Galectin-3, Inflammation, and the Risk of Atrial High-Rate Episodes in Patients with Dual Chamber Pacemakers.

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.

When to set anticoagulant therapy in asymptomatic AF? looking for a cut-off duration.

The incidence of atrial fibrillation (AF) is progressively increasing, in line with the aging of the population and with the increase in chronic diseases. The care burden of the disease and above all to its consequences (i.e. ischaemic stroke and heart failure) significantly impacts the various health systems with forecasts of exponential increase in the near future. Clinical forms of AF, i.e. those diagnosed with electrocardiogram, have a clear correlation with systemic embolic events and also with a reduction in survival. Thromboembolic prophylaxis in these patients, with anticoagulant drugs, has in fact been shown to greatly reduce the incidence of ischaemic stroke and improve survival. In recent decades, the widespread use of therapeutic intra-cardiac devices, which allow constant and continuous monitoring of myocardial electrical activity, is bringing to light a large number of atrial high rate episodes (AHREs), which are not associated with clinical manifestation. The incidence of these findings grows linearly with the duration of the observation. More independent studies have shown that AHREs are associated with a risk of stroke that is higher (about double) than controls but significantly lower than in patients with manifest AF. However, taking into consideration patients with ischaemic stroke and wearers of implantable devices, no temporal correlation emerged between the incidence of the ischaemic episode and arrhythmia. The presence of AHRE is associated with an approximately six-fold increase in the incidence of clinical AF but only a minority of these patients meet the criteria for prescribing anticoagulation. Pending the publication of the studies still in progress, the European Society of Cardiology guidelines for the treatment of AF recommend considering the initiation of anticoagulant therapy in patients with long-lasting AHRE (> 24 h) associated with a high embolic risk. In patients with episodes of shorter duration (1-24 h), especially if with high burden, anticoagulant therapy can be considered in case of very high embolic risk (e.g. secondary prevention, CHADVASc ≥ 3).

Time to benefit and harm of direct oral anticoagulants in device-detected atrial fibrillation: A pooled analysis of the NOAH-AFNET 6 and ARTESiA trials.

BACKGROUND: Direct oral anticoagulants (DOACs) reduce stroke risk in patients with device-detected atrial fibrillation (DD-AFib) but increase major bleeding risk. The time to benefit (TTB) and time to harm (TTH) are not well quantified. OBJECTIVE: The purpose of this study was to determine TTB and TTH in DOACs-treated patients with DD-AFib. METHODS: Studies were identified from PubMed searching until November 2023. The primary efficacy outcome was the time to the first stroke event, and the primary safety outcome was the time to the first major bleeding event. Pooled hazard ratio (HR) and its confidence interval (CI) were calculated through reconstructed patient-level data and study-level data. Weibull model and Markov chain Monte Carlo simulation were applied to determine time to specific absolute risk change thresholds. RESULTS: Two trials involving DOACs-NOAH-AFNET 6 (Non-vitamin K antagonist Oral anticoagulants in patients with Atrial High rate episodes) and ARTESiA (Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation)-were identified, which randomized 6548 adults with a mean age of >75 years and a median atrial high-rate episode duration ranging from 1.5 to 2.8 hours. DOACs decreased the risk of stroke (HR 0.67; 95% CI 0.50-0.90) but increased the risk of major bleeding (HR 1.57; 95% CI 1.21-2.04). A TTB of 2.67 years was needed to prevent 1 stroke per 100 DOACs-treated patients, while a TTH of 1.67 years was needed to observe 1 major bleeding. CONCLUSION: In elderly patients with low durations of DD-AFib, DOACs result in a delayed and restricted stroke-preventive benefit while posing an early-onset bleeding risk. Our findings offer new insights into the risk-benefit profile and provide clinicians an additional dimension to facilitate shared decision-making discussions with patients.

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

BACKGROUND: Patients with atrial high-rate episodes (AHREs) are at higher risk of thromboembolic events and mortality. The risk of major adverse cardiovascular events (MACE) in these patients is unknown. OBJECTIVE: 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 ≥ 5 min. AHRE was defined as > 175 bpm and lasting ≥ 5 min. We also performed a subgroup analysis in patients with the longest AHRE lasting ≥ 24 h. Cox regression analysis with time-dependent covariates was used to investigate the relationship between AHREs and MACEs. Mean age was 70.0 ± 13.6 years, and 39.3% were women: 325 patients developed AHREs ≥ 5 min [incidence rate (IR) 13.1% year 95% confidence interval (CI) 11.7-14.6] and 124 patients developed AHREs ≥ 24 h (IR 3.7%/year 95% CI 3.1-4.5). During a median follow-up of 37.0 months (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 ≥ 24 h (IR 1.13%/year) than AHREs ≥ 5 min (IR 0.63%/year, p = 0.030). Multivariable Cox regression analysis showed that AHREs ≥ 5 min (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 ≥ 24 h (HR 2.390, 95% CI 1.481-3.857, p < 0.001). CONCLUSIONS: 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.

