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.

BACKGROUND: Migraine 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. METHODS: The 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. CONCLUSION: The 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).

Paradoxical Embolic Stroke Following Percutaneous Transluminal Angioplasty in a Hemodialysis Patient.

Paradoxical embolism is a medical condition characterized by the migration of an embolus from a venous source into the systemic circulation. This occurs through a specific cardiac abnormality known as a right-to-left shunt, ultimately resulting in the possibility of arterial embolism. Patent foramen ovale (PFO) is the most common cause of intracardiac shunting. We reported a rare case of a 56-year-old man on hemodialysis with PFO and arteriovenous fistula dysfunction who suffered a paradoxical embolic ischemic stroke after percutaneous transluminal angioplasty. This case emphasized the potential risk of paradoxical embolism in hemodialysis patients with vascular access problems. We aimed to highlight the importance of searching for PFO, as it may serve as a possible source of embolism in these patients.

Patent foramen ovale closure versus drug therapy in patients over 60 years and a follow-up of 5 years.

BACKGROUND: The advantages of patent foramen ovale (PFO) closure as protection from a recurrence of stroke remains controversial compared to drug therapy, especially in patients over 60 years. HYPOTHESIS: The aim of the study is to compare recurrence of stroke in patients over 60 years old with PFO closure versus drug therapy alone. METHODS: We included 342 patients over 60 years who suffered a crytopgenic stroke, and were also accepted for a PFO closure. 199 patients refused a PFO closure and were treated with medical therapy alone, whereas 143 patients underwent a PFO closure procedure. RESULTS: The mean follow up time was 5.5 ± 1.5 years. All patients in Group B showed persistent shunt in the follow-up period (n = 199, 100%). In Group A, seven patients were diagnosed with residual shunt during echocardiography examination (5%). A new onset of atrial fibrillation occurred in seven patients in Group A (5%) and six patients in Group B (3%), p = .117. Recurrent stroke occurred in 3 patients in Group A (2%) and 11 patients in Group B (6%), p = .021. One patient died of unknown reason (1%) and two patients were lost due to neurological death (1%) in Group B, whereas no patients in Group A died during the follow-up period. CONCLUSION: Our results show that strict exclusion of patients over 60 years from PFO closure should be reconsidered. As life expectancies are increasing, patients should be considered for same treatment as younger patients, since the outcomes are improved compared to patients treated with medical therapy alone.

Management of patent foramen ovale; findings from a nationwide survey.

OBJECTIVES: Several clinical trials have provided evidence supporting the transcatheter closure of patent foramen ovale (PFO) in selected patients following a cryptogenic stroke. However, it remains unknown to what extent these guidelines have been implemented in everyday clinical practice and the familiarity of physicians from different specialties with PFO closure. The aim of our nationwide survey is to explore the implementation of transcatheter PFO occlusion in Greek clinical practice. MATERIALS AND METHODS: Attending level cardiologists, internal medicine physicians and neurologists involved in the management of PFO-related strokes working in Greece were invited to complete an online questionnaire. The questionnaire consisted of 19 questions and was designed to obtain comprehensive data on provider demographics, PFO characteristics, and specific clinical scenarios. RESULTS: A total of 51 physicians (56.9 % cardiologists, 25.5 % neurologists and 17.6 % internal medicine physicians) completed the survey, resulting in a response rate of 53 %. Cardiologists, internal medicine physicians and neurologists agree on several issues regarding PFO closure, such as PFO closure as first line treatment, management of patients with DVT or prior decompression sickness, and post-closure antithrombotic treatment, but different approaches were reported regarding closure in patients with thrombophilia treated with oral anticoagulation (p=0.012) and implantable loop recorder placement for atrial fibrillation exclusion (p=0.029 and p=0.020). CONCLUSIONS: Our findings show that cardiologists, internal medicine physicians and neurologists agree in numerous issues, but share different views in the management of patients with thrombophilia and rhythm monitoring duration. These results highlight the significance of collaboration among physicians from different medical specialties for achieving optimal results.

Recurrent stroke in a reproductive age women with patent foramen ovale.

