Risultati per: Stroke

Circulation, Volume 150, Issue Suppl_1, Page A4145568-A4145568, November 12, 2024. Background:Embolic stroke of undetermined source (ESUS) is a nonlacunar ischemic stroke with no clear cause, having a 4%-5% annual recurrence rate. The potential benefits of direct oral anticoagulants (DOACs) relative to aspirin in patients with ESUS remain unclear.Objective:We aimed to perform a systematic review and meta-analysis to determine the efficacy of the DOACs in secondary prevention for patients with ESUS compared with aspirin.Methods:MEDLINE, Embase, Cochrane, and ClinicalTrias.gov were searched for RCTs comparing DOACs versus aspirin for secondary stroke prevention after ESUS. We performed a systematic review and meta-analysis following the Preferred Reporting Items for Systematic Review (PRISMA) and Cochrane guidelines. Statistical analysis was performed using R software 4.3.2. A random-effects model was employed to measure mean differences and hazard ratios (HR) with 95% confidence intervals (CI).Results:We included 4 RCTs comprising 13,970 patients. The median age was 67 years (IQR 65.5-68.2), 61% were male, 76% had hypertension, and 51% had diabetes. DOACs were administered to 50% of the participants. No significant difference was found between groups for stroke recurrence [RR 0.95 (95% CI 0.8-1.11) p=0.52; I2=0%]. Death from any cause [HR 1.11 (95% CI 0.87-1.42) p=0.38; I2=0%], cardiovascular death [HR 1.08 (95% CI 0.61-1.94) p=0.77; I2=18%] and myocardial infarction [HR 0.92 (95% CI 0.54-1.54) p=0.76; I2=16%] were also similar between groups. However, there was a significant increase in clinically relevant non-major bleeding for patients treated with DOACs [HR 1.53 (95% CI 1.22-1.92) p

Circulation, Volume 150, Issue Suppl_1, Page A4141154-A4141154, November 12, 2024. Background:Acute ischemic stroke (AIS) is one of the leading causes of death and disability in adults worldwide, and effective treatments are still lacking. Cold-inducible RNA-binding protein (CIRP) is up-regulated in response to various stress conditions. Previous studies have indicated that CIBP could potentially influence the development of various diseases.Research questions:Nevertheless, the specific role and molecular mechanism of CIBP after AIS remain unclear.Methods:The levels of serum CIRP and other brain injury markers such as NSE, S100β, GSDMD, and NLRP3 were measured by ELISA to explore the relationship between CIRP and AIS. Additionally, middle cerebral artery occlusion models (MCAO) in rats were established to investigate its localization in brain tissue using immunofluorescence staining. Additionally, the CIRP knockout MCAO rat model was established, and evaluate the effect of CIRP deficiency on the neurological function of rats. while the role of CIRP was investigated through RNA sequencing and Western Blot analysis. Additionally, the potential protective effect of the CIRP inhibitor C23 on neural injury following AIS was examined.Results:(1) Compared to the healthy control group, the serum levels of CIRP and other brain injury markers (NSE, S100β) in AIS patients and MCAO rats were significantly elevated, and the elevated levels were positively correlated. (2) In the MCAO rat model, the CIRP was mainly located in neurons and microglia. (3) Compared with wild-type MCAO rats, CIRP knockout MCAO rats improved neurological function scores. (4) RNA-seq analysis revealed that genes differentially expressed between wild-type MCAO rats and CIRP knockout MCAO rats were enriched in inflammation-related pathways. (5) The expression of pyroptosis-related proteins (NLRP3, Caspase-1, GSDMD, and ASC) and inflammatory factors (IL-1β, TNF-α, etc.) decreased in CIRP knockout MCAO rats. (6) The CIRP inhibitor C23 significantly alleviated brain injury and improved neurological function. C23 treatment significantly decreased the expression levels of pyroptosis-related proteins and inflammatory factors.Conclusions:This study shows that CIRP plays an important role in AIS development. The levels of CIRP in AIS patients and MCAO rats are significantly increased and are positively correlated with nerve damage markers. Thus, supporting CIRP as a potential target for the treatment of AIS. This discovery provides new strategies for the treatment of AIS.

