Stroke In Atrial Fibrillation Research Articles

Bone morphogenetic protein 10: a novel risk marker of ischaemic stroke in patients with atrial fibrillation.

Biomarkers specifically related to atrial tissue may increase the understanding of the pathophysiology of atrial fibrillation (AF) and further improve risk prediction in this setting. Bone morphogenetic protein 10 (BMP10) is a protein expressed in the atrial myocardium. We evaluated the association between BMP10 and the risk of ischaemic stroke and other cardiovascular events in large cohorts of patients with AF, treated with and without oral anticoagulation (OAC). BMP10 was measured in plasma samples collected at randomisation in patients with AF without OAC in the ACTIVE A and AVERROES trials (n = 2974), and with OAC in the ARISTOTLE trial (n = 13 079). BMP10 was analysed with a prototype Elecsys immunoassay. Associations with outcomes were evaluated by Cox-regression models adjusted for clinical characteristics, kidney function, and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Median concentrations of BMP10 were 2.47 and 2.44 ng/mL, in the non-OAC and OAC cohort, respectively. Increasing BMP10 was associated with lower body mass index, older age, female sex, kidney dysfunction, and AF rhythm. BMP10 was consistently associated with ischaemic stroke. In the non-OAC cohort, BMP10 increased the concordance index of the multivariable model from 0.713 to 0.733 (P = 0.004) and in the OAC cohort from 0.673 to 0.694 (P < 0.001). Additionally, BMP10 maintained a significant prognostic value after additionally adjusting for NT-proBNP. BMP10 was not independently associated with bleeding or with death. The novel atrial biomarker BMP10 was independently associated with ischaemic stroke in patients with AF irrespective of OAC treatment. BMP10 seems to be more specifically related to the risk of ischaemic stroke in AF. In this study, BMP10 may be a novel specific biomarker of ischaemic stroke in patients with atrial fibrillation, irrespective of oral anticoagulation.

Proportion of Patients on Warfarin Therapy Who Are Eligible for Conversion to a Direct Oral Anticoagulant in the Setting of COVID-19.

Warfarin, a commonly prescribed anticoagulant, requires frequent lab monitoring. Lab monitoring puts patients at risk of COVID-19 exposure and diverts medical resources away from health care systems. Direct oral anticoagulants (DOACs) do not require routine therapeutic monitoring and are indicated first line for nonvalvular atrial fibrillation (NVAF) stroke prevention and venous thromboembolism (VTE) prevention/treatment. The purpose of the study was to determine the proportion of patients who qualify for DOACs and assess for predictors of qualification. This cross-sectional study investigated patients on warfarin managed by Michigan Medicine Anticoagulation Service. Direct oral anticoagulant eligibility criteria were established using apixaban, dabigatran, and rivaroxaban package inserts. Patient eligibility was determined through chart review. The primary outcome was the proportion of patients who qualify for DOACs based on clinical factors. Predictors of DOAC qualification were assessed. This study included 3205 patients and found 51.8% (n = 1661) of patients qualified for DOACs. Qualifying patients were older (71.9 vs 59.4 years, P < 0.0001) with a higher CHA2DS2 VASc (3.7 vs 3.4, P < 0.0007). The primary disqualifying factor was extreme weight, high and low. Accounting for a patient's sex and referral source, age > 65 (odds ratio [OR] = 1.9, P < 0.0001) and NVAF indication (OR = 5.6, P < 0.0001) were significant predictors for DOAC qualification. Approximately 52% of patients on warfarin were eligible for DOACs. This presents an opportunity to reduce patient exposure to health care settings and health care utilization in the setting of COVID-19. Increased costs of DOACs need to be assessed.

Prediction Algorithms: Is Peer Review Enough?

Prediction Algorithms: Is Peer Review Enough?

Correction to: Early Versus Delayed Non-Vitamin K Antagonist Oral Anticoagulant Therapy After Acute Ischemic Stroke in Atrial Fibrillation (TIMING): A Registry-Based Randomized Controlled Noninferiority Study.

Correction to: Early Versus Delayed Non-Vitamin K Antagonist Oral Anticoagulant Therapy After Acute Ischemic Stroke in Atrial Fibrillation (TIMING): A Registry-Based Randomized Controlled Noninferiority Study.

