF (Figure A). We then compared the effects of using a 30-, 50- or 70-day cut-off on the rate of new-onset AF and the differences in expression of fibrosis related genes. Results PREDICT AF included 150 cardiac surgery patients: 115 CABG, 11 valve surgeries and 24 combined surgeries. Participants had a median follow-up of 1.9 years [1.0–2.0], were 68±7 years old and 19 (13%) were female. POAF <30 days occurred in 63 (42%) patients. New-onset AF >30 days developed in 21 (14%) patients. Of the 21 patients with new-onset AF, 20 (95%) also had had POAF. New-onset AF defined by a cut-off of 50 days, developed in 15 (10%) patients. In total, 9 patients had an episode of AF between 30 and 50 days, of whom 6 (66.6%) had no AF episodes thereafter. Most of these patients under–went (concomitant) aortic valve surgery. The gene expression of ECM components was significantly more predictive of new-onset AF when using a cut-off of 50 days or even 70 days than when using a cut-off of 30 days (Figure B). Conclusion With stringent monitoring we detected 42% POAF <30 days. One in three POAF patients developed new-onset AF within two years after surgery. However, the majority of the patients who developed new-onset AF between 30 and 50 days postoperatively had no later episodes of AF. Moreover, applying a 50-day cut-off to discriminate POAF from new-onset AF enhanced the prediction of new-onset AF based on the ECM gene expression levels. Our data suggest that both from a biological and a clinical perspective, the cut-off for POAF should be stretched to 50 days postoperatively. New-onset AF prediction with ECM genes Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): NWO VIDI

Left atrial late gadolinium enhancement is associated with atrial fibrillation as detected by continuous monitoring

Abstract Background Left atrial late gadolinium enhancement (LA LGE) measured with cardiac magnetic resonance (CMR) imaging is emerging as a marker of atrial fibrosis and has been associated with worse outcomes in AF ablation procedures. However, the prognostic value of LA LGE for incident AF remains unknown. Methods CMR including measurement of left ventricular (LV) and LA volumes and function, as well as LV extracellular volume fraction and LA LGE, was acquired in 68 patients aged at least 70 years with risk factors for stroke. All included patients received and implantable loop recorder and were continuously monitored for previously unknown AF. Incident AF was adjudicated by senior cardiologists. Results Patients were monitored for AF with implantable loop recorder during a median of 41 [36; 43] months. AF episodes lasting ≥6 minutes were detected in 32 patients (47%) and 16 patients (24%) experienced AF episodes lasting ≥5.5-hour. In Cox regression analyses adjusted for sex, age and comorbidities, we found that LA volumes and function and LA LGE were independently associated with incident AF. For LA LGE, the hazard ratio for time to AF episodes lasting ≥6 minutes and ≥5.5 hours were 1.40 (1.03, 1.89) per 10 cm2 increase (p=0.03) and 1.63 (1.11, 2.40) per 10 cm2 increase (p=0.01), respectively. LA LGE was significantly associated with high burden of AF. The addition of LA LGE to a multivariable risk prediction model for incident AF significantly increased the predictive value. Conclusions Extent of LA fibrosis measured by LA LGE was significantly associated with incident AF detected by implantable loop recorder. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): The Innovation Fund Denmark, The Research Foundation for the Capital Region of Denmark [no grant number]

Unravelling the black box of machine learning for atrial fibrillation forecast: role of heart rate variability and of premature beats

Abstract Background The identification of patients still in sinus rhythm who will present one month later an atrial fibrillation episode is possible using machine learning (ML) techniques. However, these new ML algorithms do not provide any relevant information about the underlying pathophysiology. Purpose To compare the predictive performance for forecasting AF between a machine learning algorithm and other parameters whose pathophysiological mechanisms are known to play a role in the triggering of arrhythmias (i.e. the count of premature beats (PB) and heart rate variability (HRV) parameters) Material and methods We conducted a retrospective study from an outpatient clinic. 10484 Holter ECG recordings were screened. 250 analysable AF onsets were labelled. We developed a deep neural network model composed of convolutional neural network layers and bidirectional gated recurrent units as recurrent neural network layers that was trained for the forecast of paroxysmal AF episodes, using RR intervals variations. This model works like a black box. For comparison purposes, we used a “random forest” (RF) model of ML to obtain forecast results using HRV parameters with and without PB. This model allows the evaluation of the relevance of HRV parameters and of PB used for the forecast. We calculated the area under the curve of the receiving operating characteristic curve for the different time windows counted in RR intervals before the AF onset. Results As shown in the table, the forecasting value of the deep neural network model (ML) was not superior to the random forest algorithm. Prediction value of both decreased when analyzing the RR intervals further away from the onset of AF Conclusions These results suggest that HRV plays a predominant role in triggering AF episodes and that premature beats could add minor information. Moreover, the closer the window from AF onset, the better the accuracy, regardless of the method used. Such detection algorithms once implemented in pacemakers, might prove useful to prevent AF onset by changing pacing sequence while patients would still be in sinus rhythm, however this remains to be demonstrated Funding Acknowledgement Type of funding source: None

Antiarrhythmic effect of ranolazine in combination with selective NCX-inhibition in an experimental model of atrial fibrillation

