Foramen Ovale Research Articles

Paradoxical Embolism in Juveniles and Young Adults With Severe-to-Profound Sudden Sensorineural Hearing Loss.

Objective: Paradoxical embolism from right-to-left shunting is a common cause of cryptogenic stroke in the young. Circulatory ischemia of the cochlea is closely connected with severe-to-profound sudden sensorineural hearing loss. This study aimed to explore the role of paradoxical embolism in severe-to-profound sudden sensorineural hearing loss in juveniles and young adults. Methods: From August 2021 to September 2022, consecutive outpatients under 35 years of age with severe-to-profound sudden hearing loss were included in the study. Routine auditory electrophysiological testing and contrast transcranial Doppler ultrasonography (c-TCD) were conducted, and the results were retrospectively analyzed. Results: Seven patients (age: 19.4 ± 6.5 years) were enrolled, including 5 juveniles and 2 young adults. Three patients had severe deafness, and 4 patients had profound deafness. Right-to-left shunting was detected in all patients through c-TCD. Patent foramen ovale was found in 2 patients while pulmonary arteriovenous fistula was found in 1 patient through contrast transthoracic echocardiography or cardiac catheterization. No patients had precipitating factors for sudden sensorineural hearing loss, and none had abnormalities on head magnetic resonance imaging. Six patients underwent whole-exome sequencing, and no known deafness gene variant was detected. After standard treatment for 1 month, 2, 3, and 2 patients had complete, slight, and no hearing recovery, respectively. Conclusions: Paradoxical embolism is a possible cause of severe-to-profound sudden sensorineural hearing loss in juveniles and young adults. In young patients, c-TCD is an effective screening tool to detect right-to-left shunting, while contrast transthoracic echocardiography is a complementary examination to c-TCD.

Transcranial Doppler Ultrasound and Transesophageal Echocardiography for Intraoperative Diagnosis and Monitoring of Patent Foramen Ovale in Non-Cardiac Surgery

Transcranial Doppler Ultrasound and Transesophageal Echocardiography for Intraoperative Diagnosis and Monitoring of Patent Foramen Ovale in Non-Cardiac Surgery

Long-term impact of transcatheter closure interatrial shunts on disabling migraine

Backgrounds Effectiveness of patent foramen ovale (PFO) closure on relief of migraine, is still unclear. We sought to analyse the long-term (>10 years) effects of interatrial septal shunt repair on disabling migraine performing a retrospective non-randomised study. Methods Clinical records of patients with disabling, medication-refractory migraine and PFO or significant ASD referred to our centre for closure from 2006 to 2018, were analysed. Results Forty -six patients (38 female, mean age 40.0 ± 3.7 years) with PFO and 32 patients with significant ASD (28 female, mean age 38.0 ± 4.1 years) submitted to transcatheter closure had a pre-existing disabling migraine with mean Migraine Disability Assessment Score (MIDAS) of 35.8 ± 4.7. After a mean follow-up of 118.2 ± 19.1 months (range 96 to 144), 72 out of 78 patients were still followed-up: in all subjects, aura was abolished, and migraine improved also in patients without aura. The mean MIDAS significantly decreased from baseline value (p < 0.01). Complete migraine resolution was associated in PFO patients with a shorter history of migraine, a more severe thrombophilic profile, a more severe Right-to-Left Shunt (RLS) and larger left atrial diameter and volume, and in ASD patients with bidirectional shunt. Conclusions Device-based repair of PFO/ASD in patients with migraine was associated with abolition of aura and symptoms reduction in the long-term period.

Effectiveness of a novel integrated dilator-needle transseptal crossing device in atrial fibrillation cryoballoon ablation procedures

