The paradox of platypnoea-orthodeoxia syndrome.

Platypnoea-orthodeoxia is a rare clinical syndrome characterised by dyspnoea and oxygen desaturation in the upright position which improves when supine. It requires two components: a sufficiently sized anatomical vascular defect (typically intra-cardiac or intra-pulmonary) combined with a functional component that promotes positional right-to-left shunting. We describe the rare occurrence of a patient with platypnoea-orthodeoxia syndrome (POS) because of a paradoxical shunt through a patent foramen ovale caused by a large right atrial line-associated thrombus in a male with metastatic oesophageal cancer undergoing chemotherapy. This case is a timely reminder to consider POS amongst differentials for hypoxia as it is often treatable if recognised.

Retinal arterial occlusion and patent foramen ovale: A case study-based review.

PURPOSE: To identify all reported cases of retinal artery occlusion (RAO) associated with patent foramen ovale (PFO) in the literature and present a similar case of CRAO from our clinic. METHODS: PubMed database was searched for studies reporting RAO in individuals with PFO. Relevant data were tabulated and reviewed. We estimated each case's Risk of Paradoxical Embolism (RoPE) score. RESULTS: 23 cases of CRAO (n=10; including ours), BRAO (n=10), and CILRAO (n=3) were reviewed. Most cases were under 50 years of age (78.3%). The reported predisposing factors were: hypertension (26.1%), migraine (17.3%), smoking (13.0%), recent immobilization (13.0%), strenuous exertion (8.7%), pregnancy (8.7%), and diabetes (4.3%). A high RoPE score (≥7; suggestive of paradoxical embolism via PFO) was estimated for 71.4% of patients. In most cases, the neurological and cardiovascular examinations, laboratory studies, and imaging were unremarkable, except for the PFO±atrial septal aneurysm (present in 21.7%). In only 28.6% of cases, transthoracic echocardiography (TTE) (± saline contrast) could visualize the PFO; transesophageal echocardiography (TEE) was necessary to detect the PFO in 71.4%. Approximately one-half of the patients underwent percutaneous closure of the PFO; no complications or subsequent acute ischemic events ensued. The visual prognosis was poorer for CRAO than for BRAO or CILRAO. CONCLUSION: Timely diagnosis, acute management, and ensuring urgent initiation of stroke workup in cases with RAO or transient monocular vision loss are crucial. Clues to a possible paradoxical embolism as the cause include the absence of known cardiovascular risk factors, young age, migraine, recent immobility, vigorous exercise, and pregnancy.

Factors associated with patent foramen ovale-related stroke: SAFAS study.

BACKGROUND: Persistent foramen ovale (PFO) contributes to cryptogenic stroke and is associated with stroke recurrence, although the exact mechanism of ischemic events is not fully understood. Several biomarkers have been developed for the prediction of atrial fibrillation after stroke, but there are currently only limited data on their potential value for the diagnosis of PFO-related stroke. METHODS: This study was a prospective single-center study that included all patients hospitalized between March 31, 2018, and January 18, 2020, in the stroke department of the Dijon University Hospital for ischemic stroke without obvious cause and without a history of atrial fibrillation. PFO was systematically screened by transthoracic echocardiography and images were reviewed by an independent cardiologist blinded from clinical data. PFO was defined according to the CLOSE trial criteria: PFO associated with interatrial septal aneurysm or significant interatrial shunt (> 30 microbubbles in the left atrium within three cardiac cycles after right atrial opacification). The potential association of PFO-related stroke with biomarkers of cardiac fibrosis and inflammation such as galectin-3, GDF-15, ST-2, osteoprotegerin and NT-proBNP was tested using multivariate backward stepwise logistic regression. RESULTS: Of the 240 patients included in the SAFAS study, 229 had complete echocardiographic data, and 23 (10%) had PFO-related stroke. Patients with PFO-related stroke were significantly younger (58±14 vs. 69±14, P<0.001), had less frequent previous arterial hypertension (30 vs. 60%, P=0.008), and more frequent cerebellar territory involvement (26 vs. 9%, P=0.014) compared to the other patients. In addition, they had less frequently left atrial dilatation (left atrial index volume>34mL/m2 [9 vs. 35%, P=0.009]). After ROC curve analysis for definition of thresholds, PFO-related stroke patients more often had galectin-3<9.5ng/mL (59 vs. 27%, P=0.002), ST2<13380pg/ml (23 vs. 50%, P=0.007), GDF-15<1200ng/mL (59 vs. 27%, P=0.002), osteoprotegerin<1133pg/mL (82 vs. 58%, P=0.033) and NT-proBNP<300pg/mL (88 vs. 55%, P=0.009). After multivariate analysis, only galectin-3<9.5ng/mL (OR [95% CI] 3.4 [1.18; 9.8], P=0.024) and osteoprotegerin<1133pg/L (OR [95% CI] 5.0 [1.1; 22.9], P=0.038) were independently associated with PFO-related stroke. CONCLUSION: Patients in whom cryptogenic stroke is attributed to a significant PFO have a specific clinical and biological phenotype. Low levels of galectin-3 and osteoprotegerin may help identify patients with PFO-related strokes.

