Supplementary Material for: Frequent Early Cardiac Complications Contribute to Worse Stroke Outcome in Atrial Fibrillation

Background: Atrial fibrillation (AF) is associated with worse outcomes following ischemic stroke and more frequent cardiac complications in the general population. We aimed to establish whether early cardiac complications contribute to the poorer ischemic stroke outcomes in patients with AF, independent of baseline differences in age, stroke severity and cardiovascular risk factors. This might have important implications for acute stroke management in patients with AF. Methods: We searched VISTA-Acute, an academic database containing standardized data for 28,131 patients from 30 randomized-controlled acute stroke trials and 1 stroke registry, for imaging-confirmed placebo-treated patients with complete documentation of baseline demographics, cardiovascular risk factors, presence or absence of AF, neurologic impairment [National Institutes of Health Stroke Scale (NIHSS)], cardiac complications and 3-month outcome (modified Rankin Scale). A total of 2,865 patients from 6 randomized-controlled trials met the selection criteria, of whom 819 had AF. Binary logistic regression modeling was used to determine the independent effect of AF on stroke outcome and serious cardiac adverse events (SCAE), a composite end point including acute coronary syndrome, symptomatic heart failure, cardiopulmonary arrest, ventricular tachycardia, ventricular fibrillation and cardiac mortality. Results: All patients were enrolled into the source trials within 24 h of stroke onset. At baseline, patients with AF were older (mean 75 vs. 67 years, p < 0.001) and had greater neurologic impairment (median NIHSS 15 vs. 13, p < 0.001). The median time to first cardiac adverse event was 3 days [median difference 0, 95% confidence interval (CI) 0–1, p = 0.06] for both patients with and without AF. SCAE occurred more frequently [14.2 vs. 6%, odds ratio (OR) = 2.58, 95% CI 1.97–3.37] in patients with AF, particularly cardiac mortality (4.9 vs. 2.6%, OR = 1.89, 95% CI 1.25–2.88), symptomatic heart failure (6.5 vs. 2.2%, OR = 3.01, 95% CI 2.01–4.50), and ventricular tachycardia and/or fibrillation (2.4 vs. 0.8%, OR = 3.18, 95% CI 1.64–6.16). At 3 months, AF was independently associated with SCAE (OR = 2.14, 95% CI 1.61–2.86) and early mortality (OR = 1.44, 95% CI 1.14–1.81) after adjusting for all baseline imbalances. Conclusion: Early SCAE are common after stroke and are independently associated with the presence of AF. Given that many cardiac complications are potentially remediable, these results highlight the need for more rigorous surveillance for cardiac complications in acute ischemic stroke patients with AF.