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To investigate the effectiveness of nebulized magnesium sulfate in treating persistent pulmonary hypertension of newborn (PPHN). Twenty-eight mechanically ventilated term neonates with severe PPHN were randomized into two groups: NebMag group (n = 14), who receiving nebulized isotonic magnesium (1024 mg/h), and IVMag group (n = 14), who received intravenous magnesium (200 mg/kg over 30 min, followed by 50 mg/kg/h). The study time frame was 24 h. Outcome measures were the changes in oxygenation index (OI), mean arterial blood pressure (MABP), vasoactive inotropic score (VIS), and serum magnesium level. Baseline demographic, ventilatory, and hemodynamic characteristics were comparable between the two groups. At the end of the study, the OI decreased by 44.3% in the NebMag group compared with 35.3% in the IVMag group (mean difference −3.14; 95%CI −5.08, −1.19; p 0.003). The NebMag group had a higher MABP (mean difference 2.29 mmHg; 95% CI 1.80, 2.77; p 0.000) and lower VIS (mean difference −14.64; 95% CI −16.52, −12.77; p 0.000) at the 24-h study time point. The increase in serum magnesium level, measured at 12-h study time point, was lower in the NebMag group (mean difference −2.26 mmol/L; 95% CI −2.58, −1.96; p 0.000). Nebulized magnesium sulfate may be an effective therapeutic modality for neonates with severe PPHN on mechanical ventilation, but this should be confirmed by larger studies. Retrospectively registered at www.clinicaltrials.gov (identifier: NCT04328636).

Introduction: Minimally invasive surgery (MIS) in neonates is progressively performed. The aim of this study was to evaluate the risk for cardiovascular events during endoscopic surgery in...

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare but fatal lung disorder, which causes persistent pulmonary hypertension of the newborn (PPHN) and which is unresponsive to treatment. We report the case of two siblings, both of whom died a few hours after birth because of severe pulmonary failure. Post-mortem histology confirmed ACD/MPV as the cause of death in both cases, and genetic analysis identified the same 16p13.3 deletion. ACD/MPV can occur suddenly in apparently healthy newborns after a regular pregnancy, and always leads to death. Nevertheless, an autopsy is not always performed after the death of an infant. For these reasons ACD/MPV represents a challenge for diagnosis and therapeutic management with medicolegal implications. Prenatal assessment of ACD/MPV is very difficult, and it should be suspected when irreversible and persistent fetal circulation occurs rapidly in newborns. An early diagnosis during pregnancy would facilitate adequate counselling regarding treatment and prognosis. When death occurs, a complete autopsy with histological and genetic investigations is recommended in order to define the exact cause of death, and potentially inform appropriate genetic counselling of family members who could be affected by hereditary disorders.

Background: Persistent pulmonary hypertension (PPHN) is the persistence of the high pulmonary arterial pressure after birth which is a characteristic of the fetal circulation. PPHN is associated with substantial infant mortality and morbidity. Various treatment protocol are used according to the need of the patient. This study aimed to see the spectrum of the disease and its outcome in Bangladesh.Methods: 181 newborn babies were diagnosed as persistent pulmonary hypertension or persistent fetal circulation. After establishing diagnosis, all cases were kept in NICU and various management plans were prescribed according to necessity of a specific case. Repeat echocardiography was done after 72 hours to see the response of treatment. Residual congenital cardiac lesions were managed later on.Results: Most of the patient (69.06%) was diagnosed at first week of life. Minimum age of the patient was 1 day and maximum age 23 days. Among 181 cases 109 (66.22%) were male and 72(39.77%) were female. Associated congenital lesions like atrial septal defect was found in 52 (28.72%) cases, patent ductus arteriosus (PDA) was found in 14 (7.73%) cases and ventricular septal defect (VSD) was found in 2 (1.10%) cases. Combination of ASD & PDA was found in 75 (44.33%) cases. Systolic pulmonary artery pressure was more than 60 mmHg in 103 (56.91%) cases, more than 50 mmHg in 53 (29.28%) cases and more than 30 mmHg in 25 (13.81%) cases. Most of the patient (100%) received high flow oxygen therapy along with anti failure (66.30%) and sildenafil 98 (54.14%) therapy as per requirement of the patient. Complete cure was achieved in 95.58% cases and mortality was only 1.10%.Conclusion: These data showed a very impressive outcome of the PPHN in Bangladeshi Newborn even with minimally invasive management.Cardiovasc. j. 2018; 11(1): 17-22

