Neonatal Myocardial Ischemia-Reperfusion Injury: A Proposed Pathogenic Sequence in the Context of Maternal/Fetal Vascular Malperfusion and Paradoxical Embolism.

BACKGROUND: Neonatal myocardial infarction (MI) in a structurally normal heart is frequently an obscure event that remains undiagnosed until autopsy. Causal attributions usually cite underlying maternal or fetal conditions. Refinement in understanding of pathogenic mechanisms underlying neonatal MI is key to advancements in diagnosis, prevention, treatments and prognosis. OBJECTIVE: This study presents a 36-week gestational age female with perinatal asphyxia, congenital hemolytic anemia and umbilical vein thrombosis who sustained catastrophic MI with reperfusion injury; and it reviews pertinent literature. RESULTS: We propose a pathogenic sequence that links maternal vascular malperfusion, fetal vascular malperfusion, hemolytic anemia, umbilical venous thrombosis, and paradoxical thromboemboli. CONCLUSION: This case highlights the importance of placental examination in connecting complex neonatal events with adverse maternal/placental conditions. A high index of suspicion is essential for early diagnosis of neonatal MI.

Entrapped paradoxical thromboembolism.

A 67-year-old obese woman (BMI 38.3) was found at autopsy to have deep venous thrombosis of the left calf with bilateral peripheral and saddle pulmonary thromboemboli and a 165 mm long segment of paradoxical thromboembolus wedged between the right and left atria through a patent foramen ovale. Death was due to acute right-sided decompensation caused by obstruction of the pulmonary outflow tract from bilateral pulmonary thromboemboli. Paradoxical thromboemboli pass from the venous system into the systemic circulation through intracardiac or intrapulmonary shunts causing ischemic injury to the brain, heart, intestines, kidneys and limbs. Very rarely, as in this case, they may become entrapped in a patent foramen ovale. Due to its entrapment the paradoxical embolism did not play a role in the lethal episode.

Patent foramen ovale, paradoxical embolism and fatal coronary obstruction.

A 75-year-old woman was admitted to the emergency room with chest pain and vomiting. An electrocardiogram and laboratory results were suggestive for myocardial infarction of the posterior cardiac wall. Echocardiography was indicative of aortic dissection, and a CT scan of the thoracic arteries showed a massive pulmonary thromboembolism and thrombotic occlusion of the right coronary artery (RCA). The woman died shortly after admission. Autopsy confirmed the presence of thromboemboli in the right pulmonary artery and its lobar branches. Also, the anterior aortic sinus was filled with a 9 cm long thromboembolus that extended into the RCA, making it dilated and completely occluded. Another 3.5 cm long thromboembolus extended from the beginning of the left subclavian artery. A patent foramen ovale (PFO) was present. On the posterior wall of the left ventricle, there was an area suggestive of myocardial infarction, and histopathological examination confirmed that it was 24-48 hours old. The coronary circulation was "co-dominant". The sources of thrombotic masses were the deep veins of the lower limbs. The cause of death was myocardial infarction, caused by RCA occlusion with thromboembolus originating from the deep veins of the left lower leg after paradoxical embolism via PFO. This case illustrates that although deep venous thrombosis, pulmonary thromboembolism, and PFO are not rare findings at autopsy, their combination could be a relatively rare cause of fatal coronary artery occlusion after paradoxical embolism.

Paradoxical embolism as a cause of silent brain infarctions in healthy subjects: the ICONS study (Identification of the Cause of Silent Cerebral Infarction in Healthy Subjects).