Abstract 14037: Nonspecific Tools Performed Better in Discriminating Major Bleeding From Direct Oral Anticoagulants Than Specific Tools in a Real-World Population With Atrial Fibrillation

Background. Direct oral anticoagulants (DOACs) are the first-line guideline-recommended therapy for preventing stroke in non-valvular atrial fibrillation (AF) patients. DOACs are increasingly being prescribed in the US compared to warfarin because of lower bleeding risk overall, but the proportion of Emergency Department visits involving DOACs-related bleeding increased from 2.3% in 2011 to 37.9% in 2017. Therefore, tools that accurately predict bleeding risk from DOACs are needed. Aim. This study compared the performance of six tools for predicting major bleeding risk in non-valvular AF patients on DOACs. Methods. A retrospective cohort study was carried out with 2,364 Caucasians diagnosed with non-valvular AF and treated with rivaroxaban or apixaban at the University of Michigan Health System. Bleeding risk was calculated using six existing tools: CHA 2 DS 2 -VASc, Anticoagulation-specific Bleeding Score (ABS), HAS-BLED, ATRIA, HEMORR2HAGES, and ORBIT. Major bleeding events were retrieved from medical records and classified according to International Society of Thrombosis and Haemostasis criteria. Discrimination was estimated using the c-statistic, and the areas under the curves (AUC) were compared using the Hanley-McNeil test. RGui was used for all statistical analyses and p-values &lt;0.05 were considered statistically significant. Results. A total of 97 (4.1%) patients experienced major bleeding on DOACs over 2.27 ± 2.03 years of follow-up. HAS-BLED and ABS are tools for specifically predicting major bleeding risk, but both had significantly lower performance than ATRIA, HEMORR2HAGES, and ORBIT ( Figure 1 ). There was no significant difference in the discriminative performance between HAS-BLED and ABS, as well as between ATRIA, HEMORR2HAGES, and ORBIT. Conclusion. ATRIA, HEMORR2HAGES, and ORBIT were the tools that performed better in discriminating major bleeding in AF patients if compared to HAS-BLED and ABS.

Abstract 11021: Chest Symptoms and Subsequent Risk of Incident Cardiovascular Disease: The Atherosclerosis Risk in Communities (ARIC) Study

Introduction: The 2021 AHA/ACC Chest Pain Guideline classifies the likelihood of ischemia according to chest symptom characteristics. However, the associations of various chest symptoms with long-term risk of different cardiovascular disease (CVD) have not been fully investigated. Aim: To quantify the associations of chest pain and dyspnea with incident major CVD. Methods: In 13,200 ARIC participants (mean age 54 [SD 6] years, 56% female, 25% Blacks) without prior CVD at visit 1 (1987-89), we categorized chest pain into definite angina, possible angina, non-anginal chest pain, and no chest pain based on the WHO Rose questionnaire, and dyspnea into grade 0, 1, 2, and 3-4 based on the Medical Research Council scale. CVD outcomes included myocardial infarction (MI), heart failure (HF), atrial fibrillation (AF), and ischemic stroke (median follow-up, 26-28 years). We estimated 30-year cumulative incidence accounting for competing risk of deaths and ran multivariable Cox models. Results: Definite angina and possible angina were robustly associated with incident MI (Table), with adjusted HR 1.83 (95%CI 1.51-2.22) and 1.64 (1.26-2.13), respectively. These two chest pain types were also related to HF, AF, and ischemic stroke, although possible angina did not reach statistical significance for stroke. Even non-anginal chest pain was associated with MI, HF, and AF. Dyspnea showed graded association with all CVD outcomes, but particularly with MI and HF (bottom half of Table). For example, grade 3-4 and 2 showed HR of 2.13 (1.71-2.65) and 1.41 (1.13-1.76), respectively, for MI. When chest pain and dyspnea were modeled simultaneously, their associations were independent. Conclusions: In persons without prior CVD, chest pain and dyspnea were independently associated with different CVD events over 30 years. Our findings suggest broad prognostic implications of chest pain beyond coronary disease and emphasize the importance of recognizing dyspnea for CVD risk management.

Abstract 10643: Anticoagulation Prescriptions for Patients With Acute Precipitants of Atrial Fibrillation in the VITAL-AF Study

Introduction: Many patients with incident atrial fibrillation (AF) are diagnosed in the setting of a potentially transient precipitant. Despite substantial rates of AF recurrence and stroke in this population, prior registries and survey data suggest lower usage of oral anticoagulants (OAC). Here, we examined use of OAC on the basis of precipitated versus non-precipitated AF among patients enrolled in the VITAL-AF trial. Methods: VITAL-AF (clinicaltrials.gov NCT03515057) was a cluster randomized trial of 16 primary care practices evaluating point-of-care AF screening using single-lead ECGs among individuals aged ≥ 65 years (n=30,715). The primary outcome of newly diagnosed AF at one year occurred in 503 patients. For each incident AF event, we performed manual chart review to classify if diagnosis occurred in the setting of an acute precipitant, if the episode was transient, and if OAC was initiated. AF was considered transient if there was documented return to sinus rhythm within three months of initial diagnosis. OAC initiation required both evidence of a new prescription and corresponding provider documentation Results: Of the 503 cases of incident AF diagnosed during the VITAL-AF study period, 125 (24.9%) occurred in the setting of an acute precipitant. The mean age of patients with newly diagnosed AF was 78.3 ± 9.0 years, 46% were female, 11% were non-white, and the mean CHA 2 DS 2 -VASc score was 4.2 ± 1.6, which were similar between those with and without a precipitant. Patients with acute precipitants of AF were more likely to have transient episodes (94% vs 76%, p=0.001) and less likely to be started on OAC (60% vs 82%, p&lt;0.001) than patients without a precipitant. In a multivariable model adjusted for age, race, gender, CHA 2 DS 2 -VASc score, study arm, and screening status, AF occurring in the context of a precipitant was associated with significantly decreased odds of OAC initiation (odds ratio [OR] 0.32, 95% CI [0.20, 0.52]). Conclusions: Patients diagnosed with precipitated AF are more likely to have transient episodes with return to sinus rhythm within three months of diagnosis and less likely to be started on OAC compared to patients without a precipitant. Future analyses examining the effectiveness of OAC among patients with precipitated AF are warranted.