Objectives To investigate the effectiveness of nebulized magnesium sulfate in treating persistent pulmonary hypertension of newborn (PPHN). Methods Twenty-eight mechanically ventilated term neonates with severe PPHN were randomized into two groups: NebMag group (n = 14), who receiving nebulized isotonic magnesium (1024 mg/h), and IVMag group (n = 14), who received intravenous magnesium (200 mg/kg over 30 min, followed by 50 mg/kg/h). The study time frame was 24 h. Outcome measures were the changes in oxygenation index (OI), mean arterial blood pressure (MABP), vasoactive inotropic score (VIS), and serum magnesium level. Results Baseline demographic, ventilatory, and hemodynamic characteristics were comparable between the two groups. At the end of the study, the OI decreased by 44.3% in the NebMag group compared with 35.3% in the IVMag group (mean difference −3.14; 95%CI −5.08, −1.19; p 0.003). The NebMag group had a higher MABP (mean difference 2.29 mmHg; 95% CI 1.80, 2.77; p 0.000) and lower VIS (mean difference −14.64; 95% CI −16.52, −12.77; p 0.000) at the 24-h study time point. The increase in serum magnesium level, measured at 12-h study time point, was lower in the NebMag group (mean difference −2.26 mmol/L; 95% CI −2.58, −1.96; p 0.000). Conclusion Nebulized magnesium sulfate may be an effective therapeutic modality for neonates with severe PPHN on mechanical ventilation, but this should be confirmed by larger studies. Retrospectively registered at www.clinicaltrials.gov (identifier: NCT04328636).

Objective Risk of fetotoxicity after paracetamol exposure in the third trimester. Design Observational cohort study and retrospective case assessment. Setting Germany, 2008-2017. Population Pregnant women exposed to paracetamol. Methods Prospectively enrolled third-trimester pregnancies that had been exposed to paracetamol (604) were compared with pregnancies exposed to paracetamol in the first and/or second trimester only (1192). Exclusion criteria were exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) in the second or third trimester. Additionally, the Embryotox 'adverse drug reaction in pregnancy' database was screened for cases of fetotoxicity. Main outcome measures The prenatal study end points focused on narrowing or closure of ductus arteriosus Botalli, late fetal death, and oligohydramnios. The postnatal end points included patent ductus arteriosus (PDA), primary pulmonary hypertension (PPHT), and impaired renal function. Results In both cohorts, no fetus with intrauterine narrowing or closure of the ductus arteriosus Botalli was reported (0/604 versus 0/1192). Oligohydramnios was diagnosed at a similar frequency in both cohorts: 1.3% (8/604) versus 1.6% (19/1192). There was one stillbirth in the study cohort (1/604, 0.2%) and four stillbirths in the comparison cohort (4/1192, 0.3%). The rates of PDA in neonates were similar: 0.7% (4/615) versus 0.7% (9/1212). PPHT as well as serious postnatal renal disorders were reported once in each cohort. In 12 out of 96 retrospective cases, there were indicators for study end points; however, co-exposure to NSAIDs or complex situations weaken the assumption of paracetamol toxicity. Conclusions Fetal cardiovascular or renal toxicity of maternal third-trimester paracetamol use appears to be negligible. Tweetable abstract Paracetamol use in the third trimester does not seem to be associated with a relevant risk of fetotoxicity.

Background Cerebral vascular anatomy, specifically the circle of Willis (COW), plays an unstudied role in the development of stroke after blunt cerebrovascular injury (BCVI; carotid and vertebral). Variant anatomy is very common, and certain variants such as persistent fetal circulation (enlarged posterior communicating artery) may improve collateralization between the anterior (carotid) and posterior (vertebral) circulations. Identifying patients at increased stroke risk may allow tailored anticoagulation, the mainstay of therapy. This study constitutes the first attempt to identify vascular anatomy patterns associated with stroke, with the hypothesis that normal anatomy would protect against stroke. Study design Radiographic images from patients with BCVI-related stroke from 2005 to 2014 were identified. Patients with stroke were compared with injury-matched, non-stroke controls. Normal COW anatomy is defined as the presence of all vessels without hypoplasia. Results Of 457 patients BCVI, 22 (4.8%) BCVI-related patients with stroke and matched controls were reviewed. 9 (41%) patients with stroke and 2 (9%) controls had normal COW anatomy (OR=7.1, 95% CI 1.28 to 33.3). Persistent fetal-type circulation was found in 6 controls and 1 patient with stroke, resulting in a 7.9-fold decreased risk of stroke with this variant (OR=0.13, 95% CI 0.003 to 1.26). Conclusions Cerebral vascular anatomy has a role in BCVI-related stroke. Normal anatomy is not protective; however, the increased collateral flow provided by a persistent fetal-type enlarged posterior communicating artery is likely protective. The identification of high-risk patients may eventually allow for more tailored treatment. Prospective, multi-institutional trials are needed to further reduce the incidence BCVI-related stroke. Level of evidence Prognostic and epidemiological, level III.

