Implantable Loop Recorder Research Articles

Premature ventricular contraction burden measured by an insertable cardiac monitor and the incidence of ventricular tachycardia and fibrillation

Abstract Background Insertable cardiac monitors (ICM) have the capability to continuously monitor premature ventricular contraction (PVC) burden over time [1] as well as detect ventricular tachycardia and fibrillation (VT/VF). Objective We investigated the association of PVC burden with incidence of VT/VF in a large real-world cohort of patients implanted with ICMs. Methods Patients implanted with an ICM for various reasons for monitoring and PVC detection turned on were included from the ICM manufacturer's de-identified data warehouse. Patients were included if they had at least 90 days of PVC burden follow-up. Tachycardia episodes that were detected by the ICM were first classified as VT/VF, SVT, or oversensing using an artificial intelligence (AI) model that was pre-trained using over 60,000 manually adjudicated ICM detected tachycardia episodes. If the AI model output probability for VT/VF was greater than 0.2, then those episodes were manually adjudicated for incidence of non-induced spontaneous VT/VF. The PVC burden trends recorded by the device were divided into 4 mutually exclusive patient groups: (1) 0% PVC burden on all days, (2) 1-4% PVC burden on ≥1 day, (3) 5-9% PVC burden on ≥1 day, and (4) >10% PVC on ≥1 day. The incidence rate of spontaneous VT/VF was compared between the PVC burden patient groups using a Generalized Estimating Equations model with negative binomial distribution. Time to first spontaneous VT/VF occurrence after the first day of occurrence of PVC burden for the respective PVC burden groups were estimated using Kaplan-Meier analysis and the groups were compared using the Cox proportional hazards model. Results A total of 5,521 patients were included in the analysis. Patients had an average age of 69±15 years and 49.8% being males. There was a total of 33,393 tachycardia episodes from 2,641 patients that were detected by the ICM. After AI model probability-based adjudications, 691 spontaneous VT/VF episodes were identified from 277 patients. Patients with ≥1 day of PVC burden of 1-4%, 5-9%, and ≥10% were associated with 2.9, 7.3, and 7.8 times increased incidence rate of VT/VF episodes during follow-up period relative to patients with 0% PVC burden on all days of follow-up (Figure A). Kaplan Meier curves for incidence of first spontaneous VT/VF episode for the four groups following occurrence of the first day of qualifying PVC burden for the respective groups are shown in figure B. Patients with a day of PVC burden ≥10% were 3.5 times more likely to develop VT/VF in the future compared to patients with 0% PVC burden on all days. Conclusion Days with high PVC burden, as detected by an ICM with continuous PVC detection capability, were associated with increased risk of VT/VF events in a group of real-world patients implanted with ICMs. PVC burden measured by ICMs may be a risk stratification tool for further investigation to prevent sudden cardiac arrest.

Rates of therapeutic interventions in a large real-world cohort with insertable cardiac monitors

Abstract Background Insertable cardiac monitors (ICMs) provide up to several years of continuous monitoring and have demonstrated high diagnostic yields for arrhythmia detection. However, the rates of arrhythmia-related therapeutic interventions following ICM implant have not been comprehensively characterized across indicated patient populations. Purpose To quantify rates of arrhythmia therapies in a large, real-world U.S. cohort of ICM patients. Methods De-identified patients receiving a Reveal LINQ ICM between Oct 1, 2016 – Sept 30, 2020 with no prior cardiac implantable electronic devices (CIEDs) and ≥1 year of follow-up in the Optum Clinformatics® Data Mart claims database were identified (N=17,037). Patients were stratified by indication for ICM placement: N=431 (2.5%) of patients were indicated for AF ablation monitoring, 2,193 (12.9%) for AF management, N=4,852 (28.5%) Cryptogenic stroke, N=1,252 (7.3%) Palpitations, 1,346 (7.9%) Suspected AF, 6,716 (39.4%) Unexplained syncope, and 247 (1.4%) Ventricular tachycardia (VT). Each patient was followed in the claims database after ICM insertion until end of continuous claims enrollment, end of database, or death. Therapeutic interventions for arrhythmias were characterized during follow-up, including procedures (CIED implants, cardioversion, and ablation) and arrhythmia medication initiation (antiarrhythmics, rate-control medications, and oral anticoagulants). Results Mean(SD) follow-up in the claims database post ICM placement was 3.4(1.3) years; 52.4% of patients were female, and mean age was 70.8(11.9) years. Overall, 54.5% of patients received a therapeutic intervention during follow-up, with 25.0% of patients receiving a therapeutic procedure and 44.0% initiating an arrhythmia-related medication (table). The highest procedure rates included implantable pulse generator (IPG) implants in the Unexplained syncope population (21.4% of patients) and cardiac ablations in the populations receiving ICM for known AF (27.8% of AF ablation monitoring patients and 23.5% of AF management patients). Medication initiation rates were highest for oral anticoagulants in the Cryptogenic stroke population (31.0% of patients). The mean time from ICM insertion to therapeutic action was 13(13) months for procedures and 7(11) months for medication initiation. Conclusions In a large sample of real-world ICM patients, more than half received a therapeutic intervention after ICM placement. Time to intervention was lengthy and showed substantial variability amongst patients, underscoring the importance of long-term continuous monitoring to uncover clinically-relevant arrhythmia findings.

Dynamic QTc interval changes observed in real-world patients with implanted insertable cardiac monitors taking class III antiarrhythmic drugs

