Stroke In Atrial Fibrillation Research Articles

Trimetazidine reduces stroke risk in ischemic atrial fibrillation: a territory-wide, propensity-matched study

Abstract Introduction Trimetazidine ameliorates myocardial ischemia via potentiating glucose oxidation. Whether such metabolic reprogramming protects against stroke risk in atrial fibrillation (AF) with ischemic heart disease (IHD) was unknown. Purpose To investigate the therapeutic impact of trimetazidine dihydrochloride on ischemic stroke in AF associated with IHD. Methods We collected data from a territory-wide clinical data registry (January 1999 to December 2020) with a coverage of 7.5 million population. 200,563 patients with IHD were identified. Amongst them, 13,092 (6.5%) had baseline AF (mean [SD] age: 79.7 [10.3] years, 44.8% female), and were identified as trimetazidine users (n=1,488) versus non-users (long-acting nitrates as control, n=11,604). Propensity matching at 1:1 was performed. Multivariable Cox regression was used to derive hazard ratios (HRs) for new-onset ischemic stroke. Result Over mean follow-up over 53.5 +/- 50.4 months, trimetazidine use was associated with a lower incidence of ischemic stroke (3.4% vs 7.6%, P<.001). Kaplan-Meier analyses showed trimetazidine use was associated with increased stroke-free survival period (Mean survival: 227.9 [4.9] versus 217.5 [3.6] months, Chi-square=39.0 P<.001). After adjusting for confounding factors, trimetazidine use remained an independent predictor of reduced ischemic stroke risk (adjusted HRs, 0.54, 95% CI, 0.37-0.78, P<.001). Conclusion Trimetazidine may reduce the risk of ischemic stroke in ischemic AF. These findings will need to be confirmed by randomized controlled trials.

Proteomic and genomic evaluation of plasma protein biomarkers for atrial fibrillation

Abstract Background Atrial fibrillation (AF) is a common arrhythmia and an important cause of ischemic stroke. Several plasma proteins have been suggested as biomarkers for the risk of AF and subsequent stroke in previous studies, but validation in independent cohorts is needed. Large-scale integration of proteomics with genetic and clinical data holds potential for refinement of disease prediction and risk stratification. Purpose This study aimed to evaluate previously suggested plasma protein biomarkers of AF and ischemic stroke using plasma protein measurements in a large cohort. Methods Ten tentative protein biomarkers previously associated with AF or ischemic stroke in AF patients, were evaluated in a nested case-control study comprising 49,757 individuals from the UK biobank (UKB). Plasma proteins were measured by normalized protein expression on the Olink platform. Outcomes were incident AF and ischemic stroke. The proteins were evaluated in Cox regression models adjusted for sex, age, and clinical risk factors. To assess whether the proteins were independent predictors, they were evaluated in sensitivity analyses with additional adjustment for NT-proBNP levels. Polygenic risk scores were calculated for plasma protein concentrations using the PRS-CS-auto algorithm and tested for association with AF or ischemic stroke in an independent subset of the UKB cohort without plasma protein measurements (n=379,392). Results All ten plasma proteins were associated with incident AF in the primary model, and eight were associated with incident ischemic stroke (P-values < 0.0025 for all). Adjusted for NT-proBNP levels, the proteins interleukin-6, GDF15, angiopoietin 2, and Troponin-I remained independently associated with AF, and the proteins GDF15, Cystatin-C, interleukin-6, ADAMTS13, and FGF23 remained independently associated with ischemic stroke. Polygenic risk scores for NT-proBNP and angiopoietin 2 were associated with increased rates of AF. No polygenic scores were significantly associated with ischemic stroke. Conclusion Large-scale proteomic evaluation validated ten plasma proteins associated AF and found eight to be associated with ischemic stroke. Seven proteins were associated with AF or ischemic stroke independently of NT-proBNP levels. Additional genomic evaluation provided evidence of associations between incident AF and genetically predicted plasma levels of angiopoietin 2 and NT-proBNP. As proteomic analyses of the plasma proteome become cheaper and more readily available, these findings could contribute to future risk stratification and selection of individuals for AF screening programs.Proteins associated with AFProteins associated with ischemic stroke

Clinical impact of combined assessment of the CHADS2 score and geriatric nutritional risk index on clinical outcomes in patients with lower extremity artery disease without atrial fibrillation

