Stroke In Atrial Fibrillation Research Articles

Longitudinal changes in CHA2DS2-VASc and HAS-BLED scores are superior to baseline score values for predicting ischemic stroke and major bleeding in atrial fibrillation patients

Abstract Background Stroke and bleeding risks in atrial fibrillation (AF) are often assessed at baseline, as a “one-off” evaluation. However, these baseline values are usually applied to predict outcomes many years later, and therefore lack the consideration that the risk is not static. Purpose Our aim was to investigate if dynamic changes of CHA2DS2-VASc and HAS-BLED over time have an effect on the prediction of stroke and bleeding risks. Methods We included AF patients who were stable while taking vitamin K antagonists (INR 2.0–3.0) for 6 months attending a tertiary hospital (May 2007-December 2007). During 6-years of follow-up, ischemic strokes/transient ischemic attacks (TIAs), major bleeds, and all-cause deaths were recorded. CHA2DS2-VASc and HAS-BLED were recalculated every 2-years, and their predictive abilities were tested for outcomes in periods of 2-years (from year 0 to 2, year 2 to 4 and year 4 to 6). Results 1361 patients (693 [50.9%] females, median age 76 [IQR 71–81] years, mean CHA2DS2-VASc and HAS-BLED of 4.0±1.7 and 2.9±1.2, respectively) were included. The predictive ability for ischemic stroke/TIA of the baseline CHA2DS2-VASc for 2-years events was 0.662 (0.637–0.688, p<0.001). Compared to the baseline CHA2DS2-VASc, the CHA2DS2-VASc re-calculated at 2-years presented significantly higher predictive ability for ischemic stroke/TIA during the period 2–4 years (c-indexes: 0.701 [0.675–0.727] vs. 0.604 [0.576–0.631], p<0.001). Integrated discrimination improvement (IDI) and net reclassification improvement (NRI) showed an improvement in sensitivity of 0.014 (p<0.001) and a better reclassification (0.677, p<0.001). Similarly, the CHA2DS2-VASc re-calculated at 4-years yielded significantly better predictive performance for ischemic stroke/TIA during the period 4–6 years in comparison to the baseline CHA2DS2-VASc (c-indexes: 0.761 [0.734–0.786] vs. 0.682 [0.653–0.710], p=0.026). Again, IDI reported an improvement (IDI = 0.030, p<0.001) and there was an important enhance of the reclassification ability (NRI = 0.757, p<0.001). The c-index of the baseline HAS-BLED for events at 2-years was 0.744 (0.720–0.767, p<0.001). At 2-years, the re-calculated HAS-BLED score showed higher predictive ability compared to the baseline HAS-BLED during the period 2–4 year (c-indexes: 0.709 [0.680–0.738] vs. 0.663 [0.632–0.693], p=0.003). Accordingly, IDI and NRI demonstrated significant improvements for the re-calculated HAS-BLED compared to baseline (IDI = 0.016, p=0.001; NRI = 0.444, p<0.001). For major bleeding during the period 4–6 years, the c-index of the HAS-BLED score re-calculated at 4-years was non-significantly different to baseline HAS-BLED at baseline (0.631 [0.601–0.660] vs. 0.623 [0.593–0.652], p=0.751), although showed a slight enhance in sensitivity (IDI = 0.009, p=0.018). Conclusions In AF patients, stroke and bleeding risks are dynamic and change over time. The CHA2DS2-VASc and HAS-BLED scores should be regularly reassessed. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by the Spanish Ministry of Economy, Industry, and Competitiveness, through the Instituto de Salud Carlos III after independent peer review (research grant: PI17/01375 co-financed by the European Regional Development Fund)

Long-term outcome and risk factors associated with events in patients with atrial fibrillation treated with oral anticoagulants: The ASSAF-K registry

