Patent Foramen Ovale (PFO) and cryptogenic stroke or transient ischemic attack: a follow-up study

Aims: The overall aim of this thesis was to study the long-term clinical outcomes in terms of survival, complications, recurrent stroke or transient ischemic attack (TIA), and quality of life in a group of patients with patent foramen ovale (PFO) and cryptogenic stroke. Patients who had undergone PFO closure were compared with patients who had not. The first aim was to provide a long-term clinical follow-up of patients who had undergone PFO closure. The second aim was to study whether a multidisciplinary PFO conference could maintain stringent criteria for PFO closure to identify patients at high risk of paradoxical embolization. The third aim was to compare long-term outcomes of PFO closure versus non-closure in patients who had been carefully selected by a multidisciplinary PFO conference. The fourth aim was to assess health-related quality of life after PFO closure compared to a normal population and compared to patients with a PFO and ischemic stroke who had not undergone PFO closure. Methods: Paper I was a retrospective long-term follow-up study that included all patients who between 1997 and 2006 underwent PFO closure in the GUCH center in Gothenburg. Paper II is a descriptive study of the PFO conferences and includes all patients with a PFO who were referred to our GUCH center for PFO closure between 2006 and 2009. Paper III is a prospective clinical follow-up study and includes all the patients discussed at PFO conferences in 2006–2009. Paper IV is a prospective study in which quality of life was assessed using the SF-36 Health Survey in all patients included in Paper I and III, compared with an age- and gender-matched reference group from the Swedish SF-36 normative database. Results: In Paper I, percutaneous PFO closure was successfully performed in 85 of 86 patients. The follow-up rate was 100%. No cardiovascular or cerebrovascular deaths occurred. Two patients (both women) died of lung cancer during follow-up. The mean follow-up time was 7.3 years (5 to 12.4 years). Mean age at PFO closure was 49 years. Two patients suffered from recurrent stroke or TIA, a recurrence rate of 0.3% per year. No long-term device-related complications were observed. In Paper II, 311 patients were evaluated at the PFO conferences. The acceptance rate for closure was similar throughout these years, with an average of 46%. Patients accepted for closure were younger (mean age 50 years vs. 58 years, p<0.001). In Paper III, all patients in Paper II were followed up almost five years later. Of 314 patients, 151 (48%) were accepted for closure and 163 (52%) were not accepted. PFO closure did not provide significant benefit compared with the non-closure group for the primary endpoint (a composite of all-cause mortality, stroke and TIA) or for the secondary endpoints (stroke, TIA or all-cause mortality in isolation), either in the intention-to-treat analysis or in the as-treated analysis. Finally, Paper IV demonstrated that device closure of a PFO provides significantly better health-related quality of life at long-term follow-up, in comparison to the non-closure group; closure patients reported similar quality of life compared to an age- and gender-matched normative population (p<0.05). The non-closure group showed poorer quality of life compared to both the closure group and to an age- and gender-matched normative population (p<0.05). Conclusions: Percutaneous PFO closure is associated with very low risk of recurrent stroke and is feasible in most patients. No mortality and no long-term device-related complications related to PFO closure were observed. The acceptance rate of less than 50% at the PFO conference underscores the complex relationship between cryptogenic stroke and PFO and the importance of a multidisciplinary approach. PFO closure does not provide any improved clinical outcomes regarding the composite of all-cause mortality, stroke and TIA compared to the non-closure group. Neither could any significant differences be demonstrated regarding recurrent stroke or TIA or regarding all-cause mortality. However, percutaneous PFO closure appears to have a favorable impact on quality of life. Larger prospective observational studies and randomized studies are necessary to assess the real benefit of PFO closure and its influence on quality of lif

Percutaneous closure of PFO in patients with reduced oxygen saturation at rest and during exercise : short- and long-term results

Background. A patent foramen ovale (PFO) is a rare cause of hypoxemia and clinical symptoms of dyspnea. Due to a right-to-left shunt, desaturated blood enters the systemic circulation in a subset of patients resulting in dyspnea and a subsequent reduction in quality of life (QoL). Percutaneous closure of PFO is the treatment of choice. Objectives. This retrospective multicentre study evaluates short- and long-term results of percutaneous closure of PFO in patients with dyspnea and/or reduced oxygen saturation. Methods. Patients with respiratory symptoms were selected from databases containing all patients percutaneously closed between January 2000 and September 2018. Improvement in dyspnea, oxygenation, and QoL was investigated using pre- and postprocedural lung function parameters and two postprocedural questionnaires (SF-36 and PFSDQ-M). Results. The average follow-up period was 36 [12-43] months, ranging from 0 months to 14 years. Percutaneous closure was successful in 15 of the 16 patients. All patients reported subjective improvement in dyspnea immediately after device deployment, consistent with their improvement in oxygen saturation (from 90 +/- 6% to 94 [92-97%] on room air and in upright position) (p<0.05). Both questionnaires also indicated an improvement of dyspnea and QoL after closure. The two early and two late deaths were unrelated to the procedure. Conclusion. PFO-related dyspnea and/or hypoxemia can be treated successfully with a percutaneous intervention with long-lasting benefits on oxygen saturation, dyspnea, and QoL