Abstract Background The CHADS2 score is a well-known risk score for ischemic stroke in atrial fibrillation (AF) patients. Recently, it has been reported that the CHADS2 score was associated with an increased risk of new-onset lower extremity artery disease (LEAD) in patients without AF, the association between the CHADS2 score and clinical outcomes in patients with LEAD undergoing endovascular treatment (EVT) without AF remains unclear. Furthermore, malnutrition assessed by the geriatric nutritional risk index (GNRI) has been reported to be predictive of clinical outcomes in patients with LEAD. However, there are limited studies regarding the association of combined assessment of the GNRI and CHADS2 score and clinical outcomes in patients with LEAD without AF. Purpose The purpose of this study was to investigate the association between the combined assessment of GNRI and CHADS2 score, and mortality of LEAD patients undergoing EVT without AF. Methods This retrospective study investigated 236 consecutive LEAD patients who underwent EVT without AF. CHADS2 scores were calculated by assigning one point for heart failure, hypertension, age ≥75 years, and diabetes; and assigning 2 points for a prior history of stroke or transient ischemic attack. The GNRI on admission was calculated as follows: [14.89 × albumin (g/dL)] + [41.7 × (body weight/ideal body weight)], and the CHADS2 score and GNRI were calculated for each patient. We scored GNRI by assigning 2 points to low GNRI (GNRI <82) and 1 point to intermediate GNRI (GNRI =82 to <92). We then calculated the CHADS2 plus GNRI score for each patient and then patients were divided into the high CHADS2 plus GNRI scoregroup (CHADS2 plus GNRI score> 2, n = 123) and the low CHADS2plus GNRI score group (CHADS2 plus GNRI score≤ 2, n = 113) according to the median CHADS2 plus GNRI score. We investigated the associations between all-cause mortality in patients with LEAD who underwent EVT and the CHADS2 plus GNRI score. Results The mean age was 71.9±10.4 years, and 66.9% were men. During the median follow-up of 752 (283–1472) days, 50 patients died. Kaplan-Meier curves revealed that the cumulative incidence of all-cause death was significantly higher in the high CHADS2 plus GNRI score group than in the low CHADS2 plus GNRI score group (log-rank p = 0.003). Furthermore, even in the multivariate analysis,after adjusting for other risk factors including hemodialysis and clinical frailty scale, CHADS2 plus GNRI score was independently associated with all-cause death (per one score increase, hazard ratio: 1.26, 95% confidence interval (CI) 1.01-1.56, P=0.038). Conclusions In LEAD patients who underwent EVT without AF, a higher CHADS2 plus GNRI score was associated with an increased risk of all-cause death. A Combined CHADS2 plus GNRI score assessment may be a useful prognostic marker in patients with LEAD without AF.

Racial and ethnic disparities in the incidence of stroke and mortality in atrial fibrillation: a US nationwide study

Abstract Background Atrial fibrillation (AF) is the most common arrhythmia globally and is associated with increased risks of cardiovascular mortality and ischemic stroke. Prior research has demonstrated racial/ethnic disparities in AF outcomes yet this work has been limited to small cohorts and did not adjust for anticoagulant therapy. Purpose We compared incidence of ischemic stroke and death by race/ethnicity for patients with AF in the Veterans Health Administration (VA), the largest integrated, low-cost, national healthcare system in the US. Methods In this retrospective cohort study we identified those with an outpatient diagnosis of AF and a confirmatory diagnosis ≦ 180 days of their index AF diagnosis enrolled in VA from January 1, 2014 to December 31, 2021, with follow-up for outcomes from the index AF diagnosis date until May 31, 2022. To create a cohort of incident AF cases, we excluded patients with an AF diagnosis or anticoagulant therapy in the 2 years prior to their index AF diagnosis. We also excluded patients with pre-existing valvular heart disease, prior stroke, receiving hospice care or who died within 180 days of index AF diagnosis. We categorized our independent variable as race (i.e., non-Hispanic American Indian / Alaska Native [AI/AN], Asian, Black, or White [reference group]), and ethnicity (i.e., Hispanic). Our primary outcomes were incidence of stroke or death at any point within the study follow-up period. To compare these outcomes by race/ethnicity we conducted a survival analysis, adjusting for anticoagulant use as a time-varying covariate along with sociodemographic factors (age, sex, region, area deprivation index), clinical factors (CHADS2VA2Sc stroke risk and HAS-BLED bleeding risk), and facility type. Results There were 187,080 patients in the final cohort including 0.5% AI/AN, 1% Asian, 9% Black, 4% Hispanic, 85% White; mean age was 73 years. Over a mean study follow-up period of 4.43 years, 65,375 (34.9%) patients died and 24,910 (13.3%) developed stroke. The adjusted hazard ratio [95% CI] for death was lower for Hispanic (0.84 [0.78, 0.91]) and Black (0.94 [0.91, 0.97]) patients than White patients. In contrast, the adjusted hazard ratio for stroke incidence was higher for Black (1.21 [1.16, 1.27]) and Hispanic (1.10 [1.03, 1.17]) patients than White patients. There was no difference observed between AI/AN or Asian and White patients in either outcome. Conclusions In a national cohort of patients with incident AF, we identified significantly higher rates of stroke in Black and Hispanic than White patients even controlling for myriad factors including anticoagulant use. Conversely, racial/ethnic disparities in mortality appear to be eliminated in VA, counter to prior data. Understanding the factors, beyond anticoagulation, driving disparities in stroke outcomes and identifying factors reducing mortality among minority groups is critical to improving overall AF care in the largest integrated US health system.Adjusted Hazard Ratios of Study Outcomes