An ECG-based machine learning model for predicting new-onset atrial fibrillation is superior to age and clinical features in identifying patients at high stroke risk

Background:Several large trials have employed age or clinical features to select patients for atrial fibrillation (AF) screening to reduce strokes. We hypothesized that a machine learning (ML) model trained to predict AF risk from 12‑lead electrocardiogram (ECG) would be more efficient than criteria based on clinical variables in indicating a population for AF screening to potentially prevent AF-related stroke.Methods:We retrospectively included all patients with clinical encounters in Geisinger without a prior history of AF. Incidence of AF within 1 year and AF-related strokes within 3 years of the encounter were identified. AF-related stroke was defined as a stroke where AF was diagnosed at the time of stroke or within a year after the stroke. The efficiency of five methods was evaluated for selecting a cohort for AF screening. The methods were selected from four clinical trials (mSToPS, GUARD-AF, SCREEN-AF and STROKESTOP) and the ECG-based ML model. We simulated patient selection for the five methods between the years 2011 and 2014 and evaluated outcomes for 1 year intervals between 2012 and 2015, resulting in a total of twenty 1-year periods. Patients were considered eligible if they met the criteria before the start of the given 1-year period or within that period. The primary outcomes were numbers needed to screen (NNS) for AF and AF-associated stroke.Results:The clinical trial models indicated large proportions of the population with a prior ECG for AF screening (up to 31%), coinciding with NNS ranging from 14 to 18 for AF and 249–359 for AF-associated stroke. At comparable sensitivity, the ECG ML model indicated a modest number of patients for screening (14%) and had the highest efficiency in NNS for AF (7.3; up to 60% reduction) and AF-associated stroke (223; up to 38% reduction).Conclusions:An ECG-based ML risk prediction model is more efficient than contemporary AF-screening criteria based on age alone or age and clinical features at indicating a population for AF screening to potentially prevent AF-related strokes.

Association of Echocardiographic Parameter E/e’ With Cardiovascular Events in a Diverse Population of Inpatients and Outpatients With and Without Cardiac Diseases and Risk Factors

The echocardiographic parameter E/e' has been associated with cardiovascular (CV) events. However, few studies have analyzed multiple associated CV outcomes using E/e' in a diverse population of both inpatients and outpatients with and without cardiac diseases and risk factors. Medical records of 75,393 patients without atrial fibrillation (AF) with first available E/e' were retrieved from our hospital database. Patients with mitral valve disease were excluded, and the remainder were studied in protocol 1 (70,819 patients). Patients with hypertension, diabetes mellitus, hyperlipidemia, CV diseases, prior CV events, CV surgeries, and left ventricular ejection fraction <50% or missing left ventricular ejection fraction were further excluded, and the remaining patients were studied in protocol 2 (14,665 patients). The study outcomes are major adverse CV events (MACE), which included myocardial infarction (MI), AF, ischemic and hemorrhagic stroke (IHS), hospitalization for heart failure (HHF), and cardiac death. The primary outcomes were MACE and each of the MACE components. At the end of maximal 5-year follow-up (median 22.18months with interquartile range 7.20-49.08months for MACE in protocol 1 and 23.46months with interquartile range 8.15-49.02months for MACE in protocol 2), compared with an E/e' value of <8, an intermediate value of E/e' 8 to 15 and a high value of E/e' >15 were significantly associated with MACE, MI, AF, IHS, HHF, and cardiac death in protocol 1 (all P<.0001). In protocol 2, an intermediate E/e' value of 8 to 15 and a high value of E/e' >15 were significantly associated with MACE, MI, AF, IHS, HHF, and CV death (all P<.05), except an intermediate value E/e' 8 to 15 was not associated with AF. In a diverse population of inpatients and outpatients with and without cardiac diseases and risk factors, the echocardiographic parameter E/e' was associated with CV events and is a useful marker of risk.

