Comparison of medical treatment with percutaneous closure of patent foramen ovale in patients with cryptogenic stroke

OBJECTIVES: The purpose of this study was to compare the efficacy of medical treatment with percutaneous closure of patent foramen ovale (PFO). BACKGROUND: Patients with cryptogenic stroke and PFO are at risk for recurrent cerebrovascular events. METHODS: We compared the risk of recurrence in 308 patients with cryptogenic stroke and PFO, who were treated either medically (158 patients) or underwent percutaneous PFO closure (150 patients) between 1994 and 2000. RESULTS: Patients undergoing percutaneous PFO closure had a larger right-to-left shunt (p < 0.001; 95% confidence interval [CI] 1.38 to 3.07) and were more likely to have suffered more than one cerebrovascular event (p = 0.03; 95% CI 1.04 to 2.71). At four years of follow-up, percutaneous PFO closure resulted in a non-significant trend toward risk reduction of death, stroke, or transient ischemic attack (TIA) combined (8.5% vs. 24.3%; p = 0.05; 95% CI 0.23 to 1.01), and of recurrent stroke or TIA (7.8% vs. 22.2%; p = 0.08; 95% CI 0.23 to 1.11) compared with medical treatment. Patients with more than one cerebrovascular event at baseline and those with complete occlusion of PFO were at lower risk for recurrent stroke or TIA after percutaneous PFO closure compared with medically treated patients (7.3% vs. 33.2%; p = 0.01; 95% CI 0.08 to 0.81, and 6.5% vs. 22.2%; p = 0.04; 95% CI 0.14 to 0.99, respectively). CONCLUSIONS: Percutaneous PFO closure appears at least as effective as medical treatment for prevention of recurrent cerebrovascular events in cryptogenic stroke patients with PFO. It might be more effective than medical treatment in patients with complete closure and more than one cerebrovascular event.     

Patent Foramen Ovale Attributable Cryptogenic Embolism With Thrombophilia Has Higher Risk for Recurrence and Responds to Closure

ObjectivesThe aim of this study was to investigate the effect of management on the risk for recurrent events among patients with cryptogenic ischemic stroke or transient ischemic attack.BackgroundThe combination of patent foramen ovale (PFO) and hypercoagulability may greatly increase the risk for paradoxical embolism. However, previous randomized controlled trials evaluating the efficacy of PFO closure excluded these potential high-risk patients.MethodsPatients diagnosed with PFO attributable cryptogenic embolism were prospectively, without randomization, recruited from January 2005 to March 2018. The relationship between thrombophilia and recurrent events was evaluated in overall patients. Multivariate Cox regression was conducted to assess the relative risk for recurrence in PFO closure and medical therapy groups.ResultsA total of 591 patients with cryptogenic embolism with PFO were identified. The median duration of follow-up was 53 months, and thrombophilia significantly increased the risk for recurrent events (hazard ratio [HR]: 1.85; 95% confidence interval [CI]: 1.09 to 3.16; p = 0.024). PFO closure was superior to medical therapy in overall patients (HR: 0.16; 95% CI: 0.09 to 0.30; p < 0.001). Of the 134 patients (22.7%) with thrombophilia, there was a difference in the risk for recurrence events between the PFO closure (6 of 89) and medical therapy (15 of 45) groups (HR: 0.25; 95% CI: 0.08 to 0.74; p = 0.012). There was no potential heterogeneity in the further subgroup analysis.ConclusionsPatients with cryptogenic stroke with PFO and hypercoagulable state had increased risk for recurrent stroke or transient ischemic attack. PFO closure provided a lower risk for recurrent events compared with medical therapy alone.     

