High-risk Atrial Fibrillation Patients Research Articles

A targeted educational intervention increases oral anticoagulation rates in high-risk atrial fibrillation patients

BackgroundAnticoagulation is the cornerstone of atrial fibrillation (AF) management for stroke prevention. Recently, we showed that AF patients’ oral anticoagulation (OAC) rates in a large US multispecialty health system are above 80%. ObjectiveThis study sought to improve OAC rates in AF patients via an educational intervention targeted to primary care providers with low OAC rates. MethodsPrimary care clinicians were stratified by proportions of their AF patients at elevated stroke risk not on anticoagulation medication. Clinicians with the lowest rates of anticoagulation were assigned to a target group receiving an educational program consisting of e-mail messaging summarizing anticoagulation guidelines. All other clinicians were assigned to a comparison group. Data from a six-month lead-in phase were compared with a six-month follow-up period to determine if the proportion of AF patients treated with OACs had changed. ResultsThere were 141 primary care clinicians with patients who met the inclusion criteria, with 36 (25.53%) assigned to the educational intervention (EG) and 105 (74.47%) assigned to the comparison group (CG). At baseline there was a significant difference in percent of high-risk AF patients who were untreated in the EG (20.65%) as compared to the high-risk patients who were untreated in the CG (13.64%, p=0.001). After the educational intervention, high-risk AF patients without anticoagulation decreased in both EG (15.47% p=0.047) and CG (10.14% p=0.07) with greater absolute reduction in the EG (5.19% versus 3.50%). ConclusionA targeted education program was associated with increased anticoagulation rates for AF patients at high risk of stroke.

LAA occlusion is effective and safe in very high-risk atrial fibrillation patients with prior stroke: results from the multicentre German LAARGE registry.

Interventional left atrial appendage occlusion (LAAO) mitigates the risk of thromboembolic events in nonvalvular atrial fibrillation (AF) patientswith contraindication for long-term oral anticoagulation (OAC). Patients with prior stroke have a relevantly increased risk of recurrent stroke, so the effectiveness of LAAO could be reduced in this specific very high-risk patient group. This sub-study of the LAARGE registry investigates the effectiveness and safety of LAAO for secondary prevention in nonvalvularAF patients with a history of stroke. LAARGE is a prospective, non-randomised registry on the clinical reality of LAAO. The current sub-study employs data from index procedure and 1-year follow-up. Effectiveness and safety were assessed by documentation of all-cause mortality, non-fatal thromboembolism, procedure-related complications, and bleeding events. A total of 638 patients were consecutively included from 38 hospitals in Germany and divided into two groups: 137 patients with a history of stroke (21.5%) and 501 patients without. Successful implantation was consistent between both groups (98.5% vs. 97.4%, p = NS), while peri-procedural MACCE and other complications were rare (0% vs. 0.6% and 4.4% vs. 4.0%, respectively; each p = NS). Kaplan-Meier estimate showed no significant difference in primaryeffectiveness outcome measure (freedom from all-cause death or non-fatal stroke) between both groups at follow-up (87.8% vs. 87.7%, p = NS). The incidence of transient ischemic attack or systemic embolism at follow-up was low (0% vs. 0.5% and 0.9% vs. 0%, respectively; each p = NS). Severe bleeding events after hospitaldischarge were rare (0% vs. 0.7%, p = NS). Patients with prior stroke demonstrated similar effectiveness and safety profile for LAAO as compared to patients without prior stroke. LAAO could serve as a feasible alternative to OACfor secondary stroke prevention in this selected group of nonvalvular AF patients. NCT02230748.

Robust Artificial Intelligence Tool for Atrial Fibrillation Diagnosis: Novel Development Approach Incorporating Both Atrial Electrograms and Surface ECG and Evaluation by Head-to-Head Comparison With Hospital-Based Physician ECG Readers.

Atrial fibrillation (AF) increases risk of embolic stroke, and in postoperative patients, increases cost of care. Consequently, ECG screening for AF in high-risk patients is important but labor-intensive. Artificial intelligence (AI) may reduce AF detection workload, but AI development presents challenges. We used a novel approach to AI development for AF detection using both surface ECG recordings and atrial epicardial electrograms obtained in postoperative cardiac patients. Atrial electrograms were used only to facilitate establishing true AF for AI development; this permitted the establishment of an AI-based tool for subsequent AF detection using ECG records alone. A total of 5 million 30-second epochs from 329 patients were annotated as AF or non-AF by expert ECG readers for AI training and validation, while 5 million 30-second epochs from 330 different patients were used for AI testing. AI performance was assessed at the epoch level as well as AF burden at the patient level. AI achieved an area under the receiver operating characteristic curve of 0.932 on validation and 0.953 on testing. At the epoch level, testing results showed means of AF detection sensitivity, specificity, negative predictive value, positive predictive value, and F1 (harmonic mean of positive predictive value and sensitivity) as 0.970, 0.814, 0.976, 0.776, and 0.862, respectively, while the intraclass correlation coefficient for AF burden detection was 0.952. At the patient level, AF burden sensitivity and positive predictivity were 96.2% and 94.5%, respectively. Use of both atrial electrograms and surface ECG permitted development of a robust AI-based approach to postoperative AF recognition and AF burden assessment. This novel tool may enhance detection and management of AF, particularly in patients following operative cardiac surgery.

