Dye dilution and oximetry for detection of patent foramen ovale

Objectives - Patent foramen ovale (PFO) is a risk factor for stroke of undetermined (cryptogenic) origin. Low cost and non-invasive bedside tests for detection of PFO are needed as alternatives to contrast transesophageal echocardiography. We investigated whether dye dilution curves and oximeter recordings are useful for detecting PFO and what is the prevalence of PFO in patients with cryptogenic stroke determined with these bedside methods. We also studied whether stroke risk factors, number of brain lesions, and stroke recurrence rates were different in patients with an unexplained stroke with and without PFO. Material and methods - Dye dilution curves and oximeter recordings with non-invasive earpiece apparatus were obtained in 59 patients aged under 50 years who had had a cryptogenic brain infarction. The number of ischemic lesions in the brain was counted by MRI. Results - PFO was found in 24 (41%) of 59 patients. There was a 100% concordance in results obtained by dye dilution and by oximetry. Risk factors for stroke were similar in subjects with PFO and those without PFO. No significant association was found between PFO and Valsalva-like activity at stroke onset. Those with PFO did not have more ischemic lesions detected by MRI nor did they have more recurrent ischemic episodes. Conclusion - Dye dilution and oximetry are cheap and useful methods for detection of PFO and could be used for screening of the risk of paradoxical embolism. Because these 2 methods were not compared with the golden standard, transesophageal echocardiography, the specificity and sensitivity of the tests remain unsettled.     

卵圆孔未闭与隐源性卒中的研究进展

隐源性卒中约占所有缺血性卒中的40%,其病因、诊断和治疗一直是临床工作者的研究热 点。近年来发现,卵圆孔未闭与隐源性卒中的发病密切相关,是隐源性卒中的重要危险因素。在临床 中常用经食管超声心动图、经胸壁超声心动图、经颅多普勒发泡试验和心脏MRI等方法来检测卵圆孔 未闭。反常栓塞是卵圆孔未闭导致隐源性卒中的主要发病机制。在头部影像学检查中,绝大多数卵圆 孔未闭相关隐源性卒中患者为多血管分布区的多发散在小梗死。在药物治疗方面,抗血小板药物相 对于抗凝药物,可能更适合大多数卵圆孔未闭合并隐源性卒中的患者。此外,近期多项临床随机对照 研究均表明,卵圆孔未闭封堵术对于预防卵圆孔未闭合并隐源性卒中患者卒中再发的疗效明显优于 药物治疗。     

Sleep apnea syndrome and patent foramen ovale: a dangerous association in ischemic stroke?

BackgroundThe coexistence of patent foramen ovale (PFO) and sleep apnea syndrome (SAS) might be related to the pathogenesis of cryptogenic stroke (CS). We aimed to determine the prevalence of SAS in patients with cryptogenic stroke and PFO.MethodsThis is a prospective case-control study in which we included ischemic stroke patients consecutively admitted to our hospital's Acute Stroke Unit. Contrast transcranial Doppler (c-TCD) and sleep polygraphy within the first 72 h after stroke onset were performed to detect PFO and SAS. Demographic and clinical characteristics, time of stroke onset, score in the National Institute of Health Stroke Scale (NIHSS), and stroke subtype were registered.ResultsA total of 97 patients were studied. Overall, 76% were men, with a mean ± SD age of 61 ± 13 years, and an NIHSS of 5 ± 5. Subtype of stroke was cryptogenic (CS) in 28 (29%) and non-CS in 69 (71%) of patients. PFO was more frequent among patients with CS (64% vs 29%, p = 0.002) and without SAS (60% vs 32%, p = 0.013). SAS was diagnosed in 74% of the whole group, with a higher prevalence in patients with known stroke etiology (83% vs 53%, p = 0.003). Finally, the prevalence of SAS and PFO coexistence was similar in patients with or without cryptogenic stroke (25% vs 22%, p = 1), and when comparing the group of patients with cryptogenic wake-up stroke to the other stroke patients (43% vs 21%, p = 0.35).ConclusionsAccording to our results, there is no evidence of an association of PFO and SAS in the pathogenesis of cryptogenic stroke.     