Persistent Pulmonary Hypertension of Newborn (PPHN) is a critical neonatal problem resulting from failed circulatory adaptation at birth, associated with substantial perinatal morbidity as well as mortality. Despite significant advancement in management of PPHN across the globe, it still remains a challenge especially in developing countries like Bangladesh. So the study was conducted over five years in United Hospital Limited to determine the risk factors of PPHN in relation to gestational age. All PPHN cases diagnosed by echocardiogram were included in the study and divided into term (≥ 37 wks) and preterm group (

Object The cavernous sinus and surrounding regions—specifically the Meckel cave, posterior sector of the cavernous sinus itself, and the upper part of the petroclival region—are the location of a large variety of lesions that require individual consideration regarding treatment strategy. These regions may be reached for biopsy by a percutaneous needle inserted through the foramen ovale. The aim of this retrospective study was to evaluate the diagnostic accuracy of percutaneous biopsy in a consecutive series of 50 patients referred for surgery between 1991 and 2010. Methods Seven biopsies (14%) were unproductive and 43 (86%) were productive, among which 28 lesions subsequently underwent histopathological examination during a second (open) surgery. To evaluate the diagnostic accuracy of the procedure, results from surgery were compared with those from the biopsy. Results Sensitivity of the percutaneous biopsy was 0.83 (95% CI 0.52–0.98), specificity was 1 (95% CI 0.79–1), and κ coefficient was 0.81. Conclusions Because of its valuable diagnostic accuracy, percutaneous biopsy of the cavernous sinus and surrounding regions should be performed in patients with parasellar masses when neuroimaging does not provide sufficient information of a histopathological nature. This procedure would enable patients to obtain the most appropriate therapy, such as resective surgery, corticosteroids, chemotherapy, radiotherapy, or radiosurgery.

Due to the presence of fetal haemoglobin and the patency of anatomical shunts the fetal circulation is perfectly adapted to intrauterine life, utilizing the placenta as the organ of gas exchange. Immediate adaptation must occur at birth as the lungs take over this role. Initially the pulmonary vascular resistance is high but pulmonary blood flow progressively increases in the newborn due to vasodilatation as a consequence of increased oxygenation and activation of pulmonary stretch receptors. Changes in the pulmonary vasculature are mediated through a number of vasoactive substances, including nitric oxide. Increased pulmonary blood flow leads to an increase in left atrial pressure with subsequent closure of the foramen ovale. In some babies this normal adaptation fails and persistent fetal circulation may develop, leading to the symptoms of persistent pulmonary hypertension of the newborn. The mainstay of treatment is to maximize oxygenation by use of an appropriate ventilatory strategy and to maintain blood pH within normal range using inotropic support as indicated to sustain an adequate systemic blood pressure. Nitric oxide has proved to be an extremely effective treatment for this condition in some cases but ECMO may be required as a rescue therapy. Persistent pulmonary hypertension of the newborn still carries a 10–20% mortality rate despite modern intervention.

Patent foramen ovale (PFO) is associated with cryptogenic stroke, migraine headache, decompression sickness, and platypnea-orthodeoxia syndrome. Patients undergoing transesophageal echocardiography are often hypovolemic from preprocedural fasting and might not demonstrate right to left shunting owing to insufficient right atrial pressure generation, despite provocative maneuvers. We hypothesized that volume replenishment with saline loading could potentially unmask a PFO by favorably modulating the interatrial pressure gradient. Our study sought to examine the role of pre- or intraprocedural intravenous fluid replenishment on PFO detection during transesophageal echocardiography. A total of 103 patients were enrolled. An initial series of bubble injections was performed unprovoked and then with provocative maneuvers such as the Valsalva maneuver and coughing. The patients were then given a rapid 500 ml saline bolus, and the same sequence of bubble injections was repeated. The presence, type, and magnitude of the right to left shunts were noted before and after the saline bolus. The detection rate of PFO increased from 10.6% to 26.2% after saline loading without any provocative maneuvers. When combined with provocative maneuvers (Valsalva or cough), saline loading improved the detection rate from 17.4% to 32.0%. Overall, from amongst the 103 enrolled patients, saline bolusing resulted in a de novo diagnosis of PFO in 15 patients, atrial septal aneurysm in 15, PFO coexisting with an atrial septal aneurysm in 10, and pulmonary arteriovenous fistula in 5 patients. In conclusion, saline infusion in appropriately selected patients during transesophageal echocardiography significantly enhances the detection of PFOs and pulmonary arteriovenous fistulas.

