The impact of patent foramen ovale on left atrial reservoir strain in young patients with cryptogenic ischemic stroke - the SECRETO study

Background Up to 50% of all ischemic strokes in young adults are of undetermined etiology or cryptogenic (CIS). Premature left atrial (LA) myopathy with reduced LA reservoir strain (LASr) has been suggested as a possible cause of CIS below the age of 50. Whether the presence of a septal shunt through a patent foramen ovale (PFO), particularly when associated with a hypermobile interatrial septum, affects the LA reservoir function has not been previously explored. Purpose To assess the impact of PFO and associated high-risk characteristics (hypermobile septum) on LASr in young adults with CIS compared to age- and sex-matched controls. Methods LASr and LA contractile strain were analyzed by transthoracic speckle tracking echocardiography in 472 CIS patients aged ≤50 years and age- and sex-matched controls participating in the Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO) study. LASr was defined as low for age if <31%. The presence of PFO was detected by contrast transesophageal echocardiography (TEE) during the Valsalva maneuver. The total excursion of the septum between the right and left atrium was measured in a standard TEE bicaval view. Results In the whole cohort, lower LASr was more common in individuals with obesity, those with spontaneous contrast in the LA appendage or aortic arch atheromatosis and in cases with higher interatrial septal excursion (p<0.05, Figure 1). A PFO was more often present among CIS patients than among controls: 57% vs 26% (p<0.001). However, LASr was lower in patients than in controls both in participants with and without PFO (Figure 2). In multivariable regression analysis, lower LASr was associated with occurrence of CIS, higher body mass index and interatrial septal excursion, and lower LA appendage emptying velocity and LA contractile strain, but not with presence of PFO (R2=0.42, all p<0.05). Conclusions Young patients with CIS have lower LASr than age- and sex-matched controls independent of the presence of PFO. A lower LA reservoir function is associated with reduced LA appendage emptying function and is more common in individuals with hypermobile interatrial septum, bringing mechanistic insights into the substrate of CIS before the age of 50.