Patent Foramen Ovale and Migraine
The
foramen ovale is a channel between the atria of the foetal heart allowing blood
to flow from the right to the left atrium, which shunts oxygenated blood to the
systemic circulation during foetal development. It is not needed in adult life
when the lungs are functional, and closes after birth. Or at least it closes
most of the time, because defects in the septa between the atria are relatively
common, and a significant minority of adults have a patent (open) foramen ovale.
Patent
foramen ovale (PFO) is associated with increased risk of stroke. In recent
years it has also been associated with migraine. While closing a large PFO to
try and prevent stroke might make sense, cardiac surgery to prevent migraine,
however bad, is difficult to justify.
This
short article examines some of the literature on PFO incidence, and takes a
quick look at the current evidence on PFO closure and the effects on migraine.
Finding PFO
There
are two main methods. One is to look at the heart directly, usually after
death. When patients are alive, the main method is transoesophageal
echocardiography (TEE). The first question is whether these two methods give
the same answer, and whether they are diagnostically equivalent. The answer [1]
is that they are.
Briefly,
35 consecutive patients with prior TEE who died underwent a post mortem
examination of the heart. Post mortem PFO was found in 9/35, and TEE picked up
the same nine. Moreover, both methods gave the same PFO diameter (Figure 1). We
might expect case series using either method to give the same result, therefore.
Figure 1: Patent foramen ovale diameter measured at autopsy and by colour doppler transoesophageal echocardiography
PFO incidence
The
incidence of PFO in over 9,000 hearts was 25%, in studies going back to 1897
(Table 1). Most studies gave similar results, of about 20-30%. The two most
recent [2,3] were interesting for two reasons. A detailed US autopsy study [2]
examined 100 normal hearts (50 of each sex) for the first ten decades of life.
It found that PFO incidence was similar in men and women, and declined gently
with age (Figure 2). It also provided information about PFO size, which was 11
mm or below in all but two of 265 cases, and predominantly 5 mm or less (Figure
3).
Table 1: Anatomical studies of patent foramen ovale over the past century
| Year | ||
| 1897 | ||
| 1900 | ||
| 1918 | ||
| 1931 | ||
| 1934 | ||
| 1948 | ||
| 1972 | ||
| 1979 | ||
| 1984 | ||
| 1994 | ||
| TOTAL |
Figure 2: Incidence of patent foramen ovale at autopsy in 965 normal hearts, by age
Figure 3: Size of patent foramen ovale at autopsy in mm in 265 hearts
The
most recent French study [3] was somewhat different because it examined only
hearts from 500 people who died with acquired cardiovascular pathology, mainly
coronary artery disease. This study had the lowest PFO incidence of any of the
anatomical studies of hearts, at 15%.
A
large study involved 1,000 consecutive patients [4] referred for TEE most often
to rule out possible cardioembolic sources of stroke, in patients with an
average age of 60 years. It also found equal incidence in men and women, and
included a review of other TEE studies since 1988 (Table 2). In all these
studies combined, with 2,025 patients, the overall incidence of PFO was 10%.
Table 2: Patent foramen ovale detected by transoesophageal echocardiography
| Year | ||
| 1988 | ||
| 1989 | ||
| 1989 | ||
| 1989 | ||
| 1991 | ||
| 1991 | ||
| 1991 | ||
| 1991 | ||
| 1991 | ||
| 1995 | ||
| TOTAL |
Put
simply, then, two methods that ostensibly have equal accuracy provide different
results. A possible cause may be the type of patients investigated, with
perhaps a lower incidence of PFO in patients investigated with TEE for clinical
reasons.
PFO incidence in migraine
Consecutive
patients with migraine with aura (93) participated in a study along with
healthy individuals from hospital staff or novice divers (93), and these two
groups were similar in age and other characteristics, with about 60% women [5].
Upon examination with TEE, it was found that significantly more of the migraine
patients had PFO (47%) than controls (17%). A much larger percentage with
moderate, and especially with large shunts, had migraine (Figure 4).
