Left ventricular disease as a risk factor for adverse outcomes and stroke recurrence in patients with embolic stroke of undetermined source

Background: Severe left ventricular (LV) systolic dysfunction (ejection fraction [EF] < 30%) is a known cardiovascular risk factor and a major cause of cardioembolism. However, less severe forms of LV disease (LVD), such as mild-to-moderate LV dysfunction and LV wall motion abnormalities (LVWMAs), are considered potential minor cardiac sources in Embolic Stroke of Undetermined Source (ESUS), but their role is underexplored. This study aims to evaluate the prevalence of LVD in ESUS and its association with adverse vascular events and mortality.

Methods: Retrospective, single-center study including consecutive ESUS patients admitted from January 2016 to May 2024. LVD was defined as either global systolic dysfunction (LV ejection fraction 30%-49%) or regional LVWMAs, unrelated to acute or recent (within 4 weeks) myocardial infarction. Univariate and multivariate Cox regression analyses evaluated the association of LVD with a primary composite outcome (including ischemic stroke recurrence, acute coronary events, and all-cause mortality), and its components separately.

Results: Among the 556 ESUS patients (median age 71 years [IQR 60-80], 44.6% female), 95 (17.1%) had LVD, including 51 (53.7%) with reduced LVEF (30%-49%), and 81 (85.3%) presenting LVWMAs. During follow-up (median 30 months), LVD(+) patients had significantly higher rates of the composite outcome (41.0% vs 21.3%, p < 0.001), ischemic stroke recurrence (13.7% vs 5.9%, p = 0.007), acute coronary events (7.4% vs 2.4%, p = 0.012), and all-cause mortality (28.4% vs 15.2%, p = 0.002), compared to LVD(-) patients. Multivariate Cox regression analysis showed that LVD independently increased the risk of ischemic stroke recurrence (adjusted HR 2.13, 95%CI 1.08-4.24, p = 0.032) and the composite outcome (aHR 1.92, 95%CI 1.27-2.90, p = 0.002), but not acute coronary events (aHR 1.65; 95%CI 0.54-5.01, p = 0.374), or all-cause mortality (aHR 1.62; 95%CI 0.98-2.70, p = 0.062).

Conclusions: LVD is significantly associated with an increased risk of ischemic stroke recurrence and adverse outcomes in ESUS patients. These findings highlight the clinical importance of identifying and optimizing LVD management among ESUS to improve long-term outcomes in this population.