Atrial Fibrillation Detected After Acute Ischemic Stroke

Atrial fibrillation (AF) increases 4-5 times incidence of cardiac embolic stroke. In contrast, as many as 70% of AF cases can be detected in stroke within three days of onset, and this can affect the patient's prognosis. This case report describes the causal pathophysiology of AF and acute stroke and identifies the associated risk factors. Case 1 is a 44-year-old woman, acute stroke with acute decrease level of consciousness. The patient came with status epilepticus and a hypertensive emergency. Obtained a history of stroke, uncontrolled hypertension, and myocardial infarction. Initial Score National Institutes of Health Stroke Scale (NIHSS) was 33 and CHA2DS2-VASc was 5. Investigation non-contrast head Computed Tomography (CT) scan showed no bleeding and echocardiography (ECG) showed AF with rapid ventricular response. The patient died after 3 days of treatment. Case 2 is an 83-year-old woman, acute stroke with acute decrease level of consciousness and right motor lateralization. There was a history of hypertension and stroke with left hemiparesis. The initial NIHSS was 28 and CHA2DS2-VASc was 6. Investigations non-contrast head CT scan showed no bleeding and ECG showed AF with normal ventricular response. The patient was discharged from the hospital after being treated for 22 days with NIHSS of 20. Several risk factors for post-stroke AF are elderly, hypertension, subtype of ischemic stroke, prior stroke, and comorbidities such as DM and hypertension. Post-stroke AF can occur because of changes in heart rhythm through autonomic disorders, increased plasma catecholamine levels, and inflammatory reactions. Early Recognition of risk factors, focusing on patients at higher risk of AF detected after stroke becomes important for comprehensive management of stroke with AF.&#x0D; Keywords: acute ischemic stroke, atrial fibrillation, CHA2DS2-VASc score, risk factors.

Systematic Review of Patient Decision Aids for Stroke Prevention Therapy in Atrial Fibrillation Management.

Atrial Fibrillation (AF) is a major cause of stroke. Oral anticoagulation can reduce the risk of AF-associated stroke by 65% but it remains underused. Stroke prevention therapy in patients with AF has been considered a good target for shared decision making with patient decision aids as it is a long-term, preference-sensitive decision with known risk-benefit trade-offs. The aim of this systematic review was to summarize published literature on the effectiveness of patient decision aids on the choice of and adherence to stroke prevention therapy in individuals with AF. We conducted a structured literature search for prospective studies evaluating decision aids for AF stroke prevention therapy in adult patients with nonvalvular AF. We included studies that compared those exposed to a decision aid with a control condition for outcomes including choice of therapy, adherence, decisional conflict and patient knowledge. Quantitative meta-analysis was not feasible due to excessive between-study heterogeneity. Eight studies met inclusion and exclusion criteria. Six studies were randomized clinical trials and two were pre-post comparisons. Of the 8 studies, each evaluated a different decision aid, with only three including all contemporary oral anticoagulant drugs. All decision aids improved AF knowledge compared to baseline or control and decision aids reduced decisional conflict in four of six studies. However, there were inconsistent effects of the studied decision aids on initiation of oral anticoagulation. Adherence to initial stroke prevention therapy choice appeared to benefit from decision aid use in 2 studies that addressed this issue. Decision aids for stroke prevention increased AF patients' knowledge and decisional confidence but had variable impacts on choice of and adherence to stroke prevention therapy. The results highlight the need for well-designed decision aids that present patients with all contemporary therapeutic options.

Participation of Older Adults in Clinical Trials for New Drug Applications and Biologics License Applications From 2010 Through 2019

Older age may be accompanied by changes in the pharmacokinetics or pharmacodynamics or both of medications that can result in altered safety and efficacy profiles. To assess representation of older adults in clinical trials of new drug applications (NDAs) and biologics license applications (BLAs). This cross-sectional study analyzed US Food and Drug Administration (FDA) data for NDAs and BLAs approved from 2010 through 2019. Age distribution of clinical trial participants was compared with age distribution of the US population with the disease or disorder (prevalent population). Data were from adults enrolled in registration trials for depression, heart failure, insomnia, non-small cell lung cancer (NSCLC), nonvalvular atrial fibrillation (NVAF) stroke prevention, osteoporosis, and type 2 diabetes or adults sampled from US prevalent population in community-dwelling health data. Data were analyzed from November 2020 to February 2021. Trial enrollment. Representativeness of trial populations was assessed by the participation to prevalence ratio (PPR) defined as the percentage of patients by age group among clinical trial participants to the percentage of patients by age group among US prevalent population. Data from 166 clinical trials (229 558 participants) for 44 NDAs and BLAs were analyzed. The most consistent finding was the limited enrollment of the oldest age groups, namely those 75 years and above for type 2 diabetes and NSCLC, and 80 years and above for NVAF stroke prevention, insomnia, heart failure, and osteoporosis. Adults aged 60 to 74 years were enrolled in equal or greater proportion than the US prevalent population. In this cross-sectional study, underrepresentation of the oldest adults existed during evaluation of new drugs and biologics, yet the older adults may represent significant proportions of the treatment population. Closing the representation gap between clinical trial enrollment and potential treatment populations is essential for safe and effective use of new drugs and biologics.