BACKGROUND: Patent foramen ovale (PFO) is a known cause of ischemic stroke in young adults and combined oral contraceptives (COCs) are widely used by women of reproductive age. If young women with PFO are taking COCs, they may be subjected to a synergistic increase in the occurrence of stroke, though reports of ischemic stroke in this population are rare. We report a woman of reproductive age who was taking COC suffered repetitive ischemic strokes before a patent foramen ovale (PFO) was detected and closed, which may raise concerns in this field. CASE PRESENTATION: A 31-year-old woman presented to the emergency department with sudden-onset right upper- and lower-limb weakness and dysarthria for 1 hour, whose only risk factor of stroke was oral contraceptive use. On admission, she was alert with left gaze deviation, dysarthria, and right-sided hemiplegia. Her symptoms improved after receiving the revascularization therapy. About 24 hours later, her left eye experienced sudden painless vision loss. Then the PFO with a substantial right-to-left shunt was detected and then she received a trans-catheter closure of the defect. Over 3 months of follow-up, there were no signs of stroke, but visual loss persisted. CONCLUSION: This case of disabling stroke raises concerns regarding optimal management in primary and secondary prevention of stroke in young women on COCs with additional risk factors of stroke.

Safety and efficacy of the Amplatzer™ Trevisio™ intravascular delivery system: Post-approval study results.

BACKGROUND: The Amplatzer™ Trevisio™ Intravascular Delivery System (Trevisio DS; Abbott Laboratories, Chicago, IL, USA) facilitates the delivery of Amplatzer™ Occluders and features an ultraflexible tip, which improves assessment of occluder position before release. AIMS: To assess the safety and efficacy of the Trevisio DS for transcatheter closure of patent foramen ovale and atrial septal defect. METHODS: The Amplatzer™ Trevisio™ Intravascular Delivery System Post-Approval Study was a prospective, postmarket, single-arm, multicentre, observational study of the Trevisio DS. Enrolled patients were indicated for transcatheter closure of patent foramen ovale or atrial septal defect. In all procedures, the Trevisio DS was used to deliver Amplatzer™ Occluders. Technical success was defined as successful deployment and release of at least one occluder. Device- or procedure-related serious adverse events were tracked until discharge or day 7, whichever occurred earlier. RESULTS: The study enrolled 144 patients with patent foramen ovale and 107 patients with atrial septal defect at 22 European sites; 53 patients with atrial septal defect (49.6%) were aged<18years. The rate of technical success was 98.4% (97.2% for atrial septal defect, 99.3% for patent foramen ovale). There was one serious adverse event (0.4%), an acute periprocedural device embolization that occurred after occluder release in a patient with atrial septal defect; the device was retrieved percutaneously. This was determined by the implanter to be unrelated to the performance of the Trevisio DS. CONCLUSIONS: The Trevisio DS exhibited a high rate of technical success and an excellent safety profile during transcatheter closure of patent foramen ovale and atrial septal defect.

Comparative evaluation of intracardiac, transesophageal, and transthoracic echocardiography in the assessment of patent foramen ovale: A retrospective single-center study.

INTRODUCTION: Certain patent foramen ovale (PFO) characteristics, such as a large right-to-left shunt (RLS) or atrial septal aneurysm, identify patients who may receive the highest clinical benefit from percutaneous PFO closure. This study aimed to compare intracardiac echocardiography (ICE) with standard echocardiographic imaging in the evaluation of high-risk PFO characteristics and RLS severity in patients with PFO-associated stroke. METHODS: We conducted a retrospective review of all patients aged ≥18 years who underwent percutaneous PFO closure for PFO-associated stroke and received all three ultrasound-based cardiac imaging modalities and had interpretable results (N = 51). We then compared RLS severity, high-risk PFO characteristics, and the proportion of patients with a higher likelihood of PFO-associated stroke by ICE versus transthoracic echocardiogram (TTE) and transesophageal echocardiogram (TEE). RESULTS: The final cohort had a mean (±SE) age of 48.4 (±1.8) years and was predominantly female (58.8%). ICE was more likely to identify a large RLS versus TTE/TEE combined (66.7% vs. 45.1%; p = 0.03). The use of ICE resulted in significantly more patients being reclassified as having a higher likelihood of PFO-associated stroke (TTE vs. TEE vs. ICE: 10.4% vs. 14.6% vs. 25%; p = 0.03). A high-quality bubble study was found to be the single most important factor associated with identifying a larger RLS across all modalities (ρ [p]; TTE: 0.49 [<0.001], TEE: 0.60 [<0.001], ICE: 0.32 [0.02]). The presence of a hypermobile septum was associated with significantly greater RLS on ICE (ρ [p]: 0.3 [0.03]), especially with poor quality bubble studies (ρ [p]: 0.49 [0.02]). CONCLUSION: In this observational study of patients with PFO-associated stroke, ICE detected a large RLS more frequently than TTE and TEE; and reclassified some patients as having a higher likelihood of PFO-associated stroke.

