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PATENT FORAMEN OVALE: A RISK FACTOR FOR P.Germonpré, P.Dendale, Ph.Unger, A.Aerts, M.De Pauw, F.Vanderschueren, C.Balestra Centre for Hyperbaric Oxygen Therapy,
Military Hospital Brussels, Belgium Introduction Patency of the Foramen Ovale (PFO) is present in about 30% of the normal population. The prevalence seems to decline with ascending age groups, probably due to secondary closure (1). The anatomical details of PFO are well known: in most cases it consists of a narrow (1-6mm), rather long (7mm) channel, transgressing the inter-atrial septum from upper right posterior to lower left anterior (2). Thus, it forms a functional valve, through which in normal haemodynamic conditions, no significant passage of blood occurs, since the right atrial pressure is lower than the left atrial pressure. Only in some patients, reversal of the pressure gradient may occur during one point in the cardiac cycle, but unless there is a very large opening, no significant shunt occurs (3). If a left-to right shunt is present, the term "PFO" is not any longer appropriate, and the term “ASD” (Atrial septal defect) should be used instead. ASD, however mostly asymptomatic, is an accepted contra-indication for sports diving, whereas PFO, usually undetectable on a clinical basis, is mostly not considered a formal contra-indication. PFO is the result of an incomplete fusion of the two leaflets of the Oval Fossa after the reversal of the atrial pressures after birth. The declining prevalence of PFO in advancing age groups is probably due to the secondary adhesion and solidification of the two leaflets at a later age. There exists a (until now unproved) hypothesis that a non-patent Foramen Ovale, by one significant or by repeated less important right atrial pressure rises, can re-permeabilize during the course of life. This would have a direct consequence on the diving population's prevalence of PFO, since divers frequently induce such pressure rises voluntarily (Valsalva manoeuvre). Several of the PFO studies in divers who suffered from DCS show a markedly increased prevalence of PFO (4). A conclusive study on the prevalence of PFO in the diving population in general, however, has, to our knowledge, not yet been published. Decompression sickness (DCS) can occur in sports divers after uneventful dives, where the diver has not committed any (reported) error in the standardly accepted decompression procedures. Often, PFO is found in these divers. It is now generally accepted - be it based on animal studies with a severe dive profile, yielding a high venous nitrogen bubble load - that patency of the Foramen Ovale (PFO) can be the cause of paradoxical arterial nitrogen bubble emboli, and thus be the cause of decompression illness (5). A rise in Pulmonary Artery Pressure, and retrograde rise in Right Atrial Pressure, caused by pulmonary embolisation of nitrogen bubbles, might be responsible for a right-to-left blood shunt through a PFO. These arterial nitrogen bubbles would most likely be migrating to the brain, owing to both the aortic cross flow-patterns and the upright position of the diver during and immediately after the ascent from the dive, thus causing high-spinal, cerebral, cerebellar, vestibular or cochlear DCS symptoms. The precise pattern of PFO-related DCS however, is not entirely clear. Symptoms seem to appear usually very shortly (less than 30 minutes) after the dive (6). The higher prevalence of “cerebral” symptom DCS however, has not been found in a recent study (7). This led this author to postulate that another mechanism, rather than embolisation per se, might be involved. Even the hypothesis that so-called “undeserved” DCS would be related to PFO, is still disputed (8). Study Objectives This (ongoing) study was set up to determine, in a population of Belgian divers with neurological DCS, the prevalence of PFO. The relationship of PFO with spinal or cerebral DCS was examined, as were the dive profile and the circumstances of the dive and accident. Study Protocol All Belgian divers who suffered from DCS in the period 1991-1995 and who were treated or followed up in their course of disease in either the Ostend Naval or Brussels Military Hospital Hyperbaric Centres, were reviewed for participation in the study. Exclusion criteria were:
Arrested diving activity or history of previous DCS were not considered exclusion criteria. 37 divers with neurological DCS were included. According to the symptoms, they were classified as having suffered from “spinal” or “cerebral” (i.e. cerebral, cerebellar, high-spinal, vestibular or cochlear) DCS. Among the dive profile characteristics noted were: dive depth, bottom time, whether decompression stops were necessary, computer or table use, successive dive or not, missed decompression stops, rapid ascent (according to the dive planner used). Also, “minor” risk factors were noted, such as pre-dive fatigue, stress, alcohol consumption or possibility of pre-dive dehydration (inadequate fluid intake), physical effort or feeling of cold during the dive, and post-dive exercise. A DCS episode was classified as “undeserved” when no errors were made as to ascent rate or decompression stops, and less or equal than three of these “minor” risk factors were detected. For each participating diver, a matched control diver, who never suffered DCS, was selected from the Belgian divers’ population. Matching was performed based on the following criteria: age (±5years), sex, length and weight (Body Mass Index ±2pts), smoking habits, physical condition, diving experience (number of years diving, total number of dives, ±10%), and tubar permeability (method used for ear equalisation). 36 control divers were finally withheld. All divers underwent a standardised trans-esophageal echocardiography (TEE) with saline contrast generation. In brief, TEE was performed by means of a multiplane echocardiographic endoscope (HP Sonos 2500), in the awake or moderately sedated patient. The inter-atrial septum was located and the ultrasound probe positioned thus that a clear view of both right and left atrium was obtained. Via an antebrachial vein perfusion, shaken saline (10cc, pushed to and fro 10 times in a double syringe system) was injected to obtain contrast generation. The numbers of bubbles appearing in the left atrium within 3 heart cycles was taken as the degree of patency of the Foramen Ovale. After several readings, each with 1 minute interval in order to clear the right atrium completely of remaining bubbles, the patient was asked to perform a sustained Valsalva manoeuvre, and shaken saline was injected during this manoeuvre. At the arrival of the first bubbles in the right atrium, the patient was instructed to release the strain. Again, passage of bubbles to the left atrium was observed. The patency of the Foramen Ovale was semi-quantified in several degrees:
All TEE's were recorded onto high-resolution videotape (super-VHS),
and reviewed in a blinded manner some time afterwards.
Results The overall prevalence of PFO in DCS divers was 22/37 (59.5%), which is higher than in the matched control divers: 13/36 (36.1%, p=0.06, Fisher’s exact test). More detailed analysis, by means of the McNemar’s test for paired observations, confirmed these findings: p=0.09, with an Odds Ratio of 0.31. In divers with cerebral DCS, the prevalence of PFO was 16/20 (80%), significantly higher than in their matched controls: 5/20 (25%, p=0.012). In divers with spinal DCS, PFO prevalence (6/17, 35.2%) was comparable to the control divers’ group: 8/16 (50%, p=0.49, Fisher’s exact test). The difference between the two control groups (5/20 vs. 8/16) was not significant (p=0.17). McNemar’s test for paired observations confirmed the significant difference for the cerebral DCS group (p=0.019) but was not significant for the spinal DCS group (p=0.68). When considering only those divers that had important contrast passage, the differences are even more significant. In cerebral DCS, 14/20 (70%) had PFO grade 2 (control group: 3/20, p=0.002), whereas in spinal DCS this was 5/17 (29.4%) (control group: 6/16, p=0.29, Fisher’s exact test). McNemar’s test was significant for the whole population (p=0.0389), very significant for the cerebral DCS group (p=0.005), but not significant for the spinal DCS group (p>1.0).
Looking at other possible differences between the cerebral and spinal DCS group, an analysis was made of the accidental dives. No significant differences were found in dive depth, although cerebral DCS tended to occur at shallower depth (35±11m for cerebral DCS, vs. 41±8m for spinal DCS, p=0.75). 12/20 cerebral DCS cases could be classified as “undeserved”, for 14/17 spinal DCS cases (p=0.17, NS). There was no difference in the number of dive computer users: 10/20 vs. 6/17 (p=0.53). Computer divers did generally deeper dives (mean 37.4m vs. 31.4m for cerebral DCS, and 45.0m vs. 39.0m for spinal DCS), but none of these differences were statistically significant.
Another analysis was carried out of the biometric data, of smoking habits, of the diving experience data, middle ear equalisation method, between the two groups. No significant difference was found as to age (36.9 vs. 38.5ys, p=0.59), BMI (25.7 vs. 24.6pt, p=0.36), number of smokers (8/20 vs. 4/17, p=0.32), or dive experience. A most significant factor was the method used for middle ear equalisation. Whereas in the spinal DCS group, 8/17 divers indicated having no difficulties for ear “clearing” (yawning or only very light Valsalva), all the divers from the cerebral DCS group said they had to “push hard” or “push really hard” to clear their ears while diving (p=0.006) (Table 3: “BTV”= “Béance Tubaire Volontaire”, i.e. easy equalisation).