Regional or systemic air embolism to the heart or cerebrum during endoscopic retrograde cholangio-pancreatography (ERCP) is an increasingly recognized phenomenon. This review aims to give an overview about the current knowledge concerning pathomechanism, diagnosis, treatment, and outcome of air embolism during ERCP. A Medline search was carried out for the key words 'ERCP' in combination with 'liver dysfunction', 'air embolism', 'complication', and 'side-effect'. Altogether 18 reports about 19 patients were found matching with the key words and the topic of interest. Systemic air embolism after ERCP occurred in 14 cases and was associated with cerebral air embolism in eight of them. In six cases with cerebral air embolism the outcome was fatal. Only two patients with cerebral air embolism survived, one of them without a deficit and one with hemiparesis. In only two cases, transgression of air from the venous to the arterial branch occurred through a patent foramen ovale. In none of the patients was transgression attributable to arterio-venous shunts within the lung or other tissues, the Thebesian veins, or insertion of the caval veins directly into the left atrium. In five patients, systemic air embolism occurred in the absence of a foramen ovale. In all these cases it was assumed that air entered the vasculature through the portal or hepatic veins. In conclusion, if patients do not awake after ERCP air embolism should be considered, an acute cerebral and thoracic computed tomography scan should be ordered, and appropriate measures, including aspiration of air from the right ventricle through an acutely floated pulmonary artery catheter or hyperbaric oxygenation initiated.

The foramen ovale, an atrial septal defect which is essential in the fetal circulation, remains patent through adulthood in approximately 25% of the general population and so it represents the most common persistent abnormality of fetal origin. Patent foramen ovale (PFO) allows interatrial right-to-left blood shunting during those periods of the cardiac cycle in which the right atrial pressure exceeds the left one. An increasing number of pathological manifestations of PFO has been recently identified; among these, paradoxical systemic embolism, refractory hypoxemia in patients with right ventricular myocardium infarction or severe pulmonary disease, orthostatic oxygen desaturation in the rare platypnea-orthodeoxia syndrome, neurological decompression illness in divers, high altitude pilots and astronauts, and finally, migraine headache with aura. Nowadays many techniques allow to detect a PFO. In this study we investigated each of them, assessing their potential diagnostic role even in comparison with the main features of the other methods.

The association between the anatomic characteristics obtained by omni-plane transesophageal echocardiography (TEE) and stroke recurrence in patients with cryptogenic stroke and patent foramen ovale (PFO) remains unclear. In the present longitudinal follow-up study, we sought to investigate whether PFO findings assessed by TEE can predict stroke recurrence. Of the 1,014 consecutive patients with acute ischemic stroke referred for TEE, 184 (mean +/- SD age, 51 +/- 14 years) were classified as having cryptogenic stroke with PFO, and follow-up data were available for 181 patients. During follow-up (median 3.5 years), 14 patients (7.7%) experienced stroke recurrence. Multivariate analysis showed that atrial septal aneurysm or hypermobility of the atrial septum (hazard ratio 6.04, 95% confidence interval 1.84 to 19.86, p = 0.003) and PFO size (hazard ratio 3.00, 95% confidence interval 1.96 to 4.60, p

We prospectively compared the bubble test with agitated saline for right-to-left shunt using transcranial Doppler (TCD) of the right middle cerebral artery and second harmonic imaging duplex of the right common carotid artery (CCA) in 100 consecutive patients. Microembolic signals (MES) were counted offline. MES were classified into 6 classes: absent (class 0), 1-10 MES (class 1), 11-20 MES (class 2), 21-30 MES (class 3), 31-50 MES (class 4) and >50 MES or "curtain effect" (class 5). For TCD, classes 2-5 combined (i.e., "large" shunts), the sensitivity of duplex with the Valsalva maneuver was 95.3%, the specificity was 100%, the positive predictive 100%, the negative predictive value 96.6% and accuracy 98.0%. Second harmonic imaging duplex of the CCA may substitute TCD for the bubble test when an adequate cranial bone window is not available. This technique may also greatly increase the number of facilities where the bubble test can be carried out. However, tests with few or no MES need to be confirmed by TCD or transesophageal echocardiography.

