The impact of intravenous agitated saline contrast echocardiography on subclinical neuronal injury determined by neuron-specific enolase

Abstract Introduction Patent foramen ovale (PFO) is a congenital defect in interatrial septum with 25-30% prevelance. Diagnostic methods include transesophageal echocardiography (TEE), magnetic resonance imaging (MRI), and computed tomography (CT), but transthoracic echocardiography (TTE) is the primary diagnostic method. TTE involves the injection of agitated saline intravenously, and the passage of microbubbles from the right atrium to the left atrium is monitored. The reliability of this method has been questioned in various case series, with a low incidence (0.062%) of generally transient, mild clinical cerebrovascular events reported. Silent cerebral ischemia (SSI) is asymptomatic, radiographically identified acute neuronal damage. SSI is associated with an increased risk of stroke, dementia, and cognitive impairment. Neuron-specific enolase (NSE) with high specificity for neural cells can be used to detect SSI. While symptomatic patients have been evaluated in reported case series, there is no study determining the relationship and reliability of intravenous agitated saline echocardiography (SCE) with SSI. This study aims to determine whether TTE, performed on patients with PFO without neurological history and a healthy control group, can cause SSI by evaluating NSE with SCE. Materials and methods 52 patients undergoing SCE for color flow through interatrial septum or prominent interatrial septal aneurysm and are diagnosed with PFO were included. Additionally, 51 control patients without detected PFO or ASA were also included. Serum samples were taken from the patients before and 12 hours after the SCE test, and NSE levels were measured by the ELISA method. Results The mean baseline NSE level was 12.7 ng/mL with a median of 5.3 ng/mL in the PFO group, and in the control group, the mean was 9.1 ng/mL with a median of 6.4 ng/mL. At 12 hours, the mean NSE levels in the PFO group were 9.8 ng/mL with a median of 6.6 ng/mL, and in the control group, the mean was 12.7 ng/mL with a median of 5.8 ng/mL. The increase in NSE levels after SCE, was not statistically significant when comparing the PFO and control groups (p=0.77). No relationship was found between age, presence of interatrial septal aneurysm, presence of mitral annulus calcification, the number of bubbles passed in the SCE test, and the basal and 12-hour change in NSE levels (p=0.926). NSE level changes were found to be correlated between groups (p<0.001). Conclusion This study is the first to evaluate whether SCE causes subclinical neuronal damage. Our study suggests that when evaluated with NSE, the SCE method is safe and does not cause subclinical neuronal damage in patients without underlying neuronal susceptibility.results