Atrial High-Rate Episodes and Subclinical Atrial Fibrillation: State of the Art and Clinical Questions with Complex Solutions.

Atrial high-rate episodes (AHREs) and subclinical atrial fibrillation (AF) are frequently registered in asymptomatic patients with cardiac implantable electronic devices (CIEDs) and insertable cardiac monitors (ICMs). While an increased risk of thromboembolic events (e.g., stroke) and benefits from anticoagulation have been widely assessed in the setting of clinical AF, concerns persist about optimal clinical management of subclinical AF/AHREs. As a matter of fact, an optimal threshold of subclinical episodes' duration to predict stroke risk is still lacking and recently published randomized clinical trials assessing the impact of anticoagulation on thromboembolic events in this specific setting have shown contrasting results. The aim of this review is to summarize current evidence regarding classification and clinical impact of subclinical AF/AHREs and to discuss the latest evidence regarding the potential benefit of anticoagulation in this setting, highlighting which clinical questions are still unanswered.

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.

Apixaban vs Aspirin According to CHA2DS2-VASc Score in Subclinical Atrial Fibrillation: Insights From ARTESiA.

BACKGROUND: ARTESiA (Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation) demonstrated that apixaban, compared with aspirin, significantly reduced stroke and systemic embolism (SE) but increased major bleeding in patients with subclinical atrial fibrillation. OBJECTIVES: To help inform decision making, the authors evaluated the efficacy and safety of apixaban according to baseline CHA2DS2-VASc score. METHODS: We performed a subgroup analysis according to baseline CHA2DS2-VASc score and assessed both the relative and absolute differences in stroke/SE and major bleeding. RESULTS: Baseline CHA2DS2-VASc scores were <4 in 1,578 (39.4%) patients, 4 in 1,349 (33.6%), and >4 in 1,085 (27.0%). For patients with CHA2DS2-VASc >4, the rate of stroke was 0.98%/year with apixaban and 2.25%/year with aspirin; compared with aspirin, apixaban prevented 1.28 (95% CI: 0.43-2.12) strokes/SE per 100 patient-years and caused 0.68 (95% CI: -0.23 to 1.57) major bleeds. For CHA2DS2-VASc <4, the stroke/SE rate was 0.85%/year with apixaban and 0.97%/year with aspirin. Apixaban prevented 0.12 (95% CI: -0.38 to 0.62) strokes/SE per 100 patient-years and caused 0.33 (95% CI: -0.27 to 0.92) major bleeds. For patients with CHA2DS2-VASc =4, apixaban prevented 0.32 (95% CI: -0.16 to 0.79) strokes/SE per 100 patient-years and caused 0.28 (95% CI: -0.30 to 0.86) major bleeds. CONCLUSIONS: One in 4 patients in ARTESiA with subclinical atrial fibrillation had a CHA2DS2-VASc score >4 and a stroke/SE risk of 2.2% per year. For these patients, the benefits of treatment with apixaban in preventing stroke/SE are greater than the risks. The opposite is true for patients with CHA2DS2-VASc score <4. A substantial intermediate group (CHA2DS2-VASc =4) exists in which patient preferences will inform treatment decisions. (Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation; NCT01938248).

Outcomes of Device-detected Atrial High-rate Episodes in Patients with No Prior History of Atrial Fibrillation: A Systematic Review and Meta-analysis.

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.

Subclinical Atrial Fibrillation: To Anticoagulate or Not?

Atrial fibrillation (AF) carries a stroke risk, often necessitating anticoagulation, especially in patients with risk factors. With the advent of implantable and wearable heart monitors, episodes of short bouts of atrial arrhythmias called atrial high-rate episodes (AHREs) or subclinical AF (SCAF) are commonly identified. The necessity of anticoagulation in patients with SCAF is unclear. However, recent randomized controlled trials, the NOAH-AFNET 6 and ARTESIA, have offered insights into this matter. Furthermore, a study-level meta-analysis combining data from both these trials has provided more detailed information. Reviewing the information thus far, we can conclude that DOACs can result in a notable reduction in the risk of ischemic stroke and can potentially decrease the risk of debilitating stroke, albeit with an increased risk of major bleeding. Thus, informed, shared decision-making is essential, weighing the potential benefits of stroke prevention against the risk of major bleeding when considering anticoagulation in this patient population.

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.

No Detectable Differences in microRNA Plasma Levels between Diabetic Hypertensive Patients with and without Incident Subclinical Atrial Fibrillation.

