Atrial High-rate Episodes Burden Research Articles

Consensus on Stroke Prevention in Atrial Fibrillation and Utilization of NOACs in the Real-World Setting in India

Atrial fibrillation (AF) is the most frequent cardiac arrhythmia. Prevention of stroke and systemic thromboembolism remainsthe cornerstone of the management of AF. Even today, there are unresolved knowledge gaps in AF pathophysiology, screeningand therapeutic strategies and stroke prevention. The modified DELPHI method was used to develop the best practicerecommendations for the management of AF in a real-world setting with the participation of 500 cardiologists across India.The experts concurred that the decision to initiate antithrombotic treatment in patients with transient AF could be based onthe duration of transient AF, the co-existence of the risk factor for stroke and echocardiographic abnormalities impact thedecision. The decision to initiate anticoagulant therapy in device-detected atrial high-rate episodes (AHRE) can be decidedbased on the duration of AHRE, the burden of AHRE and the individual’s risk of stroke and thromboembolism. The benefitof early anticoagulation should be balanced with the risk of intracerebral hemorrhage (ICH), especially in elderly patientsand in severe strokes. Apixaban is the preferred drug in patients with concomitant ischemic heart disease (IHD), patientswith a history of gastrointestinal (GI) bleeding, patients with underlying malignancy, elderly patients with AF, patients withcomorbid diseases and patients with hepatic disease or renal disease. Apixaban was considered to be an affordable noveloral anticoagulant (NOAC) for Indian patients for primary and secondary stroke prophylaxis in AF patients

A multiple cut-off diagnostic meta-analysis to identify the atrial high-rate episodes threshold that better relates to thromboembolic events

Abstract Background Despite the high prevalence of atrial high-rate episodes (AHRE) detected by cardiac implantable electronic devices (CIED), clinical guidelines and consensus documents have failed to agree on a universal AHRE definition. Clear evidence on the best management strategy is lacking. Purpose The present is a diagnostic test accuracy meta-analysis aiming to derive from available literature the optimal AHRE threshold to predict thromboembolic events. Methods PubMed/MEDLINE and EMBASE databases were screened for studies on CIED patients reporting incidence of thromboembolic events referred to at least one AHRE definition. A random-effect diagnostic test accuracy meta-analysis with multiple cut-offs was performed: duration of AHRE was the "diagnostic test" (positive test if the patients experienced an AHRE lasting at least as long as the time cut-off under examination) whose performance in predicting the "disease" (thromboembolic events) was evaluated across multiple cut-offs. Two analyses, according to AHRE definition (longest episode vs. cumulative burden), were performed. Results 23 studies were included in the analyses (Fig. 1 Panel A), encompassing 46,189 patients: 19 considering the longest single AHRE and 4 the AHRE burden, respectively. Median follow-up was 40.75 (IQR 28.25-52.80) months. The analysis on the longest single AHRE indicated 0.07 minutes as the optimal cut-off to differentiate AHRE associated or not to thromboembolic events [sensitivity 65.4% (95% CI 48.8-79.0%), specificity 52.7% (95%CI 46.0-59.4%), area under the summary receiver operating characteristic curve (AUC-SROC): 0.62; Fig. 1 Panel B]. The analysis on AHRE burden indicated, instead, 1.4 minutes as the optimal cut-off [sensitivity 58.2% (95%CI 25.6-85.0%), specificity 57.5% (95% CI 42.0-71.7%), AUC-SROC 0.60; Fig. 1 Panel C]. PPV and NPV for 6 minutes and 24 hours cut-offs were similar in each analysis (Figure 2). Sensitivity analyses exclusively considering studies reporting data on patients without previous AF diagnosis and high-quality studies only yield similar results. Conclusion The present evidence-based approach suggests the presence (or not) of AHRE, rather than a specific duration, relates to an increased thromboembolic risk in CIED patients. A linear relationship between AHRE duration (both in terms of single longest episode than cumulative burden) and thromboembolic events was not observed.

Role of atrial high-rate episodes in stratifying thromboembolic risk: a multiple cut-off diagnostic meta-analysis.

