Evaluation of early electrocardiographic changes after successful percutaneous stent implantation to isolated coarctation of aorta.

BACKGROUND: Coarctation of aorta (CoA) is a congenital obstructive lesion characterized by narrowing of the aorta in which concludes as increase in afterload. Percutaneous stent implantation to CoA is a treatment of choice in older children and adults. Pathology related to CoA mainly caused by increased afterload and left ventricular hypertrophy. Electrocardiographic (ECG) findings are also related to left ventricular hypertrophy (LVH). Evidence shows that, in variety of diseases, the correction of the pathology might normalize ECG findings and ventricular dysfunction related to increase in afterload. Therefore the aim of this study was to compare the pre- and postprocedural ECG findings of the patients who underwent percutaneous intervention for isolated CoA. METHODS: After exclusion criterion was applied, 30 patients were included into study, retrospectively. ECG records before the procedure and 3 months after the procedure of the patients were evaluated. The parameters related to LVH, ventricular and atrial conduction were evaluated and compared between pre- and post-procedural ECG records. RESULTS: The findings showed that parameters of atrial conduction including P wave maximum duration (p < 0.001) and p wave dispersion (p < 0.001) were significantly decreased after stent implantation. Additionally, ventricular repolarization parameters including QT duration (p = 0.039), Tpe interval (p < 0.001), Tpe / QT (p = 0.038) and Tpe / QTc (p = 0.003) were significantly decreased after stent implantation. Sokolow-Lyon criteria (p < 0.003) and voltage in selected leads were significantly decreased after intervention. CONCLUSION: Percutaneous intervention to CoA might regress LVH parameters in ECG and improve atrial and ventricular repolarization in ECG, which might lead to decreased event of atrial and ventricular arrhythmias in patients with isolated CoA.

Utilisation of advanced MRI techniques to understand neurovascular complications of PHACE syndrome: a case of arterial stenosis and dissection.

PHACE syndrome is a rare disorder with posterior fossa brain malformations, segmental infantile haemangiomas, arterial anomalies, cardiac defects and eye anomalies. Cerebral and cervical arterial abnormalities occur commonly in these patients, predisposing subjects with PHACE syndrome to neurovascular complications including migraine-like headaches, moyamoya vasculopathy, arterial dissection and arterial ischaemia stroke. We leveraged institutional MRI protocols developed for adult neurovascular disease to better elucidate the pathogenesis of the arterial alternations observed in PHACE. Using high-resolution vessel wall and 4D flow MRI, we demonstrated enhancement, focal dissection and altered blood flow in a 7-year-old girl with PHACE syndrome. This is the first-time vessel wall imaging has been used to detail the known arterial changes in PHACE, and these findings may indicate that progressive vascular narrowing and vessel wall changes/inflammation are a factor in chronic headaches and other arterial complications seen in subjects with PHACE syndrome.

Prostaglandin E 2 in a preterm infant with coarctation of the aorta.

Prostaglandins are widely used in aortic coarctation to maintain ductal patency and preserve systemic perfusion until surgical intervention can be performed. Although the short-term use of prostaglandins to ameliorate aortic narrowing in neonates with a closed ductus has been reported, it has not been described as a longer term therapy in extremely preterm neonates. A 27-week gestation baby weighing 560 g presented at 40 days of age with coarctation and a closed ductus arteriosus. He was successfully treated with a 7-week course of prostaglandin E2 therapy because surgical intervention was not deemed feasible in view of his size. Treatment resulted in a relaxation of the aortic constriction and improvement in aortic blood flow velocity profile, highlighting the value of long-term prostaglandin therapy in this population and supporting the hypothesis that the presence of ductal tissue contributes to the development of juxtaductal aortic constriction in some extremely preterm infants.

Changes in Anesthetic and Postoperative Sedation-Analgesia Practice Associated With Early Extubation Following Infant Cardiac Surgery: Experience From the Pediatric Heart Network Collaborative Learning Study.