Abstract Background QT prolongation can lead to sustained ventricular arrhythmias . Class III Antiarrhythmic drugs (AAD) are known to cause QT prolongation. Insertable cardiac monitors (ICM) have the capability to continuously monitor and detect dynamic changes in QT. Purpose To investigate the characteristics of QTc interval changes before and after antiarrhythmic drug loading in real-world ICM patients administered with Sotalol, Amiodarone, and Dofetilide in hospital. Methods The QT detection algorithm detects the T-waves and determines the QTc intervals for every beat, thus providing continuous long-term QTc trends from ICM ECG. Real-world patients from de-identified Electronic Health Record (EHR) database linked with ICM device data warehouse with implanted ICM being administered sotalol, amiodarone or dofetilide AAD for the first time in the hospital were analyzed. The patients were broken down into groups based on the AAD taken. Patients not taking AAD were selected as control. QTc intervals 7-days pre and post administered AAD are reported, and a random 14-day period was used for control patients. The paired difference in median QTc 7 days pre and post administered AAD were analyzed using the Wilcoxon signed rank test. The Wilcoxon rank-sum test was used to analyze QTc between the different groups. Results A total of 487 patients with ICM were included in this analysis: 56 sotalol patients (avg. age: 67±10 years, 50% male), 100 amiodarone patients (avg. age: 72±10 years, 50% male), 52 dofetilide patients (avg. age: 66±12 years, 50% male), and 248 control patients (avg. age: 70±13 years, 50% male). Sotalol, amiodarone, and dofetilide patients showed significant increase in QTc 1-7 days post AAD compared to 1-7 days pre AAD (figure 1). For sotalol (post AAD median[IQR] = 426.5[408.8,446.6] msec, pre AAD median[IQR] = 415.9[391,437.3] msec, p=0.004); Dofetilide (post median[IQR] = 432.4[413,458.7] msec; pre median[IQR] = 409.3[397.5,435.2] msec, p<0.001); Amiodarone (post median[IQR] = 426.3[400.9,449] msec, pre median[IQR] = 415.5[397.5,435.2] msec, p = 0.037). The QTc 1-7 days pre AAD compared to 1-7 days post AAD for control patients was insignificant p>0.05. The median change in QTc 1-7 days post AAD from 1-7 days pre AAD was 13.0, 7.5, 21.25 and -1.0 msec for sotalol, amiodarone, dofetilide, and control patients respectively (figure 2). Dofetilide patients had a significantly higher change in QTc compared to the amiodarone patients, p=0.018. QTc for all three AAD groups when compared to control group post AAD were significantly higher, p<0.001. QTc was also higher pre AAD compared to control, p=0.003, p<0.001, p=0.009 for sotalol, amiodarone, and dofetilide respectively. Conclusions There is a significant increase in QTc detected by ICM in patients receiving index drug loading of Sotalol, amiodarone and dofetilide. QTc monitoring via ICM can detect these dynamic changes in QTc allowing for early intervention.Figure 1Figure 2

No reimbursement policy and implantable loop recorders in the real world setting

Abstract Background Prolonged heart rhythm evaluation is indicated in patients with suspected arrhythmias. Routine electrocardiographic Holter monitoring is often associated with poor adherence and may lead to little to no clinically relevant findings. Implantable loop recorders (ILRs) are small, subcutaneous cardiac devices providing semi-continuous electrocardiographic recording. Despite strong evidence supporting their effectiveness, ILRs are yet to be fully reimbursed by the National Health Fund- the public insurer in Poland. Purpose We aimed to investigate the feasibility, as well as the diagnostic yield of ILRs in a real world setting of a tertiary cardiovascular center. Methods We retrospectively analyzed data of consecutive patients admitted for ILR implantation between March 2013 nad November 2023. Hospitalization and procedural costs were covered by the clinic's statutory and hospital funds and not by the National Health Fund, the public payer. All patients were remotely monitored for device follow-up. Baseline demographic characteristics, as well as data regarding observation period, clinical outcomes and safety were collected. Results Data for 51 ILR implants in 50 patients was assessed. Insertion success rate was 100% on first attempt with no complications. Mean age was 54,43 ±18,56 years old. 52,94% of patients were female. Coronary artery disease was present in 21,57% patients, hypertension in 50,98%, diabetes in 13,73%. The indications for ILR implantation were unexplained syncope (n= 42; 82,35%), palpitations (n= 16; 31,37%), ischemic stroke of unknown origin (n= 6; 11,76%), monitoring of ventricular arrhythmia (n= 2; 3,92%). Mean time between occurrence of first symptoms and ILR implantation was 80,86 ±112,95 months. Mean monitoring period was 1067,62 ±668,89 days. 23 (45,1%) patients had an actionable event detected. Mean time to clinical outcome was 190,34 ±514,85 days. Based on the obtained recordings, in 13 (25,49%) patients a cardiac electronic device was implanted and 6 (11,76%) underwent an electrophysiological procedure. Time to intervention was 435,17 ± 542,9 days and 338,8 ± 273,44 days, respectively. ILR prompted medication modification in 14 (27,45%) patients. Antiarrhythmic drugs were modified in 6 (11,76%) patients. Oral anticoagulation was initiated in 3 (5,88%) patients. Mean time to any pharmacotherapy modification was 654,68 ± 604,32 days. Skin infections occurred in 2 patients, leading to early device removal. Conclusions This is the first study to present a comprehensive evaluation of ILR patients in Poland, along with a substantial observation period. We report a high prevalence of treatable cardiac conditions in patients with previous unsuccessful diagnostic work up. In the light of the upcoming favourable changes in governmental healthcare policy, demonstrating evidence supporting ILR application in everyday clinical practice is crucial for advocating their wider utilization and reimbursement.

Atrial fibrillation screening to prevent stroke in persons with low-normal thyrotropin

