Stroke and dementia risk in patients with and without atrial fibrillation and carotid arterial disease.

BACKGROUND: Patients with carotid arterial disease (CD) with and without atrial fibrillation (AF) are at risk of stroke. Patients with AF are at a higher risk of stroke and dementia. OBJECTIVES: We sought to understand the risks of stroke, transient ischemic attack (TIA), and dementia in patients with and without AF and CD or a combination of both as well as to determine whether therapies for each disease may influence risks. METHODS: A total of 11,572 patients were included in 4 groups, with 2893 patients populating each group (1: no AF or CD; 2: AF, no CD; 3: CD and no AF; 4: AF and CD) and matched for age, sex, and comorbidities. Long-term outcomes of stroke/TIA and dementia were assessed. Subset analyses of these outcomes were performed in patients with CD treated with revascularization and in patients with AF treated with ablation. RESULTS: CD increased the risk of stroke/TIA (hazard ratio [HR] 2.74; P < .0001) and dementia (HR 1.44; P < .0001). Similarly, AF increased the risk of stroke/TIA (HR 2.08; P < .0001) and dementia (HR 1.30; P = .004). The coexistence of AF and CD further augmented the risk of both end points. CD revascularization was associated with a decreased risk of dementia (HR 0.47; P < .0001) but not stroke. Ablation of AF improved outcomes of stroke/TIA (HR 0.55; P = .002), particularly in those with CD (HR 0.36; P < .0001), and was associated with a reduced risk of dementia (HR 0.51; P = .04). CONCLUSION: CD and AF augment risk of stroke/TIA and dementia in the general population, and the coexistence of both diseases is additive in risk. Ablation of AF was associated with lower risk, the magnitude of which was greater in those with CD.

Augmented intelligence decision tool for stroke prediction combines factors from CHA2 DS2 -VASc and the intermountain risk score for patients with atrial fibrillation.

INTRODUCTION: CHA2 DS2 -VASc and CHADS2 are computationally simple risk prediction tools used to guide anticoagulation decisions for stroke prophylaxis, but they have modest risk discrimination ability and use static dichotomous variables. The Intermountain Mortality Risk Scores (IMRS) are dynamic decision tools using standard clinical laboratory tests. This study derived new stroke prediction scores using variables from both CHA2 DS2 -VASc and IMRS. METHODS AND RESULTS: In outpatients with first atrial fibrillation (AF) diagnosis at the Intermountain Healthcare (females, n = 26 063 males, n = 29 807), sex-specific "IMRS-VASc" scores were derived using variables from CHA2 DS2 -VASc, warfarin use, the complete blood count, and the comprehensive metabolic profile. Validation was performed in an independent Intermountain outpatient AF cohort (females, n = 11 021; males, n = 12 641). Stroke occurred among 3.1% and 3.1% of females and 2.3% and 2.5% of males in derivation and validation groups, respectively. IMRS-VASc stratified stroke with similar ability in derivation (c-statistics, females: c = 0.703, males: c = 0.697) and validation groups (females: c = 0.681, males: c = 0.685). CHA2 DS2 -VASc (females: c = 0.581 and c = 0.605; males: c = 0.616 and c = 0.613 in derivation and validation, respectively) and CHADS2 (females: c = 0.581 and c = 0.608; males: c = 0.620 and c = 0.621 in derivation and validation, respectively) were substantially weaker stroke predictors. IMRS was the strongest mortality predictor (females: c = 0.783 and c = 0.782; males: c = 0.796 and c = 0.794 in derivation and validation, respectively) and all scores were poor at predicting bleeding risk. CONCLUSIONS: A temporally dynamic risk score, IMRS-VASc was derived and validated as a predictor of stroke in outpatients with AF. IMRS-VASc requires further validation and the evaluation of its use in guiding care and treatment decisions for patients with AF.

Atrial Fibrillation and Dementia: Exploring the Association, Defining Risks and Improving Outcomes.