Usefulness of left ventricular mechanical dyssynchrony for predicting atrial fibrillation and adverse outcomes following first atrial fibrillation event

Abstract Background Left ventricular mechanical dyssynchrony (LVMD) has shown to predict many cardiovascular outcomes including ventricular arrhythmias. Our hypothesis is that LVMD can reveal early atrial dysfunction. Purpose The aim of this study was to investigate whether LVMD can be used to predict atrial fibrillation (AF) and adverse outcomes following first AF event in individuals from the general population. Methods A total of 3785 individuals (mean age 55±17 years, 57% women) from the general population free of AF, heart failure (HF) and prior stroke had an echocardiographic examination performed including two-dimensional speckle tracking echocardiography. LVMD was calculated as the standard deviation of the regional time-to-peak strain from the three apical views. The primary endpoint was AF, and the secondary endpoint was complicated AF as assessed by the occurrence of either stroke or HF after the diagnosis of AF. Results During a median follow-up of 5 years (interquartile range, 4.4-6.2 years), 142 (4%) individuals were diagnosed with AF, and of these 22 (15%) individuals developed HF or stroke. LVMD was a univariable predictor of AF (per 10ms increase: HR 1.03; 95% CI (1.02-1.05), p<0.001, Figure). The association remained significant even after multivariable adjustment for age, sex, body mass index, diabetes, hypertension, heart rate, previous ischaemic heart disease, systolic blood pressure, diastolic blood pressure, smoking, left ventricular ejection fraction, global longitudinal strain, left atrial volume index (LAVI), and E/e’ (per 10ms increase: HR 1.02; 95% CI (1.00-1.04), p=0.042). LVMD also predicted complicated AF, and the association remained significant even after multivariable adjustment (per 10ms increase: HR 1.05; 95% CI (1.01-1.09), p=0.026). Furthermore, LVMD provided incremental prognostic information over the LAVI with regard to predicting AF (Harrell’s C-statistics 0.66 vs. 0.70, p=0.012). Conclusion In a low-risk general population, LVMD provides prognostic information on the risk of AF. Additionally, LVMD can identify individuals with complicated AF defined as occurrence of either stroke or HF following the diagnosis of incident AF. Furthermore, LVMD provides incremental prognostic information over the LAVI in predicting AF.

Performance of Atrial Fibrillation Burden Trends for Stroke Risk Stratification.

Atrial fibrillation (AF) is associated with an increased risk of stroke, yet the limitations of conventional monitoring have restricted our understanding of AF burden risk thresholds. Predictive algorithms incorporating continuous AF burden measures may be useful for predicting stroke. This study evaluated the performance of temporal AF burden trends as predictors of stroke from a large cohort with insertable cardiac monitors. Using deidentified data from Optum Clinformatics Data Mart (2007-2019) linked with the Medtronic CareLink insertable cardiac monitor database, we identified patients with an insertable cardiac monitor for AF management (n=1197), suspected AF (n=1611), and cryptogenic stroke (n=2205). Daily AF burden was transformed into simple moving averages, and temporal AF burden trends were defined as the comparison of unique simple moving average pairs. Classification trees were used to predict ischemic stroke, and AF burden significance was quantified using bootstrapped mean variable importance. Of 5013 patients (age, 69.2±11.7 years; 50% male; CHA2DS2-VASc, 3.7±1.9) who met inclusion criteria, 869 had an ischemic stroke over 2 409 437 days total follow-up. Prior stroke or transient ischemic attack (variable importance, 13.13) was the number 1 predictor of future stroke followed by no prior diagnosis of AF (7.35) and AF burden trends in follow-up (2.59). Temporal proximity of AF and risk of stroke differed by device indication (simple moving averages: AF management, <8 days and suspected AF and cryptogenic stroke, 8-21 days). Together, baseline characteristics and AF burden trends performed optimally for the area under the receiver operating characteristic curve (0.73), specificity (0.70), and relative risk (5.00). AF burden trends may provide incremental prognostic value as leading indicators of stroke risk compared with conventional schemes.