Abstract Background Screening for atrial fibrillation (AF) has been proposed as a method to prevent strokes in high-risk individuals. Recent trials were unable to prove efficacy for stroke prevention but suggested that a more refined approach may be beneficial. Low-normal thyroid-stimulating hormone (TSH) is a marker for AF and stroke risk and may be used to select individuals for AF screening. Purpose To explore TSH as a tool to select individuals for AF screening to prevent stroke. Methods Post hoc analysis of a clinical trial enrolling 6004 participants with stroke risk factors but no known AF randomized 1:3 to implantable loop recorder (ILR) screening for AF and initiation of oral anticoagulation (OAC) upon AF detection versus usual care (control group). The primary outcome was stroke or systemic embolism (SE). Secondary outcomes included the combination of stroke, SE, or cardiovascular (CV) death, all-cause death, AF diagnosis, and OAC initiation. All outcomes were adjudicated. Results Baseline TSH was measured in 6003 participants (99.98%); 1500 randomized to ILR vs 4503 to control. The mean age was 75±4 years, 2836 (47%) were women. The tertiles of TSH were at ≤1.2, 1.2-1.9, and >1.9 mIU/L. Participants in the first tertile had slightly higher levels of the thyroid hormones (T3, T4, and free T4), were slightly younger, had more smoking pack-years, and higher pulse rate compared to other tertiles. The median follow-up duration was 5.4 (4.9-5.8) years, and no participants were lost to follow-up. AF was diagnosed in 476 (31.7%) participants in the ILR group vs 550 (12.2%) in the control group and this difference was similar across tertiles (p-interaction=0.44). Similar patters were observed for OAC initiation. In the first TSH tertile, participants in the ILR group were significantly less likely to experience the primary outcome (hazard ratio 0.52 [0.30–0.90]; p=0.019) or the combination of stroke, SE, or CV death (hazard ratio 0.54 [0.35–0.84]; p=0.006, respectively) compared to control, while there was no effect in participants with higher TSH (p-interaction 0.029 and 0.014, respectively) and there was no effect on all-cause death in any tertile. When TSH was modelled as a continuous variable, the effect of ILR screening gradually increased with decreasing TSH, with the upper bound of the confidence interval reaching HR<1 at TSH<1.2-1.5 mIU/L. Sensitivity analyses excluding participants with baseline TSH outside reference range (0.3-4.0 mIU/L) and/or treated with thyroid hormone replacement or antithyroid agents yielded similar results. Conclusion In persons with stroke risk factors and TSH <1.2-1.5 mIU/L, ILR screening for AF and anticoagulation upon detection led to significantly decreased stroke risk. There was no effect in persons with higher TSH, though the yield of screening was similar across levels. This suggests that low-normal TSH may indicate benefit from AF screening while higher levels may lead to overdiagnosis.TableFigure

Assessing the impact of implantable loop recorder placement on anxiety level

Abstract Background Anxiety is a prolonged state of apprehension or worry that can be an independent predictor of cardiovascular events, associated with a 48% increased risk of cardiac death. About one-third of patients with arrhythmias present with high anxiety levels, and subsequently worse quality of life. In our experience of patient care, many patients feel anxious about the possibility of an arrhythmia that could lead to their demise, especially if their symptoms are undiagnosed. Purpose Our project aims to explore the change in patients’ anxiety levels following implantable loop recorder (ILR) placement. Methods This is a survey-based observational study that was performed in an outpatient clinic and hospital using validated General Anxiety Disorder-7 (GAD-7) questionnaires. Individuals who met indications to undergo ILR implantation including palpitations, syncope, subclinical atrial fibrillation, and cryptogenic stroke underwent baseline assessment of anxiety prior to implantation. Individuals had repeat assessments at 6 weeks and 12 weeks post-implantation to evaluate the effect of ILR placement. Results Our study included 50 individuals. Out of the initial subjects, 10/25 females and 11/25 males were lost to follow-up. The average initial GAD-7 score was 3.3 (Range 0, 15), average 6-week score was 1.6 (Range 0, 14), and average 12-week score was 0.9 (Range 0, 10). Total decrease in GAD-7 score after 6 weeks of having ILR was 50%. Total decrease in GAD-7 score after 12 weeks of ILR was statistically significant at 73% (P=0.03). Females showed greater improvement of GAD-7 scores in comparison to males at 6 weeks (67% vs 36%) and 12 weeks (81% vs 66%). Conclusion Studies have suggested an overall decreased level of anxiety in patients receiving implantable devices that have the potential to treat arrhythmias such as implantable cardiac defibrillators and pacemakers. Our results suggest that the benefit may extend to implantable devices that seek to provide further diagnostic information and aid in the prognostication of disease burden. As seen in our study population, GAD-7 scores showed dramatic improvement with greater percentage in female than male population. After the placement of loop recorders, many patients experience a sense of security with having a device that monitors them. Our study is the first to address the association between ILR and anxiety. Future studies evaluating this association would help increase the power of the study.Figure 1:Bar graph of GAD-7 Scores

Symptoms and atrial fibrillation burden measured by an insertable cardiac monitor in endurance athletes

Abstract Background Atrial fibrillation (AF) is the most common cardiac arrhythmia in athletes, but knowledge regarding AF burden, symptoms and quality of life (QoL) in endurance athletes with AF is limited. Purpose To study AF burden by continuous monitoring using insertable cardiac monitor (ICM), AF symptoms and QoL in endurance athletes with paroxysmal AF. Methods In endurance athletes diagnosed with paroxysmal AF who reported ≥2 episodes of AF, of which ≥1 during the past six months, we continuously monitored AF using ICM. Episodes recognized as AF by ICM were validated by a cardiologist. We defined AF burden as the cumulative duration of AF episodes lasting ≥30 secs divided by the total duration of monitoring. AF symptoms were assessed using the 21-item Atrial Fibrillation Effect on QualiTy-of-Life Questionnaire (AFEQT). AFEQT produces a summary score and three subscale scores (symptoms, daily activities, treatment concerns), ranging from 0 (complete AF-related disability) to 100 (no AF-related disability). We defined any score <80 as clinically relevant AF symptoms. We classified athletes according to the modified European Heart Rhythm Association (mEHRA) classification. Sport participation was obtained by questionnaires. Height and weight were measured and physical fitness was examined during cardiopulmonary exercise testing. Results A total of 38 athletes (3 female, 8%) were included. Table 1 shows their characteristics. Eight of the athletes (21%) had recurrent AF after previous AF ablation therapy. ICM recordings were available in 30 athletes who were monitored for an average of 53±21 days (mean±SD). Eighteen athletes (60%) had ≥1 AF episode, the median number of AF episodes was 2 (interquartile range 8.75), and the mean AF burden was 1.4±2.5%. The mean AFEQT summary score was 84±12 and 11 athletes (29%) had an AFEQT summary score <80. The mean AFEQT symptom subscale score was 78±18). While 21 athletes (55%) had a symptom subscale score <80, indicating clinically relevant symptomatic AF, 9 (24%) scored <60, indicating more severely symptomatic AF. Figure 1 shows ICM-detected AF burden across categories of mEHRA classes and categories of the AFEQT summary score. The AF burden corresponded to both AFEQT scores and mEHRA categories, with a higher AF burden associated with more symptomatic AF (Figure 1). AF burden was numerically lower in athletes with recurrent AF after previous AF ablation therapy, compared to athletes previously not treated with AF ablation (0.6% vs. 1.7%, p= 0.66), but previously ablated athletes were more symptomatic (AFEQT symptom subscale score 68 vs. 80, p= 0.04). Conclusions Despite a relatively low AF burden during continuous monitoring with ICM, a majority of the athletes had clinically relevant symptomatic AF. Athletes with recurrent AF after previous ablation therapy had a numerically lower AF burden, but were more symptomatic compared to athletes with paroxysmal AF not previously treated with AF ablation.

