Association of left pulmonary vein trunk and subclinical atrial fibrillation in patients with cardiac implantable electronic device.

The relationship between subclinical atrial fibrillation (SCAF) and left pulmonary vein anatomy is unknown. This study sought to investigate whether left pulmonary vein trunk predict the development of SCAF in patients with cardiac implantable electronic device (CIED). We also examined the relationship between the duration of SCAF and left pulmonary vein trunk. We retrospectively enrolled 162 patients who underwent implantation of dual-chamber CIEDs and follow-up by remote monitoring system. Computed tomography was used to measure the length of the left pulmonary vein. During median follow up of 2.7 years, the episodes of > 6 min and > 24 h SCAF were observed in 61 (37.7%) and 24 (14.8%) patients, respectively. The diagnosis of sinus node disease (HR: 3.66 [2.06-6.52], P < 0.01 and HR: 2.68 [1.09-6.62], P = 0.04) and left atrial diameter (HR: 1.04 [1.00-1.07], P = 0.04 and HR: 1.05 [1.00-1.10], P = 0.04) were independent predictors for > 6 min and > 24 h SCAF, respectively. Length of the left pulmonary vein trunk was an independent predictor for > 6 min SCAF (HR: 1.06 [1.02-1.10], P < 0.01), but not for > 24 h SCAF (P = 0.06). Sinus node disease, size of the left atrium and length of the left pulmonary vein trunk were related to SCAF. The left pulmonary vein trunk might especially contribute as a trigger rather than as a driver of development of atrial fibrillation.

Management of atrial arrhythmias identified by cardiac devices.

Implantable cardiac devices have shown that atrial fibrillation (AF) is more frequent than previously assumed, with subclinical, asymptomatic, self-limiting manifestations called atrial high-rate events (AHREs) or subclinical AF. The clinical significance and correct therapeutic management of these episodes of subclinical AF is less well defined than in the case of clinically manifest AF. Two important randomized studies on the topic have recently been published, NOAH-AFNET 6 and ARTESIA, which, however, have not definitively clarified the topic. In patients with AHRE or subclinical AF, the average thrombo-embolic risk is lower than that in patients with clinically manifest AF and is ∼1%. For this reason, in these patients, the possibility that the benefit of anticoagulant therapy is overshadowed by the risk of bleeding is very high. Therefore, while waiting for new tools that allow a better stratification of low-risk patients, we must rely on individual clinical evaluation and overcome the qualitative dichotomy (AHRE yes vs. AHRE no), preferring instead an approach that is as quantitative as possible and takes into account the number of episodes, their duration, and the patient's CHADSVASC score, before deciding, in each individual case, whether or not to use anticoagulant therapy.

Direct oral anticoagulants for stroke prevention in patients with device-detected atrial fibrillation: assessing net clinical benefit.

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.

Atrial Fibrillation Burden: Impact on Stroke Risk and Beyond.

Atrial fibrillation (AF) is an important independent risk factor for stroke. Current guidelines handle AF as a binary entity with risk driven by the presence of clinical risk factors, which guides the decision to treat with an oral anticoagulant. Recent studies in the literature suggest a dose-response relationship between AF burden and stroke risk, in both clinical AF and subclinical atrial fibrillation (SCAF), which differs from current guidance to disregard burden and utilize clinical risk scores alone. Within clinical classification and at the same risk levels in various scores, the risk of stroke increases with AF burden. This opens the possibility of incorporating burden into risk profiles, which has already shown promise. Long-term rhythm monitoring is needed to elucidate SCAF in patients with stroke. Recent data from randomized trials are controversial regarding whether there is an independent risk from AF episodes with a duration of less than 24 h, including the duration of SCAF greater than six minutes but less than 24 h.

[Tactics of anticoagulant therapy in patients with cardiac implantable electronic devices and subclinical atrial fibrillation: A review].

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.

Prediction of occult atrial fibrillation in patients after cryptogenic stroke and transient ischaemic attack: PROACTIA.