Abstract Background In cryoballoon ablation (CBA) procedures, left atrial (LA) access is generally achieved using a standard sheath and needle system that is exchanged for the cryoballoon delivery sheath and dilator over a long wire. Sheath exchange has been related with air embolic events in CBA procedures. A novel integrated dilator-needle system, that can be combined with the cryoballoon delivery sheath allowing direct LA transseptal access, was recently introduced. Figure. Objective The purpose of this study is to evaluate the efficacy and safety of this new integrated transseptal access tool compared with the traditional approach in CBA procedures. Methods In this prospective single-center study, consecutive patients who underwent AF CBA procedures were randomly assigned 1:1 to undergo traditional transseptal access (t-TSA) or integrated transseptal access (i-TSA). Patients with foramen ovale or interatrial communication, detected on transesophageal echocardiogram prior to the procedure, were excluded. Transseptal access time was defined as time from superior vena cava to LA insertion of the cryoballoon delivery sheath, after sheath exchange (t-TSA) or directly (i-TSA). Results We evaluated 82 patients (63 males, mean age 59 ± 10 years) indicated to CBA of atrial fibrillation, 42 patients underwent t-TSA and 40 i-TSA. The baseline characteristics of the study population were comparable between groups. Table. Mean CBS transseptal access time was 5 min 6 sec ± 2 min 5 sec in the t-TSA group and 3 min 5 sec ± 2 min 23 sec in the i-TSA group, P &amp;lt; 0.001. Challenging interatrial septa were noted in 3 patients: 1 in t-TSA (1 aneurysmal/elastic) and 2 in i-TSA group (1 lipomatous hypertrophy, and 1 abnormally thickened/fibrotic). No acute complications related to transseptal access were noted in both cohorts. The CBA procedure time and fluoroscopy time were lower in the i-TSA group. Table. There were 1 temporary phrenic nerve injury and 1 vascular complication, both in the t-TSA group. Importantly, no signs of clinical air embolism were noted in both groups. Conclusion This is the first randomized study comparing the traditional approach and the use of a new integrated dilator-needle system. Transseptal crossing in CBA procedures using this integrated tool enables a safe and more efficient workflow, reducing time for transseptal access and avoiding sheath exchange.FigureTable

The challenge of transseptal access for catheter ablation of left-sided arrhythmia substrate in infants and small children under 6 years of age

Abstract Background Young age and small cardiac dimensions are increased risk factors for catheter ablation (CA), therefore ablation below 15 kg should be recommended only in selected drug-refractory cases. The need for a transseptal puncture (TSP) may be an additional risk factor. Persistent foramen ovale (PFO) in infants can mitigate this risk and paradoxically, decrease the complication rate in the very young. Purpose This study aimed to compare the results of left-sided CA in infants under 1 year and in children between 1-6 years of age. Methods Between January 2010 and September 2023, 1703 pediatric CAs were performed, of which 17 left-sided ablations in children under 6 years without structural heart disease were retrospectively evaluated. CA results below 1 year and between 1-6 years of age were compared in terms of body size, procedural parameters, left atrial (LA) access, complication, and success rate. Results The patient group below 1 year (Group 1, n=5) has a mean age=0.13±0.03 years, mean body weight=3.6±1.1 kg, mean height=52.3±3.6 cm. Patients between 1-6 years (Group 2, n=12) have mean age=5.0±1.1 years, mean body weight=17.9±2.2 kg, mean height=111.2±7.4 cm. The arrhythmia substrate was an overt pathway in 3 pts (17.6%), concealed accessory pathway in 7 pts (41.2%), and focal LA tachycardia in 7 pts (41.2%). Foramen ovale was persistent in all 5 children in Group 1 and TSP was not required. In Group 2, only 2 pts (16.7%) had PFO, and, all other procedures required TSP. TSP was successful in 9/10 cases (90%). No complications related to LA access or other adverse events occurred in Group 1. In Group 2, there was one case of pericardial effusion that spontaneously regressed and one case of mechanical-induced advanced AV block that resolved after six days. There were no significant differences in procedure time, fluoroscopic time, and radiation dose between the two groups (Group 1: 126.4±47.0 min, 6.4±4.5 min, 4.0±5.3 cGycm2 vs. Group 2: 162.6±49.2 min, 7.9±9.4 min, 9.0±12.4 cGycm2, p&amp;gt;0.05). All CAs were performed with RF energy. The acute success rate of the procedures was 100%. Conclusion CA of left-sided arrhythmias in infants and small children may offer a safe and effective therapeutic option in selected cases. The high prevalence of PFO may explain the paradoxically less complication under 1 year of age.

De novo variation in ARID1B gene causes Coffin-Siris syndrome 1 in a Chinese family with excessive early-onset high myopia