Background: Long-term rhythm monitoring (LTRM) can detect undiagnosed atrial fibrillation (AF) in patients at risk of AF and stroke. Circulating microRNAs (miRNAs), which have been shown to play a role in atrial electrical and structural remodelling, could help to select patients who would benefit most from LTRM. The aim of this study was to investigate whether patients with diabetes mellitus (DM) and hypertension and screen-detected subclinical AF (SCAF) using an insertable cardiac monitor (ICM) have significantly different plasma baseline levels of five selected miRNAs playing a role in the modulation of atrial electrical and structural remodelling (miR-21-5p, miR-29b-3p, miR-150-5p, miR-328-3p, and miR-432-5p) compared to those without SCAF. Methods: This study was performed at the outpatient clinic of a secondary academic teaching hospital between December 2013 and November 2015. Eligible patients were ≥65 years of age with DM and hypertension but without known heart diseases. All patients received an ICM. On the day of ICM implantation, blood samples for the measurement of plasma levels of the five miRNAs were drawn. In this post hoc analysis, we investigated their expression by reverse transcription-quantitative polymerase chain reaction. MiRNA plasma levels in patients with and without newly detected SCAF were compared. Results: We included 82 consecutive patients (median age of 71.3 years (IQR 67.4-75.1)), who were followed for a median of 588 days (IQR: 453-712 days). Seventeen patients (20.7%) had ICM-detected SCAF. Plasma levels of miR-328-3p, miR-29b-3p, miR-21-5p, miR-432-5p, and miR-150-5p were slightly but not significantly different in patients with incident SCAF compared with patients without. Conclusions: In patients with hypertension and DM, newly detected SCAF was not significantly associated with changes in expression levels of miR-21-5p, miR-29b-3p, miR-150-5p, miR-328-3p, and miR-432-5p.

Automatic 3D left atrial strain extraction framework on cardiac computed tomography.

BACKGROUND AND OBJECTIVE: Strain analysis provides insights into myocardial function and cardiac condition evaluation. However, the anatomical characteristics of left atrium (LA) inherently limit LA strain analysis when using echocardiography. Cardiac computed tomography (CT) with its superior spatial resolution, has become critical for in-depth evaluation of LA function. Recent studies have explored the feasibility of CT-derived strain; however, they relied on manually selected regions of interest (ROIs) and mainly focused on left ventricle (LV). This study aimed to propose a first-of-its-kind fully automatic deep learning (DL)-based framework for three-dimensional (3D) LA strain extraction on cardiac CT. METHODS: A total of 111 patients undergoing ECG-gated contrast-enhanced CT for evaluating subclinical atrial fibrillation (AF) were enrolled in this study. We developed a 3D strain extraction framework on cardiac CT images, containing a 2.5D GN-U-Net network for LA segmentation, axis-oriented 3D view extraction, and LA strain measure. The segmentation accuracy was evaluated using Dice similarity coefficient (DSC). The model-extracted LA volumes and emptying fraction (EF) were compared with ground-truth measurements using intraclass correlation coefficient (ICC), correlation coefficient (r), and Bland-Altman plot (B-A). The automatically extracted LA strains were evaluated against the LA strains measured from 2D echocardiograms. We utilized this framework to gauge the effect of AF burden on LA strain, employing the atrial high rate episode (AHRE) burden as the measurement parameter. RESULTS: The GN-U-Net LA segmentation network achieved a DSC score of 0.9603 on the test set. The framework-extracted LA estimates demonstrated excellent ICCs of 0.949 (95 % CI: 0.93-0.97) for minimal LA volume, 0.904 (95 % CI: 0.86-0.93) for maximal LA volume, and 0.902 (95 % CI: 0.86-0.93) for EF, compared with expert measurements. The framework-extracted LA strains demonstrated moderate agreement with the LA strains based on 2D echocardiography (ICCs >0.703). Patients with AHRE > 6 min had significantly lower global strain and LAEF, as extracted by the framework than those with AHRE ≤ 6 min. CONCLUSION: The promising results highlighted the feasibility and clinical usefulness of automatically extracting 3D LA strain from CT images using a DL-based framework. This tool could provide a 3D-based alternative to echocardiography for assessing LA function.

Thromboembolic risk and oral anticoagulation in subclinical atrial fibrillation.

