Alonso, Álvaro

Background Multimorbidity is common in patients with atrial fibrillation (AF); however, the impact of the number and type of comorbid conditions on outcomes remains uncertain. Methods This cohort study included patients with new‐onset AF from a Midwest region between 2013 and 2017. Eighteen chronic conditions at the time of AF were classified into groups: cardiometabolic, other somatic, and mental health. Cox regression determined associations between the number of each condition type with death, ischemic stroke/transient ischemic attack, and congestive heart failure, stratified by age. Results Among 16 509 patients with AF (mean age, 74 years; 43% women), the mean number of cardiometabolic, other somatic, and mental health conditions was 2.7, 1.4, and 0.5, respectively. The number and type of conditions had a varying impact on outcomes and differed by age. A higher number of cardiometabolic conditions were associated with increased risk of death within 90 days only in people aged ≥85 years (≥4 conditions versus 0: hazard ratio [HR], 1.74 [95% CI, 1.05–2.87]), whereas for death after 90 days, associations were strongest in the youngest age group (<65 years: HR, 1.83 [95% CI, 1.35–2.46]; 65–74 years: HR, 1.34 [95% CI, 1.04–1.73]; 75–84 years: HR, 1.32 [95% CI, 1.09–1.60]; ≥85 years: HR, 1.14 [95% CI, 0.96–1.35]). Associations with outcomes were generally strongest in the youngest age group and attenuated with older age for higher number of other somatic conditions, whereas the pattern was less consistent for mental health conditions. Conclusions Along with cardiometabolic‐related conditions, other somatic and mental health conditions are important predictors of outcomes in AF, with effects differing by age, and should be considered when caring for these patients.

Background Multimorbidity is common in patients with atrial fibrillation (AF), yet comorbidity patterns are not well documented. Methods The prevalence of 18 chronic conditions (6 cardiometabolic, 7 other somatic, 5 mental health) was obtained in patients with new-onset AF from 2013-2017 from a 27-county region and controls matched 1:1 on age, sex, and county of residence. For AF patients and controls separately, clustering of conditions and co-occurrence beyond chance was estimated (using the asymmetric Somers’ D statistic), overall and for ages <65, 65-74, 75-84, and ≥85 years. Results Among 16,509 patients with AF (median age 76 years, 57% men), few (4%) did not have any of the 18 chronic conditions, whereas nearly one-quarter of controls (23%) did not have any chronic conditions. Clustering of cardiometabolic conditions was common in both AF patients and controls, but clustering of other somatic conditions was more common in AF. Although the prevalence of most condition pairs was higher in AF patients, controls had a larger number of condition pairs occurring together beyond chance. In persons aged <65 years, AF patients more frequently exhibited concordance of condition pairs that included either pairs of somatic conditions or a combination of conditions from different condition groups. In persons aged 65-74 years, AF patients more frequently had pairs of other somatic conditions. Conclusion Patterns of co-existing conditions differed between patients with AF and controls, particularly in younger ages. A better understanding of the clinical consequences of multimorbidity in AF patients, including those diagnosed at younger ages, is needed.

AbstractBackground and purposeLower left atrial (LA) function is associated with higher dementia risk and may be mechanistically linked through vascular brain injury, an established correlate for higher dementia risk. Using data from the Atherosclerosis Risk in Communities study, we assessed the cross‐sectional association between LA function and brain magnetic resonance imaging (MRI) markers of vascular brain injury.MethodsWe included 1488 participants who were free of prevalent dementia, stroke, or atrial fibrillation and who underwent a two‐dimensional echocardiogram and brain MRI in 2011–2013 (mean [± standard deviation] age 76 [± 5] years, 60% female, 27% Black). LA function measures (reservoir, conduit, contractile strain) were assessed in quartiles. Brain MRI measures included cerebral microbleeds, brain infarcts, and white matter hyperintensity (WMH) volume. Logistic regression was used for dichotomous outcomes. Linear regression was used for WMH volume.ResultsOverall, 343 (23%) and 344 participants (23%) had ≥1 cerebral microbleed or brain infarct. After multivariable adjustments, the lowest LA reservoir and conduit strain quartiles (vs. highest quartile) were associated with higher odds of the presence of ≥1 cerebral microbleed (odds ratios [95% confidence intervals] 1.78 [1.42–2.22] and 1.52 [1.22–1.90]). Compared to the highest quartile, participants in the lowest LA conduit strain quartile had 1.51 (95% confidence interval 1.22–1.88) times higher odds of having ≥1 brain infarct. Lower LA contractile strain was associated with lower odds of brain infarcts. No association with WMH volume was noted.ConclusionsWe found that LA reservoir and conduit strain were associated with cerebral microbleeds and brain infarcts. Lower LA function may be linked to dementia risk via vascular brain injury. Prospective studies are needed to confirm these findings.