Coffin-Siris syndrome (CSS) is a rare autosomal dominant inheritance disorder characterized by distinctive facial features, hypoplasia of the distal phalanx or nail of the fifth and additional digits, developmental or cognitive delay of varying degree, hypotonia, hirsutism/hypertrichosis, sparse scalp hair and varying kind of congenital anomalies. CSS can easily be misdiagnosed as other syndromes or disorders with a similar clinical picture because of their genetic and phenotypic heterogeneity. We describde the genotype-phenotype correlation of one patient from a healthy Chinese family with a novel genotype underlying CSS, who was first diagnosed in the ophthalmology department as early-onset high myopia (eoHM). Comprehensive ophthalmic tests as well as other systemic examinations were performed on participants to confirm the phenotype. The genotype was identified using whole exome sequencing, and further verified the results among other family members by Sanger sequencing. Real-time quantitative PCR (RT-qPCR) technology was used to detect the relative mRNA expression levels of candidate genes between proband and normal family members. The pathogenicity of the identified variant was determined by The American College of Medical Genetics and Genomics (ACMG) guidelines. STRING protein-protein interactions (PPIs) network analysis was used to detect the interaction of candidate gene-related proteins with high myopia gene-related proteins. The patient had excessive eoHM, cone-rod dystrophy, coarse face, excessive hair growth on the face, sparse scalp hair, developmental delay, intellectual disability, moderate hearing loss, dental hypoplasia, patent foramen ovale, chronic non-atrophic gastritis, bilateral renal cysts, cisterna magna, and emotional outbursts with aggression. The genetic assessment revealed that the patient carries a de novo heterozygous frameshift insertion variant in the ARID1B c.3981dup (p.Glu1328ArgfsTer5), which are strongly associated with the typical clinical features of CSS patients. The test results of RT-qPCR showed that mRNA expression of the ARID1B gene in the proband was approximately 30% lower than that of the normal control in the family, suggesting that the variant had an impact on the gene function at the level of mRNA expression. The variant was pathogenic as assessed by ACMG guidelines. Analysis of protein interactions in the STRING online database revealed that the ARID1A protein interacts with the high myopia gene-related proteins FGFR3, ASXL1, ERBB3, and SOX4, whereas the ARID1A protein antagonizes the ARID1B protein. Therefore, in this paper, we are the first to report a de novo heterozygous frameshift insertion variant in the ARID1B gene causing CSS with excessive eoHM. Our study extends the genotypic and phenotypic spectrums for ARID1B-CSS and supplies evidence of significant association of eoHM with variant in ARID1B gene. As CSS has high genetic and phenotypic heterogeneity, our findings highlight the importance of molecular genetic testing and an interdisciplinary clinical diagnostic workup to avoid misdiagnosis as some disorders with similar manifestations of CSS.

Transcatheter PFO closure for cryptogenic stroke: current approaches and future considerations.

Patent Foramen Ovale (PFO) is a common congenital atrial septal defect present in 20%-35% of the general population. Although generally considered a benign anatomic variant, a PFO may facilitate passage of a thrombus from the venous to arterial circulation, thereby resulting in cryptogenic stroke or systemic embolization. A PFO is detected in nearly one half of patients presenting with cryptogenic stroke and often considered the most likely etiology when other causes have been excluded. In this review, we discuss the contemporary role of transcatheter closure of PFO in the treatment of cryptogenic stroke, including devices currently available for commercial use in the United States (Amplatzer PFOTM Occluder and GoreTM Cardioform Septal Occluder) and a novel suture-mediated device (NobleStitchTM EL) under clinical investigation. To provide the best care for cryptogenic stroke patients, practitioners should be familiar with the indications for PFO closure and corresponding treatment options.

Clinical significance of a patent foramen ovale in patients with pulmonary embolism

The phenomenon of a patent foramen ovale in patients with pulmonary embolism increases the risk of ischemic stroke. The clinical significance of this phenomenon should be taken into account to determine the diagnostic algorithm, management tactics and choice of secondary prevention. The prognosis of a patient with pulmonary embolism depends not only on the likelihood of recurrent pulmonary embolism, the formation of chronic pulmonary hypertension, but is also associated with an increased risk of ischemic stroke through the mechanism of paradoxical embolism due to the presence of a patent foramen ovale. A venous thrombus migrates through the patent foramen ovale as a result of the operation of an intracardiac right-left shunt. The purpose of the scientific review is to raise awareness of the problem of ischemic stroke in patients with pulmonary embolism. The results of studies and registries are presented, which reflect that the presence of patent foramen ovale increases the risk of developing ischemic stroke in patients with pulmonary embolism. Ischemic stroke can occur within 2–22 days after the onset of a pulmonary embolism clinic, and the risk of ischemic stroke remains within a year. Non-invasive transcranial dopplerography is recommended for diagnosis at the first stage of identification of the right-to-left shunt and is highly sensitive method (95–98%). Transesophageal echocardiography should be considered for the second stage of diagnosis. Thrombolytic therapy or surgical thrombectomy improves the prognosis for this category of patients. Тhrombolytic therapy may be given for up to 14 days in patients with pulmonary embolism. The use of thrombolytic therapy in the development of ischemic stroke becomes a possible option to improve the prognosis patients. The choice strategy for secondary prevention is important because patients have an increased risk of relapse.