Patent foramen ovale closure to prevent secondary neurologic events

In October of 2016 the United States Food and Drug Administration approved the Amplatzer Patent Foramen Ovale (PFO) occluder device for use in patients with cryptogenic stroke, to reduce the risk of recurrent stroke. This event followed 15 years of off-label use of atrial septal occluder devices, 3 randomized trials, and enormous controversy over the efficacy of this procedure. While none of the trials reached the primary endpoint needed to prove the efficacy of PFO closure in preventing recurrent stroke, meta-analyses and 5-year follow-up of 1 trial suggest that PFO closure decreases the risk of recurrent stroke, especially in sub-groups with large shunts and atrial septal aneurysms, and especially when the Amplatzer device (rather than other devices) is used. While the relative reduction in stroke associated with PFO closure is large (about 50%), the absolute reduction is low (1–2%) and must be balanced against complications of the procedure (about 3%). Thus, PFO closure is restricted to patients with cryptogenic stroke, and depends heavily on patients' personal preferences. Uncertainties about the etiology of stroke in patients with PFO and the efficacy of PFO closure cause a difficult problem for the internal medicine specialist. At one extreme the internist may wonder if every patient with a documented PFO should be referred to a cardiologist. At the other extreme, supported by specialty society guidelines, internists may conclude that PFO closure is rarely necessary. In this paper we review the current status of PFO closure and suggest a rational strategy for this procedure.     

Closure of patent foramen ovale for paradoxical emboli: intermediate-term risk of recurrent neurological events following transcatheter device placement

OBJECTIVES: We report the largest and the longest follow-up to date of patients who underwent transcatheter patent foramen ovale (PFO) closure for paradoxical embolism. BACKGROUND: Closure of a PFO has been proposed as an alternative to anticoagulation in patients with presumed paradoxical emboli. METHODS: Data were collected for patients following PFO closure with the Clamshell, CardioSEAL or Buttoned Devices at two institutions. RESULTS: There were 63 patients (46 +/- 18 years) with a follow-up of 2.6 +/- 2.4 years. Fifty-four (86%) had effective closure of the foramen ovale (trivial or no residual shunt by echocardiography) while seven (11%) had mild and two (3%) had moderate residual shunting. There were four deaths (leukemia, pulmonary embolism, sepsis following a hip fracture and lung cancer). There were four recurrent embolic neurological events following device placement: one stroke and three transient events. The stroke occurred in a 56-year-old patient six months following device placement. A follow-up transesophageal echocardiogram showed a well seated device without residual shunting. Two of the four events were associated with suboptimal device performance (one patient had a significant residual shunt and a second patient had a "friction lesion" in the left atrial wall associated with a displaced fractured device arm). The risk of recurrent stroke or transient neurological event following device placement was 3.2% per year for all patients. CONCLUSION: Transcatheter closure of PFO is an alternative therapy for paradoxical emboli in selected patients. Improved device performance may reduce the risk of recurrent neurological events. Further studies are needed to identify patients most likely to benefit from this intervention.     

Meta-Analysis of Secondary Prevention of Cryptogenic Stroke

BackgroundCryptogenic stroke and embolic stroke of undetermined source (ESUS) are a frequently encountered categories of ischemic stroke with an uncertain cause.MethodsWe analyzed all randomized clinical trials (RCTs) that evaluated antithrombotic therapy and patent foramen ovale (PFO) closure in cryptogenic stroke and/or ESUS. We calculated aggregate hazard ratios (HRs) using direct and network meta-analysis. The primary outcome was recurrent ischemic stroke.ResultsTen RCTs with a total of 16,876 patients, randomizing 32,143 patient-years of follow-up (mean age 61.2 ± 13.5 with 39.2% female) were identified. Anticoagulation therapy was associated with significantly reduced recurrent ischemic stroke compared with antiplatelet therapy (HR = 0.66; [95% confidence interval (CI) = 0.47–0.94]). Meta-regression analysis showed significantly reduced recurrent stroke with longer duration of therapy, and significantly increased events with advanced age. Significant interactions were observed based on the presence of PFO, stroke type, and anticoagulant used. There were no significant differences with regard to the composite ischemic outcome, transient ischemic attack, any death, major bleeding, or intracranial bleeding. In the network meta-analysis, compared to antiplatelet therapy, warfarin (HR = 0.31; [95% credible interval (CrI) = 0.12–0.68]) and PFO closure (HR = 0.14; 95% CrI = 0.05–0.31]) were associated with significantly reduced recurrent ischemic stroke. In rank order, PFO closure was associated with the best outcome, followed by warfarin.ConclusionsAmong patients with cryptogenic stroke, anticoagulation therapy, as compared with antiplatelet therapy is associated with lower rate of recurrent stroke. The small sample size and high heterogeneity with regards to bleeding outcomes require further large trials. In patients with PFO, closure and warfarin are associated with the lowest rates of recurrent stroke.     

