Associations of Apixaban Dose With Safety and Effectiveness Outcomes in Patients With Atrial Fibrillation and Severe Chronic Kidney Disease.

BACKGROUND: Recommendations for apixaban dosing on the basis of kidney function are inconsistent between the US Food and Drug Administration and European Medicines Agency for patients with atrial fibrillation. Optimal apixaban dosing in chronic kidney disease remains unknown. METHODS: With the use of deidentified electronic health record data from the Optum Labs Data Warehouse, patients with atrial fibrillation and chronic kidney disease stage 4/5 initiating apixaban between 2013 and 2021 were identified. Risks of bleeding and stroke/systemic embolism were compared by apixaban dose (5 versus 2.5 mg), adjusted for baseline characteristics by the inverse probability of treatment weighting. The Fine-Gray subdistribution hazard model was used to account for the competing risk of death. Cox regression was used to examine risk of death by apixaban dose. RESULTS: Among 4313 apixaban new users, 1705 (40%) received 5 mg and 2608 (60%) received 2.5 mg. Patients treated with 5 mg apixaban were younger (mean age, 72 versus 80 years), with greater weight (95 versus 80 kg) and higher serum creatinine (2.7 versus 2.5 mg/dL). Mean estimated glomerular filtration rate was not different between the groups (24 versus 24 mL·min-1·1.73 m-2). In inverse probability of treatment weighting analysis, apixaban 5 mg was associated with a higher risk of bleeding (incidence rate 4.9 versus 2.9 events per 100 person-years; incidence rate difference, 2.0 [95% CI, 0.6-3.4] events per 100 person-years; subdistribution hazard ratio, 1.63 [95% CI, 1.04-2.54]). There was no difference between apixaban 5 mg and 2.5 mg groups in the risk of stroke/systemic embolism (3.3 versus 3.0 events per 100 person-years; incidence rate difference, 0.2 [95% CI, -1.0 to 1.4] events per 100 person-years; subdistribution hazard ratio, 1.01 [95% CI, 0.59-1.73]), or death (9.9 versus 9.4 events per 100 person-years; incidence rate difference, 0.5 [95% CI, -1.6 to 2.6] events per 100 person-years; hazard ratio, 1.03 [95% CI, 0.77-1.38]). CONCLUSIONS: Compared with 2.5 mg, use of 5 mg apixaban was associated with a higher risk of bleeding in patients with atrial fibrillation and severe chronic kidney disease, with no difference in the risk of stroke/systemic embolism or death, supporting the apixaban dosing recommendations on the basis of kidney function by the European Medicines Agency, which differ from those issued by the US Food and Drug Administration.

Pulmonary arteriovenous malformation and cryptogenic stroke / 国际脑血管病杂志

The relationship between pulmonary arteriovenous malformations (PAVMs) and stroke remains unclear. With the development of imaging technology, studies shows that PAVMs are an important cause of cryptogenic stroke (CS). Most PAVMs are not diagnosed until the onset of stroke. The main pathogenesis of PAVMs-related CS is paradoxical embolism and increased blood viscosity caused by iron deficiency anemia. Antiplatelet therapy and interventional therapy may have a preventive effect on recurrent stroke in such patients. This article summarizes the pathophysiological mechanism, diagnosis and treatment of PAVMs-related CS, hoping to provide new ideas for the diagnosis and treatment of CS.

Paradoxical brain embolism and pulmonary embolism due to a deep femoral venous aneurysm and patent foramen ovale: a case report / 中华神经科杂志

The cases of paradoxical brain embolism (PBE) due to venous aneurysms and patent foramen ovale (PFO) are extremely scarce, with only 5 cases caused by popliteal venous aneurysm reported in the literature to date, while PBE caused by deep femoral venous aneurysm (DFVA) and PFO has not been reported. Herein, an unusual case of PBE in a 15-year-old girl with PFO who still had cerebral infarction and pulmonary embolism after transcatheter closure was present. She was finally diagnosed as PFO with DFVA by angiography. Furthermore, clinical characteristics of 6 cases were summarized to improve the clinicians′ recognition of the rare risk factor of stroke-venous aneurysms of the lower extremity deep veins.

