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Aims Subclinical atrial fibrillation (AF) is associated with increased risk of progression to clinical AF, stroke, and cardiovascular death. We hypothesized that in pacemaker patients requiring dual-chamber rate-adaptive (DDDR) pacing, closed loop stimulation (CLS) integrated into the circulatory control system through intra-cardiac impedance monitoring would reduce the occurrence of atrial high-rate episodes (AHREs) compared with conventional DDDR pacing. Methods and results Patients with sinus node dysfunctions (SNDs) and an implanted pacemaker or defibrillator were randomly allocated to dual-chamber CLS (n = 612) or accelerometer-based DDDR pacing (n = 598) and followed for 3 years. The primary endpoint was time to the composite endpoint of the first AHRE lasting ≥6 min, stroke, or transient ischaemic attack (TIA). All AHREs were independently adjudicated using intra-cardiac electrograms. The incidence of the primary endpoint was lower in the CLS arm (50.6%) than in the DDDR arm (55.7%), primarily due to the reduction in AHREs lasting between 6 h and 7 days. Unadjusted site-stratified hazard ratio (HR) for CLS vs. DDDR was 0.84 [95% confidence interval (CI), 0.72–0.99; P = 0.035]. After adjusting for CHA2DS2-VASc score, the HR remained 0.84 (95% CI, 0.71–0.99; P = 0.033). In subgroup analyses of AHRE incidence, the incremental benefit of CLS was greatest in patients without atrioventricular block (HR, 0.77; P = 0.008) and in patients without AF history (HR, 0.73; P = 0.009). The contribution of stroke/TIA to the primary endpoint (1.3%) was low and not statistically different between study arms. Conclusion Dual-chamber CLS in patients with SND is associated with a significantly lower AHRE incidence than conventional DDDR pacing. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) has been associated with higher morbidity and mortality rates, especially in older patients. Subclinical atrial fibrillation (SCAF) is defined as the presence of atrial high-rate episodes (AHREs) > 190 bpm for 10 consecutive beats > 6 min and <24 h, as detected by cardiac implanted electronic devices (CIEDs). The selection of eligible patients for anticoagulation therapy among elderly individuals with AHREs detected through CIEDs remains a contentious issue. The meta-analysis of ARTESiA and NOAH-AFNET 6 clinical trials revealed that taking Edoxaban or Apixaban as oral anticoagulation therapy can reduce the risk of stroke by approximately 32% while increasing the risk of major bleeding by approximately 62%. However, it is still unclear which are, among patients with SCAF, those who can take the highest net clinical benefit from anticoagulant therapy. The present review summarizes the current evidence on this intriguing issue and suggests strategies to try to better stratify the risk of stroke and systemic embolism in patients with AHREs. We propose incorporating some parameters including chronic kidney disease (CKD), obesity, enlarged left atrial volume, the efficacy in blood pressure management, and frailty into the traditional CHA2DS2-VASc score. Future trials will be needed to verify the clinical usefulness of the proposed prognostic score mainly in the view of a personalized therapeutic approach in patients with SCAF. [ABSTRACT FROM AUTHOR]

The article discusses the findings of a study on the effects of oral anticoagulation in patients with device-detected atrial fibrillation (DDAF) without ECG-documented atrial fibrillation (AF). The study analyzed data from 2534 patients and compared outcomes and the effect of anticoagulation in patients with different risk factors. The results showed that anticoagulation did not appear to be more effective in patients with a high risk score, and the rate of stroke was low in patients without anticoagulation. The study suggests the need for new methods to identify high-risk patients who may benefit from anticoagulation. The article also provides information about financial disclosures and funding sources related to the authors of the study. [Extracted from the article]

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Background and Aims Patients with long atrial high-rate episodes (AHREs) ≥24 h and stroke risk factors are often treated with anticoagulation for stroke prevention. Anticoagulation has never been compared with no anticoagulation in these patients. Methods This secondary pre-specified analysis of the Non-vitamin K antagonist Oral anticoagulants in patients with Atrial High-rate episodes (NOAH-AFNET 6) trial examined interactions between AHRE duration at baseline and anticoagulation with edoxaban compared with placebo in patients with AHRE and stroke risk factors. The primary efficacy outcome was a composite of stroke, systemic embolism, or cardiovascular death. The safety outcome was a composite of major bleeding and death. Key secondary outcomes were components of these outcomes and electrocardiogram (ECG)-diagnosed atrial fibrillation. Results Median follow-up of 2389 patients with core lab-verified AHRE was 1.8 years. AHRE ≥24 h were present at baseline in 259/2389 patients (11%, 78 ± 7 years old, 28% women, CHA2DS2-VASc 4). Clinical characteristics were not different from patients with shorter AHRE. The primary outcome occurred in 9/132 patients with AHRE ≥24 h (4.3%/patient-year, 2 strokes) treated with anticoagulation and in 14/127 patients treated with placebo (6.9%/patient-year, 2 strokes). Atrial high-rate episode duration did not interact with the efficacy (P -interaction =.65) or safety (P -interaction =.98) of anticoagulation. Analyses including AHRE as a continuous parameter confirmed this. Patients with AHRE ≥24 h developed more ECG-diagnosed atrial fibrillation (17.0%/patient-year) than patients with shorter AHRE (8.2%/patient-year; P <.001). Conclusions This hypothesis-generating analysis does not find an interaction between AHRE duration and anticoagulation therapy in patients with device-detected AHRE and stroke risk factors. Further research is needed to identify patients with long AHRE at high stroke risk. [ABSTRACT FROM AUTHOR]

BackgroundThe electromechanical dyssynchrony associated with right ventricular pacing (RVP) has been found to have adverse impact on clinical outcomes. Several studies have shown that left bundle branch area pacing (LBBAP) has superior pacing parameters compared with RVP. We aimed to assess the difference in ventricular electromechanical synchrony and investigate the risk of atrial high-rate episodes (AHREs) in patients with LBBAP and RVP.MethodsWe consecutively identified 40 patients with atrioventricular block and no prior atrial fibrillation. They were divided according to the ventricular pacing sites: the LBBAP group and the RVP group (including the right ventricular apical pacing (RVA) group and the right side ventricular septal pacing (RVS) group). Evaluation of ventricular electromechanical synchrony was implemented using electrocardiogram and two-dimensional speckle tracking echocardiography (2D-STE). AHRE was defined as event with an atrial frequency of ≥176 bpm lasting for ≥6 min recorded by pacemakers during follow-up.ResultsThe paced QRS duration of the LBBAP group was significantly shorter than that of the other two groups: LBBAP 113.56 ± 9.66 ms vs. RVA 164.73 ± 14.49 ms, p

Abstract Background It has become important to identify and manage risk factors for subclinical atrial fibrillation (AF) with an increase in its detection rate. Thus, this research aimed to investigate whether alcohol consumption contributes to the development of subclinical AF. Methods This prospective study enrolled 467 patients without AF from a multicenter pacemaker registry. The incidence of subclinical AF (episodes of atrial rate > 220 beats per minute without symptoms) was compared between alcohol-drinking and non-drinking groups. Results During followup (median 18 months), the incidence and risk of long-duration atrial high-rate episodes (AHRE) ≥ 24 h were increased in the alcohol group compared to the non-alcohol group [5.47 vs. 2.10 per 100 person-years, adjusted hazard ratio (HR), 2.83; 95% confidence interval (CI), 1.14–7.04; P = 0.03]. After propensity score matching, the incidence and risk of long-duration AHRE were higher in the alcohol group (6.97 vs. 1.27 per 100 person-years, adjusted HR, 7.84; 95% CI, 1.21–50.93; P = 0.03). The mean burden of long-duration subclinical AF was higher in the alcohol group than in the non-alcohol group (0.18 vs. 1.61% during follow-up, P = 0.08). Conclusion Alcohol consumption was associated with an increased risk of subclinical AF. Long-duration AHRE incidence and AHRE burden were higher in alcohol drinkers than in non-drinkers.