Management of patients with stroke and a patent foramen ovale

Observational studies have established a strong association between the presence of patent foramen ovale (PFO) and increased risk of ischemic stroke. The mechanism involved is presumed to be a paradoxical embolism from a venous thrombus that travels via the PFO to the systemic circulation. The best treatment modality to prevent recurrent stroke in patients with PFO remains undefined. There are four major choices: 1) medical therapy with anticoagulants, 2) medical therapy with antiplatelet agents, 3) surgical closure, and 4) percutaneous device closure. The Patent Foramen Ovale in Cryptogenic Stroke Study has demonstrated that antiplatelet and anticoagulant therapies are of equal benefit in preventing recurrent neurologic events in stroke patients with a PFO. Medical therapy should remain as the initial choice of secondary prophylactic therapy. PFO closure, either surgical or percutaneous, may further reduce event rates; however, this remains to be demonstrated because no randomized trial to date has compared PFO closure with medical therapy.     

Patent foramen ovale and cerebrovascular diseases

Patent foramen ovale (PFO) has been linked to ischemic strokes of undetermined cause (cryptogenic strokes). PFO-a remnant of fetal circulation when the foramen ovale does not seal after birth-can permit microemboli to escape the pulmonary filter into the intracranial circulation, causing stroke. Coexistent atrial septal aneurysm, pelvic deep vein thrombosis and inherited clotting factor deficiencies could potentiate stroke risk in patients with PFO. Transcatheter PFO closure, a minimally invasive procedure, is one technique used to prevent recurrent cerebrovascular events. A connection between PFO and migraine headache has been conceptualized from retrospective evidence of reduced migraine frequency and severity after PFO closure; however, prospective randomized trials are needed to verify the efficacy of PFO closure on migraine prevention. In this review we discuss embryologic origins, diagnostic techniques and treatment options for prevention of paradoxical embolism thought to be related to PFO, and the relation of PFO to cryptogenic stroke and migraine.     

Percutaneous Closure of Patent Foramen Ovale in Patients with Cryptogenic Stroke — An Updated Comprehensive Meta-Analysis

BackgroundThe ideal treatment strategy for patients with cryptogenic stroke and patent foramen ovale (PFO) is not yet clear. Previous randomized controlled trials (RCTs) comparing transcatheter PFO closure with medical therapy in patients with cryptogenic stroke to prevent recurrent ischemic stroke showed mixed results. This meta-analysis aims to compare rates of recurrent stroke, transient ischemic attack (TIA) and all-cause mortality with PFO closure and medical therapy vs. medical therapy alone.MethodsPubMed and the Cochrane Center Register of Controlled Trials were searched for studies published through June 2018, comparing PFO closure plus medical therapy versus medical therapy alone. Six RCTs (n = 3750) comparing PFO closure with medical therapy were included in the analysis. End points were recurrent stroke, TIA and all-cause mortality. The odds ratios (OR) with 95% confidence interval (CI) were computed and p < 0.05 was considered as a level of significance.ResultsA total of 1889 patients were assigned to PFO closure plus medical therapy and 1861 patients were assigned to medical therapy only. Risk of recurrent stroke was significantly lower in the PFO closure plus medical therapy group compared to medical therapy alone. (OR 0.47, 95% CI 0.33–0.67, p < 0.0001). Rate of TIA was similar between the two groups (OR 0.76, 95% CI 0.52–1.14), p = 0.18). There was no difference in all-cause mortality between two groups (OR 0.73, CI 0.33–1.58, p = 0.42). Patients undergoing PFO closure were more likely to develop transient atrial fibrillation than medical therapy alone (OR: 5.85; CI: 3.06–11.18, p ≤0.0001) whereas the risk of bleeding was similar between the groups (OR: 0.93; CI: 0.55–1.57, p = 0.78).ConclusionsThe results of this meta-analysis suggest that transcatheter closure of PFO plus medical therapy is superior to medical therapy alone for the prevention of recurrent cryptogenic stroke. However, PFO closure in these patients has not been shown to reduce the risk of recurrent TIA or all-cause mortality. There is a higher rate of transient atrial fibrillation post PFO closure device placement, the long-term effects of which have yet to be studied.     