卵圆孔未闭并隐源性卒中的临床及影像学分析

目的探讨卵圆孔未闭(patent foramen ovale,PFO)并隐源性卒中(cryptogenic stroke,CS)的临床及影像学特征。方法连续性纳入2015年3月~2015年12月入住郑州大学附属洛阳中心医院神经内科的年龄≤65岁的急性缺血性脑卒中患者,对其进行脑血管病危险因素筛查,并行TOAST分型。对所有入组患者通过经胸超声心动图声学造影(c TTE)联合经颅多普勒声学造影(c TCD)(即发泡试验)行PFO筛查,两者均为阳性视为存在PFO。分析PFO在急性缺血性卒中中检出率,及PFO并CS的分流量、影像学分布特征及部分封堵术后疗效观察。结果共纳入141例符合标准的急性缺血性卒中患者。隐源性卒中48例(34.0%),非隐源性卒中93例(66.0%)。PFO阳性率在缺血性卒中组、CS组、非CS组中分别为31.2%(44/141)、47.9%(23/48)、22.6%(21/93)。PFO阳性组中,隐源性卒中较非隐源性卒中存在较大的分流量,且差异有统计学意义(P=0.007)。而PFO相关性隐源性卒中与非PFO相关性隐源性卒中患者在其病灶分布的部位、数量之间的差异无统计学意义。PFO封堵术后6月随访未见复发,但尚缺乏对照性研究。结论 PFO及其分流量与CS密切相关,但PFO并CS患者无特异性影像学表现,应加强对此类患者的筛查与管理。     

Factors related to recurrence of paradoxical cerebral embolism due to patent foramen ovale

Patent foramen ovale (PFO) is an important etiology of ischemic stroke in young adults. We investigated factors contributing to recurrent ischemic stroke in patients with PFO. Subjects comprised 47 patients (mean age, 56.8 ± 14.2 years; range 23-74 years) with ischemic stroke due to PFO who were admitted to our hospital between April 2007 and February 2011. Mean duration of follow-up was 34.5 ± 13 months. Recurrence occurred in 11 cases. Annual recurrence rate was 23.4%. We investigated relationships between recurrence of ischemic stroke and size of PFO (large, >4 mm; medium, 2-3.9 mm; small, <1.9 mm; absent group), maximal number of microbubbles (determined as the number of microembolic signals: small, 0-5; moderate, 6-25; and multiple, ≥ 26), massive bubble on contrast transesophageal echocardiography or atrial septal aneurysm, D-dimer level and antithrombotic therapy. Univariate analysis showed size of the PFO (P = 0.013), number of microbubbles (P = 0.021), and presence of a massive bubble on echocardiography (P = 0.04) were related to recurrence of ischemic stroke. Logistic analysis identified size of the PFO (P < 0.05) and massive bubble on echocardiography (P < 0.05) as factors related to recurrence of ischemic stroke. In conclusion, size of the PFO and presence of a massive bubble were considered to be factors associated with recurrence of ischemic stroke due to PFO.     

Patent foramen ovale and atrial septal aneurysm can cause ischemic stroke in patients with antiphospholipid syndrome

