Foramen Ovale Research Articles

Covert Cerebrovascular Changes in People With Heart Disease: A Systematic Review and Meta-Analysis.

To determine the prevalence of silent brain infarction (SBI) and cerebral small vessel disease (CSVD) in adults with atrial fibrillation (AF), coronary artery disease, heart failure or cardiomyopathy, heart valve disease, and patent foramen ovale (PFO), with comparisons between those with and without recent stroke and an exploration of associations between heart disease and SBI/CSVD. Medline, Embase, and Cochrane Library were systematically searched for hospital-based or community-based studies reporting SBI/CSVD in people with heart disease. Data were extracted from eligible studies. Outcomes were SBI (primary) and individual CSVD subtypes. Summary prevalence (95% confidence intervals [CIs]) were obtained using random-effects meta-analysis. Pooled prevalence ratios (PRs) (95% CI) were calculated to compare those with heart disease with available control participants without heart disease from studies. A total of 221 observational studies were included. In those with AF, the prevalence was 36% (31%-41%) for SBI (70 studies, N = 13,589), 25% (19%-31%) for lacune (26 studies, N = 7,172), 62% (49%-74%) for white matter hyperintensity/hypoattenuation (WMH) (34 studies, N = 7,229), and 27% (24%-30%) for microbleed (44 studies, N = 13,654). Stratification by studies where participants with recent stroke were recruited identified no differences in the prevalence of SBI across subgroups (phomogeneity = 0.495). Results were comparable across participants with different heart diseases except for those with PFO, in whom there was a lower prevalence of SBI [21% (13%-30%), 11 studies, N = 1,053] and CSVD. Meta-regressions after pooling those with any heart disease identified associations of increased (study level) age and hypertensives with more SBIs and WMH (pregression <0.05). There was no evidence of a difference in the prevalence of microbleed between those with and without heart disease (PR [95% CI] 1.1 [0.7-1.7]), but a difference was seen in the prevalence of SBI and WMH (PR [95% CI] 2.3 [1.6-3.1] and 1.7 [1.1-2.6], respectively). People with heart disease have a high prevalence of SBI (and CSVD), which is similar in those with vs without recent stroke. More research is required to assess causal links and implications for management. PROSPERO CRD42022378272 (crd.york.ac.uk/PROSPERO/).

Role of maternal hyperoxygenation in predicting need for postnatal balloon atrial septostomy in fetal d-transposition of the great arteries.

Predicting whether postnatal balloon atrial septostomy (BAS) will be necessary for fetuses with dextro-transposition of the great arteries (d-TGA) remains challenging. We sought to determine whether fetal echocardiographic measurements obtained during maternal hyperoxygenation (MH) can improve our ability to predict the need for postnatal BAS. This was a retrospective, single-institution review of d-TGA fetuses whose mothers had undergone MH at 33-38 weeks' gestation at the Children's Hospital of Philadelphia, between 1 January 2017 and 30March2020. All fetal d-TGA cases had either an intact ventricular septum or small ventricular septal defect measuring < 3 mm. Patent foramen ovale (PFO) size, measured by two-dimensional imaging (2D) and by color Doppler, and patent ductus arteriosus (PDA) shunting (antegrade vs bidirectional) were assessed in room air (RA) and during MH. BAS status and timing were recorded. Of 41 fetal d-TGA cases in the cohort, 23 underwent postnatal BAS, while 18 did not, and 14 subjects underwent emergent BAS within 3 h of delivery. On univariate analysis, PFO size measured both in RA and during MH and antegrade shunting in the PDA during MH predicted BAS. During MH, median PFO size by 2D was significantly smaller in fetuses which underwent emergent BAS compared to fetuses which did not undergo BAS (2.5 (interquartile range (IQR), 2.0-3.0) mm vs 4.1 (IQR, 3.4-5.0) mm; P < 0.001). On cut-point analysis, PFO size by 2D during MH of ≤ 3.2 mm predicted the need for emergent BAS with a sensitivity of 93% (95% CI, 66-100%) and a specificity of 78% (95% CI, 58-91%). In fetuses with d-TGA, measurement of PFO size and direction of PDA shunting during MH improves our ability to predict the need for postnatal BAS, although additional study is needed. We propose incorporating third-trimester MH when planning delivery of a d-TGA fetus. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Calcitonin gene-related peptide: a possible biomarker in migraine patients with patent foramen ovale