Interventional left atrial appendage occlusion is effective and safe in high-risk patients with prior stroke: comprehensive insights from the multicenter German LAARGE registry

Abstract Background Interventional left atrial appendage occlusion (LAAO) is an alternative therapeutic strategy equivalent to non-vitamin K antagonist oral anticoagulation (OAC) in preventing thromboembolism (TE) for non-valvular atrial fibrillation (AF) patients with contraindications to OAC. However, patients with prior stroke are at relevant higher risk for TE than general patient populations. These patients are often prone to multimorbidity, are at high risk for bleeding, and may well benefit from LAAO. Purpose To investigate the performance of LAAO in secondary prevention after prior stroke versus patients without history of stroke and to reveal any potential differences in effectiveness and safety. Methods Data from multicenter German LAARGE was used, which is a prospective, non-randomized registry on clinical reality of LAAO with different standard commercial devices. Effectiveness was primarily assessed by the combined absence of all-cause death or non-fatal stroke within 365 days after the procedure, and secondarily by the absence of transient ischemic attack (TIA) or systemic embolism. Safety was assessed with data documenting adverse events during index hospitalization or follow-up. Results 638 patients from 38 centers were consecutively included. 137 patients had a history of stroke (21.5%) and 501 patients had none. Stroke patients had a significantly pronounced cardiovascular comorbidity: CHA2DS2-VASc score 5.9+1.3 vs. 4.1+1.4 and HAS-BLED score 4.6+1.0 vs. 3.7+1.1, respectively (each p<0.001). A high procedural success (98.5 vs. 97.4%, p=NS) was accompanied by low periprocedural MACCE or major complication rates (0% vs. 0.6 and 4.4 vs. 4.0%, respectively; each p=NS). Primary effectiveness outcome measure was not statistically different between both groups on follow-up (freedom from all-cause death or non-fatal stroke: 87.8 vs. 87.7%), while TIA (0 vs. 0.5%), systemic embolism (0.9 vs. 0%) as well as severe bleeding events (0 vs. 0.7%; each p=NS) were extremely rare. Conclusions Patients with history of stroke, though showing significantly pronounced multimorbidity, demonstrated a similar effectiveness and safety profile for LAAO as compared to patients without prior stroke. LAAO could serve as a feasible alternative to OAC in this selected group of high-risk AF patients with contraindications to standard care.All-cause death or non-fatal stroke (KM)

Improving frequency and appropriateness of direct oral anticoagulant (DOAC) prescribing for af through integrated pharmacy-led care

Abstract Background Anticoagulants for stroke-risk reduction in atrial fibrillation (AF) are underutilised and international literature shows 10-25% of patients on a direct oral anticoagulant (DOAC) for AF are prescribed an inappropriate dose, increasing the risk of stroke and bleeding. NHS England targets are for 90% high-risk AF patients to be prescribed anticoagulation by 2029. Purpose A new pharmacy-led integrated care model was developed to improve the frequency and quality of prescribing and monitoring of DOACs for AF in line with national guidance. This abstract describes the results when this model of care was rolled out across a large UK city. Methods The integrated model of care was designed to provide a multi-pronged approach and empower primary care pharmacy teams to prescribe and manage DOACs for AF. The model includes an education and training programme, a weekly specialist-run virtual clinical discussion service, a 48-hour turn around advice and guidance service and a clinical tool that identifies and makes recommendations for patients on an unlicensed dose of a DOAC. Results 16,594 patients are included on the city’s AF register. From April-November 2022, an additional 1,339 (8%) patients were anticoagulated. An increase from 76.3% to 84.3% of patients on the AF register. Dosing as per manufacturers Summary of Product Characteristics (SmPC) improved for all DOACs. In April 2022 an incorrect dose was prescribed for 10%, 15% and 12% of patients respectively on apixaban, edoxaban and rivaroxaban. In November 2022 incorrect dosing reduced across the board to 7%, 8% and 7% of patients respectively. 914 patients prescribed an inappropriate dose had their dose adjusted to meet SmPC recommendations based on relevant characteristics (renal function, age, weight, serum creatinine, interacting medicines). Monitoring according to local guidelines also increased. Experience of staff was overwhelmingly positive and demonstrated growth in knowledge, skills, and activity amongst primary care pharmacy teams. Rapid access to specialist support allowed patients to be managed close to home. Conclusions This integrated care model improves frequency and appropriateness of DOAC prescribing for patients with AF. The model results in incorrect dosing lower than any described in international literature. The service model is sustainable and scalable, grows cross-sector clinical leadership and develops relationships between primary and secondary care. The next steps are to roll this model out across a large region.

Left atrial appendage closure: the journey today and tomorrow.

This review aims to discuss the rationale behind the development of percutaneous LAAC devices as a treatment option for atrial fibrillation patients ineligible for long-term anticoagulation. The evolution of LAAC, from early experiences and challenges to risk mitigation and improved devices and techniques, will be examined. Furthermore, the review will explore our current understanding of the potential and limitations of LAAC in stroke prevention. Multiple trials confirm LAAC device safety and efficacy for stroke prevention, but peri-device leak and thrombus remain concerns postimplantation. Even small leaks pose increased stroke risk. While guidelines suggest short-term anticoagulation postimplant; real-world data show equivalent efficacy with dual antiplatelet regimen. LAAC device design has evolved and now serve as a viable option for stroke prevention in high-risk atrial fibrillation patients, offering protection in the absence of anticoagulation.