Orthodeoxia Platypnea Syndrome in the Setting of Cholangiocarcinoma: A Case Report.

Platypnea-orthodeoxia syndrome is a rare cause of positional hypoxemia and dyspnea. We present the case of a 54-year-old man with right-to-left shunting through a patent foramen ovale in the setting of metastatic cholangiocarcinoma resulting in platypnea-orthodeoxia syndrome. The shunt was originally not visualized on cardiac magnetic resonance imaging but later detected with transesophageal echocardiography. This case highlights the importance of complimentary multimodality cardiac imaging in the diagnosis of both common and uncommon disorders.

[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.

Challenging Cases in Cerebrovascular Disease.

Disorders involving the vascular system of the brain are numerous and sundry. Atherosclerotic thromboembolism of large vessels and lacunar infarctions of small vessel disease are well known. Brain infarction due to cardioembolism is common as well, and even more so when diligently sought. Rupture of intracranial blood vessels results in subarachnoid and intraparenchymal hemorrhage. We present four cases of stroke of uncommon cause and remind clinicians to be open minded to the many possible causes of stroke, in particular because early recognition and treatment is often critical. Case 1 discusses a patient with inflammatory cerebral amyloid angiopathy. The presentation, ability to recur, and current treatment considerations are reviewed. Case 2 discusses microangiopathic thrombotic angiopathy. Diagnosis and treatment are considered. An association with interferon therapy and the evolving terminology of this and related conditions are discussed. Case 3 discusses intracranial hemorrhage secondary to acute promyelocytic leukemia. Patients with acute leukemias require aggressive management of their coagulopathy, thrombocytopenia, and the disease itself. Finally, Case 4 discusses ischemic stroke due to a paradoxical embolism in the setting of a patent foramen ovale (PFO). Both medical and surgical management of a PFO for stroke prevention are considered.

Life-threatening paradoxical thromboembolism in a patient with patent foramen ovale.

BACKGROUND: Venous thromboembolism represents the third most frequent acute cardiovascular syndrome worldwide. Its clinical manifestations are deep vein thrombosis and/or pulmonary embolism. Despite a considerable mortality, diagnosis is often missed.  CASE PRESENTATION: We report the management of a female patient with high-risk pulmonary thromboembolism treated initially with thromboaspiration, complicated by embolus jailing in a patent foramen ovale. In this situation, left cardiac chambers and systemic circulation were jeopardized by this floating embolus. CONCLUSIONS: High-risk pulmonary embolism requires reperfusion strategy but sometimes mechanical thromboaspiration may be not fully successful; transesophageal echocardiography led to a prompt diagnosis of this unexpected finding; in this very particular case, open surgery represented a bail-out procedure to avoid cerebral and systemic embolism.

Platypnea-Orthodeoxia Syndrome in the Setting of Patent Foramen Ovale Without Pulmonary Hypertension or Major Lung Disease.

Background Patent foramen ovale (PFO)-associated platypnea-orthodeoxia syndrome is characterized by dyspnea and hypoxemia when upright. The pathogenesis is thought to involve an increase in right atrial pressure or change in degree of right to left shunting with upright posture. Methods and Results We sought to characterize patients with platypnea-orthodeoxia syndrome related to PFO without pulmonary hypertension. We retrospectively reviewed databases at 3 tertiary referral hospitals in New South Wales, Australia from 2000 to 2019. Fourteen patients with a mean age of 69±14 years had a PFO with wide tunnel separation. Mean New York Heart Association Classification was II (±0.9) and 7 inpatients had been confined to bed (from postural symptoms). Baseline oxygen saturations supine were 93%±5% and 84%±6% upright. Two patients had a minor congenital heart defect and 4 had mild parenchymal lung disease with preserved lung function. The mean aortic root diameter was 37±6 mm and distance between aortic root and posterior atrial wall was 16±2 mm. Platypnea-orthodeoxia syndrome was preceded by surgery in 5 patients and 1 patient had mild pneumonia. Successful closure of the PFO using an Amplatzer device was performed in 11 of 14 patients. Post-closure, all patients had New York Heart Association Classification I (improvement 1.6±0.9, P<0.003) and semi-recumbent oxygen saturations increased by 13%±8% (P<0.001, n=10). Conclusions Platypnea-orthodeoxia syndrome is a debilitating condition, curable by PFO closure. Anatomical distortion of the atrial septum related to a dilated aortic root or shortening of the distance between the aortic root and posterior atrial wall may contribute to the syndrome.