BackgroundOral anticoagulant therapy for atrial fibrillation (AF) has changed dramatically. Direct oral anticoagulant (DOAC) therapy is administered by general practitioners and specialists. However, the beneficial long-term effects and safety of DOACs have not been well investigated in real-world clinical practice. MethodsThe ASSAF-K (a study of the safety and efficacy of OAC therapy in the treatment of AF in Kanagawa), a prospective, multi-center, observational study, was conducted to clarify patient characteristics, status of OAC treatment, long-term outcomes, and adverse events, including cerebrovascular disease, bleeding, and death. ResultsA total of 4014 patients were enrolled (hospital: 2500 cases; clinic: 1514 cases). The number of patients in the final dataset was 3367 (mean age, 72.6 ± 10.0 years; males, 66.3 %). CHA2DS2-VASc and HAS-BLED scores were 3.0 ± 1.6 and 2.2 ± 1.0, respectively. The risk factors of the primary composite outcome (all-cause death, serious bleeding events, cerebral hemorrhage, and stroke) were higher age, lower body mass index, lower diastolic blood pressure, lower creatine clearance, history of heart failure, history of stroke, and medication of anti-platelet agents. The event-free rates of the primary composite outcome with DOACs, warfarin, and without OACs were 92.7 %, 88.0 %, and 87.4 %, respectively. The event rate of DOACs was significantly lower than that of warfarin [HR 0.63 (95 % CI 0.48–0.81)], and similar results were observed after adjustment for AF stroke risk score [HR 0.70 (95 % CI 0.54–0.90)]. Serious bleeding events tended to occur less frequently with DOACs compared with warfarin [unadjusted HR 0.53 (95 % CI 0.31–0.91), adjusted HR 0.61 (95 % CI 0.33–1.11)]. ConclusionsThis multi-center registry demonstrated the long-term outcome in patients with AF treated with and without OACs and suggests that DOAC therapy is safe and beneficial in hospitals and clinics.

Twice- or once-daily dosing of direct oral anticoagulants and gastrointestinal bleeding in patient with atrial fibrillation

AimsDirect oral anticoagulant (DOAC) is widely used for the prevention of embolic stroke in non-valvular atrial fibrillation (NVAF) patients. However, the gastrointestinal bleeding risk in several DOAC regimens was higher than warfarin, especially in once-daily regimens. Methods and resultsWe conducted a single-center prospective registry of patients with NVAF treated with DOACs: the DIRECT registry (N = 2216; follow-up duration 650 [IQR 103–1574] days, UMIN000033283). All patients were divided into 2 groups: the twice-daily (BID) regimen group (dabigatran and apixaban) versus the once-daily (QD) regimen group (rivaroxaban and edoxaban). Out of 2216 patients, we successfully matched 904 patients in the QD group and 904 patients in the BID group using propensity score. The primary endpoint was gastrointestinal bleeding defined as any bleeding in the gastrointestinal tract that was identified through medical records regardless of bleeding site or severity. The BID group showed a significantly lower gastrointestinal bleeding rate than the QD group (3.5/100 person-year vs. 6.2/100 person-year, log-rank P < 0.0001). The secondary endpoints were all death, stroke, major bleeding, and any bleeding. The rate of major bleeding was significantly lower in patients with BID regimen group (log-rank P = 0.040). In contrast, all death, stroke, and any bleeding did not differ between both groups (log-rank P = 0.280, 0.520 and 0.066, respectively). ConclusionsThe BID regimen as compared with the QD regimen was associated with reduced risk of gastrointestinal bleeding.

Is the association of QTc with atrial fibrillation and stroke in cohort studies a matter of time?

ObjectivesTo investigate the association of the heart rate-corrected QT interval (QTc) with the risk of atrial fibrillation (AF) and ischaemic stroke.MethodsWe estimated the risk of AF and ischaemic stroke associated...

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.

Measuring Mobile Phone Application Usability for Anticoagulation from the Perspective of Patients, Caregivers, and Healthcare Professionals.

