Atrial Cardiopathy Worsens Neurological Severity, Raises Recurrence Rates, and Leads to Poor Vascular Outcomes in Patients With Embolic Stroke of Undetermined Source

Abstract

Background and purpose: Atrial cardiopathy (AC) has been studied for its significance in embolic stroke of undetermined source (ESUS). This real-world study examines the relevance of AC in ESUS and its impact on stroke severity, recurrence, and major adverse cardiovascular events (MACEs).

Methods: We analyzed patients from stroke registries of South Korean centers (2014-2019) aged ≥20 years with acute ESUS or cardiogenic stroke without a definite embolic source. AC was defined by left atrial (LA) enlargement (diameter >40 mm in men and >38 mm in women; or LA volume index >34 mL/m2) or elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP, ≥250 pg/mL) levels. Patients were classified based on AC presence and stratified by the number of factors (AC groups 0, 1, and 2). Survival analysis in original and propensity score (PS)-matched cohorts assessed the impact of AC on stroke severity and vascular outcomes.

Results: Among 5,787 patients (65.9±13.9 years; female: 39.8%), 45.0% met the AC criteria (group 1: 40.3%, group 2: 4.7%). In the original cohort, AC group 2 was associated with increased stroke recurrence (hazard ratio [HR]: 1.76, 95% confidence interval [CI]: 1.06-2.92, P=0.03). After PS-matching, stroke recurrence remained significantly increased for AC (HR: 1.37, 95% CI: 1.04-1.79, P=0.02) and group 2 (HR: 1.94, 95% CI: 1.16-3.26, P=0.01). MACE outcomes increased in the group 2 patients (HR: 1.70, 95% CI: 1.07-2.70, P=0.02). NT-proBNP (HR: 0.97, 95% CI: 0.84-1.12, P=0.69) or LA enlargement (HR: 1.15, 95% CI: 0.89-1.49, P=0.28) alone were not predictive. AC correlated with longer hospital stays, and AC stratification with higher severity.

Conclusion: Especially with multiple factors, AC was associated with adverse clinical outcome in patients with ESUS. These findings underscore the importance of AC stratification in the management of ESUS patients.

Keywords: Atrial cardiopathy; Atrial remodeling; Cardiomyopathies; Cardiovascular diseases; Ischemic stroke; Major adverse cardiovascular event.

Figure 1.

Inclusion flowchart of the real-world study of embolic stroke of undetermined source (ROS-ESUS) cohort. Patients were selected from stroke registries across all participating centers and were subsequently screened based on inclusion and exclusion criteria. Finally, they were classif ied according to the presence or absence of atrial cardiopathy. TOAST, Trial of Org 10172 in Acute Stroke Treatment; CE, cardioembolism; LAD, left atrial diameter; LAVI, left atrial volume index; NT-proBNP, N-terminal pro-B-type natriuretic peptide.

Figure 2.

AC and vascular events after propensity score matching. Outcomes were compared between the AC and non-AC groups, or between the stratified groups, AC groups 0 (or the control), 1, and 2. Below the plots are the number of patients at risk (or those not yet affected by the event at a certain time-point). The total number was 5,208 after propensity score matching. (A) The AC and the non-AC groups exhibited a difference between ischemic stroke recurrences (P=0.02). (B) Group 2 exhibited an increase in hazard compared to group 0 (HR 1.94, P=0.01). (C) The difference in MACEs was not significant due to early phase discrepancies, and (D) AC group 2 exhibited significance despite the AC and non-AC group results. AC, atrial cardiopathy; MACE, major adverse cardiovascular events; HR, hazard ratio.

Figure 3.

Stroke severity and hospitalization differences between the AC groups. Below each box plot, the median with interquartile (IQR) values or the mean with standard deviation (mean±SD) are presented, and P-values indicate comparison validity between the groups. Group 0 and group 1 comparison (*), group 1 and group 2 comparison (**), and group 0 and group 2 comparison (***). P-values are indicated in stars. (A) The Non-AC and AC groups were compared based on admission NIHSS, discharge NIHSS, and hospital stay. The former two variables did not exhibit significant differences (P>0.05), whereas hospital stay was significantly different (P<0.05). (B) Stratified groups were compared for the same variables. Groups 0 and 1 did not exhibit significant differences (P>0.05) for the first two variables. Group 2 exhibited significantly higher admission NIHSS scores and hospital stay duration compared to groups 0 and 1 (P<0.05), along with group 1 over group 0 (P<0.05) and group 2 over group 1 (P<0.05). AC, atrial cardiopathy; NIHSS, National Institutes of Health Stroke Scale; SD, standard deviation; IQR, interquartile range.