The value of right heart contrast echocardiography combined with migraine rating scale in evaluating the efficacy of patent foramen ovale closure.

OBJECTIVES: To investigate the clinical values of right heart contrast transthoracic echocardiography (cTTE) combined with migraine rating scale in evaluating the efficacy of patent foramen ovale (PFO) closure. METHODS: From January 2018 to December 2021, a total of 68 hospitalized patients, 21 males and 47 females, who were treated with transcatheter closure of PFO-induced migraine in the Heart Center of the First Affiliated Hospital of Tsinghua University were selected, with the age of 38.4 ± 11.9 years old. The changes of right heart contrast transthoracic echocardiography (cTTE), visual analogue pain score(VAS), headache impact test-6(HIT-6) and migraine disability assessment questionnaire(MIDAS) before and 6 months after PFO occlusion were compared. RESULTS: Pre-operative cTTE data show that 36 patients (52.9%) had moderate right-to-left shunt (RLS), and 32 patients (47.1%) had massive RLS. cTTE was reexamined 6 months after operation and 1 case in the moderate RLS group had minimal RLS, 2 cases in the large RLS group had minimal RLS, and no shunts were seen for the rest. The VAS, HIT-6 and MIDAS scores before and 6 months after the operation were 7.65 ± 1.39 vs. 1.28 ± 1.53, 70.78 ± 6.82 vs. 41.53 ± 6.07, and 30.60 ± 13.24 vs. 1.93 ± 3.87, respectively. All the indexes 6 months after the operation significantly improved compared with the preoperative baseline (P < 0.05). CONCLUSIONS: cTTE combined with migraine evaluation scale could be used as an objective index to evaluate the clinical effect of PFO occlusion.

[Thromboembolic diseases from a cardiological point of view]. / Thromboembolische Erkrankungen aus kardiologischer Sicht.

Thromboembolic disease is associated with a high mortality. It can be divided into two groups: embolism from a venous and embolism from an arterial side. This article gives an overview on thromboembolic disease (with a focus on pulmonary embolism and ischemic stroke) from a cardiologist's perspective.The therapeutic options for acute pulmonary embolism range from anticoagulation to fibrinolysis to interventional recanalization and surgery. The deciding factor for choice of therapy is the risk of early death. Besides clinical parameters, laboratory markers like cardiac troponin and right ventricular function on echocardiography or CTPA (computed tomography pulmonary angiography) are used to determine the early mortality risk. In hemodynamically instable patients, immediate thrombolysis is required, whereas patients with intermediate and low risk can be treated with anticoagulation. Interventional recanalization is currently being studied in patients at risk for development of CTEPH (chronic thromboembolic pulmonary hypertension) or an intermediate risk of early mortality.In ischemic stroke, early interdisciplinary workup involving a cardiologist is paramount. Post stroke screening should include monitoring for arrythmias (especially atrial fibrillation) and transthoracic echocardiography as well as sonography of extra- and intracranial arteries. If no embolic source can be detected (embolic stroke of undetermined source), transesophageal echo can be helpful to detect intracardiac shunts like patent foramen ovale (PFO) or intracardiac tumors. Post stroke care includes secondary prevention measures like risk factor modification and lipid lowering therapy as well as anticoagulation. In high risk for paradoxical embolization, interventional PFO closure can be performed. Interventional closure of the left atrial appendage (LAA) can be discussed in patients with both high thromboembolic and bleeding risk.

Management of patent foramen ovale in embolic stroke of undetermined source patients: Malaysian experts' consensus.