Comparison of right-to-left shunt characteristics in cryptogenic embolic ischemic stroke and non-cardioembolic ischemic stroke / Comparação das características do shunt direita-esquerda em pacientes com AVC isquêmico criptogênio e AVC não cardioembólico

Abstract Background: Patent foramen ovale (PFO) has been considered a potential mechanism of embolic stroke of undetermined origin. Objective: The aim of the present study was to identify the features of the right-to-left shunt (RLS) in patients with undetermined embolic ischemic stroke and compare them with those of patients with non-cardioembolic ischemic stroke. Methods: A retrospective study was conducted with 168 patients with stroke and RLS separated into the following two groups: the undetermined embolic stroke group (UES group) and non-cardioembolic stroke group (NCES group). All patients were assessed by transcranial Doppler to evaluate the presence and quantification of microembolic signals (MES) at rest and under Valsalva maneuver. Results: Of all patients evaluated in the current study, 96 were included in the UES group and 72 in the NCES group. In the UES group, 65 patients had RLS with ≥10 MES (67.7%), which was higher than that observed in the NCES group (51.4%, p=0.038). According to the moment of the cardiac cycle, 75 patients (78.1%) in the UES group had a positive test at rest compared to 42 (58.3%) in the NCES group (p=0.007). Conclusions: The current study demonstrated that almost 70% of patients with undetermined embolic stroke and PFO presented a large RLS and more than 75% had RLS at rest. These findings suggest that the size of the shunt should be taken into account when evaluating whether PFO could be a possible mechanism underlying cryptogenic stroke.

RESUMO Antecedentes: Uma das potenciais fontes embólicas no acidente vascular cerebral (AVC) de origem indeterminada é o forame oval patente (FOP). Objetivo: O objetivo do presente estudo foi identificar as características do shunt direita-esquerda em paciente com AVC de etiologia indeterminada, presumidamente embólica, e comparar tais características com pacientes apresentando AVC por outras causas não embólicas. Métodos: Trata-se de um estudo retrospectivo com 168 pacientes com AVC e forame oval patente, separados em dois grupos: AVC embólico de etiologia indeterminada e AVC por outras causas não embólicas. Todos os pacientes foram submetidos a Doppler transcraniano, para avaliar a presença de shunt direita-esquerda por meio do teste de embolia paradoxal. Além da quantificação de microbolhas, também foi avaliada a presença de shunt em repouso e sob manobra de Valsalva. Resultado: Do total, 96 pacientes foram incluídos no primeiro grupo (AVC indeterminado) e 72, no segundo grupo (AVC não embólico). No primeiro grupo, 65 pacientes exibiram shunt com passagem de mais de 10 microbolhas (67,5%), enquanto no segundo grupo isso aconteceu em 51,4% (p=0,038) dos casos. Além disso, 75 pacientes (78,1%) do primeiro grupo tiveram teste positivo ao repouso, comparados com 42 pacientes (58,3%) no segundo grupo (p=0,007). Conclusão: O presente estudo demonstrou que até 70% dos pacientes com AVC de etiologia indeterminada e forame oval apresentaram shunts maiores; em mais de 75%, houve passagem de microbolhas ao repouso. Esses achados sugerem que as características do shunt, como quantidade de microbolhas e passagem ao repouso, devem ser levadas em consideração na avaliação do FOP como possível mecanismo subjacente ao AVC.

Cryptogenic stroke in patients with patent foramen ovale: potential mechanisms and prevention strategies / 国际脑血管病杂志

Patent foramen ovale (PFO) is a congenital heart disease that occurs in about 25% of healthy adults. In recent years, more and more studies have shown that PFO is closely associated with cryptogenic stroke (CS). Although it is currently believed that paradoxical embolism is one of the main mechanisms of the pathogenesis of CS, but the exact mechanism is still controversial. In addition, the treatment of CS in patients with PFO is also the focus of controversy. Recent clinical trials have shown that PFO occlusion is significantly better than drug therapy alone in preventing stroke recurrence, especially for patients with a large right-to-left shunt and atrial septal tumor. This article reviews the potential mechanisms and prevention strategies of CS in patients with PFO.