High-Throughput Genomics Identify Novel FBN1/2 Variants in Severe Neonatal Marfan Syndrome and Congenital Heart Defects.

Fibrillin-1 and fibrillin-2, encoded by FBN1 and FBN2, respectively, play significant roles in elastic fiber assembly, with pathogenic variants causing a diverse group of connective tissue disorders such as Marfan syndrome (MFS) and congenital contractural arachnodactyly (CCD). Different genomic variations may lead to heterogeneous phenotypic features and functional consequences. Recent high-throughput sequencing modalities have allowed detection of novel variants that may guide the care for patients and inform the genetic counseling for their families. We performed clinical phenotyping for two newborn infants with complex congenital heart defects. For genetic investigations, we employed next-generation sequencing strategies including whole-genome Single-Nucleotide Polymorphism (SNP) microarray for infant A with valvular insufficiency, aortic sinus dilatation, hydronephrosis, and dysmorphic features, and Trio whole-exome sequencing (WES) for infant B with dextro-transposition of the great arteries (D-TGA) and both parents. Infant A is a term male with neonatal marfanoid features, left-sided hydronephrosis, and complex congenital heart defects including tricuspid regurgitation, aortic sinus dilatation, patent foramen ovale, patent ductus arteriosus, mitral regurgitation, tricuspid regurgitation, aortic regurgitation, and pulmonary sinus dilatation. He developed severe persistent pulmonary hypertension and worsening acute hypercapnic hypoxemic respiratory failure, and subsequently expired on day of life (DOL) 10 after compassionate extubation. Cytogenomic whole-genome SNP microarray analysis revealed a deletion within the FBN1 gene spanning exons 7-30, which overlapped with the exon deletion hotspot region associated with neonatal Marfan syndrome. Infant B is a term male prenatally diagnosed with isolated D-TGA. He required balloon atrial septostomy on DOL 0 and subsequent atrial switch operation, atrial septal defect repair, and patent ductus arteriosus ligation on DOL 5. Trio-WES revealed compound heterozygous c.518C>T and c.8230T>G variants in the FBN2 gene. Zygosity analysis confirmed each of the variants was inherited from one of the parents who were healthy heterozygous carriers. Since his cardiac repair at birth, he has been growing and developing well without any further hospitalization. Our study highlights novel FBN1/FBN2 variants and signifies the phenotype-genotype association in two infants affected with complex congenital heart defects with and without dysmorphic features. These findings speak to the importance of next-generation high-throughput genomics for novel variant detection and the phenotypic variability associated with FBN1/FBN2 variants, particularly in the neonatal period, which may significantly impact clinical care and family counseling.

PERCUTANEOUS CLOSURE OF PATENT FORAMEN OVALE AFTER A FAILED DEVICE–CLOSURE ATTEMPT: A HIGH–VOLUME SINGLE CENTRE EXPERIENCE

Abstract Introduction Persistence of patent foramen ovale (PFO) has been associated with cryptogenic stroke due to a paradoxical systemic embolism. In these cases, a percutaneous closure allows to decrease the risk of redo cerebral ischemic events. However, the presence of a complex anatomy might prevent a correct device–deployment with a high–risk o residual shunt and/or device embolization. We describe our experience about alternative technique after a failed device closure attempt. Methods We reviewed six cases wherein the device was not able to close effectively the PFO. In these cases, alternative techniques and skills were adopted to close the PFO. Results From 2021 to 2023, 194 PFO were closed in the congenital catheterization laboratory of Monaldi Hospital (Naples). In the most of cases (188/194 pts, 96.9%) an effective device closure was obtained. However, in 6 cases (3.1%) the device failed to have a PFO closure. In these 6 patients, the PFO anatomy was characterized by: a severe hypertrophy of the septum secundum (2 cases, 33%), an aneurysmatic interatrial septum (3 cases, 50%), a long stiff tunnel (6 cases, 100%). In three cases a deviceless suture–mediated system (NoblestichTM) was effective to achieve a complete PFO closure; whereas, in two cases a combined approach (suture–mediated system followed by a device deployment) allowed to achieve a complete PFO closure. In a patient with Ebstein anomaly and significant cyanosis due to right–to–left PFO shunt, a partial PFO closure (with mild residual right–to–left shunt) was obtained after NoblestichTM deployment. In this setting, the partial PFO closure was effective to achieve a significant improvement of the patient’s arterial saturation and the procedure stopped without to complete the PFO closure with a device. Conclusion Trans–catheter device closure is often effective to achieve a complete PFO closure. However, in some circumstances, the device was unable to have an appropriate PFO closure. A suture–mediated system or a combined approach (suture–mediated system with concomitant device deployment) are effective to achieve the PFO closure in these complex scenarios.