BackgroundSerum CGRP has been found to increase during migraine attack. However, whether CGRP can identify MA with PFO subtypes in MA remains unknown. This study aimed to investigate the differential expression of calcitonin gene-related peptide (CGRP) between migraine (MA) patients with and without patent foramen ovale (PFO), and to evaluate the predictive value of CGRP for MA with PFO.MethodsA total of 153 patients with MA, 51 patients with PFO and 102 patients without. Venous blood was drawn and HIT-6 score was calculated during the onset of MA, and blood routine, inflammatory indexes and serum CGRP were detected. The differences in serum markers and HIT-6 scores were compared between the two groups, and the risk factors of MA with PFO were determined by univariate and multivariate logistics regression. Furthermore, the correlation between CGRP level with right-to-left shunt (RLS) grades and headache impact test-6 (HIT-6) score in MA patients with PFO were assessed. Independent risk factors were screened out by multivariate Logistic regression analysis. We used the receiver operating characteristic (ROC) curve to analyze the diagnostic value of these risk factors in MA complicated with PFO.ResultsThe serum CGRP level and HIT-6 scores in the MA with PFO group were significantly higher than those in the MA group (P < 0.001). Multivariate regression analysis showed that CGRP was an independent risk factor for MA with PFO (OR = 1.698, 95% CI = 1.325–2.179, P < 0.001). CGRP values ​​increased with the increase of RLS grade(Spearmen rho = 0.703, P < 0.001). Furthermore, a positive correlation between CGRP and HIT-6 scores was found (Spearmen rho = 0.227; P = 0.016). ROC curve showed that the optimal cut-off value for diagnosing MA with PFO was 79 pg/mL, the area under the curve (AUC) for predicting MA with PFO was 0.845, with 72.55% sensitivity and 78.43% specificity.ConclusionsMA patients with PFO have higher serum CGRP level. elevated CGRP concentration was associated with higher RLS grade and increased HIT-6 score. Higher serum CGRP level has certain clinical value in predicting PFO in MA patients.Trial registrationThis study was approved by the Ethics Committee of Zhuhai Hospital of Integrated Traditional Chinese and Western Medicine (Ethics batch number: 20,201,215,005).

Periodontitis, Dental Procedures, and Young-Onset Cryptogenic Stroke

Periodontitis is associated with an increased risk of ischemic stroke, and the risk may be particularly high among young people with unexplained stroke etiology. Thus, we investigated in a case-control study whether periodontitis or recent invasive dental treatments are associated with young-onset cryptogenic ischemic stroke (CIS). We enrolled participants from a multicenter case-control SECRETO study including adults aged 18 to 49 y presenting with an imaging-positive first-ever CIS and stroke-free age- and sex-matched controls. Thorough clinical and radiographic oral examination was performed. Furthermore, we measured serum lipopolysaccharide (LPS) and lipotechoic acid (LTA) levels. Multivariate conditional regression models were adjusted for stroke risk factors, regular dentist visits, and patent foramen ovale (PFO) status. We enrolled 146 case-control pairs (median age 41.9 y; 58.2% males). Periodontitis was diagnosed in 27.5% of CIS patients and 20.1% of controls (P < 0.001). In the fully adjusted models, CIS was associated with high periodontal inflammation burden (odds ratio [OR], 95% confidence interval) with an OR of 10.48 (3.18–34.5) and severe periodontitis with an OR of 7.48 (1.24–44.9). Stroke severity increased with the severity of periodontitis, having an OR of 6.43 (1.87–23.0) in stage III to IV, grade C. Invasive dental treatments performed within 3 mo prestroke were associated with CIS, with an OR of 2.54 (1.01–6.39). Association between CIS and invasive dental treatments was especially strong among those with PFO showing an OR of 6.26 (1.72–40.2). LPS/LTA did not differ between CIS patients and controls but displayed an increasing trend with periodontitis severity. Periodontitis and recent invasive dental procedures were associated with CIS after controlling for multiple confounders. However, the role of bacteremia as a mediator of this risk was not confirmed.

