PFO update

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PFO update

• Dr Peter Wilmshurst
• UK Sport Diving Medical Committee
• and
• Royal Shrewsbury Hospital

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Syndromes associated with right to left shunts
(PFO)

• Causal association
• Arterial hypoxaemia
• Paradoxical thromboembolism and stroke
• Paradoxical gas embolism and decompression
  illness
• Possible causal association
• Migraine with aura
• Transient global amnesia

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Inter-relation of PFO syndromes

• Migraine and increased risk of stroke
• Migraine linked to transient global amnesia
  (Cromwell et al. Arch Neurol 19844175-9)
• Migraine and increases risk of decompression
  illness (Engel et al. War Medicine 19445304-14)
  and the link is a large PFO or other shunt
  (Clinical Science 2001100215-20)

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Causes of decompression illness

• Missed decompression stops - causes excessive
  bubble formation, which overwhelms the pulmonary
  filter to reach the systemic circulation
  (Provocative dives)
• Lung disease and rapid ascent - causes pulmonary
  barotrauma with gas invasion of pulmonary veins
  (Often conservative dives)
• Right-to-left shunts venous bubbles by-pass the
  pulmonary filter (Dives intermediate severity)

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PFOs and decompression illness

• A right to left shunt is usually across a foramen
  ovale (PFO).
• Paradoxical gas embolism causes neurological,
  cardiovascular and skin decompression illness
  (DCI).
• It causes 52 of neurological DCI. (Clinical
  Science 20009965-75)
• It causes 78 of skin DCI. (Clinical Science
  2001100539-542)

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Causes of decompression illness
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What is required for shunt mediated DCI?

• A large right to left shunt.
• Dive profile liberates venous bubble.
• Dive profile causes an appropriate inert gas load
  in critical tissues to amplify embolic bubbles.
  (Note -DCI does not occur after contrast
  echocardiography)

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Prevalence and size of shunts

• 27.3 of population have a PFO. (Mayo Clin Proc
  19845917-20)
• Using our criteria/technique 27 .6 of controls
  have a shunt but only 7.3 are large - 4.9 at
  rest and 2.4 only with Valsalva. (Clinical
  Science 20009965-75)
• Risk of DCI is related to shunt size.

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Closing a PFO in a diver who had decompression
illness

• The shunt must be large and history specific.
• Confirm that DCI was not the result of lung
  disease or a provocative dive.
• The options are to stop diving or to have
  transcatheter closure of PFO (or ASD) or, if
  amateur, to modify diving to reduce nitrogen
  load.
• Check that there is no significant residual shunt
  before return to diving after PFO closure.

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Sub-atmospheric decompression illness

• During hypobaric experiments 6-39 of subjects
  have heavy venous bubbling.
• Serious DCI (neurological, circulatory and
  cutaneous effects) is sometimes encountered.
  There is usually a resting PFO.
• Insufficient numbers to be sure about the role of
  PFO (or other shunts) in subatmospheric DCI, but
  enough evidence to advise that those with shunts
  should not be astronauts.

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The link between migraine and decompression
illness

• Known since 1944 that individuals with migraine
  with aura have increased risk of neurological
  DCI. (War Medicine 19445304-14)
• Post dive migraine aura is virtually diagnostic
  of a large shunt and indicates increased risk of
  DCI. (Clinical Science 2001100215-200)
• Migraine with aura can occur after contrast
  echocardiography in those with a large shunt.

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Right to left shunts and migraine with aura

• Using transcranial Doppler it was shown that
  right to left shunts are present in 41-48 of
  patients with migraine with aura, 23 of those
  with migraine without aura and 16-20 of controls
  (p lt 0.01).
• (Del Sette et al. Cerebrovasc Dis 19988327-330
  Anzola et al. Neurology 1999521622-1625.)

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Migraine with aura linked to right-to left shunts

• 52.9 of divers with large shunts at rest have
  migraine with aura in every day life v 11.8 of
  divers without shunts.
• There is a size-prevalence relationship.
• Migraine without aura is not related to the
  presence of a shunt.
• Post dive migraine aura is virtually diagnostic
  of a large shunt.
• (Clinical Science 2005108 365-7)

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Shunt size and migraine with aura
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Inheritance of PFO and ASD and the relationship
to familial migraine with aura (MA)

• MA is commonly dominantly inherited.
• There are a few reports of familial ASDs.
• We investigated whether PFOs and small ASDs are
  inherited and whether this is related to the
  inheritance of MA in 20 families. (Heart
  2004901315-20)

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Methods

• 20 families in which the probands had paradoxical
  embolism were studied.
• Contrast echocardiography blind to neurological
  history in family members.
• Migraine/headache history blind to contrast
  echocardiography.

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Findings

• Atrial shunts (large PFOs and ASDs) are
  dominantly inherited.
• When a proband had MA 71 of first degree
  relatives with significant shunt had MA compared
  with 21 without a significant shunt (plt0.02).
• Inheritance of MA is closely linked to
  inheritance of atrial shunts in some families.
• We have confirmed these findings in a further
  unreported series of families.

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Effect of PFO closure on migraine
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The MIST Trial

• A prospective, randomised, multicentre,
  double-blind, placebo controlled trial to
  evaluate the effectiveness of PFO closure with
  the STARFlex septal repair implant to prevent
  migraine headache.

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Design of the MIST Trial

• Headache specialists enrolled patients with
  frequent migraine attacks not controlled with 2
  or more classes of prophylactic drugs.
• Diagnostic cardiologists referred if large PFO.
• Interventional cardiologists randomised under
  GA to transcatheter closure of PFO or sham
  intervention.
• Headache specialist blind to randomisation
  follow up for 6 months.

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MIST preliminary shunt prevalence
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MIST results

• Mean PFO diameter in patients randomised to
  closure was 9.21 3.27mm.
• A 50 reduction in migraine days was achieved in
  42 of those who had closure of a large PFO v in
  23 of patients having the sham intervention (p
  0.03).
• In the implant patients there was a 37 reduction
  of headache burden v 17 in the sham group (p
  0.03).

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Conclusions

• PFO and other right to left shunts are common
  causes of certain types of decompression illness
  and migraine with aura.
• Transcatheter closure of a PFO is one option
  following shunt related decompression illness and
  may become an option for some migraine patients.