A "PARADOXICAL" MINOCA

Abstract Background The acronym MINOCA refers to myocardial infarction with normal or near–normal coronary arteries on invasive angiography. We report a case of MINOCA caused by paradoxical coronary embolism due to a right–to–left shunting through a patent fossa ovalis. Integrated multimodality imaging diagnostic work–up has been crucial for identifying the mechanism underlying MINOCA. Case Report A 48–year–old male was admitted to the Coronary Care Unit for sudden–onset oppressive chest pain lasting 1 hour, radiating to the left arm; no specific changes in ST–segment on a 12–lead ECG and elevated high–sensitive troponin I (peak value 1562 ng). Transthoracic echocardiography showed normal dimensions and function of the cardiac chambers and excluded valvular and pericardial diseases. Given the characteristics of the chest pain, we performed an urgent coronary angiography that showed normal epicardial coronary, including testing for epicardial coronary spasm and microvascular dysfunction. We also used Optical Coherence Tomography on LAD e RCA to rule out critical stenosis and sign of plaque instability. To investigate the etiology of myocardial damage the patient underwent a cardiac magnetic resonance (CMR) imaging that yielded the following findings: hypokinesis of the inferior–middle segment of the left ventricle associated myocardial edema and near transmural LGE. These features were consistent with a recent ischemic injury. Additionally, CMR showed an atrial septal aneurysm and a channel–like pattern of the interatrial septum, raising the suspicion of patent foramen ovale (PFO). The transesophageal echocardiography and transcranial Doppler with bubble test confirmed the presence of a PFO responsible for right–to–left shunting. Atrial fibrillation was excluded with ECG telemetry throughout the entire 7day hospitalization. Conclusions Based on the result of the overall clinical–instrumental evaluation, MINOCA caused by paradoxical coronary embolism due to a right–to–left shunting through a PFO was considered the most plausible diagnostic hypothesis. The patient underwent to interventional percutaneous closure of PFO and was discharged with no symptoms or complication at the follow–up.

AN OUT OF HOSPITAL CARDIAC ARREST SURVIVOR WITH PRESUMED EMBOLIC MYOCARDIAL INFARCTION: ROLE OF MULTI–MODALITY IMAGING

Abstract Background Myocardial infarction with non–obstructive coronary arteries (MINOCA) refers to a puzzling clinical entity that is characterized by symptoms suggestive of acute coronary syndrome, demonstrates troponin elevation with inconclusive coronary angiogram. The underlying pathophysiologic mechanisms include atherosclerotic cause or non–atherosclerotic causes, such as coronary dissection or coronary embolus. A standardized approach that includes multimodality imaging is necessary to determine underlying aetiology and direct appropriate treatment. Case Summary A 57–year–old male was admitted to our hospital after experiencing cardiac arrest after physical exercise (swimming) treated immediately with cardiac pulmonary resuscitation and two defibrillator–delivered electrical shocks for shockable rhythm before return of spontaneous circulation. Relevant abnormal bloods included a hs–Troponin I elevation. Invasive coronary angiography demonstrated non–obstructed coronary arteries. Subsequent cardiac magnetic resonance imaging (MRI) demonstrated akinesia and an area of subendocardic late gadolinium enhancement in the inferior–lateral wall. This pattern was in keeping with an ischaemic cause, as a recent embolic myocardial infarction. Further investigations, including contrast bubble echocardiogram, were performed in order to identify a cause and source of the embolic infarction and led to the diagnosis of tunnel–like patent foramen ovale with right to left shunting, then confirmed on trans–oesophageal echocardiogram. The patient was treated as myocardial infarction most likely due to embolic phenomena in the presence of a PFO. Therefore, a transvenous ICD was implanted for secondary prevention and the patient underwent percutaneous closure of the PFO. Discussion and Conclusion MINOCA can occur in 5–15% of all acute coronary syndromes and represents a working diagnosis. It is important to identify the underlying aetiology of their presentation to appropriately manage them. In particular, where cardiac MRI demonstraded LGE areas ichaemic patterns, myocardial infarction due to secondary embolism should be considered and the next step in clinical management is to identify potential sources of emboli performing further assessments. Multi–modality imaging with cardiac MRI and echocardiogram (transthoracic, contrast bubble and trans–oesophageal) is important in correctly identifying any source of emboli and the diagnosis of any intra–cardiac shunt.