Orzan F, Liboni W, Bonzano A, Molinari F, Ribezzo M, Rebaudengo N, Grippi G, Negri E. Follow-up of residual shunt after patent foramen ovale closure. Acta Neurol Scand: 2010: 122: 257–261. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objectives – Transesophageal echocardiography (TEE) is usually recommended in the evaluation of the patent foramen ovale (PFO). Our goal is to confirm the efficacy of contrast-enhanced transcranial Doppler (ce-TCD) in detecting residual significant right-to-left shunts (RLS) after PFO percutaneous closure. Materials and methods – Sixty-eight patients with a previous transient ischemic attack, stroke and a large PFO were investigated for residual RLS after percutaneous closure. Results – Assuming TEE as the gold standard, the sensitivity and negative predictive value of ce-TCD was 100%, whereas the specificity was 75.8% and the positive predictive value was 28%. Conclusions – ce-TCD appears to be the preferable technique to identify subjects with significant residual shunts after percutaneous closure of a PFO. In follow-up, if ce-TCD is negative, no further examination may be necessary; whereas if ce-TCD shows a residual shunt, it is advisable to perform a TEE investigation.

Atrial septal aneurysm (ASA) and patent foramen ovale (PFO) are not uncommon during routine echocardiographic scanning and were reported to be associated with stroke, transient ischemic attacks, and migrainous headache. To assess the prevalence of ASA and PFO according to ethnicity, we retrospectively studied 887 consecutive referrals to a General Cardiology and Hypertension clinics. All participants underwent trans-thoracic echocardiography (TTE). In some patients, the TTE was repeated using bubble contrast. Results: Atrial septal aneurysm was detected in 70 participants (7.9%) and PFO in 18 (2%). Atrial septal aneurysm, PFO, or their combination was detected in 12% of the Caucasian patients, 15% of the Afro-Caribbean, and 3.7% of the Indo-Asian patients. Conclusions: There was a lower prevalence of ASA and PFO and their combination in Indo-Asians and a higher rate in Afro-Caribbeans than in Caucasians. The higher prevalence in the Afro-Caribbean participants may contribute to the high incidence of stroke in black participants.

Transcatheter patent foramen ovale (PFO) closure might be effective in improving migraines. To assess the efficacy of PFO closure in migraineurs with a moderate to large right-to-left shunt and instrumental evidence of embolic cerebral damage, 76 highly symptomatic migraineurs were prospectively investigated. The presenting clinical syndrome was stroke in 16 patients, repeated transient ischemic attack in 32 patients, and lone migraine associated with cerebral ischemic lesions on magnetic resonance imaging in 28 patients. Migraine severity was assessed before PFO closure and monthly for 6 months after discontinuation of antiplatelet therapy. At the end of 12 months of follow-up, the averaged postprocedural total score was compared with the baseline score. Transcatheter PFO closure was successful in all patients, and the 12-month PFO closure rate was 97%. The baseline total migraine score was similar in patients with stroke, transient ischemic attack, and lone migraine (6.8 +/- 1.6, 6.7 +/- 1.4, and 6.9 +/- 1.7 respectively, p = NS). After a mean follow-up of 13.7 +/- 2.4 months, no recurrent cerebrovascular episodes had occurred. At the end of the follow-up period, a significant reduction in the total migraine score was observed in all groups, regardless of the initial clinical presentation. Migraine was completely abolished in 35 patients (46%), improved in 27 (36%), and unchanged in 14 (18%). The proportion of patients with migraine suppression and improvement was similar in the 3 groups. In conclusion, in highly symptomatic migraineurs with previous ischemic cerebral events and instrumental evidence of cerebral embolism, transcatheter PFO closure can result in improvement of migraine severity in a high percentage of patients. (C) 2009 Published by Elsevier Inc. (Am J Cardiol 2009;104:434-439)

Congenital diaphragmatic hernia (CDH) is characterized by a defect in the diaphragm that permits abdominal viscera to herniate into the chest. These herniated viscera are thought to compress the growing lung and cause lung parenchymal and vascular hypoplasia. The genetic defects that cause the diaphragmatic defect may also contribute primarily to lung hypoplasia. Postnatal reduction of the herniated abdominal viscera and correction of the diaphragmatic defect are easily achievable, but the lung hypoplasia persists, often leading to persistent fetal circulation and respiratory failure. This article reviews the experimental basis of fetal therapy for CDH and the US clinical experience with tracheal occlusion.

Patent foramen ovale (PFO) is a remnant of the foetal circulation, found in about a quarter of the population. PFO is an asymptomatic condition and the high prevalence infers that it is in most cases of no or only limited clinical significance. However, recent research has found an increased prevalence of PFO in cryptogenic stroke, decompression illness and migraine. The presence of a PFO has also been associated with oxygen desaturation in conditions such as obstructive pulmonary disease and obstructive sleep apnoea. The rapid evolution and widespread availability of catheter-based closing techniques have further stimulated interest. The seemingly growing significance of PFO will be discussed in this review.