Circulation, Volume 150, Issue Suppl_1, Page A4143074-A4143074, November 12, 2024. Introduction:Atrial fibrillation (AF) is a risk factor for the development of ischemic stroke. Left atrial (LA) function has been described as a predictor of AF, however, atrial stiffness has been little studied.Objectives:To determine if there is a difference in left atrial stiffness between patients with ischemic stroke who presented AF and those who did not, the association of stiffness with AF and the stiffness cut-off points.Methods:An analytical, cross-sectional, single-center study was conducted. Patients older than 18 years with a diagnosis of cryptogenic ischemic stroke who were in sinus rhythm, had no history of atrial fibrillation and underwent an echocardiogram and a 24-hour rhythm Holter during hospitalization were included in the study.The echocardiograms were performed using a Siemens ACUSON SC 2000 machine with a 2.5 MHz sectorial 4v1c transducer. The reservoir LA strain (LASr) was determined using the VVI technique. The left atrial stiffness was obtained through the ratio E/e’ between the LASr.Variables were analyzed using chi-square or Student’s t-test. ROC curves were used to determine the cutoff points for predicting AF. The association of variables with the development of AF was analyzed using logistic regression.Results:A total of 96 patients were obtained, of which 35 had documented AF, 16 women and 19 men. Two groups were formed, Group 1: patients with ischemic stroke and AF (35), Group 2: with ischemic stroke without AF (61), which were used as control (Table 1). Among patients with AF, we found they were older and had a higher prevalence of diabetes mellitus, higher E/e’ value, LA indexed volume, and greater LA stiffness as well as lower LASr values. LA stiffness ( >0.29) and LASr (

Circulation, Volume 150, Issue Suppl_1, Page A4142338-A4142338, November 12, 2024. Background:Atrial fibrillation (AF) has been known as a main cause of embolic stroke. Well-chosen candidate to be anticoagulated should be critical for secondary prevention in patients with embolic stroke with undetermined source (ESUS). Atrial mechanical remodeling presenting cardiomyopathy could lead to not only occur atrial fibrillation but also increase risk of thromboembolism.Objective:To investigate association of LA strain, and newly detected AF in patients with ESUS.Methods:A total of 45 patients diagnosed ESUS with implantable loop recorder (ILR) who were prospectively enrolled and clinically followed for newly developed AF for secondary prevention in the 3 referral centers. Transthoracic echocardiography including LA strain analysis were performed.Results:11 patients (24%) among all (mean age 67 years, 58% male) have developed newly AF and others have maintained sinus rhythm within 2 years. The mean age, proportion of hypertension and diabetes were similar between sinus rhythm and newly AF patients. LA diameter (36.3 ± 6.6 mm vs. 39.3 ± 6.0 mm) and E of E’ (11.0 ± 4.5 mm vs. 9.2 ± 1.1 mm) were also similar between two group. Even though peak and pump LA strain in the newly AF were lower than those in sinus rhythm without statistically significance (24.7 ± 6.4 vs. 22.3 ± 8.8 and 10.8 ± 3.8 vs. 9.2 ± 4.9). Pump LA strain (cut-off value9.1) was significantly associated with developing newly AF during follow-up (hazard ratio=4.8, 1.27-18.3, p=0.02)Conclusion:Our data demonstrated that the pump LA strain was significantly associated with developing newly AF in the ESUS. This result suggests that atrial mechanical remodeling could be predictable for newly developed AF in patients with ESUS

