Despite the diffusion into practice of percutaneous closure of a patent foramen ovale (PFO) in patients with cryptogenic stroke (CS), the benefits have not been demonstrated, and remain unclear. For any individual presenting with a PFO in the setting of CS, it is not clear whether the PFO is pathogenically-related to the index event or an incidental finding. Further, the overall rate of stroke recurrence is low in patients with CS and PFO. How patient-specific factors affect the likelihood that a discovered PFO is related to an index stroke or affect the risk of recurrence is not well understood. These probabilities are likely to be important determinants of the benefits of PFO closure in CS.
The goal of the Risk of Paradoxical Embolism (RoPE) Study is to develop and test a set of predictive models that can identify those patients most likely to benefit from preventive treatments for PFO-related stroke recurrence, such as PFO closure. To do this, we will construct a database of patients with CS, both with and without PFO, by combining existing cohort studies. We will use this pooled database to identify patient characteristics associated with the presence (versus the absence) of a PFO, and to use this "PFO propensity" to estimate the patient-specific probability that a PFO was pathogenically related to the index stroke (Model #1). We will also develop, among patients with both a CS and a PFO, a predictive model to estimate patient-specific stroke recurrence risk based on clinical, radiographic and echocardiographic characteristics. (Model #2). We will then combine Models #1 and #2 into a composite index that can rank patients with CS and PFO by their conditional probability that their PFO was pathogenically related to the index stroke and the risk of stroke recurrence. Finally, we will apply this composite index to completed clinical trials (currently on-going) testing endovascular PFO closure against medical therapy, to stratify patients from low-expected-benefit to high-expected-benefit.
Patent foramen ovale (PFO) has been implicated as a risk factor for cryptogenic ischemic stroke (CS). However, there is still a lack of widely accepted, undisputed indications for PFO closure. The present study describes the concept of the multidisciplinary PFO conference and a decision making process for closure versus no closure that was developed into a formalized clinical algorithm, and presents the results of implementing these, in terms of number and proportion of PFO closures as well as repeat referrals.
Five specialists in neurology, cardiology, internal medicine, thromboembolism, and echocardiography evaluated the clinical data of 311 patients at PFO conferences during 2006 to 2009. The main criteria for closure were patients with first-ever CS with PFO and atrial septal aneurysm, or patients with recurrent CS and PFO without atrial septal aneurysm.
A total of 143 patients (46%) were accepted for closure and 167 patients were rejected. Patients accepted for closure were younger (mean 50 years versus 58 years) (P < 0.001). The acceptance rate for PFO closure was similar throughout these years, with an average of 45%. Three of 167 patients (1.8%) initially rejected for PFO closure were re-referred due to recurrent stroke, and the PFO closure was subsequently performed.
The acceptance rate of less than 50% in the present study underscores the complex relationship between CS and PFO. Whatever the criteria used for PFO closure, any unit caring for these patients needs to have a rigorous process to avoid overtreatment as well as undertreatment and to ensure that personal preferences and economic incentives do not steer the selection process. Our algorithm provides a stable acceptance rate and a low rate of repeat referrals.
patent foramen ovale; cryptogenic stroke; clinical algorithm; patent foramen ovale closure
There is an association between cryptogenic stroke and patent foramen ovale (PFO). The optimal treatment strategy for secondary prevention remains unclear. The purpose of this study was to analyze aggregate data examining the safety and efficacy of transcatheter device closure versus standard medical therapy in patients with PFO and cryptogenic stroke.
A search of published data identified 3 randomized clinical trials for inclusion. The primary outcome was a composite end-point of death, stroke and transient-ischemic attack (TIA). Pre-defined subgroup analysis was performed with respect to baseline characteristics including age, sex, atrial septal aneurysm and shunt size. Data was synthesized using a random effects model and results presented as hazard ratios (HRs) with 95% confidence intervals (CIs).
A cohort of 2,303 patients with a history of cryptogenic stroke and PFO were randomized to device closure (n = 1150) and medical therapy (n = 1153). Mean follow-up was 2.5 years. Transcatheter closure was not superior to medical therapy in the secondary prevention of stroke or TIA in intention-to-treat analysis (HR: 0.66, 95% CI: 0.43 to 1.01; p = 0.056). However, the results were statistically significant using per-protocol analysis (HR: 0.64, 95% CI: 0.41 to 0.98; p = 0.043). Males had significant benefit with device closure (HR: 0.48, 95% CI: 0.24 to 0.96; p = 0.038).