AF is strongly associated with a spectrum of cranial injuries including stroke and dementia. Dementia risk is seen in patients with and without a prior stroke and includes idiopathic forms of dementia, such as Alzheimer's disease. The initiation, use and efficacy of anticoagulation have been shown in multiple observational trials to have an impact on dementia risk. Cerebral hypoperfusion during AF can result in cognitive decline and patients with cranial atherosclerosis may have unique susceptibility. Therapies to carefully control the ventricular rate and catheter ablation have been shown in observational trials to lower dementia risk. There is a need for further research in multiple areas and the observational trials will require prospective trials confirmation. Recent guidelines for AF have advocated the initiation of effective anticoagulation, the treatment of associated disease conditions that may influence the progression of AF and catheter ablation, with long-term management of risk factors to lower risk of dementia.

CHA2DS2-VASc scores and Intermountain Mortality Risk Scores for the joint risk stratification of dementia among patients with atrial fibrillation.

BACKGROUND: High CHA2DS2-VASc scores in atrial fibrillation (AF) patients are generally associated with increased risks of stroke and dementia. At lower CHA2DS2-VASc scores, there remains an unquantifiable cranial injury risk, necessitating an improved risk assessment method within these lower-risk groups. OBJECTIVE: The purpose of this study was to determine whether sex-specific Intermountain Mortality Risk Scores (IMRS), a dynamic measures of systemic health that comprises commonly performed blood tests, can stratify dementia risk overall and among CHA2DS2-VASc score strata in AF patients. METHODS: Female (n = 34,083) and male (n = 39,998) AF patients with no history of dementia were studied. CHA2DS2-VASc scores were assessed at the time of AF diagnosis and were stratified into scores of 0-1, 2, and ≥3. Within each CHA2DS2-VASc score stratum, patients were further stratified by IMRS categories of low, moderate, and high. Multivariable Cox hazard regression was used to determine dementia risk. RESULTS: High-risk IMRS patients were generally older and had higher rates of hypertension, diabetes, heart failure, and prior stroke. Higher CHA2DS2-VASc score strata (≥3 vs ≤1: women, hazard ratio [HR] 7.77, 95% confidence interval [CI] 5.94-10.17, P < .001; men: HR 4.75, 95% CI 4.15-5.44, P < .001) and IMRS categories (high vs low: women, HR 3.09, 95% CI 2.71-3.51, P < .001; men, HR 2.70, 95% CI 2.39-3.06, P < .001) were predictive of dementia. When stratified by CHA2DS2-VASc scores, IMRS further identified risk in each stratum. CONCLUSION: Both CHA2DS2-VASc scores and IMRS were independently associated with dementia incidence among AF patients. IMRS further stratified dementia risk among CHA2DS2-VASc score strata, particularly among those with lower CHA2DS2-VASc scores.

Improving CHA2DS2-VASc stratification of non-fatal stroke and mortality risk using the Intermountain Mortality Risk Score among patients with atrial fibrillation.

Background: Oral anticoagulation (OAC) therapy guidelines recommend using CHA2DS2-VASc to determine OAC need in atrial fibrillation (AF). A usable tool, CHA2DS2-VASc is challenged by its predictive ability. Applying components of the complete blood count and basic metabolic profile, the Intermountain Mortality Risk Score (IMRS) has been extensively validated. This study evaluated whether use of IMRS with CHA2DS2-VASc in patients with AF improves prediction. Methods: Patients with AF undergoing cardiac catheterisation (N=10 077) were followed for non-fatal stroke and mortality (mean 5.8±4.1 years, maximum 19 years). CHA2DS2-VASc and IMRS were calculated at baseline. IMRS categories were defined based on previously defined criteria. Cox regression was adjusted for demographic, clinical and treatment variables not included in IMRS or CHA2DS2-VASc. Results: In women (n=4122, mean age 71±12 years), the composite of non-fatal stroke/mortality was stratified (all p-trend <0.001) by CHA2DS2-VASc (1: 12.6%, 2: 22.8%, >2: 48.1%) and IMRS (low: 17.8%, moderate: 40.9%, high risk: 64.5%), as it was for men (n=5955, mean age 68±12 years) by CHA2DS2-VASc (<2: 15.7%, 2: 30.3%, >2: 51.8%) and IMRS (low: 19.0%, moderate: 42.0%, high risk: 65.9%). IMRS stratified stroke/mortality (all p-trend <0.001) in each CHA2DS2-VASc category. Conclusions: Using IMRS jointly with CHA2DS2-VASc in patients with AF improved the prediction of stroke and mortality. For example, in patients at the OAC treatment threshold (CHA2DS2 -VASc = 2), IMRS provided ≈4-fold separation between low and high risk. IMRS provides an enhancing marker for risk in patients with AF that reflects the underlying systemic nature of this disease that may be considered in combination with the CHA2DS2-VASc score.