Circulation, Volume 150, Issue Suppl_1, Page A4140775-A4140775, November 12, 2024. Background:Stroke is the leading cause of neurological disability worldwide and contributes substantially to mortality. Colchicine is a microtubule inhibitor that has anti-inflammatory properties. In recent years, colchicine has been investigated as a potential therapeutic agent for reducing the risk of adverse cardiovascular events. Few studies have reported the risks of stroke with colchicine, with controversial results to date.Aim:This meta-analysis aimed to compare the efficacy of colchicine versus placebo for stroke prevention.Methods:We conducted a comprehensive systematic search of the major databases from inception until May 3, 2024, to identify randomized controlled trials (RCTs) comparing colchicine to placebo. Risk ratios (RR) with 95% confidence intervals (CI) were pooled using an inverse-variance random-effects model. Statistical significance was set at p < 0.05.Results:We included 13 RCTs with 13629 patients (6823: Colchicine and 6806: Placebo). The mean age in the Colchicine group was 62.1 ± 9.4 years and in the placebo group was 62.4 ± 9.1 years. Colchicine was associated with a significantly lower risk of stroke [RR: 0.51; 95% CI: -0.32, 0.80; p=0.003] than placebo. However, the risk of all-cause mortality [RR: 1.01; 95% CI: 0.66, 1.54; p=0.97] was similar between the two groups.Conclusion:This study demonstrated the efficacy of colchicine in reducing the risk of stroke. However, colchicine did not reduce the risk of all-cause mortality. Future RCTs are required to investigate this risk reduction on a larger, multicenter scale.

Circulation, Volume 150, Issue Suppl_1, Page A4145554-A4145554, November 12, 2024. Background:Cancer and obstructive sleep apnea (OSA) individually elevate cardiovascular diseases (CVD) and stroke risk. However, it is unclear whether OSA contributes additional CVD risk in persons with pre-existing cancer.Methods:Using the TriNetX, an electronic healthcare records-based database from large healthcare organizations, we compared adverse CVD outcomes and ischemic stroke incidence between patients with and without OSA diagnosed with cancer between 01/2012 and 06/2023. Adverse CVD outcomes was defined as a composite of incident heart failure, incident atrial fibrillation / flutter, incident myocardial infarction or all-cause mortality. Patients were eligible to enter the cohort on the day of cancer diagnosis. The follow-up period for outcome events began one year after patients entered the cohort and patients contributed follow-up time till the outcome event occurred or till the end of the study period.After propensity risk score matching on demographics and comorbidities we conducted a time-to-event analyses.Results:A total of 509,477 patients with both cancer and OSA were propensity score matched to 509,477 patients with cancer but without OSA. The table shows the demographic and comorbidities of the matched groups. Among persons with cancer, OSA diagnosis was associated with increased risk of adverse CVD outcomes (HR: 1.37, 95% CI: 1.36 – 1.38). OSA in persons with cancer increased the risk of heart failure, atrial fibrillation / flutter and myocardial infarction. OSA also increased the risk of ischemic stroke. However, total mortality risk was reduced among those with OSA. See the table for details.Conclusion:OSA increases the risk of adverse CVD outcomes and ischemic stroke in persons with cancer. These analyses suggest that persons with cancer should be screened and treated for OSA. Future studies will need to determine the impact of OSA treatment e.g., positive airway pressure (PAP) therapy on CVD related outcomes in persons with cancer. Further investigation into the paradoxical reduction in all-cause mortality with OSA is warranted.

