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Dr Rockesh Gurtu

Cardiovascular Research Fellow

Patent Foramen Ovale and Paradoxical Embolisation

Patent foramen ovale (PFO) is a common congenital cardiac defect, occurring in 25% of the general population, and is the commonest cause of a venous to arterial circulation shunt (v-aCS). Although, previously thought to be benign, it is being implicated in an increasing number of clinically significant conditions in which paradoxical embolisation of emboli or vasoactive chemicals through a PFO are thought to play a role. PFO closure, using a minimally invasive technique, is now a therapeutic option, but identification of patients that may benefit from this remains a challenge.

Previous BHF funded studies in our department have demonstrated an association between PFO and ischaemic stroke in young adults (YAMIS study) and between PFO and migraine with aura. In other studies, we have shown that paradoxical embolisation through a PFO may contribute to cognitive impairment or dementia. We have also developed validated criteria for identification of PFO using contrast- transcranial Doppler (c-TCD) ultrasound. Our present focus of research includes investigating the genetics of PFO and the role of paradoxical embolisation in the development of cognitive impairment in patients undergoing long-term haemodialysis.

Genetics of PFO

The genetic basis of PFO has not previously been investigated. We are using a combination of approaches to investigate the heritability and genetics of PFO. This includes twin studies to investigate the heritability of PFO, candidate gene analysis and a multi-centre collaboration to identify specific genetic variants associated with persistence of PFO using whole genome sequencing. A greater understanding of the genetic basis of PFO may help in the optimal management of individuals with associated diseases including stroke and migraine with aura. Detection of specific genetic variants associated with PFO may help in the identification and risk stratification of individuals most likely to benefit from PFO closure.

Does paradoxical embolisation through PFO contribute to cognitive impairment in patients undergoing long-term haemodialysis?

Cognitive impairment is common in patients with end-stage renal failure undergoing chronic haemodialysis. The dialysis circuit is known to generate emboli and these have been shown to pass into the venous circulation of patients undergoing haemodialysis. We are investigating the role of chronic paradoxical embolisation through PFO in the development of acute and chronic cognitive changes in patients undergoing long-term haemodialysis therapy. The presence of v-aCS, return venous and cerebral emboli and cerebral haemodynamic changes are determined by transcranial Doppler. Degree of cognitive impairment is assessed by a standardised battery of cognitive function tests. If PFO plays a significant role in the development of cognitive impairment in these patients, PFO closure or optimising antiplatelet or anticoagulant regimens would result in significant improvements in morbidity and quality of life.