MID–TERM OUTCOMES OF ENDOSCOPIC MITRAL VALVE REPAIR VIA RIGHT ANTERIOR MINI–THORACOTOMY

Abstract The adoption of less–invasive mitral repair (MVr) surgery is increasing, backed by evidence of satisfactory short–term results and lower major morbidity. We assessed mid–term follow–up results of our experience, and compared two techniques: isolated leaflet resection and neochord implantation for posterior leaflet (PML) prolapse. Between 2012–2021, 700+ operations were performed with a video–assisted right mini–thoracotomy (RMT) approach. We report 309 consecutive patients who had endoscopic MVr, including those receiving concomitant tricuspid repair, ablation for atrial fibrillation, closure of patent foramen ovale and/or left atrial appendage. The early and mid–term follow–up results were ascertained. Primary outcome was the incidence of mortality and significant mitral regurgitation (MR) during follow–up which were summarized by Kaplan–Meier estimator and compared between treatment arms via log–rank test. Secondary outcomes were the early–postoperative results including 30–days mortality and major complications. All patients had endoscopic MVr via RMT at the 3rd/4th intercostal space (IS). A soft–tissue retractor is used, accompanied or not by a rib spreader, and two ports in the fourth and sixth IS are used for 3D thoracoscopy and carbon dioxide insufflation. Femoral vessels exposure through a right groin incision and echo–guided cannulation sec. Seldinger is achieved post–heparinization. Thoracic fascia bisection is performed during single–lung ventilation using a double–lumen endotracheal tube, integral to our anesthetic management, including percutaneous right internal jugular vein cannulation. The pericardium is opened and an aortic root cannula for cardioplegia delivery and venting is placed via working incision. After establishing cardiopulmonary bypass, a Chitwood clamp is passed through the second IS and cardioplegia is delivered. Endoaortic balloon clamping is primarily used in redo cases. With ring annuloplasty, 136 (44%) patients received PML resection (122 isolated) and 97 (31%) PML chords implantation (88 isolated). Forty–nine patients had annuloplasty alone. In–hospital mortality was 1.0%. Mean follow–up was 29±22 months (max 8.3 years). Kaplan–Meier 5–year survival was 97.3±1.0%. MR (3/4+) free–survival at 5 years was 94.5±2.3%. Subgroup time–to–event analysis for the indexed outcomes showed no statistical significance between techniques. In conclusion, endoscopic MVr is safe with excellent mid–term outcomes.

Evaluation of ultrasound-guided PFO occlusion in the treatment of vestibular migraine.

Currently, surgery is the mainstay of the clinical treatment of vestibular migraine. To investigate the clinical efficacy and safety of using transesophageal echocardiography-guided interventional closure of the patent foramen ovale (PFO) in the treatment of vestibular migraine. The study included 52 patients with vestibular migraine who were admitted to our hospital between June 2019 and June 2021. All selected patients underwent a transesophageal echocardiography-guided interventional closure of the PFO and were followed up for one year after surgery. We observed the clinical efficacy and surgical success rate one year after surgery and compared the improvement in clinical symptoms and perioperative safety at different time points. The overall remission rate and the surgical success rate for the 52 patients with vestibular migraine one year after surgery were 86.54% and 96.15%, respectively. Compared to the pre-surgery levels, there was a significant progressively decreasing trend in the scores on the Headache Impact Test-6 (HIT-6), Visual Analogue Scale (VAS), Migraine Disability Assessment (MIDAS) questionnaire, frequency of headaches, and duration of headaches in patients with vestibular migraine at 1, 3, and 6 months after surgery (P< 0.05). Among the 52 patients, one developed atrial fibrillation three hours after surgery, which then spontaneously converted to sinus rhythm, and none of the other patients had adverse outcomes such as hematoma at the puncture site during the perioperative period. Transesophageal echocardiography-guided interventional closure of the PFO for treating vestibular migraine significantly improved the symptoms of migraine in patients, with a high surgical success rate, significant clinical efficacy, and favorable safety.

BETWEEN SCYLLA AND CHARYBDIS: MULTIPLE LEFT ATRIAL THROMBI DESPITE ORAL ANTICOAGULATION AND ANTIPLATELET THERAPY IN A PATIENT CANDIDATE FOR LEFT ATRIAL APPENDAGE OCCLUSION