The left atrial appendage exclusion for prophylactic stroke reduction (leaaps) trial: rationale and design

IntroductionLeft atrial appendage exclusion (LAAE) has been shown in randomized trials to reduce ischemic stroke risk in patients undergoing cardiac surgery with known atrial fibrillation (AF). Many patients undergoing cardiac surgery without pre-existing AF are at risk of stroke and may benefit from LAAE. MethodsLeft Atrial Appendage Exclusion for Prophylactic Stroke Reduction (LeAAPS) is an international, prospective, randomized, multicenter, blinded trial evaluating the effectiveness of LAAE in preventing ischemic stroke or systemic embolism in patients undergoing cardiac surgery at increased risk of AF and ischemic stroke. The trial will enroll 6500 patients at increased risk of stroke in whom a cardiac surgery is planned at 250 sites worldwide. Eligible patients are ≥18 years old, have no pre-existing AF but are at increased risk for AF and stroke (based on age, CHA2DS2-VASc score, left atrium size or brain natriuretic peptide). Patients are randomized 1:1 to receive either LAAE with AtriClip or no LAAE during cardiac surgery. Healthcare providers outside of the operating room and the patient will be blinded to allocation. The primary effectiveness endpoint is the first occurrence of ischemic stroke, systemic arterial embolism, or surgical or endovascular LAA closure. The powered secondary effectiveness endpoint is ischemic stroke or systemic arterial embolism. The primary safety endpoint is the occurrence of one of the following events (through 30 days): pericardial effusion requiring percutaneous or surgical treatment, peri-operative major bleeding, deep sternal wound infection, or myocardial infarction. Other endpoints include mortality, rehospitalizations, clinically diagnosed AF, transient ischemic attack, and cognitive and quality of life assessments. Follow-up is every 6 months for a minimum of 5 years; primary analysis occurs when 469 patients have had an ischemic stroke or systemic embolism. ConclusionThe results of the LeAAPS trial will demonstrate whether LAAE with AtriClip at the time of other routine cardiac surgery reduces stroke or systemic arterial embolism during long-term follow-up in patients at high risk of stroke without pre-existing AF. Trial RegistrationClinicalTrials.gov, Identifier: NCT05478304, https://clinicaltrials.gov/study/NCT05478304?term=%20NCT05478304&rank=1

Anticoagulation Therapy Timing in patients with Atrial Fibrillation after Acute and Chronic Subdural Haematoma (ATTAACH): a pilot randomised controlled trial

IntroductionSubdural haematomas (SDHs), acute or chronic, are common neurosurgical diagnoses. These problems can occur among patients requiring direct oral anticoagulation (DOAC) for atrial fibrillation. There are currently no guidelines regarding...

Is dabigatran a good alternative to warfarin in patients with atrial fibrillation accompanied by valvular and nonvalvular heart diseases? A systematic review and meta-analysis

Abstract Background There is ongoing discussion regarding the terminology used when atrial fibrillation (AF) is present alongside either valvular heart disease (VHD) or non-valvular heart disease (NVHD). Warfarin has been used for decades for stroke (S) and systemic embolism (SE) prophylaxis in atrial fibrillation (AF) patients. However, due to its drug and food interactions, pharmacogenetic approach via VKORC1, narrow therapeutic window, frequent monitoring, and high risk of intracranial hemorrhage (ICH), it is not preferred as a first-line anticoagulant for AF patients. Is it time to retire warfarin and replace it with dabigatran? Aim and objectives We conducted this meta-analysis to assess the effectiveness and safety of dabigatran compared to warfarin and find out how likely it could be used instead of warfarin in AF patients with VHD and NVHD. Methods PubMed, SCOPUS, Web of Science, and Cochrane CENTRAL were searched online from inception till June 2023, and eligible randomized controlled trials (RCTs) were selected. The outcomes were analyzed and calculated using the risk ratio (RR), and its confidence interval (CI) using STATA software. The Cochrane Risk of Bias 2.0 tool (ROB2) was used to assess the included studies. Results In the NVHD subgroup, dabigatran 150 mg showed a significantly low risk of S and SE (RR 0.74, 95% CI: [0.62,0.88]), ICH (RR 0.38, 95% CI: [0.26,0.56]), death (RR 0.85, 95% CI: [0.74,0.99]), and high risk of gastrointestinal bleeding (GIB) (RR 1.47, 95% CI: [1.17,1.85]) compared to Warfarin. Dabigatran 110 mg showed a low risk of ICH (RR 0.31, 95% CI: [0.21,0.47]), and no significant differences in S/SE (RR 1.02, 95% CI: [0.87,1.19]) and death (RR 0.94, 95% CI: [0.82,1.09]) compared to warfarin. In the VHD subgroup, dabigatran showed no significant differences in S/SE (RR 2.57, 95% CI: [0.57,11.56]), major bleeding (RR 1.14, 95% CI: [0.35,3.68]), and death (RR 0.35, 95% CI: [0.07,1.81]) compared to warfarin. In the catheter ablation subgroup, dabigatran showed a significant reduction only in groin hematoma (RR 0.19, 95% CI: [0.05,0.73]), compared to warfarin. Conclusion Dabigatran 150 mg was superior to warfarin in AF patients with NVHD; except with GIB; otherwise, Dabigatran 110 mg was superior only to warfarin in reducing ICH. In catheter ablation, dabigatran only reduced the groin hematoma. In AF patients with VHD, dabigatran did not show either superiority or inferiority to warfarin, further studies are needed. “Non-valvular AF” term is outdated and should be replaced with “type II VHD” to differentiate it from other valvular heart diseases that are accompanied by AF.