Central Retinal Artery Occlusion Secondary to Paradoxical Embolism Across a Patent Foramen Ovale

Central Retinal Artery Occlusion Secondary to Paradoxical Embolism Across a Patent Foramen Ovale

Patent Foramen Ovale (PFO) in Patients of Cryptogenic Stroke AND Transient Ischemic Attack (TIA): A Real World Experience

Background: Stroke, a leading cause of brain tissue damage, presents a significant health concern globally. Cryptogenic stroke (CS), with an unclear origin, poses diagnostic challenges, with the patent foramen ovale (PFO) implicated in some cases. This study aims to investigate PFO prevalence in North India among patients with cryptogenic stroke, addressing current research gaps.&#x0D; Objective: To assess PFO occurrence in patients with cryptogenic stroke and Transient Ischemic Attack (TIA) using Echocardiography.&#x0D; Methods &amp; Results: This preliminary study analyzed PFO prevalence in patients with CS and TIA from February 2020 to November 2021, involving 25 participants. Descriptive statistics and the Chi-square test were employed. Key findings include a mean age of 44.80±9.13 years, 64% men, and 36% women. Ischemic stroke accounted for 72% of cases, while TIA represented 28%. PFO prevalence was 44%, with no significant gender-PFO association. No correlations were found between stroke type and PFO presence, nor were comorbidities like hypertension and diabetes observed.&#x0D; Conclusion: The study highlights a clinically significant distribution of PFO presence but no notable association between stroke type and PFO presence. These findings contribute to understanding PFO's role in cryptogenic stroke and have implications for clinical practice.

Anesthesia management for a child with the Koolen-de Vries syndrome: a case report

BackgroundThe Koolen-de Vries syndrome (KdVS) is a relatively new rare disease caused by micro-deletion of 17q21.31 which was first reported by Koolen in 2006. Typical phenotypes for KdVS include hypotonia, developmental delay, moderate intellectual disability, and characteristic facial dysmorphism. Up to now, there was only one case report about anesthesia management of patient diagnosed KdVS. It was a 2-year-old girl who experienced an MRI exam under anesthesia.Case presentationWe described a 21-month-old boy who planned to undergo an orchidopexy under general anesthesia diagnosed with KdVS. He had an intellectual disability, characteristic facial dysmorphism, tracheo/laryngomalacia, patent foramen ovale, and cryptorchidism related to KdVS. Due to the complex condition especially the presence of tracheo/laryngomalacia, we took some special measures, including reducing the amount of long-acting opioid, keeping the spontaneous breath, performing a caudal block, and applying the laryngeal mask. But the laryngeal mask was changed to an endotracheal tube because it failed to provide adequate ventilation. The boy experienced mild laryngeal spasm and hypoxia after extubation, but lateral position and etomidate eased his breathing problem and re-intubation was avoided. It is indicated that anesthesia management for patients with orphan disease is a real challenge for all anesthesia providers.ConclusionsThe Koolen-de Vries syndrome is a relatively new orphan disease involving multiple systems. Keeping spontaneous breath, evaluating airway potency to anesthetics, applying endotracheal tube, and post-extubation lateral or prone position may be helpful for airway management for patient with hypotonia and tracheo/laryngomalacia. KdVS patient needs prolonged post-anesthesia monitoring and/or medication for airway complications.

