Background: Patent foramen ovale (PFO) is a congenital defect of the interatrial septum with 25%-30% prevalence. Diagnostic echocardiography involves the injection of agitated saline, and microbubble passage from the right to the left atrium is monitored. The reliability of this method has been questioned in case series, with a low incidence (0.062%) of generally transient, mild clinical cerebrovascular events. This study aimed to examine whether transthoracic echocardiography, which was performed on patients with PFO and atrial septal aneurysm (ASA) without neurological history, and healthy controls can cause silent neuronal injury by evaluating neuronspecific enolase (NSE) with saline contrast echocardiography (SCE).

Methods: Fifty-two patients who underwent SCE for color flow through the interatrial septum or prominent interatrial septal aneurysm and were diagnosed with PFO were included. Fifty-one control patients without PFO or ASA were included. Serum samples were collected from the patients before and 12 hours after the SCE test, and NSE levels were measured by Enzyme Linked Immunosorbent Assay (ELISA).

Results: Median baseline NSE levels were 6.4 (2.8-9.6) ng/mL in the PFO/ASA group and 5.3 (3.6-9.1) ng/mL in controls. At 12 hours, median NSE levels remained similar (6.6 (3.8-11.5)
vs. 5.8 (4.6-9.6) ng/mL; P = .90). The median change in NSE (ΔNSE) did not differ between groups [1.19 (−1.01 to 2.23) vs. 0.73 (−1.16 to 2.25) ng/mL; P = .58]. There was no relationship between age, presence of interatrial septal aneurysm, mitral annulus calcification, number of bubbles passed in the SCE test, and baseline and 12-h change in NSE levels (P = .926). Neuronspecific enolase level changes were found to be correlated between groups (P < .001).


Conclusion: This study is the first to evaluate whether SCE causes silent neuronal injury. It is suggested that when evaluated with NSE, the SCE method is safe and does not cause silent neuronal injury in patients without underlying neuronal susceptibility.