Prenatal diagnosis of isolated coronary artery fistulas: progression and outcome in five cases.

OBJECTIVES: The aim of this study was to describe the clinical characteristics, progression, treatment, and outcomes in isolated coronary artery fistula cases diagnosed prenatally. METHODS: We carried out a retrospective review of babies diagnosed prenatally with coronary artery fistulas between January, 2000 and December, 2013; five fetuses were included. Echocardiographic features and measurements were noted during pregnancy and after birth. Treatment and outcome were noted. RESULTS: Gestational age at initial diagnosis was between 19 and 22 weeks; four coronary artery fistulas originated from the right and one from the left circumflex coronary artery. Drainage was into the right atrium in four cases and into the left ventricle in one case. There was cardiomegaly in two cases at the initial scan. The size of the fistulas increased during pregnancy in all except one. All prenatal diagnoses were confirmed postnatally. Among all, two patients developed congestive cardiac failure soon after birth and required transcatheter closure of the coronary artery fistula, 5 and 17 days after birth, respectively; three patients remained asymptomatic, and all of them showed progressive dilation of the feeding artery and had closure of the fistula at 20 months, 4 years, and 7 years of age, respectively. During the follow-up period, which ranged 2-14 years, all the patients were alive and well. CONCLUSIONS: Coronary artery fistulas can be diagnosed accurately during fetal life. Some babies may develop congestive cardiac failure soon after birth requiring early treatment. Those treated conservatively should be kept under review as intervention may be required later.

Nomenclature and systems of classification for cardiomyopathy in children.

There has been a progressive evolution in systems of classification for cardiomyopathy, driven by advances in imaging modalities, disease recognition, and genetics, following initial clinical descriptions in the 1960s. A pathophysiological classification emerged and was endorsed by World Health Organisation Task Forces in 1980 and 1995: dilated, hypertrophic, restrictive, and arrhythmogenic right ventricular cardiomyopathies; subdivided into idiopathic and disease-specific cardiomyopathies. Genetic advances have increasingly linked "idiopathic" phenotypes to specific mutations, although most linkages exhibit highly variable or little genotype-phenotype correlation, confounded by age-dependent changes and varying penetrance. The following two dominant classification systems are currently in use, with advocates in both continents. First, American Heart Association (2006): "A heterogeneous group of diseases of the myocardium associated with mechanical and/or electrical dysfunction that usually exhibit inappropriate ventricular hypertrophy or dilatation due to a variety of causes that frequently are genetic". These are subdivided to those predominantly involving the heart - primary - due to genetic mutation, including ion channelopathies, acquired disease, or mixed; and those with systemic involvement in other organ systems - secondary. Second, European Society of Cardiology (2008): "A myocardial disorder in which heart muscle is structurally and functionally abnormal… sufficient to cause the observed myocardial abnormality", with subdivision to familial and non-familial, excluding ion channelopathies, and split to specific disease subtypes and idiopathic. Further differences exist in the definitions for hypertrophic cardiomyopathy; however, whichever high-level classification is used, the clinical reality remains phenotype driven. Clinical evaluation and diagnostic imaging dominate initial patient contact, revealing diagnostic red flags that determine further specific tests. Genetic testing is undertaken early. A recent attempt to harmonise these competing systems named the MOGE(S) system, based on descriptive logical nosology, currently remains unproven as a fully practical solution.

Transvenous atrial pacing from the superior vena cava stump after the hemi-fontan operation--a new approach.

BACKGROUND: The placement of a standard endocardial pacemaker system is challenging after a superior cavopulmonary connection (hemi-Fontan operation or Glenn shunt) as the continuity between the superior vena cava (SVC) and right atrium is divided. The standard transvenous approach for endocardial lead placement has therefore in general been avoided, and epicardial leads have been placed. METHODS: In three patients after a hemi-Fontan procedure, we found viable atrial tissue in the SVC stump of the superior cavopulmonary anastomosis, which was still connected electrically to the right atrium into which active-fixation leads could be safely implanted. RESULTS: There was excellent short- and long-term atrial pacing and sensing characteristics in the SVC stump. CONCLUSIONS: We describe a technique for transvenous pacing in patients after the hemi-Fontan procedure using the conventional subclavian vein approach and pectoral placement of the generator. For ventricular pacing, it was possible to cross the patch dividing the right atrium from the SVC either using a spontaneous leak or by needle puncture.