Oral anticoagulants (OAC) are recommended for preventing stroke and systemic embolism in atrial fibrillation. Proper use is imperative for maximizing anticoagulation therapy’s effectiveness and safety. In preparation for the implementation of a smartphone-based SmartMed app (application) aiming to promote patient self-management, medication adherence, and data collection for patients on anticoagulation therapy, its usability assessment can ensure the value of OAC app development and adoption. We evaluated the SmartMed app’s usability using the System Usability Scale (SUS) and the app-specific domain of the Mobile App Rating Scale (MARS) for its perceived impact on taking OAC regularly. We recruited 25 OAC users and their home caregivers and 59 healthcare professionals, including pharmacists, nurses, and cardiac surgeons from one medical center and one regional hospital in Taiwan. All participants (n = 84) thought the SmartMed app was useful, with mean SUS and MARS scores of 81.49 (±14.42) and 4.65 (±0.49), respectively. Usability evaluation revealed that fewer experiences with smartphone apps and different healthcare professionals (pharmacists versus nurses or cardiac surgeons) were associated with lower SUS scores and perceived impact. Throughout the evaluation process, the SmartMed app’s design was considered helpful from multiple stakeholders’ perspectives. Further ongoing mobile technology supports are necessary to establish the SmartMed app’s effectiveness.

Assessment of Left Atrial Structure and Function by Echocardiography in Atrial Fibrillation.

Atrial fibrillation (AF) is the most common arrhythmia with significant morbidity and mortality. Exacerbated by the aging population, the prevalence of AF is gradually increasing. Accurate evaluation of structure and function of left atrium (LA) has important prognostic significance in patients with AF. Echocardiography is the imaging technique of first choice to assess LA structure and function due to its better availability, accessibility and safety over cardiac computed tomography and cardiac magnetic resonance. Therefore, the aim of this review is to summarize the recent research progress of evaluating LA size by three-dimensional echocardiography and LA function by speckle tracking echocardiography (STE) in predicting the occurrence and recurrence of AF and determining the risk of stroke in AF. In addition, we summarized the role of traditional echocardiography in detecting AF patients that are at high risk of heart failure or cardiovascular death.

Drug-induced intracerebral hemorrhage

Intracerebral hemorrhage (ICH), which is a form of hemorrhagic stroke, is an extremely serious disease. This pathology is characterized by very high levels of disability and mortality. Despite the improvement in the treatment of those diseases that can lead to ICH, its frequency is currently increasing, which is largely due to the use of drugs, in which case the term «drug-induced intracerebral hemorrhage» (DI ICH) is used. One of the main reasons for drug-induced ICH is an increase in the frequency of prescribing anticoagulant therapy for the prevention of ischemic stroke in atrial fibrillation, as well as dual antithrombotic therapy. In addition to anticoagulants, thrombolytic drugs can lead to the development of this pathology. According to the literature, an increase in the risk of developing ICH is also associated with therapy with antidepressants from the group of selective serotonin reuptake inhibitors, as well as high doses of statins. Risk factors for this adverse reaction are age, smoking, hypertension, and thrombocytopenia. Treatment of DI ICH is an extremely difficult task and includes the withdrawal of the culprit medication, antihypertensive therapy, correction of intracranial hypertension, and, in some cases, the administration of antidotes. The main method of prevention is the use of antiplatelet drugs and other drugs, the use of which is associated with an increased risk of developing DI ICH, in strict accordance with modern protocols and recommendations.

Tolerability and Efficacy of Rivaroxaban vs Warfarin for Non Valvular Atrial Fibrillation

Introduction: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is seen in 1–2% of the general population. Objectives: The main objective of the study is to find the tolerability and efficacy of rivaroxaban Vs warfarin for non valvular atrial fibrillation. Material and methods: This cross sectional comparative study was conducted in Pakistan Institute of Medical Sciences Islamabad during January 2021 to June 2021. After permission from hospital ethical committee, total 70 patients meeting the inclusion and exclusion criteria was enrolled in the study from OPDs of cardiology and allied Departments of hospital. Detailed history and physical examination was done to meet the inclusion and exclusion criteria. Informed consent was obtained. Results: Out of 70 patients enrolled in total, 15 were excluded because of the above-mentioned exclusion criteria; 6 patients of NOAC group denied to participate and left cohort; and 4 patients lost the follow-up. Out of 45 participants, 21 were treated with rivaroxaban, while 24 were treated with warfarin. Conclusion: It is concluded that oral anticoagulant drugs for prevention of stroke in non-valvular AF have been evolved and adding new options and advantages for patients and physicians such as fewer frequency of drug and food interactions, no need for monitoring, broad therapeutic index and tolerated better by patients.

