1. PFO Dr Peter Wilmshurst Royal Shrewsbury Hospital Co-workers: Simon Nightingale, Lindsay Morrison, Matthew Pearson, Kevin Walsh, Phil Bryson, John Davis, J de Giovanni, Chris Byrne and MIST Trial investigators

2. NO CONFLICT OF INTEREST TO DECLARE

3. Syndromes associated with right to left shunts Paradoxical thromboembolism and stroke (atrial >>>>> pulmonary shunts)

4. Syndromes associated with right to left shunts Paradoxical thromboembolism and stroke (atrial >>>>> pulmonary shunts) Paradoxical gas embolism and decompression illness (atrial >> pulmonary shunts)

5. Syndromes associated with right to left shunts Paradoxical thromboembolism and stroke (atrial >>>>> pulmonary shunts) Paradoxical gas embolism and decompression illness (atrial >> pulmonary shunts) Migraine with aura (atrial > pulmonary shunts)

6. Syndromes associated with right to left shunts Paradoxical thromboembolism and stroke (atrial >>>>> pulmonary shunts) Paradoxical gas embolism and decompression illness (atrial >> pulmonary shunts) Migraine with aura (atrial > pulmonary shunts) Arterial hypoxaemia (pulmonary >>>>> atrial shunts)

7. Prevalence of migraine with aura related to shunt size 4% of general population 4% of those with small right-to-left shunts 25% of those with medium shunts at rest 21% of those with large shunt with Valsalva 53% of those with large shunt at rest 53% of those with Hereditary Haemorrhagic Telangiectasia

8. Determinants of size of the shunt through a PFO Dimensions of the foramen Size of the flap Compliance of the flap Pressure gradient* Atrial flow characteristics* *variable

10. Migraine with aura and increased incidence of cryptogenic stroke Large atrial shunts (PFO & ASD) are present in: 7.3% - population controls 38.1% - migraine with aura but no stroke 84% - stroke and migraine with aura (Am J Card 2006;98:831-3)

12. Migraine with aura and risk of decompression illness People with migraine with aura have increased risk of neurological DCI (War Medicine 1944;5:304-14) The increased risk is confined to migraineurs with a large PFO or other large right-to-left shunt (Clinical Science 2001;100:215-20).

15. Recurrence of symptoms after PFO closure Symptoms are not shunt-related and PFO is bystander.

16. Recurrence of symptoms after PFO closure Symptoms are not shunt-related and PFO is bystander. PFO closure device responsible for recurrence (e.g. migraine triggering effect of device, stroke caused by thrombus on device or AF post implantation).

17. Recurrence of symptoms after PFO closure Symptoms are not shunt-related and PFO is bystander. PFO closure device responsible for recurrence (e.g. migraine triggering effect of device, stroke caused by thrombus on device or AF post implantation). Significant residual shunt through PFO, another atrial defect or a pulmonary shunt.