Figure 4: Size of atrial shunt in normal subjects and patients with migraine with aura
The
higher incidence of PFO in patients with migraine with aura confirmed a
previous Polish study [6] that investigated 62 patients with migraine with
aura, 60 without aura, and 65 controls. Using TEE it found no difference
between patients with migraine without aura and controls, but a PFO incidence
twice as high in patients with migraine with aura (Figure 5).
Figure 5: Incidence of PFO in patients with different types of migraine
Closing the shunt
Several
studies have shown the increased prevalence of PFO and shunting in patients
with migraine, and the expectation, therefore, might be that by closing the
defect the migraine will be improved. An editorial reviewed six studies (17 to
215 patients) that looked at the effect of PFO closure on migraine, but only
one of them, with 17 patients, looked only at migraine. In all, only 205
patients had migraine in a set of mainly retrospective studies, but there was a
tendency to see resolution or improvement in quite a high proportion.
As
often happens, though, early enthusiasm is tempered by later experience. A
large retrospective study of all patients undergoing percutaneous atrial septal
defect closures in Oslo was able to include 75 patients with migraine s(66% of
the total [7]). It found no difference in before and after incidence for
migraine with and without aura. In some patients (12/75) migraine disappeared,
but migraine appeared for the first time in 10 others.
Comment
It
may all come down to swings and roundabouts. If you ask about migraine
disappearance you get one answer. Ask about new migraine, and you get another.
Tsimikas [7] gives a number of reasons why linking atrial septal closure with
migraine disappearance may be all hype.
- There aren't many patients in these studies.
- None is a randomised trial.
- The studies depend on recall, and most are retrospective.
- There was no blinding for patients or carers, and expectation may have played a part.
- Patients undergoing cardiac procedures have lots of medications afterwards, and we don't know about the effect of those medicines alone or in combination.
- New migraine after septal closure is not confined to the Norwegian study [8].
- Completeness of closure does not seem to be associated with migraine relief.
- Apart from septal closure and postoperative medicines, there are other things going on in these studies that have not been controlled for, so there is no evidence for causality even if there were evidence for a link.
- And last, someone has to explain why prevalence of PFO is equal between the sexes, while migraine occurs three or four times more frequently in women.
Healthy
scepticism should be the watchword here. On the basis of current evidence, it
would hardly be wise to have cardiac surgery for migraine, when even in the
best hands there is always the risk of something going seriously wrong.
Let's keep an open mind, but bearing in mind what Bertrand Russell said:
the trouble with the world is that the stupid are cocksure and the intelligent
are full of doubt.
References:
- B Schneider et al. Diagnosis of patent foramen ovale by transesophageal echocardiography and correlation with autopsy findings. American Journal of Cardiology 1996 77: 1202-1209.
- PT Hagen et al. Incidence and size of patent foramen ovale during the first 10 decades of life: an autopsy study of 965 normal hearts. Mayo Clinic Proceedings 1984 59: 17-20.
- P Penther. Patent foramen ovale: an anatomical study. Apropos of 500 consecutive autopsies. Arch Mal Coeur Vass 1994 87: 15-21.
- DC Fisher et al. The incidence of patent foramen ovale in 1,000 consecutive patients. A contrast transesophageal echocardiography study. Chest 1995 107: 1504-1509.
- M Schwerzmann et al. Prevalence and size of directly detected patent foramen ovale in migraine with aura. Neurology 2005 65: epub ahead of print.
- I Domitrz et al. The prevalence of patent foramen ovale in patients with migraine. Neurol Neurochir Pol 2004 38: 89-92.
- S Tsimikas. Transcatheter closure of patent foramen ovale for migraine prophylaxis: hype or hope? Journal of the American College of Cardiology 2005 45: 496-488.
- K Mortelmans et al. The influence of percutaneous atrial septal defect closure on the occurrence of migraine. European Heart Journal 2005 26: 1533-1537.