BACKGROUND: In healthy elderly people, silent brain infarctions (SBIs) have been recognized as common lesions. In this study, we evaluated the association between SBI located outside the perforating artery territory (PAT) and paradoxical embolism detected by agitated saline transcranial Doppler (TCD) monitoring in healthy subjects. METHODS: This was a prospective observational study undertaken by a university health promotion center for healthy subjects and by a university stroke center for acute stroke patients. We defined SBI as evidence on fluid-attenuation inversion recovery (FLAIR) magnetic resonance imaging (MRI) of one or more infarcts, without history of corresponding stroke or transient ischaemic attack. We also evaluated in all subjects the neuroimaging indicator of microangiopathy leukoaraiosis (LA). This study is registered with ClinicalTrials.gov, number NCT01429948. RESULTS: Amongst 1103 consecutive healthy adults who underwent MRI, 347 (31%) had one or more SBIs located outside the PAT, suggesting embolism. Amongst them, 253 subjects underwent agitated saline TCD monitoring and 128 (51%) had right-to-left shunts (RLS). The prevalence of RLS was similar to cryptogenic embolic stroke (62.0%, P = 0.056), but higher than in patients with other stroke subtypes (36.2%, P = 0.021). Amongst subjects with SBI, absence of LA was the only factor associated with RLS (OR 1.78; 95% CI 1.01-3.14; P = 0.046). CONCLUSION: Our results suggest that paradoxical embolism may play an important role in the development of SBI outside the PAT in apparently healthy adults.

Paradoxical thrombosis, part 2: anticoagulant and antiplatelet therapy.

Arterial thrombosis is the leading causes of morbidity and mortality worldwide, whereas venous thrombosis is the most common preventable cause of hospital death. In either case, venous and arterial thrombosis should be considered autonomous entities, with only minor overlaps in terms of risk factors, predisposing conditions and pathogenesis. Besides the widespread perception of embolization originating from low-pressure venous system and triggering ischemic stroke or peripheral arterial occlusion, "paradoxical" thrombosis might also develop or occur within clinical or biological circumstances where the blood should be less predisposed to clot, and wherein this risk is mostly unpredictable or overlooked. In this article we review epidemiological evidence and potential pathogenetic mechanisms of paradoxical thrombosis developing during antithrombotic therapy with vitamin K antagonists and heparin (i.e. heparin-induced thrombocytopenia), or antiplatelet agents such as aspirin, glycoprotein IIb/IIIa inhibitors or clopidogrel, and mostly attributable to direct effect of the agent.

Paradoxical embolism and pulmonary embolism in a patient with patent foramen ovale: a case report.

Paradoxical embolism may occur in patients with acute pulmonary thromboembolism, when a patent foramen ovale(PFO) coexists with a right to left shunt associated to pulmonary hypertension. We presented the case of a 83 year old woman with paradoxical embolism to both legs, in the setting of pulmonary embolism. She was successfully treated with peripheral thrombectomy and anticoagulation. Patent foramen ovale closure wasn't performed because of its small size and right to left shunt absence after clinical stability.

Interatrial thrombus-in-transit resulting in paradoxical thromboembolism.

Patent foramen ovale (PFO) is reported in up to 50% of patients with cryptogenic stroke. However, the role of PFO in acute myocardial infarction is less reported. In this case report, the relationship between PFO, myocardial infarction, and an interatrial paradoxical thromboembolism (aka thrombus-in-transit) was diagnosed with the use of non-invasive technique, percutaneous procedures, as well as gross surgical specimen.

The ultimate proof of paradoxical embolism and a percutaneous solution.

Central venous catheters (CVCs) and ports are frequently used for the administration of total parenteral nutrition, antibiotics, and chemotherapeutic agents. Their use may be associated with serious complications, such as venous thrombosis, embolization, and catheter rupture. Catheter fragments most commonly embolize to the right atrium, right ventricle, and pulmonary artery (Surov et al., Angiology 2008;59:90-97). We report the first case of a CVC that embolized across a patent foramen ovale (PFO) into the left atrium in a 72-year-old female who presented with symptoms of a transient ischemic attack (TIA). Treatment consisted of retrieving the embolized portacath, which had lodged in the right upper pulmonary vein followed by percutaneous PFO closure.

Recurrent events following patent foramen ovale closure in patients above 55 years of age with presumed paradoxical embolism.

