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Patent Foramen Ovale and Migraine

Finding PFO
PFO incidence
PFO incidence in migraine
Closing the shunt
Comment

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
Hearts
PFO (%)
1897
399
26
1900
306
32
1918
1809
29
1931
4083
25
1934
500
17
1948
492
23
1972
144
35
1979
64
31
1984
965
27
1994
500
15
TOTAL
9262
25




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
Hearts
PFO (%)
1988
40
2.5
1989
50
12
1989
64
27
1989
479
6.1
1991
50
26
1991
50
8
1991
150
20
1991
79
17
1991
63
3.2
1995
1000
9.2
TOTAL
2025
10



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.

  1. There aren't many patients in these studies.
  2. None is a randomised trial.
  3. The studies depend on recall, and most are retrospective.
  4. There was no blinding for patients or carers, and expectation may have played a part.
  5. Patients undergoing cardiac procedures have lots of medications afterwards, and we don't know about the effect of those medicines alone or in combination.
  6. New migraine after septal closure is not confined to the Norwegian study [8].
  7. Completeness of closure does not seem to be associated with migraine relief.
  8. 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.
  9. 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:


  1. 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.
  2. 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.
  3. P Penther. Patent foramen ovale: an anatomical study. Apropos of 500 consecutive autopsies. Arch Mal Coeur Vass 1994 87: 15-21.
  4. 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.
  5. M Schwerzmann et al. Prevalence and size of directly detected patent foramen ovale in migraine with aura. Neurology 2005 65: epub ahead of print.
  6. I Domitrz et al. The prevalence of patent foramen ovale in patients with migraine. Neurol Neurochir Pol 2004 38: 89-92.
  7. 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.
  8. K Mortelmans et al. The influence of percutaneous atrial septal defect closure on the occurrence of migraine. European Heart Journal 2005 26: 1533-1537.

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