The foramen ovale is an interatrial connection that is essential in fetal life; however, after birth, it closes in the majority of people. The foramen ovale does not close in ~25–30% of adults, allowing left-to-right shunt; this is called the patent foramen ovale.Reference Hagen, Scholz and Edwards 1 Even when it is functionally closed, in some conditions such as straining or coughing the shunt has a potential to become right to left. This may explain some neurological conditions and diseases in patients with patent foramen ovale.Reference Kenny, Turner and Martin 2 Some studies have shown a high incidence of patent foramen ovale in patients with transient ischaemic attack, stroke, and migraine;Reference Lechat, Mas and Lascault 3 – Reference Del Sette, Angeli and Leandri 5 therefore, closing the patent foramen ovale in such patients has become a choice of treatment, especially in adulthood. In children, the approach is mostly conservative, and experience is limited.
We therefore contacted patients who had undergone patent foramen ovale device closure in our hospital and questioned them about the continuity of their ailments that initially led to closure of the patent foramen ovale.
Methods
This retrospective study was carried out at the department of Paediatric Cardiology at Hacettepe University Faculty of Medicine. The medical records of children aged between 0 and 18 years who underwent device closure of the patent foramen ovale between January, 2005 and February, 2014 were systematically reviewed. This study was approved by the ethics committee of the university. Relevant demographic and clinical characteristics were retrieved from the medical records and recorded on pre-prepared forms.
We retrospectively collected data on patient demographics, clinical symptoms, findings, and work-up evaluation in the pre-procedural period, procedural details, devices used, complications, and post-procedure outcomes. We obtained details on the post-procedural clinical status of patients who were not followed-up via telephone, whose contact numbers were registered in the library system. Patients who could not be reached for follow-up data were excluded from the study.
Procedure
For the diagnosis of patent foramen ovale, all the patients had been examined by transthoracic echocardiography, and suspected patients had been evaluated with transcranial Doppler and transoesophageal echocardiography. The decision to close the patent foramen ovale had been taken by the council of the paediatric cardiology unit. Families of the patients had been informed about the procedure.
All interventions were performed under general anaesthesia. The implantation procedure was guided by both fluoroscopy and transoesophageal echocardiography. Devices were implanted successfully in all patients by paediatric cardiologists. No residual shunts were seen during the transoesophageal echocardiography performed at the end of the procedure. All patients were discharged on the day after the procedure, following clinical and femoral access-site review and transthoracic echocardiography. After the procedure, all patients were prescribed aspirin for 6 months. No procedural complications or adverse events were observed.
All patients were evaluated by electrocardiography, Holter electrocardiography, and transthoracic echocardiography after 1 month, 6 months, and 1 year after the procedure as a routine. Transcranial Doppler was performed in patients who were suspected of having interatrial residual defects. Patients with normal examinations continued follow-up annually.
Statistical analyses
All statistical analyses were performed using the Statistical Package for the Social Sciences programme for Windows, version 16.0. Descriptive statistical methods were used to analyse the results. Normality of distribution of numerical variables was evaluated by the Kolmogorov–Smirnov or the Shapiro–Wilk test. Values for numerical variables are given as mean±standard deviation or as medians (minimum–maximum), depending on the normality of distribution.
Results
Patients
A total of 17 patients (7 males; 10 females) with a mean age of 11.1±3.7 years (with a range from 4 to 16 years) underwent closure of the patent foramen ovale with different devices. Among them, 10 patients had recurrent transient ischaemic attacks, four patients had stroke history, and three patients had significant migraine attacks. On transthoracic echocardiography, there were no coexisting pathological findings except for minimal mitral insufficiency in two patients and minimal aortic insufficiency in one patient. The diagnosis of right-to-left shunt was confirmed with both transcranial Doppler and transthoracic echocardiography in all patients. Patient general characteristics and procedural data are illustrated in Table 1. The details of all 17 patients are summarised in Table 2.
Table 1 General characteristics of the patients and procedural data.
Table 2 Detailed features of the patients in the study group.
Amp=Amplatzer; ASO=Amplatzer septal occluder; Cr MR=cranial magnetic resonance; F=female; F V=factor 5; M=male; MTHFR=methylenetetrahydrofolate reductase; NP=not performed; PAI=plasminogen activator inhibitor; PFO=patent foramen ovale; TCD=transcranial Doppler; TIA=transient ischaemic attacks
We examined 8 patients for predisposition to thrombophilia. Electroencephalographies of these patients were found to be normal, except the third patient who had a subacute infarct in the left parietal lobe, observed during cranial magnetic resonance. Patient number 12 had a diagnosis of Crohn’s disease, and patient number 16 had a diagnosis of Hashimoto’s disease.