In this meta-analysis, using intention-to-treat analysis, transcatheter device closure of PFO was not superior to standard medical therapy in the secondary prevention of cryptogenic stroke. Transcatheter closure was superior using per-protocol analysis.
Patent foramen ovale; Inter atrial shunt; Transcatheter closure; Cryptogenic stroke
Recent studies support the hypothesis of a close aetiological and pathogenic association between the presence of patent foramen ovale (PFO) and cryptogenic stroke. The therapeutic options currently used in the treatment of these patients range from standard antiaggregation and standard-dose anticoagulation to the percutaneous occlusion of the PFO. The use or recommendation of treatment is based both on clinical risk factors associated with PFO, such as age, detection of states of hypercoagulability and previous history of stroke, and on the risks associated to right-to-left shunt (RLSh) and PFO, such as the size of PFO, magnitude of RLSh and the presence of atrial septal aneurysm (ASA). However, there is currently no consensus regarding the most suitable treatment and it is surprising to observe the widespread use of certain therapeutic approaches which are not supported by clinical evidence.
In this revision, we analyse the relevance of PFO in cryptogenic stroke, consider the main evidence available for determining the best management of these patients and make diagnostic and therapeutic management recommendations.
Patent foramen ovale; right-to-left shunt; cryptogenic stroke; transcranial Doppler; echocardiography.
Several studies have shown an association of cryptogenic stroke and embolism with patent foramen ovale (PFO), but the question how to prevent further events in such patients is unresolved. Options include antithrombotic treatment with warfarin or antiplatelet agents or surgical or endovascular closure of the PFO. The PC-Trial was set up to compare endovascular closure and best medical treatment for prevention of recurrent events.
The PC-Trial is a randomized clinical trial comparing the efficacy of percutaneous closure of the PFO using the Amplatzer PFO occluder with best medical treatment in patients with cryptogenic embolism, i.e. mostly cryptogenic stroke. Warfarin for 6 months followed by antiplatelet agents is recommended as medical treatment. Randomization is stratified according to patients age (<45 versus ≥45 years), presence of atrial septal aneurysm (ASA yes or no) and number of embolic events before randomization (one versus more than one event). Primary endpoints are death, nonfatal stroke and peripheral embolism.
patients were randomized in 29 centers of Europe, Canada, and Australia. Randomization started February 2000. Enrollment of 414 patients was completed in February 2009. All patients will be followed-up longitudinally. Follow-up is maintained until the last enrolled patient is beyond 2.5 years of follow-up (expected in 2011).
Trial listed in ClinicalTrials.gov as NCT00166257 and sponsored by AGA Medical, Plymouth, MN, USA
Patent foramen ovale (PFO) is associated with clinical conditions including cryptogenic stroke, migraine and varicose veins. Data from studies in humans and mouse suggest that PFO and the secundum form of atrial septal defect (ASDII) exist in an anatomical continuum of septal dysmorphogenesis with a common genetic basis. Mutations in multiple members of the evolutionarily conserved cardiac transcription factor network, including GATA4, cause or predispose to ASDII and PFO. Here, we assessed whether the most prevalent variant of the GATA4 gene, S377G, was significantly associated with PFO or ASD. Our analysis of world indigenous populations showed that GATA4 S377G was largely Caucasian-specific, and so subjects were restricted to those of Caucasian descent. To select for patients with larger PFO, we limited our analysis to those with cryptogenic stroke in which PFO was a subsequent finding. In an initial study of Australian subjects, we observed a weak association between GATA4 S377G and PFO/Stroke relative to Caucasian controls in whom ASD and PFO had been excluded (OR = 2.16; p = 0.02). However, in a follow up study of German Caucasians no association was found with either PFO or ASD. Analysis of combined Australian and German data confirmed the lack of a significant association. Thus, the common GATA4 variant S377G is likely to be relatively benign in terms of its participation in CHD and PFO/Stroke.