Implantable loop recorders in children and adolescents with Brugada syndrome: the YoungBruLoop study

Abstract Background Young (<18 years of age) patients with Brugada syndrome (BrS) are often underrepresented in BrS studies and their management, especially related to syncopal episodes, remains unclear. Purpose To describe the arrhythmia prevalence and clinical implication derived from continuous rhythm monitoring by implantable loop recorder (ILR) among patients younger than 18 years of age, and to assess the etiology behind syncope of undetermined origin. Methods A total of 147 BrS patients with ILR were enrolled in 12 international centers and divided into pediatric (age <12 years; n=77, 52%) and adolescents (age 13 to 18 years; n=70, 48%). Results Mean age was 11.3 years (36.1% females, 21.1% spontaneous type I ECG). Forty-six patients (31.2%) underwent ILR implant due to syncope. Over a median follow-up of 3.6 years, an arrhythmic event was recorded in 22.4% of patients and in the vast majority of cases it was of non-ventricular origin (44% atrial, 47% bradyarrhythmias). Predictors of arrhythmias at univariate Cox Regression analysis were spontaneous type I ECG (HR 2.1 - 95%C.I. 1.1-4.1), history of syncope (HR 3.1 - 95%CI 1.5-6.3) and age >12 years (HR 2.0 - 95%C.I. 1.0-3.3). Ventricular arrhythmias occurred in 4 patients, all with spontaneous BrS, and were related to fever in half of cases. In patients with recurrent syncope, the prevalence of truly arrhythmic syncope was 17.8%, and it was due to brady-, atrial- and ventricular arrhythmias in 40%, 20% and 40% of cases, respectively. Conclusions Continuous rhythm monitoring with ILRs in BrS pediatric patients detects a broad range of heart rhythm disturbances including life-threatening arrhythmias. Ventricular arrhythmias occur predominantly in patients with spontaneous type I ECG and in half of cases are fever-related. Despite the young age, brady- and atrial arrhythmias are overall frequent and represent the cause of arrhythmic syncope in 60% of patients. Young BrS patients with syncope of undetermined origin may benefit from ILR implant.

Selective use of implatable loop recorders improves diagnostic potential for unexplained syncope

Abstract Background Syncope remains a common medical problem with significant socio-economic consequences. Recently, the role of dedicated Syncope Units (SU) and implantable loop recorders (ILR) has emerged, in the investigation of unexplained syncope. Purpose To investigate the possibilities for a more rational and targeted use of various diagnostic tools. Methods In this retrospective study, 196 patients with Unexplained Syncope admitted in a single SU, between March 2019 and February 2023 were included. Various diagnostic tools were utilised during the investigational process, according to clinical judgement. Patients were retrospectively allocated into Group A including those who, among other tests, underwent ILR insertion and Group B including patients investigated without ILR implantation. Data were also compared with Group C, including patients assessed prior to SU establishment. Results There was no difference between Group A (n=133) and Group B (n=63) in the diagnostic yield (74% vs. 76%, p=0.22). There was significant difference between Group A and B regarding age (67.3 ± 16.9 years vs. 48.3 ± 19.1 years, p<0.001) and regarding cause of syncope (cardiogenic in 69% of group A and reflex syncope in 77% of group B, p<0.001). The diagnosis was based on electrocardiography (ECG) in 55% of group A and in 19% of group B (p<0.001). Time to diagnosis was 4.2 ± 2.7 months in patients with ILR implantation and 7.5 ± 5.6 months in Group B, p<0.001. In Group C, the diagnostic yield was 57.9% and the ECG-based diagnostic yield was 18.3%. Conclusions A selective use of ILR according to the clinical and electrocardiographic characteristics represents an acceptable diagnostic pathway that increases the effectiveness of the structured SU-approach by further preserving financial resources

Circadian rhythm in atrial fibrillation detected by implantable loop recorder: a post-hoc analysis of a randomized clinical trial

Abstract Introduction Previous studies suggest the existence of circadian, weekly, and seasonal rhythms in the occurrence of atrial fibrillation (AF), which may be utilized to improve the yield of screening. The heterogeneity of AF natural history also necessitates better phenotyping to overcome the challenges of identifying candidates for screening and treatment. Purpose To explore the potential circadian rhythm in AF occurrence in persons without known arrhythmia but at high risk of AF and stroke. Methods Post-hoc analysis of the LOOP study (Atrial Fibrillation Detected by Continuous Electrocardiogram Monitoring Using Implantable Loop Recorder to Prevent Stroke in High-Risk Individuals), which randomized 6004 AF naïve participants (≥70 years old with additional stroke risk factors) 1:3 to receive implantable loop recorder screening or usual care. All loop recorder data was extracted to obtain the date and time of AF episode onset, AF duration, mean and max heart rate (HR) during AF, and symptom annotations. New-onset AF episodes lasting ≥6 minutes were adjudicated, and all subsequent episodes were included in the analysis. Results A total of 41,713 AF episodes (median duration 18 (8-64) minutes) were identified among 430 participants (Table 1). The median number of episodes for each participant with AF was 21 (4-82) and the median AF burden was 0.17% (0.04%-0.83%) of time from debut to end of monitoring. The most and least frequent days of AF onset were Sunday (15.3%) and Friday (13.6%), respectively, while AF occurred slightly more often during spring (26%) than in other seasons. The median time of onset was 09:57:15 AM (05:15:30 AM – 03:33:00 PM). The most frequent time of onset was at 09:00 AM (rounded to the nearest hour), which was two times more likely than at 09:00 PM, and 22% of all episodes occurred between 08:00 and 11:00 AM (Figure 1). A total of 25,329 (61%) episodes occurred between midnight and noon (AM). Nocturnal episodes, defined as episodes with onset between 10:00 PM and 07:00 AM, occurred in 368 (86%) AF participants and constituted a median of 40% of all episodes and 37% (14%-63%) of each participant’s episodes. The median duration of nocturnal episodes was 28 (10-104) minutes compared to 14 (8-44) minutes for daytime episodes. The averaged heart rate during AF was 81 (71-96) beats per minute (BPM), while 330 (77%) participants had AF episodes with heart rates equal to or above 100 BPM, and the duration of these episodes was 50 (15-201) minutes compared to 30 (21-85) minutes for slower episodes (below 100 BPM). Conclusion A circadian pattern was observed for screening-detected AF. AF onset occurred predominantly between 08:00 and 11:00 AM, representing more than one in five episodes. Nocturnal AF occurred in most participants with AF and accounted for almost half of all episodes, while these episodes also lasted longer than daytime episodes. This may warrant future studies investigating the timing of AF screening.