Nonprocedural bleeding after left atrial appendage closure versus direct oral anticoagulants: A subanalysis of the randomized PRAGUE-17 trial.

Observational studies have shown low bleeding rates in patients with atrial fibrillation (AF) treated by left atrial appendage closure (LAAC); however, data from randomized studies are lacking. This study compared bleeding events among patients with AF treated by LAAC and nonvitamin K anticoagulants (NOAC). The Prague-17 trial was a prospective, multicenter, randomized trial that compared LAAC to NOAC in high-risk AF patients. The primary endpoint was a composite of a cardioembolic event, cardiovascular death, and major and clinically relevant nonmajor bleeding (CRNMB) defined according to the International Society on Thrombosis and Hemostasis (ISTH). The trial enrolled 402 patients (201 per arm), and the median follow-up was 3.5 (IQR 2.6-4.2) years. Bleeding occurred in 24 patients (29 events) and 32 patients (40 events) in the LAAC and NOAC groups, respectively. Six of the LAAC bleeding events were procedure/device-related. In the primary intention-to-treat analysis, LAAC was associated with similar rates of ISTH major or CRNMB (sHR 0.75, 95% CI 0.44-1.27, p = 0.28), but with a reduction in nonprocedural major or CRNMB (sHR 0.55, 95% CI 0.31-0.97, p = 0.039). This reduction for nonprocedural bleeding with LAAC was mainly driven by a reduced rate of CRNMB (sHR for major bleeding 0.69, 95% CI 0.34-1.39, p = .30; sHR for CRNMB 0.43, 95% CI 0.18-1.03, p = 0.059). History of bleeding was a predictor of bleeding during follow-up. Gastrointestinal bleeding was the most common bleeding site in both groups. During the 4-year follow-up, LAAC was associated with less nonprocedural bleeding. The reduction is mainly driven by a decrease in CRNMB.

Left atrial appendage occlusion combined with cryoballoon or radiofrequency ablation: One-year follow-up comparison.

A one-stop procedure involving catheter ablation and left atrial appendage occlusion (LAAO) is an option for high-risk atrial fibrillation patients. Few studies have reported the efficacy and safety of cryoballoon ablation (CBA) combined with LAAO, and no studies have compared the combination of LAAO with CBA or radiofrequency ablation (RFA). A total of 112 patients were enrolled in the present study; 45 patients received CBA combined with LAAO (group 1), and 67 patients received RFA combined with LAAO (group 2). Patient follow-up was performed for 1 year to detect peri-device leaks (PDLs) and safety outcomes (defined as a composite of peri-procedural and follow-up adverse events). The number of PDLs at the median 59 days follow-up was comparable between the two groups (33.3% in group 1 vs. 37.3% in group 2, p = 0.693). Safety outcomes were also comparable between the two groups (6.7% in group 1 vs. 7.5% in group 2, p = 1.000). Multivariable regression showed that PDLs risk and safety outcomes were all similar between the two groups. Subgroup analysis of PDLs indicated no significant differences. Follow-up safety outcomes were related to anticoagulant medication, and patients without PDLs were more likely to discontinue antithrombotic therapy. The total procedure and ablation times were all significantly shorter for group 1. When compared with left atrial appendage occlusion combined with radiofrequency, left atrial appendage occlusion combined with cryoballoon ablation has the same risk of peri-device leaks and safety outcomes, but the procedure time was significantly reduced.

The effectiveness of atrial fibrillation special clinic on oral anticoagulant use for high risk atrial fibrillation patients managed in the community

BackgroundService gaps exist in oral anticoagulant (OAC) use among patients with atrial fibrillation (AF) in primary care. The purpose of this study was to explore the clinical effectiveness of a community dwelling Atrial Fibrillation Special Clinic (AFSC) run by primary care physicians by evaluating its impact on OAC use and the control of modifiable cardiovascular disease (CVD) risk factors in high risk AF patients.MethodQuasi-experimental study was conducted in AFSC run by public primary care physicians in Hong Kong. Study subjects were high risk AF patients with CHA2DS2-VASc scores ≥ 2, who had been followed up (FU) at AFSC for at least one year from 01 August, 2019 to 31 October, 2020. OAC usage and modifiable CVD risk factor control were compared before and after one year of FU at AFSC. Drug-related adverse events, emergency attendance or hospitalisation episodes, survival and mortality rates after one year FU at AFSC were also reviewed.ResultsAmong the 299 high risk AF patients included in the study, significant increase in OAC use was observed from 58.5% at baseline to 82.6% after one year FU in AFSC (P < 0.001). Concerning CVD risk factor control, the average diastolic blood pressure level was significantly reduced (P = 0.009) and the satisfactory blood pressure control rate in non-diabetic patients was markedly improved after one year FU (P = 0.049). However, the average HbA1c and LDL-c levels remained static. The annual incidence rate of ischaemic stroke/systemic embolism was 0.4%, intra-cranial haemorrhage was 0.4%, major bleeding episode was 3.2% and all-cause mortality was 4.3%, all of which were comparable to reports in the literature.ConclusionAFSC is effective in enhancing OAC use and maintaining optimal modifiable CVD risk factor control among high risk AF patients managed in primary care setting, and therefore may reduce AF-associated morbidity and mortality in the long run.