Stroke is a leading cause of death and long-term disability worldwide. Although a minority of ischemic strokes in the community affect younger adults, up to 40% of acute ischemic strokes in young adults are cryptogenic in nature, that is, no cause is determined. Underlying pathologies of stroke of unknown cause are multiple, including patent foramen ovale (PFO). The PFO is the most common defect of atrial septum of the heart. This study evaluated the frequency of PFO in brain stroke with unknown etiology in patients younger than 50 years of age in Kerman.
This cross-sectional study was done in Shafa Medical Center of Kerman University of Medical Sciences in 2008. For detection of the PFO, we used agitated saline test with transcranial Doppler sonography in brain stroke patients with unknown etiology and also a control group (normal persons).
PFO was found in 53% of patients. No significant difference was observed between sexes. The rate in the control group was 20%. Patients with large PFO had 2 or more attacks of stroke. Subjects in the control group did not have large PFO.
One of the most important underlying causes in young adults with cryptogenic stroke is PFO. It is better to prescribe antiplatelet drugs in patients with the first attack of stroke, but as for patients with recurrent stroke, closure of PFO must be considered.
Stroke; Young Adults; Patent Foramen Ovale; Agitated Normal Saline Test.
Treatment of patients with concomitant patent foramen ovale (PFO) and atrial septal aneurysm (ASA) poses a number of challenges; while some authors have suggested the off-label use of the Amplatzer Cribriform Occluder in such anatomy, the long-term outcomes of this strategy is unknown. Our study aimed to assess the long-term impact on closure rate, left atrial functional remodelling, and clinical outcomes of off-label implantation of Amplatzer ASD Cribriform Occluder in patients with PFO and ASA.
We prospectively enrolled 160 consecutive patients with previous stroke (mean age 36 ± 9.5 years, 109 females), significant PFO and ASA. All patients were treated with Amplatzer Cribriform Occluder to ensure the most complete possible coverage of the ASA. Residual shunt and LA passive and active emptying, LA conduit function, and LA ejection fraction were computed before and after 6 months from the procedure and then yearly. All patients underwent successful transcatheter closure (mean ratio device/diameter of interatrial septum = 0.74).
Incomplete ASA coverage during intraprocedural intracardiac echocardiography was observed in 71 patients. During mean follow-up of 3.6 ± 1.8 years, when compared to patients with complete coverage, there were no differences in LA functional parameters and complete occlusion achieved in 150/160 patients (93.7%). No new cerebral ischemic events, aortic erosions or device thrombosis were recorded during the follow-up.
The use of the Amplatzer ASD Cribriform to treat PFO and associated ASA seems safe and effective: relatively small Occluder devices are probably effective enough to promote left atrial functional remodelling.
Patent foramen ovale; stroke; embolism; cardiac anatomy; echocardiography
While the prevalence of patent foramena ovale (PFOs) in the general population is around 25%, it is approximately doubled among cryptogenic stroke (CS) patients. This has generally been attributed to paradoxical embolism and many physicians recommend PFO closure to prevent recurrence. However, the benefit of PFO closure in patients with stroke has not been demonstrated. Further, the epidemiology of stroke recurrence in patients with CS with PFO versus without PFO, and in those with large right-to-left shunts versus small right-to-left shunts, has yielded results that appear difficult to reconcile with the hypothesis that paradoxical embolism is an important cause of stroke recurrence. The purpose of this review is to critically examine the epidemiological evidence that PFO is a potentially modifiable risk factor for stroke recurrence in patients with cryptogenic stroke. The evidence suggests that many patients with CS and PFO have strokes that are PFO-attributable, but that many have strokes that are unrelated to their PFO.. We introduce the concept of “PFO-propensity”, defined as the patient-specific probability of finding a PFO in a patient with cryptogenic stroke based on their age and other risk factors. We show that this value is directly related to the probability that a CS is PFO-attributable. Because there is substantial heterogeneity both in PFO-propensity and in recurrence risk among patients with PFO and cryptogenic stroke, stratification for closure by these joint probabilities will likely prove crucial for appropriate patient selection.
