Victoria Jacobs

Time outside of therapeutic range in atrial fibrillation patients is associated with long-term risk of dementia

BACKGROUND The mechanisms behind the association of atrial fibrillation (AF) and dementia are unknown. One possibility is that exposure to chronic microembolism or microbleeds results in repetitive cerebral injury that is manifest by cognitive decline. OBJECTIVE The purpose of this study was to test the hypothesis that AF patients with a low percentage of time in the therapeutic range (TTR) are at higher risk for dementia due to under- or overanticoagulation. METHODS Patients anticoagulated with warfarin (target international normalized ratio [INR] 2-3), managed by the Intermountain Healthcare Clinical Pharmacist Anticoagulation Service with no history of dementia or stroke/transient ischemic attack, were included in the study. The primary outcome was dementia incidence defined by ICD-9 codes. Percent time in TTR was calculated using the method of linear interpolation and stratified as >75%, 51%-75%, 26%-50%, and ≤25%. Multivariable Cox hazard regression was used to determine dementia incidence by percentage categories of TTR. RESULTS A total of 2605 patients (age 73.7 ± 10.8 years, 1408 [54.0%] male) were studied. The CHADS2 score distribution was 0: 216 (8.3%); 1: 579 (22.2%); 2: 859(33.0%); 3: 708 (27.2%); and ≥4: 243 (9.3%). The percent TTR averaged 63.1 ± 21.3, with percent INR <2.0: 25.6% ± 17.9% and percent INR >3.0: 16.2% ± 13.6%. Dementia was diagnosed in 109 patients (4.2%) (senile: 37 [1.4%]; vascular: 8 [0.3%]; Alzheimer: 64 (2.5%]). After adjustment, decreasing categories of percent TTR were associated with increased dementia risk (vs >75%): <25%: hazard ratio (HR) 5.34, P < .0001; 26%-50%: HR 4.10, P < .0001; and 51%-75%: HR = 2.57, P = .001. CONCLUSION Quality of anticoagulation management represented as percent TTR among AF patients without dementia was associated with dementia incidence. These data support the possibility of chronic cerebral injury as a mechanism that underlies the association of AF and dementia.

The impact of risk score (CHADS2 versus CHA2DS2-VASc) on long-term outcomes after atrial fibrillation ablation

BACKGROUND Risk stratification tools are needed to select the right candidates for catheter ablation of atrial fibrillation (AF). Both the CHADS2 and CHA2DS2-VASc scores have utility in predicting AF-related outcomes and guiding anticoagulation treatment. OBJECTIVE We sought to determine whether these risk scores predict long-term outcomes after AF ablation and whether one risk score provides comparatively superior performance. METHODS CHADS2 and CHA2DS2-VASc scores were calculated in 2179 patients who underwent a first ablation procedure for AF enrolled in the Intermountain Heart Collaborative Study. CHADS2 and CHA2DS2-VASc scores were categorized as 0-1, 2-4, and ≥5. Patient outcomes were analyzed over 5 years for AF/atrial flutter recurrence and major adverse cardiovascular events (MACE: composite of death, stroke, and heart failure hospitalization). RESULTS The mean age was 65.7 ± 10.5 years, and 61.1% were men. Both scores incrementally predicted risk of AF recurrence, stroke, heart failure, and death at 5 years. Increasing CHADS2 (hazard ratio [HR] 1.19; P < .001) and CHA2DS2-VASc (HR 1.15; P < .0001) scores were both associated with AF/atrial flutter recurrence. The results were similar for MACE where increasing CHADS2 (HR 1.54; P < .0001) and CHA2DS2-VASc (HR 1.32; P < .0001) scores were associated with risk. When CHADS2 and CHA2DS2-VASc scores were modeled together, only CHA2DS2-VASc scores significantly predicted AF recurrence (HR 1.13; P = .001), but both were associated with MACE. CONCLUSION Both the CHADS2 and CHA2DS2-VASc scores were excellent in stratifying patients for 5-year outcomes after AF ablation. However, the CHA2DS2-VASc score was superior to the CHADS2 score in predicting AF recurrence and AF-related morbidities.

Five-Year Outcomes of Catheter Ablation in Patients with Atrial Fibrillation and Left Ventricular Systolic Dysfunction

Catheter ablation of atrial fibrillation (AF) is an established therapy for symptomatic patients. The long‐term efficacy and impact of catheter ablation among patients with severe systolic heart failure (SHF) requires additional study to understand if outcomes achieved at 1 year are maintained and mechanisms of AF recurrence.

Atrial fibrillation and dementia.

Emerging evidence has shown a consistent association between AF and risk of dementia, including Alzheimer׳s disease. It is likely that a constellation of various mechanisms combine to cause dementia in AF patients. Both AF and dementia share multiple common risk factors, and as such these may be targets of early prevention strategies to reduce risk. In patients with AF, choices regarding type and duration of anticoagulation as well as rhythm- and rate-control strategies can influence dementia risk.