Finally, we looked at those divers that had a so-called “undeserved” DCS episode. Of the 12 cases from the cerebral DCS group, 1 had PFO grade 1 and 9 had grade 2. In the spinal DCS group (14 cases), 2 had PFO grade 1 and 4 grade 2. For PFO in general (grade 1 + grade 2) these differences were almost significant (p=0.051, Fisher’s exact test). For grade 2 PFO, significance was reached (p=0.047). Divers with PFO had very significantly more cerebral DCS (16/22, 73%) than divers without PFO (4/15, 26%) (p=0.0084, Fisher’s exact test). Considering PFO grade 2, this difference was still significant (14/19 vs. 6/18, p=0.021). The Odds Ratio could be determined as 7.33 and 5.6, respectively. Discussion Neurological DCS is fortunately a rare occurrence in Belgium. Annually, some 30 cases of DCS are treated. The majority of these cases are neurological. Sometimes, because of the minor, vague and subjective symptoms reported, the diagnosis of neurological DCS is only tentative. Most of these cases, despite equally rapid and aggressive hyperbaric treatment, do not respond well, shedding more doubt as to the initial diagnosis. These cases, almost 50%, were excluded. Because of the study set-up, cases were also excluded where the diving history was not available or when major inconsistencies were present in the diving history. These mounted up to approximately 25%. From the remaining 25%, six divers were excluded because of refusal to undergo TEE. Some of these divers did undergo a transthoracic contrast echocardiography (TTE) but because of the low sensibility of TTE as compared to TEE, especially when trying to semi-quantify the PFO (9), they were nevertheless excluded from analysis. A lot of attention was given to selecting matched control divers. Since DCS is in most cases a multifactorial event, all possible interfering parameters were matched, both as to possibilities of nitrogen uptake (age, sex, body mass index, physical fitness), as to factors influencing pulmonary fragility (smoking) or lack of diving experience. Because of the (as yet unproved) hypothesis that diving and/or repeated Valsalva manoeuvres could be associated with a failure to fuse or secondary re-opening of a Foramen Ovale, we also selected control divers upon diving experience and ear equalisation method used. All quantitative criteria were matched within ±10%; yes/no criteria were strictly met. With regard to PFO, it is naturally impossible to match for perinatal circumstances, but we assumed that both the DCS divers group and the control divers group were representative samples from the normal non-diving population before they took up diving. The TEE method was strictly standardised. Two cardiologists reviewed and practised this technique before applying it to all subjects. Divers were instructed to perform a high-strain prolonged Valsalva manoeuvre, which was held for approximately 10 seconds before release. Injection of 10cc of shaken saline resulted in a massive opacification of the right atrium, and only bubbles that appeared in the left atrium within 3 cardiac cycles were considered pathological. All TEE’s were recorded onto high-resolution videotape and reviewed at a later stage by both cardiologists together, in a blinded manner. Care was taken to exclude “false contrast” by turbulence (10). Only then was the final PFO score attributed. A semi-quantitative approach was adopted, and the difference between slight and important contrast passage was arbitrarily chosen at 20 bubbles. Clearly, divers do not experience such a massive bubble load after most of the dives. Since it seems unlikely that very few microbubbles can provoke clinically overt DCS, this classification can be used to distinguish minor patency from possibly clinically important patency. Our results seem to confirm this hypothesis. Divers with cerebral symptoms from DCS have a significantly higher PFO prevalence than the control divers (p=0.012), whereas the prevalence in spinal DCS is similar to that of controls. This difference is even more significant when only the grade 2 PFO’s are considered (p=0.002). The prevalence of PFO in control divers is higher than what is reported from autopsy studies, but in the same range as that reported from other contrast echocardiographic studies. Because of possible other factors affecting DCS risk and/or risk of specific localisation of DCS symptoms (Wilsmurst 1994), the two groups were also analysed for biometry and dive characteristics. No differences were found, except for the ear equalisation method used. It is striking that all of the cerebral DCS cases declared they have to exert a fairly high strain in order to “clear” the ears, whereas in the spinal DCS group, this was the case in only half of the subjects. Finally we looked at those DCS episodes that could not be explained by decompression errors or multifactorial enhanced DCS susceptibility (26/37, 70.3%). This high percentage can be explained by the exclusion of all “doubtful DCS cases” from the study, where the percentage of “deserved” accidents is higher. Overall, the ratio “deserved-undeserved” lies around 50%. Here again, a much higher prevalence of PFO was found in the cerebral DCS group (10/12, 83%) than in the spinal DCS group (6/14, 43%, p=0.051). When only considering the “important” PFO’s (grade 2), this difference was significant (p=0.047). Conclusions A significant correlation between PFO and cerebral DCS, but not
spinal DCS, seems likely. This is in accordance with the pathophysiological
model, in which nitrogen bubbles, passing through the PFO into
the arterial circulation, subsequently migrate preferably into
the carotid and/or vertebral arteries.
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