Outcome after percutaneous closure of a patent foramen ovale using the Intrasept™ device

Objectives : This multi‐centre study reports safety and efficacy of percutaneous patent foramen ovale (PFO) closure, using the fourth generation Intrasept? device. Background : PFO has been associated with paradoxical embolism and cryptogenic stroke. Percutaneous PFO closure seems to reduce the risk for recurrent paradoxical thrombo‐embolism. Currently, different devices are used for PFO closure. Methods : Patients, who underwent a PFO closure with the Intrasept device (Cardia, Eagan, MN) between July 2002 and September 2006, were included in the study. The primary endpoint was defined as reoccurrence of stroke, transient ischemic attack (TIA), or peripheral thrombo‐embolism. Peri‐procedural and mid‐term complications were reported. Results : Four‐hundred thirty patients (mean age 50.7 ± 13.0 years, 231 men) underwent closure. The indications were cryptogenic stroke (69.8%), TIA (23.5%), peripheral embolism (3.3%), and other (3.5%). The median follow‐up time was 0.8 years, range 3.9 years. The primary endpoint occurred in 0.5% for stroke, in 2.5% for TIA, and in none for peripheral embolism. Peri‐procedural complications were reported in 11.5% of cases, from which 0.2% was defined as major. No severe complications occurred during mid‐term follow‐up. A residual shunt was present in 12.5% of patients who did not suffer from a recurrent event, compared to 36.4% of patients who reached the primary endpoint (P = 0.04). Conclusion : This multi‐centre study suggests that percutaneous closure of a symptomatic PFO with the fourth generation Intrasept device is safe and might be effective to prevent the recurrence of paradoxical thrombo‐embolic events. © 2008 Wiley‐Liss, Inc.     

卵圆孔未闭封堵治疗隐源性脑卒中预防复发效果的meta分析

目的 卵圆孔未闭（PFO）封堵治疗隐源性脑卒中效果的meta分析。 方法 通过Web of Science，EMBASE，PubMed和Cochrane图书馆等数据库进行了以药物对照的随机对照试验的相关检索。主要终点是复发性卒中和短暂性脑缺血发作（TIA）。 提取原始数据、风险比（HR）及95%置信区间（95%CI）的数值用以计算汇总效应大小。 结果 Meta分析发现，在PFO患者缺血性脑卒中和（或）TIA的预防上，在意向性人群中封堵器组要明显优于药物治疗组（HR = 0.47，95% CI: 0.27-0.84，I2 = 55.4%，P<0.01）。随访期间封堵器组的全因死亡率较药物治疗组差异无统计学意义（OR = 0.83，95% CI: 0.37 - 1.85，I2 = 21.8%，P = 0.655）。在封堵器组患者中，发生新发房颤的风险较药物治疗组显著增加（OR = 5.44，95% CI: 2.92 - 10.15，I2 = 35.3%，P<0.01）。meta分析结果亦表明，在大量分流的患者中，经封堵器治疗后，卒中的复发率较药物治疗组显著减少（OR = 0.31，95% CI: 0.14 - 0.69，I2=0，P < 0.01）。而在与药物治疗相比中，PFO并发房间隔膨出瘤（ASA）的患者亦明显受益于封堵器治疗（OR = 0.44，95% CI: 0.23-0.81，I 2 = 63.3%，P<0.01）。 结论 与单纯药物治疗相比,PFO封堵治疗隐匿性脑卒中患者复发脑卒中的风险明显减低。在有大量分流和房间隔膨出瘤的患者中，PFO封堵的获益更大。PFO的封堵与新发心房颤动的发生率较高有关。      