Risk of Paradoxical Embolism (RoPE)-Estimated Attributable Fraction Correlates With the Benefit of Patent Foramen Ovale Closure: An Analysis of 3 Trials.

BACKGROUND AND PURPOSE: In patients with cryptogenic stroke and patent foramen ovale (PFO), the Risk of Paradoxical Embolism (RoPE) Score has been proposed as a method to estimate a patient-specific "PFO-attributable fraction"-the probability that a documented PFO is causally-related to the stroke, rather than an incidental finding. The objective of this research is to examine the relationship between this RoPE-estimated PFO-attributable fraction and the effect of closure in 3 randomized trials. METHODS: We pooled data from the CLOSURE-I (Evaluation of the STARFlex Septal Closure System in Patients With a Stroke and/or Transient Ischemic Attack due to Presumed Paradoxical Embolism through a Patent Foramen Ovale), RESPECT (Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current Standard of Care Treatment), and PC (Clinical Trial Comparing Percutaneous Closure of Patent Foramen Ovale [PFO] Using the Amplatzer PFO Occluder With Medical Treatment in Patients With Cryptogenic Embolism) trials. We examine the treatment effect of closure in high RoPE score (≥7) versus low RoPE score (<7) patients. We also estimated the relative risk reduction associated with PFO closure across each level of the RoPE score using Cox proportional hazard analysis. We estimated a patient-specific attributable fraction using a PC trial-compatible (9-point) RoPE equation (omitting the neuroradiology variable), as well as a 2-trial analysis using the original (10-point) RoPE equation. We examined the Pearson correlation between the estimated attributable fraction and the relative risk reduction across RoPE strata. RESULTS: In the low RoPE score group (<7, n=912), the rate of recurrent strokes per 100 person-years was 1.37 in the device arm versus 1.68 in the medical arm (hazard ratio, 0.82 [0.42-1.59] P=0.56) compared with 0.30 versus 1.03 (hazard ratio, 0.31 [0.11-0.85] P=0.02) in the high RoPE score group (≥7, n=1221); treatment-by-RoPE score group interaction, P=0.12. The RoPE score estimated attributable fraction anticipated the relative risk reduction across all levels of the RoPE score, in both the 3-trial (r=0.95, P<0.001) and 2-trial (r=0.92, P<0.001) analyses. CONCLUSIONS: The RoPE score estimated attributable fraction is highly correlated to the relative risk reduction of device versus medical therapy. This observation suggests the RoPE score identifies patients with cryptogenic stroke who are likely to have a PFO that is pathogenic rather than incidental.

Paradoxical cerebral embolism caused by pulmonary arteriovenous fistula: a case report / 中华神经科杂志

A young female patient with paradoxical cerebral embolism caused by pulmonary arteriovenous fistula,mainly presented the right limbs asthenia,and brain magnetic resonance imaging examination showed multiple acute cerebral infarctions in the left hemisphere,which belongs to left middle cerebral artery and left posterior cerebral artery blood areas.After excluding the common risk factors of cerebrovascular disease,foaming test suggested the right-to-left shunt.The esophageal ultrasound examination excluded the patent foramen ovala.The lung CT angiography examination confirmed the intracranial embolism caused by pulmonary arteriovenous fistula.There was no recurrence of ischemic stroke after the patient was treated with pulmonary arteriovenous fistula embolization.

Concomitant embolism in the subclavian and pulmonary artery.

