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.