Discriminative Accuracy of CHA2DS2-VASc Score, and Development of Predictive Accuracy Model Using Machine Learning for Ischemic Stroke Risk in Cardiac Amyloidosis and Atrial Fibrillation

Background: Cardiac amyloidosis (CA) in conjunction with atrial fibrillation (AF) presents unique management challenges. CHA2DS2VASc score in these patients is believed to underestimate the risk of ischemic stroke, necessitating a better predictive model in these patients. Methods: Data was obtained from the National Readmission Database (NRD). Outcomes between CA-AF and no-CA-AF were compared using multivariate regression analysis to calculate adjusted odds ratios (aOR). AutoScore; an interpretable machine learning framework, was used to develop a stroke risk prediction model, the predictive accuracy of which was evaluated with an area under the curve (AUC) using the receiver operating characteristic analysis. Results: A total of 11,860,804 (CA-AF 22,687 [0.19%] and no-CA-AF 11,838,117) patients were identified from 2015-2019. The adjusted odds of mortality (aOR 1.41 and 1.29), stroke (aOR 1.78 and 1.74), non-intracranial hemorrhage (aOR 2.10 and aOR 1.85), and intracranial hemorrhage (aOR 14.4 and aOR 4.26) were significantly higher in CA-AF compared with non-CA-AF at both index admission and 30-days, respectively. The CHA 2 DS 2 VASc score had a poor discriminative accuracy for stroke at 30-days in CA-AF (AUC 49%, 95%CI 47%-51%, p=0.54). The machine learning autoscore integrative model revealed that the predictive ability of our newly proposed E-CHADS score (end-stage renal disease (ESRD), congestive heart failure, hypertension, active cancer, dementia, and diabetes mellitus) for 30-day risk of ischemic stroke in CA-AF was excellent (for a cutoff of 52 points random forest score) with an AUC of 80% (95%CI 74%-86%) Conclusion: Cardiac amyloidosis carries a high risk of ischemic stroke that is not accurately predicted by the CHA 2 DS 2 VASc score. Our proposed model (E-CHADS) identifies 3 new variables (ESRD, dementia, and cancer) that have higher discriminative accuracy for ischemic stroke in these patients.

Establishing new approaches for the prevention and treatment of stroke relies on identifying modifiable risk factors that contribute to the development of this complex disease. Mendelian randomization (MR) studies, analogous to naturally occurring randomized trials, can assess causality of potentially modifiable biomarkers and offer new insights into biological pathways. Stroke is the second leading cause of death worldwide and the chief determinant of long-term disability. Stroke is a heterogeneous disease arising from several distinct underlying pathologies and is typically classified as ischemic or hemorrhagic, and further subclassified using imaging data. Ischemic stroke (IS), including its 3 main subtypes: small vessel disease, large vessel disease, and cardioembolic stroke, accounts for ≈80% of stroke and is the result of an interrupted blood supply, leading to localized areas of ischemia in the brain. Small vessel disease may be a consequence of nonatherosclerotic, as well as atherosclerotic, mechanisms that result in an occlusion of the small perforating arteries, whereas large vessel disease results from occlusions or emboli from plaque rupture in larger vessels, such as a carotid artery. Cardioembolic stroke arises typically from emboli from the heart. By contrast, hemorrhagic stroke is a consequence of intracerebral hemorrhage (bleeding into the brain) or subarachnoid hemorrhage (bleeding into the subarachnoid space). These diverse stroke subtypes have distinct underlying pathologies reflecting different risk factor distributions. MR studies, using genetic variants as instrumental variables, afford a powerful approach to assessing causality of risk factors and avoid biases inherent in observational studies, including confounding and reverse causation. This review considers the contribution of MR studies to stroke epidemiology and their relevance to understanding risk factors and new therapeutic targets for stroke. Meta-analyses of large prospective studies have enhanced our knowledge of classical and emerging risk factors for stroke.1–4 Classical risk factors for stroke include nonmodifiable characteristics, …

Aim: To evaluate the role of CHADS2 and CHA2DS2-VASc scores in predicting the risk of ischemic stroke or transient ischemic attack (TIA) outcomes in patients with interatrial block (IAB) without a history of atrial fibrillation (AF).Methods: A retrospective study was conducted, including 1,046 non-anticoagulated inpatients (612 males, 434 females; mean age: 63 ± 10 years) with IAB and without AF. IAB was defined as P-wave duration > 120 ms using a 12-lead electrocardiogram. CHADS2 and CHA2DS2-VASc scores were retrospectively calculated. The primary outcomes evaluated were ischemic stroke or TIA.Results: During the mean follow-up period of 4.9 ± 0.7 years, 55 (5.3%) patients had an ischemic stroke or TIA. Receiver operating characteristic (ROC) curve analysis showed that the CHADS2 score [area under the curve (AUC), 0.638; 95% confidence interval (CI), 0.562–0.715; P = 0.001] and the CHA2DS2-VASc score (AUC, 0.671; 95% CI, 0.599–0.744; P <0.001) were predictive of ischemic strokes or TIA. Cut-off point analysis showed that a CHADS2 score ≥ 3 (sensitivity = 0.455 and specificity = 0.747) and a CHA2DS2-VASc score ≥ 4 (sensitivity = 0.564 and specificity = 0.700) provided the highest predictive value for ischemic stroke or TIA. The multivariate Cox regression analysis showed that CHADS2 [hazard ratio (HR), 1.442; 95% CI, 1.171–1.774; P = 0.001] and CHA2DS2-VASc (HR, 1.420; 95% CI, 1.203–1.677; P <0.001) scores were independently associated with ischemic stroke or TIA following adjustment for smoking, left atrial diameter, antiplatelet agents, angiotensin inhibitors, and statins.Conclusions: CHADS2 and CHA2DS2-VASc scores may be predictors of risk of ischemic stroke or TIA in patients with IAB without AF.

