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Sleep and physical activity levels are both associated with cognitive performance among older adults; however, the brain mechanisms underlying these beneficial relationships remain poorly understood. This study investigated cross-sectional associations of actigraphic estimates of physical activity and sleep with cognition and diffusion imaging-based measures of medial temporal lobe (MTL) gray matter microstructural integrity in adults free of dementia. Participants were 132 older adults from the Biomarkers of Cognitive Decline Among Normal Individuals (BIOCARD) cohort study (119 cognitively unimpaired and 13 with mild cognitive impairment; mean age=70.8 years). Multiple linear regression analyses assessed the relationships between total volume of physical activity (TVPA), total sleep time (TST), and sleep efficiency (SE) with cognitive performance and MTL microstructural integrity. Results indicated that greater TVPA and SE were both independently associated with higher hippocampal and parahippocampal microstructure integrity (indicated by lower mean diffusivity) and better visuospatial processing abilities, independent of the volume of these structures and of amyloid burden, measured by positron emission tomography. Additionally, higher hippocampal microstructure statistically mediated the independent associations of physical activity and sleep with visuospatial abilities, independent of MTL volume and Aβ load. These findings suggest that physical activity and sleep are independently associated with cognitive performance, and that hippocampal microstructural integrity may be an underlying mechanism supporting these associations., Competing Interests: Conflict of Interest Vadim Zipunnikov consults with Takeda Pharmaceuticals. The details of the contracts are disclosed through the Johns Hopkins University eDisclose system and have no direct or apparent relationship with the current paper. Adam Spira received payment for serving as a consultant for Merck, received honoraria from Springer Nature Switzerland AG for guest editing special issues of Current Sleep Medicine Reports, and is a paid consultant to Sequoia Neurovitality, BellSant, Inc., and Amissa, Inc. These roles have no direct or apparent relationship with the current paper. Arnold Bakker is a paid consultant to AgeneBio, Inc. Arnold Bakker’s role in the current study was in compliance with the conflict of interest policies of the Johns Hopkins School of Medicine. His consulting role has no direct or apparent relationship with the current paper. The authors verify that each of the following statements is true pertaining to the submitted manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Aims: Physical inactivity and poor sleep are common in older adults and may interact to contribute to age- and disease-related cognitive decline. However, prior work regarding the associations among physical activity, and cognition in older adults is primarily limited to subjective questionnaires that are susceptible to inaccuracies and recall bias. Therefore, this study examined whether objectively measured physical activity and sleep characteristics, each estimated using actigraphy, are independently or interactively associated with cognitive performance., Methods: The study included 157 older adults free of dementia (136 cognitively unimpaired; 21 MCI; M age = 71.7) from the BIOCARD cohort., Results: Using multiple linear regression, cognition was regressed on estimated total volume of physical activity (TVPA), sleep efficiency (SE), wake after sleep onset (WASO), and total sleep time (TST) (adjusted for age, sex, education, diagnosis, vascular risk factors, and Apolipoprotein E (APOE)-e4 genetic status). Models were also run for domain-specific cognitive composite scores. TVPA and SE each were positively associated with a global cognitive composite score. TVPA was positively associated with executive function and language composites, and SE was positively related to executive function, visuospatial, and language composites. Importantly, a TVPA by SE interaction (p = 0.015) suggested that adults with the poorest SE experienced the greatest benefit from physical activity in relation to global cognition. The other sleep metrics were unrelated to cognitive performance., Conclusion: These results suggest that TVPA and SE may synergistically benefit cognition in older adults., Competing Interests: Conflicts of Interest: Dr. Vadim Zipunnikov consults with Takeda Pharmaceuticals. The details of the contracts are disclosed through the Johns Hopkins University eDisclose system and have no direct or apparent relationship with the current paper. Adam Spira received payment for serving as a consultant for Merck, received honoraria from Springer Nature Switzerland AG for guest editing special issues of Current Sleep Medicine Reports, and is a paid consultant to Sequoia Neurovitality and BellSant, Inc. Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Greater physical activity and better sleep are associated with reduced risk of cognitive decline and dementia among older adults, but little is known about their combined associations with measures of brain function and neuropathology. This study investigated potential independent and interactive cross-sectional relationships between actigraphy-estimated total volume of physical activity (TVPA) and sleep patterns [i.e., total sleep time (TST), sleep efficiency (SE)] with resting-state functional magnetic resonance imaging (rs-fMRI) measures of large scale network connectivity and positron emission tomography (PET) measures of amyloid-β. Participants were 135 non-demented older adults from the BIOCARD study (116 cognitively normal and 19 with mild cognitive impairment; mean age = 70.0 years). Using multiple linear regression analyses, we assessed the association between TVPA, TST, and SE with connectivity within the default-mode, salience, and fronto-parietal control networks, and with network modularity, a measure of network segregation. Higher TVPA and SE were independently associated with greater network modularity, although the positive relationship of SE with modularity was only present in amyloid-negative individuals. Additionally, higher TVPA was associated with greater connectivity within the default-mode network, while greater SE was related to greater connectivity within the salience network. In contrast, longer TST was associated with lower network modularity, particularly among amyloid-positive individuals, suggesting a relationship between longer sleep duration and greater network disorganization. Physical activity and sleep measures were not associated with amyloid positivity. These data suggest that greater physical activity levels and more efficient sleep may promote more segregated and potentially resilient functional networks and increase functional connectivity within specific large-scale networks and that the relationship between sleep and functional networks connectivity may depend on amyloid status., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Higher physical activity levels are associated with reduced cognitive decline among older adults; however, current understanding of underlying brain mechanisms is limited. This cross-sectional study investigated the relationship between actigraphy-estimated total volume of physical activity (TVPA) and magnetic resonance imaging (MRI) measures of white matter hyperintensities (WMH), and functional and structural brain connectivity, measured by resting-state functional MRI and diffusion tensor imaging. Study participants (N = 156, mean age = 71 years) included 136 with normal cognition and 20 with Mild Cognitive Impairment. Higher TVPA was associated with greater functional connectivity within the default-mode network and greater network modularity (a measure of network specialization), as well as with greater anisotropy and lower radial diffusion in white matter, suggesting better structural connectivity. These associations with functional and structural connectivity were independent of one another and independent of the level of vascular risk, APOE-ε4 status, cognitive reserve, and WMH volume, which were not associated with TVPA. Findings suggest that physical activity is beneficial for brain connectivity among older individuals with varying levels of risk for cognitive decline., (Copyright © 2022. Published by Elsevier Inc.)

Background: Contrast-enhanced cardiac computed tomography (CE-CT) provides useful substrate characterization in patients with ventricular tachycardia (VT)., Objective: The purpose of this study was to describe the association between endocardial electrogram measurements and myocardial characteristics on CE-CT, in particular the field of view of electrogram features., Methods: Fifteen patients with postinfarct VT who underwent catheter ablation with preprocedural CE-CT were included. Electroanatomic maps were registered to CE-CT, and myocardial attenuation surrounding each endocardial point was measured at a radius of 5, 10, and 15 mm. The association between endocardial voltage and attenuation was assessed using a multilevel random effects linear regression model, clustered by patient, with best model fit defined by highest log likelihood., Results: A total of 4698 points were included. There was a significant association of bipolar and unipolar voltage with myocardial attenuation at all radii. For unipolar voltage, the best model fit was at an analysis radius of 15 mm regardless of the mapping catheter used. For bipolar voltage, the best model fit was at an analysis radius of 15 mm for points acquired with a conventional ablation catheter. In contrast, the best model fit for points acquired with a multipolar mapping catheter was at an analysis radius of 5 mm., Conclusion: Myocardial attenuation on CE-CT indicates a smaller myocardial field of view of bipolar electrograms using multipolar catheters with smaller electrodes in comparison to standard ablation catheters despite similar interelectrode spacing. Smaller electrodes may provide