Introduction: Isolated cases of liver injury associated with the use of non-vitamin K antagonist oral anticoagulants (NOACs) have been reported. However, the comparative incidence of liver injury in users of different oral anticoagulants is unknown. Methods: We studied 113,717 patients (mean age 70, 39% women) with non-valvular atrial fibrillation (AF) included in the MarketScan® Commercial and Medicare Supplemental databases with a first prescription for oral anticoagulation after November 4, 2011, followed through December 31, 2014. Of these, 56,879 initiated warfarin, 17,286 initiated dabigatran, 30,347 initiated rivaroxaban, and 9,205 initiated apixaban. Liver injury hospitalizations were identified using selected inpatient diagnostic codes. Multivariable Cox models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of liver injury by anticoagulant type. Results: During a median follow-up of 12 months, 960 hospitalizations with liver injury were identified. Rates of liver injury hospitalization (per 1000 person-years) by oral anticoagulant were 9.0 (warfarin), 4.0 (dabigatran), 6.6 (rivaroxaban), and 5.6 (apixaban). After multivariable adjustment, rates of liver injury hospitalization were lower in initiators of NOACs compared to warfarin: HR (95%CI) of 0.57 (0.46, 0.71), 0.88 (0.75, 1.03) and 0.70 (0.50, 0.97) for initiators of dabigatran, rivaroxaban, and apixaban, respectively (Table). Compared to dabigatran initiators, rivaroxaban initiators had a 56% increased risk of liver injury hospitalization (HR 1.56, 95%CI 1.22, 1.99). In addition to type of anticoagulant, prior liver, gallbladder, and kidney disease, cancer, anemia, heart failure, and alcoholism significantly predicted liver injury hospitalization. Conclusions: Among patients with non-valvular AF, NOACs were associated with lower risk of liver injury hospitalization compared to warfarin, with dabigatran showing the lowest risk.

Moritz F Sinner, 2012 Finalist and Presenting Author

Background: Lower (worse) left atrial (LA) function is associated with higher dementia risk. It is unclear whether lower LA function is associated with vascular brain injury on brain MRI, an established correlate for higher dementia risk. Using data from the Atherosclerosis Risk in Communities (ARIC) study, we assessed the cross-sectional association between LA function measures and brain MRI markers of vascular brain injury (cerebral microbleeds, brain infarcts). Hypothesis: Participants with lower LA function will be more likely to have presence of > 1 cerebral microbleed or brain infarct. Methods: ARIC participants who had both an echocardiogram and brain MRI at visit 5 (2011-13) were included. We excluded those with prevalent dementia, stroke, or atrial fibrillation. LA function measures were obtained from 2D-echocardiograms and assessed in quartiles (highest quartile was the reference). Brain MRI measures were assessed as the presence or absence of > 1 cerebral microbleed or brain infarct. Logistic regression was used. Results: Of the 1502 participants (mean [SD] age 76 [5], 60% female, 27% Black) in this analysis, 345 (23%) and 351 (23%) had > 1 cerebral microbleed or brain infarct present. Compared to the highest quartile, lower LA reservoir and conduit strain quartiles were associated with higher odds of cerebral microbleeds. LA contractile strain was not associated with cerebral microbleeds. Compared to the highest quartile, the lowest LA conduit strain quartile, but not reservoir strain, was associated with higher odds of brain infarcts. LA contractile strain was inversely associated with brain infarcts. Conclusion: In this community-based cohort, lower LA function was cross-sectionally associated with cerebral microbleeds and brain infarcts. The inverse relationship with LA contractile strain may be due to contractile function compensating for a decrease in early diastolic filling. Prospective studies are needed to confirm these findings.

Background: Multimorbidity is common in atrial fibrillation (AF), particularly among older patients who generally have multiple cardiovascular and non-cardiovascular chronic conditions. However, less is known about the accumulation of chronic conditions in younger patients with AF. Methods: Patients aged <65 with incident AF from 2013-2019 from a 27-county region in the Midwest (N=4907) were matched 1:1 on age (±5 years) and sex to referents from the same community. The index date for the matched pair was the date of first diagnosis of AF. Diagnosis of 20 other chronic conditions was ascertained from 3 years prior to index through 12/31/2022. Mean cumulative function curves were used to visualize the accumulation of conditions; Andersen-Gill models estimated associations between AF/referent status and accumulation of conditions. Results: The mean age was 55 years for both patients with AF and matched referents; 71% were male. In the 3 years leading up to AF diagnosis, only 4% of patients with AF had no additional chronic conditions and 69% had ≥3 chronic conditions. In contrast, 35% of referents had 0 and 32% had ≥3 chronic conditions. The accumulation of chronic conditions was accelerated in patients with AF compared to referents prior to AF diagnosis/index (Figure). After index, patients with AF had increased accumulation of chronic conditions (HR (95% CI): 1.93 (1.71-2.20), 1.82 (1.62-2.05), 1.68 (1.55-1.83), and 1.53 (1.44-1.64) for ages <50, 50-54, 55-59, and 60-64 years, respectively). After 1 year, the differences were attenuated in all age groups with no difference observed between patients with AF and referents in the oldest age group (1.26 (1.08-1.46), 1.28 (1.11-1.47), 1.13 (1.02-1.24), and 1.05 (0.97-1.13) for ages <50, 50-54, 55-59, and 60-64 years). Conclusion: Patients <65 years with AF have an increased accumulation of chronic conditions compared to those without AF, in particular prior to their AF diagnosis and within the first year after AF diagnosis.

