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Refining Prediction of Atrial Fibrillation-Related Stroke Using the P2-CHA2DS2-VASc Score.

ABSTRACT: BACKGROUND:In people with atrial fibrillation (AF), periods of sinus rhythm present an opportunity to detect prothrombotic atrial remodeling through measurement of P-wave indices (PWIs)-prolonged P-wave duration, abnormal P-wave axis, advanced interatrial block, and abnormal P-wave terminal force in lead V1. We hypothesized that the addition of PWIs to the CHA2DS2-VASc score would improve its ability to predict AF-related ischemic stroke. METHODS:We included 2229 participants from the ARIC study (Atherosclerosis Risk in Communities) and 700 participants from MESA (Multi-Ethnic Study of Atherosclerosis) with incident AF who were not on anticoagulants within 1 year of AF diagnosis. PWIs were obtained from study visit ECGs before development of AF. AF was ascertained using study visit ECGs and hospital records. Ischemic stroke cases were based on physician adjudication of hospital records. We used Cox proportional hazards models to estimate hazard ratios and 95% CIs of PWIs for ischemic stroke. Improvement in 1-year stroke prediction was assessed by C-statistic, categorical net reclassification improvement, and relative integrated discrimination improvement. RESULTS:Abnormal P-wave axis was the only PWI associated with increased ischemic stroke risk (hazard ratio, 1.84; 95% CI, 1.33-2.55) independent of CHA2DS2-VASc variables, and that resulted in meaningful improvement in stroke prediction. The ? estimate was approximately twice that of the CHA2DS2-VASc variables, and thus abnormal P-wave axis was assigned 2 points to create the P2-CHA2DS2-VASc score. This improved the C-statistic (95% CI) from 0.60 (0.51-0.69) to 0.67 (0.60-0.75) in ARIC and 0.68 (0.52-0.84) to 0.75 (0.60-0.91) in MESA (validation cohort). In ARIC and MESA, the categorical net reclassification improvements (95% CI) were 0.25 (0.13-0.39) and 0.51 (0.18-0.86), respectively, and the relative integrated discrimination improvement (95% CI) were 1.19 (0.96-1.44) and 0.82 (0.36-1.39), respectively. CONCLUSIONS:Abnormal P-wave axis-an ECG correlate of left atrial abnormality- improves ischemic stroke prediction in AF. Compared with CHA2DS2-VASc, the P2-CHA2DS2-VASc is a better prediction tool for AF-related ischemic stroke.

SUBMITTER: Maheshwari A

PROVIDER: S-EPMC6481672 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Refining Prediction of Atrial Fibrillation-Related Stroke Using the P<sub>2</sub>-CHA<sub>2</sub>DS<sub>2</sub>-VASc Score.

Maheshwari Ankit A Norby Faye L FL Roetker Nicholas S NS Soliman Elsayed Z EZ Koene Ryan J RJ Rooney Mary R MR O'Neal Wesley T WT Shah Amil M AM Claggett Brian L BL Solomon Scott D SD Alonso Alvaro A Gottesman Rebecca F RF Heckbert Susan R SR Chen Lin Y LY

Circulation 20190101 2

<h4>Background</h4>In people with atrial fibrillation (AF), periods of sinus rhythm present an opportunity to detect prothrombotic atrial remodeling through measurement of P-wave indices (PWIs)-prolonged P-wave duration, abnormal P-wave axis, advanced interatrial block, and abnormal P-wave terminal force in lead V1. We hypothesized that the addition of PWIs to the CHA<sub>2</sub>DS<sub>2</sub>-VASc score would improve its ability to predict AF-related ischemic stroke.<h4>Methods</h4>We included ...[more]