Abstract 13457: Ability of CHARGE-AF and CHA 2 DS 2 -VASc Scores to Predict Prevalent Atrial Fibrillation in a High-Risk Population

Introduction: The CHARGE-AF score estimates 5-year risk of developing atrial fibrillation (AF) using information on age, race, weight, height, systolic and diastolic blood pressure, diabetes, smoking, use of antihypertensive medication, and prevalence of heart failure and myocardial infarction. Similarly, the CHA 2 DS 2 -VASc score for estimation of stroke risk in AF has been proposed as a useful tool for incident AF prediction. It is unclear whether these scores can predict AF in a high-risk population. We evaluated whether the CHARGE-AF and CHA 2 DS 2 -VASc scores predict the prevalence of AF in the Emory Cardiovascular Biobank cohort (EmCAB) that recruited patients undergoing cardiac catheterization with suspected or confirmed coronary artery disease. Methods: In 6951 EmCAB participants, logistic regression was used to determine the association between baseline characteristics, CHARGE-AF and CHA 2 DS 2 -VASc scores and the presence of prevalent AF. To assess the discrimination of the CHARGE-AF and CHA 2 DS 2 -VASc models, we estimated the C-statistic. Internal calibration was determined with the Hosmer-Lemeshow test. Results: Mean age of patients was 62 (SD=13), 64% male, 76% White. Median 5-year risk of AF using the CHARGE-AF score was significantly higher in those with compared to those without prevalent AF (11% vs. 4%, p=&lt;0.001). However, the median CHA 2 DS 2 -VASc scores were similar in both groups (3.0). The C-statistic for predicting prevalent AF was better with the CHARGE-AF compared to the CHA 2 DS 2 -VASc score (0.662 vs. 0.606). The strongest risk predictor of prevalent AF was heart failure (OR 2.52, 95%CI 2.13-2.98). Conclusion: In a high risk cohort of patients with CAD, the CHARGE-AF score had a moderate discrimination ability to predict AF and showed better performance than the CHA 2 DS 2 -VASc score. Whether the CHARGE-AF score is useful in predicting incident AF in high risk patients needs to be further investigated.

Impact of ABC pathway adherence in high-risk patients with atrial fibrillation: an analysis from the ESC-EHRA EORP-AF long-term general registry

Abstract Background The impact of Atrial Fibrillation Better Care (ABC) pathway adherence among high-risk subgroups of patients with atrial fibrillation (AF), ie. those with chronic kidney disease (CKD), advanced age and/or prior thromboembolism remains unknown. We evaluated the impact of ABC pathway adherence on clinical outcomes in these high-risk AF patients. Methods The EORP-AF General Long-Term Registry is a prospective, observational registry from 250 centres across 27 European countries. High-risk patients were defined as those with either CKD (eGFR &amp;lt;60 mL/min/1.73 m2), older age (≥75 years) and/or prior thromboembolism. The primary outcome was a composite event of all-cause death, any thromboembolism and acute coronary syndrome, evaluated according to ABC pathway adherence. Results A total of 6646 patients with AF were included (median age was 70 [IQR 61–77] years; 40.2% females). There were 3304 (54.2%) `high risk' patients with either CKD (n=1750), older age (n=2236) or prior thromboembolism (n=728). Among these there were 924 (28.0%) managed as adherent to ABC. At 2-year follow-up, a total of 966 (14.5%) patients reported the primary outcome. The incidence of the primary outcome was significantly lower in high-risk patients managed as adherent to ABC pathway (IRR 0.53 [95% CI, 0.43–0.64]). Consistent results were obtained in the individual subgroups [Table]. Using multivariable Cox proportional hazards analysis, ABC adherence in the high-risk cohort was independently associated with a lower risk of primary outcome (aHR 0.64 [95% CI, 0.51–0.80]), as well as in the CKD (aHR 0.51 [95% CI, 0.37–0.70]) and elderly subgroups (aHR 0.69 [95% CI, 0.53–0.90]). Overall, there was greater reduction in the risk of primary outcome as more ABC criteria were fulfilled, both in the overall high-risk patients, as well as in the individual subgroups [Figure]. Conclusion In a large, contemporary European AF cohort there was a significant proportion of high-risk patients. Among these, a low prevalence of integrated care, as assessed by adherence to ABC pathway, was found. Nonetheless, a clinical management adherent to the ABC pathway was associated with a significant reduction in the risk of adverse outcomes, the benefits of which were more significant with increasing number of ABC criteria adherent. Funding Acknowledgement Type of funding sources: None.