INTRODUCTION: Pulmonary embolism is a life-threatening condition that causes obstruction of the pulmonary arteries by an embolus, most often originating from the venous system of the lower limbs or pelvic veins. Depending on the extent of the embolism, an acute right-sided heart failure may result, with subsequent death. Paradoxical embolism is a condition in which a venous thrombus is embolized into the systemic circulation arteries by a right-to-left heart shunt. This condition most commonly occurs in the interatrial septum. The aim of treatment for pulmonary embolism is to remove the obstruction of the lung. Depending on the extent of the embolism and the patients hemodynamic status, thrombolytic or surgical treatment can be chosen. Thrombolytic therapy has become the basis of treatment for all types of acute pulmonary embolism. Currently, open surgery is indicated in hemodynamically unstable patients with massive pulmonary embolism, and increasingly frequently in submassive embolism where thrombolytic therapy is not effective or contraindicated. CASE REPORT: The case report describes a less common condition of pulmonary and concurrently systemic embolization in the subclavian artery. Thrombolytic therapy was contraindicated in this case due to the high risk of secondary embolism to the brain. Surgical embolectomy was performed from the pulmonary arteries simultaneously with direct embolectomy from the subclavian and brachiocephalic artery. The surgical management of acute pulmonary embolism is a suitable method of treatment for both massive pulmonary embolism where the procedure is performed as a life-saving indication, and submassive embolism where less invasive treatment would not be effective. CONCLUSION: Direct embolectomy of subclavian and brachiocephalic artery is associated with minimal risk of iatrogenic embolism into the arteries supplying the brain compared to indirect embolectomy performed from the cubital or brachial artery. Key words: embolism paradoxical embolization - embolectomy foramen ovale stroke.

Trombo a través de foramen oval permeable: embolia paradojal cerebral y factores de alto riesgo de recurrencia. Caso clínico / Paradoxical embolism due to a persistent patent foramen ovale: report of one case

Abstract: Patent Foramen Ovale (PFO) is one of the most frequent congenital defects in adults. Its prevalence in middle-aged adults is close to 25-30% and may cause paradoxical embolic phenomena. We report a 45 years old male admitted for an ischemic stroke with an occlusion of the left terminal internal carotid artery. A thrombectomy was performed. Searching for possible sources of emboli, a patent foramen ovale was detected in an echocardiography, with an hypoechogenic examination image passing through it. Anticoagulant therapy was started and the patient had an uneventful evolution.

[Neuroimaging characteristics of cryptogenic stroke with and without patent foramen ovale].

Objective: To explore the neuroimaging characteristics associated with the presence of patent foramen ovale(PFO) for patients with cryptogenic stroke. Methods: We retrospectively collected the clinical and imaging data of cryptogenic stroke patients with PFO and without PFO from Henan Province People's Hospital from January 1, 2013 to June 30, 2017. Lesion patterns and pertinent vascular territory were compared between the two groups. Multivariate logistic regression analysis was used to explore the independent predictors for the presence of PFO. Results: A total of 54 cryptogenic stroke patients with PFO and 50 cases without PFO were recruited. Compared with PFO(-) stroke group, more patients in PFO(+ ) stroke group had migraine(P=0.036), and patients in PFO(+ ) stroke group had higher Risk of Paradoxical Embolism(RoPE) score(P=0.030). The lesion pattern of PFO(+ ) stroke was more frequently observed as multiple lesions in multicirculatory (P=0.035), and infarcts were more likely to be distributed in the vertebrobasilar artery territory (P=0.041); the most frequently involved vessel was the posterior cerebral artery region (P=0.006). More patients with PFO(+ ) stroke had old silent stroke lesion(P=0.021). On multivariate analysis, infarction distributed in the posterior cerebral artery region(OR=4.292, 95% CI 1.469-12.543, P=0.008), silent stroke lesion (OR=6.688, 95% CI 1.277-35.029, P=0.024), and high RoPE score (OR=1.393, 95% CI 1.026-1.893, P=0.034) were independent parameters that could predict the presence of PFO. Conclusions: Multiple lesions in multicirculatory and the posterior predominance are neuroimaging characteristics of cryptogenic stroke with PFO. Infarction distributed in the posterior cerebral artery region, silent stroke lesion and high RoPE score are independent predictors of the presence of PFO.

[InterAtrial Shunt Device in diastolic heart failure]. / InterAtrial Shunt Device bei diastolischer Herzinsuffizienz.