Percutaneous closure of patent foramen ovale in symptomatic patients

BACKGROUND: Patent foramen ovale (PFO) and atrial septal aneurysm (ASA) have been associated with stroke in young adults. Patients with PFO suffering from paradoxical embolism are at increased risk for recurrent events. Percutaneous PFO closure is a new treatment modality aimed at secondary prevention. METHODS AND RESULTS: Since April 1994, 132 consecutive patients, aged 51 +/- 12 years with PFO and with at least one paradoxical embolic event, underwent percutaneous PFO closure using six different device types. The embolic index event was an ischemic stroke in 62% of patients, a transient ischemic attack (TIA) in 33% of patients, and a peripheral embolism in 5% of patients. Thirty-six (27%) patients had PFO associated with ASA, whereas 96 (73%) patients had PFO only. The implantation procedure was successful in 130 (98%) patients. During and up to 6 years of follow-up (mean 1.8 +/- 1.6 years, 231 patient years), a total of eight recurrent embolic events were observed, with six TIAs, two peripheral emboli, and no ischemic stroke. The actuarial freedom from recurrence of the combined end point of TIA, ischemic stroke, and peripheral embolism was 95.3% (95% confidence interval [CI], 91.0%-96.4%) at 1 year and 90.5% (95% CI, 83.6%-97.2%) at 6 years. CONCLUSIONS: Percutaneous PFO closure can be performed with a high success rate. The procedure appears a promising therapeutic modality for secondary prevention of recurrent embolism in patients with PFO. Randomized trials must define its therapeutic value.     

Causes of recurrent focal neurologic events after transcatheter closure of patent foramen ovale with the CardioSEAL septal occluder

Transcatheter patent foramen ovale (PFO) closure has been undertaken to eliminate paradoxical emboli as a cause for recurrent strokes/transient ischemic attacks (TIAs). We report the results of investigations to determine causes of all significant focal neurologic events (FNEs) after PFO closure reported to our center. Records of 216 consecutive patients who underwent PFO closure were reviewed. Patients had to have had > or =1 preceding clinical event consistent with stroke/TIA considered by a neurologist to be consistent with an embolic episode. Follow-up was recommended at 24 hours, 1 month, 6 months, 1 year, and every 1 to 2 years thereafter. All patients were requested to report any new FNE possibly suggestive of stroke/TIA to our center. Reports of evaluations were reviewed in detail. Twenty patients had an FNE 0.1 month to 40.2 months after PFO closure over 438 person-years of follow-up (mean 2.1 years, range 1 month to 7.1 years). There were 4 recurrent strokes, 2 likely directly device related. Ten patients had TIA and 6 patients had clear evidence of pathology unrelated to the device. Event rate for recurrent strokes was 0.9% per year (95% confidence interval for difference 0.3 to 2.4) and combined event rate for stroke/TIA was 3.4% per year (95% confidence interval for difference 2 to 5.6). In conclusion, transcatheter PFO occlusion can be accomplished as an outpatient procedure with minimal immediate morbidity. Patients may have multiple possible causes of recurrent FNE. Recurrence rate of cryptogenic FNE compares favorably with reports of medical management. Analysis of results from ongoing randomized trials of transcatheter PFO closure versus medical management may improve our ability to select the best treatment for individual patients.     

Long-term efficacy of transcatheter patent foramen ovale closure on migraine headache with aura and recurrent stroke.

OBJECTIVES: To assess the long-term results of transcatheter patent foramen ovale (PFO) closure on migraine headache with aura (MHA) and on the risk of recurrent stroke. Background: Transcatheter PFO closure is associated with an early improvement of MHA, and a reduction or the risk of recurrent cerebral ischemia, but the long-term outcome after the procedure is unknown. METHODS: We analyzed follow-up data of 38 consecutive patients who had undergone transcatheter PFO closure at our institution because of cryptogenic stroke and had been followed-up for at least 3 years after the procedure. Mean age at closure was 43 +/- 13 years. Thirteen patients (34%) had a diagnosis of MHA made by the primary care physician or the referring neurologist. Migraine disability assessment questionnaire (MIDAS) was used to assess MHA incidence and severity. RESULTS: After a mean follow-up of 4.8 +/- 1.4 years, two patients had a recurrent stroke (13 and 15 months after the procedure, respectively). Recurrence rate 5 years after the procedure was 5.3%. After 4.9 +/- 1.4 years from the intervention, 12/13 patients (92%, 95% CI 65-99%) had complete resolution in their MHA. Overall, MIDAS score decreased significantly (38.6 +/- 26.3 vs. 4.4 +/- 5.1, P < 0.0001) after the procedure. One patient did not report any improvement of MHA after transcatheter PFO closure, whereas one patient reported a severe relapse of MHA about 1 year after PFO closure. Freedom from recurrent MHA 5 years after the procedure was 85% (95% CI 57-97%). CONCLUSIONS: The rate of recurrent cerebral ischemia and recurrent MHA seems to be low at long-term follow-up after transcatheter PFO closure. Recurrent cerebral ischemia and relapse of MHA seem to be confined to the first 15 months after the procedure.     