From cryptogenic to ESUS: Toward precision medicine?

Cryptogenic infarctions are infarctions without a defined cause, despite a complete work-up. They differ from infarctions of undetermined causes, which may involve overlapping causes or an incomplete investigation. It is also different from uncommon heritable and non-heritable causes. The term embolic stroke of undetermined source (ESUS) proposed in 2014 is defined as a non-lacunar brain infarct without proximal arterial stenosis or cardioembolic sources. The major advantage of this definition compared to cryptogenic definition is the proposition of a specific work-up. In a general population, frequent potential sources of embolism in patients with ESUS have been suggested since a long time and include: patent foramen ovale (PFO), covert atrial fibrillation (AF), complex aortic arch atheroma, large vessel atheroma with stenosis<50%, carotid web, atrial cardiomyopathy, thrombophilia associated with cancer. It took almost 30 years to show, in patients under 60 with a cryptogenic stroke and a PFO, that PFO occlusion was superior to medical treatment alone for recurrent stroke. PFO under 60 is therefore no longer a cryptogenic cause of infarction. The concept of cryptogenic stroke and its refinement in ESUS have been fruitful for the identification of PFO associated as a cause. Covert AF can be detected by different techniques but its risk significance for recurrent stroke might be different from the simple electrocardiographic detection of AF. With the development of direct oral anticoagulants (DOAs), randomized studies in patients with ESUS, were run for stroke prevention but no difference was observed between patients treated by DOA compared to aspirin. These studies showed however the heterogeneity of ESUS patients. Further ESUS classification should be considered as a tool to identify homogeneous groups. We propose to further split the ESUS group into different subgroups: ESU-PFO>60-year-old, ESUS-ATH with stenosis<50%, ESUS-AF (covert AF & atrial cardiomyopathy), ESUS-cancer and others. Precision medicine is the ability to make targeted healthcare decisions based on the specific risks of individual patients. One preliminary stage is therefore to identify homogeneous groups suitable in the future for new therapeutic trials and, at the end, for new specific treatments.

Posture Dependent Hypoxia Following Lobectomy: The Achilles Tendon of the Lung Surgeon?

Background: Platypnoea-Orthodeoxia Syndrome is an uncommon phenomenon characterized by dyspnea/arterial desaturation in the standing position, resolving in recumbency. Some patients present with Platypnoea-Orthodeoxia Syndrome in the early-or-late post-operative period after major lung resection (lobectomy/pneumonectomy). The main cause of Platypnoea-Orthodeoxia Syndrome is an intracardiac anomaly (Patent Foramen Ovalis/Atrial Septal Defect) leading to right-to-left shunt.Objectives: To identify the causes of post-lobectomy Platypnoea-Orthodeoxia Syndrome, and the possible pathophysiologic mechanism.Methods A Pubmed database-EMBASE systematic review was performed in order to find all reports, reporting the occurrence of dyspnea/hypoxemia after lobectomy.Results: 8 studies were found concerning ten patients during the period from 1983-2019.There was 6 male/4 female. The mean age was 62 years. All patients underwent resection of the right lung. The time-interval between the operation and the Platypnoea-Orthodeoxia Syndrome was from 2 days to 3 years. A Patent Foramen Ovalis was present in 90% and in 10% an Atrial Septal Defect was diagnosed. The mean Right Atrial Pressure was 7.5 mmHg, the mean Left Atrial Pressure was 6.6 mmHg and the mean Pulmonary artery pressure was 18.5 mmHg. The mean size of the interatrial communication was 1.62 cm. The inter-atrial communication was closed by open-chest surgical procedure in 3 cases (30%) and in 7 patients (70%) a percutaneous transcatheter device was implanted.Conclusions: Platypnoea-Orthodeoxia Syndrome after lobectomy is a rare cause of post-operative dyspnea/hypoxia. It is the result of right-to-left shunt via an interatrial communication. Mediastinal relocation, stretching of the atrial septum and aortic root dilatation are among the functional elements necessary for the Platypnoea-Orthodeoxia Syndrome manifestation.