In a large dataset of primary care patients, use of CHA2DS2-VA score leads to almost universal recommendation for anticoagulation in those aged 65 years and over with atrial fibrillation

Abstract Background Treatment with oral anticoagulants (OAC) for high-risk atrial fibrillation (AF) patients can reduce stroke risk by two-thirds. From 2012–14, the OAC treatment recommendation threshold in international guidelines moved from CHADS2 ≥2 to CHA2DS2-VASc ≥2 (men) or ≥3 (women), equivalent to a “sexless” CHA2DS2-VA≥2. This move aimed to identify truly low risk patients who did not need OAC treatment. General practitioners (GPs) report barriers about assessing patient suitability for OAC. Objectives To compare the proportion of AF patients for whom OAC treatment is recommended under CHADS2 ≥2 and CHA2DS2-VA ≥2, and to look at the drivers of any differences, using an existing dataset. Methods Analyses were conducted on a large Australian general practice dataset collated during previous studies (2011–2019), with deidentified data extracted from the clinical records system at a single timepoint for regularly-attending adult patients from 164 practices. CHADS2 and CHA2DS2-VA scores were calculated for AF patients with sufficient data available and the proportion with CHADS2 and CHA2DS2-VA ≥2 was compared using chi-square tests. Results There were records for 340,463 patients, of which 285,635 (8,294 with AF) had sufficient data to calculate CHADS2 and CHA2DS2-VA scores. Among AF patients of all ages, the CHA2DS2-VA ≥2 threshold captured a significantly higher proportion than CHADS2≥2 (85% vs 68%, p&amp;lt;0.0001). In AF patients aged ≥65 years, the CHA2DS2-VA ≥2 threshold also captured a significantly higher proportion than CHADS2 ≥2 (96% vs 76%, p&amp;lt;0.0001). Almost all older patients (≥65 years) who were captured by CHA2DS2-VA ≥2 but not CHADS2 ≥2 (n=1395) qualified on the basis of age, with only 1.4% eligible because of age 65–74 years and vascular disease history. Conclusions The change from CHAD2 to CHA2DS2-VA has resulted in a significantly higher proportion of patients with AF being recommended OAC treatment under the guidelines, driven almost entirely by the revised scoring for age. Among AF patients aged ≥65 years, almost all (96%) were recommended OAC treatment under CHA2DS2-VA, demonstrating that AF is strongly associated with other vascular pathology. These findings support the Canadian guidelines, which recommend OAC treatment for all AF cases aged ≥65 years. The findings also reinforce the argument that AF screening in those aged ≥65 years is justified, as almost all patients with prevalent AF in that age group are eligible for OAC treatment. These results suggest could be an argument for simplifying the treatment message for GPs, which may reduce barriers and further improve treatment rates. High rates of associated vascular pathology in AF patients suggest that additional management strategies are also justified, including promotion of exercise, smoking cessation, and treatment of associated conditions such as hypertension and diabetes. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): RACGP Foundation / HCF Research Foundation GrantUniversity of Notre Dame Australia Research Grant

Pharmacist-led multidisciplinary approach in preventing strokes in people with atrial fibrillation

Abstract Background/Introduction Targets set by Public Health England (PHE) state that 90% of patients with atrial fibrillation (AF) are expected to receive anticoagulation by 2029. In 2019/2020, across three London boroughs serving a population of 770,000, the percentage of AF patients at high risk of stroke (CHA2DS2VASc&amp;gt;2) anticoagulated was below the target set by PHE. In addition, optimisation of risk factors can significantly reduce the risk of cardiovascular disease and associated mortality in these patients. Purpose To provide specialist input from a cardiovascular pharmacist to prevent AF-related strokes through improvement of anticoagulation rates and optimisation of cardiovascular risk factors in patients with AF across three London boroughs over one year, as well as minimising bleed risk in patients on dual antithrombotic therapy. Methods A specialist cardiovascular pharmacist was commissioned to identify high-risk AF patients (CHA2DS2VASc&amp;gt;2) by working with primary care clinicians. Utilising “proactive care frameworks” created by UCLPartners and Clinical Effectiveness Group Queen Mary University of London, patients were stratified and prioritised for review. Patients not on anticoagulation were deemed to be at highest risk, requiring an urgent review to assess suitability for anticoagulation. A virtual multidisciplinary team (MDT) would review any complex patients and agree an action plan. Patients on dual antithrombotic therapy were also assessed to determine if antiplatelet therapy was indicated to minimise risk of major bleeding. All AF patients were reviewed for suitability of statin initiation to optimise cardiovascular risk prevention. Results At baseline, 86% (7581/8582) of AF patients with a CHA2DS2VASc&amp;gt;2 across the three boroughs were anticoagulated. 1001 patients were reviewed by a specialist pharmacist, with 84% (841/1001) of patients having a CHA2DS2VASc between 2–5, and 28% (280/1001) on antiplatelet monotherapy. Analysis at 12 months following intervention reported that 95% (7888/8280) of AF patients with a CHA2DS2VASc&amp;gt;2 were suitably anticoagulated, an improvement of 9%. 6% (61/1001) of patients were switched from antiplatelets and 25% (246/1001) were newly initiated on anticoagulation. 13% (130/1001) of patients required specialist MDT input to determine appropriateness for anticoagulation initiation. There was also a reduction in dual anticoagulation and antiplatelet therapy from 429 to 252 patients (41% reduction). Lastly of those reviewed, 2609 patients received a recommendation to start a statin for either primary (n=1981) or secondary prevention (n=628). Conclusion(s) Provision of a specialist cardiovascular pharmacist supported a multidisciplinary workforce to significantly improve and optimise cardiovascular risk, and reduce the risk of stroke in this high-risk population for people with AF across all three boroughs. By extrapolating these results nationally, 3600 strokes could be averted over 18 months. Funding Acknowledgement Type of funding sources: None.

Pilot study of peripheral blood chemokines as biomarkers for atrial fibrillation-related thromboembolism and bleeding in elderly patients.