Patent foramen ovale; Risk factors for stroke; Secondary stroke prevention; Cryptogenic Stroke
Transcatheter patent foramen ovale (PFO) closure is an alternative to antiplatelet or anticoagulative therapy in patients with cryptogenic stroke, and it is associated with a small incidence of periprocedural sequelae. Because embolization of PFO closure devices is a very rare procedural complication, data on its frequency, causes, and management are sparse. We sought to review the medical literature and the cases of PFO closure-device embolization at our institution with the aim of identifying likely problems and reporting potential solutions. Out of 310 adult patients who underwent transcatheter PFO closure from June 2002 through April 2011, there were 2 cases (0.6%) of PFO closure-device embolization. In both patients, hypermobile septum primum and thick septum secundum were present. In one patient, failure to use a sizing balloon might have resulted in an underestimation of the PFO's size. In both patients, device embolization was identified in a timely fashion, the embolized device was safely retrieved, and the PFO was percutaneously closed with success.
The incidence of PFO closure-device embolization is very low. The cases described here underscore the importance of imaging in the identification of morphologic predispositions to closure-device malpositioning, in the recognition of impending embolization, and in the timely management of embolization.
Contrast media/diagnostic use; device removal/methods; echocardiography, transesophageal; fluoroscopy; foramen ovale, patent/radiography/therapy/ultrasonography; foreign body migration; ischemic attack, transient/prevention & control; prosthesis implantation/adverse effects; septal occluder device/adverse effects; stroke/prevention & control
Up to 40% of acute ischaemic strokes in young adults are cryptogenic in nature, that is, no cause is determined. In more than half of these patients, patent foramen ovale (PFO) is seen along with an increased incidence of atrial septal aneurysm. The commonest method of investigation is echocardiography (preferably transoesophageal echocardiography). On the basis of available evidence, low risk patients are treated with antiplatelet agents and high risk patients with warfarin. There are inconclusive data on the efficacy of PFO closure to prevent stroke recurrence. However, if there is recurrent stroke or intolerance to medical therapy, percutaneous closure is carried out.
atrial septal defect; cryptogenic stroke; patent foramen ovale
Association of atrial septal aneurysm (ASA) with patent foramen ovale (PFO) is considered an important risk factor for cardioembolism frequently forwarding paradoxical embolism in patients with cryptogenic or unexplained cerebral ischemic events. We herein describe the case of a 69-year-old male patient reporting uncontrolled movements of the right arm due to a muscle weakness, slurred speech, and paresthesia in the oral region some seconds after he had blown his nose. These neurological symptoms had improved dramatically within a few minutes and were completely regressive at admission to our hospital about two hours later. On transesophageal echocardiography (TEE) a huge ASA associated with PFO was detected. Diagnosis of the large-sized ASA was also confirmed by cardiac magnetic resonance imaging. Due to the early complete recovery from his neurological symptoms, the patient was diagnosed with a transient ischemic attack (TIA). After nine days he was discharged in a good clinical condition under the treatment with oral anticoagulation. It is concluded that in cryptogenic or unexplained stroke or TIA TEE should always be performed to rule out ASA and PFO as potential sources for paradoxical embolism in those inconclusive clinical situations.
congenital cardiac abnormality; atrial septal aneurysm; nose blowing; paradoxical embolism; patent foramen ovale; transient ischemic attack
Although individuals with sickle cell disease (SCD) are at increased risk for stroke, the underlying pathophysiology is incompletely understood. Intracardiac shunting via a patent foramen ovale (PFO) is associated with cryptogenic stroke in individuals without SCD. Recent evidence suggests that PFOs are associated with stroke in children with SCD, although the role of PFOs in adults with stroke and SCD is unknown. Here, we report 2 young adults with SCD, stroke, and PFOs. The first patient had hemoglobin SC and presented with a transient ischemic attack and a subsequent ischemic stroke. There was no evidence of cerebral vascular disease on imaging studies and the PFO was closed. The second patient had hemoglobin SS and two acute ischemic strokes. She had cerebral vascular disease with moyamoya in addition to a peripheral deep venous thrombosis (DVT). Chronic transfusion therapy was recommended, and the DVT was managed with warfarin. The PFO was not closed, and the patients' neurologic symptoms were stabilized. We review the literature on PFOs and stroke in SCD. Our cases and the literature review illustrate the dire need for further research to evaluate PFO as a potential risk factor for stroke in adults with SCD.