The purpose of the present study was to evaluate the contributions of embolic etiologies, patent foramen ovale (PFO) and atrial septal aneurysm (ASA) to the pathogenesis of ischemic stroke in patients with antiphospholipid syndrome (APS). We performed transesophageal echocardiography (TEE) examination for consecutive stroke patients who had been diagnosed with APS (APS group) to detect potential embolic sources. APS was diagnosed based on the modified Sapporo criteria. The control stroke group comprised age- and sex-matched cryptogenic stroke patients undergoing TEE. We assessed and compared the clinical characteristics and TEE findings between stroke patients with APS and control stroke groups. Among 582 patients, nine patients (nine women; mean age, 50 ± 18 years) were classified into the APS group. In 137 patients undergoing TEE, 41 age-matched female stroke patients were recruited to the control stroke group. Prevalences of PFO and ASA were significantly higher in the APS group than in the control stroke group (89 vs. 41 %, p = 0.027; 67 vs. 20 %, p = 0.015, respectively). Multiple logistic regression analysis showed that PFO (odds ratio (OR), 13.71; 95 % confidence interval (CI), 1.01–185.62; p = 0.049) and ASA (OR, 8.06; 95 % CI, 1.17–55.59; p = 0.034) were independently associated with the APS group. PFO and ASA were strongly associated with the APS group, and could thus represent potential embolic sources in ischemic stroke patients with APS.     

Patent foramen ovale and stroke: what we do and don't know

Paradoxical embolism through a patent foramen ovale (PFO) is a commonly identified mechanism of ischemic stroke, especially in young patients. The ability to detect PFOs in life improved dramatically with the development of aerated ultrasound contrast, transesophageal echocardiography, and transcranial Doppler ultrasound. Similarly, the ability to detect source venous thromboemboli is improving with pelvic magnetic resonance venography. Coexisting atrial septal aneurysm is the only definite potentiator of stroke risk in patients with PFO. PFO size and degree of functional shunting may be additional risk factors. Currently, PFOs are treated variably with antiplatelet agents, anticoagulants, surgical closure, or, increasingly, percutaneous closure devices. Completion of randomized clinical trials is urgently needed to clarify if the risks of invasive endovascular device placement are outweighed by a long-term reduction in recurrent vascular events.     

The prevalence of patent foramen ovale in patients with migraine

BACKGROUND AND PURPOSE: Migraine is a common neurologic disorder whose etiology remains unknown. Migraine has been reported as a possible risk factor for ischemic stroke, especially in young women. The relationship between migraine and stroke is stronger in patients suffering from migraine with aura compared to those with common migraine. Coexistence of migraine and patent foramen ovale (PFO) should be also considered. The aim of our study was to evaluate the frequency of PFO in patients with migraine with aura (MA) and compare it with the prevalence of PFO in migraine patients without aura (M) and in a healthy age-matched control group. MATERIAL AND METHODS: We assessed 62 patients (48 females) suffering from migraine with aura, 60 without aura (53 females) and 65 normal controls (51 females). In order to detect PFO the contrast transcranial Doppler was performed during Valsalva maneuver. RESULTS: The presence of PFO was found in 33/62 (53%) patients with MA compared to 15/60 (25%) without aura, and in 16/65 (25%) control subjects. The difference in PFO prevalence between MA patients and M patients and the difference between MA patients and the control group was statistically significant (p<0.05). CONCLUSIONS: Our findings suggest that at least some attacks of migraine with aura may be associated with paradoxical embolism.     

Risk of recurrent ischemic stroke in patients with patent foramen ovale: The role of D-dimer

BackgroundParadoxical embolism under elevated thromboembolic conditions is known to be the primary mechanism of patent foramen ovale (PFO)-related stroke. We hypothesized that higher levels of D-dimer, a marker of thromboembolism, could increase the risk of stroke recurrence in patients with PFO.MethodsWe conducted a retrospective analysis of data from 1226 consecutive patients with acute ischemic cryptogenic stroke (CS) who underwent transesophageal echocardiography (TEE). D-dimer was assessed during admission. We used a multivariate Cox proportional hazards model to evaluate the association of long-term outcomes between the presence of PFO and levels of D-dimer.ResultsOf the 1226 patients, the study included 461 who underwent TEE. Among them, 242 (52.5%) had PFOs. Among PFO patients, those with a D-dimer level >1.0 mg/L had a significantly higher risk of stroke recurrence compared to those with <0.5mg/L (adjusted hazard ratio (aHR) 4.04, 95% confidence interval [CI] 1.63–10.02). A pattern of increased risk of event with increasing D-dimer levels was observed (P_trend=0.008). However, there was no significant difference in the risk of stroke recurrence at any D-dimer level compared to D-dimer level <0.5 mg/L among patients without PFO. In these patients, there was little evidence of increased risk with increasing D-dimer levels (P_trend=0.570).ConclusionsThis study demonstrated that the elevated D-dimer level increased the recurrence of stroke in CS patients with PFO, particularly showing a dose-dependent relationship between D-dimer levels and recurrence. However, no such effect was observed in patients without PFO. These findings provide valuable insights into the potential benefits of anticoagulation for strokes related to PFO.     