[Effect of green tea flavonols on the function of the endoplasmic reticulum]. / Zöldtea-flavanolok hatása az endoplazmás retikulum muködésére.

The various (e.g. anti-tumor and anti-diabetic) health effects of green tea attributed to its flavonols, primarily to epigallocatechin-gallate, got into the focus of interest. The endoplasmic reticulum, which plays key role in the metabolism of carcinogens, in the synthesis of secreted or cell surface proteins as well as in the glucose production, might be a potential target for anti-tumor and anti-diabetic agents. Therefore, it is an important question how the flavonols affect its functions. Experiments carried out in microsomes and hepatoma cells revealed that flavonols inhibit glucuronide transport in the endoplasmic reticulum, which may reduce the reactivation of carcinogens; they inhibit glucosidase II, which may cause endoplasmic reticulum stress and apoptosis in hepatoma cells; and they hinder glucose efflux, which may decrease hepatic glucose production and blood glucose level. These observations are useful for further investigation of the relevant transport processes and transporters and also contribute to the better understanding of the mechanisms of flavanol effects.

Green tea flavonols inhibit glucosidase II.

Green tea is getting into the focus of scientific interest due to its beneficial health effects, most of which are attributed to its catechin content. Polyphenolic tea catechins have antioxidant, antiproliferative, antiangiogenic and proapoptotic effects, which makes them promising anticancer compounds. Other poly-hydroxy molecules have similar antitumor potentials through the inhibition of glucosidase II, which affects the glycoprotein maturation and quality control in the endoplasmic reticulum. We investigated the effect of tea catechins on glucosidase II activity in rat liver microsomes using 4-methylumbelliferyl glucoside and 4-nitrophenyl glucoside as substrates. A concentration-dependent inhibition with non-competitive kinetics was found. The IC50 and Ki values for certain tea catechins were comparable with those of N-butyldeoxynojirimycin, the widely used glucosidase inhibitor. The possible interference of tea catechins with the glycoprotein processing in the endoplasmic reticulum should be considered as a potential mechanism of their dietary or pharmacological effects.

Twenty-Seven Years Experience With Transvenous Pacemaker Implantation in Children Weighing <10 kg.

BACKGROUND: Epicardial pacemaker implantation is the favored approach in children weighing <10 kg in many units. The high incidence of premature failure and fractures with earlier epicardial leads led our unit to undertake transvenous pacemaker implantation in neonates and infants from 1987. To date there have been no long-term follow-up reports of what is for many a controversial strategy. METHODS AND RESULTS: Between 1987 and 2003, 37 neonates and infants-median age 6.7 months (1 day to 3 years) and median weight 4.6 kg (2.7-10 kg)-had a permanent transvenous pacing system implanted. Pacing leads were placed into the right ventricular apex/outflow tract through a subclavian vein puncture with a redundant loop in the atrium. Three patients were lost to follow-up, 4 patients died from complications of cardiac surgery, and 2 patients had their system removed. At long-term follow-up in 28 patients at a median of 17.2 (range, 11.2-27.4) years, 10 patients have a single chamber ventricular pacemaker, 14 a dual chamber pacemaker, 3 a biventricular pacemaker, and 1 has a single chamber implantable cardioverter defibrillator. Subclavian vein patency was assessed in 26 patients. The overall subclavian vein occlusion rate was 10 of 13 (77%) <5 kg and 2 of 13 (15%) >5 kg during long-term follow-up. After a median of 14.3 (range, 13.4-17.6) years of pacing, 7 patients continue with their original lead. CONCLUSIONS: Transvenous pacing in infants <10 kg results in encouraging short- and long-term clinical outcomes. Subclavian vein occlusion remains an important complication, occurring predominantly in those weighing <5 kg.

Highlights of the annual meeting of the Association for European Paediatric and Congenital Cardiology.

The 47th annual meeting of the Association for European Paediatric and Congenital Cardiology was held on 22-25th May 2013 in London, UK. This is one of the largest scientific meetings in Europe within the field of congenital cardiac disease and was held in association with the Japanese Society of Pediatric Cardiology and Cardiac Surgery, and Asia Pacific Pediatric Cardiology Society. There were 900 submitted abstracts and over 1000 delegates from 57 countries attended. We have summarized some of the highlights of the meeting below.