Meconium aspiration syndrome (MAS) mainly affects term and post-term infants. It ranges from mild respiratory distress to life-threatening cardiorespiratory failure. Prevention and treatment strategies are evolving. Amnioinfusion is no longer recommended for women with meconium staining of the amniotic fluid (MSAF). Pharyngeal suction prior to delivery of the fetal shoulders and tracheal suction of vigorous infants after birth do not prevent MAS and may be harmful. Tracheal suction is recommended for non-vigorous infants with MSAF but has not been studied prospectively. Bolus surfactant therapy, high frequency oscillatory ventilation and inhaled nitric oxide may be beneficial in severe cases. Surfactant lavage reduces the combined risk of death or requirement for extracorporeal membrane oxygenation (ECMO) when compared with no surfactant treatment but its role in the routine management of MAS is uncertain and it should be compared with bolus surfactant in prospective studies. ECMO reduces the risk of mortality in severe cases so it is of paramount importance to discuss the transfer of severely ill infants to an ECMO centre.

Background: Hypoxic–ischemic encephalopathy (HIE) is an important complication that results from birth asphyxia or some other adverse conditions and has a high risk of neonatal morbidity and mortality. It is unclear, however, whether the elevated pulmonary arterial pressure (PAP) can aggravate the condition and prognosis of HIE. The purpose of the present study was to investigate the relationship between the changes of PAP and HIE in term infants after birth asphyxia. Methods: The left/right ventricle pre-ejection phase (LPEP/RPEP), left/right ventricle ejection time (LVET/RVET) and the ratios of LPEP/LVET and RPET/RVET were evaluated in 40 term infants with HIE and 40 healthy controls on days 1, 3, 7, and 12–14 after birth using echocardiogram. PAP such as pulmonary arterial diastolic pressure (PADP, mmHg), pulmonary arterial resistance (PAR, mmHg), and pulmonary arterial resistance/systemic resistance ratio (PAR/RS) was calculated using these indexes. Patient mortality was also evaluated. Results: PADP, PAR, and PAR/RS were significantly higher in HIE patients than in healthy controls during the first week after birth, particularly in severe-degree HIE patients. And until the end of the first week of life, these indexes may return to the levels of healthy controls. Persistent fetal circulation (PFC) was found in nine patients (7/16 severe, 2/12 moderate HIE patients), and non-PFC was found in mild HIE patients. Two patients with PFC died. No patients without PFC died. The course of HIE was longer in patients with pulmonary hypertension than in those without. Conclusion: Increased PAP is an important pathophysiological process that may influence the course and prognoses of HIE in infants after birth asphyxia, particular in severe HIE patients who often have PFC. Thus it is important to assess changes in PAP using echocardiography.

Background and Purpose— To further determine the mechanisms of cryptogenic stroke or transient ischemic attack in young patients, we evaluated indices of atherosclerosis in patients ≤55 years old diagnosed with cryptogenic cerebrovascular event comparing those with patent foramen ovale (PFO) with those without PFO. Methods— This was a prospective study including 100 consecutive patients ≤55 years old (mean age, 45±8 years; 56 males) diagnosed with cryptogenic stroke/transient ischemic attack. PFO was identified in 59 of these patients with the use of transesophageal echocardiography with contrast study. The following surrogate markers of atherosclerosis were evaluated in all patients: carotid intima media thickness as measured by carotid ultrasonography and endothelial function as determined by brachial flow-mediated vasodilation. The same measurements were obtained in a control group of 50 age- and sex-matched control subjects. Results— Patients without PFO were more likely to be current smokers and obese and more frequently had a history of hypertension and dyslipidemia. Carotid intima media thickness measurements were higher ( P P =0.02). There were no differences in carotid intima media thickness and flow-mediated vasodilation between patients with stroke/transient ischemic attack with PFO and control subjects. The presence of PFO was independently associated with reduced carotid intima media thickness ( P P =0.019). Conclusions— In patients ≤55 years old diagnosed with cryptogenic stroke/transient ischemic attack, the presence of PFO was associated with a lower atherosclerotic burden as measured by carotid intima media thickness and endothelial function with no differences compared with a control group without cerebrovascular event. These results suggest that an atherosclerotic-mediated mechanism may be involved in cryptogenic stroke/transient ischemic attack in patients without PFO, whereas a nonatherosclerotic mechanism may mediate the cerebrovascular event in the presence of PFO.