AIMS: Studies with implantable cardiac monitors (ICMs) show that one-third of patients with cryptogenic stroke/transient ischaemic attack (TIA) have episodes of subclinical atrial fibrillation (SCAF) and benefit switching from antiplatelet- to anticoagulant therapy. However, ICMs are costly and resource demanding. We aimed to build a score based on participant's baseline characteristics that could assess individual risk of SCAF. METHODS AND RESULTS: In a prospective study, 236 eligible patients with a final diagnosis of cryptogenic stroke/TIA had an ICM implantated during the index hospitalization. Pre-specified evaluated variables were: CHA2DS2-VASc, P-wave duration, P-wave morphology, premature atrial beats (PAC)/24 h, supraventricular tachycardia/24 h, left atrial end-systolic volume index (LAVI), Troponin-T, NT-proBNP, and D-dimer. SCAF was detected in 84 patients (36%). All pre-specified variables were significantly associated with SCAF detection in univariate analysis. P-wave duration, followed by PAC/24 h, NT-proBNP, and LAVI, had the largest ratio of SCAF prevalence between its upper and lower quartiles (3.3, vs. 3.2, vs. 3.1 vs. 2.8, respectively). However, in a multivariate analysis, only PAC/24t, P-wave duration, P-wave morphology, and LAVIs remained significant predictors and were included in the PROACTIA score. Subclinical atrial fibrillation prevalence was 75% in the highest vs. 10% in the lowest quartile of the PROACTIA score with a 10-fold higher number of patients with an atrial fibrillation burden >6 h in the highest vs. the lowest quartile. CONCLUSION: The PROACTIA score can identify patients with cryptogenic stroke/TIA at risk of subsequent SCAF detection. The large difference in SCAF prevalence between groups may provide a basis for future tailored therapy. CLINICAL TRIAL REGISTRATION: Clinical Trial Registration: ClinicalTrials.gov; NCT02725944.

Circulating biomarkers, echocardiographic parameters, and incident subclinical atrial fibrillation in patients with diabetes and hypertension.

BACKGROUND: Long-term rhythm monitoring (LTRM) can detect undiagnosed atrial fibrillation (AF) in patients at high risk of AF and stroke. Biomarkers and echocardiographic parameters could, however, help identify patients benefitting most from LTRM. The aim of this study was to investigate, whether circulating biomarkers of cardiac and vascular function (brain natriuretic peptide (BNP), cardiac troponin I (cTnI), copeptin, and mid-regional proadrenomedullin (MR-proADM)) and echocardiographic parameters were associated with incident subclinical AF (SCAF) in a population at high risk of stroke in the presence of AF. For this purpose, we investigated individuals ≥65 years of age with hypertension and diabetes mellitus, but no history or symptoms of AF or other cardiovascular disease (CVD). METHODS: We included 82 consecutive patients (median age 71.3 years (IQR 67.4-75.1)). All patients received an insertable cardiac monitor (ICM) and were followed for a median of 588 days (IQR 453-712). On the day of ICM implantation, a comprehensive echocardiogram and blood samples were obtained. RESULTS: During a median follow-up of 588 days (IQR: 453-712 days), incident SCAF occurred in 17 patients (20.7%) with a median time to first-detected episode of 91 days (IQR 41-251 days). MR-proADM (median 0.87 nmol/L (IQR 0.76-1.02) vs 0.78 nmol/L (IQR 0.68-0.98)) and copeptin (median 13 pmol/L (IQR 9-17) vs 8 pmol/L (IQR 4-18)) levels were insignificantly higher in patients with incident SCAF. BNP and cTnI concentrations and echocardiographic parameters were similar in the two groups. CONCLUSIONS: MR-proADM, BNP, cTnI, copeptin, and several echocardiographic parameters were not associated with incident SCAF in this cohort of patients with hypertension and diabetes, but without any underlying CVD.