Background: The communities in which people live affect their health. We aimed to determine whether neighborhood characteristics are associated with outcomes in patients with atrial fibrillation (AF) in a Midwest community. Methods: Patients with incident AF from 2013-2017 from a 27-county region who survived >90 days after their diagnosis were identified (N=14,725). Patient addresses were linked to publicly-available data on population density (rural-urban commuting area; RUCA) and neighborhood socioeconomic status (area deprivation index; ADI). Patients were followed for ischemic stroke or transient ischemic attack (TIA), heart failure (HF), dementia/delirium, and all-cause death through 2021. Cox regression determined risk of outcomes by RUCA category (urban, micropolitan, small rural, isolated) and ADI quartile after adjustment for age, sex, race/ethnicity, and CHA2DS2-VASc score. Results: After excluding persons missing race/ethnicity (n=46), RUCA (n=1,465), and ADI (n=1,640), 13,233 patients with AF (mean age 73.8 years, 57% men) remained. After a median follow-up of 4.7 years, 5,989 patients died; 582 experienced a stroke/TIA, 4,122 (of 9,156 patients at risk) developed HF, and 1,758 (of 12,154 patients at risk) developed dementia/delirium. Persons living in isolated areas (HR 1.14, 95% CI 1.05-1.24) and the highest ADI quartile (HR 1.59, 95% CI 1.37-1.85) experienced the greatest risk of death (Figure). A trend toward an increased risk of HF was observed for the 2 highest ADI quartiles (p-trend <0.01), although the estimates did not reach statistical significance. The risk of other outcomes did not differ by RUCA or ADI category. Conclusion: Patients with AF residing in isolated areas and neighborhoods with greater area deprivation experience increased risks of death. Additional research is needed to better understand how neighborhood characteristics influence treatment, co-morbid conditions, and other outcomes in patients with AF.

AbstractBackgroundRecent evidence indicates that abnormal P‐wave parameters (PWPs)—ECG markers of atrial myopathy—are associated with incident dementia, independent of atrial fibrillation (AF) and clinical ischemic stroke. However, the mechanisms remain unclear and may include subclinical vascular brain injury. Hence, we evaluated the association of abnormal PWPs with brain MRI correlates of vascular brain injury in the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC‐NCS).MethodsARIC‐NCS participants who underwent 3T brain MRI scans in 2011–2013 were included. PWPs were measured from standard 12‐lead ECGs. Brain MRI outcomes included cortical infarcts, lacunar infarcts, cerebral microhemorrhages, brain volumes, and white matter disease (WMD) volume. We used weighted multivariable logistic and linear regression to evaluate the associations of abnormal PWPs with brain MRI outcomes.ResultsAmong 1715 participants (mean age, 76.1 years; 61% women; 29% Black), 797 (46%) had ≥1 abnormal PWP. After multivariable adjustment, including adjusting for prevalent AF, abnormal P‐wave terminal force in lead V1 (aPTFV1) and prolonged P‐wave duration (PPWD) were associated with increased odds of both cortical (OR 1.41; 95% CI, 1.14 to 1.74 and OR 1.30; 95% CI, 1.04 to 1.63, respectively) and lacunar infarcts (OR 1.36; 95% CI, 1.15 to 1.63 and OR 1.37; 95% CI, 1.15 to 1.65, respectively). Advanced interatrial block (aIAB) was associated with higher odds of subcortical microhemorrhage (OR 2.04; 95% CI, 1.36 to 3.06). Other than a significant association between aPTFV1 with lower parietal lobe volume, there were no other significant associations with brain or WMD volume.ConclusionIn this exploratory analysis of a US community‐based cohort, ECG surrogates of atrial myopathy are associated with a higher prevalence of brain infarcts and microhemorrhage, suggesting subclinical vascular brain injury as a possible mechanism underlying the association of atrial myopathy with dementia.