improved spatial resolution for the definition of myocardial substrate for VT ablation., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Epicardial adipose tissue (EAdT) is metabolically active and likely contributes to atrial fibrillation (AF) through the release of inflammatory cytokines into the myocardium or through its rich innervation with ganglionated plexi at the pulmonary vein ostia. The electrophysiologic mechanisms underlying the association between EAdT and AF remain unclear., Objective: The purpose of this study was to investigate the association of EAdT with adjacent myocardial substrate., Methods: Thirty consecutive patients who underwent cardiac computed tomography as well as electroanatomic mapping in sinus rhythm before an initial AF ablation procedure were studied. Semiautomatic segmentation of atrial EAdT was performed and registered anatomically to the voltage map., Results: In multivariable regression analysis clustered by patient, age (-0.01 per year) and EAdT (-0.29) were associated with log bipolar voltage as well as low-voltage zones (<0.5 mV). Age (odds ratio [OR]: 1.02 per year), male gender (OR: 3.50), diabetes (OR: 2.91), hypertension (OR: 2.55), and EAdT (OR: 8.56) were associated with fractionated electrograms, and age (OR: 2.80), male gender (OR: 3.00), and EAdT (OR: 7.03) were associated with widened signals. Age (OR: 1.03 per year) and body mass index (OR: 1.06 per kg/m 2 ) were associated with atrial fat., Conclusion: The presence of overlaying EAdT was associated with lower bipolar voltage and electrogram fractionation as electrophysiologic substrates for AF. EAdT was not a statistical mediator of the association between clinical variables and AF substrate. Body mass index was directly associated with the presence of EAdT in patients with AF., (Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Type II diabetes mellitus (DM) increases risk for cognitive decline and is associated with brain atrophy in older demented and non-demented individuals. We investigated (1) the cross-sectional association between fasting blood glucose level and cortical thickness in a sample of largely middle-aged, cognitively normal adults, and (2) whether these associations were modified by genes associated with both lipid processing and dementia. To explore possible modifications by genetic status, we investigated the interaction between blood glucose levels and the apolipoprotein E (APOE) ε4 allele and the translocase of the outer mitochondrial membrane (TOMM) 40 '523 genotype on cortical thickness. Cortical thickness measures were based on mean thickness in a subset of a priori-selected brain regions hypothesized to be vulnerable to atrophy in Alzheimer's disease (AD) (i.e., 'AD vulnerable regions'). Participants included 233 cognitively normal subjects in the BIOCARD study who had a measure of fasting blood glucose and cortical thickness measures, quantified by magnetic resonance imaging (MRI) scans. After adjustment for age, sex, race, education, depression, and medical conditions, higher blood glucose was associated with thinner parahippocampal gyri (B=-0.002; 95% CI -0.004, -0.0004) and temporal pole (B=-0.002; 95% CI -0.004, -0.0001), as well as reduced average thickness over AD vulnerable regions (B=-0.001; 95% CI -0.002, -0.0001). There was no evidence for greater cortical thinning in ε4 carriers of the APOE gene or in APOE ε3/3 individuals carrying the TOMM40 VL/VL genotypes. When individuals with glucose levels in the diabetic range (≥126mg/dL), were excluded from the analysis, the associations between glucose levels and cortical thickness were no longer significant. These findings suggest that glucose levels in the diabetic range are associated with reduced cortical thickness in AD vulnerable regions as early as middle age., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Prognostic significance of left atrial (LA) function in patients with atrial fibrillation (AF) is poorly defined., Objective: To examine the association of LA function measured with cardiac magnetic resonance (CMR) feature-tracking and AF recurrence following catheter ablation., Methods: One hundred and twenty-one AF patients (72% paroxysmal, mean age 59 ± 10 years) were enrolled. Baseline LA function was measured by calculating passive, active, and total emptying fractions (LAEF) and analysis of global longitudinal strain and strain rates. Patients were followed up for recurrence of AF or atrial tachycardia (AT). Hazard ratios for recurrence were calculated using Cox proportional models adjusted for potential clinical confounders, type of AF, left ventricular ejection fraction, AF duration, LA volume, and late gadolinium enhancement (LGE)., Results: During a mean follow-up of 18 ± 9 months, 52 patients (43%) experienced recurrent AF/AT. Patients with recurrent AF/AT had higher baseline LA volume index and lower LA passive, and total LAEF (P < .05 for all). The baseline peak LA strain and strain rates in all phases of LA function were lower in the AF/AT recurrence group (P < .01 