Abstract Introduction Left atrial (LA) thrombosis usually occurs in patients affected by atrial fibrillation (AF), generally involving the left atrial appendage (LAA). We present the unexpected echocardiographic finding of multiple LA thrombi despite an adequate antithrombotic strategy. Case Presentation A 76–year–old lady underwent transesophageal echocardiographic examination (TOE) to assess eligibility for percutaneous LAA occlusion (LAAO) procedure due to high bleeding risk. Her medical history included AF and a recent percutaneous coronary revascularization; therefore, her antithrombotic therapy included apixaban 2.5 mg bid and clopidogrel 75 mg od. The TOE showed LA structural and functional remodeling with spontaneous echo contrast and multiple thrombi involving the LAA (one [12 x 9 mm] overflowing the orifice and attached to the Coumadin Ridge and the second [12 x 7 mm] attached and arising from the tunnel of patent foramen ovale). Mitral valve stenosis was excluded (Fig.1). Due to TOE findings, the patient was not considered eligible for percutaneous LAAO. Due to the concomitant very high thromboembolic risk, despite the previous intracranial bleeding, we decided to stop apixaban and to start parenteral anticoagulation for 3 weeks with low–molecular weight heparin (100 UI/kg bid) followed by the switch to a vitamin k antagonist (VKA). We also prescribed a hematological evaluation to exclude a hypercoagulability disorder. Our patient’s daughter was a carrier of a mutation in both the methylenetetrahydrofolatereductase and Thrombin genes. A TOE after 30 days showed the persistence of LA thrombi, although with significantly reduced size and mobility (Fig.2). The follow–up was clinically uneventful. We suggested to continue anticoagulation therapy with VKA, and we planned a new TOE after 4 weeks. Discussion Although proper anticoagulation decreases cardioembolic risk in patients with AF, atrial thrombosis may occur due to LA remodeling, high CHA2DS2–VASc score and other factors, including hypercoagulability disorders. The presence of multiple LA thrombi represents a challenge for clinicians, especially in case of concomitant high thromboembolic and bleeding risk. However, the best treatment strategies for these extreme conditions are not defined, so far. Therefore, the therapeutic choice is often tailored to the single patient and based on the clinical judgment, bearing in mind that avoiding Charybdis means passing to close to Scylla and vice versa.

European Stroke Organisation (ESO) Guidelines on the diagnosis and management of patent foramen ovale (PFO) after stroke.

Patent foramen ovale (PFO) is frequently identified in young patients with cryptogenic ischaemic stroke. Potential stroke mechanisms include paradoxical embolism from a venous clot which traverses the PFO, in situ clot formation within the PFO, and atrial arrhythmias due to electrical signalling disruption. The purpose of this guideline is to provide recommendations for diagnosing, treating, and long-term managing patients with ischaemic stroke and PFO. Conversely, Transient Ischaemic Attack (TIA) was not considered an index event in this context because only one RCT involved TIA patients. However, this subgroup analysis showed no significant differences between TIA and stroke outcomes. The working group identified questions and outcomes, graded evidence, and developed recommendations following the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach and the European Stroke Organisation (ESO) standard operating procedure for guideline development. This document underwent peer-review by independent experts and members of the ESO Guideline Board and Executive Committee. The working group acknowledges the current evidentiary gap in delineating an unequivocal diagnostic algorithm for the detection of PFO. Although transoesophageal echocardiography is conventionally held as the most accurate diagnostic tool for PFO identification, its status as the 'gold standard' remains unsubstantiated by rigorously validated evidence. We found high-quality evidence to recommend PFO closure plus antiplatelet therapy in selected patients aged 18-60 years in whom no other evident cause of stroke is found but a PFO (i.e. PFO-associated stroke). The PASCAL classification system can be used to select such candidates for PFO closure. Patients with both a large right-to-left shunt and an atrial septal aneurysm benefit most from PFO closure. There is insufficient evidence to make an evidence-based recommendation on PFO closure in patients older than 60 and younger than 18 years. We found low quality evidence to suggest against PFO closure in patients with unlikely PFO-related stroke according to the PASCAL classification, except in specific scenarios (Expert Consensus). We suggest against long-term anticoagulation in patients with PFO-associated stroke unless anticoagulation is indicated for other medical reasons. Regarding the long-term AF monitoring after PFO closure, the working group concluded that there remains significant uncertainty regarding the risks and benefits associated with the use of long-term cardiac monitoring, such as implantable loop recorders. This document provides additional guidance, in the form of evidence-based recommendations or expert consensus statements, on diagnostic methods for PFO detection, and medical management after PFO closure.

A whole-exome sequencing study of patent foramen ovale: investigating genetic variants and their association with cardiovascular disorders.