Alcohol and Stroke. An Epidemiological Labyrinth

Effects of Genetic Variants on Stroke Risk.

Impact of metabolic syndrome on the risk of ischemic stroke in non-anticoagulated atrial fibrillation patients having low CHA2DS2-VASc scores

The CHA2DS2-VASc score and the risk of ischemic stroke in community-dwelling individuals with and without atrial fibrillation: The Atherosclerosis Risk In Communities (ARIC) study

ObjectiveConflicting results have been reported on whether metabolic syndrome (MetS) confers an increased risk of ischaemic stroke in atrial fibrillation (AF). We investigated the risk of ischaemic stroke according to...

European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) expert consensus on risk assessment in cardiac arrhythmias: use the right tool for the right outcome, in the right population

Risk of ischemic stroke in patients with end-stage renal disease receiving peritoneal dialysis with new-onset atrial fibrillation.

Should Atrial Fibrillation Patients With 1 Additional Risk Factor of the CHA2DS2-VASc Score (Beyond Sex) Receive Oral Anticoagulation?

Comparison of stroke risk according to sinus node disease, atrial fibrillation and bradycardia-tachycardia syndrome: A French nationwide cohort-study

Association between statin adherence and the risk of stroke among South Korean adults with hyperlipidemia

Previous cross-sectional studies have demonstrated a higher incidence of dehydration in patients admitted for stroke suggesting a possible association. However, the temporality of the association has not been well established. We examined whether dehydration increases the risk of ischemic stroke in patients with a recent hospitalization for atrial fibrillation (AF). Data was from 1994 to 2012 from the Myocardial Infarction Data Acquisition System (MIDAS), a repository of in-patient records New Jersey hospitals, for AF hospitalizations (n = 1,282,787). Estimates for the association between AF hospitalization with/without dehydration and ischemic stroke within 30days post-AF discharge were determined using log-linear multivariable modeling adjusting for socio-demographic factors and comorbid conditions. Within 10days of discharge for AF, patients 18-80years old (YO) with comorbid dehydration had a 60% higher risk of ischemic stroke compared to AF patients without comorbid dehydration (adjusted risk ratio (ARR) 1.60, 95% confidence interval (CI) 1.28-2.00). Eighteen- to 80-YO patients had a 34% higher risk of ischemic stroke in days 11-20 post-AF discharge (ARR 1.34, 95% CI 1.04, 1.74). There was no difference in the risk of stroke in 18-80-YO patients with or without prior dehydration during days 21-30 post-AF discharge. We also found no difference in the risk of ischemic stroke during any time period in patients over 80YO. Dehydration may be a significant risk factor for ischemic stroke in patients 18-80YO with AF.

Background: CHA2DS2-VASc score has been shown to be predictive of risk of ischemic stroke (IS) in persons without atrial fibrillation (AF). These observations raise the question whether it is AF per se or the associated vascular risk factors that elevate the risk of IS. Hypothesis: AF elevates the risk of IS over and above vascular risk factors in the CHA2DS2-VASc score and as the CHA2DS2-VASc score increases, AF plays a more important role in determining the risk of stroke. Methods: Using the ARIC study_a biracial, community-based prospective cohort study we compared (a) the model discrimination of the CHA2DS2-VASc score for IS in participants with vs. without AF, and (b) the risk of IS by CHA2DS2-VASc score among participants with vs. without AF. We included 1395 participants with AF who were matched to 4060 participants without AF based on age, race, and CHA2DS2-VASc score (mean age, 62 years; 57% women; 22% blacks). Participants with prevalent IS or anticoagulant use at baseline were excluded. AF was ascertained from hospitalization discharge codes and study ECGs. IS was physician-adjudicated. Results: Median follow-up was 14.7 years and 288 (5.3%) participants developed IS. The C-statistic of the CHA2DS2-VASc score for IS was not significantly different in participants with vs. without AF (Table). The incidence rate difference of IS increases with increasing CHA2DS2-VASc score in participants with vs. without AF (Table, p for interaction between AF and CHA2DS2-VASc score &lt;0.0001). Conclusion: Model discrimination of the CHA2DS2-VASc score for IS in individuals with AF is comparable to those without AF. However, with increasing score, the incidence rate of IS in individuals with AF increases to a greater extent than in those without AF. These findings suggest that as the CHA2DS2-VASc score increases, the disorganized rhythm of AF or other AF-related factor (e.g., left atrial dysfunction or enlargement) plays an even greater role to elevate the risk of IS.