Predictive value of neutrophil to lymphocyte ratio for clinical outcome in patients with atrial fibrillation: a systematic review and meta-analysis.

The association between the Neutrophil-to-Lymphocyte Ratio (NLR) and the prognosis of Atrial Fibrillation (AF) has been extensively studied, yet clinical outcomes have varied. Consequently, this analysis was undertaken to explore the link between NLR and the prognostic markers of AF. We conducted an exhaustive search across electronic databases, including PubMed, Embase, Web of Science, and the Cochrane Library, to investigate the correlation between the NLR and indicators of adverse clinical outcomes associated with AF from the database establishment date through March 31, 2024. In this study, the recurrence rate of AF was the primary outcome measure, while the secondary outcome measures were mortality, stroke, and left atrial thrombus. Odds ratio (OR), relative risk (RR), hazard ratio (HR) and standard mean difference (SMD) with a 95% confidence interval (CI) were integrated for assessment, and the stability of prognostic outcomes and publication bias were verified by sensitivity analysis and Egger's test, respectively. Subgroup analyses were performed to pinpoint the sources of heterogeneity. This analysis included 20 studies, encompassing a total of 59,256 patients. Our statistical analysis of both categorical and continuous variables revealed that an elevated NLR was significantly associated with increased risks in AF patients for recurrence (categorical variable: OR = 1.39, 95% CI = 1.21-1.60; continuous variable: SMD = 0.49, 95% CI = 0.24-0.74), mortality (categorical variable: OR = 1.87, 95% CI = 1.59-2.20), stroke (categorical variable: OR = 1.56, 95% CI = 1.13-2.17; continuous variable: SMD = 0.77, 95% CI = 0.63-0.91), and left atrial thrombus (categorical variable: OR = 1.87, 95% CI = 1.27-2.75; continuous variable: SMD = 0.59, 95% CI = 0.30-0.89). Subgroup analyses found that high NLR was significantly linked to AF recurrence when the NLR was >3. High NLR was significantly linked to the risk of stroke in AF when the NLR was ≤3. This study suggested that a high NLR is significantly linked to prognostic risk markers of AF, and NLR may be an effective biomarker for the prognosis of AF in clinical practice. PROSPERO (CRD42024530970).

3D Transesophageal Echocardiography in the Selection of Occluder Size for Left Atrial Appendage Occlusion: A Meta-Analysis

Background: Left atrial appendage occlusion (LAAO) can effectively reduce the risk of stroke in atrial fibrillation (AF) patients. However, the structure of left atrial appendage (LAA) varies greatly among individuals, and the size of the occluder influences the surgical success rate and prognosis. This study used a meta-analysis to investigate whether three dimensional-transesophageal echocardiography (3D-TEE) can prompt physicians to select the appropriate size of the occluder, thereby improving prognosis in patients with LAAO. Methods: Studies on 3D-TEE-assisted selection of occluder sizes in the treatment of LAAO were searched in pubmed, cochrane, Web of Science, CNKI, Wanfang, and Weipu public databases from the inception of each database to June 10, 2024. The QUADAS-2 tool was used to assess the quality of the studies. Results: 10 studies published between 2016 and 2024 were finally included, with a total sample size of 552 cases. The maximum opening of the LAA obtained by 3D-TEE, coronary angiography (CAG) and video-assisted thoracic surgery (VATS) significantly correlated with the size of the occluder (p &lt; 0.05). 3D-TEE was superior to 2D-TEE in measuring the maximum (p = 0.04) and minimum diameters (p = 0.01) of LAA openings, and to DSA in measuring depth (p = 0.01). Conclusion: 3D-TEE can be applied to obtain LAA opening data close to the size of the occluder with minimal side effects and to assist physicians in selecting the appropriate occluder.