Patent foramen ovale: The never-ending story

Opinion statement Several uncontrolled studies suggested a relationship between patent foramen ovale (PFO) and stroke. But recent data indicate that previous studies may overestimate the association between PFO and stroke. First, among patients who have had a cryptogenic stroke under treatment (with either warfarin or aspirin), the main data from the French PFO/atrial septal aneurysm (ASA) and PICSS (Patent Foramen Ovale in Cryptogenic Stroke Study), analyzed separately and in combination, indicate that PFO alone does not announce a significantly increased risk of recurrent stroke or death. But a small increase or decrease in risk cannot be excluded by this metaanalysis. Second, the data concerning the association between PFO and ASA are not clear and variable: the French PFO/ASA study found a significantly increased risk of recurrent stroke in patients with cryptogenic stroke and an association between PFO and ASA when treated medically. In contrast, PICSS found no association between the combined PFO-ASA with stroke or death, but the two populations had meaningful differences. Patients in the PICSS were much older than those in the French PFO/ASA study and had more risk factors for stroke, such as hypertension, diabetes, and history of prior stroke. Third, there were inadequate data to conclude about ASA alone. Possible practice recommendations could come from this meta-analysis: the evidence indicates that the risk of recurrent stroke or death is not different for patients with a PFO who underwent cryptogenic stroke compared to patients without a PFO who underwent a cryptogenic stroke under treatment with either aspirin or warfarin. But aspirin is more preferable (300 mg/d). However, it seems that the association between PFO and ASA confers an increased risk of recurrent stroke in medically treated patients who are less than 55 years of age. This subgroup of younger stroke patients may benefit from other treatments, such as the percutaneous closure of PFO or mini-invasive surgery to a lesser extent, but their efficacy and safety are not yet assessed by large randomized trials. However, we must also keep in mind that some stroke patients with PFO are psychologically attached to their PFO and prefer to close it.     

Prevention of recurrent cerebral ischemic events in patients with patent foramen ovale and cryptogenic strokes or transient ischemic attacks