Availability of devices capable of continuous rhythm monitoring such as smartwatches, implantable loop recorders, or pacemakers/defibrillators is continuously increasing. Importantly, device detected "subclinical" atrial fibrillation seems to convey a significantly lower risk of thromboembolism than "clinical" atrial fibrillation verified by a conventional ECG recording. While current guidelines indicate a possible role of oral anticoagulation in selected high-risk patients with subclinical AF, recent trials show an ambiguous risk/benefit relationship of anticoagulation in this setting. The present review therefore summarizes current data on the role of oral anticoagulation in subclinical AF, aims at aiding in the decision process of anticoagulation, and illustrates current gaps in evidence regarding subclinical AF.

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.

Anticoagulation-Associated Bleeding in Patients Screened for Atrial Fibrillation versus Usual Care-A Post Hoc Analysis from the LOOP Study.

Background Atrial fibrillation (AF) prevalence is rising; however, data on the bleeding risks associated with the detection of subclinical AF are needed. Objective Our objective was to determine the bleeding increment associated with implantable loop recorder (ILR) screening for subclinical AF and subsequent anticoagulation initiation compared with usual care. Methods This post hoc study utilized LOOP trial data from 6,004 elderly patients with stroke risks randomized to either ILR ( n = 1,503) or usual care ( n = 4,503). The mean follow-up time was 64.5 months, and none were lost to follow-up. The primary exposure was the initiation of oral anticoagulation, and the main outcome was the risk of major bleeding events following initiation of oral anticoagulants (OACs), determined by time-dependent cox regression. Second, we investigated antithrombotic prescription patterns and major bleeding events after antiplatelet treatment and in subgroups. Results OAC was initiated in 1,019 participants with a mean age (years) of 78.8 (± 4.67) in control versus 77.0 (± 4.84) in ILR, p < 0.0001. Altogether did 202 participants end or pause OAC treatment. Among AF patients (n = 910) had 40 (28%) completely ended OAC and 105 (72%) temporarily paused OAC during follow-up. Major bleeding events totaled 221 (3.7%). Forty-seven major bleeding events followed an OAC initiation in 1,019 participants (4.6%); 26 versus 21 events in the control and ILR groups, respectively. The hazard ratio (HR) for major bleeding after OAC initiation compared with before initiation was 2.08 (1.50-2.90) p < 0.0001 overall, 2.81 (1.82-4.34) p < 0.0001 for control and 1.32 (0.78-2.23) p = 0.31 for the ILR group ( p = 0.07 for interaction). Antiplatelet treatment resulted in an overall adjusted HR of 1.3 (0.96-1.75) p = 0.09. For OAC users aged ≥75 years in the ILR group, the rate of major bleeding was 1.73 (0.92-2.96) compared with 0.84 (0.36-1.66) for an age <75 years, and the rate of the corresponding control subgroup aged ≥75 years was 2.20 (1.23-3.63) compared with 1.64 (0.82-2.93) for an age <75 years. Conclusion The individual risk of major bleeding increased twofold after initiation of oral anticoagulation for all patients in this study. However, the patients screened for subclinical AF did not have a higher bleeding risk after initiation of anticoagulation compared with those in usual care. Trial Registration: The LOOP study is registered at ClinicalTrials.gov, identifier: NCT020364 50.

Prevalence of Subclinical Atrial Fibrillation in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Atrial fibrillation (AF) is common in patients with heart failure with preserved ejection fraction (HFpEF) and is associated with poorer clinical outcomes. The prevalence of subclinical AF in patients with HFpEF remains unknown. OBJECTIVES: The aim of this study was to determine whether subclinical AF was more prevalent in individuals with HFpEF than in individuals without histories of heart failure (HF). METHODS: Patients with HFpEF with no prior diagnoses of AF were screened for subclinical AF, and the prevalence of subclinical AF was compared with that among control subjects without HF drawn from MESA (Multi-Ethnic Study of Atherosclerosis) who underwent the same electrocardiographic monitoring. Multivariable logistic regression was used to adjust for demographic and clinical comorbidities. RESULTS: Ninety patients with HFpEF and 1,230 MESA participants were included. Patients with HFpEF were younger (median age 69 years [Q1-Q3: 63-76 years] vs 72 years [Q1-Q3: 66-80 years]; P = 0.02), more obese (median body mass index 36 kg/m2 [Q1-Q3: 30-45 kg/m2] vs 27 kg/m2 [Q1-Q3: 24-30 kg/m2]; P < 0.001), and more likely to have diabetes (34% vs 21%; P = 0.01). The prevalence of subclinical AF was 8.9% in patients with HFpEF and 4.1% in non-HF participants. After multivariable adjustment for age, sex, race, body mass index, diabetes, smoking, and total analyzable time on electrocardiographic monitor, there was a significantly higher odds of subclinical AF in patients with HFpEF compared with MESA (OR: 3.01; 95% CI: 1.13-7.99; P = 0.03). CONCLUSIONS: Patients with HFpEF had a higher prevalence of subclinical AF than participants without HF from a community-based study. Screening for atrial arrhythmias may be appropriate among patients with HFpEF for timely initiation of thromboembolic prophylaxis and may identify individuals at greater risk for clinical decompensation.