Construction and validation of a nomogram for predicting remission of migraine patients with patent foramen ovale after closure

ObjectiveThis study aimed to construct and validate a nomogram model that predicts the remission of migraine attacks by screening factors that affect the prognosis of migraine patients with patent foramen ovale (PFO) after closure. MethodRetrospective analysis was conducted in migraine patients with PFO who underwent PFO closure in the Department of Cardiology of Jiangsu Province Hospital from September 2020 to April 2023. Based on the Migraine Disability Assessment (MIDAS) scores from the 1-year follow-up after PFO closure, all patients who met the inclusion criteria were categorized into a remission group and a non-remission group. The primary efficacy endpoint was remission of migraine headache. After collecting clinical data, transcranial doppler sonography (TCD) results and MIDAS scores, LASSO (least absolute shrinkage and selection operator) regression and multivariable logistic regression analysis were used to filter variables predictive to migraine remission and construct the nomogram model. The Nomogram's accuracy and consistency were respectively assessed through Receiver Operating Characteristic (ROC) curves and calibration curves. Additionally, an analysis of decision curves (DCA) was conducted to evaluate the clinical utility of this newly developed model. ResultA total of 241 consecutive patients were included in the study. The remission group included 21 males and 93 females, with a median age of 39 (30.25,50) years. The non-remission group included 26 males and 101 females, with a median age of 35 (25.5,47.5) years. All Patients were randomly divided into a training cohort and a validation cohort. Multivariable logistic regression analysis showed that 5 independent predictors, including MIDAS before closure (p = 0.0002), mitigating factors (p = 0.0057), number of attacks/month (p = 0.0058), TCD (p = 0.0093) and Platelet Crit (PCT) (p = 0.0351), played a significant role in the prediction of remission of migraine patients with PFO after closure. Based on these independent predictors, the predictive nomogram model of migraine remission in PFO patients was constructed. The application of the nomogram in the training cohort exhibited good discrimination (area under the ROC curve was 0.7763[95% CI 0.7108–0.8418]), which was confirmed in the validation cohort (AUC was 0.704[95% CI 0.5533–0.8547]). The calibration curve showed that the nomogram model demonstrated good calibration performance. Additionally, the decision curve analysis indicated the clinical utility of the nomogram model. ConclusionThe construction of the nomogram model had a considerable predictive accuracy for migraine remission in patients after PFO closure, which may provide constructive guidance for clinical decision making.

Incorporation of Automated Robotic Transcranial Doppler to Screen for Patent Foramen Ovale and Quantify Right to Left Shunt Severity in the Evaluation of Ischemic Stroke Patients for Stroke Etiology at a Comprehensive Stroke Center (S41.005)

Incorporation of Automated Robotic Transcranial Doppler to Screen for Patent Foramen Ovale and Quantify Right to Left Shunt Severity in the Evaluation of Ischemic Stroke Patients for Stroke Etiology at a Comprehensive Stroke Center (S41.005)

Patent Foramen Ovale Closure for Secondary Stroke Prevention in Patients Aged 60 or Older Is Safe (P10-5.011)

Patent Foramen Ovale Closure for Secondary Stroke Prevention in Patients Aged 60 or Older Is Safe (P10-5.011)

Cryptogenic HACEK CNS Abscess in Otherwise Healthy Patient with Patent Foramen Ovale (P8-13.004)

Cryptogenic HACEK CNS Abscess in Otherwise Healthy Patient with Patent Foramen Ovale (P8-13.004)

Rationale and design of the SPRING trail: effectivity and safety of Pfo closuRe vs medIcine in alleviatiNg migraine, a multicenter, randomized and open-label trail

BackgroundMigraine is a leading cause of disability worldwide. Several retrospective studies have suggested that the closure of the Patent Foramen Ovale (PFO) may provide relief from migraines. However, three randomized controlled trials did not meet their primary endpoints regarding migraine cessation, reduction in monthly migraine days, and responder rates.MethodsThe SPRING study is a multicenter, prospective, randomized, and open-label trial designed to compare the effectiveness and safety of PFO closure versus medication in the relief of migraines. The primary endpoint is the total cessation of migraines, as recorded in patient headache diaries during the follow-up period. Additional diagnostic tools include echocardiography with agitated saline contrast, transcranial Doppler, and routine laboratory measurements.ConclusionThe SPRING trial aims to assess the effectiveness and safety of PFO closure versus medication in mitigating migraines in real-world settings. (Clinical Trails ID: NCT04946734).