Circulation, Volume 150, Issue Suppl_1, Page A4139515-A4139515, November 12, 2024. Background:Recent clinical trials demonstrate the benefit of oral anticoagulation (OAC) for all device-recognized atrial fibrillation (AF) > 6 minutes. However, AF is not binary and those with greater AF burden generally have a higher risk of stroke. To date, there are limited data on a specific threshold of AF duration that is independently associated with the risk of ischemic stroke.Objective:To assess the association between baseline maximum daily AF duration (MDAFD) and ischemic stroke among patients with cardiac implantable electronic devices (CIEDs) capable of continuous AF detection.Methods:Using the Optum®de-identified electronic health record (EHR) (2007-2021) linked with the Medtronic CareLink®heart rhythm database, CIED patients with healthcare activity recorded in the EHR >12 months pre- and >6 months post-CIED implant were identified. Exclusion criteria included presence of a prescription for OAC. MDAFD was assessed during the first 30 days post-implant (baseline period). Associations between baseline MDAFD and ischemic stroke in follow-up were evaluated, adjusting for CHA2DS2-VASc and chronic kidney disease.Results:Of 26,400 patients (68±13 years; 60% male) analyzed, 2,544 (9.6%) had AF at baseline. The distribution of maximum daily AF duration during baseline was as follows: 6 min-5.5 hours of MDAFD was needed to increase the risk of ischemic stroke compared to those with no AF. These results suggest that there is a threshold of MDAFD, measured in hours, that may benefit from treatment with OAC.

Circulation, Volume 150, Issue Suppl_1, Page A4144346-A4144346, November 12, 2024. Background:Stroke is a leading cause of death globally. Atrial fibrillation (AF) is an important modifiable risk factor for stroke. Ascertaining the burden of stroke in AF, its temporal trends and demographic disparities can inform public health policy measures.AimsTo describe national temporal trends of ischemic stroke-related mortality in patients with AF and identify any differences by gender, race, ethnicity, or region.Methods:In this cross-sectional analysis we used death certificate data from the national CDC Wide-Ranging ONline Data for Epidemiologic Research (WONDER) database for adults aged 35-84 years between 1999 and 2020. We queried for both ischemic stroke and AF as contributing or underlying cause of death. Crude and age-adjusted mortality rates (AAMR) were computed for the overall population and stratified by sex, race/ethnicity, geographic region, state, and rural/urban status. Joinpoint Regression Analysis software was used for trend analysis. Average annual percentage change (APC) in AAMR were computed using log-linear regression models.ResultsA total of 32,386 ischemic-stroke related deaths occurred in patients with AF between 1999 and 2020. Overall mortality trends were stable until 2014, sharply rose between 2014 and 2017 (APC 27.6% [95% confidence interval, CI, 18.8-33.4]), slowing down between 2017 and 2020 (APC 2.48 [95% CI, -4.81-7.03]). Overall AAMR per 100,000 was higher in men (1.00 vs 0.86 in women; Figure 1); Non-Hispanic Whites (0.98 versus 0.81 in Non-Hispanic Blacks and 0.70 in Hispanics; Figure 2), individuals in the Western census region (1.07 vs 0.95 in Southern, 0.92 in Midwestern and 0.78 in Northeast regions; Figure 3) and non-metropolitan areas (1.06 versus 0.91 in metropolitan). The rate of increase in AAMR over recent years was significantly greater in Black populations.Conclusion:Stroke mortality in AF rose sharply since 2014. Our findings underscore racial and geographic differences that exist in stroke-related deaths in the US.

Circulation, Volume 150, Issue Suppl_1, Page A4146152-A4146152, November 12, 2024. Background:Exploring the risk of young-onset stroke (YOS) in Asian Americans and Pacific Islanders (AAPIs), our study helps fill a critical gap in medical literature. By identifying unique risk factors and trends, the findings can guide early identification and targeted interventions for young AAPI individuals at high risk of stroke.Method:AAPIs aged 18-44 with and without YOS hospitalization were retrospectively identified from the National Inpatient Sample (2016-2020). Study population, comorbidities, and outcomes were queried using ICD-10-CM codes. All-cause in-hospital mortality (ACIHM) was the primary outcome and secondary outcomes were measures of healthcare resource utilization. Multivariable regression analysis was performed to analyze cardiovascular disease risk (CVD) factors as predictors of YOS and associated all-cause in-hospital mortality (ACIHM). Linear-by-linear trend analysis was performed. Statistical significance was defined at p