Clinical outcomes in patients receiving edoxaban or phenprocoumon for prevention of stroke in atrial fibrillation: a German real-world cohort study

BackgroundAppropriate and timely anticoagulant therapy with vitamin K antagonists (VKAs) or non-vitamin K oral antagonists (NOACs) is essential for stroke prevention in non-valvular atrial fibrillation (NVAF). Comparative data regarding effectiveness and safety for edoxaban vs phenprocoumon, the predominant VKA in Germany, are scarce.ObjectivesThe study evaluates effectiveness and safety of edoxaban vs phenprocoumon in NVAF patients in a German real-world setting.MethodsGerman statutory health insurance claims data of the Institute for Applied Health Research Berlin (InGef) Research Database from 2014 until 2019 were analyzed. In NVAF patients, new users of edoxaban and phenprocoumon were compared to assess effectiveness (stroke/systemic embolism (SE)) and safety (bleeding) during therapy. Hazard ratios (HR) were estimated through multiple outcome-specific cox proportional hazard models adjusting for baseline characteristics. Outcomes of geriatric patients were analyzed in subgroup analyses.ResultsBetween 2015 and 2018, 7,975 and 13,319 NVAF patients newly initiated treatment with edoxaban or phenprocoumon. After adjusting for baseline confounders, the risk of stroke/SE (HR: 0.85, 95% CI: 0.70–1.02) was numerically but not significantly lower, while the risk of major bleeding (HR: 0.69, 95% CI: 0.58–0.81) was significantly lower for edoxaban. In the geriatric subgroups, homogenous results compared to the main analysis were obtained.ConclusionThe results of this real-world analysis indicated better effectiveness and safety outcomes in patients with NVAF initiating edoxaban treatment compared to phenprocoumon. The findings confirm that the beneficial effects observed in the pivotal ENGAGE AF-TMI 48 trial can also be achieved in real-world use of edoxaban.

Protocol for Home-Based Solution for Remote Atrial Fibrillation Screening to Prevent Recurrence Stroke (HUA-TUO AF Trial): a randomised controlled trial

IntroductionCurrent international guidelines recommend ECG monitoring after an ischaemic stroke to detect atrial fibrillation (AF) in order to prevent stroke recurrence. However, optimal strategies to detect AF and the downstream...

Study on the predictive ability of emergency CHADS2 score and CHA2DS2-VASc score for coronary artery disease and prognosis in patients with acute ST-segment elevation myocardial infarction.

BackgroundAcute ST-segment elevation myocardial infarction (STEMI) has a high morbidity and mortality rate. The congestive heart failure, hypertension, age, diabetes, previous stroke/transient ischemic attack (2 points) (CHADS2) and CHADS2 score with 2 points assigned for age >75 years-vascular disease (CHA2DS2-VASc) scores are widely used for risk stratification management of non-valvular atrial fibrillation stroke and have high prognostic value in cardiovascular disease. This study aims to investigate the predictive value of the emergency CHADS2 and CHA2DS2-VASc score on coronary artery lesions and prognosis in patients with acute STEMI.MethodsA total of 524 patients with STEMI from May 2018 to October 2021 were selected for emergency CHADS2 and CHA2DS2-VASc. Clinical data and laboratory indicators were collected. Patients were evaluated for coronary artery disease (CAD) and prognosis. Logistic regression and the receiver operating characteristic (ROC) curve were used to analyze the data.ResultsIn severe group, CysC levels, CHADS2, CHA2DS2-VASc score and the proportion of diabetes, stroke or transient ischemic attack (TIA), congestive heart failure, smoking history, Killip class ≥2 was higher than that in mild and moderate group. In poor prognosis group, levels of serum creatinine (Crea), CysC, hemoglobin (Hb), CHADS2, CHA2DS2-VASc score and the proportion of hypertension, diabetes, stroke or TIA, congestive heart failure, smoking history, and Killip class ≥2 was higher than that in good prognosis group. Diabetes (OR, 3.678; 95% CI: 2.876–5.872, 0.008), CHADS2 (OR, 3.829; 95% CI: 2.310–5.832, 0.003) and CHA2DS2-VASc score (OR, 4.671; 95% CI: 3.125–6.187, 0.000) were independent risk factors for the severity of CAD (P<0.05). Diabetes (OR, 3.287; 95% CI: 2.231–5.123, 0.012), Killip class ≥2 (OR, 2.212; 95% CI: 1.023–2.987, 0.045), LVEF (OR, 3.110; 95% CI: 2.124–5.031, 0.023), CHADS2 (OR, 3.228; 95% CI: 2.133–5.886, 0.005) and CHA2DS2-VASc score (OR, 3.988; 95% CI: 2.987–5.873, 0.001) were independent risk factors for prognosis of acute STEMI patients. Area under curve (AUC) value of CHA2DS2-VASc score in evaluating CAD and prognosis was 0.947, 0.931, higher than that of the CHADS2 score (0.836, 0.812) (P<0.05).ConclusionsMultiple factors jointly affect the severity and prognosis of CAD in patients with acute STEMI. The CHA2DS2-VASc score is better than the CHADS2 score in predicting the severity of coronary artery lesions and prognosis of patients, providing theoretical support for clinical practice.