BackgroundThe scoring systems currently used to identify the potential for thrombosis and bleeding events in high-risk atrial fibrillation patients have certain limitations. The aim of this pilot study was to identify inflammatory chemokines with potential utility as sensitive biomarkers for the risk of thrombosis and bleeding in elderly patients with non-valvular atrial fibrillation.MethodsFrom January 1, 2014, to December 31, 2017, 200 consecutive elderly patients with atrial fibrillation (average age: 87.6 ± 7.7 years) were enrolled and followed up for 2 years to observe thromboembolic (arterial and venous) and bleeding events. Serum was collected upon enrollment, and the baseline levels of 27 chemokines were analyzed. During the 2-year follow-up, 12 patients were lost to follow-up. Among the 188 patients, there were 32 cases (17.0%) of AF-related thrombosis, 36 cases (19.1%) of arterial thrombosis, and 35 cases (18.6%) of major bleeding events.ResultsAmong 188 patients, 30 patients without clinical events (control group), 23 with arterial thrombosis, 15 with atrial fibrillation-related venous thromboembolism, and 12 with major bleeding were selected and randomly matched to compare chemokine levels. The baseline levels of interleukin-6, interleukin-10, vascular cell adhesion molecule-1, chemokine C-C-motif ligand, B-lymphocyte chemoattractant 1, interleukin-4, E-selectin, fractalkine, C-X-C motif chemokine 12, and granulocyte chemotactic protein 2 were found to differ statistically among the four groups (p < 0.05). Compared with that in the control group, the level of interleukin-4 in patients with atrial fibrillation-related thrombosis, arterial thrombosis, or major bleeding increased by 53-fold (0.53 vs. 0.01 pg/ml), 17-fold (0.17 vs. 0.01 pg/ml), and 19-fold (0.19 vs. 0.01 pg/ml), respectively. Compared with that in the control group, the level of interleukin-6 in patients with arterial thrombosis increased by six-fold (39.78 vs. 4.98 pg/ml).ConclusionsAmong elderly patients with atrial fibrillation at high risk of thromboembolism and bleeding, the baseline levels of interleukin-6, interleukin-4, and E-selectin were significantly increased in those that experienced thrombosis and bleeding events during the 2-year follow-up, indicating that these chemokines may serve as potential biomarkers for an increased risk of thrombosis and bleeding in this population.Clinical trial registration numberChiCTR-OCH-13003479.

Contrast defect of left atrial appendage on computed tomography is associated with higher risk of recurrence after catheter ablation in patients with paroxysmal atrial fibrillation.

The previous study has shown that the contrast defect of the left atrial appendage (LAA) on contrast-enhanced cardiac computed tomography (CT) is associated with a higher rate of stroke in patients with atrial fibrillation (AF). This study aimed to investigate the association between LAA CT contrast defect and the risk of arrhythmia recurrence after catheter ablation (CA) in patients with paroxysmal AF. A total of 283 paroxysmal AF patients [age: 67 ± 10years, 185 (65%) males] who underwent cardiac CT before CA were retrospectively analyzed. The presence or absence of LAA CT contrast defect was visually assessed using early phase CT images. Recurrence was an episode of atrial arrhythmia beyond the first 90days post-ablation. LAA flow velocity was measured using transesophageal echocardiography in 246 paroxysmal AF patients. Sixty-eight (24%) patients had an LAA CT contrast defect. LAA flow velocity was significantly reduced in patients with LAA CT defect compared to those without (56.8 ± 28.7cm/s vs. 41.1 ± 19.1cm/s, p < 0.001). During a median follow-up period of 858days, arrhythmia recurrence was identified in 85 (30%) patients. On a Kaplan Meier curve, patients with LAA CT contrast defect had significantly higher recurrence rates than those without (p = 0.043). On a multivariable Cox regression analysis, LAA CT contrast defect was a significant and independent predictor after adjustment of age, sex and left atrial volume index (hazard ratio: 1.79, 95% confidence interval: 1.03-3.07, p = 0.036). LAA CT contrast defect was associated with decreased LAA flow velocity and a higher rate of arrhythmia recurrence after CA, suggesting its usefulness as a non-invasive predictor for high-risk AF patients resistant to CA therapy.

Benefit and harm of anticoagulation in the prevention of thromboembolic stroke for non-valvular atrial fibrillation in haemodialysis patients: a Top End of Northern Australia study.

Warfarin for the prevention of non-valvular atrial fibrillation (AF)-related thromboembolic stroke in patients on maintenance haemodialysis is controversial. Despite the exclusion of haemodialysis patients in randomised control trials, the American Heart Association/American College of Cardiology has recommended warfarin in high-risk AF patients. To retrospectively examine the utility of warfarin anticoagulation therapy in our prevalent haemodialysis patients over 10 years of follow up. Eligible patients were retrospectively identified and stratified to two cohorts based on whether warfarin was prescribed. The outcomes of interest were ischaemic stroke, haemorrhagic stroke and death from any cause. Rate ratio and Cox proportional hazard regression model were used to compare the differences in outcome between the two cohorts. The Kaplan-Meier method was used to analyse survival. Three ischaemic strokes and four haemorrhagic strokes occurred in the unexposed group of 166 patients over 484.44 patient-years of follow up. One ischaemic stroke and no cases of haemorrhagic stroke occurred in the exposed warfarin group of 16 patients over 39.32 patient-years of follow up. Eighty-seven percent of patients in both groups were indigenous. More than 90% of each cohort had a CHA2DS2-VaSc score ≥2. One hundred and one deaths, 90 in the unexposed group and 11 in the warfarin group, occurred in the follow-up period. A non-statistically significant trend towards increasing mortality was observed in the warfarin group (hazard ratio=1.63; P = 0.13). This retrospective study of prevalent haemodialysis patients with co-existing history of non-valvular AF failed to demonstrate sufficient evidence for the routine use of warfarin for prophylaxis of thromboembolic stroke.

