Clinical Implications
LA remodeling is a time-dependent adaptive change in the atrial cardiomyocyte that is followed by biomechanical changes17 affecting all the three phases of LA function 26. Thus, LA strain is a surrogate of atrial fibrosis and remodeling16. Previous studies have shown a correlation between enlarged LA chamber size with adverse cardiovascular outcomes including the risk of strokes and arrhythmias27, 28. Our study shows the association of reduced LA strain with ESUS compared to NCE, further potentiating previously reported LA strain’s association with cryptogenic stroke13, 19. In addition, it also demonstrates that reduced LA conduit and contractile strains are more commonly associated with ESUS compared to NCE stroke. This may be explained by underlying atrial fibrosis, remodeling, and biomechanical dysfunction causing stiffening of the atrial chamber, which impairs the compliance and booster-pump function of the atrium leading to atrial reservoir and contractile dysfunction. LA reservoir strain has been shown to be a predictor of thrombus formation in LA appendage in patients with sinus rhythm29. Our study adds to the existing literature showing significant association of all phases of reduced LA strain with ESUS subtype in patients in sinus rhythm with midrange and normal LVEF and in the absence of acute heart failure30.
Furthermore, the extent of atrial fibrosis inversely correlates with LA reservoir strain in AF irrespective of chamber size31and independently predicts progression from paroxysmal AF to persistent AF32. Our study demonstrates the association of all phases of reduced LA strain with AF in ESUS patients. This adds to the previously reported association of AF with reduced LA strain in cryptogenic stroke patients33 . However, our study demonstrates the association of AF with ESUS subtype, which is a more enriched population with a high recurrence rate of stroke within the spectrum of cryptogenic stroke subtype. Our findings also confirm recently published studies showing contractile strain as an emerging echocardiographic parameter for predicting AF in cryptogenic stroke patients34, 35. This provides a mechanistic pathway for the occurrence of ESUS, where atrial cardiomyopathy and biomechanical dysfunction provide a potential substrate for embolic source and also increases the likelihood of AF detection.
Recent trials, NAVIGATE ESUS5 and RE-SPECT ESUS6, did not show any benefit of oral anticoagulants over antiplatelet therapy for secondary prevention in ESUS patients overall. This is likely explained by significant heterogeneity in the underlying mechanisms of the ESUS subtype. However, anticoagulation may not work for all ESUS patients but may benefit those with atrial cardiopathy36 and those with ESUS and moderate to severe LV dysfunction37.
Our study demonstrates the utility of LA strain as a measure of early atrial cardiopathy in identifying the subset of ESUS patients that can benefit from a more rigorous cardiovascular risk factor modification, intensive cardiac arrhythmia surveillance with prolong atrial fibrillation monitoring, and potentially anticoagulation therapy.