N-terminal pro-B-type natriuretic peptide and D-dimer combined with left atrial diameter to predict the risk of ischemic stroke in nonvalvular atrial fibrillation.

We aimed to explore the potential role of N-terminal pro-B-type natriuretic peptide (NT-proBNP), d-dimer, and the echocardiographic parameter left atrial diameter (LAD) in identifying and predicting the occurrence of ischemic stroke (IS) in patients with nonvalvular atrial fibrillation (NVAF). We conducted a retrospective study of 445 patients with NVAF in the First Affiliated Hospital of Nanchang University. They were divided into the NVAF (309 cases) and NVAF with stroke (136 cases) groups according to whether acute ischemic stroke (AIS) occurred at admission. Multivariate logistic regression was used to analyze the odds ratio (OR) of NT-proBNP, d-dimer, and LAD for IS. The predictive value of NT-proBNP, d-dimer, and LAD in identifying the occurrence of IS in NVAF was determined by plotting the receiver operating characteristic (ROC) curves. NT-proBNP, d-dimer, and LAD levels were significantly higher in the NVAF with stroke group than in the NVAF group (p < .05). NT-ProBNP, d-dimer, and LAD were independently associated with IS in NVAF patients (odds ratio [OR] = 1.12, 95% confidence interval [CI]: 1.08-1.16; OR = 1.87, 95% CI: 1.37-2.55; OR = 1.21, 95% CI: 1.13-1.28, p < .01). The optimal cutoff points for NT-ProBNP, d-dimer, and LAD levels to distinguish the NVAF group from the NVAF with stroke group were 715.0 pg/ml, 0.515 ng/ml, and 38.5 mm, respectively, with the area under the curve (AUC) being [0.801 (95% CI: 0.76-0.84); 0.770 (95% CI: 0.72-0.85); 0.752 (95% CI: 0.71-0.80), p < .01]. The combined score of NT-proBNP, d-dimer, and LAD improved the predictive efficacy of the single index, with an AUC of 0.846 (95% CI: 0.81-0.88, p < .01), sensitivity of 77.2%, and specificity of 76.4%. NT-proBNP, d-dimer, and the echocardiographic parameter LAD have outstanding value in predicting the risk of IS in patients with NVAF.

Prevalence of silent atrial fibrillation and cardiovascular disease in patients with obstructive sleep apnea

ObjectivePatients with silent and undiagnosed atrial fibrillation (AF) have increased risk of ischemic stroke. Patients with obstructive sleep apnea (OSA) have an increased risk of both AF and ischemic stroke. Our aim was to investigate the prevalence of silent AF and associated risk factors in patients investigated for OSA or with known OSA. MethodsThis prospective observational study was performed in two sites; one outpatient sleep-clinic at Zealand University Hospital and one private Ear-Nose- and Throat clinic. Patients were investigated with a type-3 portable sleep-monitoring device, while heart rhythm was home-monitored for 7 days with an event-triggered loop recorder. Patients were stratified in groups of mild, moderate and severe OSA based on Apnea-Hypopnea-Index (AHI). ResultsIn a cohort of 303 patients, 238 (78.5%) were diagnosed with moderate/or severe OSA and 65 (21.5%) with no/mild OSA who constituted the control group. In 238 patients with moderate and severe OSA, AF was detected in 21 patients (8.8%) vs. 1 patient (1.5%,[p=0.045]) with mild OSA. Candidates for anticoagulation therapy were referred for further cardiovascular treatment. The majority of patients had known hypertension (n = 200,66%) and dyslipidemia (n = 235,[77.6%]) In patients with moderate/or severe OSA (AHI≥15), hypertension was more dysregulated (p=0.005) and more patients suffered from unknown prediabetes (n = 36, 3.1% vs. 14.3%[p<0.001]). ConclusionUndiagnosed AF and undertreated cardiovascular modifiable risk factors are common in a cohort of patients with OSA. With this study we propose that long-period home-monitoring in these patients is useful for identifying candidates for preventive anticoagulation, cardiovascular treatment and possibly prevent future ischemic stroke.

Early Versus Delayed Non-Vitamin K Antagonist Oral Anticoagulant Therapy After Acute Ischemic Stroke in Atrial Fibrillation (TIMING): A Registry-Based Randomized Controlled Noninferiority Study.