Background and Objectives
Patent foramen ovale (PFO) has been implicated in the pathogenesis of cryptogenic stroke or transient ischemic attack (TIA) due to paradoxical embolism, and in the pathogenesis of migraine. This paper reports the intermediate and long-term results of transcatheter closure of PFO associated with cerebrovascular accidents (CVAs), TIAs and migraine, using the Amplatzer PFO occluder. This paper also reports a case of pulmonary embolism which developed in one patient after PFO closure.
Subjects and Methods
From January 2003 to May 2010, 16 patients with PFO (seven males and nine females) with a history of at least one episode of cryptogenic stroke/TIA, CVA, or migraine and who underwent percutaneous transcatheter closure of PFO using the Amplatzer occluder. All the procedures were performed under general anesthesia and were assisted by transesophageal echocardiography.
The device was implanted without any significant complications in all the patients, and the PFOs were effectively closed. At an average follow-up period of 54 months, the 15 patients with TIA/CVA had no recurrence of any thromboembolic event. The symptoms in one patient with migraine subsided after occlusion of the PFO. In this study, pulmonary embolism occurred five months after PFO closure in one patient, but the cause of pulmonary embolism was not identified. However, it is believed that the pulmonary embolism occurred without stroke recurrence because occlusion of the PFO was performed when the patient had a stroke event.
It can be concluded that according to the intermediate and long-term follow-up results, transcatheter PFO closure is an effective and safe therapeutic modality in the prevention of thromboembolic events, especially in the patients with cryptogenic stroke/TIA, and PFO closure is helpful in the treatment of migraine. However, this study involved a small number of patients and also the follow-up period was not long enough. Hence, randomized, controlled trials are necessary to determine if this approach is preferable to medical therapy for the prevention of recurrent stroke or as primary treatment for patients with migraine headache.
Patent foramen ovale; Stroke; Transient ischemic attack; Migraine; Pulmonary embolism
Patent foramen ovale (PFO) percutaneous closure has previously been an accepted intervention for the prevention of recurrent cryptogenic stroke on the basis of observational studies. However, randomized trials have been lacking until now. Three recently published randomized trials (CLOSURE I, PC and RESPECT) do not demonstrate the superiority of this intervention versus optimal medical therapy, therefore making this practice questionable. Nonetheless, these trials have had certain pitfalls, mainly a lower than initially estimated number of patients recruited, therefore lacking sufficient statistical power. On the other hand, different closure devices were used in the three trials. In two of them (PC and RESPECT), the Amplatzer PFO Occluder was used and the STARflex device was used in the other one (CLOSURE I). Taken altogether, a meta-analysis of these three trials does not demonstrate a statistically significant benefit of percutaneous PFO closure (1.9% vs 2.9%; P = 0.11). However, if we analyze only the PC and RESPECT trials together, in which the Amplatzer PFO Occluder was used, a statistically significant benefit of percutaneous PFO closure is observed (1.4% vs 3.0%, P = 0.04). In conclusion, our interpretation of these trials is that the use of a dedicated, specifically designed Amplatzer PFO device could possibly reduce the risk of stroke in patients with PFO and cryptogenic stroke. This consideration equally applies to patients who have no contraindications for anticoagulant or antithrombotic therapy.
Patent; Foramen; Ovale; Closure; Percutaneous; Device; Cryptogenic; Stroke; Risk
Percutaneous patent foramen ovale (PFO) closure seems to reduce the risk of recurrent thromboembolism. We report the safety and efficacy of percutaneous PFO closure in our centre.
All patients, >16 years of age, who underwent a percutaneous PFO closure in our centre were included. Reoccurrence of stroke, transient ischaemic attack (TIA) and peripheral thromboembolism were assessed. Periprocedural and midterm complications are reported.