Background and Purpose— Few studies have prospectively examined the risk of recurrent stroke associated with patent foramen ovale. We present the results of the Spanish right-to-left shunt (RLSh) multicenter study. Methods— Four hundred eighty-six patients with cryptogenic stoke were included at 17 participating hospitals. Patients were examined by contrast transcranial Doppler methods at baseline. The magnitude of RLSh was quantified during the Valsalva maneuver. Transthoracic and/or transesophageal echocardiography, computed tomography scan, or magnetic resonance imaging was performed. Functional outcome and stroke recurrence were evaluated at 3 months and yearly thereafter. The independent relation between RLSh magnitude and stroke recurrence was analyzed by logistic-regression analysis in the whole group and in the younger subgroup ( Results— Massive RLSh was detected in 200 patients (41.2%). The mean follow-up was 729±411 days. Stroke recurrence was low (5.8%, n=28) and similar in patients with massive RLSh, with nonmassive RLSh, and with no RLSh, in both the younger group (3.4% vs 2.3% vs 4.5%, respectively; P =0.75) and in the whole population (5.0% vs 6.2% vs 6.3%, respectively; P =0.58). Regression analysis found no association between massive RLSh and recurrent stroke in either group (in the whole population, odds ratio=0.94; 95% CI, 0.36 to 2.40; P =0.89; in the younger population, odds ratio=0.93; 95% CI, 0.18 to 4.91; P =0.93). These results were similar when concurrent atrial septal aneurysm and massive RLSh were analyzed and when antithrombotic treatment and concomitant stroke risk factors were included. Conclusions— These results suggest that neither massive RLSh nor massive RLSh with concurrent atrial septal aneurysm is an independent risk factor for recurrent stroke, in either the general or younger stroke populations.

To investigate the feasibility of 64-section multidetector computed tomography (CT) by using CT angiography (a) to demonstrate anatomic detail of the interatrial septum pertinent to the patent foramen ovale (PFO), and (b) to visually detect left-to-right PFO shunts and compare these findings in patients who also underwent transesophageal echocardiography (TEE).In this institutional review board-approved HIPAA-compliant study, electrocardiographically gated coronary CT angiograms in 264 patients (159 men, 105 women; mean age, 60 years) were reviewed for PFO morphologic features. The length and diameter of the opening of the PFO tunnel, presence of atrial septal aneurysm (ASA), and PFO shunts were evaluated. A left-to-right shunt was assigned a grade according to length of contrast agent jet (grade 1,or=1 cm; grade 2,1 cm to 2 cm; grade 3,2 cm). In addition, 23 patients who underwent both modalities were compared (Student t test and linear regression analysis). A difference with P.05 was significant.A flap valve, seen in 101 (38.3%) patients, was patent at the entry into the right atrium (PFO) in 62 patients (61.4% of patients with flap valve, 23.5% of total patients). A left-to-right shunt was detected in 44 (16.7% of total) patients (grade 1, 61.4%; grade 2, 34.1%; grade 3, 4.5%). No shunt was seen in patients without a flap valve. Mean length of PFO tunnel was 7.1 mm in 44 patients with a shunt and 12.1 mm in 57 patients with a flap valve without a shunt (P.0001). In patients with a tunnel length of 6 mm or shorter, 92.6% of the shunts were seen. ASA was seen in 11 (4.2%) patients; of these patients, a shunt was seen in seven (63.6%). In 23 patients who underwent CT angiography and TEE, both modalities showed a PFO shunt in seven.Multidetector CT provides detailed anatomic information about size, morphologic features, and shunt grade of the PFO. Shorter tunnel length and septal aneurysms are frequently associated with left-to-right shunts in patients with PFO.

Despite the growing recognition of the patent foramen ovale (PFO), particularly when associated with an atrial septal aneurysm, as risk factor for several disease manifestations (above all paradoxical embolism), the optimal treatment strategy for symptomatic patients remains controversial. Percutaneous PFO closure is a minimally invasive procedure which can be performed with high success and low morbidity. For secondary prevention of recurrent embolic events, it appears to be clinically at least as effective as oral anticoagulation. Ventricular septal defects (VSDs) are the most common congenital heart defects. Percutaneous VSD closure is more intricate than PFO closure. It is associated with a significant risk of both peri-interventional and mid-term complications. In suitable patients with congenital VSD, device closure may well be the preferred treatment both for muscular or perimembranous VSDs and for residual defects after surgical VSD closure. The risk of complete atrioventricular conduction block remains a concern in the perimembranous group. The history, technique and clinical role of percutaneous PFO and VSD closure are discussed, with emphasis on current problems and future developments.