Management of right-to-left shunt in cryptogenic cerebrovascular disease: results from the observational Austrian paradoxical cerebral embolism trial (TACET) registry

Paradoxical embolism due to a patent foramen ovale (PFO) is a possible cause of ischemic stroke, particularly in young cryptogenic stroke patients. In most cases, however, it is difficult to establish a firm etiological association and the debate about management is ongoing. The Austrian Paradoxical Cerebral Embolism Trial was designed as a prospective, national, multi-center, non-randomized registry to add further data on this topic before the completion of randomized controlled trials. Over 27 months 188 cryptogenic stroke/TIA patients ≤55 years were entered by 15 Austrian stroke units. Contrast transesophageal echocardiography demonstrated a cardiac right-to-left shunt (RLS) in 176 patients; a pulmonary RLS was assumed in 10, and 2 showed both. Ninety-seven (55 %) patients with cardiac RLS underwent interventional treatment, and this was more likely for patients with stroke as index event, a symptomatic infarction on MRI and a large size of PFO. Over 2 years, recurrences occurred at a rate of approximately 1.3 % for stroke and 4.3 % for TIA, and were especially frequent in patients with pulmonary RLS. When comparing outcomes in patients with cardiac RLS there was a trend for fewer recurrences with interventional management (closure: four TIA in four patients vs. medical: three strokes and seven TIA in nine patients; p = 0.066 for events, p = 0.085 for patients). The complication rate was 13.4, and 5.7 % had residual shunting. The possible causes for paradoxical embolism in young patients with cryptogenic stroke appear more variable than usually considered, and other causes than PFO should not be neglected. Interventional treatment of a cardiac RLS may offer a small benefit, but has to be weighed against possible complications and the problem of establishing causality.     

Abnormalities of interatrial septum and ischemic stroke in young people

OBJECTIVE: To verify the frequency of patent foramen ovale (PFO) among patients with ischemic stroke (cryptogenic or with a known cause) investigated by transcranial doppler (TCD) and transesophageal echocardiography. Secondarily, to determine the diagnostic validity of the former, compared with the later method. METHOD: Retrospectively, 124 patients (<51 years old) with ischemic stroke were submitted to TCD and or transesophageal echocardiography. The patients were classified as cryptogenic stroke or not. RESULTS: We could found an important association between cryptogenic ischemic stroke and PFO (odds ratio 4.3--CI 95% 1.7-10.7). Only five cases of interatrial septal aneurysm were diagnosed among patients with PFO. Sensitivity, specificity and positive and negative predictive values exhibited values upper of 85%, equivalents, at least based on confidence intervals. CONCLUSION: We could determine, for the first time in our country, a strong association between cryptogenic ischemic stroke and PFO. The TCD is a valuable diagnostic resource in this context since its validity was considered excellent. A detailed investigation in these cases should always be done due to the possibility of FOP closure.     