OBJECTIVES: The Pediatric Heart Network sponsored the multicenter Collaborative Learning Study that implemented a clinical practice guideline to facilitate early extubation in infants after repair of isolated coarctation of the aorta and tetralogy of Fallot. We sought to compare the anesthetic practice in the operating room and sedation-analgesia management in the ICU before and after the implementation of the guideline that resulted in early extubation. DESIGN: Secondary analysis of data from a multicenter study from January 2013 to April 2015. Predefined variables of anesthetic, sedative, and analgesia exposure were compared before and after guideline implementation. Propensity score weighted logistic regression analysis was used to determine the independent effect of intraoperative dexmedetomidine administration on early extubation. SETTING: Five children's hospitals. PATIENTS: A total of 240 study subjects who underwent repair of coarctation of the aorta or tetralogy of Fallot (119 preguideline implementation and 121 postguideline implementation). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinical practice guideline implementation was accompanied by a decrease in the median total intraoperative dose of opioids (49.7 vs 24.0 µg/kg of fentanyl equivalents, p < 0.001) and benzodiazepines (1.0 vs 0.4 mg/kg of midazolam equivalents, p < 0.001), but no change in median volatile anesthetic agent exposure (1.3 vs 1.5 minimum alveolar concentration hr, p = 0.25). Intraoperative dexmedetomidine administration was associated with early extubation (odds ratio 2.5, 95% CI, 1.02-5.99, p = 0.04) when adjusted for other covariates. In the ICU, more patients received dexmedetomidine (43% vs 75%), but concomitant benzodiazepine exposure decreased in both the frequency (66% vs 57%, p < 0.001) and cumulative median dose (0.5 vs 0.3 mg/kg of ME, p = 0.003) postguideline implementation. CONCLUSIONS: The implementation of an early extubation clinical practice guideline resulted in a reduction in the dose of opioids and benzodiazepines without a change in volatile anesthetic agent used in the operating room. Intraoperative dexmedetomidine administration was independently associated with early extubation. The total benzodiazepine exposure decreased in the early postoperative period.

Preoperative administration of propranolol reduced the surgical risks of PHACES syndrome in a 14-month-old girl.

PHACES syndrome is an uncommon neurocutaneous disorder first identified in 1996. Patients with PHACES syndrome often require surgical treatment for their anomalies, including intracranial vasculopathy, coarctation/interruption of the aorta, intracardiac defects, glaucoma/cataract and sternal defects. Risk factors associated with the symptoms of intraoperative/perioperative management include ischaemic stroke due to the cerebral vasculopathy, airway obstruction due to the subglottic/tracheal haemangiomas and massive bleeding due to the large haemangiomas. Recently, propranolol is considered as first-line therapy for patients with infantile haemangiomas (IHs). However, until now, there have been no reported cases of PHACES syndrome treated by propranolol to reduce the surgical risks associated with IH. In this report, we describe a case of a 14-month-old Japanese girl with PHACES syndrome treated by propranolol for IH before surgical closure of the ventricular septum defect. Oral administration of propranolol was effective in decreasing the size of IH, leading to the uneventful perioperative course.

Human genotyping and an experimental model reveal NPR-C as a possible contributor to morbidity in coarctation of the aorta.

Coarctation of the aorta (CoA) is a common congenital cardiovascular (CV) defect characterized by a stenosis of the descending thoracic aorta. Treatment exists, but many patients develop hypertension (HTN). Identifying the cause of HTN is challenging because of patient variability (e.g., age, follow-up duration, severity) and concurrent CV abnormalities. Our objective was to conduct RNA sequencing of aortic tissue from humans with CoA to identify a candidate gene for mechanistic studies of arterial dysfunction in a rabbit model of CoA devoid of the variability seen with humans. We present the first known evidence of natriuretic peptide receptor C (NPR-C; aka NPR3) downregulation in human aortic sections subjected to high blood pressure (BP) from CoA versus normal BP regions (validated to PCR). These changes in NPR-C, a gene associated with BP and proliferation, were replicated in the rabbit model of CoA. Artery segments from this model were used with human aortic endothelial cells to reveal the functional relevance of altered NPR-C activity. Results showed decreased intracellular calcium ([Ca2+]i) activity to C-type natriuretic peptide (CNP). Normal relaxation induced by CNP and atrial natriuretic peptide was impaired for aortic segments exposed to elevated BP from CoA. Inhibition of NPR-C (M372049) also impaired aortic relaxation and [Ca2+]i activity. Genotyping of NPR-C variants predicted to be damaging revealed that rs146301345 was enriched in our CoA patients, but sample size limited association with HTN. These results may ultimately be used to tailor treatment for CoA based on mechanical stimuli, genotyping, and/or changes in arterial function.

Beneficial effects of phycobiliproteins from Spirulina maxima in a preeclampsia model.

