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.