On one hand the characteristics and predictors of ESUS are still unknown [7]. On the other hand, a growing number of studies have demonstrated the association between left ventricular hypertrophy (LVH) and left atrial dilatation, that reflect the aggravation of stroke of different origins as well as cryptogenic stroke [8].
Echocardiographic findings of normal ejection fraction (exceeding 50%), LVH and left atrial dilatation are strong predictors for heart failure with a preserved ejection fraction (HFpEF) [9]. Patients with heart failure are at risk from thromboembolic events which is a result of Virchow’s triad of risk factors for thrombus formation. In addition, undetected (paroxysmal) AF may be common in patients with HFpEF and not detecting this may lead to associated cerebral infarcts [10].
Interestingly, nearly half of all patients with heart failure have a preserved ejection fraction and its prevalence is rising, with morbidity and mortality, equal to that of reduced ejection fraction [11]. Little is known about the incidence of stroke in HFpEF yet, Cogswell et al., hypothesized that stroke risk in patients with HFpEF without atrial fibrillation (AF) and AF only was similar [12].
The results of the present study showed significant increase in LVH measured by left ventricular mass index and increased left atrial volume index, measuring left atrial dilatation, among ESUS patients, which is in agreement with many studies.
In the study by Lee et al., the authors compared the LAVI values between ESUS patients with patent foramen ovale (PFO) and healthy subjects with PFO and found that the ESUS patients had larger left atrial (LA) volumes than controls regardless of the presence of PFO. What is interesting is that LA enlargement, but not the amount of shunting, was associated with cortical infarcts, which could imply recurrent embolic strokes. In addition, Lee et al. suggested that left atrial dysfunction could be a marker of incident AF, atrial thrombi, and thromboembolic risks of AF [13].
Baturova et al. reported that left atrial dilatation assessed by LAVI independently predicted AF after stroke in patients without prior AF history, while the other clinical or electrocardiography (ECG) markers were not predictive for AF detection early after ischemic stroke. The authors suggest that initially, there is development of subtle structural changes predictive for future AF seen in echocardiography (for example, increased LAVI) [14].
The increased LAVI in the aspect of ESUS stroke may also be important as a predictor of paroxysmal AF as a true cause of stroke. Detecting AF after ischemic stroke is challenging because of its paroxysmal nature and often silent, asymptomatic course, as was confirmed in studies with implantable devices [14].
Accordingly, patients with Echocardiographic features of HFpEF should be considered at risk of cardioembolic cerebrovascular accidents with consequently, anticoagulation with new oral anticoagulants should be considered as a primary preventive measure for cardioembolic stroke.
It is clear that the design of this study was observational, which can only demonstrate associations and is susceptible to giving confounding results. Therefore, there is a need for larger scale multicenter randomized control trials to confirm the association between LVH measured by left ventricular mass index and increased LAVI, measuring left atrial dilatation, and ESUS.
Limitations
The sample size was small. Verification of results on a larger sample size is required. Echocardiographic indices are not the only markers to detect ESUS. Biomarkers of other modalities need to be explored to detect pathogenesis of ESUS events.