AIMS: Considering phycobiliproteins of Spirulina maxima has shown a wide margin of security in pregnant and non-pregnant animals as well as antioxidant properties, present study aimed to investigate if the cardiovascular and metabolic effects of an experimental model of preeclampsia can be prevented by the administration of this compound. MAIN METHODS: Subrenal aortic coarctation (SRAC) practiced to female Wistar rats of 8 weeks of age. Animals were divided randomly to conform non-pregnant and pregnant groups and pregnant with SRAC showed fetoplacental ischemia and were considered preeclamptic (PE). Groups were treated with saline solution (control group) or phycobiliproteins solution (100 mg/kg/day ig) for the last 7, 14 or 20 days of pregnancy. KEY FINDINGS: PE animals showed increased systolic blood pressure, weight gain, glucose and GTT as well as vascular contractility. Also, PE animals showed decreased SOD, GPx activities while MDA was increased. Phycobiliproteins oral treatment for 3 weeks significantly decreased systolic blood pressure and reestablished glucose, weight gain and vascular contractility as well as enzyme activities of PE rats to those of normal pregnant animals. SIGNIFICANCE: Our results show that phycobiliproteins can prevent the damage produced by fetoplacental ischemia and provides evidence of free radical species contribution to the physiopathology of the disease. Also, we conclude phycobiliproteins can be an alternative to reduce preeclampsia manifestations, however, more studies are recommended.

Oral propranolol in the treatment of proliferating infantile haemangiomas: British Society for Paediatric Dermatology consensus guidelines.

BACKGROUND: Infantile haemangiomas (IH) are the most common vascular tumours of infancy. Despite their frequency and potential complications, there are currently no unified U.K. guidelines for the treatment of IH with propranolol. There are still uncertainties and diverse opinions regarding indications, pretreatment investigations, its use in PHACES (posterior fossa malformations-haemangiomas-arterial anomalies-cardiac defects-eye abnormalities-sternal cleft and supraumbilical raphe) syndrome and cessation of treatment. OBJECTIVES: To provide unified guidelines for the treatment of IH with propranolol. METHODS: This study used a modified Delphi technique, which involved an international treatment survey, a systematic evidence review of the literature, a face-to-face multidisciplinary panel meeting and anonymous voting. RESULTS: The expert panel achieved consensus on 47 statements in eight categories, including indications and contraindications for starting propranolol, pretreatment investigations, starting and target dose, monitoring of adverse effects, the use of propranolol in PHACES syndrome and how to stop treatment. CONCLUSIONS: These consensus guidelines will help to standardize and simplify the treatment of IH with oral propranolol across the U.K. and assist in clinical decision-making.

Chronic Low Dose Prostaglandin and Neonatal Heart Block.

Long-term prostaglandin use is commonly associated with side effects such as cortical proliferation of the bones, hypertrophic pyloric stenosis, and soft tissue swelling of the extremities. We report a neonate with critical coarctation of the aorta, who developed second and third degree atrioventricular blocks associated with prolonged prostaglandin E1 (PGE1) infusion. Interestingly, these conduction blocks only occurred at low PGE1 dose. The rhythm disturbances resolved promptly with the discontinuation of PGE1 following surgical repair.

Indomethacin induced and prostaglandin relieved coarctation of the aorta in right aortic arch with left arterial duct: a case report.

We describe the case of an infant with DiGeorge syndrome born with a right aortic arch and left arterial duct. Despite the remote location of the right aortic arch from the left arterial duct, he developed coarctation of the aorta during treatment with indomethacin. This was relieved by prostaglandin treatment. This case highlights the fact that, even in the absence of an arterial duct, ductal tissue can still be present in the aorta, and cause coarctation when exposed to indomethacin. We also demonstrate the utility of prostaglandin for relief of this type of obstruction.

Inhibition of TNF-α-mediated NF-κB Activation by Ginsenoside Rg1 Contributes the Attenuation of Cardiac Hypertrophy Induced by Abdominal Aorta Coarctation.

Ginsenoside Rg1 (Rg1), a protopanaxadiol saponin extracted from Chinese medicine Panax ginseng C.A. Meyer, has been demonstrated to inhibit the cardiac hypertrophy. However, the molecular mechanisms underlying the inhibition remain poorly understood. Activation of nuclear factor-kappa B (NF-κB) mediated by tumor necrosis factor α (TNF-α) gets involved in the cardiac hypertrophy. This study is designed to investigate the effects and the potential mechanism of Rg1 on the abdominal aorta coarctation (AAC)-induced cardiac hypertrophy with focus on TNF-α/NF-κB signaling pathway. The results showed that oral administration of Rg1 dose-dependently improved the pathological changes, decreased the ratios of left ventricular weight/body weight (LVW/BW) and heart weight/BW (HW/BW), corrected the dysfunction of the cardiac hemodynamics by decreasing the left ventricular systolic pressure and left ventricular end-diastolic pressure and increasing the maximal rate of left ventricular systolic and diastolic pressure (±dp/dtmax) compared with the AAC alone. Rg1 also downregulated the atrial natriuretic peptide mRNA expression and decreased the mRNA and protein expression of TNF-α in the heart tissue of rats compared with the AAC alone. In addition, Rg1 and BAY, the specific inhibitor of NF-κB, decreased the protein content and downregulated the mRNA expression of atrial natriuretic peptide in neonatal rat ventricular myocytes treated with TNF-α. Furthermore, Rg1 increased the protein expression of p65, the subunit of NF-κB, in cytoplasm and decreased the expression p65 in nucleus of the heart tissue of rats undergoing the AAC and of neonatal rat ventricular myocytes treated with TNF-α. The results suggested that Rg1 attenuates the AAC-induced cardiac hypertrophy through inhibition of TNF-α/NF-κB signaling pathway.