Effect of Catheter-Based Patent Foramen Ovale Closure on the Occurrence of Arterial Bubbles in Scuba Divers

ObjectivesThis study sought to evaluate the effect of catheter-based patent foramen ovale (PFO) closure on the occurrence of arterial bubbles after simulated dives.BackgroundPFO is a risk factor of decompression sickness in divers due to paradoxical embolization of bubbles. To date, the effectiveness of catheter-based PFO closure in the reduction of arterial bubbles has not been demonstrated.MethodsA total of 47 divers (age 35.4 ± 8.6 years, 81% men) with a PFO (PFO group) or treated with a catheter-based PFO closure (closure group) were enrolled in this case-controlled observational trial. All divers were examined after a simulated dive in a hyperbaric chamber: 34 divers (19 in the PFO group, 15 in the closure group) performed a dive to 18 m for 80 min, and 13 divers (8 in the PFO group, 5 in the closure group) performed a dive to 50 m for 20 min. Within 60 min after surfacing, the presence of venous and arterial bubbles was assessed by transthoracic echocardiography and transcranial color-coded sonography, respectively.ResultsAfter the 18-m dive, venous bubbles were detected in 74% of divers in the PFO group versus 80% in the closure group (p = 1.0), and arterial bubbles were detected in 32% versus 0%, respectively (p = 0.02). After the 50-m dive, venous bubbles were detected in 88% versus 100%, respectively (p = 1.0), and arterial bubbles were detected in 88% versus 0%, respectively (p < 0.01).ConclusionsNo difference was observed in the occurrence of venous bubbles between the PFO and closure groups, but the catheter-based PFO closure led to complete elimination of arterial bubbles after simulated dives. (Nitrogen Bubble Detection After Simulated Dives in Divers With PFO and After PFO Closure; NCT01854281

Early recurrent ischemic lesions in patients with cryptogenic stroke and patent foramen ovale: an observational study

Background: Randomized controlled trials indicate that patent foramen ovate (PFO) closure reduces risk of stroke recurrence in patients with cryptogenic stroke and PFO. However, the optimal time point for PFO closure is unknown and depends on the risk of stroke recurrence. Objective: We aimed to investigate risk of early new ischemic lesions on cerebral magnetic resonance imaging (MRI) in cryptogenic stroke patients with and without PFO. Methods: Cryptogenic stroke patients underwent serial MRI examinations within 1 week after symptom onset to detect early new ischemic lesions. Diffusion-weighted imaging (DWI) lesions were delineated, co-registered, and analyzed visually for new hyperintensities by raters blinded to clinical details. A PFO was classified as stroke-related in patients with PFO and a Risk of Paradoxical Embolism (RoPE) score >5 points. Results: Out of 80 cryptogenic stroke patients, risk of early recurrent DWI lesions was not significantly different in cryptogenic stroke patients with and without PFO. Similar results were observed in patients <= 60 years of age. Patients with a stroke-related PFO even had a significantly lower risk of early recurrent ischemic lesions compared to all other patients with cryptogenic stroke (unadjusted odds ratio 0.23 [95% confidence interval 0.06-0.87], P = 0.030). Conclusion: Our data argue against a high risk of early stroke recurrence in patients with cryptogenic stroke and PFO

What general practitioners need to know about patent foramen ovale

A patent foramen ovale (PFO) consists of a hole between the right and left atriums of the heart that did not close the way it should after birth. Twenty five percent of the population have a PFO, but this usually does not cause problems, because the opening is functionally closed by the difference in pressure between the heart and the chest. This study is a literature review about the clinical significance of PFO and its management in three clinical situations: cryptogenic strokes, migraine with aura and scuba divers who sustained a decompression sickness. PFOs had been linked with various medical conditions such as strokes, migraine, and with certain types of decompression sickness (DCS). In general, this association is not very well established. Young patients who sustain a cardiovascular event without a known cause (cryptogenic stroke) have resulted in the tendency to screen these patents becoming the norm and more PFOs are being closed using standard methods and devices. The association of PFOs and migraine attacks is less clear. In the case of scuba divers the risk of suffering from a decompression accident is increased if one has a PFO. The management of these patients remains difficult.peer-reviewe

Migraine and patent foramen ovale: exploring the association and a possible treatment option

Migraine is a very common type of headache. With a prevalence of 10-12%, migraine ranks 19th among diseases causing worldwide morbidity. Number of studies have shown a high prevalence of patent foramen ovale (PFO) in patients with migraine, especially migraine with aura. The right to left shunting of blood in a PFO could serve as a conduit for chemicals that would exert a trigger effect on hyper excitable neurons leading to the development of migraine. Furthermore patients with PFO and migraine also show a marked improvement in their symptoms after percutaneous closure of the PFO. This review is a close look at this association and also explores whether subsequent closure of the shunt can be looked upon as a viable treatment option