Practical laboratory-based clinical decision tools and associations with short-term bleeding and mortality outcomes.

BACKGROUND: The red cell distribution width (RDW) predicts mortality in numerous populations. The Intermountain Risk Scores (IMRS) predict patient outcomes using laboratory measurements including RDW. Whether the RDW or IMRS predicts in-hospital outcomes is unknown. METHODS: The predictive abilities of RDW and two IMRS formulations (the complete blood count [CBC] risk score [CBC-RS] or full IMRS using CBC plus the basic metabolic profile) were studied among percutaneous coronary intervention patients at Intermountain (males: N = 6007, females: N = 2165). Primary endpoints were a composite bleeding outcome and in-hospital mortality. RESULTS: IMRS predicted the composite bleeding endpoint (females: χ2 = 47.1, odds ratio [OR] = 1.13 per +1 score, p < 0.001; males: χ2 = 108.7, OR = 1.13 per +1 score, p < 0.001) more strongly than RDW (females: χ2 = 1.6, OR = 1.04 per +1%, p = 0.20; males: χ2 = 11.2, OR = 1.09 per +1%, p < 0.001). For in-hospital mortality, RDW was predictive in females (χ2 = 4.3, OR = 1.13 per +1%, p = 0.037) and males (χ2 = 4.4, OR = 1.11 per +1%, p = 0.037), but IMRS was profoundly more predictive (females: χ2 = 35.5, OR = 1.36 per +1 score, p < 0.001; males: χ2 = 72.9, OR = 1.40 per+1 score, p < 0.001). CBC-RS was more predictive than RDW but not as powerful as IMRS. CONCLUSIONS: The IMRS, the CBC-RS, and RDW predict in-hospital outcomes. Risk score-directed personalization of in-hospital clinical care should be studied.

Vagus nerve injury symptoms after catheter ablation for atrial fibrillation.

BACKGROUND: Vagus nerve injury during catheter ablation for atrial fibrillation can significantly impact quality of life and result in lingering gastrointestinal symptoms. This study was designed to define risk factors of vagus nerve injury, symptoms, prevalence, and temporal resolution. METHODS: A total of 100 patients undergoing radiofrequency catheter ablation (RFCA) were enrolled and consented to participate in the study. Patients completed a 22-item questionnaire that included questions specific to vagus nerve injury symptomatology during their baseline visit and at 1 and 3 months post-RFCA. RESULTS: The average age of the population was 63 ± 10.6 years and 68% were male. A total of 100 patients completed their baseline questionnaire (90 patients completed the 1-month questionnaires and 85 patients completed the 3-month questionnaires). Symptoms rated as moderate were prevalent at baseline (trouble swallowing 13%, bloating 26%, feeling full 20%), and increased in all categories analyzed at 1 month and with the exception of trouble swallowing returned to the preablation percentages at 3 months (heartburn 22.4%, trouble swallowing 18.8%, bloating 16.5%, nausea 8.2%, vomiting 3.5%, constipation 18.8%, diarrhea 16.4%, feeling full 15.3%). Severe rated symptoms of trouble swallowing (2-5.5%), bloating (5-7.6%), and early satiety (5-9.8%) increased at 1 month and bloating and early satiety percentages remained approximately two times higher at 3 months (trouble swallowing 2.4%, bloating 8.2%, early satiety 7.1%). CONCLUSION: The majority of symptoms were resolved by 3 months, although those patients who rate bloating and early satiety at a severe rating may have persistent symptoms.