Atrial fibrillation (AF) has been associated with higher morbidity and mortality rates, especially in older patients. Subclinical atrial fibrillation (SCAF) is defined as the presence of atrial high-rate episodes (AHREs) > 190 bpm for 10 consecutive beats > 6 min and 2DS2-VASc score. Future trials will be needed to verify the clinical usefulness of the proposed prognostic score mainly in the view of a personalized therapeutic approach in patients with SCAF.

Background: It has become important to identify and manage risk factors for subclinical atrial fibrillation (AF) with an increase in its detection rate. Thus, this research aimed to investigate whether alcohol consumption contributes to the development of subclinical AF. Methods: This prospective study enrolled 467 patients without AF from a multicenter pacemaker registry. The incidence of subclinical AF (episodes of atrial rate > 220 beats per minute without symptoms) was compared between alcohol-drinking and non-drinking groups. Results: During followup (median 18 months), the incidence and risk of long-duration atrial high-rate episodes (AHRE) ≥ 24 h were increased in the alcohol group compared to the non-alcohol group [5.47 vs. 2.10 per 100 person-years, adjusted hazard ratio (HR), 2.83; 95% confidence interval (CI), 1.14–7.04; P = 0.03]. After propensity score matching, the incidence and risk of long-duration AHRE were higher in the alcohol group (6.97 vs. 1.27 per 100 person-years, adjusted HR, 7.84; 95% CI, 1.21–50.93; P = 0.03). The mean burden of long-duration subclinical AF was higher in the alcohol group than in the non-alcohol group (0.18 vs. 1.61% during follow-up, P = 0.08). Conclusion: Alcohol consumption was associated with an increased risk of subclinical AF. Long-duration AHRE incidence and AHRE burden were higher in alcohol drinkers than in non-drinkers. [ABSTRACT FROM AUTHOR]

Objectives: Atrial high‐rate episodes (AHRE) are asymptomatic atrial tachy‐arrhythmias detected through continuous monitoring with a cardiac implantable electronic device (CIED). AHRE's have been associated with increased risks of developing clinically manifested atrial fibrillation (AF), thromboembolism, cardiovascular events, and mortality. Several variables has been researched and identified to predict AHRE development. The aim of this study, which compared the six frequently‐used scoring systems for thromboembolic risk in AF (CHA2DS2‐VASc, mC2HEST, HAT2CH2, R2‐CHADS2, R2‐CHA2DS2‐VASc, and ATRIA) in terms of their prognostic power in predicting AHRE. Materials and methods: This retrospective study included 174 patients with CIED's. The study population was divided into two groups according to presence of AHRE: patients with AHRE (+) and patients without AHRE (‐). Thereafter, patients baseline characteristics and scoring systems were analyzed for prediction of AHRE. Results: The distribution of patients' baseline characteristics and scoring systems according to presence of AHRE was evaluated. Furthermore, ROC curve analyses of the stroke risk scoring systems have been investigated in terms of predicting the development of AHREs. ATRIA, which predicted AHRE with a specificity of 92% and sensitivity of 37.5% for ATRIA values of >6, performed better than other scoring systems in predicting AHRE (AUC: 0.700, 0.626‐0.767 95% confidence interval (CI), p =.004) Conclusion: AHRE is common in patients with a CIED. In this context, several risk scoring systems have been used to predict the development of AHRE in patients with a CIED. This study's findings revealed that The ATRIA stroke risk scoring system performed better than other commonly used risk scoring systems in predicting AHRE. [ABSTRACT FROM AUTHOR]

Atrial high-rate episodes (AHRE) are atrial tachyarrhythmias detected by continuous rhythm monitoring by pacemakers, defibrillators, or implantable cardiac monitors. Atrial high-rate episodes occur in 10–30% of elderly patients without atrial fibrillation. However, it remains unclear whether the presence of these arrhythmias has therapeutic consequences. The presence of AHRE increases the risk of stroke compared with patients without AHRE. Oral anticoagulation would have the potential to reduce the risk of stroke in patients with AHRE but is also associated with a rate of major bleeding of ∼2%/year. The stroke rate in patients with AHRE appears to be lower than the stroke rate in patients with atrial fibrillation. Wearables like smart-watches will increase the absolute number of patients in whom atrial arrhythmias are detected. It remains unclear whether anticoagulation is effective and, equally important, safe in patients with AHRE. Two randomized clinical trials, NOAH-AFNET6 and ARTESiA, are expected to report soon. They will provide much-needed information on the efficacy and safety of oral anticoagulation in patients with AHRE. [ABSTRACT FROM AUTHOR]

Atrial high-rate episodes (AHREs) are atrial tachyarrhythmias that are exclusively detected by cardiac implantable electronic devices (CIEDs) with an atrial lead. The objective of this study was to investigate the incidence and predictive factors for AHREs, and to evaluate the ability of inflammation biomarkers to predict the occurrence of AHREs. 102 patients undergoing CIED procedure who received a dual chamber pacemaker were included. CIED interrogation was performed 1 year after the implantation procedure. Patients were divided into groups according to the occurrence of AHREs, which was the primary endpoint of the study. The mean age of the patients was of 73 ± 8.6 years and 48% were male. The incidence of AHREs was 67% at 1 year follow-up. Patients with AHREs were older, had higher left atrial indexed volume (LAVi), higher baseline galectin-3 levels (1007.5 ± 447.3 vs. 790 ± 411.7 pg/mL) and received betablockers more often, along with amiodarone and anticoagulants. Interestingly, the CHADSVASC score did not differ significantly between the two groups. A cut-off value of galectin > 990 pg/mL predicted AHREs with moderate accuracy (AUC of 0.63, 95% CI 0.52 to 0.73, p = 0.04), and this association was confirmed in the univariate regression analysis (OR 1.0012, 95% CI 1.0001 to 1.0023, p = 0.0328). However, based on the multivariate regression analysis, galectin lost its prognostic significance under the effect of LAVi, which remained the only independent predictor of AHREs (OR 1.0883, 95% CI 1.0351 to 1.1441, p = 0.0009). AHREs are common in CIEDs patients. Galectin-3 may bring additional data in the prediction of AHREs. [ABSTRACT FROM AUTHOR]

The underlying mechanisms of atrial remodeling in cardiac implanted electronic device(CIED)-detected atrial high-rate episodes(AHRE) remains to be elucidated. A cardiac computed tomography and a strain echocardiography were performed to delineate the structural and functional characteristics of both atria. Biatrial volumes, emptying fraction(EF) and peak atrial longitudinal/contractile strain(PALS/PACS) were evaluated. All AHRE were analyzed. A total of 80 CIED patients with AHRE were categorized by AHRE duration into 3 groups: Group 1: <6 min(n = 42), Group 2: 6 min ∼ 6 h(n = 23), and Group 3: >6 h(n = 15). Left atrial(LA) maximal volume(V max), atrial precontraction volume(V apc), minimal volume(V min), LAEF, and PALS/PACS were all increasingly worsened among the patients in the 3 groups (p value for trend <0.05). Compared to Group 1, Group 2 had decreased LA PALS/PACS. There was no significant difference in LA volume or EF between Group 1 and 2. Group 3 had enlarged biatrial volumes (LAV max : 57.1(SD 16.0) vs. 45.4(SD 9.2) mL/m2, p = 0.002; LAV min : 42.6(SD 18.2) vs. 28.2(SD 7.2) mL/m2, p < 0.001), impaired total LAEF (28.0(SD 13.7) vs. 38.2(SD 7.7)%, p = 0.004) and reduced PALS/PACS compared to Group 1. Atrial remodeling in those with AHRE >6 h had increased LA volumes, impaired LAEF and reduced PALS/PACS compared to those with AHRE <6 h. Functional remodeling of the atria manifested after AHRE >6 min. Increased biatrial volumes and decreased LA reservoir and pump function occurred when AHRE were > 6 h. These LA structural and functional may be considered surrogate imaging markers for stroke risk assessment in patients with CHA 2 DS 2 -VASc ≥2 and AHRE. [Display omitted] • Functional remodeling of the atria manifested as reduced strain after atrial high-rate episode (AHRE) >6 min. • Increased biatrial volumes and decreased left atrial (LA) reservoir/pump function occurred when AHRE were >6 h. • No obvious LA volume differences occurred when comparing the group of AHRE <6 min to those whose AHRE were 6 min ∼ 6 h. • These imaging items may be considered surrogate markers for stroke risk assessment in patients with AHRE. [ABSTRACT FROM AUTHOR]