Circulation, Volume 150, Issue Suppl_1, Page A4142210-A4142210, November 12, 2024. The importance of transesophageal echocardiogram (TEE) to exclude left atrial (LA) and left atrial appendage (LAA) thrombus prior to cardioversion for atrial fibrillation (AF) has been debated in patients who are anticoagulated prior to cardioversion. Despite comprehensive anticoagulation protocols, discrepancies in pharmacologic responses due to patient-specific factors such as adherence to anticoagulation, renal function, and genetics suggest that imaging studies may still be critical for patient safety. Although anticoagulation prior to cardioversion is thought to be adequate to prevent thromboembolic disease after cardioversion, there are studies to suggest imaging is always associated with lower incidence of stroke (Palla, et al., 2023). This study evaluates the impact of TEE before cardioversion on stroke reduction in a contemporary cohort of patients with persistent AF, regardless of adequate anticoagulation time.Question:Do patients with newly diagnosed persistent AF who receive a TEE prior to cardioversion have lower incidence of transient ischemic attack /ischemic stroke compared to those who are anticoagulated for at least four weeks without interruption and cardioverted without thrombus exclusion?Method:This single-center, retrospective observational study involved 454 patients ( >18 years) with newly diagnosed persistent AF undergoing cardioversion. Patients were divided into two groups: those who underwent TEE before cardioversion (n=382) and those who did not receive TEE after a four-week period of uninterrupted anticoagulation. Primary outcomes measured were the incidence of stroke within one-year post-cardioversion. Secondary outcome was mortality.Results:The incidence of stroke was significantly lower in the TEE group, with a hazard ratio of 0.1358 (95% CI 0.06531-0.2824; p < 0.0001). Mortality rates within a year did not differ significantly between the two groups. There was no significant difference in age, race, CHADS2VASc score, INR, GFR and platelet count between the two groups based on multivariate analysis.Discussion:TEE prior to cardioversion in patients with newly diagnosed persistent AF significantly reduces the risk of stroke compared to cardioversion after anticoagulation alone. In aligning with the results found in earlier trials such as ACUTE and AFFIRM, this study supports the paradigm that pre-cardioversion imaging to rule out LA/LAA thrombus could be beneficial even amongst patients who have been adequately anticoagulated.

Circulation, Volume 150, Issue Suppl_1, Page A4141940-A4141940, November 12, 2024. Objective:Examine the sociodemographic and clinical profiles of Middle Eastern patients with atrial fibrillation (AF) who have a history of prior ischemic stroke or systemic embolism (SSE) and compare the risk of adverse events between AF patients from the Middle East with and without a history of SSE.Methods:The study population was drawn from the JoFib study, a multicenter, nationwide, prospective registry of AF patients from the Middle East. Patients with a history of prior hemorrhagic stroke were excluded from this analysis. The remaining patients were divided into two groups based on their history of prior SSE to compare baseline sociodemographic and clinical characteristics and the one-year risk of all-cause death, cardiovascular death, non-cardiovascular death, SSE, and major bleeding between AF patients with and without prior SSE. Multivariable Cox proportional hazards models and Fine-Gray sub-distribution hazards models were used to adjust for confounding factors. Additionally, multivariable logistic regression models were applied to compare the secondary outcome of clinically relevant non-major bleeding (CRNMB) between the two groups.Results:The study included 2,003 AF patients, divided into two groups: 318 patients (15.9%) with a history of prior SSE and 1,685 patients (84.1%) without. Patients with prior SSE were older than those without (45.3% vs. 30.4%, p