All types of heart failure are associated with reduced cardiac output and/or increased left atrial (LA) pressure. In diastolic heart failure (heart failure with preserved ejection fraction [HFpEF]), the increased LA pressure plays a central role, leading to pulmonary venous hypertension (PVH) and increased pulmonary artery pressure. These pressure parameters are presumably decisive for the symptoms and mortally of heart failure, particularly of the diastolic form. This is the basis for treatment with an interarterial shunt to reduce LA pressure in patients with diastolic heart failure and PVH. At first glance, this appears paradoxical, since closure of an atrial septum defect serves to prevent increased pulmonary vascular resistance and paradoxical embolism. Prevention of increased pulmonary vascular resistance and paradoxical embolism is thus an essential aspect in the development of devices for establishing an interarterial shunt. Reports on the InterAtrial Shunt Device (IASD®) and the V­Wave have been published, both of which can be implanted with a low risk and few complications. The V­Wave device is equipped with a valve to prevent paradoxical embolisms. However, paradoxical embolisms were also not observed with the IASD®, and the valve of the V­Wave exhibited considerable degenerative changes and valve closure. Hemodynamic and clinical data of patients with an IASD® or an open V­Wave device demonstrated a sustained hemodynamic improvement. Physical performance capacity and quality of life were increased. Whether IASD® may be broadly applicable in patients with diastolic heart failure is currently under investigation. In selected highly symptomatic patients with diastolic heart failure and PVH, the IASD® is already in clinal use.

Pulmonary and paradoxical coronary embolism with a patent foramen ovale.

Paradoxical embolism through a patent foramen ovale is a very unusual event considering that this cardiac anomaly may be present in as much as 26% of the general population. We describe the case of a 68-year-old man with a pulmonary and paradoxical coronary embolism in the presence of a patent foramen ovale. The finding of a worm-shaped thrombus though the atrial septum together with the risk of further embolization through the atrial septum prompted surgical treatment.

Closure of Patent Foramen Ovale Versus Medical Therapy in Patients With Cryptogenic Stroke or Transient Ischemic Attack: Updated Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: Previous systematic reviews and meta-analyses compared the efficacy and safety of patent foramen ovale (PFO) closure versus medical treatment in patients with cryptogenic stroke or transient ischemic attack (TIA). Recently, new evidence from randomized trials became available. METHODS: We searched PubMed until September 24, 2017, for trials comparing PFO closure with medical treatment in patients with cryptogenic stroke/TIA using the items: stroke or cerebrovascular accident or TIA and patent foramen ovale or paradoxical embolism and trial or study. RESULTS: Among 851 identified articles, 5 were eligible. In 3627 patients with 3.7-year mean follow-up, there was significant difference in ischemic stroke recurrence (0.53 versus 1.1 per 100 patient-years, respectively; odds ratio [OR], 0.43; 95% confidence intervals (CI), 0.21-0.90; relative risk reduction, 50.5%; absolute risk reduction, 2.11%; and number needed to treat to prevent 1 event, 46.5 for 3.7 years). There was no significant difference in TIAs (0.78 versus 0.98 per 100 patient-years, respectively; OR, 0.80; 95% CI, 0.53-1.19) and all-cause mortality (0.18 versus 0.23 per 100 patient-years, respectively; OR, 0.73; 95% CI, 0.34-1.56). New-onset atrial fibrillation occurred more frequently in the PFO closure arm (1.3 versus 0.25 per 100 patient-years, respectively; OR, 5.15; 95% CI, 2.18-12.15) and resolved in 72% of cases within 45 days, whereas rates of myocardial infarction (0.12 versus 0.09 per 100 patient-years, respectively; OR, 1.22; 95% CI, 0.25-5.91) and any serious adverse events (7.3 versus 7.3 per 100 patient-years, respectively; OR, 1.07; 95% CI, 0.92-1.25) were similar. CONCLUSIONS: In patients with cryptogenic stroke/TIA and PFO who have their PFO closed, ischemic stroke recurrence is less frequent compared with patients receiving medical treatment. Atrial fibrillation is more frequent but mostly transient. There is no difference in TIA, all-cause mortality, or myocardial infarction.