BACKGROUND: Patent foramen ovale (PFO) is found in up to 50% of patients less than 55 years of age who have had a stroke. Therapeutic options include no therapy, antiplatelet therapy, warfarin and surgical closure of the PFO. OBJECTIVES: To determine the relative and attributable risks of PFO for recurrent cerebral ischemic events in young patients with stroke or transient ischemic attacks. The predictors of recurrent cerebral ischemic events and the effects of different therapies on recurrence rates were sought. DESIGN: Follow-up of a retrospective cohort of patients with cryptogenic stroke or transient ischemic attacks identified from an echocardiography database. SETTING: University-based regional neurology referral centre. PATIENTS: Consecutive group of 90 patients less than 60 years of age who underwent transesophageal echocardiography following a cryptogenic transient ischemic attack (TIA) or stroke (cerebrovascular accident [CVA]) between 1991 and 1997. INTERVENTIONS: Structured telephone interviews and chart reviews. RESULTS: Fifty-two patients had a PFO, and 38 patients did not have a PFO. During a mean follow-up of 46 months, 19 recurrent cerebral ischemic events (12 TIA and seven CVA) occurred in 14 patients with PFO, and eight recurrent events (three TIA and five CVA) occurred in six patients without PFO. The recurrence rates were 12% and 5%/patient/year in the PFO and control groups, respectively, for a crude recurrence rate ratio of 2.39 (95% CI 1.01 to 6.32, P < 0.03). The attributable risk of PFO in recurrent neurological events was 7%/patient/year. In a Cox regression model, predictors of recurrent neurological events were presence of PFO (hazard ratio 5.27, 95% CI 1.58 to 17.6, P < 0.007), history of migraine (hazard ratio 4.54, 95% CI 1.11 to 18.52, P < 0.035), hypertension requiring therapy (hazard ratio 3.5, 95% CI 1.33 to 9.01, P < 0.01), and antiplatelet or no therapy instead of warfarin therapy (hazard ratio 2.88, 95% CI 1.11 to 8.7, P < 0.04). Fourteen patients underwent surgical closure of PFO; there were no neurological recurrences during a mean follow-up of 43 months (crude incidence rate difference 12%/patient/year, 95% CI 6.6 to 17.9, P < 0.02). CONCLUSIONS: Patients with PFO had a significantly higher rate of recurrent cerebral ischemic events than those without PFO. Surgical PFO closure prevented any recurrences during a mean follow-up of 43 months. Warfarin was better than antiplatelet therapy or no therapy in preventing recurrences.     

RESPECT远期随访结果能否结束PFO封堵疗效的争论？

RESPECT研究是一项前瞻性多中心随机对照试验,对卵圆孔未闭（PFO）并发不明原因脑卒中患者应用Amplatzer PFO 封堵器（St.Jude Medical,Inc.,St.Paul,MN）经导管PFO封堵+药物治疗与单独药物治疗进行对比,比较其二者在降低脑卒中复发风险方面是否有统计学差异。初步研究结果于2013年发表在新英格兰医学杂志上,其结果表明在预防不明原因脑卒中复发方面,经导管PFO封堵与药物治疗相比无统计学差异。但2015年10月15日在美国TCT会议上,公布了RESPECT研究的长期随访结果,得出了预防不明原因脑卒中复发,使用Amplatzer PFO封堵器行经导管PFO封堵优于药物治疗的最终结论。本文主要简介了RESPECT研究的主要内容和近期、远期结果,并对其作出笔者的评价。     

Transcatheter Closure of Patent Foramen Ovale in Patients with Paradoxical Embolism. Procedural and Follow-up Results after Implantation of the Starflex® Occluder Device with Conjunctive Intensified Anticoagulation Regimen

Background: Prevalence of patent foramen ovale (PFO) is higher in patients with paradoxical embolism and associated with increased risk for recurrent thromboembolic events. By percutaneous closure of PFO, surgical closure or permanent oral anticoagulation can be avoided. So far, published series included different occluder systems and various indications and regimens of postprocedural anticoagulation. The aim of the present study was to evaluate the short- and long-term results after implantation of the Starflex^® occluder in patients with PFO using an intensified anticoagulation regimen.
Methods and Results: 154 patients with PFO (94 men; age: 44 ± 13 years) and > 1 thromboembolic event were included. Other causes for embolism were excluded. PFO closure was successful in 147 patients (95.5%). All patients were treated with phenprocoumon (INR 2.5) and aspirin (100 mg/die) for 6 months. Transesophageal echocardiography (TEE) was repeated at 6 months. Mean clinical follow-up period was 26 ± 18 months.
After 6 months, five patients had a significant residual shunt, and five patients had suspected thrombus formation on the occluder. In three of these five patients, the occluder was surgically removed and foreign body reaction was noted. During follow-up, nine patients suffered from neurological events (two strokes, seven transient ischemic attacks [TIA]), though complete closure of the PFO was documented by TEE. Two patients died during follow-up; three patients had bleeding complications.
Conclusion: Percutaneous closure of PFO in symptomatic patients by Starflex^® occluder represents an effective therapy with a low incidence of periinterventional complications and recurrent thromboembolism. However, thrombus formation at the occluder system may occur in some patients despite an aggressive anticoagulation regimen.     