Left atrial appendage closure using WATCHMAN device in chronic kidney disease and end-stage renal disease patients.

Chronic kidney disease (CKD) and end-stage renal disease are considered independent risk factors for developing atrial fibrillation (AF). Percutaneous occlusion of left atrial appendage (LAAC) using WATCHMAN device is a widely accepted alternative to anticoagulation therapy to prevent ischemic stroke in AF in patients who are not candidates for anticoagulation. There is limited data regarding the utilization and periprocedural safety of this intervention in patients with CKD/ESRD. We retrospectively reviewed all hospitalizations from 2016 to 2017 with (ICD-10) procedure diagnosis code of LAA closure using WATCHMAN procedure with and without a secondary diagnosis of CKD/ESRD in acute-care hospitals across the United States using the national inpatient sample. Demographic variables (gender, race, income, hospital characteristics, medical comorbidities) were collected and compared. The primary outcomes were inpatient mortality, hospital length, and cost of stay. There were over 71 million discharges included in the combined 2016 and 2017 NIS database. Sixteen thousand five hundred five hospitalizations were for adult patients with a procedure code for LAA closure via watchman procedure. Of 16,505 patients, 3245 (19.66%) had CKD and ESRD. There was no statistically significant difference in mortality, length, and cost of stay in patients with and without CKD/ESRD. There were no statistically significant differences in periprocedural cerebrovascular accidents in both groups. Patients with and without ESRD/CKD who undergo LAA occlusion with Watchman have similar procedure related, in-hospital mortality, and complications.

Cost-Utility Analysis of Dabigatran and Warfarin for Stroke Prevention Among Patients With Nonvalvular Atrial Fibrillation in India

ObjectivesDabigatran has a better safety profile and requires less monitoring, but is costlier than warfarin. This study evaluated the cost-utility of dabigatran relative to warfarin for preventing stroke in nonvalvular atrial fibrillation (NVAF) in India. MethodsA Markov decision analysis model was developed to compare dabigatran (110 or 150 mg twice a day) to warfarin titrated to target prothrombin time in patients with NVAF at high risk of stroke. Model utilities and transition probabilities were based on literature and costs on market prices. Data on out-of-pocket expenses and income lost were taken from a nationally representative survey. We adopted a societal perspective and discounted both costs and outcomes at 3%. Ischemic stroke, intracranial bleed, other major bleeds, and death were outcomes of NVAF. The model projected the costs, life-years, and quality-adjusted life-years (QALYs) for each intervention over a lifetime. We used gross domestic product per capita of India (US dollars [US$]1889) as the cost-effectiveness threshold. Sensitivity analyses were conducted. ResultsTreatment with either dose of dabigatran was associated with gain in life-years and QALYs compared with warfarin. The discounted incremental cost-effectiveness ratios/QALYs for both doses of dabigatran (110 mg US$7519; 150 mg US$6634) were above the cost-effectiveness threshold, and the probability of being cost-effective at this threshold was low. Cost of dabigatran was an important factor in determining incremental cost-effectiveness ratio. Price reduction of 150 mg dose by 49% will make it cost-effective. ConclusionsDabigatran is not cost-effective in the Indian societal context. Reducing the price of dabigatran 150 mg by half will make it cost-effective.