Real-world performance of the atrial fibrillation monitor in patients with a subcutaneous ICD.

INTRODUCTION: The third-generation subcutaneous implantable cardioverter-defibrillator (S-ICD) (EMBLEM™ A219, Boston Scientific) contains a new diagnostic tool to detect atrial fibrillation (AF) in S-ICD patients, without the use of an intracardiac lead. This is the first study to evaluate the performance of the S-ICD AF monitor (AFM). METHODS: The AFM algorithm analyzes a subcutaneous signal for the presence of AF, similar to the signals collected by implantable and wearable diagnostic devices. The AFM algorithm combines heart rate (HR) scatter analysis with an HR histogram. The algorithm was tested against publicly available electrocardiogram databases (simulated performance). Real-world performance of the algorithm was evaluated by using the S-ICD LATITUDE remote monitoring (RM) database. RESULTS: The simulated performance of the AFM algorithm resulted in a sensitivity of 95.0%, specificity of 100.0%, and positive predictive value (PPV) of 100.0%. To evaluate the real-world performance of the AFM, 7744 S-ICD devices were followed for up to 30 months by RM, whereof 99.5% had the AFM enabled. A total of 387 AF episodes were randomly chosen for adjudication, resulting in a PPV of 67.7%. The main cause of misclassification was atrial and ventricular ectopy. CONCLUSION: The AFM exhibited a very high sensitivity and specificity in a simulated setting, designed to maximize PPV in order to minimize the clinical burden of reviewing falsely detected AF events. The real-world performance of the AFM, enabled in 99.5% of S-ICD patients, is a PPV of 67.7%.

What do we do about atrial high rate episodes?

Atrial high rate episodes (AHREs) are defined as asymptomatic atrial tachyarrhythmias detected by cardiac implantable electronic devices with atrial sensing, providing automated continuous monitoring and tracings storage, occurring in subjects with no previous clinical atrial fibrillation (AF) and with no AF detected at conventional electrocardiogram recordings. AHREs are associated with an increased thrombo-embolic risk, which is not negligible, although lower than that of clinical AF. The thrombo-embolic risk increases with increasing burden of AHREs, and moreover, AHREs burden shows a dynamic pattern, with tendency to progression along with time, with potential transition to clinical AF. The clinical management of AHREs, in particular with regard to prophylactic treatment with oral anticoagulants (OACs), remains uncertain and heterogeneous. At present, in patients with confirmed AHREs, as a result of device tracing analysis, an integrated, individual and clinically-guided assessment should be applied, taking into account the patients' risk of stroke (to be reassessed regularly) and the AHREs burden. The use of OACs, preferentially non-vitamin K antagonists OACs, may be justified in selected patients, such as those with longer AHREs durations (in the range of several hours or ≥24 h), with no doubts on AF diagnosis after device tracing analysis and with an estimated high/very high individual risk of stroke, accounting for the anticipated net clinical benefit, and informed patient's preferences. Two randomized clinical trials on this topic are currently ongoing and are likely to better define the role of anticoagulant therapy in patients with AHREs.

Subclinical atrial fibrillation detection with a floating atrial sensing dipole in single lead implantable cardioverter-defibrillator systems: Results of the SENSE trial.