Despite the high prevalence rate of atrial high-rate episodes (AHREs) detected using cardiac implantable electronic devices (CIEDs), clinical guidelines and consensus documents have disagreed on a universal AHRE definition and a temporal cut-off related to subsequent thromboembolic events. This diagnostic test accuracy meta-analysis aims to derive the optimal temporal threshold of clinically significant AHREs from the available literature. The PubMed/MEDLINE and EMBASE databases were screened for studies on CIED patients reporting the incidence of thromboembolic events related to at least one AHRE temporal cut-off. A total of 23 studies were included: 19 considering the longest single AHRE and four the AHRE burden, respectively. A random-effect diagnostic test accuracy meta-analysis with multiple cut-offs was performed. Two analyses were performed according to the AHRE temporal cut-off subtype (longest episode vs. cumulative burden). The analysis on the longest single AHRE indicated 0.07 min as the optimal duration to differentiate AHRE associated or not with thromboembolic events [sensitivity 65.4% (95% CI 48.8%-79.0%), specificity 52.7% (95% CI 46.0%-59.4%), and area under the summary receiver operating characteristic curve (AUC-SROC): 0.62]. The analysis on AHRE burden indicated 1.4 min as the optimal cut-off [sensitivity 58.2% (95% CI 25.6%-85.0%), specificity 57.5% (95% CI 42.0%-71.7%), and AUC-SROC 0.60]. A sensitivity analysis excluding patients with a history of atrial fibrillation and including high-quality studies only yielded similar results. The presence of AHRE, rather than a specific duration, relates to an increased, albeit low, thromboembolic risk in CIED patients. Any AHRE should constitute an additional element in patient-specific thromboembolic risk assessment.

Association between alcohol consumption and subclinical atrial fibrillation

BackgroundIt 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.MethodsThis 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.ResultsDuring 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).ConclusionAlcohol 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.

Multimodality imaging assessment of the Biatrial remodeling of the burden of atrial high-rate episodes in patients with cardiac implanted electronic devices

AimsThe underlying mechanisms of atrial remodeling in cardiac implanted electronic device(CIED)-detected atrial high-rate episodes(AHRE) remains to be elucidated. MethodsA 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. ResultsA 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(Vmax), atrial precontraction volume(Vapc), minimal volume(Vmin), 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 (LAVmax: 57.1(SD 16.0) vs. 45.4(SD 9.2) mL/m2, p = 0.002; LAVmin: 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. ConclusionFunctional 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 CHA2DS2-VASc ≥2 and AHRE.

Multimodality Imaging Assessment of the Biatrial Remodeling of the Burden of Atrial High-Rate Episodes in Patients with Cardiac Implanted Electronic Devices

Multimodality Imaging Assessment of the Biatrial Remodeling of the Burden of Atrial High-Rate Episodes in Patients with Cardiac Implanted Electronic Devices

The Association between Physical Activity and Cardiovascular Implantable Electronic Device-Detected Atrial High Rate Episodes.

Atrial fibrillation is the most common arrhythmia and it is associated with a higher risk of mortality and morbidity. The goal of this study was to assess the correlation between physical activity (PA) and atrial high rate episodes (AHREs) detected by cardiovascular implantable electronic devices (CIEDs). We prospectively collected data from 81 patients from March 2017 to June 2019. Device-detected PA (hours per day) through an accelerometer and occurrence/burden of AHREs were determined at each outpatient clinic visit. Modest AHREs and long AHREs were defined as at least 1 episode of AHREs lasting ≥ 12 hours and 24 hours, respectively. The percentage of total AHREs in the follow-up period was defined as the burden of AHREs. Generalized estimating equations were used to explore the association between PA and occurrence/burden of AHREs to account for repeated measures within a participant. The patients had 336 follow-up visits (mean 4.1 visits each). The prevalence rates of device-detected modest AHREs and long AHREs were 4.8% and 3.9%, respectively. More PA (hours per day) was associated with a lower risk of modest AHREs [odds ratio (OR) 0.671, 95% confidence interval (CI) 0.452-0.997, p = 0.048] and long AHREs (OR 0.536, 95% CI 0.348-0.824, p = 0.004) after adjusting for age, sex, and basic characteristics. More PA had a trend of association with fewer AHREs (β -0.255, 95% CI -0.512 to 0.001, p = 0.051). More PA was associated with a lower risk of AHREs detected by CIEDs in older patients. PA may reduce the risk of AHREs.

Association between atrial high rate episode burden and autonomic and vascular function in patients with implanted cardiac device