The value of transesophageal echocardiography in the investigation and management of cryptogenic cerebral ischemia: a single-center experience

The diagnostic utility of transesophageal echocardiography (TEE) has often been challenged in patients with cryptogenic stroke (CS). We estimated the prevalence of different findings on TEE examination of CS patients, their impact on secondary stroke prevention and the presence of potential age or gender disparities. We reviewed all TEE examinations that were performed in a single echocardiography laboratory during a 7-year-old period to identify CS patients that underwent investigation with TEE. Of the 518 total TEE examinations, we identified 88 CS patients. TEE revealed abnormal findings in 69.3 % of them. Patent foramen ovale (PFO) and atrial septal aneurysm (ASA) were identified in 30.6 and 22.7 % of the patients. Ascending aorta and aortic arch atheromatosis was present in 26.1 % of the patients, with complex atheromatosis diagnosed in 14.7 % of them. Cardiac myxomas were uncovered in 2.3 %. Thrombi in the left atrium and in cardiac valves were reported in 3.4 and 2.3 % of the patients, respectively. Based on TEE findings, the therapeutic management would be very likely modified in 9.1 % of the patients. Subgroup analysis revealed no gender disparities on the prevalence of TEE findings and in secondary stroke prevention, while linear regression analyses revealed significant associations of age with the prevalence of PFO, ASA, aorta atheromatosis and complex aorta atheromatosis. TEE examination should be included in the diagnostic work-up of all CS patients, irrespective of age and gender status, since it can reveal potential sources of embolism and has a significant impact for secondary stroke prevention.     

Cryptogenic stroke, aortic arch atheroma and patent foramen ovale

Cryptogenic stroke represents a diagnostic challenge. Several conditions have been found to be more frequent in patients with cryptogenic stroke. Aortic arch atheroma (AAA) and patent foramen ovale (PFO) have been shown to be highly prevalent in the adult population, especially in patients with ischemic cerebrovascular events, particularly cryptogenic strokes. In both conditions, clinical relevance and stroke risk are related to age, with AAA being more frequent and severer in patients >55 years, and the relationship between stroke and PFO being stronger in those <55 years of age. This review is focused on the prevalence, risk of stroke and therapeutic strategies in patients with cryptogenic stroke related to AAA or PFO.     

Patent foramen ovale increases the risk of acute ischemic stroke in patients with acute pulmonary embolism leading to right ventricular dysfunction

Background

Patent foramen ovale (PFO) is an established risk factor for ischemic stroke. Since acute right ventricular dysfunction (RVD) observed in patients with PE can lead to right-to-left inter-atrial shunt via PFO, we hypothesized that PFO is a risk factor for ischemic stroke in PE with significant right ventricular dysfunction.

Methods

55 patients (31 F, 24 M), median age 49 years (range 19–83 years) with confirmed PE underwent echocardiography for RVD and PFO assessment. High risk acute PE was diagnosed in 3 (5.5%) patients, while 16 (29%) hemodynamically stable with RVD patients formed a group with intermediate-risk PE. PFO was diagnosed in 19 patients (34.5%). Diffusion-weighted MRI of the brain for acute ischemic stroke (AIS) was performed in all patients 4.91 ± 4.1 days after admission.

Results

AIS was detected by MRI in 4 patients (7.3%). Only one stroke was clinically overt and resulted in hemiplegia. All 4 AIS occurred in the PFO positive group (4 of 19 patients), and none in subjects without PFO (21.0% vs 0%, p = 0.02). Moreover, all AIS occurred in patients with RVD and PFO, and none in patients with PFO without RVD (50% vs 0%, p = 0.038).

Conclusion

Our data suggest that acute pulmonary embolism resulting in right ventricular dysfunction may lead to acute ischemic stroke in patients with patent foramen ovale. However, the clinical significance of such lesions remains to be determined.     

The impact of cerebral microbleeds on intracerebral hemorrhage and poor functional outcome of acute ischemic stroke patients treated with intravenous thrombolysis: a systematic review and meta-analysis