Prevalence of atrial high-rate episodes and the risk factors in Indian patients with cardiac implantable electronic devices: Real-world data.

BACKGROUND: In patients with cardiac implantable electronic devices (CIEDs), atrial high-rate episodes (AHREs) are associated with an increased risk of developing atrial fibrillation (AF) and thromboembolism. We report here the characteristics of "real-world" patients that may be associated with the occurrence of AHREs. METHODS: This was an observational, cross-sectional, data collection study. Data of 234 patients with dual-chamber CIEDs, who visited our clinic over a period of 3 months, were evaluated. Occurrence of AHRE was defined as atrial tachyarrhythmia with an atrial rate of ≥180 beats/min lasting for ≥5 minutes. Multivariate logistic regression analyses were performed to evaluate clinical risk factors associated with AHRE. RESULTS: The mean age of the group was 66.9 ± 9.95 years, and 25% were females. AHREs were recorded in 48 (21%) patients. Multivariate logistic regression analysis revealed that hypertension (HTN) (OR = 4.14; 95% CI: 1.74-9.85; P = .0013) and type II diabetes mellitus (T2DM) (OR = 2.09; 95% CI: 1.04-4.23; P = .0392) were significantly and independently associated with the occurrence of AHRE. CONCLUSION: This real-world data report the prevalence of and risk factors associated with AHRE occurrence in Indian patients with dual-chamber CIED. Known risk factors for AF, such as HTN and diabetes mellitus, were also associated with AHRE occurrence, thus supporting the risk prediction for AF, stroke, or thromboembolism in such patient population.

Inflammation and the risk of atrial high-rate episodes (AHREs) in patients with cardiac implantable electronic devices.

INTRODUCTION: Atrial high-rate episodes (AHREs) are associated with an increased risk of developing atrial fibrillation and thromboembolism. The characteristics of 'real world' patients developing AHREs are poorly known. METHODS: We included 496 consecutive patients with cardiac implantable electronic devices (CIEDs). Primary endpoint was occurrence of AHREs, defined as > 175 bpm and lasting > 5 min, in a median follow-up of 16.5 (IQR 3.9-38.6) months (1082.4 patient-years). We also tested the predictive value of clinical risk scores for AHREs. RESULTS: Mean age was 68.8 ± 14.0 years, and 35.5% were women; AHREs were recorded in 173 patients [34.7%, 16.0%/year, 95% confidence interval (CI) 13.7-18.6]. Multivariable Cox regression analysis showed that age [hazard ratio (HR) 1.020, 95% CI 1.004-1.035, p = 0.011], prior AF (HR 3.521, 95% CI 2.831-5.206, p < 0.001), white cell count (HR 1.039, 95% CI 1.007-1.072, p = 0.016) and high C reactive protein (CRP; HR 1.039, 95% CI 1.021-2.056, p = 0.038) were independently associated with AHREs. ROC curve analysis showed that the APPLE score (C statistic 0.53, 95% CI 0.48-0.59; p = 0.296) ALARMEc score (C statistic 0.51, 95% CI 0.44-0.57; p = 0.810) were non-significantly associated with AHRE. Similar results were obtained for CHADS2 and CHA2DS2VASc score CONCLUSION: AHREs are common in CIEDs patients, with age, prior AF, inflammatory markers (high CRP, white cell count) being factors associated with AHREs onset. Clinical risk scores showed limited value for AHREs prediction in this cohort.

How to recognize silent atrial fibrillation in pacemakers and defibrillators-the value of atrial electrograms.

Today's pacemakers and defibrillators include diagnostic tools for detecting and treating cardiac arrhythmias like silent atrial fibrillation as atrial high rate episodes (AHREs). This diagnostic capability is crucial to prevent the potential embolic complications this AHREs are related to. However, sometimes data retrieved from diagnostic counters may be misleading reflecting limitations of detection algorithms, which must follow mathematical rules to classify events on a beat-to-beat basis. The incorporation of stored electrograms has been an important milestone in improving the diagnostic capabilities of these devices confirming the arrhythmia diagnosis.