Objectives: Atrial high-rate episodes (AHRE) are associated with an increased risk of subclinical atrial fibrillation (SCAF) and can be identified in patients with cardiac implantable electronic devices (CIEDs). This first study from Pakistan aims to determine the incidence of AHREs and the characteristics of a Pakistani cohort with AHREs. Methodology: In this bicentric Cross-sectional study, there were 162 patients of more than 18 years with CIEDs presenting to the device clinics were enrolled. The AHREs cutoff was predefined and AHREs were documented if they last for >30 seconds. Patients with known atrial fibrillation were excluded. Results: Mean age of the patients was 64.69±11.64 years and men were of 62.3%. AHREs were found in 22 (13.6%) patients out of which 13(8%) lasted more than 5 minutes. Mean AHREs cutoff 182.27±20.93. Mean CHA2DS2-VASc score; 3.10±1.47. 54.9% on beta-blockers, and 37% on angiotensin receptor blockers (ARB). Dual-chamber pacemaker (75.3%) and AV block (60.5%) mostly complete AV block, were the most common CIED and indication for an implant respectively. 43.8% had mildly dilated LA, only 1.2 % had severe mitral stenosis, and 3.1% had severe mitral regurgitation. Multivariable binary logistic regression analysis showed that patients on ARB had fewer episodes of AHREs (OR=0.2, 95% CI= 0.05 -0.8, P-value =0.023) while positive family history for coronary artery disease (CAD) was associated with more episodes (OR=5.62, 95% CI=1.58 -20, P-value =0.008). Conclusion: The incidence of AHREs was considerably lower in our population on CIEDs interrogation as compared to prior studies, although the CHA2DS2 -VASc score is higher. ARB use and positive family history of CAD had a statistically significant association with AHRE occurrence. [ABSTRACT FROM AUTHOR]

Screening for atrial fibrillation (AF) has attracted considerable attention recently. Of special interest are patients with cardiac implantable electronic devices (CIEDs) that allow for recording episodes of atrial arrhythmias of various durations, including asymptomatic ones, in which case they are referred to as subclinical atrial fibrillation (SCAF). The available data suggest that the risk of thromboembolic events varies between patients with SCAF and clinically overt AF. As of today, the question regarding anticoagulant therapy in patients with SCAF remains unresolved. The article presents an overview of previous and ongoing studies on this issue, as well as current guidelines on anticoagulant use in patients with SCAF and CIEDs.

Purpose: Atrial high-rate episodes (AHREs) recorded with cardiac implantable electronic devices (CIEDs) have been associated with the development of clinical atrial fibrillation (AF) and increase in stroke and death risk. We sought to perform a systematic review with a meta-analysis to evaluate the prevalence of AHREs detected by CIEDs, their association with stroke risk, development of clinical AF, and mortality among patients without a documented history of AF. Methods: We searched several databases, ClinicalTrials.gov, references of reviews, and meeting abstract books without any language restrictions up to 9 September 2020. We studied patients with CIEDs in whom AHREs were detected. Exclusion criterion was AF history. Our primary outcome was the risk of ischemic stroke in patients with AHREs. Results: We deemed eligible eight studies for the meta-analysis enrolling a total of 4322 patients with CIED and without a documented AF history. The overall AHRE incidence ratio was estimated to be 17.56 (95% CI, 8.61 to 35.79) cases per 100 person-years. Evidence of moderate certainty suggests that patients with documented AHREs were 4.45 times (95% CI 2.87–6.91) more likely to develop clinical AF. Evidence of low confidence suggests that AHREs were associated with a 1.90-fold increased stroke risk (95% CI 1.19–3.05). AHREs were not associated with a statistically significant increased mortality risk. Conclusion: The present systematic review and meta-analysis demonstrated that among patients without a documented history of AF, the detection of AHREs by CIEDs was associated with significant increased risk of clinical AF and stroke. Registration Number (DOI) : Available in https://doi.org/10.17605/OSF.IO/ZRF6M. [ABSTRACT FROM AUTHOR]

• The epidemiology of Subclinical Atrial Fibrillation (SCAF) is unclear • Patients with SCAF have a higher burden of thromboembolic risk factors • SCAF is common in patients with Cardiac Implantable Electronic Devices • Age and follow-up times are associated with SCAF occurrence In recent years, attention to subclinical atrial fibrillation (SCAF), defined as the presence of atrial high-rate episodes (AHREs), in patients with cardiac implantable electronic devices (CIEDs), has gained much interest as a determinant of clinical AF and stroke risk. We aim to perform a systematic review and meta-regression of the available scientific evidence regarding the epidemiology of SCAF in patients receiving CIEDs. PubMed and EMBASE were searched for all studies documenting the prevalence of AHREs in patients (n =100 or more, <50% with history of AF) with CIEDs from inception to 20th August 2021, screened by two independent blind reviewers. This study was registered in PROSPERO: CRD42019106994. Among the 2614 results initially retrieved, 54 studies were included, with a total of 72,784 patients. Meta-analysis of included studies showed a pooled prevalence of SCAF of 28.1% (95%CI: 24.3-32.1%), with high heterogeneity between studies (I2=98%). A multivariable meta-regression was able to explain significant proportion of heterogeneity (R 2=61.9%, p <0.001), with age and follow-up time non-linearly, directly and independently associated with occurrence of SCAF. Older age, higher CHA 2 DS 2 -VASc score, history of AF, hypertension, CHF, and stroke/TIA were all associated with SCAF occurrence. In this systematic review and meta-regression analysis, SCAF was frequent among CIED recipients and was non-linearly associated with age and follow-up time. Older age, higher thromboembolic risk, and several cardiovascular comorbidities were associated with presence of SCAF. [ABSTRACT FROM AUTHOR]

Long-term and continuous ECG monitoring using cardiac implantable electronic devices and insertable cardiac monitors has improved the capability of detecting subclinical atrial fibrillation (AF) and atrial high-rate episodes. Previous studies demonstrated a high prevalence (more than 20%) in patients with cardiac implantable electronic devices or insertable cardiac monitors. Subclinical AF and atrial high-rate episodes are often suspected as the cause of prior or potential future ischemic stroke. However, the clinical significance is still uncertain, and the evidence is limited. This review aims to present and discuss the current evidence on the clinical impact of subclinical AF and atrial high-rate episodes. It focuses particularly on the association between the duration of the episodes and major clinical outcomes like thromboembolic events. As subclinical AF and atrial high-rate episodes are presumed to be associated with ischemic strokes, detection will be particularly important in patients with cryptogenic stroke and in high-risk patients for thromboembolism. In this context, it is also interesting whether there is a temporal relationship between the detection of subclinical AF and atrial high-rate episodes and the occurrence of thromboembolic events. In addition, the review will examine the question whether there is a need for a therapy with oral anticoagulation. [ABSTRACT FROM AUTHOR]

Background: Atrial pacing (AP) can unmask or aggravate a preexisting interatrial block (IAB). The aim of our study was to determine whether AP is associated with the development of atrial high‐rate episodes (AHRE) during follow‐up. Methods: Patients with dual‐chamber cardiac implantable electronic devices (CIEDs), no previous documented atrial fibrillation, and with a 6‐month minimum follow‐up were included. In all patients, sinus and paced P‐wave duration were measured. AHRE was defined as an episode of atrial rate ≥225 bpm with a minimum duration of 5 min, excluding those documented during the first 3 months after implantation. Results: A total of 220 patients were included (75 ± 10 years, 61% male). After a mean follow‐up of 59 ± 25 months, 46% of patients presented AHRE. Mean paced P‐wave duration was significantly longer than the sinus P‐wave duration (154 ± 27 vs. 115 ± 18 ms; p <.001). Sinus and paced P‐waves were significantly longer in those who developed AHRE (sinus: 119 ± 20 vs. 112 ± 16; p =.006; paced: 161 ± 29 vs. 148 ± 23; p <.001). A paced P‐wave ≥160 ms was the best predictor of AHRE, especially those lasting >24 h (odds ratio [OR] 4.2 [95% confidence interval (CI)] [1.6–11.4]; p =.004). Conclusions: AP significantly prolongs P‐wave duration and is associated with further development of AHRE. A paced P‐wave ≥160 ms is a strong predictor of AHRE and should be taken into consideration as a new definition of IAB in the presence of AP. [ABSTRACT FROM AUTHOR]