Cardiac metastasis causes paradoxical malignant embolism.

BACKGROUND: Embolic events play an important role in clinical everyday practice. Malignant arterial embolism is a rare nevertheless often fatal entity for cardiac, cerebral or systemic ischemia, requiring immediate diagnosis and treatment. CASE: This is a case report of a 65 years-old female, suffering from pulmonal adenocarcinoma, who was hospitalized due to neurological deficits caused by an acute ischemic stroke, followed by anterior myocardial infarction within 3 days. Diagnostic work-up revealed metastasis of the pulmonal adenocarcinoma in the right atrium and a patent foramen ovale. Histopathological examination of the coronary embolus verified paradoxical arterial embolism of the pulmonal adenocarcinoma into a coronary vessel and consequently cerebral arteries. CONCLUSION: The present case underlines the need for (i), consideration of malignant embolism, (ii) histopathological examination of the embolus to determine its etiology, and (iii) interdisciplinary discussion of individual therapeutic and prevention strategies in cancer patients with cerebral, cardiac or systemic embolic events.

[Heart and thromboembolic events: situation in 2021]. / Cœur et événements thromboemboliques : situation en 2021.

In daily practice, ischemia of embolic origin is frequent. The clinical spectrum can range from minor ischemia to stroke or myocardial infarction. This article summarizes the common etiologies of a cardioembolic event, such as atrial fibrillation or atrial flutter, presence of a patent foramen ovale or intracardiac masses (endocarditis, thrombi or tumors). This paper aims to serve as a short repository of information to guide every physician might need to initiate the diagnostic investigations and therapy according to recent recommendations.

Dans son quotidien, le praticien sera couramment confronté à une ischémie d'origine embolique. L'éventail clinique va d'une ischémie mineure à un AVC ou un infarctus du myocarde. Cet article résume les étiologies courantes d'un événement cardioembolique, notamment la fibrillation ou le flutter auriculaire, la présence d'un foramen ovale perméable ou de masses intracardiaques (végétations, thrombi, tumeurs). Il vise à guider le praticien dans sa prise en charge diagnostique et thérapeutique selon les recommandations cliniques récentes. Cette prise en charge est très souvent multidisciplinaire.

Stroke During Hip Surgery.

During hip replacement, acetabular and femur bone preparation may cause bone marrow extravasation. Paradoxical fat embolism occurs when emboli pass from the pulmonary to the systemic circulation by either a patent foramen ovale or pulmonary capillaries. Impaired consciousness in the immediate postoperative period of orthopedic surgery frequently results from hypovolemia, anemia, or residual anesthesia. A high index of suspicion is required to consider the possibility of paradoxical fat embolism.

Patent foramen ovale presenting with platypnoea-orthodeoxia syndrome and stroke after multi-organ resection.

Platypnoea-orthodeoxia syndrome (POS) is defined by oxygen desaturation and dyspnoea in upright position that improves by lying down. It results from a right to left shunt at the intracardiac or intrapulmonary level. A 53-year-old ovarian cancer patient presented with POS that was refractory to oxygen therapy. The symptoms began after an extensive abdominal and pelvic surgery as treatment of her cancer with a complex hospital course. A patent foramen ovale was found with the use of transoesophageal echocardiography. A percutaneous closure was done with positive outcome and dyspnoea disappearance. In this case with its challenging clinical setting, we present a unique clinical scenario of an immediate postoperative POS syndrome. We address the different therapeutic modalities and the need for a multidisciplinary medical approach.

Acute Ischemic Stroke as a Result of Paradoxical Embolus in a Patient with Renal Cell Carcinoma, Intravenous Tumor Thrombus Extension, and Patent Foramen Ovale.

INTRODUCTION: Patent foramen ovale is a common congenital cardiac abnormality. An association with acute ischemic stroke is well described. Extension of renal cell carcinoma (RCC) into the adjacent veins is common. Surgical resection is felt to be an effective approach to treatment, even in the setting of extensive venous involvement. CASE REPORT: A 55-year-old woman with recently diagnosed right renal mass and cavoatrial tumor thrombus was transferred to our facility for surgical resection. She subsequently underwent open radical right nephrectomy, regional lymph node dissection, inferior vena cava and right atrial tumor thrombectomy, and resection of the infrahepatic vena cava. An intraoperative transesophageal echocardiogram confirmed the absence of tumor thrombus from the inferior vena cava and right atrium and also identified a patent foramen ovale (PFO). Upon weaning sedation, she was noted to be agitated and have left hemiplegia. Her National Institutes of Health Stroke Scale (NIHSS) was 30 and Glasgow Coma Scale (GCS) 6. The computerized tomography scan of head revealed extensive hypoattenuation right in the middle and left posterior cerebral artery territories. There was associated cerebral edema and 5-mm midline shift. In the setting of devastating neurological injury, her family elected to transition to comfort care and the patient died on the postoperative day 7. CONCLUSIONS: This is the first reported case of intraoperative paradoxical embolism in the setting of RCC with cavoatrial extension and PFO. The presence of PFO may be a risk factor for severe cerebrovascular complications in the surgical management of RCC with venous involvement.