Summary Background Patent foramen ovale is an anomaly responsible for paradoxical embolizations and cerebral ischemic events. Aims We want to show second harmonic transthoracic echography sensitized by contrast agent perfusion is as well as transesophageal echography to patent foramen ovale detection. Methods Onene hundred twenty one patients referred for transesophageal echocardiography for patent foramen ovale detection, underwent additive second harmonic transthoracic echocardiography with one of three randomized contrast agents: a mixture A of dextrose and air, mixture B of dextrose and air and blood, or mixture C of hydroxyethylamidon. The severity of atrial shunting was evaluated on recordings by semi-quantitative scoring. Intensity of contrast was also assessed by objective quantitative videodensitometry. Results No difference was observed between the two techniques, nor between mixture A, B and C in terms of PFO detection during each exam. However, quantitative contrast analysis showed higher intensity with mixtures B and C with mixture A during transthoracic echography. Conclusions When performed with a contrast agent, second harmonic transthoracic echography and transoesophageal echography are comparable when it comes to patent foramen ovale detection. Although the composition of the contrast agent does not appear to affect the rate of this detection, contrast quality in the right atrium during transthoracic exam is better with mixtures B and C than with mixture A.

The aim of this study was to assess (1) the incidence of patent foramen ovale (PFO) in carcinoid syndrome (CS) and (2) the feasibility of percutaneous closure procedure in selected patients with CS. One hundred eight patients were prospectively studied: 54 with CS and an age- and gender-matched control group. All patients underwent conventional and contrast echocardiography. Patients with clinical signs of dyspnea (New York Heart Association classor =III), cyanosis, carcinoid heart disease (CHD), and severe PFO were referred for the percutaneous closure of PFO. The prevalence of PFO was 41% in patients with CS and 22% in the control group (p = 0.03) and was significantly higher in patients with CHD (59%, p = 0.009). Four patients (14% of those with CHD) were referred for the percutaneous closure of PFO, and 3 patients ultimately underwent PFO closure (using Amplatzer septal occluders). At 6-month follow-up, New York Heart Association class was improved in all patients, as well as arterial blood gas results (p = 0.04) and 6-minute walking distance (p = 0.03), but all patients presented residual right-to-left shunts. In conclusion, this prospective study demonstrates that in patients with CHD, the prevalence of PFO is high and that percutaneous closure of PFO is feasible, with a reduction in symptoms but with residual shunting.

The purpose of our study was to show the feasibility of ECG-gated, 64-MDCT cardiac angiography for the detection of patent foramen ovale (PFO).Chart review was performed on 214 consecutive patients referred for clinically indicated 64-MDCT angiography. The study cohort consisted of 20 patients who had previously undergone transesophageal echocardiography (TEE). Blinded consensus review of each CT angiography was performed by two experienced cardiac radiologists and results were compared with TEE, which served as a reference standard. CT criteria for the diagnosis of PFO were distinct left atrial "flap" in the expected location of the septum primum, continuous column of contrast material connecting this flap to the right atrium, and a "jet" of contrast material from the column into the right atrium.Of the 20 patients who underwent both TEE and cardiac CT angiography, six (30%) were found to have a PFO by TEE. Using the presence of a left atrial flap as the only diagnostic criterion, all six cases of PFO were detected using CT (sensitivity = 100%). Of the 14 patients with no PFO seen on TEE, 12 of these were correctly identified using CT (specificity = 86%). Using all three criteria together, the sensitivity decreased to 66% and the specificity increased to 100%.ECG-gated cardiac CT angiography performed with a 64-MDCT scanner can be used to reliably detect PFO.

Background— Patent foramen ovale (PFO) is prevalent in patients with migraine with aura. Observational studies show that PFO closure resulted in migraine cessation or improvement in ≈80% of such patients. We investigated the effects of PFO closure for migraine in a randomized, double-blind, sham-controlled trial. Methods and Results— Patients who suffered from migraine with aura, experienced frequent migraine attacks, had previously failed ≥2 classes of prophylactic treatments, and had moderate or large right-to-left shunts consistent with the presence of a PFO were randomized to transcatheter PFO closure with the STARFlex implant or to a sham procedure. Patients were followed up for 6 months. The primary efficacy end point was cessation of migraine headache 91 to 180 days after the procedure. In total, 163 of 432 patients (38%) had right-to-left shunts consistent with a moderate or large PFO. One hundred forty-seven patients were randomized. No significant difference was observed in the primary end point of migraine headache cessation between implant and sham groups (3 of 74 versus 3 of 73, respectively; P =0.51). Secondary end points also were not achieved. On exploratory analysis, excluding 2 outliers, the implant group demonstrated a greater reduction in total migraine headache days ( P =0.027). As expected, the implant arm experienced more procedural serious adverse events. All events were transient. Conclusions— This trial confirmed the high prevalence of right-to-left shunts in patients with migraine with aura. Although no significant effect was found for primary or secondary end points, the exploratory analysis supports further investigation. The robust design of this study has served as the model for larger trials that are currently underway in the United States and Europe.