for all). In multivariable analysis total LAEF, peak LA strain, and systolic and late diastolic strain rates were associated with recurrence. Both peak LA strain and total LAEF improved prediction of recurrent AT/AF compared to the baseline clinical model, including LA LGE (C statistic 0.82 vs 0.77, P < .05 for both total LAEF and peak LA strain)., Conclusions: LA reservoir function was independently associated with recurrent AF/AT after PVI and can additionally improve risk stratification in patients undergoing PVI., (Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: The extent of left atrial (LA) late gadolinium enhancement (LGE), as a surrogate for fibrosis, has been associated with atrial fibrillation (AF) recurrence after catheter ablation. Furthermore, there is ex vivo evidence that islands of fibrosis may anchor fibrillatory rotors., Objective: The purpose of this study was to examine the anatomical association of AF rotors with LA and right atrial (RA) LGE on cardiac magnetic resonance., Methods: The cohort included 9 patients with persistent AF (mean age 61.1 ± 9.7 years) who underwent LGE cardiac magnetic resonance before AF ablation using the focal impulse and rotor modulation system. The extent of LA and RA LGE was quantified globally and in each of the 7 sectors: LA posterior/inferior wall, anterior wall, roof, left and right pulmonary vein antra, and RA lateral and septal regions. The multivariable association of rotor incidence with global and per sector LGE extent was examined using multivariable Bernoulli logistic regression estimated by generalized estimating equations., Results: The mean RA and LA volumes were 113.2 ± 37.31 and 143.03 ± 58.25 mL, respectively. The mean RA and LA LGE burden was 17.2% ± 11.0% and 17.4% ± 14.4%, respectively. A total of 18 LA rotors and 9 RA rotors were identified in all patients. No univariable or multivariable association was observed between global or per sector LGE extent and focal impulse and rotor modulation rotor incidence., Conclusion: In this cohort of patients, there was no association between AF rotor incidence and the global or regional extent of RA and LA LGE., (Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Symptomatic left atrial (LA) flutter (LAFL) is common after atrial fibrillation (AF) ablation., Objective: The purpose of this study was to examine the association of baseline LA function with incident LAFL after AF ablation., Methods: The source cohort included 216 patients with cardiac magnetic resonance (CMR) before initial AF ablation between 2010 and 2013. Patients who underwent cryoballoon or laser ablation, patients with AF during CMR, and those with suboptimal CMR, or missing follow-up data were excluded. Baseline LA volume and function were assessed by feature-tracking CMR analysis., Results: The final cohort included 119 patients (mean age 58.9 ± 11 years; 76.5% men; 70.6% patients with paroxysmal AF). During a median follow-up of 421 days (interquartile range 235-751 days), 22 patients (18.5%) had incident LAFL. Baseline LA volume was similar between the 2 groups. In contrast, baseline reservoir, conduit, and contractile function of the LA were significantly impaired in patients with incident LAFL. Baseline global peak longitudinal atrial strain (PLAS) <22.65% predicted incident LAFL with 86% sensitivity and 68% specificity (C statistic 0.76). In a multivariable model adjusting for age, heart failure, and LA volume, PLAS (hazard ratio 0.9 per % increase in PLAS; P = .003) and LA linear lesions (hazard ratio 2.94; P = .020) were independently associated with incident LAFL. The coexistence of PLAS <22.65% and linear lesions was associated with 9-fold increased hazard of incident LAFL., Conclusion: Baseline LA function and linear lesions were independently associated with incident LAFL after AF ablation. Linear lesions should be limited to selected cases, especially in patients with impaired LA function., (Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objectives: The aims of this study were to: 1) use a novel method of late gadolinium enhancement (LGE) quantification that uses normalized intensity measures to confirm the association between LGE extent and atrial fibrillation (AF) recurrence following ablation; and 2) examine the presence of interaction and effect modification between LGE and AF persistence., Background: Recurrent AF after catheter ablation has been reported to associate with the baseline extent of left atrial LGE on cardiac magnetic resonance. Traditional methods for measurement of intensity lack an objective threshold for quantification and interpatient comparisons of LGE., Methods: The cohort included 165 participants (mean age 60.0 ± 10.2 years, 77% men, 57% with persistent AF) who underwent initial AF ablation. The association of baseline LGE extent with AF recurrence was examined using multivariable Cox proportional hazards models. Multiplicative and additive interactions between AF type and LGE extent were examined., Results: During 10.2 ± 5.7 months of follow-up, 63 