Abstract Background Patients who experience frequent atrial high rate episodes (AHREs), recorded on implantable cardiac devices, are at an increased risk of stroke and systemic embolism. Increased duration of AHRE is related to higher risk of thromboembolic event. The underlying pathophysiology is unclear; however, autonomic and/or endothelial dysfunction may contribute. Purpose We tested the hypothesis that patients with high AHRE burden have worse autonomic and vascular function compared to patients with low AHRE burden. Design We studied 44 patients split in two groups: high AHRE burden (longest AHRE ≥24 hours; n=22) and low AHRE burden (longest AHRE &amp;lt;24 hours; n=22). Resting time- and frequency-domain measures of HRV were determined to index cardiac autonomic function. High-resolution ultrasound was used to measure brachial artery diameter at rest and during reactive hyperaemia (endothelium-dependent flow mediated dilation (FMD)). Results FMD was higher in the low AHRE burden group compared to high AHRE group (5.5% [95% confidence interval (CI):3.4–7.6] vs 3.1% [95% CI: 1.9–6.2]; p=0.04) (table 1). Mean heart rate (p&amp;lt;0.001) and AHRE burden (p=0.02) were independent predictors of FMD on multivariate analysis. Time-domain, frequency-domain and non-linear indices of HRV were not significantly different between the groups. A slower heart rate (Spearman's rho 0.369; p=0.01) and high AHRE burden (Spearman's rho −0.315; p=0.04) were independently associated with changes seen on FMD following adjustment for multiple variables (p=0.001 and p=0.03 respectively). Conclusion Endothelium-dependent FMD is impaired in patients with high AHRE burden, while HRV derived indices of autonomic function were not affected by AHRE burden. Endothelial dysfunction may play an important role in the adverse outcomes seen in patients who experience frequent AHRE. Funding Acknowledgement Type of funding sources: None.

Altered Expression of Circadian Clock Genes in Patients with Atrial Fibrillation Is Associated with Atrial High-Rate Episodes and Left Atrial Remodeling.

A prominent circadian variation is present in atrial fibrillation (AF) attacks that may be related to the expression of circadian clock genes. Little is known about the expression of circadian clock genes in AF. We prospectively enrolled 73 patients who had received pacemaker implantation, in order to define the burden of atrial high-rate episodes (AHREs) accurately. AF was diagnosed clinically in 43 (59%) patients (15 with persistent AF and 28 with paroxysmal AF). The expression levels of circadian clock genes of peripheral blood leukocytes were checked. There were more males and patients with a larger left atrial (LA) size and lower expression levels of BMAL1, CRY2, NR1D1, NR1D2, PER2, RORA, RORC, and TIM genes in persistent AF group than in other groups. There was a significant correlation between higher AHRE burden and larger LA size and between higher AHRE burden and decreased expression of circadian clock genes in patients with AF. LA volume and the expression of CRY1, NR1D1, and RORA are significantly associated with AHRE burden. However, the underlying mechanism needs to be elucidated in further studies.

Atrial high-rate episodes and risk of major adverse cardiovascular events in patients with cardiac implantable electronic devices.

Patients with atrial high-rate episodes (AHREs) are at higher risk of thromboembolic eventsand mortality. The risk of major adverse cardiovascular events (MACE) in these patients is unknown. To investigate the risk of MACE in patients implanted with cardiac implantable electronic devices (CIEDs) developing AHREs METHODS AND RESULTS: We included 852 consecutive patients undergoing CIEDs implantation. Primary outcome was a composite endpoint of MACEs occurring after AHREs ≥ 5min. AHRE was defined as > 175bpm and lasting ≥ 5min. We also performed a subgroup analysis in patients with the longest AHRE lasting ≥ 24h. Cox regression analysis with time-dependent covariates was used to investigate the relationship between AHREs and MACEs. Mean age was 70.0 ± 13.6years, and 39.3% were women: 325 patients developed AHREs ≥ 5min [incidence rate (IR) 13.1% year 95% confidence interval (CI) 11.7-14.6] and 124 patients developed AHREs ≥ 24h (IR 3.7%/year 95% CI 3.1-4.5). During a median follow-up of 37.0months (IQR 19.0-64.3, 316,132 patient-years), 152 MACEs occurred (IR 4.85%/year, 95% CI 4.11-5.68). The IR of MACE occurring after AHREs onset was higher in patients developing AHREs ≥ 24h (IR 1.13%/year) than AHREs ≥ 5min (IR 0.63%/year, p = 0.030). Multivariable Cox regression analysis showed that AHREs ≥ 5min (HR 1.788, 95% CI 1.247-2.562, p = 0.002), diabetes (HR 1.909, 95% CI 1.358-2.683, p < 0.001), heart failure (HR 2.203, 95% CI 1.527-3.178, p < 0.001), and coronary artery disease (HR 1.862, 95% CI 1.293-2.681, p = 0.001) were associated to MACE. This association was even stronger for AHREs ≥ 24h (HR 2.390, 95% CI 1.481-3.857, p < 0.001). Patients implanted with CIEDs developing AHREs show a significant risk for MACE, which is dependent on AHREs burden. Cardiovascular prevention strategies in this patient population are warranted.