Circulation, Volume 150, Issue Suppl_1, Page A4140884-A4140884, November 12, 2024. Background:Evidence on the use of digital health technologies by older adults is growing. However, the impact of these technologies in health promotion and disease prevention among older adults at risk for cardiovascular disease is not fully explored.Aims:This study aimed to compare the effect of two digital health technology-based interventions on engagement in healthy behaviors, weight loss, and psychological well-being over time (baseline [pre-intervention] to three months [post-intervention] to six months [long-term]) and explore outcome predictors.Methods:This randomized, longitudinal study examined the intermediate (three months) and long-term (six months) effects of two digital health technologies,Get FITvs.Get FIT+. Over 12 weeks,Get FITparticipants (n = 24) received one face-to-face counseling session on healthy food and exercise, an activity tracker (Fitbit Charge), and access to a nutrition app (MyFitnessPal app). TheGet FIt+group (n = 30) received all the same components asGet FIT, plus weekly personalized text messages to motivate and encourage them to meet their goals. General Linear Models were used for analysis.Results:Fifty-four older adults (mean age 65.6 ± 5.8 years, 60% women, 65.5% Hispanic) were randomly assigned into the two groups.Table 1shows the group comparisons betweenGet FITvs.Get FIT+in terms of healthy behaviors, weight loss, and psychological well-being outcomes at the three time-points. At six months, the group assignment was associated with greater weight loss, higher physical activity levels, reduced calorie intake, and lower depression scores. Being Hispanic was associated with higher weight, whereas being non-Hispanic and higher education with higher levels of depression.Conclusion:Digital health technologies increased the adoption of healthy behaviors, weight loss, and better psychological well-being over time, with greater improvements observed in theGet FIT+group. Likewise,Get FIT+participants sustained these improvements in the long term. A large randomized clinical trial is needed to evaluate the efficacy of both interventions in older adults at risk for cardiovascular disease.

Circulation, Volume 150, Issue Suppl_1, Page A4146671-A4146671, November 12, 2024. Background:Xe-liposome therapy has shown cerebroprotection in adult stroke animals. This study aims to validate the Xe therapeutic effect by MRI in adult rats and the therapeutic effect in an aged animal.Method:A 2-hour MCAO was induced in adult rodents. The MCAO animals were then divided into two groups: one receiving no treatment and the other receiving Xe-liposomal treatment (3 doses within 2-6 hours after stroke followed by 1 dose per day). Diffusion-weighted MRI conducted at 2, 6, and 24 hours post-MCAO, were analyzed by our image center. For aged rats (14 rats, 74 weeks old, male and female), MCAO (1.5 hours) was induced and then divided into two groups: stroke without treatment (n=5) and stroke with Xe-liposome treatment (n=9) and given 3 doses at day one and once per day for following days. Neurological function was tested by Limb placement and rotarod, and infarct volumes were measured two days post-stroke/treatment.Results:MRI (Fig.) demonstrated that infarct volume growth ratio was lower in the Xe-treated animals than those without treatment, indicating a protective effect of Xe against ischemic injury. MCAO induced 25% ± 5.4% infarct volume in the aged animals. Xe- reduced the infarct size to 6.7% ± 3.4%. Xe treatment demonstrated improved neurological functional recovery in these aged stroke animals.Conclusions:Xe-liposomal treatment reduces ischemic core growth in adult rats and has a therapeutic effect in aged stroke animals. These results support further development of Xe-based therapies for stroke.

Circulation, Volume 150, Issue Suppl_1, Page A4120957-A4120957, November 12, 2024. Background:Endovascular therapy (EVT) has revolutionized the treatment of acute ischemic stroke due to large vessel occlusions. Despite the increasing evidence for EVT, its efficacy remains understudied in patients with acute ischemic stroke with large infarcts. Patients with large-volume ischemic strokes are excluded from major randomized controlled trials (RCTs) despite contributing up to 25% of all acute ischemic strokes.Aim:This study aimed to compare clinical outcomes with endovascular thrombectomy versus medical management in patients with acute ischemic stroke with large infarct.Methods:We conducted a systematic literature review on PubMed, Embase, Scopus and Cochrane Library from inception to 15th May 2024 for RCTs. The inverse-variance random-effects model was used to pool odds ratio (OR) and risk ratio (RR) with 95% confidence intervals. The statistical significance was set at p