Subclinical, device-detected atrial fibrillation (AF) is frequently recorded by pacemakers and other implanted cardiac rhythm devices. Patients with device-detected AF have an elevated risk of stroke, but a lower risk of stroke than similar patients with clinical AF captured with surface electrocardiogram. Two randomized clinical trials (NOAH-AFNET 6 and ARTESiA) have tested a direct oral anticoagulant (DOAC) against aspirin or placebo. A study-level meta-analysis of the two trials found that treatment with a DOAC resulted in a 32% reduction in ischaemic stroke and a 62% increase in major bleeding; the results of the two trials were consistent. The annualized rate of stroke in the control arms was ∼1%. Several factors point towards overall net benefit from DOAC treatment for patients with device-detected AF. Strokes in ARTESiA were frequently fatal or disabling and bleeds were rarely lethal. The higher absolute rates of major bleeding compared with ischaemic stroke while on treatment with a DOAC in the two trials are consistent with the ratio of bleeds to strokes seen in the pivotal DOAC vs. warfarin trials in patients with clinical AF. Prior research has concluded that patients place a higher emphasis on stroke prevention than on bleeding. Further research is needed to identify the characteristics that will help identify patients with device-detected AF who will receive the greatest benefit from DOAC treatment., Competing Interests: Conflict of interest: W.F.M. reports research grants and speaking fees from Trimedics Inc. A.P.B. reports lecture fees from Bristol Myers Squibb and AstraZeneca and participation in an educational programme supported by Boston Scientific (‘Fellowship Herzrhythmus’). N.T. has no disclosures. A.B. reports research grants and lecture fees from Bristol Myers Squibb, Theravance, the Zealand Region, the Canadian Institutes of Health Research, the Danish Heart Foundation, the European Union Interreg 5A Programme, and the Independent Research Fund Denmark, outside the submitted work. R.D.L. reports research grants or contracts from Amgen, Bristol Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi-Aventis; funding for educational activities or lectures from Pfizer, Daiichi Sankyo, and Novo Nordisk; and funding for consulting or other services from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, and Novo Nordisk. J.S.H. reports research grants and speaking fees from Medtronic, Boston Scientific, Bristol Myers Squibb, Servier, and Novartis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Subclinical atrial fibrillation (AF) is associated with increased risk of progression to clinical AF, stroke, and cardiovascular death. We hypothesized that in pacemaker patients requiring dual-chamber rate-adaptive (DDDR) pacing, closed loop stimulation (CLS) integrated into the circulatory control system through intra-cardiac impedance monitoring would reduce the occurrence of atrial high-rate episodes (AHREs) compared with conventional DDDR pacing., Methods and Results: Patients with sinus node dysfunctions (SNDs) and an implanted pacemaker or defibrillator were randomly allocated to dual-chamber CLS (n = 612) or accelerometer-based DDDR pacing (n = 598) and followed for 3 years. The primary endpoint was time to the composite endpoint of the first AHRE lasting ≥6 min, stroke, or transient ischaemic attack (TIA). All AHREs were independently adjudicated using intra-cardiac electrograms. The incidence of the primary endpoint was lower in the CLS arm (50.6%) than in the DDDR arm (55.7%), primarily due to the reduction in AHREs lasting between 6 h and 7 days. Unadjusted site-stratified hazard ratio (HR) for CLS vs. DDDR was 0.84 [95% confidence interval (CI), 0.72-0.99; P = 0.035]. After adjusting for CHA2DS2-VASc score, the HR remained 0.84 (95% CI, 0.71-0.99; P = 0.033). In subgroup analyses of AHRE incidence, the incremental benefit of CLS was greatest in patients without atrioventricular block (HR, 0.77; P = 0.008) and in patients without AF history (HR, 0.73; P = 0.009). The contribution of stroke/TIA to the primary endpoint (1.3%) was low and not statistically different between study arms., Conclusion: Dual-chamber CLS in patients with SND is associated with a significantly lower AHRE incidence than conventional DDDR pacing., Competing Interests: Conflict of interest: G.L.B. received speaker’s fee from Abbott, Biotronik, Boston Scientific, Medtronic, and MicroPort. M.D.M., D.G., and A.G. are employees of Biotronik Italia S.p.A., an affiliate of Biotronik SE & Co. KG (study sponsor and manufacturer of investigational devices). All remaining authors have declared no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Atrial high-rate episodes (AHREs) are atrial tachyarrhythmias that are exclusively detected by cardiac implantable electronic devices (CIEDs) with an atrial lead. The objective of this study was to investigate the incidence and predictive factors for AHREs, and to evaluate the ability of inflammation biomarkers to predict the occurrence of AHREs. 102 patients undergoing CIED procedure who received a dual chamber pacemaker were included. CIED interrogation was performed 1 year after the implantation procedure. Patients were divided into groups according to the occurrence of AHREs, which was the primary endpoint of the study. The mean age of the patients was of 73 ± 8.6 years and 48% were male. The incidence of AHREs was 67% at 1 year follow-up. Patients with AHREs were older, had higher left atrial indexed volume (LAVi), higher baseline galectin-3 levels (1007.5 ± 447.3 vs. 790 ± 411.7 pg/mL) and received betablockers more often, along with amiodarone and anticoagulants. Interestingly, the CHADSVASC score did not differ significantly between the two groups. A cut-off value of galectin > 990 pg/mL predicted AHREs with moderate accuracy (AUC of 0.63, 95% CI 0.52 to 0.73, p = 0.04), and this association was confirmed in the univariate regression analysis (OR 1.0012, 95% CI 1.0001 to 1.0023, p = 0.0328). However, based on the multivariate regression analysis, galectin lost its prognostic significance under the effect of LAVi, which remained the only independent predictor of AHREs (OR 1.0883, 95% CI 1.0351 to 1.1441, p = 0.0009). AHREs are common in CIEDs patients. Galectin-3 may bring additional data in the prediction of AHREs.

Simple Summary: Atrial high rate episodes (AHRE) detected by cardiac implantable electronic devices (CIEDs) may be associated with a risk of progression towards long-lasting episodes (≥24 h) and clinical atrial fibrillation (AF). Identification of this subset of patients is key to promptly starting oral anticoagulant therapy and possibly avoiding stroke and systemic thromboembolism. In the present study, we describe the clinical characteristics of 104 retrospectively enrolled patients with AHRE episodes lasting 5 min–23 h 59 min, no AF at 12-lead ECG, and no history of prior clinical AF. Moreover, we define predictors of the composite outcome of clinical AF and/or AHRE episodes lasting ≥24 h. Over a median follow-up of 24.3 (10.6–40.3) months, 31/104 (29.8%) patients experienced the composite outcome. Baseline CHA2DS2-VASc score and the longest AHRE episode at enrollment lasting 12 h–23 h 59 min were independently associated with the composite outcome and with incident clinical AF as well. To conclude, in patients with AHRE, the incidence of clinical AF or AHRE episodes lasting ≥24 h is high. Baseline patients' characteristics (CHA2DS2-VASc score) and AHRE duration may help to intensify monitoring and decision-making, being independently associated with clinical AF in a two-year follow-up. Background. Atrial high rate episodes (AHRE) detected by cardiac implantable electronic devices (CIEDs) may be associated with a risk of progression towards long-lasting episodes (≥24 h) and clinical atrial fibrillation (AF). Methods. Consecutive CIED patients presenting AHRE (with confirmation of an arrhythmia lasting 5 min–23 h 59 min, atrial rate ≥175/min, with no AF at 12-lead ECG and no prior clinical AF) were retrospectively enrolled. The aims of this study were to describe patients' characteristics and the incidence of adverse events, and second, to identify potential predictors of the composite outcome of clinical AF and/or AHRE episodes lasting ≥24 h. Results. 104/107 (97.2%) patients (median age 79.7 (74.0–84.2), 33.7% female) had available follow-up data. Over a median follow-up of 24.3 (10.6–40.3) months, 31/104 (29.8%) patients experienced the composite outcome of clinical AF or AHRE episodes lasting ≥24 h. Baseline CHA2DS2-VASc score and the longest AHRE episode at enrollment lasting 12 h–23 h 59 min were independently associated with the composite outcome (Hazard ratio (HR); 95% CI: 1.40; 1.07–1.83 and HR: 8.15; 95% CI 2.32–28.65, respectively). Baseline CHA2DS2-VASc score and the longest AHRE episode at enrollment lasting 12 h–23 h 59 min were the only independent predictors of incident clinical AF (HR: 1.45; 95% CI 1.06–2.00 and HR: 4.25; 95% CI 1.05–17.20, respectively). Conclusions. In patients with AHRE, the incidence of clinical AF or AHRE episodes lasting ≥24 h is high in a two-year follow-up. Baseline patients' characteristics (CHA2DS2-VASc score) and AHRE duration may help to intensify monitoring and decision-making, being independently associated with clinical AF at follow-up. [ABSTRACT FROM AUTHOR]