There are no evidence-based recommendations on the optimal time point to initiate non-vitamin K antagonist oral anticoagulants (NOACs) after acute ischemic stroke in patients with atrial fibrillation. We aimed to investigate the efficacy and safety of early versus delayed initiation of NOAC in these patients. TIMING (Timing of Oral Anticoagulant Therapy in Acute Ischemic Stroke With Atrial Fibrillation) was a registry-based, randomized, noninferiority, open-label, blinded end-point study at 34 stroke units using the Swedish Stroke Register for enrollment and follow-up. Within 72 hours from stroke onset, patients were randomized to early (≤4 days) or delayed (5-10 days) NOAC initiation, with choice of NOAC at the investigators' discretion. The primary outcome was the composite of recurrent ischemic stroke, symptomatic intracerebral hemorrhage, or all-cause mortality at 90 days. The prespecified noninferiority margin was 3%. Secondary outcomes included the individual components of the primary outcome. Between April 2, 2017, and December 30, 2020, 888 patients were randomized to either early (n=450) or delayed (n=438) initiation of NOAC. No patient was lost to 90-day follow-up. Mean age was 78.3 years (SD, 9.9 years); 46.2% were women; 49.1% had previously known atrial fibrillation; and 17.5% prior stroke. The primary outcome occurred in 31 patients (6.89%) assigned to early initiation and in 38 patients (8.68%) assigned to delayed NOAC initiation (absolute risk difference, -1.79% [95% CI, -5.31% to 1.74%]; Pnoninferiority=0.004). Ischemic stroke rates were 3.11% and 4.57% (risk difference, -1.46% [95% CI, -3.98% to 1.07%]) and all-cause mortality rates were 4.67% and 5.71% (risk difference, -1.04% [95% CI, -3.96% to 1.88%]) in the early and delayed groups, respectively. No patient in either group experienced symptomatic intracerebral hemorrhage. Early initiation was noninferior to delayed start of NOAC after acute ischemic stroke in patients with atrial fibrillation. Numerically lower rates of ischemic stroke and death and the absence of symptomatic intracerebral hemorrhages implied that the early start of NOAC was safe and should be considered for acute secondary stroke prevention in patients eligible for NOAC treatment. URL: http://www. gov; Unique identifier: NCT02961348.

Left ventricular longitudinal contraction impacts the left atrial appendage function and the occurrence of thromboembolic events in patients with atrial fibrillation

Abstract Introduction Previous research has revealed a relationship between left ventricular (LV) function and incidence of stroke in atrial fibrillation (AF) but the mechanism remains unknown. Purpose Given that the left atrial appendage (LAA) is located in the vicinity of the LV base we hypothesized that the LV longitudinal contraction has an impact on the LAA function, LAA thrombus (LAAT) formation, and occurrence of ischemic stroke (Figure 1A). The aim of this study was to investigate this phenomenon using transesophageal echocardiography (TEE). Material and methods We included in our study 105 consecutive patients (age 59±11; 55 men) undergoing TEE-guided cardioversion for AF. LV longitudinal function was assessed using the mitral annulus plane systolic excursion (MAPSE). LAA function was evaluated using the LAA emptying velocity (LAAEV) and LAA ejection fraction (LAAEF) (Figure 1B). The presence LAAT and spontaneous echo contrast (SEC) were evaluated as well. Results Our patients had a median CHADS2vasc score = 3 (IQR 2–4), LVEF=50±11%, and MAPSE=7.3±1.7mm. MAPSE showed a positive significant correlation with both LAAEV (r=0.34; p&amp;lt;0.01) and LAAEF (r=0.23; p&amp;lt;0.05) (Figure 2). LVEF correlated significantly with LAAEV (r=0.42, p&amp;lt;0.01), and LAA area (r=−0.34; p&amp;lt;0.05), respectively. Additionally, patients who exhibited SEC had significantly lower LAAEF as well as LAAEV when compared with patients without SEC: 31±12% vs 38±12% P=0.022 and 35±18cm/s vs 49±21cm/s P=0.005. Patients who displayed both SEC and LAAT had wider LAA neck when compared to the rest of the group (21.46±3.96mm vs. 18.23±3.78mm; P=0.021). Logistic regression analysis revealed that MAPSE independently predicted the occurrence of ischemic stroke both in univariate and multivariate models that also included the CHADSvasc2 score. Conclusions LV longitudinal contraction appears to influence LAA function. This relationship could potentially have an impact on occurrence of thromboembolic events in patients with atrial fibrillation. Funding Acknowledgement Type of funding sources: None.

Impact of metabolic syndrome on the risk of ischemic stroke in non-anticoagulated atrial fibrillation patients having low CHA2DS2-VASc scores