INTRODUCTION: About 20 to 40% of ischaemic stroke causes are cryptogenic. Embolic stroke of undetermined source (ESUS) is a subtype of cryptogenic stroke which is diagnosed based on specific criteria. Even though patent foramen ovale (PFO) is linked with the risk of stroke, it is found in about 25% of the general population, so it might be an innocent bystander. The best way to treat ESUS patients with PFO is still up for discussion. MATERIALS AND METHODS: Therefore, based on current evidence and expert opinion, Malaysian expert panels from various disciplines have gathered to discuss the management of ESUS patients with PFO. This consensus sought to educate Malaysian healthcare professionals to diagnose and manage PFO in ESUS patients based on local resources and facilities. RESULTS: Based on consensus, the Malaysian expert recommended PFO closure for embolic stroke patients who were younger than 60, had high RoPE scores and did not require long-term anticoagulation. However, the decision should be made after other mechanisms of stroke have been ruled out via thorough investigation and multidisciplinary evaluation. The PFO screening should be made using readily available imaging modalities, ideally contrasttransthoracic echocardiogram (c-TTE) or contrasttranscranial Doppler (c-TCD). The contrast-transesophageal echocardiogram (c-TEE) should be used for the confirmation of PFO diagnosis. The experts advised closing PFO as early as possible because there is limited evidence for late closure. For the post-closure follow-up management, dual antiplatelet therapy (DAPT) for one to three months, followed by single antiplatelet therapy (APT) for six months, is advised. Nonetheless, with joint care from a cardiologist and a neurologist, the multidisciplinary team will decide on the continuation of therapy.

Management of Patients With Patent Foramen Ovale and Stroke: A National Survey of Interventional Cardiologists and Vascular Neurologists.

Background Results from multiple clinical trials support patent foramen ovale closure after cryptogenic stroke in select patients, but it remains unclear how new data and updated professional society guidelines have impacted clinical practice. Here, we aimed to compare how stroke neurologists and interventional cardiologists approach patients with cryptogenic stroke with patent foramen ovale and how critical anatomic and clinical factors influence decision making. Methods and Results An electronic survey was administered to 1556 vascular neurologists and 1057 interventional cardiologists throughout the United States. The survey addressed factors such as patient age, preclosure workup, and postclosure antithrombotics. Clinical vignettes highlighted critical variables and used a 5-point Likert scale to assess the providers' level of support for closure. There were 491 survey responses received from 301 (of 1556) vascular neurologists and 190 (of 1057) interventional cardiologists, with an overall response rate of 19%. Vascular neurologists were more likely to recommend against closure on the basis of older age (P<0.001). Interventional cardiologists are more supportive of closure across a range of clinical vignettes, including a very carefully selected patient with cryptogenic stroke (P<0.001), a patient with a high-risk alternative stroke cause (P<0.001), and a range of cases highlighting clinical variables where data are lacking. The majority of interventionalists (88%) seek neurology consultation before pursuing patent foramen ovale closure. Conclusions lnterventional cardiologists are more likely than vascular neurologists to support patent foramen ovale closure across a range of situations. This emphasizes the importance of collaboration and shared decision making, but also reveals an opportunity for professional society educational outreach.

Left atrial disc device thrombosis after atrial defect closure with the Gore® Cardioform septal occluder: A case series.

Device thromboses after patent foramen ovale (PFO) and atrial septal defect (ASD) closure are rare but serious complications. They have been reported in different devices of virtually all manufacturers. Here, we report three cases of left atrial device thrombosis after atrial defect closure with the Gore® Cardioform septal occluder (GSO) in our recent institutional experience. All patients were symptomatic with new-onset neurological impairments and evidence of cerebral thromboembolism. Device thromboses have occurred despite antiplatelet therapy in two patients and moreover were observed late, at approximately 2 years after implantation, in two patients. One device was surgically explanted while in two cases, thrombi completely resolved with initiated anticoagulation. All patients had a favorable neurological recovery. Our observations suggest that regular follow-up echocardiography beyond 6 months after device implantation might be advisable in patients with GSO devices to rule out late device thromboses. More long-term follow-up data considering safety and late complications of contemporary PFO and ASD devices is required to establish confident evidence-based recommendations on long-term follow-up management and antithrombotic therapy regimen after PFO and ASD closure.

Short- and Long-Term Outcomes in Patients With Thrombophilia Undergoing Transcatheter Closure of Patent Foramen Ovale.

