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.

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.

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.

The association of patent foramen ovale morphology and stroke size in patients with paradoxical embolism.

BACKGROUND: Patent foramen ovale (PFO) has been implicated in the pathogenesis of cryptogenic stroke through paradoxical embolization to the cerebral circulation. This study evaluated the relationship between the morphological and functional size of the PFO by echocardiography compared with cerebral infarct volume identified on MRI. METHODS AND RESULTS: Patients who were referred to interventional cardiology with the diagnosis of cryptogenic stroke were included and had either a transesophageal echocardiogram or an intracardiac echo and a brain MRI at the time of stroke. Transesophageal echocardiogram or intracardiac echo was used to obtain PFO measurements. MRI of the brain with 3 sequences (T2, diffusion-weighted imaging, and fluid-attenuated inversion recovery) was used to diagnose acute stroke and measure the infarct volume. In the 72 patients studied, the median measured stroke volume was 4.3 cm(3) on diffusion-weighted imaging, 4.1 cm(3) on T2, and 3.5 cm(3) on fluid-attenuated inversion recovery. There was no significant correlation between the PFO height, length, septum secundum thickness, or echo bubble grade and the infarct volume measured from the 3 MRI sequences. There was a significant correlation between septal excursion distance and infarct volume (r=0.35; P=0.005), but the 12 patients with atrial septal aneurysm did not have the largest strokes. CONCLUSIONS: This analysis revealed that septal excursion distance correlates with stroke size by MRI. However, smaller PFO size without the presence of atrial septal aneurysm may still be associated with significant strokes. There was no significant association between PFO height, length by echo, or shunt grade by transcranial Doppler study and brain infarct volume. Therefore, PFO size or morphology should not be the only criteria to decide whether a PFO should be closed.

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.

Entrapment: thrombus within a patent foramen ovale.

A 61-year-old gentleman presented to our institute with increasing dyspnoea. He had a previous diagnosis of a deep vein thrombus and was maintained on coumarin therapy. Investigations to evaluate the cause of his dyspnoea included a chest computed tomography (CT) scan and a bronchoscopy. The CT scan suggested the presence of granulomatous lung disease although subsequent sampling for acid-fast bacilli and sarcoidosis were negative. The patient's health declined and an urgent transthoracic echocardiogram was performed. This demonstrated the presence of a large thrombus lodged within a patent foramen ovale. The patient died shortly later. At postmortem, a large thrombus was confirmed to be straddling across a patent foramen ovale. Lung histology demonstrated that the micronodular opacities visualized on the chest CT scan were in fact pulmonary emboli with fibrosis. We present the echocardiographic appearance of the patent foramen ovale thrombus and its rare pathological correlate at postmortem.