Cardiac implanted electronic devices (CIEDs), that perform atrial sensing via an atrial electrode, commonly detect self‐terminating atrial arrhythmias. Nomenclature of these arrhythmias is defined as atrial high‐rate episodes (AHREs) and subclinical atrial fibrillation (SCAF). We have provided a comprehensive summation of the trials regarding the incidence and adverse outcomes of AHREs. The reported incidence of AHRE varies considerably (approximately 10%–70%) between studies depending on the definition of AHRE, duration of follow‐up and the clinical profile of the population. There is increasing evidence related with the association between AHREs' and stroke and/or systemic embolism. However, risk of stroke and/or systemic embolism seems to be less than the risk associated with clinical AF. There is still lack of sufficient evidence related with oral anticoagulation (OAC) in patients with AHRE to reduce thromboembolic risk. Although, the strongest association of OAC treatment with reduction in stroke has been reported to be observed among patients with device detected SCAF episodes of >24 h; it is still questionable whether AHRE is a direct cause of thromboembolic event or just a marker of increased risk. Results of ongoing randomized clinical trials (NOAH‐AFNET 6 and ARTESIA) will provide robust evidence on effect of OAC therapy on AHREs. [ABSTRACT FROM AUTHOR]

Objectives: Left atrial (LA) remodeling itself is an independent risk factor for ischemic stroke and mortality, with or without atrial fibrillation (AF). Macrophage inflammatory protein-1 alpha (MIP-1α) has been reported to be involved in the induction of autoimmune myocarditis and dilated cardiomyopathy. Little is known about whether MIP-1α can be used to predict LA remodeling, especially in patients with AF.Methods: We prospectively enrolled 78 patients who had received a cardiac implantable electronic device due to sick sinus syndrome in order to define AF accurately. AF was diagnosed clinically before enrollment, according to 12-lead electrocardiography (ECG) and 24-h Holter test in 54 (69%) patients. The serum cytokine levels and the mRNA expression levels of peripheral blood leukocytes were checked and echocardiographic study was performed on the same day within 1 week after the patients were enrolled into the study. The 12-lead ECG and 24-h Holter test were performed on the same day of the patients' enrollment, and the device interrogation was performed every 3 months after enrollment. The enrolled patients were clinically followed up for 1 year.Results: There was no difference in baseline characteristics, cytokine levels and mRNA expression between patients with and without AF. Larger LA volume was positively correlated with higher levels of MIP-1α (r = 0.461, p ≤ 0.001) and the atrial high-rate episodes (AHREs) burden (r = 0.593, p < 0.001), and negatively correlated with higher levels of transforming growth factor (TGF)-β1 (r = −0.271, p = 0.047) and TGF-β3 (r = −0.279, p = 0.041). The higher AHREs burden and MIP-1α level could predict LA volume independently. The mRNA expression of RORC was negatively associated with the MIP-1α level.Conclusions: This study showed that higher MIP-1α was significantly associated with LA remodeling and may have the potentials to predict LA remodeling in terms of a larger LA volume, and that circadian gene derangement might affect the expression of MIP-1α.

Background: The HAT2CH2 score has been evaluated for predicting new onset atrial fibrillation, but never for adverse systemic thromboembolic events (STE) in elderly. We aimed to evaluate the HAT2CH2 score and comparing to atrial high rate episodes (AHRE) ≥24 h for predicting STE in older patients with cardiac implantable electronic devices (CIED) implantation.Methods: We retrospective enrolled 219 consecutive patients ≥ 65 years of age undergoing CIED implantation. The primary endpoint was subsequent STE. For all patients in the cohort, the CHA2DS2-VASc, C2HEST, mC2HEST, HAVOC, HAT2CH2 scores and AHRE ≥ 24 h were determined. AHRE was defined as > 175 bpm lasting ≥ 30 s. Multivariate Cox regression analysis with time-dependent covariates was used to determine variables associated with independent risk of STE.Results: The median patient age was 77 years, and 61.2% of the cohort was male. During follow-up (median, 35 months), 16 STE occurred (incidence rate, 2.51/100 patient-years; 95% CI, 1.65–5.48). Multiple Cox regression analysis showed that the HAT2CH2 score (HR, 3.405; 95% CI, 2.272–5.104; p < 0.001) was an independent predictor for STE. The optimal HAT2CH2 score cutoff value was 3, with the highest Youden index (AUC, 0.907; 95% CI, 0.853–0.962; p < 0.001). The STE rate increased with increasing HAT2CH2 score (p < 0.001).Conclusions: This study is the first to show the prognostic value of the HAT2CH2 score for STE occurrence in older patients with CIEDs.

Background: Patients with sustained atrial high-rate episodes (AHRE) have a high risk of major adverse cardio/cerebrovascular events (MACCE). However, the prediction model and factors for the occurrence of AHRE are unknown. We aimed to identify independent factors and various risk models for predicting MACCE and AHRE.Methods: We retrospectively enrolled 314 consecutive patients who had cardiac implantable electronic devices (CIEDs). The primary endpoint was MACCE after AHRE ≥3, 6 min, and 6 h. Atrial high-rate episodes was defined as >175 bpm (Medtronic®) lasting ≥30 s. Multivariate Cox and logistic regression analysis with time-dependent covariates were used to determine variables associated with independent risk of MACCE and occurrence of AHRE ≥3 min, respectively.Results: One hundred twenty-five patients (39.8%) developed AHRE ≥3 min, 103 (32.8%) ≥6 min, and 55 (17.5%) ≥6 h. During follow-up (median 32 months), 77 MACCE occurred (incidence 9.20/100 patient years, 95% CI 5.66–18.39). The optimal AHRE cutoff value was 3 min for MACCE, with highest Youden index 1.350 (AUC, 0.716; 95% CI, 0.638–0.793; p < 0.001). Atrial high-rate episodes ≥3 min−6 h were independently associated with MACCE. HATCH score and left atrial diameter were independently associated with AHRE ≥3 min. The optimal cutoff for HATCH score was 3 and for left atrial diameter was 4 cm for AHRE ≥3 min.Conclusion: Patients with CIEDs who develop AHRE ≥3 min have an independently increased risk of MACCE. Comprehensive assessment using HATCH score and echocardiography of patients with CIEDs is warranted.

Background: Outcomes of device-detected AF remain unclear in individuals without a prior history of AF., Methods: A meta-analysis was conducted to evaluate outcomes in individuals with no prior history of AF who experienced device-detected AF. Outcomes assessed were clinical AF, thromboembolism and all-cause mortality. A fixed-effects model was used to calculate RRs with 95% CI., Results: Compared to individuals who did not experience device-detected AF, those who did had increased risks of clinical AF (RR 3.33, 95% CI [1.99.5.57]; p<0.0001) and thromboembolic events (RR 2.21; 95% CI [1.72.2.85]; p<0.0001). The risk of all-cause mortality was similar between both groups (RR 1.19; 95% CI [0.95.1.49]; p=0.13). Subgroup analysis revealed an increased risk of thromboembolic events among device-detected AF .24 hours (RR 12.34; 95% CI [2.70.56.36])., Conclusion: While there is an increased risk of clinical AF and thromboembolism in individuals with device-detected AF, mortality was insignificant., Competing Interests: Disclosure: AG reports speaking for Philips and Edwards Lifesciences and consulting for Philips and Inari Medical. All other authors have no conflicts of interest to declare., (Copyright © The Author(s), 2024. Published by Radcliffe Group Ltd.)