[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.

Left atrial appendage strain predicts subclinical atrial fibrillation in embolic strokes of undetermined source.

Aims: Left atrial (LA) strain is promising in prediction of clinical atrial fibrillation (AF) in stroke patients. However, prediction of subclinical AF is critical in patients with embolic strokes of undetermined source (ESUS). The aim of this prospective study was to investigate novel LA and left atrial appendage (LAA) strain markers in prediction of subclinical AF in ESUS patients. Methods and results: A total of 185 patients with ESUS, mean age 68 ± 13years, 33% female, without diagnosed AF, were included. LAA and LA function by conventional echocardiographic parameters and reservoir strain (Sr), conduit strain (Scd), contraction strain (Sct), and mechanical dispersion (MD) of Sr were assessed with transoesophageal and transthoracic echocardiography. Subclinical AF was detected by insertable cardiac monitors during follow-up. LAA strain was impaired in 60 (32%) patients with subclinical AF compared to those with sinus rhythm: LAA-Sr, 19.2 ± 4.5% vs. 25.6 ± 6.5% (P < 0.001); LAA-Scd, -11.0 ± 3.1% vs. -14.4 ± 4.5% (P < 0.001); and LAA-Sct, -7.9 ± 4.0% vs. -11.2 ± 4% (P < 0.001), respectively, while LAA-MD was increased, 34 ± 24 ms vs. 26 ± 20 ms (P = 0.02). However, there was no significant difference in phasic LA strain or LA-MD. By ROC analyses, LAA-Sr was highly significant in prediction of subclinical AF and showed the best AUC of 0.80 (95% CI 0.73-0.87) with a sensitivity of 80% and a specificity of 73% (P < 0.001). LAA-Sr and LAA-MD were both independent and incremental markers of subclinical AF in ESUS patients. Conclusion: LAA function by strain and mechanical dispersion predicted subclinical AF in ESUS patients. These novel echocardiographic markers may improve risk stratification in ESUS patients.

European Stroke Organisation (ESO) guideline on screening for subclinical atrial fibrillation after stroke or transient ischaemic attack of undetermined origin.

We aimed to provide practical recommendations for the screening of subclinical atrial fibrillation (AF) in patients with ischaemic stroke or transient ischaemic attack (TIA) of undetermined origin. These guidelines are based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. Five relevant Population, Intervention, Comparator, Outcome questions were defined by a multidisciplinary module working group (MWG). Longer duration of cardiac rhythm monitoring increases the detection of subclinical AF, but the optimal monitoring length is yet to be defined. We advise longer monitoring to increase the rate of anticoagulation, but whether longer monitoring improves clinical outcomes needs to be addressed. AF detection does not differ from in- or out-patient ECG-monitoring with similar monitoring duration, so we consider it reasonable to initiate in-hospital monitoring as soon as possible and continue with outpatient monitoring for more than 48 h. Although insertable loop recorders (ILR) increase AF detection based on their longer monitoring duration, comparison with non-implantable ECG devices for similar monitoring time is lacking. We suggest the use of implantable devices, if feasible, for AF detection instead of non-implantable devices to increase the detection of subclinical AF. There is weak evidence of a useful role for blood, ECG and brain imaging biomarkers for the identification of patients at high risk of AF. In patients with patent foramen ovale, we found insufficient evidence from RCT, but prolonged cardiac monitoring in patients >55 years is advisable for subclinical AF detection. To conclude, in adult patients with ischaemic stroke or TIA of undetermined origin, we recommend longer duration of cardiac rhythm monitoring of more than 48 h and if feasible with IRL to increase the detection of subclinical AF.

Epidemiology of subclinical atrial fibrillation in patients with cardiac implantable electronic devices: A systematic review and meta-regression.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 (R2=61.9%, p<0.001), with age and follow-up time non-linearly, directly and independently associated with occurrence of SCAF. Older age, higher CHA2DS2-VASc score, history of AF, hypertension, CHF, and stroke/TIA were all associated with SCAF occurrence. CONCLUSIONS: 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.

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.