Pharmacist-led multidisciplinary approach in preventing strokes in people with atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: None. Background/Introduction In England, 90% of patients with atrial fibrillation (AF) are expected to receive anticoagulation as part of targets set by Public Health England by 2029. In 2019/2020, across three London boroughs serving a population of 770,000, the percentage of AF patients at high risk of stroke (CHA2DS2VASc&amp;gt;2) anticoagulated was 87%, 83% and 84%. This placed two of the three localities in the bottom 10% compared to others in England. In addition, optimising cholesterol and lifestyle choices can significantly reduce the risk of cardiovascular disease and associated mortality in these patients. Purpose To prevent AF-related strokes by improving anticoagulation rates and optimising cardiovascular risk factors in patients with AF in all general practices across three London boroughs over one year, and to minimise risk of bleeding in patients on concurrent anticoagulation and antiplatelet therapy. Methods A specialist cardiovascular pharmacist was commissioned to systemically identify high-risk AF patients (CHA2DS2VASc&amp;gt;2) by working with primary care clinicians, including up-skilling of primary care pharmacists. Through utilisation of ‘proactive care frameworks’ created by the Clinical Effectiveness Group Queen Mary University of London and UCL Partners, patients were able to be stratified and prioritised for review. AF patients not on anticoagulation or on antiplatelet monotherapy were deemed to be at highest risk, and these patients were reviewed to assess suitability for anticoagulation. Subsequently, patients on concurrent anticoagulation and antiplatelets were assessed to determine if dual antithrombotic prescribing was still indicated to minimise risk of major bleeding. Lastly, to optimise cardiovascular risk prevention, all AF patients were reviewed for suitability of statin initiation for primary or secondary prevention. A virtual multidisciplinary team was convened for complex patients, which included a cardiologist, haematologist, general practitioner and pharmacist to review and agree an action plan. Results An interim analysis at 9 months reported that 94% (6745/7145) of patients with a CHA2DS2VASc&amp;gt;2 across the three boroughs were suitably anticoagulated, an improvement of 6% on the initial 88% (6585/7391). There was a reduction in concurrent anticoagulation and antiplatelet therapy from 381 to 262 patients (31.2% reduction) following specialist review. Lastly 2285 patients were reviewed with a recommendation to start a statin for either primary (n=1783) or secondary prevention (n=502). Conclusion(s) Provision of a specialist cardiovascular pharmacist supported a multidisciplinary workforce with significant improvement in anticoagulation rates across all three boroughs, reducing the risk of stroke in this high-risk population. In addition, we were able to reduce the risk of bleeding in this cohort of patients by stopping inappropriate antiplatelet therapy, and reduced the risk of cardiovascular disease through statin initiation.

Oral Anticoagulants in Patients with Atrial Fibrillation and Active Cancer

Background: Atrial fibrillation (AF) is associated with an increased risk of heart failure, death and thromboembolism. AF is prevalent in patients with cancer. Although current guidelines suggest the application of oral anticoagulants (OACs) for thromboembolic event prevention in high-risk AF patients, owing to the high thromboembolic and bleeding risks of active-cancer patients, there is no consensus on the use of OACs in such a population. Therefore, we conducted this retrospective cohort study to investigate the applicability of the CHA2DS2-VASc score and to evaluate the efficacy and safety outcomes of OAC therapy in active-cancer patients with AF. Methods: This retrospective cohort study enrolled patients diagnosed with cancer at National Cheng Kung University Hospital between November 2012 and August 2019. The primary outcomes included all-cause mortality, thromboembolic events (stroke/transient ischemic attack and systemic emboli), acute myocardial infarction (AMI), hospitalization for HF and major bleeding events. Results: We enrolled 2429 patients with active cancer. Among these patients, 1060 patients (43.6%) had AF. After 1:2 propensity score matching, 690 cancer patients with AF were enrolled for the final analysis, grouped as follows: 225 patients taking OACs and 465 patients without OAC treatment. The OAC-treated group had lower all-cause mortality than the patients without OAC treatment (all-cause mortality rate in OAC treatment vs. non-OAC treatment: 24.4% vs. 37.4%, hazard ratio 0.58 [95% confidence interval (CI) 0.43–0.78], p &lt; 0.001). However, there was no difference in thromboembolic events, myocardial infarction or heart failure hospitalization between the OAC-treated and non-OAC-treated groups. Importantly, the risk of major bleeding composition (i.e., major gastrointestinal bleeding and intracranial hemorrhage) was similar between these two groups. Moreover, the CHA2DS2-VASc score could not predict thromboembolic events in the enrolled active-cancer patients with AF (OR 1.23, 95% CI 0.98–1.56). Conclusions: OAC treatment may significantly reduce the risk of death, without safety concerns, in active-cancer patients with AF. OAC treatment may not prevent thromboembolic events in patients with active cancer and AF. However, we found that OAC treatment is associated with improved prognosis without increasing the risks of major bleeding, despite several limitations in this study. Further studies are required to determine the optimal use of anticoagulation therapy in this high-risk population.