The Role of Patent Foramen Ovale Closure in the Secondary Prevention of Cryptogenic Stroke: a Meta-Analysis Report

Abstract Background: Patent foramen ovale (PFO) closure has been compared to medical therapy for secondary prevention of recurrent cryptogenic stroke. Objectives: To produce an updated meta-analysis including only data from the primary analyses of clinical trials and to evaluate the role of PFO closure in the secondary prevention of recurrent stroke. Methods: Search in Medline (PubMed) and in ISI Web of Knowledge. Parameters under analysis and meta-analyses were: stroke, transient ischemic attack (TIA) and atrial fibrillation (AF). Comprehensive Meta-analysis Software V.2.0 (Biostat) was used. Random-effects analyses were carried out. A level of significance of 5% was used. Results: In this study six, randomized trials enrolling 3,750 patients were included. Unlike other published meta-analyses on the same topic, in this case, only clinical trial data, and not follow-up data, were used. PFO closure, as compared with medical therapy alone, demonstrated superiority in reducing the rate of recurrent stroke (risk ratio with PFO closure vs. medical therapy, 0.37; 95% confidence interval [CI], 0.17 to 0.78; p = 0.01). PFO closure did not offer a significant benefit in prevention of TIA (risk ratio with PFO closure vs. medical therapy, 0.96; 95% CI, 0.64 to 1.44; p = 0.85). Among patients assigned to closure group, an increased risk of atrial fibrillation was seen (risk ratio with PFO closure vs. medical therapy, 4.64; 95% CI, 2.38 to 9.01; p < 0.01). Conclusions: In patients with cryptogenic stroke who had a patent foramen ovale, a protective effect of closure was seen concerning the risk of recurrent stroke, but not regarding the prevention of TIA.

Increased Risk of Perioperative Ischemic Stroke in Patients Who Undergo Noncardiac Surgery with Preexisting Atrial Septal Defect or Patent Foramen Ovale.

OBJECTIVES: To evaluate whether a preoperative diagnosis of atrial septal defect (ASD) or patent foramen ovale (PFO) is associated with perioperative stroke in noncardiac surgery and their outcomes. DESIGN: Retrospective cohort analysis. SETTING: United States hospitals. PARTICIPANTS: Adults patients (≥18 years old) who underwent major noncardiac surgery from 2010 to 2015 were identified using the Healthcare Cost and Utilization Project's National Readmission Database. INTERVENTIONS: Preoperative diagnosis of ASD or patent foramen ovale. MEASUREMENTS AND MAIN RESULTS: Among the 19,659,161 hospitalizations for major noncardiac surgery analyzed, 12,248 (0.06%) had a preoperative diagnosis of ASD/PFO. Perioperative ischemic stroke occurred in 723 (5.9%) of patients with ASD/PFO and 373,291 (0.02%) of those without ASD/PFO (adjusted odds ratio [aOR], 16.7; 95% confidence interval [CI]: 13.9-20.0). Amongst the different types of noncardiac surgeries, obstetric, endocrine, and skin and burn surgery were associated with higher risk of stroke in patients with pre-existing ASD/PFO. Moreover, patients with ASD/PFO also had an increased in-hospital mortality (aOR, 4.6, 95% CI: 3.6-6.0), 30-day readmission (aOR, 1.2, 95% CI: 1.04-1.38), and 30-day stroke (aOR, 7.2, 95% CI: 3.1-16.6). After adjusting for atrial fibrillation, ischemic stroke remained significantly high in the ASD/PFO group (aOR: 23.7, 95%CI 19.4-28.9), as well as in-hospital mortality (aOR: 5.6, 95% CI 4.1-7.7), 30-day readmission (aOR: 1.19, 95%CI 1.0-1.4), and 30-day stroke (aOR: 9.3, 95% CI 3.7-23.6). CONCLUSIONS: Among adult patients undergoing major noncardiac surgery, pre-existing ASD/PFO is associated with increased risk of perioperative ischemic stroke, in-hospital mortality, 30-day stroke, and 30-day readmission after surgery.