Background: The electromechanical dyssynchrony associated with right ventricular pacing (RVP) has been found to have adverse impact on clinical outcomes. Several studies have shown that left bundle branch area pacing (LBBAP) has superior pacing parameters compared with RVP. We aimed to assess the difference in ventricular electromechanical synchrony and investigate the risk of atrial high-rate episodes (AHREs) in patients with LBBAP and RVP., Methods: We consecutively identified 40 patients with atrioventricular block and no prior atrial fibrillation. They were divided according to the ventricular pacing sites: the LBBAP group and the RVP group (including the right ventricular apical pacing (RVA) group and the right side ventricular septal pacing (RVS) group). Evaluation of ventricular electromechanical synchrony was implemented using electrocardiogram and two-dimensional speckle tracking echocardiography (2D-STE). AHRE was defined as event with an atrial frequency of ≥176 bpm lasting for ≥6 min recorded by pacemakers during follow-up., Results: The paced QRS duration of the LBBAP group was significantly shorter than that of the other two groups: LBBAP 113.56 ± 9.66 ms vs. RVA 164.73 ± 14.49 ms, p  < 0.001; LBBAP 113.56 ± 9.66 ms vs. RVS 148.23 ± 17.3 ms, p  < 0.001. The LBBAP group showed shorter maximum difference (TDmax), and standard deviation (SD) of the time to peak systolic strain among the 18 left ventricular segments, and time of septal-to-posterior wall motion delay (SPWMD) compared with the RVA group (TDmax, 87.56 ± 56.01 ms vs. 189.85 ± 91.88 ms, p  = 0.001; SD, 25.40 ± 14.61 ms vs. 67.13 ± 27.40 ms, p  < 0.001; SPWMD, 28.75 ± 21.89 ms vs. 99.09 ± 46.56 ms, p  < 0.001) and the RVS group (TDmax, 87.56 ± 56.01 ms vs. 156.46 ± 55.54 ms, p  = 0.003; SD, 25.40 ± 14.61 ms vs. 49.02 ± 17.85 ms, p  = 0.001; SPWMD, 28.75 ± 21.89 ms vs. 91.54 ± 26.67 ms, p  < 0.001). The interventricular mechanical delay (IVMD) was shorter in the LBBAP group compared with the RVA group (-5.38 ± 9.31 ms vs. 44.82 ± 16.42 ms, p  < 0.001) and the RVS group (-5.38 ± 9.31 ms vs. 25.31 ± 21.36 ms, p  < 0.001). Comparing the RVA group and the RVS group, the paced QRS duration and IVMD were significantly shorter in the RVS group (QRS duration, 164.73 ± 14.49 ms vs. 148.23 ± 17.3 ms, p  = 0.02; IVMD, 44.82 ± 16.42 ms vs. 25.31 ± 21.36 ms, p  = 0.022). During follow-up, 2/16 (12.5%) LBBAP patients, 4/11 (36.4%) RVA patients, and 8/13 (61.5%) RVS patients had recorded novel AHREs. LBBAP was proven to be independently associated with decreased risk of AHREs than RVP (log-rank p  = 0.043)., Conclusion: LBBAP generates narrower paced QRS and better intro-left ventricular and biventricular contraction synchronization compared with traditional RVP. LBBAP was associated with a decreased risk of AHREs compared with RVP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Yang, Di, Peng and Sun.)

Background: Patients with atrial high‐rate episode (AHRE) are at higher risk of neurological events. This study aimed to identify the optimal cutoff threshold for AHRE duration in patients with dual chamber permanent pacemakers (PPM) without prior atrial fibrillation. Methods: We included 355 consecutive patients receiving dual chamber pacemaker implantation. Primary outcome was composite endpoint of subsequent neurological events after various AHRE durations. AHRE was defined as >175 bpm (MEDTRONIC) or > 200 bpm (BIOTRONIK) for longer than 30 s. Cox regression analysis with time‐dependent covariates was conducted. Results: The mean age of included patients was 75.6 ± 11.3 years. Among 355 included patients, some had multiple AHREs; 125 patients (35.2%) developed AHRE ≥2 min, 107 (30.1%) had ≥5 min, 55 (15.5%) had ≥6 h, and 37 (10.4%) had ≥24 h. The mean follow‐up was 42.1 ± 31.2 months. During follow‐up, 19 neurological events occurred. After adjustment for CHA2DS2‐VASc score and device type, multivariate Cox regression analysis indicated AHRE ≥2 min (HR 13.605, 95% CI 3.010–61.498), and AHRE ≥5 min (HR 5.819, 95% CI 2.056–16.470) were significantly associated with neurological events. Hence, the optimal AHRE cutoff value was 2 min with the highest Youden index (sensitivity, 89.5%; specificity, 67.8%; AUC, 0.823, 95% CI, 0.763–0.884; p < 0.001). Conclusions: Patients with dual chamber PPM who develop AHRE have increased risk of neurological events. Comprehensive assessment of the risks and benefits of prescribing anticoagulants should be considered in PPM patients with AHRE ≥2 min. [ABSTRACT FROM AUTHOR]

• Atrial high-rate episodes (AHRE) have a high risk of cardio-cerebrovascular events (CCEs). • The optimal cut-off for AHRE duration and CHA2DS2-VASc score is unknown. • All categories of AHRE duration were independently associated with CCE. • The occurrence of CCE increased with variable AHRE durations and CHA 2 DS 2 -VASc score. Patients with atrial high-rate episodes (AHRE) have a high risk of cardiovascular and cerebrovascular events (CCE); however, the optimal cut-off threshold for AHRE duration and the prediction power of AHRE with CHA 2 DS 2 -VASc score is unknown. We enrolled 355 consecutive patients undergoing dual chamber pacemaker implantations. The primary endpoint was subsequent CCE after AHRE ≥ 30 seconds, 1 minute, 2 minutes, 5 minutes, 6 hours, and 24 hours. AHRE was defined as >175 bpm (Medtronic, Dublin, Ireland) or >200 bpm (Biotronik, Berlin, Germany) lasting ≥30 seconds. Multivariate Cox regression analysis with time-dependent covariates was used to determine the variables associated with higher risks of CCE. The average age of the patients was 75.6 ± 11.3 years, and 162 patients (45.6%) developed AHRE ≥ 30 seconds, 145 (40.8%) ≥1 minute, 125 (35.2%) ≥2 minutes, 107 (30.1%) ≥5 minutes, 55 (15.5%) ≥6 hours, and 37 (10.4%) ≥24 hours. During follow-up (mean 42.1 ± 31.2 months), 145 CCE occurred in 107 patients (incidence rate 11.64/100 patient-years, 95% CI 9.99-13.70). The optimal AHRE cut-off value was 1 minute (sensitivity, 57.9%; specificity, 66.0%; area-under-the-curve, 0.631; 95% CI, 0.563–0.698; p < 0.001). Multivariate Cox regression analysis demonstrated that all categories of AHRE duration were independently associated with CCE. The occurrence of CCE increased with AHRE ≥30 seconds and CHA 2 DS 2 -VASc score ≥2 (males) or ≥3 (females). Patients with dual chamber pacemakers who develop AHRE ≥ 30 seconds have an increased risk of CCE. The combination of AHRE duration ≥30 seconds and CHA 2 DS 2 -VASc score ≥2 (males) or ≥3 (females) is a useful risk-stratification predictor for subsequent CCE. [ABSTRACT FROM AUTHOR]