Treated obstructive sleep apnoea and incident arrhythmias

Abstract Background Obstructive sleep apnoea (OSA) is prevalent in approximately 15% of western populations. Cardiovascular disease and arrhythmia are extremely common in this group with significant morbidity overlap. Whilst treatment of OSA with continuous positive airways pressure (CPAP) appears to reduce hypertension, bradycardia and recurrence of atrial fibrillation (AF), large randomised control trials and meta-analyses do not demonstrate a significant reduction of incident tachyarrhythmias such as atrial fibrillation or sudden cardiac death. Some smaller studies suggest that AF may have up to 20% incidence. Analysis of these studies suggest that there may be significant heterogeneity in both CPAP usage and OSA phenotype, confounding the results. Furthermore, standard arrhythmia detection often underestimates paroxysmal arrhythmias. This on-going trial investigates a treated OSA population using CPAP monitoring and implantable loop recorders (ILR). Purpose This study aims to identify the incidence of arrhythmia in a treated OSA population with comprehensive arrhythmia monitoring and CPAP usage. It also explores the mechanisms linking OSA and arrhythmia such as heart rate variability and turbulence and cardiac biomarkers in order to identify at risk sub populations. Methods Continuous moderate-to-severe OSA patients were recruited from a major UK sleep centre after ECG and medical history confirmed the absence of arrhythmia. Each patient was then randomised to receive either standard-care or standard-care with an ILR with 24-hour heart rate variability/turbulence measurements, echocardiography (where possible) and cardiac biomarkers at baseline and 12 months. All patients had remote CPAP usage monitoring (where possible). The trial ended at 36 months after enrolment. Results 200 patients were recruited to the trial. Current mean average follow-up is 28 months in this on-going trial. Mean age and apnoea hypopnea index at enrolment was 53 years and 43.8 respectively. To date we have diagnosed atrial fibrillation in 15% of the ILR group compared to 2% in the standard care group. Other arrhythmias detected in the ILR group include two with supraventricular tachycardia and 2 with significant pauses but not requiring further treatment. Final analysis of arrhythmia incidence with CPAP usage and heart rate variability/turbulence, and cardiac biomarkers is ongoing with final results due by the time of final submission. Conclusion Arrhythmias, particularly AF, are highly incident in OSA despite CPAP treatment. This study may determine if heterogenous CPAP usage confounds the above observation and whether there may be predictors of arrhythmia that may indicate a need for arrhythmia screening in the OSA population.

Rhythm classifier: artificial intelligence for rhythm classification in insertable cardiac monitor

Abstract Background Though detections improved significantly, separating atrial tachycardia/atrial flutter (AT/AFL) from atrial fibrillations (AF) in insertable cardiac monitors (ICM) remains a challenge. Objective Using artificial intelligence (AI) algorithms to classify AF and AT/AFL in ICM detected episodes, which may reduce episode review burden. Methods Both raw EGM signal and the QRS diminished version of the raw signal were used to extract 14 AF and AT/AFL features from each episode. Extracted features were then represented as an ensemble of features and used to train and test the AI model. Modified ResNet18 network was used as the AI model. All episodes from a random selection of 80% of patients were used as training dataset, another 10% were used as validation, and 10% were used as test dataset, to evaluate model performance. AI model probability threshold was chosen based on validation set results. Episode detection sensitivity, specificity, and area under the curve (AUC) of receiver operating characteristics (ROC) curve in the independent test dataset are reported. Results AF and AT/AFL episodes detected in 918 LINQ ICM patients (5,253 AF and 4,705 AT/AFL – 745 pts and 8,950 false detection episodes) were included. Training dataset consisted of 15,183 episodes (735 pts), validation set consisted of 1,901 episodes (91 pts), and test set consisted of 1,824 episodes (92 pts). At chosen threshold in validation set, AF and AT/AFL detection had sensitivity of 90% and 73.3%, respectively, and specificity of 93.2% and 95%, respectively, with AUC of 0.966. In test data, AF and AT/AFL obtained relative sensitivity of 84.7% and 85.7%, respectively, with specificity of 88% and 86.5%, respectively (Fig. A). With ROC-AUC of 0.956 (Fig. B), the relative diagnostic yield of AF and AT/AFL on test data was 95.6%. Conclusion The trained AI model provides a relative sensitivity of about 85% for AF vs. AT/AFL classification and reduces inappropriate ICM detections by 79%. Adding more episodes may improve the performance.

Quality of life after screening for atrial fibrillation: a substudy from a randomised screening trial