Safety and efficacy of apixaban versus warfarin in peritoneal dialysis patients with non-valvular atrial fibrillation: protocol for a prospective, randomised, open-label, blinded endpoint trial (APIDP2)

IntroductionSeveral randomised controlled trials have demonstrated that novel oral anticoagulants are safer compared with vitamin K antagonists for the management of non-valvular atrial fibrillation (NVAF) to prevent thromboembolic events in...

Risk of spontaneous intracerebral hemorrhage associated with NOACs compared with aspirin and warfarin: A long-term single hospital follow-up study

BackgroundNon-vitamin K antagonist oral anticoagulants (NOACs) are currently the mainstay treatment for preventing thrombosis-induced ischemic stroke in patients with atrial fibrillation (AF), deep vein thrombosis (DVT), or previous infarction. However, such management may potentially induce antithrombotic-associated intracranial hemorrhage, leading to significantly adverse clinical outcomes. To investigate the risk of spontaneous intracranial hemorrhage (sICH) in patients under therapeutic anticoagulation. MethodsThis retrospective cohort study used a database established by Kaohsiung Veterans General Hospital to estimate the risk of first onset sICH in patients with AF, DVT or previous stroke who were 18 years old or older, and who had been on at least three months continuous long-term treatment with the oral anticoagulants aspirin, warfarin, or NOACs. In addition, we used propensity-score matching to minimize bias and Cox proportional hazards ratio to compare the risk of sICH among patients prescribed these anticoagulants. ResultsWe analyzed the data of 546 patients (182 aspirin users, 182 warfarin users, and 182 NOAC users). 180 (20 taking aspirin, 74 warfarin, and 86 NOACs) developed new onset sICH before seven years. No new onset cases were found after 7 years. Importantly, those taking NOACs were found to be at a higher risk of early onset hemorrhage (47.80 %) compared to the groups taking aspirin (11.10 %) and warfarin (47.80 %) with a median time-to-occurrence being 2.50, 4.00, and 4.40 years, respectively. ConclusionsThough NOACs prevented ischemic stroke, they were used with a higher risk of early onset spontaneous ICH at our large medical center.

Heart Failure Risk Assessment Using Biomarkers in Patients With Atrial Fibrillation: Analysis From COMBINE-AF

BackgroundHeart failure (HF) is common among patients with atrial fibrillation (AF), and accurate risk assessment is clinically important. ObjectivesThe goal of this study was to investigate the incremental prognostic performance of N-terminal pro–B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), and growth differentiation factor (GDF)-15 for HF risk stratification in patients with AF. MethodsIndividual patient data from 3 large randomized trials comparing direct oral anticoagulants (DOACs) with warfarin (ARISTOTLE [Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation], ENGAGE AF-TIMI 48 [Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis In Myocardial Infarction 48], and RE-LY [Randomized Evaluation of Long-Term Anticoagulation Therapy]) from the COMBINE-AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation) cohort were pooled; all patients with available biomarkers at baseline were included. The composite endpoint was hospitalization for HF (HHF) or cardiovascular death (CVD), and secondary endpoints were HHF and HF-related death. Cox regression was used, adjusting for clinical factors, and interbiomarker correlation was addressed using weighted quantile sum regression analysis. ResultsIn 32,041 patients, higher biomarker values were associated with a graded increase in absolute risk for CVD/HHF, HHF, and HF-related death. Adjusting for clinical variables and all biomarkers, NT-proBNP (HR per 1 SD: 1.68; 95% CI: 1.59-1.77), hs-cTnT (HR: 1.39; 95% CI: 1.33-1.44), and GDF-15 (HR: 1.20; 95% CI: 1.15-1.25) were significantly associated with CVD/HHF. The discrimination of the clinical model improved significantly upon addition of the biomarkers (c-index: 0.70 [95% CI: 0.69-0.71] to 0.77 [95% CI: 0.76-0.78]; likelihood ratio test, P < 0.001). Using weighted quantile sum regression analysis, the contribution to risk assessment was similar for NT-proBNP and hs-cTnT for CVD/HHF (38% and 41%, respectively); GDF-15 provided a statistically significant but lesser contribution to risk assessment. Results were similar for HHF and HF-related death, individually, and across key subgroups of patients based on a history of HF, AF pattern, and reduced or preserved left ventricular ejection fraction. ConclusionsNT-proBNP, hs-cTnT, and GDF-15 contributed significantly and independently to the risk stratification for HF endpoints in patients with AF, with hs-cTnT being as important as NT-proBNP for HF risk stratification. Our findings support a possible future use of these biomarkers to distinguish patients with AF at low or high risk for HF.