Patent foramen ovale (PFO) has a genetic predisposition and is closely associated with cryptogenic stroke (CS), migraine, decompression sickness, and hypoxemia. Identifying PFO-related mutant genes through whole-exome sequencing (WES) can help in the early recognition of cardiovascular genetic risk factors, guide timely clinical intervention, and reduce the occurrence of cardiovascular events. We analyzed mutant genes from ClinVar and OMIM databases. WES was performed on 25 PFO patients from Zhejiang Provincial Hospital of Chinese Medicine. Pathogenicity of variants was evaluated using American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology. (AMP) guidelines. In ClinVar (4 Feb 2023), 113 coding gene mutations were found, including 83 associated with PFO. From OMIM (18 Apr 2023), 184 gene mutations were analyzed, with 110 mutant coding genes. WES identified pathogenic mutations in two of 25 PFO patients (8%). LDLR, SDHC, and NKX2-5 genes were linked to PFO and primarily involved in myocardial tissue function. NKX2-5 may play a crucial role in PFO development, interacting with NOTCH1, GATA4, MYH6, SCN5A signaling pathways regulating cardiomyocyte characteristics. We identified pathogenic mutations in LDLR, SDHC, and NKX2-5 genes, implying their role in PFO development. Functional enrichment analysis revealed NKX2-5's interaction with signaling pathways regulating cardiomyocyte function. These findings enhance our understanding of PFO's genetic basis, suggesting potential therapeutic targets for future research.

Value of Intracardiac Echocardiography in the Interventional Closure of Patent Foramen Ovale with Adjacent Atrial Septal Defect

Objective. This study aimed to investigate the application value of intracardiac echocardiography (ICE) in transcatheter closure of a patent foramen ovale (PFO) combined with an adjacent atrial septal defect (ASD). Methods. This retrospective study included five patients with PFO combined with adjacent ASD who underwent transcatheter closure and were admitted to the Zhongshan Hospital of Fudan University from June to September 2023. General conditions, ultrasound and ICE findings, and operative data were recorded and followed up for 2–6 months. Results. Of the five patients, two and three had embolic stroke of undetermined source and migraine, respectively, aged 45.6 ± 12.0 years. All patients underwent successful transcatheter closure via the PFO tunnel under the guidance of ICE, without complications or new stroke, and showed significantly reduced migraine at the follow-up. Conclusion. In patients with PFO combined with adjacent ASD, closure of a PFO tunnel could be successfully achieved under ICE guidance; its clinical efficacy was accurate and worthy of promotion.

Real-World Patent Foramen Ovale (PFO) Closure in Japan - 30-Day Clinical Outcomes From the AmplatzerTM PFO Occluder Japan Post-Marketing Surveillance Study.

The AmplatzerTM PFO Occluder was approved for marketing in Japan in May 2019, and the Amplatzer PFO Occluder Japan Post-marketing Surveillance (PFO Japan PMS) study was initiated in December 2019. This analysis presents 30-day clinical outcomes for PFO Japan PMS study patients. PFO Japan PMS is a prospective single-arm non-randomized multicenter clinical study. Eligible patients were indicated for patent foramen ovale (PFO) closure and underwent an implant attempt with the AmplatzerTM PFO Occluder. Technical success was defined as successful delivery and release of the occluder; procedural success was defined as technical success with no serious adverse events (SAEs) within 1 day of the procedure. The primary safety endpoint includes predefined device- and/or procedure-related SAEs through 30 days after the procedure. From December 2019 to July 2021, 500 patients were enrolled across 53 Japanese sites. The mean (±SD) patient age was 52.7±15.4 years, and 29.8% of patients were aged >60 years. Technical and procedural success rates were both high (99.8% and 98.8%, respectively). Further, there was only one primary safety endpoint event (0.2%): an episode of asymptomatic paroxysmal atrial fibrillation that occurred 26 days after the procedure. In this real-world Japanese study with almost one-third of patients aged >60 years, PFO closure with the AmplatzerTM PFO Occluder was performed successfully and safely, with a low incidence of procedure-related atrial arrhythmias.

Retrogasserian trigeminal radiofrequency-thermorhizotmoy for trigeminal neuralgia

Based on a personal experience of 4200 surgeries, radiofrequency thermocoagulation is useful lesional treatment for those trigeminal neuralgias (TNs) not amenable to microvascular decompression (idiopathic or secondary TNs). Introduced through the foramen ovale, behind the trigemnial ganglion in the triangular plexus, the needle is navigated by radiology and neurophysiological testing to target the retrogasserian fibers corresponding to the trigger zone. Heating to 55–75 °C can achieve hypoesthesia without anaesthesia dolorosa if properly controlled. Depth of anaesthesia varies dynamically sedation for cannulation and lesioning, and awareness during neurophysiologic navigation. Proper technique ensures long-lasting results in more than 75% of patients.