INTRODUCTION: Subclinical atrial fibrillation (AF), in the form of cardiac implantable device-detected atrial high rate episodes (AHREs), has been associated with increased thromboembolism. An implantable cardioverter-defibrillator (ICD) lead with a floating atrial dipole may permit a single lead (DX) ICD system to detect AHREs. We sought to assess the utility of the DX ICD system for subclinical AF detection in patients, with a prospective multicenter, cohort-controlled trial. METHODS AND RESULTS: One hundred fifty patients without prior history of AF (age 59 ± 13 years; 108 [72%] male) were enrolled into the DX cohort and implanted with a Biotronik DX ICD system at eight centers. Age-, sex-, and left ventricular ejection fraction-matched single- and dual-chamber ICD cohorts were derived from a Cornell database and from the IMPACT trial, respectively. The primary endpoint were AHRE detection at 12 months. During median 12 months follow-up, AHREs were detected in 19 (13%) patients in the DX, 8 (5.3%) in the single-chamber, and 19 (13%) in the dual-chamber cohorts. The rate of AHRE detection was significantly higher in the DX cohort compared to the single-chamber cohort (P = .026), but not significantly different compared to the dual-chamber cohort. There were no inappropriate ICD therapies in the DX cohort. At 12 months, only 3.0% of patients in the DX cohort had sensed atrial amplitudes less than 1.0 mV. CONCLUSION: Use of a DX ICD lead allows subclinical AF detection with a single lead DX system that is superior to that of a conventional single-chamber ICD system.

Wearable and implantable diagnostic monitors in early assessment of atrial tachyarrhythmia burden.

Atrial fibrillation (AF) is the cause of substantial direct patient morbidity and a frequent cause of emergency room visits. Even when asymptomatic, AF remains a major cause of stroke, particularly among the elderly. As the risk of both AF and stroke increase with age, the importance of AF-related stroke is growing as a result of demographic shifts in many countries. Oral anticoagulation is highly effective at preventing stroke due to AF; however, AF remains undetected in a large number of individuals. The last decade has witnessed the development of many new technologies to detect AF. Screening studies using single-time point or repeated discrete screening methods have uncovered previously undiagnosed AF in 1-3% of asymptomatic individuals. However, continuous monitoring with implanted devices demonstrates short-lasting AF in over one-third of older individuals with cardiovascular risk factors. Debate remains regarding the minimum burden of AF that is associated with an increase in stroke risk, and the threshold for using oral anticoagulation. Over the next 5 years, ongoing studies will help clarify how wearable and implantable technology can be used to improve outcomes in patients with previously unrecognized AF.

Clinical Impact of Oral Anticoagulation in Patients with Atrial High-rate Episodes.

BACKGROUND: Atrial high-rate episodes (AHREs) are common in pacemaker patients. Our aims were to compare patients with AHREs to those without them and to assess if, in those with AHREs, the initiation of oral anticoagulation (OAC) has any clinical impact on the occurrence of ischemic and hemorrhagic events. METHODS: From 2014-2017 we selected patients with pacemaker in whom AHREs were detected. AHREs were defined as episodes lasting more than 6 minutes if the electrogram was available or more than 6 hours if not. We used an age- and gender-matched population with pacemaker but no AHRE as a control group (observational study). Those with AHRE were referred to their assistant physician to decide OAC initiation, based on individual circumstances (interventional study). In interventional study, the primary outcome was a composite of systemic thromboembolism or major bleeding. Secondary outcomes were clinical relevant nonmajor bleeding, major and nonmajor bleeding, CV death, and death from all causes. RESULTS: AHREs were detected in 86 patients: 69 patients initiated OAC and the remaining 17 patients did not. When comparing patients with and without AHRE, baseline characteristics were not different between the groups, except for indexed left atrium volume-40 mL (IQR: 34-50) in AHRE group versus 35 mL (IQR: 34-40) in control group (P = .014). AHREs were associated with future development of atrial fibrillation (AF) and the risk was higher if AHRE duration was superior to 6 hours. Death and cardiovascular (CV) death were not significantly different between the groups with and without AHRE. Primary outcome occurred in 4.9 per 100 person-year in OAC group versus 3.4 per 100 person-year in non-OAC group (HR 1.4, 95% CI .2-11.3, P = .78). Secondary outcomes were not significantly different in the groups. CONCLUSIONS: In this group of patients with pacemakers, the presence of AHREs was useful for predicting the future development of AF and the risk of AF was higher in those with a longer duration of AHRE. In the AHRE group, OAC therapy was not associated with a significant difference in the risk of thromboembolism or major bleeding.