patients (38.2%) experienced AF recurrence. Baseline LGE extent was independently associated with AF recurrence after adjusting for confounders (hazard ratio: 1.5 per 10% increased LGE; p < 0.001). The hazard ratio for AF recurrence progressively increased as a function of LGE. The magnitude of association between LGE >35% and AF recurrence was greater among patients with persistent AF (hazard ratio: 6.5 [p = 0.001] vs. 3.6 [p = 0.001]); however, there was no evidence for statistical interaction., Conclusions: Regardless of AF persistence at baseline, participants with LGE ≤35% have favorable outcomes, whereas those with LGE >35% have a higher rate of AF recurrence in the first year after ablation. These findings suggest a role for: 1) patient selection for AF ablation using LGE extent; and 2) substrate modification in addition to pulmonary vein isolation in patients with LGE extent exceeding 35% of left atrial myocardium., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Myocardial fat deposition (FAT-DEP) has been frequently observed in regions of chronic myocardial infarction in patients with ischemic cardiomyopathy. The role of FAT-DEP within scar-related ventricular tachycardia (VT) circuits has not been investigated., Objective: This pilot study aimed to assess the impact of myocardial FAT-DEP on local electrograms and VT circuits in patients with ischemic cardiomyopathy., Methods: Contrast-enhanced computed tomography was performed in 22 patients with ischemic VT. Electroanatomic map points were registered to the corresponding contrast-enhanced computed tomography images. Myocardial FAT-DEP was identified and characterized using a postprocessing image overlay that highlighted areas below 0 Hounsfield units (HU). The mean attenuation of local myocardial regions corresponding to sampled electrograms was measured on short-axis images. The associations of mean attenuation with bipolar and unipolar amplitudes, left ventricular wall thickness, and VT circuit sites were investigated., Results: Of 1801 electroanatomic map points, 519 (28.8%) were located in regions with FAT-DEP. Significant differences were observed in mean intensity (23.2 ± 35.6 HU vs 81.7 ± 21.9 HU; P < .001), bipolar (0.75 ± 0.83 mV vs 2.9 ± 2.4 mV; P < .001) and unipolar (3.1 ± 1.7 mV vs 7.4 ± 4.3 mV; P < .001) amplitudes, and left ventricular wall thickness (5.2 ± 1.7 mm vs 8.2 ± 2.5 mm; P < .001) between regions with and without FAT-DEP. Lower HU was strongly associated with lower bipolar and unipolar amplitudes (P < .0001, respectively). Importantly, FAT-DEP was associated with critical VT circuit sites with fractionated or isolated potentials., Conclusion: FAT-DEP was associated with electrogram characteristics and VT circuit sites. Further work will be needed to determine whether FAT-DEP plays a causal role in the generation of ischemic scar-related VT circuits., (Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Previous studies have shown that contrast-enhanced multidetector computed tomography (CE-MDCT) could identify ventricular fibrosis after myocardial infarction. However, whether CE-MDCT can characterize atrial low-voltage regions remains unknown., Objective: The purpose of this study was to examine the association of CE-MDCT image attenuation with left atrial (LA) low bipolar voltage regions in patients undergoing repeat ablation for atrial fibrillation recurrence., Methods: We enrolled 20 patients undergoing repeat ablation for atrial fibrillation recurrence. All patients underwent preprocedural 3-dimensional CE-MDCT of the LA, followed by voltage mapping (>100 points) of the LA during the ablation procedure. Epicardial and endocardial contours were manually drawn around LA myocardium on multiplanar CE-MDCT axial images. Segmented 3-dimensional images of the LA myocardium were reconstructed. Electroanatomic map points were retrospectively registered to the corresponding CE-MDCT images., Results: A total of 2028 electroanatomic map points obtained in sinus rhythm from the LA endocardium were registered to the segmented LA wall CE-MDCT images. In a linear mixed model, each unit increase in the local image attenuation ratio was associated with 25.2% increase in log bipolar voltage (P = .046) after adjusting for age, sex, body mass index, and LA volume, as well as clustering of data by patient and LA regions., Conclusion: We demonstrate that the image attenuation ratio derived from CE-MDCT is associated with LA bipolar voltage. The potential ability to image fibrosis via CE-MDCT may provide a useful alternative in patients with contraindications to magnetic resonance imaging., (Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Postablation atrial fibrillation recurrence is positively associated with the extent of preexisting left atrial (LA) late gadolinium enhancement (LGE) on magnetic resonance imaging (MRI), but negatively associated with the extent of postablation LGE regardless of proximity to the pulmonary vein antra. The characteristics of pre- vs postablation LA LGE may provide insight into