PHACE syndrome--clinical features, aetiology and management.

UNLABELLED: PHACE syndrome comprises a spectrum of anomalies including posterior fossa malformations, haemangioma, arterial anomalies, cardiac defects and eye anomalies. PHACE should be considered in any patient with a large facial segmental infantile haemangioma (IH), and multidisciplinary management is crucial. Low-dose propranolol is effectively for the treatment of IH associated with PHACE syndrome. Recent evidence suggests IH is comprised of mesoderm-derived haemogenic endothelium. CONCLUSION: The embryonic developmental anomaly nature of IH provides an insight into the origin of PHACE syndrome.

Orbital Hemangioma with Intracranial Vascular Anomalies and Hemangiomas: A New Presentation of PHACE Syndrome?

We present two cases of infants with a similar constellation of clinical findings: retro-orbital infantile hemangioma (IH), internal carotid artery (ICA) arteriopathy, and intracranial IH. In both cases, intracranial vascular anomalies and hemangiomas were found incidentally during evaluation of unilateral proptosis. Neither infant had evidence of cutaneous segmental IH of the face or neck, which might have provided a clue to the diagnosis of PHACE syndrome or of intracranial hemangiomas. In one case, intracranial involvement was particularly extensive and function threatening, with mass effect on the brain parenchyma. These cases serve to highlight the fact that clinical findings of proptosis, globe deviation, and strabismus should prompt immediate imaging to confirm the presence of orbital IHs and to exclude other diagnoses. Moreover, based on our cases and the embryologic origin of the orbit as a unique developmental unit, patients with confirmed retro-orbital IHs should undergo evaluation for anomalies associated with PHACE syndrome. Patients with orbital IHs and an additional major criterion for PHACE syndrome should be considered to have definite, and not just possible, PHACE syndrome.

Medical management of aortic coarctation is feasible & durable in selected patients: a case report & literature review.

Long-term survival in patients with complete aortic coarctation (AC) without surgical repair has not been well characterized and is rarely documented. We report a case of an 84 year old male with complete aortic coarctation with history of hypertension for more than 40 years. Since the diagnosis was made in early 1950's medical treatment to control hypertension was initiated as patient was deemed high risk for surgical intervention. He has survived to the age of 84 years with minimal medical problems. This report also reviews the few documented cases of prolonged survival in patients with aortic coarctation. This report demonstrates that prolonged survival is possible in patients with documented complete coarctation and awareness of this report may influence the decision to use medical treatment for selected elderly patients with high risk of mortality associated with surgical repair.

PHACE syndrome, a series of six patients: clinical and morphological manifestations, propranolol efficacy, and safety.

INTRODUCTION: PHACE syndrome is defined by infantile hemangiomas associated with a spectrum of malformations. These abnormalities involve posterior fossa of the brain, cerebral vasculature, heart or aorta, eyes, and midline thorax or sternum. CASE REPORTS: Six cases of PHACE syndrome were diagnosed between 2002 and 2011 in the Department of Dermatology at Besançon Hospital. All patients were female and had an infantile hemangioma of the face over 5 cm in size. Five of them had encephalic abnormalities, and arterial malformations were found in three patients. Only one patient showed an ocular abnormality. None of them presented any cardiac, aortic, or sternal malformations. Two patients benefited from treatment with propranolol with good effectiveness and safety. DISCUSSION: The presence of an infantile hemangioma over 5 cm in size on the face should be a suspected sign for PHACE syndrome and requires the completion of a systematic evaluation. Diagnosis is based on recently revised criteria and demonstrates the large polymorphism of the malformations that may be encountered. CONCLUSION: This descriptive series is in accordance with literature data including female preponderance and the frequent involvement of the posterior fossa. It also underlines the effectiveness of propranolol for this indication.