Subclinical Atrial Fibrillation and Risk of Stroke: Past, Present and Future.

Subclinical atrial fibrillation (SCAF) describes asymptomatic episodes of atrial fibrillation (AF) that are detected by cardiac implantable electronic devices (CIED). The increased utilization of CIEDs renders our understanding of SCAF important to clinical practice. Furthermore, 20% of AF present initially as a stroke event and prolonged cardiac monitoring of stroke patients is likely to uncover a significant prevalence of SCAF. New evidence has shown that implanting cardiac monitors into patients with no history of atrial fibrillation but with risk factors for stroke will yield an incidence of SCAF approaching 30-40% at around three years. Atrial high rate episodes lasting longer than five minutes are likely to represent SCAF. SCAF has been associated with an increased risk of stroke that is particularly significant when episodes of SCAF are greater than 23 h in duration. Longer episodes of SCAF are incrementally more likely to progress to episodes of SCAF >23 h as time progresses. While only around 30-40% of SCAF events are temporally related to stroke events, the presence of SCAF likely represents an important risk marker for stroke. Ongoing trials of anticoagulation in patients with SCAF durations less than 24 h will inform clinical practice and are highly anticipated. Further studies are needed to clarify the association between SCAF and clinical outcomes as well as the factors that modify this association.

Subclinical and Asymptomatic Atrial Fibrillation: Current Evidence and Unsolved Questions in Clinical Practice.

Atrial Fibrillation (AF) may be diagnosed due to symptoms, or it may be found as an incidental electrocardiogram (ECG) finding, or by implanted devices recordings in asymptomatic patients. While anticoagulation, according to individual risk profile, has proven definitely beneficial in terms of prognosis, rhythm control strategies only demonstrated consistent benefits in terms of quality of life. In fact, evidence collected by observational data showed significant benefits in terms of mortality, stroke incidence, and prevention of cognitive impairment for patients referred to AF catheter ablation compared to those medically treated, however randomized trials failed to confirm such results. The aims of this review are to summarize current evidence regarding the treatment specifically of subclinical and asymptomatic AF, to discuss potential benefits of rhythm control therapy, and to highlight unclear areas.

Rationale and Design of the Evaluation of Oral Anticoagulation for Reduction of Thrombo-embolism in Chinese Patients with Device-Detected Subclinical Atrial Fibrillation (ART-CAF) Trial: an Open-Label Registry-Based Clinical Trial.

PURPOSE: Subclinical atrial fibrillation (AF) was found in a large number of pacemaker patients. It is not certain whether there is a similar risk/benefit ratio for oral anticoagulation in patients with subclinical AF compared to patients with similar risk profiles and clinically diagnosed AF. Given the weakness of clinical evidence for oral anticoagulation in patients with device-detected subclinical AF, specific recommendations in most guidelines for this population are scarce and rarely similar. METHODS: ART-CAF trial was primarily designed to evaluate the efficacy and safety of oral anticoagulant agent use in patients with device-detected subclinical AF at the approved dosage to prevent stroke and systemic arterial embolism. It is an open-label, registry-based, prospective, multicenter, cohort study, recruiting patients with subclinical AF first detected by a pacemaker, implantable cardioverter-defibrillator, or insertable cardiac monitor after device implantation for more than 3 months. The primary outcome is a composite of ischemic stroke and systemic arterial embolism. The primary safety outcome is the occurrence of clinically overt major bleeding. Approximately 750 patients will be needed to be enrolled to the two treatment groups in a 1:1 ratio until 66 primary efficacy outcomes are observed. The anticipated follow-up period is approximately 70 months from the enrollment of the first patient. CONCLUSIONS: ART-CAF evaluates the feasibility of selecting high-risk patients suitable for anticoagulation by AF burden combined with CHA2DS2-VASc score after pacemaker implantation and aims to select patients who could benefit from anticoagulation. TRIAL REGISTRATION: http://www.chictr.org.cn/index.aspx ChiCTR1800016221.