Percent Time With a Supratherapeutic INR in Atrial Fibrillation Patients Also Using an Antiplatelet Agent Is Associated With Long‐Term Risk of Dementia

Patients with atrial fibrillation (AF) are at higher risk of developing dementia. AF patients treated with warfarin with poor time in therapeutic ranges are significantly more likely to develop dementia. AF patients are also frequently treated with antiplatelet agents due to coexistent vascular disease. We hypothesize that AF patients with anticoagulation and antiplatelet therapies will be at higher risk of dementia, particularly with chronic exposure to over‐anticoagulation.

Atrial Fibrillation Patients Treated With Long‐Term Warfarin Anticoagulation Have Higher Rates of All Dementia Types Compared With Patients Receiving Long‐Term Warfarin for Other Indications

Background The mechanisms behind the association of atrial fibrillation (AF) and dementia are unknown. We previously found a significantly increased risk of dementia in AF patients taking warfarin with a low percentage of time in therapeutic range. The purpose of this study was to determine the extent to which AF itself increases dementia risk, in addition to long‐term anticoagulation exposure. Methods and Results A total of 10 537 patients anticoagulated with warfarin (target INR 2–3), managed by the Clinical Pharmacist Anticoagulation Service with no history of dementia were included. Warfarin indication was for AF (n=4460), thromboembolism (n=5868), and mechanical heart valve(s) (n=209). Patients in the latter 2 categories were included only if they had no prior history of AF. The primary outcome was dementia. Patients with AF were older and had higher rates of hypertension, diabetes, heart failure, and stroke. AF patients experienced higher rates of total dementia (5.8% versus 1.6%, P<0.0001), Alzheimer disease (2.8% versus 0.9%, P<0.0001), and vascular dementia (1.0% versus 0.2%, P<0.0001). A propensity analysis of 6030 patients was performed to account for baseline demographics differences. Long‐term risk of dementia remained significant in AF patients compared with matched non‐AF patients (total dementia: hazard ratio [HR]=2.42 [1.85–3.18], P<0.0001; Alzheimer: HR=2.04 [1.40–2.98], P<0.0001; senile: HR=2.46 [1.58–3.86], P<0.0001). Low percent therapeutic range compared with a higher percent therapeutic range was associated with dementia risk in both AF (26–50% versus >75%: HR=2.51, P=0.005) and non‐AF groups (≤25% versus >75%: HR=3.92, P<0.0001). Conclusions The presence of AF significantly increases risk of dementia, including Alzheimers disease, compared with matched patients receiving warfarin anticoagulation for other reasons. Quality of anticoagulation management remains an important risk factor for dementia in all patients.

Long-Term Natural History of Adult Wolff–Parkinson–White Syndrome Patients Treated With and Without Catheter Ablation

Background—There are a paucity of data about the long-term natural history of adult Wolff–Parkinson–White syndrome (WPW) patients in regard to risk of mortality and atrial fibrillation. We sought to describe the long-term outcomes of WPW patients and ascertain the impact of ablation on the natural history. Methods and Results—Three groups of patients were studied: 2 WPW populations (ablation: 872, no ablation: 1461) and a 1:5 control population (n=11 175). Long-term mortality and atrial fibrillation rates were determined. The average follow-up for the WPW group was 7.9±5.9 (median: 6.9) years and was similar between the ablation and nonablation groups. Death rates were similar between the WPW group versus the control group (hazard ratio, 0.96; 95% confidence interval, 0.83–1.11; P=0.56). Nonablated WPW patients had a higher long-term death risk compared with ablated WPW patients (hazard ratio, 2.10; 95% confidence interval: 1.50–20.93; P<0.0001). Incident atrial fibrillation risk was higher in the WPW group compared with the control population (hazard ratio, 1.55; 95% confidence interval, 1.29–1.87; P<0.0001). Nonablated WPW patients had lower risk than ablated patients (hazard ratio, 0.39; 95% confidence interval, 0.28–0.53; P<0.0001). Conclusions—Long-term mortality rates in WPW patients are low and similar to an age-matched and gender-matched control population. WPW patients that underwent the multifactorial process of ablation had a lower mortality compared to nonablated WPW patients. Atrial fibrillation rates are high long-term, and ablation does not reduce this 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. &NA; Graphical abstract Figure. No Caption available.

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

ABSTRACT 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.

Five-year impact of catheter ablation for atrial fibrillation in patients with a prior history of stroke

Catheter ablation of atrial fibrillation (AF) is an established therapeutic rhythm approach. Patients with a prior history of a stroke (CVA) represent a unique high‐risk population for recurrent thromboembolic events. The role of antiarrhythmic treatment on the natural history of stroke recurrence in these patients is not fully understood.