Follow-up
The median follow-up time was 5 years (2–10 years). No pathological findings were observed on electrocardiography, transthoracic echocardiography, and Holter electrocardiography during the follow-up period. No residual shunts were detected in the transcranial Doppler in 10 patients. We contacted all 17 patients and asked them about continuity of their ailments after the procedure: 15 patients were symptom free, and two patients with migraine had significant improvement in their headaches; they were not using preventive treatment anymore.
Discussion
There are several reports that establish a relationship between patent foramen ovale and some neurological events. It has been clearly shown that patent foramen ovale incidence is higher in patients with stroke, transient ischaemic attack, or migraine than in the normal population. Most of these reports involve adult age groups. McCandless et alReference McCandless, Arrington, Nielsen, Bale and Minich 6 and Choi et alReference Choi, Shin, Cho, Lee and Park 7 showed high prevalence of patent foramen ovale in children with migraine, especially migraine with aura. As cerebrovascular events are lower in children than in adults, there are no enough data investigating patent foramen ovale in children with cryptogenic stroke or transient ischaemic attack. Benedik et alReference Perkovič-Benedik, Zaletel, Pečarič-Meglič and Podnar 8 – Reference Benedik, Zaletel, Meglic and Podnar 10 showed high incidence of patent foramen ovale in children with transient ischaemic attack and high incidence of right-to-left shunt in children with arterial ischaemic stroke. Agnetti et alReference Agnetti, Carano and Sani 9 reported patent foramen ovale as the cause for stroke in two children. Most of these studies made an expectation that closing the patent foramen ovale may be the cure for these neurological events.
In 1999, Cujec et alReference Cujec, Mainra and Johnson 11 declared that surgical closure of the patent foramen ovale prevented recurrences of cerebral ischaemic events in their 14 patients. Orgera et alReference Orgera, O’Malley and Taylor 12 found that surgical patent foramen ovale closure in these patients is comparable with warfarin therapy in their meta-analysis. Butera et alReference Butera, Bini, Chessa, Bedogni, Onofri and Carminati 13 found no recurrence of thromboembolic events during their 1-year follow-up of patients with patent foramen ovale and cryptogenic stroke after transcatheter closure. Many studies with the same results have been published since then. Schwerzmann et alReference Schwerzmann, Wiher and Nedeltchev 14 showed similar benefit in migraine with aura.
There are only a few studies questioning the patent foramen ovale–neurological events relationship, however. Davis et alReference Davis, Gregson, Willeit, Stephan, Al-Shahi Salman and Brayne 15 mentioned that these pairwise associations do not strongly suggest a casual role for patent foramen ovale in their meta-analysis. Garg et alReference Garg, Servoss and Wu 16 found no relationship between migraine and patent foramen ovale.
In light of these arguments, in our department, transcatheter closure of the patent foramen ovale is a very rarely performed procedure. In these last 10 years, there were only 17 children with this condition among ~9000 catheter angiography patients. Patients were chosen very carefully, and decisions were taken by both neurologists and cardiologists. All diagnoses of patent foramen ovale were made not only by transthoracic echocardiography but also by transcranial Doppler and transoesophageal echocardiography. After the procedure, patients were followed-up by transthoracic echocardiography. As there were no further complaints, we did not require any other examination for follow-up, except in ten patients who underwent control transcranial Doppler.
Data on patent foramen ovale closure in childhood are limited. Bartz et alReference Bartz, Cetta and Cabalka 17 reported device closure of the patent foramen ovale as a safe alternative therapeutic option for children and young adults. Their median patient age was 29 years, and the median follow-up time was 5.3 months. Menon et alReference Menon, Grove, McFadden, Korgenski and Cowley 18 found complete resolution or reduction of symptoms in 143 of their 153 patients (93%) after patent foramen ovale closure. In this largest study in the literature, the median age was 16 years, and the median follow-up time was 12 months; however, a strong placebo effect was found. In our study, 15 patients were symptom-free, and two patients showed significant decrease in headaches after device closure of the patent foramen ovale. All of them were in the paediatric age group, and the follow-up time was long enough to rule out a placebo effect. Even the patient number was less to form a precise opinion, we suggest that under the right circumstances device closure of the patent foramen ovale is a safe solution for cryptogenic ischaemic events and migraine.
Acknowledgement
None.
Financial Support
This research received no specific grant from any funding agency or from commercial or not-for-profit sectors.
Conflicts of Interest
None.