Real world outcomes of minimally invasive epicardial surgical left atrial appendage exclusion in atrial fibrillation patients with high risk of stroke and bleeding

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): AtriCure, Inc Introduction The left atrial appendage (LAA) is the site of thrombus formation in patients with atrial fibrillation (AF) and first line therapy for reducing the risk of stroke is oral anticoagulation (OACs). A subset of patients with AF carry a very high risk of stroke and bleeding and are ineligible for OAC and percutaneous LAA occlusion; these patients may be suitable for minimally invasive thoracoscopic epicardial surgical LAA exclusion (LAAE) which can be used with a wide variety of LAA morphologies with a ~98% rate of complete exclusion. While use of LAAE is well studied as a concomitant procedure, there are relatively few data on its use as a stand-alone procedure. Purpose To compare real-world outcomes of LAAE versus no-LAAE in AF patients at high risk of stroke and bleeding who are not on OACs. Methods We performed an analysis of Medicare beneficiaries with AF who were not on OACs and received LAAE (ICD10-PCS code 02L74CK, Oct 2015 – Dec 31, 2017) in the absence of a concomitant surgical or catheter AF ablation procedure. Patients were propensity-matched (1:4) to otherwise similar patients who did not receive LAAE (control), using age, gender, race, region, AF type, CHA2DS2-VASc, HAS-BLED, and co-morbidities. The primary endpoint was hospital readmission for a thromboembolic event (ischemic stroke, systemic embolism, or transient ischemic attack). Kaplan Meier event rates were calculated and 95% CI were generated via bootstrapping. Results A total of 243 patients who underwent LAAE and 1.7M control patients met study criteria. In the matched cohort, the mean age was 75 years, 61% were men, 77% had non-paroxysmal AF, and the mean CHADS2-VASC and HAS-BLED scores were 5.5 and 4.2, respectively. The 1-year rate of thromboembolism in the LAAE and control arms were 7.3% (95% CI 4.3% -10.9%) and 13.6 (95% CI 11.0% -16.4%) (Figure), respectively, with an absolute and relative risk reduction of 6.2% (95% CI 2.0-10.3, p-value=0.001, NNT 17) and 0.54 (95% CI 0.29-0.68, p=0.001). Conclusion Among high-risk AF patients who were not on OAC, LAAE was associated with a clinically meaningful and significantly lower risk of TE. Additional studies are needed to confirm these finding.

Cost-effectiveness Of Insertable Cardiac Monitors For Detection Of Undiagnosed Atrial Fibrillation In High-risk Patients With Heart Failure

<h3>Introduction</h3> Atrial fibrillation (AF) is a major risk factor for stroke, the risk of which is mitigated through AF detection and subsequent treatment with oral anticoagulation. The REVEAL AF study demonstrated that ICMs detect a high rate of AF in high-risk patients, and a resulting cost-effectiveness analysis found ICM use to be cost-effective in preventing strokes. Given the known deleterious relationship between AF and heart failure (HF), this analysis sought to examine the cost effectiveness of ICMs in the sub-population of the REVEAL AF study with HF. <h3>Methods</h3> A lifetime Markov model assessed the cost-effectiveness of ICM vs. SoC from a US payer perspective. Patient characteristics, health utilities, and AF detection rates for the ICM group were based on the heart failure subgroup within the REVEAL-AF study (N=81). Standard of care AF detection rates were based on a subsequent simulation of the REVEAL-AF study. The observed two-year AF diagnostic yields of 38.4% with ICM and 1.4% in SoC were extrapolated to the 3-year device lifespan using logarithmic extrapolation (ICM = 43.8%; SOC=1.7%). AF detection was assumed to prompt switching from aspirin to direct oral anticoagulation (DOAC), unless precluded by prior bleeds. Subsequent risks of ischemic strokes and bleeding events were modeled based on published literature. U.S. payer-perspective costs, extracted from Medicare and commercial payer administrative datasets, and drug effects were discounted at 3% annually. <h3>Results</h3> ICM in REVEAL-AF sub-population with HF was associated with a 0.19 quality-adjusted life year (QALY) gain compared to SoC (7.11 vs. 6.92) and $5,895 higher per-patient costs, resulting in an incremental cost-effectiveness ratio (ICER) of $31,452 per QALY gained. In sensitivity analyses, where we assumed no further AF was detected after 2 years (38.4% diagnostic yield at year 3), the ICER increased to $35,358, whereas a linear extrapolation (48% diagnostic yield at year 3) reduced the ICER to $29,026. The ICER was also sensitive to use of warfarin (ICER=$49,525) rather than DOAC anticoagulation in the base case analysis, and device and insertion procedure cost (+/- 30%: ICER=$42,724; $20,179, respectively). Further, increasing the device longevity to 4.5 years yielded an ICER of $29,146. <h3>Conclusions</h3> ICMs are a cost-effective diagnostic tool for the prevention of ischemic strokes in patients with heart failure and at high risk for atrial fibrillation. Improvements in ICM battery life could further enhance their clinical and economic value.