Eighty-three consecutive patients (mean age 49±13 years) were included. Indications for PFO closure were cryptogenic stroke (59.0%), TIA (33.7%), peripheral embolism (2.4%) and other (4.8%). For PFO closure, a Cardioseal/Starflex device was used in 63 patients and an Amplatzer PFO occluder device in 20 patients. Stroke recurred in 1.2%, TIA in 3.6%, peripheral embolism in 0% during a mean follow-up of 1.9±1.2 years. Major periprocedural complications occurred in 1.2%. The mid-term complication rate was 2.4% and only consisted of minor complications. During follow-up, a residual right-to-left shunt was present in 5.7% of the patients. No significant difference in outcome, complications or residual shunting could be documented between the two device types.
In our centre, the percutaneous closure of a PFO seems to be a safe and effective procedure to prevent recurrence of paradoxical thrombo-embolic events. (Neth Heart J 2008;16:332-6.)
patent foramen ovale; percutaneous closure; cryptogenic stroke; safety
Percutaneous transcatheter closure of patent foramen ovale (PFO) in cryptogenic stroke is an alternative to medical therapy. There is still debate on different outcome for each currently available device. The impact of residual shunting after PFO-clo- sure on recurrent arterial embolism is unknown.
(i) To evaluate the prevalence of residual interatrial shunting after device- closure of PFO, (ii) to identify risk factors predicting residual interatrial shunting after device implantation, and (iii) to investigate the outcome of patients after PFO-closure during long- term follow- up (FU).
Methods and results
Between 2000- 2005 PFO-closure was performed in 124 patients using four different devices: Amplatzer PFO-(n = 52), CardioSeal (n = 33), Helex (n = 23) and Premere (n = 16) occluder. All patients underwent serial contrast-enhanced transesophageal echocardiography (TEE) for 24 months after PFO- closure; clinical FU was at minimum 5 years up to 9.75 years (mean 6.67 ± 1.31 years). Overall-closure rate was 87% at 2 years, device-specific closure time curves differed significantly (p-logrank = 0.003). Independent risk factors for residual-shunting were implantation of a Helex occluder (hazard ratio [HR] 12.6, 95% confidence interval [CI] 2.6- 57.4, p = 0.002), PFO- canal- lengths (HR 1.2, 95%CI 1.1- 1.3, p = 0.004) and extend of atrial-septal-aneurysm (HR 1.1, 95%CI 0.9- 1.3; p = 0.05). 4 (3.2%) arterial embolic events occurred during a FU-period of 817.2 patient-years, actuarial annual thromboembolic-risk was 0.49%. All ischemic events were not related to residual PFO-shunting or device-related thrombus- formation.
Success rates of PFO- closure are mainly dependent on occluder-type, extend of concomitant atrial-septum-aneurysm and PFO-canal- length. Importantly, residual shunting after PFO-closure was not associated with recurrence of arterial embolism during long-term follow-up.
Purpose. We investigated stroke recurrence in patients with acute ischemic stroke of undetermined aetiology, with or without a patent foramen ovale (PFO). Methods. Consecutive stroke patients underwent to Transcranial Doppler and Transesophageal Echocardiography for PFO detection. Secondary stroke prevention was based on current guidelines. Results. PFO was detected in 57/129 (44%) patients. The rate of recurrent stroke did not significantly differ between patients with and without a PFO: 0.0% versus 1.4% (1 week), 1.7% versus 2.7% (1 month), and 3.5% versus 4.2% (3 months), respectively. The 2-year rates were 10.4% (5/48) in medically treated PFO and 8.3% (6/72) in PFO-negative patients (P = 0.65), with a relative risk of 1.25. No recurrent events occurred in 9 patients treated with percutaneous closure of PFO. Conclusion. PFO was not associated with increased rate of recurrent stroke. Age-related factors associated with stroke recurrence in cryptogenic stroke should be taken into account when patients older than 55 years are included in PFO studies.
Objectives. The aim was to estimate the recurrence rate and to define subgroups at increased risk for recurrent cerebral ischaemia in patients with patent foramen ovale (PFO) and so called cryptogenic stroke due to paradoxical embolism.
Methods. Patent foramen ovale was diagnosed in 318 patients with otherwise unexplained ischaemic stroke or transient ischaemic attack (TIA). One hundred and fifty nine were treated medically (oral anticoagulation 79, platelet inhibitors 80) and represent the study population. The remaining 159 patients underwent endovascular or surgical closure of the PFO and are not part of this study.