Characteristics and outcomes of atrial fibrillation detected before and after acute ischemic stroke.

Atrial fibrillation (AF) can be known before the stroke (KAF) or be newly detected after stroke (AFDAS). It is unknown whether the outcome of stroke differs between KAF and AFDAS. We performed a propensity-matched analysis to investigate the outcome of patients with AFDAS and their counterparts with KAF. We analysed a consecutive series of patients enrolled into the EIDASAF study, a single centre, retrospective study of ischemic stroke patients with a diagnosis of AF before or after the event who had been admitted to the Hyperacute Stroke Unit of Imperial College Healthcare NHS Trust between 2010 and 2017. Overall, our cohort included 959 patients with AF and acute ischemic stroke. After propensity score matching, 547 patients were matched (404 KAF group and 143 AFDAS group). The rates of in hospital death and of haemorrhagic transformation were significantly higher in KAF patients compared to AFDAS patients. Logistic regression analysis did not reveal a statistically significant influence of AF subtypes on the outcome of death. However, in logistic regression analysis KAF was associated with increased probability of haemorrhagic transformation (OR 9.64; CI 1.29-71.68, p = 0.022) after the index event. KAF is associated with an increased risk of haemorrhagic transformation but not of death when compared to AFDAS.

Anticoagulation Patterns in Ischemic Stroke Patients with Atrial Fibrillation in Developing Country: Insights from the Stroke Registry in Vietnam.

(1) Background: Atrial fibrillation (AF) poses a growing cardiovascular challenge globally, with significant implications in Vietnam. This study aimed to investigate the impact of AF on ischemic stroke/transient ischemic attack (TIA) and clinical outcomes, as well as the utilization of oral anticoagulation (OAC) therapy in Vietnam. (2) Methods: Data from the Registry of Stroke Care Quality (RES-Q) across 66 hospitals in Vietnam between 2017 and 2023 were utilized. Patients diagnosed with ischemic stroke or TIA were included, and clinical characteristics, pre- and post-hospitalization medication, and hospitalized outcomes were examined. (3) Results: Of 94,144 patients, 15.1% had AF. Patients with AF were older and had a higher prevalence of heart failure and more severe strokes. AF was associated with increased mortality during hospitalization and a poorer prognosis. In AF patients, anticoagulation therapy utilization increased from 15.8% pre-hospitalization to 82.4% at discharge, with a preference for direct oral anticoagulants. (4) Conclusions: AF significantly impacts ischemic stroke/TIA outcomes in Vietnam. Pre-hospitalization and anticoagulation therapy utilization were low but improved at discharge. These findings emphasize the need for improved AF management and stroke prevention strategies in developing countries.

Residual Stroke Risk Among Patients With Atrial Fibrillation Prescribed Oral Anticoagulants: A Patient-Level Meta-Analysis From COMBINE AF.

Despite oral anticoagulation, patients with atrial fibrillation (AF) remain at risk of ischemic stroke and systemic embolism (SE) events. For patients whose residual risk is sufficiently high, additional therapies might be useful to mitigate stroke risk. Individual patient data from 5 landmark trials testing oral anticoagulation in AF were pooled in A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in AF (COMBINE AF). We calculated the rate of ischemic stroke/SE among oral anticoagulation-treated patients with a CHA2DS2-VASc score≥2, across strata of CHA2DS2-VASc score, stroke history, and AF type, as either paroxysmal or nonparoxysmal. We included 71 794 patients with AF (median age 72 years, interquartile range, 13 years, 61.3% male) randomized to a direct oral anticoagulant or vitamin K antagonist, and followed for a mean of 2.1 (±0.8) years. The median CHA2DS2-VASc score was 4 (interquartile range, 3-5), 18.8% had a prior stroke, and 76.4% had nonparoxysmal AF. The overall rate of stroke/SE was 1.33%/y (95% CI, 1.27-1.39); 1.38%/y (95% CI, 1.31-1.45) for nonparoxysmal AF, and 1.15%/y (95% CI, 1.05-1.27) for paroxysmal AF. The rate of ischemic stroke/SE increased by a rate ratio of 1.36 (95% CI, 1.32-1.41) per 1-point increase in CHA2DS2-VASc, reaching 1.67%/y (95% CI, 1.59-1.75) ≥4 CHA2DS2-VASc points. Patients with both nonparoxysmal AF and CHA2DS2-VASc ≥4 had a stroke/SE rate of 1.75%/y (95% CI, 1.66-1.85). In patients with a prior stroke, the risk was 2.51%/y (95% CI, 2.33-2.71). AF type, CHA2DS2-VASc score, and stroke history can identify patients with AF, who despite oral anticoagulation have a residual stroke/SE risk of 1.5% to 2.5% per year. Evaluation of additional stroke/SE prevention strategies in high-risk patients is warranted.