• Diastolic wall strain (DWS) was associated with the prevalence of atrial high-rate episodes (AHREs) in pacemaker patients. • Patients who progressed to persistent AHREs were associated with lower DWS. • Our findings may provide additional prognostic information for other factors. Cardiac implantable electronic device-detected atrial high-rate episodes (AHREs) have been reported to be associated with thromboembolic risks. The present study aimed to investigate the association of echocardiographic and clinical parameters with the occurrence of AHREs in patients with a dual-chamber pacemaker (PMI). One hundred forty-seven patients (76 males, 75.2 ± 8.9 years) who did not show atrial tachyarrhythmia before the implantation of the PMI were studied. Diastolic wall strain (DWS) and other measurements were assessed during sinus rhythm using transthoracic echocardiography before the PMI. DWS was calculated from the M-mode echocardiographic measurement of the left ventricular (LV) posterior wall thickness at end-systole (PWs) and end-diastole (PWd), and DWS was defined as (PWs-PWd) / PWs. AHREs (defined as AHREs duration >6 min and atrial rate >180 bpm) were detected in 50 / 147 patients during follow up (38.3 ± 13.8 months). Patients in the AHREs group had reduced DWS (0.29 ± 0.07 vs. 0.39 ± 0.06, p < 0.0001), larger left atrial volume index, thicker LV posterior diameter, higher rate of patients taking β-blocker / diuretics, and higher prevalence of sinus node dysfunction. On multivariable analysis, only DWS was independently associated with AHREs. Patients with reduced DWS (<0.33) had a higher risk of incidences of AHREs. LV stiffness assessed by DWS was associated with AHREs in patients with a PMI. [ABSTRACT FROM AUTHOR]

Background. Atrial high rate episodes (AHRE) detected by cardiac implantable electronic devices (CIEDs) may be associated with a risk of progression towards long-lasting episodes (≥24 h) and clinical atrial fibrillation (AF). Methods. Consecutive CIED patients presenting AHRE (with confirmation of an arrhythmia lasting 5 min–23 h 59 min, atrial rate ≥175/min, with no AF at 12-lead ECG and no prior clinical AF) were retrospectively enrolled. The aims of this study were to describe patients’ characteristics and the incidence of adverse events, and second, to identify potential predictors of the composite outcome of clinical AF and/or AHRE episodes lasting ≥24 h. Results. 104/107 (97.2%) patients (median age 79.7 (74.0–84.2), 33.7% female) had available follow-up data. Over a median follow-up of 24.3 (10.6–40.3) months, 31/104 (29.8%) patients experienced the composite outcome of clinical AF or AHRE episodes lasting ≥24 h. Baseline CHA2DS2-VASc score and the longest AHRE episode at enrollment lasting 12 h–23 h 59 min were independently associated with the composite outcome (Hazard ratio (HR); 95% CI: 1.40; 1.07–1.83 and HR: 8.15; 95% CI 2.32–28.65, respectively). Baseline CHA2DS2-VASc score and the longest AHRE episode at enrollment lasting 12 h–23 h 59 min were the only independent predictors of incident clinical AF (HR: 1.45; 95% CI 1.06–2.00 and HR: 4.25; 95% CI 1.05–17.20, respectively). Conclusions. In patients with AHRE, the incidence of clinical AF or AHRE episodes lasting ≥24 h is high in a two-year follow-up. Baseline patients’ characteristics (CHA2DS2-VASc score) and AHRE duration may help to intensify monitoring and decision-making, being independently associated with clinical AF at follow-up.

Background: Left bundle branch area pacing (LBBAP) demonstrated beneficial effects on clinical outcomes. Comparative data on the risk of atrial high-rate episodes (AHREs) between LBBAP and right ventricular pacing (RVP) are lacking., Aims: This study aimed to investigate whether LBBAP can reduce the risk of new-onset AHREs compared with RVP in patients with atrioventricular block (AVB)., Methods: We enrolled 175 consecutive AVB patients with no history of atrial fibrillation undergoing dual-chamber pacemaker implantation (LBBAP or RVP). Propensity score matching for baseline characteristics yielded 43 matched pairs. The primary outcome was new-onset AHREs detected on a scheduled device follow-up. Changes in echocardiographic measurements were also compared between the groups., Results: New-onset AHREs occurred in 42 (24.0%) of all enrolled patients (follow-up 14.1 [7.5] months) and the incidence of new-onset AHREs in the LBBAP group was lower than in the RVP group (19.8% vs. 34.7%; P = 0.04). After propensity score matching, LBBAP still resulted in a lower incidence of new-onset AHREs (11.6% vs. 32.6%; P = 0.02), and a lower hazard ratio for new-onset AHREs compared with RVP (HR, 0.274; 95% CI, 0.113-0.692). At 1 year, LBBAP achieved preserved left ventricular ejection fraction (LVEF) (63.0 [3.2]% to 63.1 [3.1]%; P = 0.56), while RVP resulted in reduced LVEF (63.4 [4.9]% to 60.5 [7.3]%; P = 0.01]). Changes in LVEF were significantly different between the 2 groups (by 2.6% [0.2 to 5.0]%; P = 0.03)., Conclusion: LBBAP demonstrated a reduced risk of new-onset AHREs compared with RVP in patients with AVB.

INTRODUCTION[|]Technological advances have allowed cardiac implantable electronic devices (CIEDs) to detect, analyze, and store atrial high-rate episodes (AHREs), which are surrogate for the term silent atrial fibrillation (AF). The association of AHREs with adverse clinical events has been demonstrated in several recent studies, implying that morbidity and mortality can be significantly prevented by prompt recognition and intervention. Inflammation and oxidative stress are among several mechanisms that contribute to the pathogenesis of AF. The monocyte-to-high-density lipoprotein ratio (M/H ratio) is a novel indicator of both inflammation and oxidative stress. In this study, we aimed to investigate the value of the M/H ratio for predicting AHREs detected by CIEDs.[¤]METHODS[|]A total of 203 patients (mean age: 57.5+9.1 years, 60.1% male) implanted with a dual pacemaker because of sick sinus syndrome were included. Blood samples were obtained from the patients after 12 h of fasting for the analysis of routine biochemistry tests and the lipid panel in the morning of device implantation. At a clinical visit 6 months after CIED implantation, the devices were interrogated to detect the occurrence of AHREs. AHREs were defined as atrial episodes faster than 220 bpm and lasting longer than 5 min. The patients were divided into two groups depending on the presence of AHREs during pacemaker interrogation: Group 1 (AHRE present) and Group 2 (AHRE absent).[¤]RESULTS[|]At the clinical visit 6 months after CIED implantation, 51 (25.1%) patients had at least one AHRE. The M/H ratio was significantly higher in patients in Group 1 (11.41+-1.24) than in those in Group 2 (8.17+-1.02) (p

Self-terminating atrial arrhythmias are commonly detected on continuous rhythm monitoring, e.g. by pacemakers or defibrillators. It is unclear whether the presence of these arrhythmias has therapeutic consequences. We sought to summarize evidence on the prevalence of atrial high-rate episodes (AHREs) and their impact on risk of stroke. We performed a comprehensive, tabulated review of published literature on the prevalence of AHRE. In patients with AHRE, but without atrial fibrillation (AF), we reviewed the stroke risk and the potential risk/benefit of oral anticoagulation. Atrial high-rate episodes are found in 10-30% of AF-free patients. Presence of AHRE slightly increases stroke risk (0.8% to 1%/year) compared with patients without AHRE. Atrial high-rate episode of longer duration (e.g. those >24 h) could be associated with a higher stroke risk. Oral anticoagulation has the potential to reduce stroke risk in patients with AHRE but is associated with a rate of major bleeding of 2%/year. Oral anticoagulation is not effective in patients with heart failure or survivors of a stroke without AF. It remains unclear whether anticoagulation is effective and safe in patients with AHRE. Atrial high-rate episodes are common and confer a slight increase in stroke risk. There is true equipoise on the best way to reduce stroke risk in patients with AHRE. Two ongoing trials (NOAH-AFNET 6 and ARTESiA) will provide much-needed information on the effectiveness and safety of oral anticoagulation using non-vitamin K antagonist oral anticoagulants in patients with AHRE. [ABSTRACT FROM AUTHOR]