It is still controversial whether pre-existing cerebral microbleeds (CMBs) increase the risks of intracranial hemorrhage (ICH) and poor functional outcome (PFO) in acute ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT). Therefore, we performed a systematic review and meta-analysis to determine the impact of CMBs on ICH and PFO of AIS patients with IVT. We searched PubMed, EMBASE and Web of Science from inception to August 3, 2016, with language restriction in English. We included studies that reported the relationship between CMBs and ICH or PFO after thrombolysis. Two retrospective and nine prospective studies met inclusion criteria (total 2702 patients). The overall prevalence of CMBs on pre-IVT MRI scans was 24.0%. Pre-existing CMBs on MRI scans were not significantly associated with a higher risk of early sICH (OR 1.74; 95% CI 0.91–3.33; I ² = 44.5%). Subgroup analyses did not substantially influence these associations. The presence of CMBs was associated with the increased risk of 3-month PFO (OR 1.58; 95% CI 1.08–2.31; I ² = 54.2%), PH (OR 2.14; 95% CI 1.34–3.42; I ² = 11.0%) and any ICH (OR 1.42; 95% CI 1.04–1.95; I ² = 0.0%), respectively. This meta-analysis showed that CMBs presence was not significantly associated with the increased risk of early sICH after IVT. However, the results also demonstrated that CMBs presence increased the risks of 3-month PFO, PH and any ICH after IVT. Due to a small number of included studies and methodological limitations, the results of this meta-analysis should be interpreted cautiously. CMBs presence should not be a contraindication to IVT for AIS patients based on the existing evidence.     

Prevalence of atrial septal abnormalities in older patients with cryptogenic ischemic stroke or transient ischemic attack

OBJECTIVE: To evaluate the association of atrial septal abnormalities - patent foramen ovale (PFO), atrial septal aneurysm (ASA), or the combination of both (PFO+ASA) - with cryptogenic stroke or transient ischemic attack (TIA) in older patients. METHODS: We examined the prevalences of PFO, ASA, and PFO+ASA in 132 consecutive patients aged 55 years or more who underwent transesophageal echocardiography (TEE) for evaluation of ischemic stroke or TIA. We compared patients with cryptogenic stroke/TIA and those with stroke/TIA of known cause. RESULTS: PFO+ASA was more common in patients with cryptogenic stroke/TIA than in patients with stroke/TIA of known cause (12/62 or 19% vs. 2/70 or 3%; adjusted odds ratio, 7.4; 95% CI, 1.4-38.2). Differences between groups for isolated PFO, and isolated ASA were not significant. The association of PFO+ASA with cryptogenic stroke/TIA was confirmed in the subgroup of patients aged 75 years or more (odds ratio, 15.0; 95% CI, 1.5-146.7). CONCLUSION: This study indicates a significant association of PFO+ASA with cryptogenic stroke or TIA in older patients.     

经颅多普勒发泡实验在筛查隐源性卒中合并卵圆孔未闭的应用价值

目的探讨经颅多普勒发泡实验(C-TCD)在筛查隐源性卒中合并卵圆孔未闭中的应用价值。方法回顾分析60例隐源性卒中患者,包括发病特点,既往史,检验检查,分析相关数据。结果 60例患者均明确诊断为急性脑梗死、短暂性脑缺血发作,行经颅多普勒超声发泡试验(c-TCD)发现,阳性33例,阴性27例,经食道超声心动(TEE)检查证实有26例合并心脏卵圆孔未闭,16例合并下肢静脉血栓形成。结论 PFO在隐源性卒中中为常见病因,但常规检查很难发现,本研究通过c-TCD初步筛查PFO,阳性率及敏感性高于TEE,特异性亦较高,对于隐源性卒中合并PFO,可作为病因筛查的首选。     

Neurosonological examinations]

Neurosonological examinations play an important role in the diagnosis of cerebrovascular disease. The target used to be limited to the extracranial carotid artery but is now extended to the intracranial arteries. Carotid artery ultrasound can evaluate not only the degree of stenosis but also the vulnerability of plaque. Transcranial Doppler can detect the micro-embolus in the intracranial artery. Transesophagial echocardiography and cruralvein ultrasound are indispensable to detect embolic source. Transesophagial echocardiography is able to detect thrombus, tumor and vegitation in the heart, patent foramen ovale (PFO) and atheroma of aorta. Because PFO is found rather commonly in healthy subjects, the detection of deep vein thrombosis (DVT) is essential for the diagnosis of paradoxical embolism. In stroke patients with PFO, RI venography can rarely detect DVT, while cruralvein ultrasound commonly detect DVT in small vein. The demand of neurosonological examinations is considered to increase more and more because of their non-invasiveness and convenience.     