Digital tools and scores for estimating the risk of stroke and bleeding in atrial fibrillation

Digital tools and scores for estimating the risk of stroke and bleeding in atrial fibrillation

Associations Between Changes in Maximum Daily Atrial Fibrillation Duration, Ischemic Stroke, and Mortality.

Atrial fibrillation (AF) outcomes are strongly associated with continuous measures of AF burden. This study sought to assess the association between changes in maximum daily AF duration (MDAFD) and stroke or mortality in patients with cardiac implantable electronic devices (CIEDs). The Optum deidentified electronic health record data set (2007-2021) was linked with the Medtronic CareLink heart rhythm database. Patients with CIEDs and health care activity recorded in the electronic health record were included, excluding those with oral anticoagulation prescription. MDAFD was assessed 30days post implant (baseline period) and 30days before censoring or an event. HRs for the primary analysis were adjusted for components of CHA2DS2-VASc, baseline MDAFD category, and chronic kidney disease. Of 26,400 patients (age 68 ± 13 years; follow-up 2.6 ± 1.6 years) analyzed, 2,544 (9.6%) had AF during baseline. Increased (vs stable or decreased) MDAFD category in follow-up was associated with a higher adjusted rate of stroke and mortality (HR: 1.80; 95%CI: 1.61-2.01). There was no association between decreased MDAFD in follow-up and the combined endpoint (HR: 0.82; 95%CI: 0.68-1.00). Subgroup analysis by baseline MDAFD category demonstrated that increased MDAFD in follow-up was associated with a greater risk of stroke or mortality among patients with no AF at baseline, and decreased MDAFD in follow-up was associated with a lower risk of stroke or mortality among patients with baseline MDAFD of 1 to<5.5 hours and 5.5 to<23.5 hours. In CIED patients not on oral anticoagulation, increased MDAFD in follow-up was associated with a higher rate of stroke and mortality. These results suggest that AF burden, and associated risk, s not stable over time.

Neurofilament Light Chain and Risk of Stroke in Patients With Atrial Fibrillation.

Biomarkers reflecting brain injury are not routinely used in risk assessment of stroke in atrial fibrillation (AF). Neurofilament light chain (NFL) is a novel biomarker released into blood after cerebral insults. We investigated the association between plasma concentrations of NFL, other biomarkers, and risk of stroke and death in patients with AF not receiving oral anticoagulation. For this observational study, baseline plasma samples were available from 3077 patients with AF randomized to aspirin in ACTIVE A (Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events; 2003 to 2008) and AVERROES (Apixaban Versus Acetylsalicylic Acid [ASA] to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment; 2007 to 2009). Median follow-up was 1.5 years. NFL was analyzed with a Single Molecule Array (Simoa). Associations with outcomes (total stroke or systemic embolism, ischemic stroke, cardiovascular death, and all-cause death) were explored with Cox regression models. In the combined cohort, the median NFL level was 16.9 ng/L (interquartile range, 11.1-26.5 ng/L), the median age was 71 years, 58% were men, and 13% had a history of previous stroke. NFL was associated with older age, higher creatinine, lower body mass index, previous stroke, female sex, and diabetes but not cardiac rhythm. Higher NFL was associated with a higher risk of stroke or systemic embolism (n=206) independently of clinical characteristics (hazard ratio, 1.27 [95% CI, 1.10-1.46] per doubling of NFL) and other biomarkers (hazard ratio, 1.18 [95% CI, 1.01-1.37]) and including in patients without previous stroke (hazard ratio, 1.23 [95% CI, 1.02-1.48]). NFL was also independently associated with cardiovascular (n=219) and all-cause (n=311) death. The C index for stroke using only NFL was 0.642, on par with the currently used clinical risk scores. Addition of information on NFL improved discrimination in a model also including clinical information, NT-proBNP (N-terminal pro-B-type natriuretic peptide), and high-sensitivity cardiac troponin T, yielding a C index of 0.727. NFL reflects overt and covert episodes of cerebral ischemia and improves risk assessment of stroke and death in patients with AF without oral anticoagulation, including in patients without previous stroke. The combination of NFL with information on age, history of stroke, and other biomarkers should be explored as a future avenue for stroke risk assessments in patients with AF.