Incidence of subclinical atrial fibrillation in a South Asian population.

BACKGROUND: South Asians have a lower prevalence of atrial fibrillation (AF) compared with Caucasians despite higher rates of conventional risk factors and a higher incidence of stroke. It is not clear whether South Asians truly experience less AF or whether this is due to underdetection of the arrhythmia. Therefore, we aimed to determine whether South Asian patients with pacemakers have a lower incidence of device-detected subclinical episodes of AF compared with Caucasian controls. METHODS: We performed a retrospective cohort study of South Asian and Caucasian patients who underwent pacemaker implantation between 2006 and 2016. Subclinical AF episodes, detected during subsequent device clinic follow-up visits, were identified and the occurrence of clinical AF, cerebrovascular events, and all-cause mortality was recorded. RESULTS: A total of 5 648 patients underwent pacemaker implantation at the Yorkshire Heart Centre, UK, during the study period. Of these, 169 were South Asian and 72 met the eligibility criteria. The cumulative incidence of subclinical AF was significantly lower in South Asians compared with Caucasians (logrank P  =  0.002) with an annual event rate of 6.9% versus 13.9%, and South Asian ethnicity was an independent predictor of a lower incidence of subclinical AF (odds ratio =  0.43; 95% confidence interval  =  1.01-5.38). CONCLUSIONS: South Asians with an implanted pacemaker have a lower rate of subclinical AF compared with Caucasians.

Silent atrial fibrillation in patients with an implantable cardioverter defibrillator and coronary artery disease (INDICO AF) trial: study rationale and design.

BACKGROUND: Timely detection of atrial fibrillation (AF) in implantable cardioverter defibrillator (ICD) patients is clinically important for prevention of AF-related complications and inappropriate shocks. Patients with coronary artery disease (CAD) and a dual or triple chamber ICD show a high incidence of device-detected AF. Whether CAD patients with a single chamber ICD carry a similar risk for device-detected AF remains unknown. STUDY DESIGN: The INDICO AF trial is an investigator-initiated, multicentre, observational study evaluating the incidence of subclinical AF (SCAF) in CAD patients who will receive a single chamber ICD as primary prevention for sudden cardiac death (SCD). Fifty patients will receive a single chamber ICD with an integrated RR interval based AF detection algorithm. In combination with remote monitoring, rhythm data will be collected monthly. The primary endpoint is the incidence of SCAF at 1 year of follow-up; secondary endpoints include time until 10 and 20% of the patients have a first episode of SCAF. All patients in whom SCAF is detected will be invited for an outpatient visit and will receive adequate anticoagulation treatment when appropriate according to the CHA2DS2-VASc score and current guidelines. CONCLUSION: The INDICO AF trial will quantify the incidence of SCAF in patients with an ICD and CAD. The study will underscore the clinical value of SCAF detection in single chamber ICD patients using remote patient monitoring and may improve patient care. This trial is registered at trialregister.nl with trial NTR6910.

Atrial high-rate episodes and stroke prevention.

While the benefit of oral anticoagulants (OACs) for stroke prevention in patients with atrial fibrillation (AF) is well established, it is not known whether oral anticoagulation is indicated in patients with atrial high-rate episodes (AHRE) recorded on a cardiac implantable electronic device, sometimes also called subclinical AF, and lasting for at least 6 min in the absence of clinically diagnosed AF. Clinical evidence has shown that short episodes of rapid atrial tachycarrhythmias are often detected in patients presenting with stroke and transient ischaemic attack. Patients with AHRE have a higher likelihood of suffering from subsequent strokes, but their stroke rate seems lower than in patients with diagnosed AF, and not all AHRE episodes correspond to AF. The prognostic and pathological significance of AHRE is not yet fully understood. Clinical trials of OAC therapy are being conducted to determine whether therapeutic intervention would be beneficial to patients experiencing AHRE in terms of reducing the risk of stroke.