Patent foramen ovale and neurosurgery in sitting position: a systematic review

We have conducted a systematic review of air embolism complications of neurosurgery in the sitting position and patent foramen ovale (PFO) closure. It assesses the risk and benefit of PFO closure before neurosurgery in the sitting position. The databases Medline, Embase, and Cochrane Controlled Trial Register were systematically searched from inception to November 2007 for keywords in both topics separately. In total, 4806 patients were considered for neurosurgery in sitting position and 5416 patients underwent percutaneous PFO closure. The overall rate of venous air embolism during neurosurgery in sitting position was 39% for posterior fossa surgery and 12% for cervical surgery. The rate of clinical and transoesophageal echocardiography detected paradoxical air embolism was reported between 0% and 14%. The overall success rate for PFO closure using new and the most common closure devices was reported 99%, whereas the average risk of major complications is <1%. On the basis of our systematic review, we recommend screening for PFO and considering closure in cases in which the sitting position is the preferred neurosurgical approach. Our proposed management including the time of PFO closure according to available data is presented. However, the conclusions from our systematic review may be limited due to the lack of level A evidence and from using data from observational cohort studies. Thus, definite evidence-based recommendations require prospective evaluation of the issue in well-designed studie

Patent Foramen Ovale, Ischemic Stroke and Migraine: Systematic Review and Stratified Meta-Analysis of Association Studies

BACKGROUND: Observational data have reported associations between patent foramen ovale (PFO), cryptogenic stroke and migraine. However, randomized trials of PFO closure do not demonstrate a clear benefit either because the underlying association is weaker than previously suggested or because the trials were underpowered. In order to resolve the apparent discrepancy between observational data and randomized trials, we investigated associations between (1) migraine and ischemic stroke, (2) PFO and ischemic stroke, and (3) PFO and migraine. METHODS: Eligibility criteria were consistent; including all studies with specifically defined exposures and outcomes unrestricted by language. We focused on studies at lowest risk of bias by stratifying analyses based on methodological design and quantified associations using fixed-effects meta-analysis models. RESULTS: We included 37 studies of 7,686 identified. Compared to reports in the literature as a whole, studies with population-based comparators showed weaker associations between migraine with aura and cryptogenic ischemic stroke in younger women (OR 1.4; 95% CI 0.9–2.0; 1 study), PFO and ischemic stroke (HR 1.6; 95 CI 1.0–2.5; 2 studies; OR 1.3; 95% CI 0.9–1.9; 3 studies), or PFO and migraine (OR 1.0; 95% CI 0.6–1.6; 1 study). It was not possible to look for interactions or effect modifiers. These results are limited by sources of bias within individual studies. CONCLUSIONS: The overall pairwise associations between PFO, cryptogenic ischemic stroke and migraine do not strongly suggest a causal role for PFO. Ongoing randomized trials of PFO closure may need larger numbers of participants to detect an overall beneficial effect

Percutaneous Closure of Patent Foramen Ovale for the Treatment of Refractory Migraine Headaches

Background: Migraine headaches both with and without aura vary in frequency, duration and intensity, affecting the quality of life of up to 10% of the total population. Migraines are treated with both prophylactic and acute medications. Patent foramen ovale (PFO) is one likely cause of migraine headaches and this is present in up to 25% of the total population. Percutaneous PFO closure is a likely option for definitive treatment for migraine. Once proven refractory to medical treatment, do patients with PFO and migraine respond to percutaneous PFO closure to reduce the frequency, duration and intensity of migraine headaches? Methods: An exhaustive search of available medical literature was conducted using Medline/Ovid, CINAHL and Evidence-Based Medicine Reviews Multifile using the keywords: patent foramen ovale, migraine disorders, therapeutics and refractory. Inclusion criteria consisted of participants with a known patent foramen ovale and migraine headaches refractory to medical treatment, as well as studies performing percutaneous PFO closure measuring cessation or reduction in frequency, duration and intensity of migraine headaches. All articles were assessed for quality using GRADE. Results: One randomized controlled trial, three prospective observational studies and one retrospective observational study fit the inclusion criteria. All observational studies demonstrated resolution of migraine with aura along with improved migraine symptomology in MIDAS score, frequency, duration and intensity of migraines. However the only randomized controlled trial (RCT) to date demonstrated no resolution of migraine headaches after six months. No other endpoints were measured such as frequency, duration or intensity. Many complications, both minor and serious, resulted in this RCT. After GRADE assessment, the RCT was determined to be high validity and all observational studies very low validity. Conclusion: Four observational studies show some benefit to percutaneous PFO closure as treatment for refractory migraine headaches. However, one randomized controlled trial shows no benefit, unable to meet its endpoints. At this time, a recommendation cannot be made for percutaneous PFO closure in patients with refractory migraine headaches until further RCTs are performed and improvements are made in future studies