Carotid Atherosclerosis and Patent Foramen Ovale in Embolic Stroke of Undetermined Source

BackgroundCarotid atherosclerosis and likely pathogenic patent foramen ovale (PFO) are two potential embolic sources in patients with embolic stroke of undetermined source (ESUS). The relationship between these two mechanisms among ESUS patients remains unclear.AimTo investigate the relation between carotid atherosclerosis and likely pathogenic PFO in patients with ESUS. We hypothesized that ipsilateral carotid atherosclerotic plaques are less prevalent in ESUS with likely pathogenic PFO compared to patients with likely incidental PFO or without PFO.MethodsThe presence of PFO was assessed with transthoracic echocardiography with microbubble test and, when deemed necessary, through trans-oesophageal echocardiography. The presence of PFO was considered as likely incidental if the RoPE (Risk of Paradoxical Embolism) score was 0–6 and likely pathogenic if 7–10.ResultsAmong 374 ESUS patients (median age: 61years, 40.4% women), there were 63 (49.6%) with likely incidental PFO, 64 (50.4%) with likely pathogenic PFO and 165 (44.1%) with ipsilateral carotid atherosclerosis. The prevalence of ipsilateral carotid atherosclerosis was lower in patients with likely pathogenic PFO (7.8%) compared to patients with likely incidental PFO (46.0%) or patients without PFO (53.0%) (p<0.001). After adjustment for multiple confounders, the prevalence of ipsilateral carotid atherosclerosis remained lower in patients with likely pathogenic PFO compared to patients with likely incidental PFO or without PFO (adjusted OR=0.32, 95%CI:0.104-0.994, p=0.049).ConclusionsThe presence of carotid atherosclerosis is inversely related to the presence of likely pathogenic PFO in patients with ESUS.     

Significant association of atrial vulnerability with atrial septal abnormalities in young patients with ischemic stroke of unknown cause

BACKGROUND AND PURPOSE: Atrial septal abnormalities have been associated with cryptogenic ischemic stroke in young patients, but the causal link has not yet been established. Paradoxical embolism is considered the most likely mechanism but is rarely proven. It can be hypothesized that, in those patients, paroxysmal atrial arrhythmias, potentially favored by the anatomic abnormalities, can be another cause of thrombus formation and subsequent embolism to the brain. In this study we assessed the relationship between atrial vulnerability, reflecting arrhythmogenic properties of the atria, and atrial septal abnormalities in young patients with cryptogenic ischemic stroke. METHODS: We enrolled 62 consecutive patients aged <55 years who had ischemic stroke of unknown cause and transesophageal echocardiography to assess atrial septal aneurysm (ASA) or patent foramen ovale (PFO) (ie, atrial septal abnormalities). These patients underwent electrophysiological study to measure atrial refractoriness and conduction time defining a vulnerability index (ie, latent atrial vulnerability) and to assess the inducibility of sustained (lasting >60 seconds) atrial fibrillation with the use of programmed atrial stimulation. Actual atrial vulnerability was defined by the presence of both latent vulnerability and inducibility of sustained atrial fibrillation lasting >60 seconds. RESULTS: We found atrial vulnerability in 58% of patients with atrial septal abnormalities and in 25% of patients without (odds ratio=4.1 [95% CI, 1.3 to 12.7; P<0.02]). The difference between patients with and without PFO or between patients with both PFO and ASA and those without were also significant. Patients with inducible sustained atrial fibrillation had more frequent past history of palpitations and syncope than patients without (P<0.02). CONCLUSIONS: Atrial vulnerability is associated with atrial septal abnormalities in patients with cryptogenic stroke. This result raises the question of the potential role of transient atrial arrhythmias in thrombus formation in the presence of PFO or ASA.