Results. Mean age was 50.7 (SD 13.5) years. The event leading to the diagnosis of PFO was a TIA in 38 patients (23.9%), an ischaemic stroke in 119 (74.8%), and an amaurosis fugax in two patients (1.3%). Forty four patients (27.7%) had experienced multiple cerebrovascular ischaemic events before the diagnosis of the PFO. During mean follow up of 29 (SD 23) months 21 patients (13.4%) had a recurrent cerebrovascular event (seven strokes and 14 TIAs). The average annual rate of recurrent strokes was 1.8% and that of recurrent strokes or TIAs was 5.5%. When patients with PFO with multiple cerebrovascular events before the diagnosis of the PFO were analyzed separately, the average annual rates of recurrent cerebral ischaemia were 3.6% for recurrent strokes and 9.9% for recurrent strokes or TIAs. These rates were significantly higher than in patients with first ever stroke or TIA (p=0.02).
Conclusions. The study confirms a risk of stroke recurrence that is similar to the rates of previously published series of patients with PFO and cryptogenic strokes. Patients with more than one previous event were at increased risk of recurrent cerebral ischaemia.
Secundum Atrial septal defect (ASD) and Patent foramen ovale (PFO) is becoming the most popular field of interest for catheter-based interventions. While there is a common agreement about the management of ASD patients, there is no complete agreement on which is the best management of PFO patients. In PFO patients, the real challenge for the clinician, beside secondary prevention of recurrent stroke, is to understand which the higher risk patients to refer for treatment are and which is the proper device to use. In this setting, the anatomo-functional characterization of interatrial septum seems to be of paramount importance for both ASD and PFO, not only for the device selection but also for therapeutic decision-making. In the present review the author overviews the main anatomic a functional characteristics of interatrial septum, obtained with the current available diagnostic tools, such as transcranial Doppler, transthoracic and transesophageal echocardiography and intracardiac echocardiography, and discusses the impact of such characteristics on catheter based closure.
Secundum Atrial septal defect (ASD); Patent foramen ovale (PFO); catheter-based interventions; anatomo-functional characterization
A patent foramen ovale (PFO) is strongly associated with cryptogenic stroke (CS), neurological and other phenomena. The reported prevalence of PFO varies according to the imaging technique used and population studied.
To measure prospectively, the prevalence of PFO in a cohort of consecutive patients attending for routine “coronary” CT angiography using standard, everyday coronary protocols including low-dose prospective ECG gated studies.
Standard coronary imaging protocols were used. PFOs were graded according to the classification of Williamson et al.1
261 patients were studied. A PFO was identified in 22.6% (11.5% grade 1 (closed flap), 6.5% grade 2 (open flap) and 4.6% grade 3 (open flap with jet)). A further 6.1% had an atrial septal aneurysm.
The prevalence of all grades of PFO (22.6%) and open flap PFO (11.1% = grade 2 and 3) with this technique compares with 24.3% by trans-oesophageal echocardiography (TOE) and 14.9% by saline contrast echocardiography (SCE)2, 3 Further comparative studies are required but we believe an open flap PFO or ASA should be identified and recorded during cardiac CT. This approach may identify those at risk of cryptogenic stroke as well as avoid unnecessary tests in stroke patients.
Patent foramen ovale; atrial septum; cardiac anatomy; computed tomographic angiography; non-invasive angiography
(1) Estimate risk of recurrent stroke/TIA/death in the subgroup of the Patent foramen ovale in the Cryptogenic Stroke Study (PICSS) cohort with patent foramen ovale (PFO) and antiphospholipid antibodies (aPL) and (2) Estimate risk of recurrent stroke/TIA/death in aPL positive patients who have thickened left-sided heart valves (VaT).
PFO is associated with cryptogenic ischemic stroke. Also, the presence of aPL is associated with ischemic cerebrovascular disease.