Abstract Background Screening for atrial fibrillation (AF) is rising, yet trials have failed to show efficacy for stroke prevention from screening and subsequent anticoagulation. Quality of life is an important outcome for patients and physicians, however, it is largely unknown how this outcome is affected by screening for AF. The adverse effects of screening should be considered before implementing systematic screening. Purpose To explore changes in quality of life associated with screening for AF and subsequent anticoagulant treatment upon AF detection. Methods We used quality of life data from 6,004 persons with stroke risk factors randomised to usual care (n=4,503) or screening for AF using implantable loop recorder and anticoagulation for AF episodes lasting ≥6 minutes (n=1,501). The validated EQ-5D-5L tool evaluates health-related quality of life in five domains (mobility, selfcare, usual activities, pain/discomfort and anxiety/depression), rendering a final score in EQ-index (worst=-0.76 best=1.00) combined with an EQ-VAS score (worst=0, best=100). EQ-index and EQ-VAS were analysed with linear mixed models from baseline through year three. The domains were also analysed with logistic regression to report the risk of major problems (defined as a rating of 3, 4, or 5 in the range [1-5], where 1 corresponds to no problem and 5 corresponds to an extreme problem within a given domain) overall and separately. Sensitivity analyses with imputation for missing data were performed. Results Data were available for 5,162 (86.0%) participants at baseline and in year three, and 227 (5.0%) in usual care and 65 (4.3%) in the screened group had died before the last assessment. At baseline, 1,202 of 5,162 (23.3%) participants reported major pain/discomfort problems, and 666 of 5,162 (12.9%) reported major mobility problems (Figure 1). Major selfcare problems were the least frequent problem reported by 83 of 5,162 participants (1.6%). The occurrence of major problems was increased after 3 years in all domains and in both randomisation groups, with a 2% higher occurrence of major pain/discomfort in the control group compared to the screened group. At baseline, the average EQ-index was 0.88 (±0.16) and EQ-VAS 78.4 (±16.2). After three years, the EQ-index decreased by -0.05 (-0.05; -0.04), p<0.0001 in the control group vs. -0.04 (-0.05; -0.02) in the screened group and EQ-VAS with -6.06 (-6.54; -5.57) in the control group vs. -5.18 (-6.52; -3.78) in the screened group, resulting in no statistically significant difference between the groups (p=0.063 and p=0.056) (Figure 2). The screened group was equally likely to report at least one major problem in quality of life after three years (odds ratio 0.93 (0.77;1.13)), but was less likely to report major pain/discomfort (odds ratio 0.84 (0.72;0.98)), compared with the control group. Conclusion Systematic and intensive screening for atrial fibrillation did not improve quality of life compared to usual practice.

The impact of cardiovascular risk factors on longitudinal changes in cardiac structure and function in an older population of hypertensive patients

Abstract Background Hypertension is associated with cardiac structural and functional changes, with left ventricular hypertrophy and diastolic dysfunction as strong predictors of adverse cardiac events. Limited data exist on how cardiovascular (CV) risk factors accelerate left ventricular (LV) mass and diastolic dysfunction over time in older hypertensive patients. Purpose To investigate the association between CV risk factors and accelerated deterioration of LV mass, left atrial volume (LAV), global longitudinal strain (GLS), and tissue Doppler E/e’ ratio in an older population of hypertensive patients. Methods Post-hoc analysis of a randomized clinical trial that investigated whether atrial fibrillation screening, using an implantable loop recorder, and subsequent initiation of anticoagulation, could prevent stroke in high-risk individuals. Only individuals with hypertension who had transthoracic echocardiography performed on two occasions, with a median of 5 years between echocardiograms, were included in this sub-study (n = 570). Multivariable linear regression analysis was performed to investigate the association between risk factors and changes in LV mass, LAV, GLS and E/e’. ß-values were calculated per 1 SD change for all variables. Results Mean age was 74±3 years, and 55% were men. Mean body mass index (BMI) was 27.8±4.3 kg/m2, 26% had diabetes, 58% used statins, 12% had a history of ischemic heart disease, and 4% had heart failure. The median use of antihypertensive drugs was 2 (IQR: 1,2), mean systolic blood pressure was 148.6±18.2 mmHg. During a median follow-up of 5 years, the mean increase in LV mass was 6.5±38.3g. Male sex (ß 0.24, p < 0.001) and increasing BMI (ß 0.29, p <0.001) were significantly associated with an accelerated increase in LV mass (Fig. 1). The mean increase in LAV was 14.6±15.7ml. Diabetes (ß -0.16, p = 0.006) and high sensitivity C-reactive protein (hsCRP) (ß 0.14, p = 0.007) were significantly associated with changes in LAV (Fig. 2). The absolute decline in mean GLS was 0.27%. Increasing age (ß -0.09, p = 0.027), heart failure (ß -0.10, p = 0.020), ischemic heart disease (ß -0.16, p < 0.001), hsCRP (ß -0.12, p = 0.003) and s-creatinine (ß -0.09, p = 0.033) were all significantly associated with an accelerated decline in GLS (Fig. 1). E/e’ declined with an average 0.96±2.89. Increasing age (ß 0.12, p = 0.001), female sex (ß 0.09, p = 0.049), and increasing systolic blood pressure (ß 0.13, p = 0.004) were associated with an increase in E/e’ (Fig. 2). Conclusion Male sex and increasing BMI were independently associated with an accelerated increase in LV mass. Diabetes was independently associated with LAV decline, while hsCRP was significantly associated with increasing LAV. Increasing age, heart failure, ischemic heart disease, hsCRP, and s-creatinine were independently associated with an accelerated decline in GLS. Increasing age, systolic blood pressure and female sex were independently associated with increasing E/e’.

Weight change does not impact long-term outcomes following cryoballoon pulmonary vein isolation

Abstract Background Weight loss has been suggested to reduce frequency and burden of atrial fibrillation (AF) in overweight patients (pts). However, there are limited data on weight loss impact on outcomes in pts with AF who have undergone pulmonary vein isolation (PVI). Purpose To understand the impact of weight change on long-term outcomes, as assessed by freedom from recurrent AF in pts undergoing cryoballoon (CB) PVI. Methods We enrolled consecutive pts with AF who underwent CB PVI; all had implantable loop recorders (ILR) for long-term ECG monitoring. The cohort was divided into 4 groups based on weight change 1-year post ablation: (1) optimal weight loss (OWL) – weight decrease ≥ 10%; (2) minimal weight loss (MWL) - weight loss (WL) 3-9% weight decrease; (3) no weight change (NWC) - weight change < 3%, (4) weight gain (WG) ≥ 3% weight increase. We assessed for AF recurrence after excluding a 3-month post-ablation blanking period. Results Out of a total of 322 pts who underwent ablation, 241 (75%) pts (69 ± 10 years; 159 (66%) male; 133 (55%) PAF; CHA2DS2-VASc 2.7 ± 1.5; BMI 30 ± 5) had weight information available at ablation and last follow-up. All were off antiarrhythmics by 1 year. There were no differences in the 4 cohorts with respect to baseline characteristics. During the first year, about ¼ of pts were able to lose ≥ 3% of weight but only 8 pts (3%) were able to lose ≥ 10%. AF recurred in 153 (63%); they were older, more likely to have persistent AF (PeAF), and a higher CHA2DS2-VASc score. However, weight change did not impact outcome (Figure). In a multivariate Cox Regression hazards analysis, PAF vs. PeAF at ablation was the only factor associated with any recurrence at follow-up (Figure). Conclusions Post CB PVI only about ¼ of pts are able to lose weight. Weight changes in the first-year post ablation in obese pts did not alter outcomes with respect to likelihood of recurrent AF. These data should be taken into account when considering catheter ablation.