High frequency of anticoagulation management errors preceding ischaemic strokes in atrial fibrillation.

Anticoagulants are recommended to prevent cardioembolic stroke in most patients with atrial fibrillation (AF). Management errors with anticoagulation and use of aspirin instead of anticoagulants have been documented worldwide, especially with vitamin K antagonists. To assess the rate of anticoagulant mismanagement errors in patients admitted with ischaemic stroke and the clinical correlates with stroke outcomes in the era of non-vitamin K oral anticoagulants. We performed a retrospective analysis of patients admitted with ischaemic stroke and history of AF to a single-centre tertiary hospital stroke unit in Melbourne, Australia, between January 2016 and June 2019. We assessed management errors as defined using European Heart Rhythm Association criteria with anticoagulation in the 2 weeks prior to the index stroke. A total of 306 patients with AF and ischaemic stroke was included, of whom 196 (64%) had management errors. Patients with management errors were older (median age 84 vs 81 years; P = 0.002) and more often female (53% vs 38%; P = 0.02). Of those with management errors, 74 (37%) were not prescribed any anticoagulation despite increased stroke risk and absence of contraindications and 40 (20%) had anticoagulation inappropriately ceased. Mortality at 3 months was 32% in those with management errors, compared with 17% in the appropriately anticoagulated group (P = 0.005). Inappropriate management of anticoagulants is present in the majority of acute ischaemic stroke in the 2 weeks preceding the event and is linked to higher mortality. Improved anticoagulation practice has the potential to substantially reduce stroke rates in patients with AF.

Frequency of cardioversions as an additional risk factor for stroke in atrial fibrillation – the FinCV-4 study

Background Patients with atrial fibrillation (AF) are selected for oral anticoagulation based on individual patient characteristics. There is little information on how clinical AF burden associates with the risk of ischaemic stroke or systemic embolism (SSE). The aim of this study was to explore the association of the frequency of cardioversions (CV) as a measure of clinical AF burden on the long-term SSE risk, with a focus on patients at intermediate stroke risk based on CHA2DS2-VASc score. For these patients, additional SSE risk stratification by assessing CV frequency may aid in the decision on whether to initiate oral anticoagulation. Methods This retrospective analysis of FinCV Study from years 2003–2010 included 2074 patients who were not using any oral anticoagulation (long term or temporary) after CVs and undergoing a total of 6534 CVs for AF from emergency departments of three hospitals. Two study groups were formed: high CV frequency (mean interval between CVs ≤12 months and low frequency (>12 months). Results A total of 107 SSEs occurred during a mean follow-up of 5.4 years. The event rates per 100 patient-years were 1.82 and 0.67 in high versus low CV frequency groups, respectively. After adjustment for CHA2DS2-VASc score, CV frequency independently predicted SSE (HR, 2.87 [95% CI, 1.47 to 5.64]; p = .002) at 3 years. Competing risk analysis also identified CV frequency (sHR, 2.70 [95% CI, 1.38–5.31]; p = .004) as an independent predictor for SSE. In patients with CHA2DS2-VASc score 1 and low CV frequency, the SSE risk was only 0.08 per 100 patient-years. Conclusions Frequency of CVs for symptomatic AF episodes provides additional information on stroke risk in AF patients with CHA2DS2-VASc score 1. Key messages This retrospective study offers a unique opportunity to observe the natural course of AF patients with infrequent episodes of clinical arrhythmia when they were not using OAC (before introduction of CHA2DS2-VASc score). Stroke or systemic embolism rate was very low (0.08 per 100 patient-years) in patients with one CHA2DS2-VASc point who visited the emergency room for cardioversion less than once a year. Frequency of cardioversions can be used for additional risk stratification in patients at intermediate risk of stroke based on CHA2DS2-VASc score.