Does the CHA2DS2-VASc score reliably predict atrial arrhythmias? Analysis of a nationwide database of remote monitoring data transmitted daily from cardiac implantable electronic devices

CHA2DS2-VASc is a validated score for predicting stroke in patients with atrial fibrillation (AF). The purpose of this study was to assess whether the CHA2DS2-VASc score can predict new-onset AF in a cohort of patients with a cardiac implantable electronic device (CIED) followed with remote monitoring. Using the database of the Home Monitoring Expert Alliance project, we selected 2410 patients with no documented AF who had received a CIED with diagnostics on atrial high rate episodes (AHREs). The primary endpoint was time to first day with cumulative AHRE burden ≥15 minutes, 5 hours, 24 hours, and ≥7 consecutive days. During a median duration of 24.1(11.5-42.9) months, the incidence of AHRE increased with increasing CHA2DS2-VASc. At 6 years, occurrence of ≥15-minute AHRE was 80.2% (CHA2DS2-VASc ≤1) vs 93.7% (CHA2DS2-VASc ≥5), whereas ≥5-hour AHRE incidence was 68.4% (CHA2DS2-VASc ≤1) vs 92.5% (CHA2DS2-VASc ≥5). Occurrence of ≥24-hour and ≥7-day AHREs also increased with increasing CHA2DS2-VASc: 9.1% and 3.9% (CHA2DS2-VASc ≤1) vs 40.4% and 28.7% (CHA2DS2-VASc ≥5), respectively. Adjusted hazard ratio for unitary CHA2DS2-VASc increase ranged from 1.09 (confidence interval 1.04-1.14; P<.001) with AHRE burden ≥15 minutes to 1.26 (confidence interval 1.11-1.42; P <.001) with AHRE burden ≥7 days. At receiver operating curve analysis, CHA2DS2-VASc ≥2 was estimated to predict persistent forms of AHREs with 95.8% sensitivity but 11.7% specificity at 3 years. CHA2DS2-VASc ≥5 had 77.0% specificity but 34.6% sensitivity. In a CIED population with no previous diagnosis of clinical AF, AHRE incidence increased with increasing CHA2DS2-VASc score. The association was stronger with longer AHREs, but the accuracy of CHA2DS2-VASc as AHRE predictor was moderate.

Burden of atrial high-rate episodes and risk of stroke: a systematic review.

Atrial fibrillation (AF) patients have increased risk of stroke. In paroxysmal AF, the combination of duration and frequency of episodes defines AF burden. In patients with cardiac implantable electronic devices (CIEDs), atrial high-rate episodes (AHREs) can be monitored continuously and are considered as a proxy for AF. This systematic review aims to determine the relationship between AF burden and risk of thrombo-embolic events (TBEs). We searched Medline, Embase, PubMed, and Cochrane Library databases and performed a review and meta-analysis. Eligible studies reported rhythm registration with specified AF burden and 3 months of follow-up for TBEs. Of the 8849 identified publications, 7 met the inclusion criteria. Of the 18943 included patients, 215 (1.1%) patients developed a TBE. We detected only studies registering AHRE with a duration over 5 min detected by CIED. In a meta-analysis, patients with an AHRE burden over 6 min had an increased risk of TBE when compared with patients without AHRE, but this risk did not increase for an AHRE burden over 6 h [hazard ratio (HR) 1.82 vs. 1.78]. In a second meta-analysis, only patients with AHRE burden over 24 h had an increased risk for stroke (HR 3.2, 95% confidence interval 1.75-5.86), while patients with an AHRE burden shorter than 24 h did not. Patients with an AHRE burden over 6 min have an increased risk for stroke. A trend in which a higher AHRE burden leads to a higher risk for TBEs was observed but not substantiated due to heterogeneity and low numbers.

Management of atrial high-rate episodes detected by cardiac implanted electronic devices.

Cardiac implanted electronic devices (CIEDs), including pacemakers and implantable defibrillators that perform atrial sensing typically using an atrial electrode, frequently detect subclinical atrial high-rate episodes (AHREs). When the intracardiac electrograms are carefully examined, the majority of AHREs are atrial fibrillation (AF) or other atrial tachyarrhythmias, which have been shown to be associated with both an increased risk of stroke, and subsequent development of clinical AF. However, the absolute risk of stroke among patients with AHREs is less than might be expected for clinically diagnosed paroxysmal AF. In addition, a close temporal relationship between AHREs and stroke is seen in only 15% of strokes in patients with a CIED: the majority have either no AHREs before the stroke, or AHREs very distant from incident stroke, suggesting that AHREs might be more of a risk marker than a risk factor for stroke. Management of AHREs should not be the same as for clinical AF, and a degree of uncertainty underpins the rationale for much-needed, ongoing, randomized trials of oral anticoagulation in patients with CIED-detected AHREs. We propose a management algorithm that takes into account both the stroke risk and the AHRE burden, but highlights the current uncertainty and evidence gaps for this condition.