PMID: 30586710

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Project description:Background and Purpose- Despite modest predictive ability for ischemic stroke (IS), the CHA2DS2-VASc score is widely used for stroke prediction in atrial fibrillation. Among patients with atrial fibrillation, we aimed to (1) compare the IS or transient ischemic attack (TIA) incidence by CHA2DS2-VASc in blacks and Hispanics versus whites; (2) compare predictive ability of CHA2DS2-VASc score for IS or TIA in blacks and Hispanics versus whites; and (3) determine improvement in predictive ability of CHA2DS2-VASc score from addition of race/ethnicity. Methods- Using data from Optum Clinformatics, a large administrative claims database, we analyzed patients with atrial fibrillation enrolled in commercial and Medicare Advantage health plans from 2009 to 2015. We computed IS or TIA incidence rates, improvement in C statistic, continuous and categorical net reclassification improvement, and relative integrated discrimination improvement from addition of race/ethnicity to CHA2DS2-VASc. Results- A total of 267 419 patients (mean age, 73.1 [SD, 12.3] years; 46.6% women; 84.2% white, 8.5% black, 7.3% Hispanic) were studied. After a mean follow-up of 22 months, there were 6202 IS or TIA events. IS or TIA incidence rates were higher in blacks than Hispanics or whites (1.65, 1.40, and 1.22 cases per 100 person-years, respectively) and increased with higher CHA2DS2-VASc, with no race/ethnicity-based differences ( P for interaction=0.17). The CHA2DS2-VASc and CHA2DS2-VASc+race/ethnicity C statistic (95% CI) were 0.679 (0.670-0.686) and 0.679 (0.671-0.688). The CHA2DS2-VASc C statistic in the 3 groups were comparable. With addition of race/ethnicity, the categorical net reclassification improvement, continuous net reclassification improvement, and relative integrated discrimination improvement were -0.045 (95% CI, -0.067 to -0.025), 0.045 (95% CI, 0.025-0.068), and 0.016 (95% CI, 0.014-0.018). Conclusions- The predictive ability of CHA2DS2-VASc for IS or TIA in atrial fibrillation is comparable among whites, blacks, and Hispanics; hence, it can be used in the latter 2 groups. Addition of race/ethnicity to the CHA2DS2-VASc does not improve its predictive ability.

Project description:The ABC-stroke score (age, biomarkers [N-terminal fragment B-type natriuretic peptide, high-sensitivity troponin], and clinical history [prior stroke/transient ischemic attack]) was proposed to predict stroke in atrial fibrillation (AF). This score was derived/validated in 2 clinical trial cohorts in which patients with AF were highly selected and carefully followed-up. However, the median follow-up was 1.9 years in the trial cohort; therefore, its long-term predictive performance remains uncertain. This study aimed to compare the long-term predictive performances of the ABC-stroke and CHA2DS2-VASc (cardiac failure or dysfunction, hypertension, age ≥75 [doubled], diabetes mellitus, stroke [doubled]-vascular disease, age 65 to 74 years and sex category [female]) scores in a cohort of anticoagulated patients with AF. We recruited 1125 consecutive patients with AF who were stable on vitamin K antagonists and followed-up for a median of 6.5 years. ABC-stroke and CHA2DS2-VASc (cardiac failure or dysfunction, hypertension, age ≥75 [doubled], diabetes mellitus, stroke [doubled]-vascular disease, age 65 to 74 years and sex category [female]) scores were calculated and compared. Median CHA2DS2-VASc and ABC-stroke scores were 4 (interquartile range 3-5) and 9.1 (interquartile range 7.3-11.3), respectively. There were 114 ischemic strokes (1.55% per year) at 6.5 years. The C-index of ABC-stroke at 3.5 years was significantly higher than CHA2DS2-VASc (0.663 versus 0.600, P=0.046), but both C-indexes were nonsignificantly different at 6.5 years. Integrated discrimination improvement showed a small improvement (<2%) in sensitivity at 3.5 and 6.5 years with ABC-stroke. For ABC-stroke, net reclassification improvement was nonsignificantly different at 3.5 years, and showed a negative reclassification at 6.5 years compared with CHA2DS2-VASc. Decision curve analyses did not show a marked improvement in clinical usefulness of the ABC-stroke score over the CHA2DS2-VASc score. In anticoagulated patients with AF followed-up over a long-term period, the novel ABC-stroke score does not offer significantly better predictive performance compared with the CHA2DS2-VASc score.