Pulmonary embolism complicated with abnormal spinal cord embolism due to lack of protein S activity: a case report / 中华神经科杂志

Spinal vascular disease is rare in clinic, especially in cases of spinal cord embolism caused by abnormal embolism. It is rare in clinic and has not been reported in China. We report a case of pulmonary embolism complicated with abnormal spinal cord embolism due to lack of protein S activity and analyze its clinical data in order to improve clinical understanding of the disease.

Surgical treatment for thrombus straddling a patent foramen ovale

Abstract We present a case of a 41-year-old female with deep vein thrombosis after abdominal surgery. The patient quickly developed severe pulmonary embolism and stroke representative of paradoxical embolism. Echocardiography showed a thrombus straddling a patent foramen ovale, which was confirmed intraoperatively. An accurate diagnosis and rapid treatment decisions are crucial for preventing patient deterioration in the form of new pulmonary embolisms or stroke.

Hyperdense Middle Cerebral Artery Sign Together with Pulmonary Thromboembolism.

BACKGROUND: Hyperdense middle cerebral artery sign is an appearance of the middle cerebral artery on non-contrast-enhanced computed tomography. Embolic occlusion of the pulmonary arterial system is referred to as pulmonary embolism. When pulmonary embolism coexists with a patent foramen ovale, increased pressure in the right atrium may result in widening of the foramen and consequently, cause serious conditions due to paradoxical embolus. Coexistence of hyperdense middle cerebral artery sign and pulmonary thromboembolism is very rare in the literature. CASE REPORT: We presented a 60-year-old female patient who had both hyperdense middle cerebral artery sign and pulmonary thromboembolism. CONCLUSIONS: To our knowledge, togetherness of hyperdense MCA sign and pulmonary thromboembolism is extremely rare in the literature. In our case, we found both pulmonary embolism due to DVT and paradoxical embolism due to existing patent foramen ovale.

Stroke in Commercial Flights.

BACKGROUND AND PURPOSE: Stroke on board aircraft has been reported in retrospective case series, mainly focusing on economy class stroke syndrome. Data on the actual incidence, pathogenesis, and prognosis of stroke in commercial flights are lacking. METHODS: A prospective registry was designed to include all consecutive patients referred from an international airport (40 million passengers a year) to our hospital with a diagnosis of ischemic stroke or transient ischemic attack and onset of symptoms during a flight or immediately after landing. RESULTS: Forty-four patients (32 ischemic strokes and 12 transient ischemic attacks) were included over a 76-month period (January 2008 to April 2014). The estimated incidence of stroke was 1 stroke in 35 000 flights. Pathogeneses of stroke or transient ischemic attack were atherothrombotic in 16 (36%), economy class stroke syndrome in 8 (18%), cardioembolic in 7 (16%), arterial dissection in 4 (9%), lacunar stroke in 4 (9%), and undetermined in 5 (12%) patients. Carotid stenosis >70% was found in 12 (27%) of the patients. Overall prognosis was good, and thrombolysis was applied in 44% of the cases. The most common reason for not treating patients who had experienced stroke onset midflight was the delay in reaching the hospital. Only 1 patient with symptom onset during the flight prompted a flight diversion. CONCLUSIONS: We found a low incidence of stroke in the setting of air travel. Economy class stroke syndrome and arterial dissection were well represented in our sample. However, the main pathogenesis was atherothrombosis with a high proportion of patients with high carotid stenosis.

Cryptogenic stroke in patients w ith patent foramen ovale / 国际脑血管病杂志

Cryptogenic stroke refers to ischemic stroke that can not be defined by routine examination at present. Studies have show n that patent foramen ovale may be a common cause of cryptogenic stroke, and its possible mechanism is the paradoxical embolism. With the development of imaging technology , more and more studies have show n that patent foramen ovale is closely associated w ith cryptogenic stroke. This article review s cryptogenic stroke in patients w ith patent foramen ovale.