Abstract Background Metabolic syndrome (MetS) predisposes to a thromboembolic state. However, conflicting results have been reported on whether MetS confers an increased risk of ischemic stroke in atrial fibrillation (AF), especially in patients with low CHA2DS2-VASc score who are not indicated for oral anticoagulant therapy. Purpose We investigated the risk of ischemic stroke according to the presence of MetS, the number of MetS components (metabolic burden), and the individual metabolic components in non-anticoagulated AF patients with low CHA2DS2-VASc score. Methods A total of 76,015 oral anticoagulant-naïve AF patients with low CHA2DS2-VASc score (0,1 in male and 1 in female) were included from the Korean National Health Insurance Service database. The status of MetS and individual metabolic components were evaluated based on health examination data within two years of AF diagnosis. We estimated the risk of ischemic stroke according to MetS, metabolic burden, and an individual component of MetS using Cox proportional-hazards models. Results The mean age was 49.8±11.1 years and 52,388 (68.9%) were male. The average CHA2DS2-VASc score was 0.7±0.5 and MetS was prevalent among 21,570 (28.4%) of the study population. During a mean follow-up of 5.1 years, ischemic stroke was developed in 1,395 (1.84%) patients. MetS was associated with a higher risk of ischemic stroke after adjustment for age, sex, lifestyle behaviors, low income, and cardiovascular comorbidities: adjusted hazard ratio (aHR) 1.19, 95% confidence interval (CI) 1.06–1.33, p=0.002. A positive linear correlation was observed between metabolic burden and ischemic stroke risk. Patients with five MetS components showed the highest aHR of 1.55 (95% CI 1.14–2.11, Figure 1 and Figure 2), whereas those with a single MetS component had a marginal risk of ischemic stroke (aHR 1.18, 95% CI 0.99–1.41). Among individual metabolic components, elevated blood pressure and increased waist circumference was significantly associated with an increased risk of ischemic stroke: aHR (95% CI), 1.45 (1.30–1.62), p&amp;lt;0.001, and 1.15 (1.03–1.30), p=0.016, respectively. Conclusions Among AF patients initially with CHA2DS2-VASc score 0 and 1 with no anticoagulation, the presence of MetS is associated with an increased risk of ischemic stroke. Given the linear incremental correlation between metabolic burden and ischemic stroke, special attention to the care of metabolic derangements is required in AF patients who are not indicated for anticoagulation. Funding Acknowledgement Type of funding sources: None.

Multimorbidity, frailty and malnutrition: moving beyond traditional risk factors for risk assessment in atrial fibrillation. The Murcia Atrial Fibrillation Project II

Abstract Background The management of atrial fibrillation (AF) has evolved over the last decade with a more towards a more multidisciplinary, integrated and holistic approach. However, several conditions that may influence the prognosis and management of AF patients are still under-recognised. Purpose Our aim was to investigate if multimorbidity, frailty and malnutrition are associated with the risk of worse clinical outcomes in patients with recent diagnosis of AF starting oral anticoagulation (OAC) therapy. Methods Prospective cohort study including outpatients newly diagnosed with AF starting vitamin K antagonist (VKA) therapy from July 1, 2016 to June 30, 2018. Morbidity was assessed with the crude number of comorbidities. Frailty was assessed with the Clinical Frailty Scale (CFS). Nutrition status was assessed with the Controlling Nutritional Status (CONUT) score. During 2-years of follow-up, we recorded all ischemic strokes/transient ischemic attacks (TIAs), major bleeds (according to the 2005 International Society on Thrombosis and Haemostasis criteria), and all-cause deaths. Results We included 1050 patients (540 [51.4%] females, median age 77 [IQR 70–83] years), with median CHA2DS2-VASc of 4 [IQR 3–5] and median HAS-BLED of 2 [IQR 2–3]. The median crude number of comorbidities was 3 [IQR 2–5], whereas the median CFS and CONUT score were 2 [IQR 2–3] and 2 [IQR 1–3], respectively. The crude number of comorbidities, CFS and CONUT score demonstrated a significant positive correlation (p&amp;lt;0.001 for all correlations). After adjusting for several risk factors (age, sex, hypertension, diabetes, previous stroke, vascular disease, heart failure, chronic kidney disease, dyslipidemia, sleep apnoea, hepatic disease, and cancer), the CFS was independently associated with major bleeding (adjusted HR 1.25, 95% CI 1.07–1.45) and all-cause mortality (aHR 1.20, 95% CI 1.09–1.32). The crude number of comorbidities (aHR 1.30, 95% CI 1.14–1.49) was also associated with major bleeding, and the CONUT score (aHR 1.25, 95% CI 1.15–1.35) was associated with all-cause mortality. Any frailty degree (i.e CFS ≥5) was associated with a 3-fold higher risk of major bleeding (aHR 3.04, 95% CI 1.67–5.52) and a 2-fold higher risk of death (aHR 2.04, 95% CI 1.39–3.01), whereas the moderate/severe malnutrition (i.e. CONUT ≥5) was an independent risk factor for ischemic stroke/TIA and (aHR 2.25, 95% CI 1.11–4.56) and death (aHR 3.21, 95% CI 2.14–4.83) (Figures 1 and 2). Conclusions Frailty and malnutrition are important risk factors for bleeding, stroke and mortality in AF. The frailty degree and nutritional status should be assessed in all AF patients in order to address them properly and provide a truly integrated management. 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)

Prognosis and antithrombotic practice patterns in recurrent and transient atrial fibrillation following acute coronary syndrome: a nationwide study