The paradox of platypnoea-orthodeoxia syndrome.

Platypnoea-orthodeoxia is a rare clinical syndrome characterised by dyspnoea and oxygen desaturation in the upright position which improves when supine. It requires two components: a sufficiently sized anatomical vascular defect (typically intra-cardiac or intra-pulmonary) combined with a functional component that promotes positional right-to-left shunting. We describe the rare occurrence of a patient with platypnoea-orthodeoxia syndrome (POS) because of a paradoxical shunt through a patent foramen ovale caused by a large right atrial line-associated thrombus in a male with metastatic oesophageal cancer undergoing chemotherapy. This case is a timely reminder to consider POS amongst differentials for hypoxia as it is often treatable if recognised.

Use of Adult Gerontology Acute Care Nurse Practitioners on a Neurocardiology Team

The neurocardiology team provides innovative, evidence-based care for patients with cryptogenic stroke, stroke associated with a patent foramen ovale, and atrial fibrillation-related stroke in patients unsuitable for long-term anticoagulation. Considerable evidence supports the value of advanced practice registered nurses on process improvement metrics and clinical outcomes; however, current literature in stroke management almost exclusively emphasizes interdisciplinary collaboration between physicians. This clinical feature discusses ways in which the adult gerontology acute care nurse practitioner can aid in the delivery of evidence-based stroke care and contribute to educational, administrative, and research missions as a collaborative member of a multidisciplinary neurocardiology team.

The sphenopterygoid canal and pterygoid foramen.

In human anatomy, there are well-known the foramina of the greater sphenoidal wing, the foramen rotundum, the foramen ovale, the foramen spinosum, as well as the inconstant sphenoidal emissary foramen of Vesalius and the foramen of Arnold. Different canals are found in several species of rodents, such as the alisphenoid and sphenopterygoid (SPC) canals. It was re-explored an archived computed tomography angiogram of a 60 y.o. female case. Bilateral superior recesses of the pterygoid fossae (SRPF) and a right SPC were found. The SRPF on each side penetrated the non-lamellar pterygoid root and superiorly reached the sphenoidal sinus wall. Upper fibres of medial pterygoid muscles were inserted into each SRPF. An unexpected SPC was found on the right side. It opened superiorly on the lateral side of the foramen rotundum and inferiorly at a pterygoid foramen in the superior end of the posterior margin of the lateral pterygoid plate. A sphenoidal emissary vein traversed that SPC to drain into the pterygoid plexus. The SRPF and SPC could also be found in humans. As the sphenoidal emissary veins are surgically relevant, they should not be further regarded as exclusively crossing the foramen of Vesalius but also the SPC.

Trigger factors in patients with a patent foramen ovale-associated stroke: A case-crossover study.

Patent foramen ovale (PFO) is a congenital anatomical variant which is associated with strokes in young adults. Contrary to vascular risk factors and atherosclerosis, a PFO is present from birth. However, it is completely unknown how an anatomical structure that is already present at birth in a large proportion of the population can convert into a PFO that causes stroke in a few. Recent studies reported a significant association between certain trigger factors and ischemic stroke in young adults. This study aims to investigate these triggers in PFO-associated stroke. The ODYSSEY study, a multicenter prospective cohort study between 2013 and 2021, included patients aged 18-49 years experiencing their first-ever ischemic event. Participants completed a questionnaire about exposure to potential trigger factors. A case-crossover design was used to assess the relative risks (RR) with 95% confidence intervals (95% CI). The primary outcome was the RR of potential trigger factors for PFO-associated stroke. Overall, 1043 patients completed the questionnaire and had an ischemic stroke, of which 124 patients had a PFO-associated stroke (median age 42.1 years, 45.2% men). For patients with PFO-associated stroke, the RR was 26.0 (95% CI 8.0-128.2) for fever, 24.2 (95% CI 8.5-68.7) for flu-like disease, and 3.31 (95% CI 2.2-5.1) for vigorous exercise. In conclusion, flu-like disease, fever, and vigorous exercise may convert an asymptomatic PFO into a stroke-causing PFO in young adults. The raw and anonymized data used in this study can be made available to other researchers on request. Written proposals can be addressed to the corresponding author and will be assessed by the ODYSSEY investigators for appropriateness of use, and a data sharing agreement in accordance with Dutch regulations will be put in place before data are shared.