Project description:Atrial fibrillation (AF) is associated with increased mortality, predictors of which are poorly characterized. We investigated the predictive power of the commonly used CHA2DS2-VASc score (congestive heart failure, hypertension, age ≥ 75 years [doubled], diabetes, stroke/transient ischemic attack/thromboembolism [doubled], vascular disease [prior myocardial infarction, peripheral artery disease, or aortic plaque], age 65-75 years, sex category [female]), the HAS-BLED score (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio [INR], elderly [age ≥ 65 years], drugs/alcohol concomitantly), and their combination for mortality in AF patients. The PREvention oF thromboembolic events-European Registry in Atrial Fibrillation (PREFER in AF) was a prospective registry including AF patients across seven European countries. We used logistic regression to analyze the relationship between the CHA2DS2-VASc and HAS-BLED scores and outcomes, including mortality, at one year. We evaluated the performance of logistic regression models by discrimination measures (C-index and DeLong test) and calibration measures (Hosmer and Lemeshow goodness-of-fit and integrated discrimination improvement (IDI), with bootstrap techniques for internal validation. In 5209 AF patients with complete information on both scores, average one-year mortality was 3.1%. We found strong gradients between stroke/systemic embolic events (SSE), major bleeding and-specifically-mortality for both CHA2DS2-VASc and HAS-BLED scores, with a similar C-statistic for event prediction. The predictive power of the models with both scores combined, removing overlapping components, was significantly enhanced (p < 0.01) compared to models including either CHA2DS2-VASc or HAS-BLED alone: for mortality, C-statistic: 0.740, compared to 0.707 for CHA2DS2-VASc or 0.646 for HAS-BLED alone. IDI analyses supported the significant improvement for the combined score model compared to separate score models for all outcomes. Both the CHA2DS2-VASc and the HAS-BLED scores predict mortality similarly in patients with AF, and a combination of their components increases prediction significantly. Such combination may be useful for investigational and-possibly-also clinical purposes.

Project description:ImportanceCurrent guidelines support treating atrial fibrillation (AF) and atrial flutter (AFL) as equivalent risk factors for ischemic stroke stratified by CHA2DS2-VASc scores, recommending anticoagulation therapy for patients with a CHA2DS2-VASc score of 2 or higher, but some studies found differences in clinical outcomes.ObjectiveTo investigate differences in clinical outcomes among AF, AFL, and matched control cohorts.Design, setting, and participantsThis nationwide cohort study analyzed data from the Taiwan National Health Insurance Research Database from January 1, 2001, through December 31, 2012. Follow-up and data analysis ended December 31, 2012. A total of 219 416 age- and sex-matched individuals participated in the study. Clinical outcomes were compared after stratification by CHA2DS2-VASc score (possible score range, 0-9; higher scores indicate greater risk of ischemic stroke).Main outcomes and measuresIschemic stroke, heart failure hospitalization, and all-cause mortality among the AF, AFL, and matched control cohorts were analyzed using Cox proportional hazards regression.ResultsThis study comprised 188?811 patients in the AF cohort (mean [SD] age, 73.8 [13.4] years; 104 703 [55.5%] male), 6121 patients in the AFL cohort (mean [SD] age, 67.7 [15.8] years; 3735 [61.0%] male), and 24?484 patients in the matched control cohort (mean [SD] age, 67.3 [15.6] years; 14 940 [61.0%] male). The patients with AF were older, were more predominantly female, and had higher CHA2DS2-VASc scores than the patients with AFL and the control participants. After stratification by CHA2DS2-VASc score, the incidence densities (IDs; events per 100 person-years) of ischemic stroke (AF cohort: ID, 3.08; 95% CI, 3.03-3.13; AFL cohort: ID, 1.45; 95% CI, 1.28-1.62; controls: ID, 0.97; 95% CI, 0.92-1.03), heart failure hospitalization (AF cohort: ID, 3.39; 95% CI, 3.34-3.44; AFL cohort: ID, 1.57; 95% CI, 1.39-1.74; controls: ID, 0.32; 95% CI, 0.29-0.35), and all-cause mortality (AF cohort: ID, 17.8; 95% CI, 17.7-17.9; AFL cohort: ID, 13.9; 95% CI, 13.4-14.4; controls: ID, 4.2; 95% CI, 4.1-4.4) were significantly higher in the AF cohort than in the matched control cohort. For the AFL cohort vs the matched control cohort, the incidences of heart failure hospitalization and all-cause mortality were significantly higher across all levels, but the incidence of ischemic stroke was only significantly higher at CHA2DS2-VASc scores of 5 to 9. For the AF cohort vs the AFL cohort, the incidences of ischemic stroke and heart failure hospitalization were significantly higher at a CHA2DS2-VASc score of 1 or higher, but the incidence of all-cause mortality was significantly higher only at CHA2DS2-VASc scores of 1 to 3.Conclusions and relevanceThis study found different clinical outcomes between patients with AFL and AF and those without AF and AFL. The current recommended level of the CHA2DS2-VASc score in preventing ischemic stroke in patients with AFL should be reevaluated.

Dataset Information

Refining Prediction of Atrial Fibrillation-Related Stroke Using the P2-CHA2DS2-VASc Score.

Publications

Refining Prediction of Atrial Fibrillation-Related Stroke Using the P<sub>2</sub>-CHA<sub>2</sub>DS<sub>2</sub>-VASc Score.

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