Validation of diagnostic wearable ECG data from high-risk patients and integration into the atrial fibrillation catheter ablation pathway

Abstract Background Wearables like the Apple Watch (AW) offer non-invasive, long-term monitoring and patient-led, single-lead ECG recordings. Although validated for Atrial Fibrillation (AF) detection in the general population, the accuracy and clinical utility of the single-lead ECG recording feature for the diagnosis of AF has not been evaluated in patients at high risk of atrial arrhythmias.(1) An evaluation of the accuracy of the Wearable-derived labels is important to determine the feasibility of integrating AW-based remote monitoring into clinical pathways. Objective To evaluate the accuracy and data burden from AW-based, patient-led ECG monitoring in patients undergoing AF catheter ablation. Methods Patients referred for first-time AF catheter ablation to the Study Institution between January 2022 and March 2023 were invited to enrol in the AF Follow-up with Apple Watch (AFFU-AW) Trial. Patients randomised to the active arm of the study received 12 months of post-ablation follow-up using a loaned Apple Watch. Participants underwent an education session and were asked to perform daily ECGs; sending through any labelled as AF, inconclusive, or in the context of symptoms. The accuracy of the automated ECG labelling was determined against blinded, independent labelling by two experienced Electrophysiologists. Results 1093 remote transmissions were emailed in for evaluation from 52 patients to the Study team. This was a median of 6 [2, 17] per patient and a receiver burden of 2 [1, 4] ECGs per day. 475 were categorised by the AW as AF with a sensitivity of 0.71 and specificity of 0.96 compared to expert labelling. 342 (31%) were not categorised by the wearable, with an ‘inconclusive’ interpretation (161 [47%]) or ‘high heart rate’ (108 [32%]) as the most cited reasons. 178 (55%) of the uncategorised ECGs were subsequently overread as AF. Accompanying symptoms were reported with 324 (30%) ECGs, most commonly palpitations. Conclusion This is the first reported evaluation of the AF diagnostic feature based on AW ECG recordings as part of a remote patient rhythm surveillance pathway after catheter ablation. The high positive predictive value of ‘Sinus Rhythm’ and ‘AF’ labels and the high specificity of the ‘AF’ label are comparable to diagnostic algorithms in implantable loop recorders.(2) The source code to automate data curation and structured databasing of wearable ECGs has been made available for care providers to integrate the service into device monitoring workflows.(3)

Atrial fibrillation detection on implantable loop recorders in embolic stroke of undetermined source

Abstract Introduction Embolic stroke of undetermined source (ESUS) represents 17% of all ischaemic strokes, and has a 5% annual stroke recurrence risk. Recent large randomised control trials failed to demonstrate a benefit of empirical anticoagulation for all ESUS patients, with sub-analyses supporting the need for a tailored approach to those patients at greatest risk of atrial fibrillation (AF) development. Understanding how the increased incidence of ILR-detected AF in the ESUS cohort, compares with ILR-detected AF in other cohorts is an essential step in understanding the significance of this finding. Purpose To compare the incidence of ILR-detected AF following ESUS against patients undergoing ILR implantation for non-stroke indications for example syncope and palpitations. Methods We retrospectively studied all patients without known AF who were referred to our institution for ILR implantation following ESUS, syncope or palpitations from 2009 to 2019. The primary endpoint was any detection of AF or atrial flutter (AFL) by ILR. Kaplan-Meier and multivariable Cox-regression analyses were utilised to account for time-to-event. Results A total of 750 patients were included and followed up for a mean of 731 days (SD 443). An ILR was implanted following ESUS in 323 patients and for another reason in 427 patients (figure 1). The incidence of AF was significantly higher among patients with ESUS compared to the non-ESUS group; 48.6% versus 13.8% (for any duration of AF) and 32.2% versus 12.4% (for AF lasting > 30 seconds) both p <0.001. Kaplan-Meier analysis (figure 2), showed significantly higher incidence of AF for ESUS for any duration of AF. This was driven predominantly by AF duration <6 minutes and between 5.5 hours and 24 hours. Importantly, in a multivariable Cox regression analysis, ESUS independently conferred an almost 5-fold increase in the hazard for any duration of AF (Hazard Ratio 4.948, 95% confidence interval 3.587 – 6.825, p<0.001). Conclusion The incidence of AF is significantly higher amongst ESUS versus non-ESUS patients monitored constantly by an ILR. A high number of ESUS survivors have short duration AF episodes. Further work is needed to determine the optimal treatment strategy of these AF episodes in ESUS considering AF duration and overall burden.

Clinical implications of atrial fibrillation recurrence vs. burden following catheter ablation: outcome data from 3 contemporary clinical trials using an insertable cardiac monitor

Abstract Background Recurrence of atrial fibrillation (AF) following catheter ablation is typically defined in clinical trials in a binary fashion, e.g. > 30 seconds or none. However, the clinical implications of this endpoint, adopted from formal guidelines, have been questioned. Purpose We hypothesized that assessment of AF burden can provide incremental clinical and management implications to the dichotomous definition of AF recurrence following ablation. Methods The study population comprised 147 patients enrolled in 3 ongoing multicenter randomized clinical trials (ICM REDUCE-AF [N=67]); HYBRID-AF (N=55] and DAPA-AF [N=25]), each employing an insertable cardiac monitor (ICM) to assess post-ablation AF recurrence and burden. The rate of cardiovascular (CV)-related healthcare utilization (CV-HCU, defined as the total number CV admissions, ED visits, cardioversions, procedures, and unplanned office visits) was compared based on AF recurrence (defined as >2 minutes of ICM-detected AF) vs. based on AF burden post-ablation (defined as time in AF divided by total monitoring time). Results Among the 147 study patients, mean age was 65 years; 53 (36%) were women; and 78 (53%) had persistent AF. At 12-months post-ablation (excluding blanking), the cumulative probability of AF recurrence was 60% (Figure 1A). However, 27% of AF recurrences were associated with a very low AF burden (≤0.1%) and low CV-HCU (10 events per 100 patient-months), similar to patients without AF recurrence (11 events per 100 patient-months). In contrast, recurrences with a higher AF burden (>0.1%; mean 17% ± 25%) were associated with a 3-fold higher rate of CV-HCU (31 events per 100 patient-months, p<0.001; Figure 1B). Findings were consistent regardless of AF-type, comorbidities or LVEF. Conclusions A substantial proportion of AF recurrences following contemporary AF ablation are associated with a very low AF burden without apparent effect on CV outcomes, whereas higher AF burden is associated with increased CV-HCU. These findings stress the need to move beyond a dichotomous definition of AF recurrence and to monitor AF burden post-ablation to guide management decisions in contemporary clinical practice.Figure 1