A computed tomography-based retrospective study on the foramen ovale and foramen spinosum in a Nigerian population

Abstract Background: This study investigated the shapes and dimensions of the foramen ovale (FO) and foramen spinosum (FS) in a specific population sample from Delta State, Nigeria, emphasizing their significance in various neurosurgical procedures. Materials and Methods: Following ethical clearance, this retrospective study analyzed 250 brain computed tomography (CT) images from the Radiology Department of a teaching hospital in Delta State, Nigeria. The sample included images from 100 females and 150 males, all aged 18 years or older. The dimensions of the FO and FS were measured on axial sections using a standardized protocol. Statistical analyses were conducted with Statistical Package for Social Sciences (IBM, Chicago, Illinois, United States) software, categorizing data by gender and age groups. Inferential statistics, including Student t test, analysis of variance, and Pearson’s correlation, were performed, with findings considered significant at P &lt; 0.05. Results: The predominant shapes of the FO and FS were oval and round, respectively. Significant side differences were observed in the length of the right FS (P = 0.040). Gender differences were noted in the length of the bilateral FO (P = 0.010) and the width of the left FO (P = 0.001). A significant correlation with age was found for the width of the left FO (P = 0.006) and the distance from the right FO to FS (P = 0.037). The FS was absent in 24 cases (9.6%). Conclusion: This study highlights age-, side-, and gender-related differences in the shapes and dimensions of the FO and FS. It emphasizes the importance of precise preoperative radiological assessments to ensure optimal outcomes for neurosurgical planning.

Open-door extended endoscopic transorbital technique to the paramedian anterior and middle cranial fossae: technical notes, anatomomorphometric quantitative analysis, and illustrative case.

The superior eyelid endoscopic transorbital approach (SETOA) provides a direct and short minimally invasive route to the anterior and middle skull base. Nevertheless, it uses a narrow corridor that limits its angles of attack. The aim of this study was to evaluate the feasibility and potential benefits of an "extended" conservative variant of the "standard" endoscopic transorbital approach-termed "open-door"-to enhance the exposure of lesions affecting the paramedian aspect of the anterior and middle cranial fossae. First, the authors described the technical nuances of the open-door extended transorbital approach (ODETA). Next, they documented its morphometric advantages over standard SETOA. Finally, they provided a clinical-anatomical application to demonstrate enhanced exposure and better angles of attack to treat lesions occupying the paramedian anterior and middle cranial fossae. Five adult cadaveric specimens (10 sides) initially underwent standard SETOA and then extended open-door SETOA (ODETA to the paramedian anterior and middle fossae). The adjunct of hinge-orbitotomy, through three surgical steps and straddling the frontozygomatic suture, converted conventional SETOA to its extended open-door variant. CT scans were performed before dissection and uploaded to the neuronavigation system for quantitative analysis. The angles of attack on the axial plane that addressed four key landmarks, namely the tip of the anterior clinoid process (ACP), foramen rotundum (FR), foramen ovale (FO), and trigeminal impression (TI), were calculated for both operative techniques and compared. Hinge-orbitotomy of the extended open-door SETOA resulted in several surgical, functional, and esthetic advantages: it provided wider axial angles of attack for each of the target points, with a gain angle of 26.68° ± 1.31° for addressing the ACP (p < 0.001), 29.50° ± 2.46° for addressing the FR (p < 0.001), 19.86° ± 1.98° for addressing the FO (p < 0.001), and 17.44° ± 2.21° for addressing the lateral aspect of the TI (p < 0.001), while hiding the skin scar, avoiding temporalis muscle dissection, preserving flap vascularization, and decreasing the rate of bone infection and degree of orbital content retraction. The extended open-door technique may be specifically suited for selected patients affected by paramedian anterior and middle fossae lesions, with prevalent anteromedial extension toward the anterior clinoid, the foremost compartment of the cavernous sinus and FR and not completely controlled with the pure endoscopic transorbital approach.