this seeming paradox and inform future strategies for ablation., Objective: The purpose of this study was to define the characteristics of preexisting vs ablation-induced LA LGE., Methods: LGE-MRI was prospectively performed before and ≥3 months after initial ablation in 20 patients. The intracardiac locations of ablation points were coregistered with the corresponding sites on axial planes of postablation LGE-MRI. The image intensity ratio (IIR), defined as the LA myocardial MRI signal intensity divided by the mean LA blood pool intensity, and LA myocardial wall thickness were calculated on pre- and postablation images., Results: Imaging data from 409 pairs of pre- and postablation axial LGE-MRI planes and 6961 pairs of pre- and postablation image sectors were analyzed. Ablation-induced LGE revealed a higher IIR, suggesting greater contrast uptake and denser fibrosis, than did preexisting LGE (1.25 ± 0.25 vs 1.14 ± 0.15; P < .001). In addition, ablation-induced LGE regions had thinner LA myocardium (2.10 ± 0.67 mm vs 2.37 ± 0.74 mm; P < .001)., Conclusion: Regions with ablation-induced LGE exhibit increased contrast uptake, likely signifying higher scar density, and thinner myocardium as compared with regions with preexisting LGE. Future studies examining the association of postablation LGE intensity and nonuniformity with ablation success are warranted and may inform strategies to optimize ablation outcome., (Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: The measurement of late gadolinium-enhanced magnetic resonance imaging (LGE-MRI) intensity in arbitrary units limits the objectivity of thresholds for focal scar detection and interpatient comparisons of scar burden., Objective: To develop and validate a normalized measure, the image intensity ratio (IIR), for the assessment of left atrial (LA) scar on LGE-MRI., Methods: Electrocardiogram- and respiratory-gated 1.5 Tesla LGE-MRI was performed in 75 patients (75% men; 62 ± 8 years) before atrial fibrillation ablation. The local IIR was defined as LA myocardial signal intensity for each of the 20 sectors on contiguous axial image planes divided by the mean LA blood pool image intensity. Intracardiac point-by-point sampled electroanatomic map points were coregistered with the corresponding image sectors., Results: The average bipolar voltage for all 8153 electroanatomic map points was 0.9 ± 1.1 mV. In a mixed effects model accounting for within patient clustering, and adjusting for age, LA volume, mass, body mass index, sex, CHA2DS2-VASc score, atrial fibrillation type, history of previous ablations, and contrast delay time, each unit increase in local IIR was associated with 91.3% decrease in bipolar LA voltage (P < .001). Local IIR thresholds of >0.97 and >1.61 corresponded to bipolar voltage <0.5 and <0.1 mV, respectively., Conclusions: Normalization of LGE-MRI intensity by the mean blood pool intensity results in a metric that is closely associated with intracardiac voltage as a surrogate of atrial fibrosis., (© 2013 Heart Rhythm Society Published by Heart Rhythm Society All rights reserved.)

Background: Atrial fibrillation (AF) is an important cause of stroke. Given the morbidity and mortality associated with stroke, the risk stratification of patients based on left atrial appendage (LAA) characteristics is of great interest., Objective: To explore the association between LAA morphology and LAA characteristics including the extent of trabeculations, orifice diameter, and length with prevalent stroke in a large cohort of patients with drug refractory AF who underwent AF ablation to develop mechanistic insight regarding the risk of stroke., Methods: An institutional cohort of 1063 patients referred for AF ablation from 2003 to 2012 was reviewed to identify patients that underwent preprocedural cardiac computed tomography (CT). LAA morphology was characterized as chicken wing, cactus, windsock, or cauliflower by using previously reported methodology. Left atrial size and LAA trabeculations, morphology, orifice diameter, and length were compared between patients with prevalent stroke and patients without prevalent stroke., Results: Of 678 patients with CT images, 65 (10%) had prior stroke or transient ischemic attack. In univariate analyses, prevalent heart failure (7.7% in cases vs 2.8% in controls; P = .033), smaller LAA orifice (2.26 ± 0.52 cm vs 2.78 ± 0.71 cm ; P < .001), shorter LAA length (5.06 ± 1.17 cm vs 5.61 ± 1.17 cm; P < .001), and extensive LAA trabeculations (27.7% vs 14.4%; P = .019) were associated with stroke. LAA morphologies were unassociated with stroke risk. In multivariable analysis, smaller LAA orifice diameter and extensive LAA trabeculations remained independently associated with thromboembolic events., Conclusions: The extent of LAA trabeculations and smaller LAA orifice diameter are associated with prevalent stroke and may mediate the previously described association of cauliflower LAA morphology with stroke., (© 2013 Heart Rhythm Society Published by Heart Rhythm Society All rights reserved.)