Incidence of atrial fibrillation detected by an insertable cardiac monitor in a large real-world cohort of heart failure patients with reduced and preserved ejection fraction

Abstract Background Subcutaneous implantable cardiac monitors (ICM) have the capability to detect atrial fibrillation (AF) episodes with high degree of accuracy [1]. Objective We investigated the incidence of AF in patients implanted with an ICM and a clinical history of heart failure (HF) with reduced or preserved left ventricular ejection fraction (LVEF). Methods Patients with history of HF admissions who were implanted with an ICM were identified from the aggregated and de-identified electronic health record (EHR) database during 2007-2021. The device collected data were merged with the EHR data to create a de-identified database of real-world patients. Patients were included if they had ≥180 days of device follow-up. ICMs detect AF based on incoherence of RR intervals and absence of single p-wave between two R-waves [1]. All ICM detected AF episodes stored with at least 30 seconds of ECG at onset were adjudicated using an artificial intelligence (AI) model. The AI model was previously trained and validated using over 60K manually adjudicated episodes and was shown to have an accuracy of over 97% [2]. ICM detected AF episodes with AI model based true probability of AF ≥ 0.9 was analyzed. The Kaplan-Meier incidence curves for AF incidence as a function of episode duration, clinical history of AF, and LVEF are reported. Results A total of 1020 LINQ ICM patients with history of HF admission prior to implant were identified from the deidentified real-world dataset. LVEF was available in 889 (87%) patients, of whom 394 (44%) had EF <50%, and 495 (56%) had EF≥50%. NYHA class was available in 296 (29%) patients, of whom 39 (13%) were class I, 126 (43%) were class II, 112 (38%) were class III, and 19 (6%) were class IV. Patients had an average age of 68±13 years with 52% being males and had clinical history of hypertension in 95%, diabetes in 56%, coronary artery disease in 75%, AF in 57%, stroke/TIA in 51%, and renal dysfunction in 53%. A total of 911 patients with ≥180 days of follow-up (average follow-up of 25.8 months) were included. A total of 8407 episodes from 358 patients were classified by the AI model as true AF. The incidence of AF as a function of episode duration, clinical history of AF and reduced vs preserved LVEF are shown in Figures A, B, and C respectively. Incidence of AF, as detected by an ICM over 42 months of follow-up, was estimated to be 38% to 46% depending on AF episode duration. Estimated 42-month AF incidence was 23% in patients with no clinical history of AF. The 42-month AF incidence was 44% vs 47% in HF patients with reduced versus preserved LVEF. Conclusion Incidence of AF, as detected by an ICM over 3 years of follow-up, was estimated to be in close to half of ICM patients with history of HF events. Close to one fourth of the patients with no prior clinical history of AF had newly detected AF. AF incidence was similar in HF patients with preserved versus reduced LVEF in this real-world cohort.

Insights from an international clinic survey on CIED patient management practices and perceptions

Abstract Background Remote monitoring (RM) is recommended as standard of care to manage patients with cardiac implantable electronic devices (CIEDs). However, implementation within overall follow-up (FU) practice is challenging with many organizational aspects to consider. While the 2023 HRS/EHRA/APHRS/LAHRS consensus on management of remote device clinics provided guidance, data on current patient management practice is lacking to understand existing gaps. Purpose This survey of device clinic staff characterized the state and perceptions of CIED patient management. Methods A Delphi panel of US and EU clinical experts guided the research objectives, structure, and content of the survey. Once consensus was reached, the online survey (Qualtrics) was deployed in partnership with HRS. An available case analysis was performed to handle missing data. Results A total of 471 responses were received between September 2023-January 2024 (66% US, 19% Europe, 15% other). Overall, performing a combination of in-office visits and RM was the most frequent FU practice for all devices. Remote-only management was only commonly reported for insertable cardiac monitors (ICM). Adoption of RM was lower in EU compared to US for therapeutic devices, especially pacemakers for which in-person only FU remained high (Figure 1). Frequency of routine visits and transmissions is reported in Figure 2. While the majority of respondents (48-67%, depending on device type) expressed that less than 20% routine visits are actionable, adopting a practice of FU visits scheduled every 2 years as suggested in the 2023 consensus was rarely reported for therapeutic devices. However, alert-based RM seems to emerge for ICM without routine FU. In the US, frequency of scheduled transmissions appeared aligned with reimbursement rules (monthly for ICMs; quarterly for therapeutic devices), whereas there was more variability in EU where RM often lacks clear funding. Divided opinion was observed regarding staff sufficiency as 43% found staffing levels somewhat/very sufficient, while 42% rated it as somewhat/very insufficient. Managing disconnected patients, initial transmission review, and patient phone calls were identified as most burdensome tasks and were the ones for which there was most willingness to outsource. Although 60% respondents rated their practice as somewhat/very efficient, the majority (45%) did not report monitoring performance. The minority (29%) assessing patient management performance primarily tracked workload volume rather than quality-related metrics. Conclusion This large international survey characterized contemporary CIED patient management practices. While the 2023 HRS/EHRA/APHRS/LAHRS consensus highlighted the potential for alert-based RM, reducing in-person visits, and third-party resources to streamline patient FU, these practices have yet to be fully implemented. As such, there is opportunity to standardize and optimize workflows to drive efficiency and quality of care.Follow-up paradigm by regionFrequency of routine follow-up