Abstract Background Previous studies showed an antiarrhythmic effect of ranolazine in different clinical and experimental studies. The aim of this study was to investigate the effects of a combination of ranolazine with different selective NCX-inhibitors in an established experimental model of atrial fibrillation. Methods and results 18 hearts of New Zealand white rabbits were retrogradely perfused. Left and right atrial catheters were used to record monophasic action potentials. Hearts were paced at three different cycle lengths (350ms, 250ms, 150ms). Thereby, cycle-length dependent atrial action potential durations (aAPD90), atrial effective refractory periods (aERP) and atrial post-repolarization refractoriness (aPRR=aERP-aAPD90) were obtained. Vulnerability to AF was tested by a standardized protocol employing several trains of burst pacing. After generating baseline data, the hearts were perfused with a combination of acetylcholine (ACh, 1μM) and isoproterenol (Iso, 1μM) to increase occurrence of AF. Afterwards, the hearts were assigned to two groups and additionally perfused with a combination of 10 μM ranolazine and 1 μM of the selective NCX-inhibitor ORM-10103 (group 1: Rano-ORM) or 10 μM ranolazine and 1 μM of another NCX-inhibitor, SEA0400 (group 2: Rano-SEA). Infusion of ACh/Iso led to a shortening of aAPD90 (group 1/2: −27.2ms/−24.5ms p<0.05), aERP (−29.2ms/−35.6ms p<0.05), aPRR (−12.2ms/−13.7ms p=ns) and the occurrence of AF-Episodes was significantly increased (group 1: baseline 6 episodes to 34 episodes under ACh/Iso p<0.05, group 2: baseline 7 episodes to 26 episodes under ACh/Iso p<0.05). Additional perfusion with ranolazine and ORM-10103 did not alter aAPD90 (−0,47ms) while effective refractory periods (+21.4ms, p<0.05) and aPRR (+43ms, p<0.05) were significantly prolonged and AF episodes were effectively reduced to 15 episodes (p<0.05). In group 2, Rano-SEA led to a slight decrease in aAPD90 (−9.5ms) while aERP (+13.3ms, p<0.05) and aPRR (+19.8ms, p<0.05) were prolonged. The occurrence of AF episodes was reduced to 15 episodes (p=0.1). Conclusion To our knowledge this is the first study investigating the effect of ranolazine combined with different selective NCX-inhibitors in an isolated whole-heart model of AF. Atrial repolarization was not significantly changed with either of the combinations. However, both combinations prolonged aERP and aPRR and thereby suppressed induction of AF. Combining novel cellular targets may therefore lead to new potentially interesting options for antiarrhythmic AF therapy that have to be tested in clinical studies. Funding Acknowledgement Type of funding source: None

New onset atrial fibrillation after percutaneous Patent Foramen Ovale closure: how serious is this problem?

Abstract Background Percutaneous Patent Foramen Ovale (pPFO) closure benefits for secondary prevention after cardio-embolic stroke have recently been proved. With the increasing number of cases and procedures, a concern with new onset atrial fibrillation (NOAF) has been raised. Purpose To evaluate long-term outcome regarding NOAF rate and to identify its predictors and clinical impact, in a real population submitted to pPFO closure. Methods From 2000 to 2017, consecutive patients (P) submitted to pPFO closure in a tertiary centre were prospectively enrolled. The primary endpoint was NOAF rate and secondary endpoints were all-cause, neurologic and cardiac mortality rates and recurrent ischemic events. Previous and follow-up electrocardiographic, echocardiographic and 24-hour heart rhythm monitoring data were analysed. Follow-up was performed through medical visits, medical charts consultation and a phone call based system, in order to assess clinical status, on-going treatment and events. Results 496 patients were submitted to pPFO. Immediate success was achieved in 98.8% and 9.1% presented a residual shunt on the 1st year TEE. Mean age was 45.0±11.2 years-old with 50.2% of males. The prevalence of hypertension, hypercholesterolemia and atrial septum aneurysm (ASA) was 25.7%, 45.0% and 46.3%, respectively. Pre-procedural mean left atrial (LA) diameter was 36.0±5.3 mm. FU data was available for 490 (98.6%), for a mean FU time of 7.41±3.51 years. 34 P (6.9%) presented ischemic events recurrence (26 strokes and 8 TIA). The primary endpoint was observed in 21 P (4.3%) during the FU period. Median time to 1st AF episode since PFO closure was 5.90±5.53 years. 11 P (52.3%) initiated oral anticoagulation. In univariate analysis, age (44.6±11.3 vs 51.8±6.0 years, p=0.005) and hypertension (24.7% vs 47.6%, p=0.019) were predictors of NOAF in this population. In multivariated analysis, only age remained a predictor of NOAF (OR 1.05 (1.007–1.101), p=0.025). LA pre pPFO closure dimensions, ASA, device type or size and the presence of residual shunt in TEE were not determinants of AF occurrence. The incidence of NOAF was associated with the need for hospitalization due to cardiac causes (19% vs 3.2%, p=0.001) and a trend towards higher rate of recurrent stroke (4.9% vs 14.3%, p=0.06). Conclusion Despite being a highly successful and safe procedure in most patients, pPFO closure was associated with a non-negligenciable rate of NOAF during long-term follow-up. NOAF predictors were related with classical cardiovascular risk factors, such as age and hypertension. None of the procedure or device features were associated with NOAF. Yet, a clinical impact was attributed to NOAF, with more hospitalizations and a trend towards ischemic events recurrence. As young patients submitted to pPFO closure grow older, prevention strategies to diagnose and treat NOAF should be endeavoured. Funding Acknowledgement Type of funding source: None