BACKGROUND: Patients with thrombophilia are underrepresented in studies evaluating outcomes after closure of patent foramen ovale (PFO). Real-world data on long term outcomes in this population are very limited. OBJECTIVES: This study compared outcomes in patients with and without thrombophilia undergoing PFO closure, using data from a large, clinical database linked to population-based databases. METHODS: This retrospective cohort study included consecutive patients who had a transcatheter PFO closure and had preprocedural thrombophilia screening. Data from a retrospective, clinical registry were linked to population-based administrative databases in Ontario Canada to evaluate outcomes. Outcomes were reported as rates per 100 person-years and compared using Poisson regression. RESULTS: We included 669 patients, with a mean age of 56.4 years, 97.9% of whom underwent PFO closure for a cryptogenic stroke. Thrombophilia was diagnosed among 174 (26.0%), of which 86% had inherited mutations. In-hospital, procedural complications were observed in 3.1% of patients with no difference by thrombophilia status. Similarly, no differences were observed in 30-day emergency department visits and readmissions. Over the median follow-up of 11.6 years, the most common adverse outcome was new-onset atrial fibrillation (1.0 per 100 person-years; 95% CI: 0.8-1.2), followed by recurrent cerebrovascular events (0.8 per 100 person-years; 95% CI: 0.6-1.1) with no differences between the groups (P > 0.05). CONCLUSIONS: After PFO closure, no differences were observed in long-term adverse outcomes between patients with and without thrombophilia. Though these patients have been excluded from randomized clinical trials of PFO closure in the past, real-world evidence supports their eligibility for the procedure.

Patent foramen ovale closure after cryptogenic stroke: sometimes uncertain benefit maybe, or even potential harm in the long run?

The main published studies on patent foramen ovale (PFO) closure after cryptogenic stroke tend to consider it positively, in light of the reported both procedural risk profile and outcomes. On the other hand, many blind spots and controversial issues of the topic are still present, mainly including both early procedural complications, and mid- and long-term associated comorbidities as well. Oftentimes, several biases appear to be present, with the evident risk of modifying indications for both intervention, and decision-making process. Biases should be considered and discussed during the diagnostic approach as well, including the supposed evidence of correlation, or cause-effect relationship, between the clinical event and patent foramen ovale. Furthermore, such studies have mostly shown results based on short-term follow-up and very low event rates. Conversely, those patients will keep the device lifelong, generally with long life expectancy, and the increased possibility of recurrent stroke from any other cause over time, along with many potential device-related comorbidities (e.g. atrial fibrillation, nearby anatomical structures impairment, and thrombosis). Consequently, it is hard to demonstrate the mid-term and long-term device-related advantages, due to the possible higher incidence of stroke associated with iatrogenic or concurrent factors. Thus, larger, well designed, long-term, multicentric, and more inclusive studies are needed, aimed to demonstrate a net clinical benefit, ideally including a number-needed-to-treat calculation at short-term, mid-term, and long-term, as well as taking into account and comparing the long-term complications, related outcomes, and recurrent events in patients with and without devices.

Anatomical predictors for suture-based closure of the patent foramen ovale: A multicenter experience.

BACKGROUND: NobleStitch EL is a novel suture-based technique used for patent foramen ovale (PFO) closure and an alternative to traditional double-disc devices without the need for antithrombotic therapy. However, successful closure rates are still unknown, and certain anatomies may be unfavorable for successful closure. AIMS: We assessed the efficacy of the NobleStitch EL and sought to identify patient-related anatomical features associated with successful suture-based closure. METHODS: We included 55 patients who underwent PFO closure with the NobleStitch EL in The Netherlands and Switzerland. Successful closure was defined as residual right-to-left shunt grade ≤1 with Valsalva maneuver at a cardiac ultrasound. Predefined possible anatomical determinants for effective closure included PFO length, atrial septal aneurysm, PFO entry- and exit diameter. RESULTS: Successful closure was achieved in 33 patients (60%). The PFO length was shorter in patients with successful closure compared to unsuccessful closure with a median length of 9.6 mm (IQR 8.0-15.0) versus 13.3 mm (IQR 11.4-18.6) on preprocedural ultrasound (p = 0.041) and 9.9 mm (IQR 8.0-13.1) versus 12.5 mm (IQR 9.7-15.4) on angiography (p = 0.049). Additionally, the PFO exit diameter and PFO volume were smaller in patients with successful closure than unsuccessful closure, with a mean diameter of 7.0 ± 3.1 mm versus 9.5 ± 3.8 mm (p = 0.015) and a median volume of 381 mm3 (IQR 286-894) versus 985 mm3 (IQR 572-1550) (p = 0.016). CONCLUSION: In our study cohort, the successful PFO closure rate using NobleStitch EL was relatively low (60%). With this alternative procedure, patients with a small PFO driven by a short PFO tunnel length and small exit diameter seem to be eligible for successful suture-based closure.