Combined data from 2 major sub studies of the Warfarin Aspirin Recurrent Stroke Trial (WARSS) were evaluated. PICSS subjects were included if they were enrolled in the Antiphospholipid Antibodies and Stroke Study (APASS) and had a baseline aPL test (lupus anticoagulant, anticardiolipin antibodies, or both) within one month of the stroke. All patients in PICSS underwent transesophageal echocardiography for PFO as well as VaT, which was performed blinded to aPL status and treatment arm (325mg/d aspirin or adjusted dose warfarin, target INR 1.4–2.8). The primary outcome event was the 2-year risk of recurrent stroke/TIA/death and was evaluated using Cox proportional hazards model. As there was no treatment effect, warfarin and aspirin groups were combined to increase power. For the combined endpoint, power to detect a HR of 2 was 47.8% for the PFO and aPL positive group, and 75.3% for the valve thickening and aPL positive group, assuming two-sided type I error of 0.05
525 subjects were tested for the combined presence of PFO and aPL and were available for evaluation. The primary outcome event rate was 23.9% (HR 1.39, 95% CI 0.75–2.59) in the PFO positive/aPL positive group, compared to 13.9% (HR 0.83, 95% CI 0.44–1.56) in the PFO positive/aPL negative group and 19.9% (HR 1.16 95% CI 0.68–1.90) in the PFO negative/aPL positive group.
545 subjects tested for combined presence of aPL and left sided cardiac VaT were available for evaluation. The primary event rate was 22.6% (HR1.65, 95% CI 0.88–3.09) in the VaT positive/aPL positive group, compared to 19.4% (HR 1.50, 95% CI 0.82–2.75) in the VaT positive/aPL negative group and 20.2% (HR 1.63, 95% CI 0.81–3.25) in the VaT negative /aPL positive group.
The combined presence of aPL with either a PFO or with left sided cardiac VaT did not significantly increase risk of subsequent cerebrovascular events in this PICCS/APASS cohort of patients.
patent foramen ovale; anti-phospholipid antibodies; cardiac valve thickening; stroke recurrence risk; stroke risk factors; Risk Factors
Up to 40% of ischemic strokes have no known cause (cryptogenic). The prevalence of persistent foramen ovale (PFO) amongst patients with cryptogenic stroke (CS) is twice as high as that of the normal population, therefore suggesting a causal relationship between the two entities. However, PFO by itself is not sufficient to cause stroke, as an embolic source is needed. This source is often unknown, making the causal relationship between CS and PFO hard to demonstrate. The most frequent, although still seldom, identifiable cause of embolism in an otherwise cryptogenic stroke associated with PFO is a deep venous thrombosis (DVT) of the lower extremities. Here, we present a unique case of brachiocephalic venous DVT associated with PFO and ischemic stroke in a young patient. As the search for DVT in patients with PFO and stroke is often limited to the lower extremities, this case may suggest that an unspecified number of DVTs are overlooked. Our report lends support to paradoxical embolism as a mechanism of stroke in patients with PFO and does, at least in selected cases, suggest a more detailed search for DVT beyond the lower extremities.
Deep venous thrombosis; Persistent foramen ovale; Cryptogenic stroke; Ischemic stroke
Platelets play a major role in thromboembolic events. Increased mean platelet volume (MPV) indicates higher platelet reactivity and also a tendency to thrombosis. Patent foramen ovale (PFO), persistence of the fetal anatomic shunt between right and left atria, is strongly associated with cryptogenic stroke. The aim of this study is to determine the relationship between MPV and PFO and if such an association exists, whether higher MPV levels may require antiplatelet therapy before a thromboembolic event happens, together with a literature review.
Material and methods
Thirty patients (15 women, 15 men), free of any cerebrovascular events, were diagnosed with PFO by transesophageal echocardiography (TEE), enrolled as the study group. Thirty consecutive patients (16 women and 14 men), who were diagnosed as normal in TEE, were enrolled as the control group. These two groups were compared according to MPV and anatomical features of the right atrium.
There was no significant difference between study and control groups in clinical features and also no difference was observed in platelet counts; however, MPV in the PFO group was significantly higher than the control group (8.38 ±0.93 fl and 7.45 ±0.68 fl respectively).
Our results indicate that elevated MPV may be detected in patients with PFO. This might be one of the explanations for the relationship between PFO and cryptogenic stroke; however, larger cohorts are warranted in order to define further mechanisms.
echocardiography; mean platelet volume; patent foramen ovale; stroke
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.
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.
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.
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.
Systematic review; Meta-analysis; Patent foramen ovale; Cryptogenic stroke; Migraine