Mechanism of Association
A number of potential mechanisms for ESUS have been identified which
include substenotic or aortic arch atherosclerosis, patent foramen
ovale, occult paroxysmal AF, LA cardiopathy and LV dysfunction7, 38.
Notably, atrial cardiopathy involves a complex interplay of electrical
and biomechanical changes at cellular and molecular levels causing
atrial remodeling and electro-mechanical
dysfunction39-41. These changes lead to stasis of
blood promoting thrombus formation in the LA chamber and at sites of
adversely remodeled endocardial borders, thereby predisposing to
thrombo-embolic events. To assess atrial dysfunction, different
techniques have been utilized, including echocardiography,
electrocardiography (EKG), and biomarker analysis. Enlarged left atrial
chamber, prolongation of the peak P wave terminal force and PR interval
on EKG42, 43, and elevated biomarkers like cardiac
troponin and N-Terminal pro-Brain Natriuretic Peptide have been
associated with myocardial injury, atrial remodeling, fibrosis, and
dysfunction44. These factors have been identified as
potential risk factors for thrombus formation and can independently
predict future embolic events in patients with non-valvular atrial
fibrillation44, 45. However, STE can detect atrial
dysfunction at an earlier stage, even before the changes identified by
these other techniques become apparent. In addition, cardiac magnetic
resonance (CMR) imaging has shown comparable amounts of fibrosis in
patients with ESUS and those with AF, regardless of prior stroke history
in AF group. Interestingly, both these groups were also found to have
higher LA fibrosis than those with lacunar strokes 46.
Therefore, LA strain analysis using STE may be a useful tool to further
risk stratify ESUS patients for recurrence and future AF detection.