Background Although previous studies showed that atrial high-rate episodes (AHREs) are associated with a higher risk of developing incident atrial fibrillation (AF) and thromboembolic events, their clinical significance is still unclear. The purpose of this study was to define whether there is any clinical impact on the occurrence of ischemic and hemorrhagic events in patients with AHREs and initiation of oral anticoagulation (OAC). Methodology Patients with AHREs who had received cardiac implantable electronic devices (CIEDs, i.e., dual-chamber pacemaker [PM] or implantable cardioverter defibrillator [ICD]) were included in the study. OAC initiation was decided by the assistant doctor. Patients who received OACs comprised the OAC group, while patients who were not referred for OAC initiation were included in the control group. The primary endpoint was the time to the event of the occurrence of thromboembolic events (thromboembolic event-free survival). Results A total of 154 individuals (77 in each group) were enrolled in the study, with a mean age of 72.5 years. The mean follow-up period for the OAC group was 19.1 months and for the control group, 18.9 months ( P =  0.9). Thromboembolic events were noticed only in seven patients. Six of them were in the control group, and only one in the OAC group ( P =  0.05). Major bleeding events were noticed in five patients, one of whom was in the control group and the rest in the OAC group ( P = 0.17). Conclusions OAC therapy in patients with AHREs was not associated with a significant difference in the risk of thromboembolic and bleeding events. Baseline patient characteristics and AHRE duration may be useful to intensify the monitoring and management of patients with AHREs. Bleeding events may be indicators of cancer in patients with AHREs receiving OACs., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Dimou et al.)

Atrial fibrillation (AF) is associated with morbidity and mortality. Modern pacemakers can detect atrial high-rate episodes (AHREs) as a surrogate for AF. It remains controversial whether inflammation is a cause or a consequence of AF. This study investigated whether the inflammatory biomarker high-sensitivity C-reactive protein (hs-CRP) can predict subsequent AHREs. This study gathered prospective data from patients with pacemakers and a left ventricle EF ≥ 50% between 2015 and 2019. The hs-CRP and other cardiac biomarkers at baseline and device-detected AHREs, defined as atrial rate ≥ 180 bpm and duration ≥ 6 min, were determined. Cox regression analysis was used to estimate the independent predictors for AHREs. A total of 171 consecutive patients were included. During the median follow-up of 614 days, 66 patients (39%) developed subsequent AHREs. In the univariate Cox regression analysis, sick sinus syndrome (p = 0.005), prior AF (p < 0.001), mitral A velocity (p = 0.008), and hs-CRP (p = 0.013) showed significant association with the increased risk of AHREs. In the multivariate Cox regression model, hs-CRP (HR = 1.121, 95% confidence interval = 1.015–1.238, p = 0.024) retained its significance. Our results suggest that elevated hs-CRP could predict subsequent AHREs and that inflammation could play a role in AF pathogenesis in patients with preserved EF.

Atrial high-rate episodes (AHRE) are atrial tachyarrhythmias detected by continuous rhythm monitoring by pacemakers, defibrillators, or implantable cardiac monitors. Atrial high-rate episodes occur in 10-30% of elderly patients without atrial fibrillation. However, it remains unclear whether the presence of these arrhythmias has therapeutic consequences. The presence of AHRE increases the risk of stroke compared with patients without AHRE. Oral anticoagulation would have the potential to reduce the risk of stroke in patients with AHRE but is also associated with a rate of major bleeding of ∼2%/year. The stroke rate in patients with AHRE appears to be lower than the stroke rate in patients with atrial fibrillation. Wearables like smart-watches will increase the absolute number of patients in whom atrial arrhythmias are detected. It remains unclear whether anticoagulation is effective and, equally important, safe in patients with AHRE. Two randomized clinical trials, NOAH-AFNET6 and ARTESiA, are expected to report soon. They will provide much-needed information on the efficacy and safety of oral anticoagulation in patients with AHRE., Competing Interests: Conflict of interest: T.T. received speaker fees from Medtronic and honoraria from Boston Scientific. A.B. received honorarium from Boehringer-Ingelheim, Bristol-Myers Squibb and received research grants from Theravance, Zealand Region, Canadian Institutes of Health Research and the Danish Heart Foundation. N.F. received a grant from Biotronik, speaker fees from Abbott, Medtronic, all outside the submitted work. J.R.G. receives consultant or speaker fees from Atricure, Daiichi Sakyo, Bayer, and Novartis. He received research funding through institution from Abbott, Boston Scientific, Medtronic, Atricure, and Owner RhythmCare. E.M. receives consultant fees from Abbott, Bayer, Boston Scientific, Medtronic, and Zoll Carina Blomström Lundqvist received honorarium from Medtronic, Boston Scientific, Abbott, Bayer, Sanofi, Organon, Milestone, Philips, Cathprint outside this work. G.-A.D. receives speaker and consultation fees from Boehringer Ingelheim, Bayer, Novartis, Berlin Chemie, Amgen, Sanofi; nothing linked to the submitted work. B.M. received speaker fees from Abbott, Astra Zeneca, Biotronik, Boehringer Ingelheim, Novartis. Paulus Kirchhof receives research support for basic, translational, and clinical research projects from European Union, British Heart Foundation, Leducq Foundation, Medical Research Council (UK), and German Centre for Cardiovascular Research, from several drug and device companies active in atrial fibrillation and has received honoraria from several such companies in the past, but not in the last 3 years (unrelated to the submitted work). P.K. is listed as inventor on two patents held by University of Birmingham (Atrial Fibrillation Therapy WO 2015140571, Markers for Atrial Fibrillation WO 2016012783). All remaining authors have declared no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Cryptogenic ischemic stroke, defined as stroke of undetermined etiology, accounts for 7–25% of all ischemic strokes. Stroke severity is reported to be less severe than cardioembolic stroke and similar to large-artery atherosclerosis. Because its etiology is believed to be mostly an embolic type, it is often called “embolic strokes of undetermined source” (ESUS). In patients with ESUS, it is of significant importance to seek an embolic source with intensive diagnostic assessment, which mostly originates from the heart. Covert atrial fibrillation (AF) and atrial high-rate episodes (AHRE) detected by cardiac implantable electronic devices are believed to contribute to the pathogenesis of ESUS. AHRE is common not only in device-implanted patients, but also in older patients with cardiovascular risk factors. However, it is unclear whether AHRE is a direct cause or simply a risk marker of stroke. Furthermore, indication of anticoagulation therapy for stroke prevention in patients with AHRE remains undetermined. In this review, we focus on the roles of covert AF and AHRE in the pathogenesis of cryptogenic ischemic stroke or ESUS. Detection of covert AF and AHRE, and possible management strategies are also discussed. [ABSTRACT FROM AUTHOR]

Aims: Atrial high-rate episodes (AHREs) compatible with silent AF detected in pacemakers (PM) are related to an increased risk of stroke and silent ischaemic brain lesions (IBL) on CT scan. AHREs soon after PM implantation could be related with the procedure itself and the prognosis might be different.Methods and results: We analysed the incidence of AHREs >5 min and the presence of silent IBL in 110 patients (56% men, aged 75 ± 9 year-old) with PM and no history of AF, in relation to time from implantation (≤3 months vs. >3 months) and the atrial lead fixation (LF) (active vs. passive). Mean CHADS2 and CHA2DS2VASc scores were 1.9 ± 1.2 and 3.5 ± 1.5, respectively. Time from implantation was ≤3 months in 88 patients (80%). Active LF was used in 55 patients (50%). After 24 ± 9 months, AHREs were present in 40 patients (36.4%). CT-scan showed silent IBL in 26 patients (23.6%). The presence of AHREs at 3 months was more frequent in the patients with recent PM implantation (17% vs. 4.5%, P = 0.09) and significantly related to active LF (OR 5.36, 1.43-20.07; P < 0.05). The presence of silent IBL was related to the detection of AHREs during follow up (OR 3.12, 1.29-7.97; P < 0.05) but not with AHREs at first 3 months (OR 1.58, 0.49-5.05; P = 0.44).Conclusions: AHREs occur frequently during the first 3 months after PM implantation and could be related with procedure itself and the use of active LF. AHREs in this period might not be related to worse outcomes and should be interpreted cautiously. [ABSTRACT FROM AUTHOR]