Abstract Background First-time detected atrial fibrillation (AF) during acute coronary syndrome (ACS) aggravates the prognosis and increases the risk of ischemic stroke. In this setting, AF may present as brief and transient or with recurrent episodes after discharge. However, data on the association between transient or recurrent AF and ischemic stroke in patients with ACS are sparse. Further, despite being associated with ischemic stroke, first-time detected AF patients have been reported with low oral anticoagulation (OAC) rates. Purpose To examine the associated rate of ischemic stroke and mortality in ACS survivors with transient or recurrent AF and to assess the antithrombotic practice patterns one year after ACS. Methods Using data from Danish nationwide registries, we identified all patients with first-time ACS, without known AF prior to ACS, from 2000–2017 who were alive one year after ACS discharge (index date). According to a grace period between ACS discharge and one year after ACS discharge, patients were categorized into: i) no AF; ii) first-time detected AF during ACS admission without AF recurrence (transient AF); and iii) first-time detected AF during ACS admission with a subsequent recurrent AF episode (recurrent AF). Patients who developed AF during the grace period were excluded. Patients were followed from one year post ACS discharge, and two-year rates of ischemic stroke and mortality were compared using multivariable adjusted Cox proportional hazards analysis. Further, we assessed the prescribed OAC rates in a three-month period following the index date. Results We included 116,793 patients surviving one year post ACS discharge: 111,708 (95.6%) without AF (64.9% male, median age 64 years), 2,671 (2.3%) with transient AF (58.0% male, median age 74 years), and 2,414 (2.1%) with recurrent AF (55.2% male, median age 76 years). The cumulative two-year incidence of ischemic stroke was 0.9%, 1.5%, and 2.3% for patients without AF, transient AF, and recurrent AF, respectively (Figure 1). The cumulative two-year incidence of mortality was 7.4%, 12.1%, and 20.3% for patients without AF, transient AF, and recurrent AF, respectively (Figure 1). Compared to those without AF, the adjusted two-year rates of outcomes were as follows: ischemic stroke: HR 1.15 (95% CI: 0.81–1.61) for patients with transient AF and HR 1.50 (95% CI: 1.14–1.98) for patients with recurrent AF; mortality: HR 0.98 (95% CI: 0.87–1.10) for patients with transient AF and HR 1.35 (95% CI: 1.23–1.49) for patients with recurrent AF (Figure). We identified that 20.9% for transient AF and 42.2% for recurrent AF were prescribed OAC therapy in the three-month period after one year. Conclusion In patients surviving one year after ACS with first-time detected AF, a recurrent AF episode was associated with an increased long-term rate of ischemic stroke and mortality, while transient AF yielded no statistically difference as compared with patients without AF. Funding Acknowledgement Type of funding sources: None.

Temporal trends, characteristics and comorbidities of patients with hypertrophic cardiomyopathy in Denmark from 2005 to 2018: a nationwide cohort study

Abstract Background The majority of patients with Hypertrophic cardiomyopathy (HCM) are mildly symptomatic or unaware of their condition, but some develop serious complications such as heart failure, atrial fibrillation (AF) as well as sudden cardiac death. Previous studies have suggested that HCM detection-rates in women are significantly lower than in men. This leads to diagnosis often being delayed to later stages of the disease in women, where symptoms are more severe. Further characterization of HCM patients to improve early detection of adverse outcomes and warning signs might improve long-term outcomes. Purpose To describe the characteristics of Danish patients diagnosed with HCM between 2005–2018 and determine trends and changes in these factors over time. Methods All patients aged 16 years or older with a diagnosis of HCM between the 1st of January 2005 and the 31st of December 2018 were identified in Danish nationwide administrative registers and included in the study. Time trends were calculated, and differences analyzed using the Cochran-Armitage trend test and linear regression. Results A total of 3856 patients were diagnosed with HCM in the study period and included in the study. The median age at diagnosis was 68 years (IQR 56 and 78 years), 53% were male, and 44% were diagnosed with obstructive HCM, while the number of patients diagnosed with HCM each year overall increased. At the time of diagnosis, 22,3% patients were previously diagnosed with ischemic heart disease, 17% with AF, 7,5% with ischemic stroke, 13,6% with heart failure. Median age and gender distribution remained stable over time, while the proportion of obstructive HCM among the newly diagnosed decreased (p = &amp;lt;0.001) (Figure1). During the study period, there was a significant decrease in the prevalence of heart failure (p = &amp;lt;0.001), ischemic heart disease (p = &amp;lt;0.001), and chronic obstructive pulmonary syndrome (p = &amp;lt;0.001), while the prevalence of AF, hypertension and ischemic stroke remained stable (Figure 2). Conclusion Despite previous studies describing a gender gap in patients diagnosed with HCM, gender distribution was near equal in this cohort. The number of patients diagnosed with non-obstructive HCM is increasing and the prevalence of comorbidities such as heart failure, ischemic heart disease, and COPD decreased over time. Whether these findings are the result of improved early detection of HCM warrants further research and examination. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Herlev-Gentofte Hospital, Denmark