Circulation, Volume 150, Issue Suppl_1, Page A4146972-A4146972, November 12, 2024. Introduction:Acute ischemic stroke (AIS) represents a significant long-term complication following cardiac surgery, often linked with unfavorable outcomes. Left atrial (LA) mechanics, notably LA strain, have been identified as predictors for both stroke and atrial fibrillation in various populations. However, conflicting evidence exists regarding the clinical relevance of postoperative atrial fibrillation (POAF), and its contribution to the relationship between LA mechanics and ischemic stroke remains uncertain.Objective:Our study examined the significance of left atrial strain parameters as autonomous predictors of acute ischemic stroke (AIS) among patients undergoing coronary artery bypass grafting (CABG). Additionally, we investigated the association between AIS and postoperative atrial fibrillation (POAF) in CABG patients.Methods and Materials:For a retrospective cohort analysis, we enrolled patients undergoing isolated coronary artery bypass grafting between 2021 and 2023. Transthoracic echocardiography was conducted preoperatively. The main outcome assessed was ischemic stroke. We explored the relationship between left atrial (LA) reservoir strain and ischemic stroke using uni- and multivariable Cox proportional hazards regression models, with adjustments for postoperative atrial fibrillation.Results:We analyzed a cohort comprising 410 patients, among whom 78 (19%) developed postoperative atrial fibrillation (POAF). Over a median follow-up period of 1.4 years, 19 patients (4.6%) experienced ischemic stroke. In univariable analysis, a significant association was observed between left atrial (LA) reservoir strain and ischemic stroke (hazard ratio [HR] 1.34, 95% confidence interval [CI] 0.97–1.23, p < 0.005) per 1% absolute decrease. Even after adjusting for factors including LA volume index (LAVi) and prior stroke, LA reservoir strain remained a significant predictor of ischemic stroke (HR 1.07, 95% CI 1.01–1.21, p < 0.005 per 1% absolute decrease; HR 3.6, 95% CI 1.23–11.04, p < 0.005 for < vs. >median). The inclusion of POAF as a covariate did not affect the significance of LA reservoir strain in the model.Conclusion:Our study concluded that among patients who underwent CABG, LA reservoir strain independently predicted ischemic stroke over the long term.

Circulation, Volume 150, Issue Suppl_1, Page A4139504-A4139504, November 12, 2024. Background:Atrial fibrillation (AF) outcomes are strongly associated with continuous measures of AF burden.Objectives:To assess the association between changes in maximum daily AF duration (MDAFD) and the combined endpoint of ischemic stroke and mortality among patients with cardiac implantable electronic devices (CIEDs) capable of continuous AF detection.Methods:The Optum®de-identified electronic health record (EHR) (2007-2021) was linked with the Medtronic CareLink®heart rhythm database for this study. CIED patients with healthcare activity recorded in the EHR >12 months pre- and >6 months post-CIED implant were included, excluding those with oral anticoagulation (OAC) prescription. MDAFD was assessed during the first 30 days post-implant (baseline period) and the 30 days prior to censoring or an event. Associations between change in MDAFD and the combined endpoint were evaluated, adjusting for the individual components of CHA2DS2-VASc, baseline MDAFD category and chronic kidney disease (CKD).Results:Of 26,400 patients (68±13 years; 60% male; follow-up 2.6±1.6 years) analyzed, 2,544 (9.6%) had AF during baseline. In all patients, increased (vs. stable or decreased) MDAFD in follow-up was associated with a higher adjusted rate of stroke and mortality (HR 1.80 [1.61-2.01]). There was no association between decreased MDAFD in follow-up and the combined endpoint. 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 adjusted risk of stroke or mortality among patients with baseline MDAFD 1hour-