Inhibition of microsomal cortisol production by (-)-epigallocatechin-3-gallate through a redox shift in the endoplasmic reticulum--a potential new target for treating obesity-related diseases.

Conversion of cortisone to cortisol by 11ß-hydroxysteroid dehydrogenase type 1 (11ßHSD1) in the endoplasmic reticulum (ER) of the target cells is a major determinant of glucocorticoid action, and plays an important role in the development of obesity-related diseases. Inhibition of 11ßHSD1 activity is, therefore, considered as a promising novel strategy for the treatment of metabolic syndrome and diabetes. Tea flavanols and their major representative, epigallocatechin gallate are known as antiobesity and antidiabetic agents. Their impacts on blood glucose level, hepatic glucose production, and insulin responsiveness resemble those observed on inhibition or depletion of 11ßHSD1. We aimed to study the effect of epigallocatechin gallate on 11ßHSD1 activity in ER-derived rat liver microsomes by measuring cortisone and cortisol with HPLC. Cortisol production was efficiently suppressed in a concentration dependent manner in intact microsomal vesicles. However, this effect was abolished by membrane permeabilization; and the three proteins involved in the overall process (11ßHSD1, hexose 6-phosphate dehydrogenase, and glucose 6-phosphate transporter) were not or only mildly affected. Further investigation revealed the oxidation of luminal NADPH to NADP⁺, which attenuates cortisone reduction and favors cortisol oxidation in this compartment. Such a redox shift in the ER lumen might contribute to the beneficial health effects of tea flavanols and should be regarded as a promising strategy for the development of novel selective 11ßHSD1 inhibitors to treat obesity-related diseases.

Tea flavan-3-ols as modulating factors in endoplasmic reticulum function.

Regular green tea consumption has been shown to reduce the risk of cancer and diabetes mellitus. These effects are attributed to tea flavan-3-ols, especially to epigallocatechin gallate; however, the molecular targets and mechanisms of action are still subject of extensive research. The special roles of the endoplasmic reticulum (ER) in biotransformation, protein synthesis, calcium homeostasis, and glucose production make this organelle a potential target of the antitumor and antidiabetic effects of tea flavan-3-ols. The purpose of this review is to present evidence for the biologic actions of tea flavan-3-ols on specific ER targets associated with normal function and disease. Reactivation of chemical carcinogens can be reduced by tea flavan-3-ols through inhibition of glucuronide transport across the ER membrane. Catechins modulate Ca(2+) release from the ER lumen and interfere with glycoprotein maturation, which can lead to decreased viability and increased drug sensitivity of tumor cells. Epigallocatechin gallate inhibits glucose transport across the ER membrane, which can underlie the reduction of hepatic glucose production by tea flavan-3-ols. These mechanisms likely contribute to the chemopreventive and glucose-lowering effects of tea catechins. Investigating the effects of flavan-3-ols on ER functions is a promising field of medical and biochemical research to understand disease and improve health.

Inhibition of glycoprotein synthesis in the endoplasmic reticulum as a novel anticancer mechanism of (-)-epigallocatechin-3-gallate.

(-)-Epigallocatechin-3-gallate (EGCG) has been found to trigger the unfolded protein response (UPR) likely due to the inhibition of glucosidase II, a key enzyme of glycoprotein processing and quality control in the endoplasmic reticulum (ER). These findings strongly suggest that EGCG interferes with glycoprotein maturation and sorting in the ER. This hypothesis was tested in SK-Mel28 human melanoma cells by assessing the effect of EGCG and deoxynojirimycin (DNJ) on the synthesis of two endogenous glycoproteins. Both tyrosinase and vascular endothelial growth factor (VEGF) protein levels were remarkably reduced despite unaltered mRNA expression in EGCG- or DNJ-treated cells compared to control. The hindrance of tyrosinase and VEGF protein synthesis could be prevented by proteasome inhibitor, lactacystine. Collectively, our results support that glucosidase II inhibitor EGCG interferes with protein processing and quality control in the ER, which diverts tyrosinase, VEGF, and likely other glycoproteins towards proteasomal degradation. This mechanism provides a novel therapeutic approach in dermatology and might play an important role in the antitumor effect or hepatotoxicity of EGCG.