Neurological disorders associated with patent foramen ovale

The foramen ovale between the right and left atria remains open in 15–25% of people over 18 years of age and in most of them it does not manifest itself clinically. At the same time, the defect is associated with a number of diseases and conditions: the development of atrial fibrillation, worsening the degree of hypoxemia in patients with pulmonary diseases, etc. There are studies devoted to the influence of a patent foramen ovale on the occurrence and course of cryptogenic stroke, migraine, syncope, dizziness, transient global amnesia, visual impairment and ocular movement disorders. However, the actual contribution of patent foramen ovale to the development of neurological disorders remains a matter of debate. The purpose of this work was to assess the significance of a patent foramen ovale in the development of neurological disorders in adults and children by analyzing literature data for the period from 2012 to 2022. In the process of studying the literature, a high prevalence of the defect was identified among patients with stroke and migraine (especially migraine with aura). At the same time, data from randomized clinical trials in patients with stroke and migraine showed selectively high effectiveness of closure of the patent foramen ovale in certain groups of patients. The association of patent foramen ovale with transient global amnesia, syncope, and dizziness has been confirmed in a limited number of studies. Cases of visual impairment and ocular movement disorders associated with the presence of a patent foramen ovale have been described. Thus, it was concluded that a patent foramen ovale is a risk factor for the development of neurological disorders only in certain groups of patients with stroke and migraine. The connection between the defect and the development of transient global amnesia, syncope, dizziness, visual impairment, as well as the development of neurological pathology in children requires further research.

Comparative diagnostic accuracy of transcranial Doppler and contrast-enhanced transthoracic echocardiography for the diagnosis of patent foramen ovale and atrial septal defect.

Recognition of right-to-left shunt is crucial in the work-up of patients with suspected patent foramen ovale (PFO) or atrial septal defect (ASD). While transesophageal echocardiography (TEE) remains the gold standard diagnostic tool for the anatomic assessment of PFO/ASD, transcranial Doppler (TCD) and contrast-enhanced transthoracic echocardiogram (CE-TTE) hold the promise of providing minimally invasive yet accurate clinical details. Their comparative accuracy remains however debated. We conducted a retrospective observational study leveraging our extensive institutional experience with systematic TCD and CE-TTE in patients with suspected PFO/ASD. Several measures of diagnostic test accuracy were computed, with point estimates and 95% confidence intervals, when applicable. A total of 1358 patients were included, with age 48±14 years and 772 (58%) women. Tests were performed for diagnostic purposes in 797 (58.6%) and during follow-up in 740 (54.5%). A PFO was eventually diagnosed in 1038 (77.9%) patients, and an ASD in 60 (4.5%). Agreement between TCD and CE-TTE occurred in 1309 (85.2%) cases, with TCD yielding worse findings than CE-TTE in 91 (5.9%) patients, and vice versa in 137 (8.9%), yielding a Cohen kappa of 78.6% (95% CI: 76.3-81.1%) and a highly significant P value at McNemar test (P<0.001). After dichotomization, and using TCD as benchmark, CE-TTE yielded sensitivity 96.9%, specificity 95.1%, area under the curve 92.1%, and P=0.249. Similar findings were obtained when focusing only on diagnostic tests or follow-up ones (Cohen kappa respectively 74.0% [70.2-77.1%], P<0.001 and 80.3% [76.4-84.3%], P<0.001). Notably, Valsalva was necessary to disclose the presence of shunt during TCD in 487 (31.7%) patients and during CE-TTE in 482 (31.4%) cases. Finally, performance of TCD and CE-TTE in a subset of patients eventually undergoing TTE was quite similar. The diagnostic accuracy of CE-TTE appears favorable, and this imaging test may identify patients who may be missed if only TCD is used to screen patients with suspected PFO/ASD. Accordingly, CE-TTE is recommended as an adjunct diagnostic modality for all patients with a high pre-test probability of PFO/ASD and right-to-left shunt.