OBJECTIVES: The aim of this article is to summarize our experience of patent foramen ovale (PFO) closure in patients above the age of 55 years. BACKGROUND: PFO is associated with cryptogenic thromboembolic events (TEs) in patients younger than 55 years. Little is known about the recurrence rate of TE in patients above the age of 55 years undergoing PFO closure for presumed paradoxical embolism. METHODS: PFO closure was performed in 1,055 patients, 423 of whom were above 55 years of age. Implantation of the device was guided by fluoroscopy and transesophageal or intracardiac echocardiography. RESULTS: A PFO occluding device was implanted successfully in all patients. Residual shunt was documented in 10% of patients above 55 years of age and in 8.4% of patients aged 55 years or younger (P = 0.325). During a median follow-up period of 18 months (range, 0-162 months) the annual incidence of recurrent TE in patients above 55 years was 1.8% while patients aged 55 or below had an annual incidence of recurrent TE of 1.3%. TE-free survival was similar in patients above 55 years of age compared with those aged 55 years and below. CONCLUSIONS: PFO closure in older patients is as efficient and seems comparable to those under the age of 55. Although traditional cardiovascular risk factors may be more frequent in the older age group compared with those younger than 55 years, PFO closure should not be withheld as a possible therapeutic option in this age group.

Hereditary hemorrhagic telangectasia and spinal cord infarct: case report with a review of the neurological complications of HHT.

Hereditary hemorrhagic telangectasia (HHT), also known as Osler-Weber-Rendu disease, is an autosomal dominant vascular dysplasia with high penetrance and variable expressivity. A wide variety of neurological complications have been reported in association with this condition. We report the first case of spinal cord infarction likely due to paradoxical embolization with HHT and review the literature on the neurological complications of this disorder. MEDLINE was employed to identify all published reports of HHT with neurological complications. We identified 44 references with a total of 436 cases of neurological complications of HHT. The most common complication was ischemic stroke and the main etiology for the vascular neurological complications in patients with HHT was pulmonary arteriovenous malformation. HHT should be considered in the differential diagnosis of any patient with cutaneous or mucosal telangiectasia or a history of unexplained epistaxis. HHT is associated with a diverse array of neurological disorders; most commonly ischemic and hemorrhagic stroke, transient ischemic attack, and brain abscess. While myelopathy secondary to arteriovenous malformation with HHT has been previously reported, this is the first instance of spinal cord infarction due to paradoxical embolization in this disorder.

Paradoxical brain embolism associated with HCV-related type II mixed cryoglobulinemia.

Central nervous system involvement in hepatitis C virus (HCV)-related cryoglobulinemia is uncommon. We report a patient with HCV-related type II mixed cryoglobulinemia who suffered a transient ischemic attack (TIA) associated with deep venous thrombosis and pulmonary embolism. The mechanism of TIA was diagnosed as paradoxical embolism, and we suspect that the cause of the TIA was associated with HCV-related type II mixed cryoglobulinemia.

Saddle Pulmonary Embolism with Paradoxical Coronary Artery Embolism through a Patent Foramen Ovale.

A 35-year-old male patient was found in cardiac arrest in his vehicle, with no apparent injuries after a minor motor vehicle collision. The decedent was found to have a saddle pulmonary embolus with a thromboembolus impacted across a patent foramen ovale and a paradoxical embolism in the circumflex coronary artery, as well as significant clotting in the deep veins of both lower extremities. There were no risk factors in his history to explain the deep venous thrombosis; family history suggested the possibility of an unrecognized clotting disorder.

Primary right atrial synovial sarcoma manifesting as transient ischemic attacks.

Primary tumors of the heart are rare and most of them benign. The majority of benign cardiac tumors are myxomas while almost all malignant cardiac tumors are sarcomas. We present a case of primary right atrial synovial sarcoma, a form of sarcoma particularly rare in the heart. The tumor manifested clinically as transient ischemic attacks probably related to a patent foramen ovale allowing paradoxical tumor embolization.