Given the putative association between AC and ESUS, the main goal of this study was to evaluate LA mechanical function using myocardial deformation analysis by STE and FT-Cardiac MR.
In line with current literature, our study showed that ESUS patients had a higher prevalence of cardiovascular risk factors26–28 and PFO28. In our ESUS population 23.0% had AC, which was also consistent with published data29, but surprisingly, compared with age and sex-matched controls the prevalence was not significantly different. In addition, LA dimensions were similar between groups.
Formerly, LA evaluation was restricted to its dimensions, however, the role of LA mechanical function in several diseases was recently highlighted and myocardial deformation analysis has been increasingly used, since it allows detection of LA dysfunction before structural changes30.
In our study LA myocardial deformation analysis did not show significant differences between patients and controls. Furthermore, when analysing the ESUS patients with and without AC we found no significant differences in all LA echocardiogram findings. Considering the possibility of PFO being the source of ESUS through paradoxical embolism, we excluded these patients and repeated the analysis, but the results were similar. Considering the higher spatial resolution and better endocardial border definition of Cardiac MR31, we also performed a LA myocardial deformation analysis using FT, which confirmed the previous findings.
Therefore, these findings suggest that in our young ESUS patients AC or LA dysfunction were not the major embolic mechanism. A possible explanation is the heterogeneity of the population which could have implications for smaller studies.
A similar case-control published in 2020, evaluated LA dynamics in 30 young CS patients (73% with ESUS) and found no differences regarding LA maximum volume, although patients had a lower epsilon peak26. However, in contrast with our study, LAS was evaluated using tissue Doppler imaging, which is angle-dependent and less trustworthy32.
Moreover, a prospective cohort published in 2021, that evaluated the association of LAS using STE and stroke subtype, did not find any association with CS33.
In addition, our study revealed a significantly lower absolute and relative LAA ostium variation in the ESUS group, which persisted after exclusion of the PFO study subjects. Furthermore, during the analysis of ESUS patients with and without AC, LAA ostium variation was similar between groups, which suggests that the LAA role may be independent of AC. In cardiac MR analysis, no differences were found in LAA ostium variation between groups. This discrepancy could be explained by a much smaller sample and flow artefacts that compromise small structure evaluation.
LAA is a remnant of the original embryonic LA and is a reservoir of blood during fluid overload34. Previously published data already highlighted the role of LAA in IS14, however data in ESUS is scarce.
Reduced LAA flow velocity promotes stasis, mainly if less than 20cm/s, in AF patients14,35. Additionally, 55% of CS patients had enlarged LAA36 and non-chicken wing morphology and the number of lobes are independent risk factors of thromboembolic events37–38.
In summary, our study in line with current literature suggests that LAA may play a major role in ESUS pathophysiology, since lower ostium variation may hypothetically be associated with stasis and according to Virchow’s triad, thrombus formation. The role of LAA warrants further studies.
LAS did not add value for risk stratification in this group of patients.