Left atrium hemodynamic in atrial fibrillation and normal subjects

Abstract Funding Acknowledgements Type of funding sources: None. Background A computational fluid-dynamics (CFD) model previously developed with the aim of evaluating cardioembolic risk in patient affected by atrial fibrillation (AF) was used for the characterization of the left atrium (LA) hemodynamic in normal subjects (NL), patients affected by paroxysmal atrial fibrillation (PAR-AF) and patients affected by persistent atrial fibrillation (PER-AF). Based on the fluid-dynamics simulations results, we aimed at enhancing differences in blood flow in AF patients and NL and at better understanding the relationship between AF progression and stroke risk on a patient-specific basis. Methods 3D patient-specific anatomical and motion models were derived from ECG-gated coronary artery CT acquired with retrospective protocol. These models represented the computational domain for CFD simulations in which inflow initial conditions were derived from PW Doppler at the mitral valve and at the pulmonary veins. Velocity field and vortex structures both within the LA and left atrial appendage (LAA) were assessed in 10 NL, 5 PAR-AF and 4 PER-AF. Blood stasis was evaluated by populating the LAA with 500 particles and counting the number of particles still present after five cardiac cycles. Results Velocities inside the LA and in the LAA presented different amplitude and distribution in the 3 groups (peak velocity – NL: 50÷60 cm/s, PAR-AF: 40÷50 cm/s, PER-AF: 15÷25 cm/s). The mean velocity resulted lower in the PER-AF compared with PAR-AF (mean velocity – PAR-AF: 25÷35 cm/s, PER-AF: 8÷20 cm/s) at the LAA ostium and inside the LAA, in which the wash-out effect was strongly reduced (Figure 1). On the other hand, the mean velocity in the NL was higher with respect of AF patients (mean velocity – NL: 40÷45 cm/s). A higher number of vortex structures was observed in NL compared with AF patients, thus favouring the hypothesis of a more efficient wash-out of the LA and of the LAA. Blood stasis in terms of number of particles in the LAA after five cardiac cycles confirmed these results (NL: 5±2, PAR-AF: 18±3, PER-AF: 41±10). Conclusions The developed approach quantifies differences in LA hemodynamic between AF and NL patients, also allowing a stratification of the atrial disease progression in terms of variations in the blood velocity, organization of blood flow and quantification of blood stasis.

The role of CHA2DS2-VASc score in predicting atrial fibrillation recurrence in patients undergoing pulmonary vein isolation with cryoballoon ablation

Abstract Funding Acknowledgements Type of funding sources: None. Background Pulmonary vein isolation by cryoablation (PVI-C) is a standard therapy for the treatment of atrial fibrillation (AF) with high safety and efficacy profiles. The CHA2DS2 -VASc score is also a well-established predictor of AF stroke. Importantly, the role of CHA2DS2-VASc score is still unknown regarding the long-term clinical outcomes following PVI-C. Purpose The aim of this analysis is to evaluate the role of CHA2DS2-VASc score in predicting AF recurrence during long term follow up after PVI-C. Methods Patients with recurrent and symptomatic AF underwent an index PVI-C. Data were collected prospectively in the framework of 1STOP ClinicalService® project. Patients were categorized into two groups Low risk (LR) and high risk (HR) (CHA2DS2-VASc score = 0-1 and CHA2DS2 -VASc score ≥2, respectively). Results Out of 3313 patients, 1910 (57.6%) had CHA2DS2-VASc score = 0-1, while 1403 (42.3%) were in the HR score group (CHA2DS2 -VASc score ≥2). As expected, patient baseline characteristics were significantly different between the two cohorts including: age, sex, BMI, percentage of paroxysmal AF, history of stroke, diabetes, ischemic cardiomyopathy. On the contrary, procedural times and the incidence of acute complications were comparable between the two groups. The 36-month freedom from AF after a single procedure was 72.5% (95% CI 69.8% - 75.0%) in the LR group and 65.9% (62.3% - 69.2%) in the HR score group (HR: 1.26, 95% CI 1.08-1.47, p= 0003, Figure 1). At multivariate analysis, higher CHA2DS2 -VASc score was still a significant predictor of the risk of AF recurrence [HR: 1.33 (1.10 - 1.60, p=0.003] Conclusions PVI-C is highly effective in the treatment of AF over the long term. A CHA2DS2 -VASc score ≥2 is an independent predictor of AF recurrence during the follow-up and should be taken into account in the clinical management after the index procedure.