Atrial Fibrillation Ablation and its Impact on Stroke.

Atrial fibrillation (AF) is a commonly encountered arrhythmia, which is not yet fully understood. Catheter ablation has shown to be an effective strategy for rhythm management and several small or retrospective studies have shown that stroke rates are decreased in ablated AF patients compared to those medically managed. Several studies even show that ablation returns stroke risk to that of non-AF patients. Large scale, prospective trials will further illuminate this connection and provide mechanistic understanding of the role of the procedure versus the process of selection for the procedure and peri- and post-procedural therapy and management. Furthermore, modification of risk factors associated with AF show a significant increase in the sustained success of AF ablation and can also moderate the progression of AF.

Anticoagulant use in atrial fibrillation and risk of dementia: review of contemporary knowledge.

INTRODUCTION: Atrial fibrillation (AF) is strongly associated with dementia, including idiopathic dementias such as Alzheimer's disease. The relative risk of dementia is highest in AF patients 70 years and younger, and the burden of exposure to arrhythmia appears to underlie part of the risk. Areas covered: Anticoagulation choices and approach influence dementia risk. In warfarin patients, inadequate time spent in therapeutic range is highly associated with the increased dementia risk long-term. This risk is further accentuated with frequent over anticoagulation in patients also receiving aspirin. Direct oral anticoagulant therapies in early observational studies show that there is potential for improving long-term risk of dementia when compared to warfarin, although prospective trials are needed. AF and dementia are end manifestations of systemic disease; a systemic approach is needed with early treatment of shared risk factors to prevent disease presentation altogether. Expert commentary: In this review, we will bring together available data with regards to the link between anticoagulant use for AF and dementia. Anticoagulation initiation timing, use, and efficacy remain critical risk factors for dementia in AF patients and consequently provide opportunities to decrease risk.

Atrial fibrillation incrementally increases dementia risk across all CHADS2 and CHA2DS2VASc strata in patients receiving long-term warfarin.

BACKGROUND: Patients with atrial fibrillation (AF) are at higher risk for developing dementia. Warfarin is a common therapy for the prevention of thromboembolism in AF, valve replacement, and thrombosis patients. The extent to which AF itself increases dementia risk remains unknown. METHODS: A total 6030 patients with no history of dementia and chronically anticoagulated with warfarin were studied. Warfarin management was provided through a Clinical Pharmacy Anticoagulation Service. Patients were stratified by warfarin indication of AF (n=3015) and non-AF (n=3015) and matched by propensity score (±0.01). Patients were stratified by the congestive heart failure, hypertension, age >75 years, diabetes, stroke (CHADS2) score calculated at the time of warfarin initiation and followed for incident dementia. RESULTS: The average age of the AF cohort was 69.3±11.2 years, and 52.7% were male; average age of non-AF cohort was 69.3±10.9 years, and 51.5% were male. Increasing CHADS2 score was associated with increased dementia incidence, P trend=.004. When stratified by warfarin indication, AF patients had an increased risk of dementia incidence. After multivariable adjustment, AF patients continued to display a significantly increased risk of dementia when compared with non-AF patients across all CHADS2 scores strata. CONCLUSIONS: In patients receiving long-term warfarin therapy, dementia risk increased with increasing CHADS2 scores. However, the presence of AF was associated with higher rates of dementia across all CHADS2 score strata. These data suggest that AF contributes to the risk of dementia and that this risk is not solely attributable to anticoagulant use. Dementia may be an end manifestation of a systemic disease state, and AF likely contributes to its progression.