Cardiac Procedures to Prevent Stroke: Patent Foramen Ovale Closure/Left Atrial Appendage Occlusion

Stroke is a major contributor to population morbidity and mortality. Cardiac thromboembolic sources are an important potential cause of stroke. Left atrial appendage (LAA) thromboembolism in association with atrial fibrillation is a major contributor to stroke occurrence, particularly in elderly individuals. Patent foramen ovale (PFO) acts as a potential conduit from the right-sided circulation to the brain, and has been suggested to be an important factor in cryptogenic stroke in the young patients. Advances in interventional cardiology have made it possible to deal with these potential stroke sources (LAA and PFO), but the available methods have intrinsic limitations that must be recognized. Furthermore, the potential value of LAA and PFO closure depends on our ability to identify when the target structure is importantly involved in stroke risk; this is particularly challenging for PFO. This article addresses the clinical use of PFO and LAA closure in stroke prevention. We discuss technical aspects of closure devices and methods, questions of patient selection, and clinical trials evidence. We conclude that for PFO closure, the clinical trials evidence is thus far negative in the broad cryptogenic stroke population, but closure might nevertheless be indicated for selected high-risk patients. LAA closure has an acceptable balance between safety and efficacy for atrial fibrillation patients with high stroke risk and important contraindications to oral anticoagulation. Much more work needs to be done to optimize the devices and techniques, and better define patient selection for these potentially valuable procedures.     

Cryptogenic stroke in patients with patent foramen ovale

Paradoxical embolism through a patent foramen ovale (PFO) is a commonly identified potential mechanism of ischemic stroke, especially in young patients. The recurrent stroke rate among young cryptogenic stroke patients with a PFO is modest, but higher than normal for their age. Co-existing atrial septal aneurysm is a substantial, and the only definite, potentiator of stroke risk in patients with PFO, but PFO size, degree of functional shunting, and co-existing hypercoagulable state likely are additional risk factors. Pelvic CT and magnetic resonance venography have improved our ability to detect source venous thromboemboli and underlie new management strategies. Treatment strategies for PFOs in ischemic stroke patients include antiplatelet agents, anticoagulants, surgical closure, or percutaneous closure devices. The completion of ongoing, randomized clinical trials comparing percutaneous closure devices with medical management is likely to be hastened by the recent withdrawal of humanitarian device exemption approvals, and is urgently needed to clarify if the risks of invasive endovascular device placement are outweighed by a long-term reduction in recurrent vascular events.     

Transcatheter closure of patent foramen ovale in patients with paradoxical embolism. Procedural and follow-up results after implantation of the Starflex occluder device with conjunctive intensified anticoagulation regimen.

BACKGROUND: Prevalence of patent foramen ovale (PFO) is higher in patients with paradoxical embolism and associated with increased risk for recurrent thromboembolic events. By percutaneous closure of PFO, surgical closure or permanent oral anticoagulation can be avoided. So far, published series included different occluder systems and various indications and regimens of postprocedural anticoagulation. The aim of the present study was to evaluate the short- and long-term results after implantation of the Starflex occluder in patients with PFO using an intensified anticoagulation regimen. METHODS AND RESULTS: 154 patients with PFO (94 men; age: 44 +/- 13 years) and >or=1 thromboembolic event were included. Other causes for embolism were excluded. PFO closure was successful in 147 patients (95.5%). All patients were treated with phenprocoumon (INR 2.5) and aspirin (100 mg/die) for 6 months. Transesophageal echocardiography (TEE) was repeated at 6 months. Mean clinical follow-up period was 26 +/- 18 months. After 6 months, five patients had a significant residual shunt, and five patients had suspected thrombus formation on the occluder. In three of these five patients, the occluder was surgically removed and foreign body reaction was noted. During follow-up, nine patients suffered from neurological events (two strokes, seven transient ischemic attacks [TIA]), though complete closure of the PFO was documented by TEE. Two patients died during follow-up; three patients had bleeding complications. CONCLUSION: Percutaneous closure of PFO in symptomatic patients by Starflex occluder represents an effective therapy with a low incidence of periinterventional complications and recurrent thromboembolism. However, thrombus formation at the occluder system may occur in some patients despite an aggressive anticoagulation regimen.