Cryptogenic stroke in atrial fibrillation without intra-heart thrombi: possible mechanisms

Background. Up to 45% of ischemic strokes are cryprogenic.Aim is to study which variant of permanent AF without intra-heart thrombi is the most unfavorable in appearing of stroke.Methods. We observed 202 patients with permanent AF without intra-heart thrombi and hemodynamically not significant carotid bifurcation atherosclerotic stenosis. We performed echocardiography, 24-hours monitoring of electrocardiography (ECG), ultrasound of brachiocephalic arteries, sphygmography of common carotid arteries, computer tomography of the brain, hemostasiograms, lipid profile, hemoglobin A1c. According to the 24-hours ECG monitoring data, we divided patients into two groups up to the maximum pauses between ventricular complexes in AF: patients with a pause &lt;1,5 seconds (113); ≥1,5 seconds (89). Both groups were on the same standard therapy including novel oral anticoagulants. We observed the patients during 1 year to analyze the verified stroke or transient ischemic attack (TIA).Results. In ultrasound, there was an increase of linear blood flow velocity in the area of carotid stenosis during the spread of the pulse wave after the long pause between ventricular contractions in group 2 up to 2,5 m/sec as in hemodynamically significant stenosis. In 1-year observation, there was the higher stroke in group 2.Conclusion. The appearance of stroke and TIA in AF is higher in patients who have 1,5 seconds and more of maximum duration pauses between ventricular contractions. The reason of cryptogenic stroke can be the atherosclerotic plaque defragmentation with further embolism, caused by additional mechanical impact of increased hemodynamical parameters of pulse wave after long pause between ventricular contractions.

Analyzing Corin-BNP-NEP Protein Pathway Revealing Differential Mechanisms in AF-Related Ischemic Stroke and No AF-Related Ischemic Stroke.

BackgroundThe incidence of atrial fibrillation (AF)-related stroke increases with aging. Natriuretic peptides (NPs) family, including Corin-B type natriuretic peptide (BNP)-neprilysin (NEP) protein levels increased with age and are risk markers of cardiovascular and cerebrovascular diseases, such as AF and cardioembolic stroke. Aging is also linked to epigenetics, specifically DNA methylation. However, only a few studies have investigated the effect of DNA methylation on the NP system. Thus, the present study aimed to investigate whether the Corin-BNP-NEP protein pathway is involved in the pathogenesis of AF-stroke and CpG methylation in the promoter region of the Corin protein gene has an effect on AF-related ischemic stroke.MethodsA total of 82 patients hospitalized with acute ischemic strokes were enrolled in this study. The differences in clinical information were compared between the AF-stroke (n = 37) and no AF-stroke groups (n = 45). Plasma-soluble Corin and NEP were detected using an ELISA kit. CpG methylation in the promoter region of the gene was assessed by a next-generation sequencing-based bisulfite sequencing polymerase chain reaction (BSP).Results(1) Patients in AF-stroke were older, had higher initial NIHSS score, 90-day mRs, higher D2-dimer, INR, and APTT, and low TG, TC, and HbA1c (all p < 0.05). (2) Serum levels of Corin and BNP in the AF-stroke group were significantly higher than that in the no AF-stroke group (p < 0.05). No significant difference was detected in the serum levels of NEP between the two groups. (3) The levels of CpG methylation in the promoter region of the Corin protein gene in the AF-stroke group was significantly lower than that in the no AF-stroke group (p < 0.05). The CpG sites with maximal methylation differences between the two groups were CORIN:678, CORIN:682, CORIN:694, and CORIN:700.ConclusionThe current findings raise the possibility that the Corin–BNP–NEP protein pathway may be involved in the pathogenesis of AF-related ischemic stroke. Deficient CpG methylation in the promoter region of the Corin protein gene is associated with AF-related ischemic stroke.