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To compare actual with predicted long term growth after early repair of tetralogy of Fallot (TOF).Serial preoperative and postoperative anthropometric data were converted with z scores. The presence of restrictive physiology was assessed by echocardiography.45 otherwise healthy patients who underwent repair at median age 1.6 years (range 0.2-4.9) were studied. Predicted height was determined from mid-parental height corrected for sex.Mean (SD) weight and height z scores at the time of surgery were significantly depressed (-1.04 (0.82) and -0.93 (0.95), respectively; p0.0001 for both). At latest follow up at a median age of 14.2 years (range 11-20.5), mean weight and height z scores were 0.16 (1.1) and -0.05 (0.81) (p = 0.32 and p = 0.41, respectively). The improvement between surgical and late weight and height z scores was significant (p0.0001 for each comparison). Catch up growth was largely complete within two years. Age at correction, duration of follow up, and prior surgical procedures were unrelated to growth. Mean current height z scores were similar to those predicted by mid-parental height. Patients with restrictive right ventricular physiology (n = 24) had a significantly greater late z score for weight (0.49 v -0.34; p = 0.01), with a similar trend for height. Low birth weight patients experienced comparable catch up growth but remained shorter than patients with normal birth weight (mean height z score -0.64 v 0.06; p = 0.03).Early repair of TOF results in significant acceleration of weight and height, with normalisation of long term growth and fulfilment of genetic growth potential.

Objective: To compare surgical and device closure of isolated secundum atrial septal defect (ASD) in terms of hospital costs, clinical outcome, and impact on the patient and family. Design: Prospective, observational study. Setting: Paediatric tertiary referral centre. Patients: Consecutive local children with a secundum ASD, admitted between 1 May 1999 and 1 May 2001. Methods: Parents completed a standardised questionnaire at recruitment (on admission), at discharge, and one month after the procedure. Clinical and hospital generated cost data were collated at discharge. Results: 62 children were included in the analysis: 19 who underwent surgical repair and 43 who underwent device closure with the Amplatzer septal occluder. Median procedure times and hospital stay were significantly longer for surgical patients (170 (147 to 180) v 92 (70 to 115) minutes and 88 (78 to 112) v 29 (28 to 30) hours, respectively; p < 0.01). There was no difference in the complication rate. No device patients required intensive care or blood products. The median values for postoperative pain score, analgesia use, and convalescence time were greater for surgical patients. The median cost of each procedure was similar, but higher nursing and laboratory costs contributed to a slightly greater total cost for surgical repair (Aus$12 969 ($11 569 to $14 215) v Aus$11 845 ($10 669 to $12 555), p = 0.03). Conclusions: Device closure of ASD involves a shorter hospital stay, causes less discomfort and familial disturbance, and carries less cost than surgical closure. However, there should be guarded acceptance of this technique until long term data are available.

Advanced glycated end-products (AGEs) are known drivers of cardiovascular complications such as vascular calcification, which is currently untreatable, and are increased in diabetic subjects in part due to oxidative stress and poor glycaemic control. Our previous studies using smooth muscle cells (SMCs) isolated from patients with peripheral arterial disease (PAD) have implicated a number of signalling pathways involved in their osteogenic differentiation in vitro, including OPG/RANK. We have also shown that alterations in the cell surface glycocalyx regulates cell function, suggesting that non-sugar glycosaminoglycan mimics can potentially modulate cell phenotypes. We aim to investigate how modified LDL and PAD serum affects the progression of calcification of SMCs in vitro and whether this pathology can be prevented by novel glycosaminoglycan mimics, using qPCR, ELISA, Alkaline phosphatase (ALP) activity, and Western blotting. Gly-LDL (10 µg/ml) increased an early marker of calcification (ALP activity) at 4 days and enhanced calcification at 21 days, compared to controls (p Glycomimetics have potential as an anti-calcification strategy, inhibiting mineralisation in SMCs induced by both gly-LDL and patient serum in vitro. The protective effect of glycomimetics against calcification may occur via regulation of CREB phosphorylation and subsequent modulation of downstream osteogenic markers, including upregulation of OPN and OPG and reduction of OCN, leading to the development of therapeutics to treat vascular calcification.

Many of the calculations used in the evaluation of haemodynamic abnormalities are relatively simple and can be performed rapidly with a hand held calculator or (for the mentally agile) “in the head”. Others are more complex and require a more time consuming process of analysis of the recorded data, often performed some time after the actual procedure. Currently available catheter laboratory equipment for physiological monitoring and analysis will often provide a range of semi automatic calculations which will save time and allow the production of a comprehensive report at the conclusion of the procedure. It is vital, however, that cardiologists continue to have a clear understanding of the basis of such calculations and the limitations/pitfalls intrinsic to them and to some of the data on which they are based. Some of the calculations that can be made are of limited clinical utility while others are potentially misleading unless the data from which they are derived are carefully checked for accuracy and have been obtained using rigorous methodology. When, as is all too often the case, the data have been acquired largely automatically and have not been carefully scrutinised by someone familiar with the potential errors, the figures for pulmonary and systemic blood flow, shunt flows and resistances may be almost meaningless and can readily lead to inappropriate and potentially dangerous decisions. In practice most of the important calculations—shunt ratio (Qp:Qs), pulmonary blood flow, and pulmonary vascular resistance—can be estimated, albeit imprecisely, on the basis of straightforward and quick “guesstimates” which provide a rapid and generally useful “cross check” of the figures produced by the computer (or by a more time consuming and comprehensive manual method). While such rapid calculations are not a substitute for a careful and detailed analysis of the data, they are an effective way of understanding how …

Vascular calcification is implicated in a range of cardiovascular disease mechanisms, leading to an associated increase in morbidity and mortality. One such trigger are advanced glycation endproducts (AGEs), the tissue accumulation of which increases with age and is more prevalent in diabetic subjects due to oxidative stress and poor glycaemic control. The aim of this study was to investigate the osteogenic potential of AGEs and elucidate mechanisms of inhibiting these processes in a smooth muscle cell (SMC) culture model. Osteogenic differentiation of SMCs was induced using I²-glycerophosphate (I²-GP), carboxymethyllysine (CML), carboxyethyllysine (CEL) methylglyoxal (MGO) and glycated low density lipoprotein (gly-LDL). The cells were subsequently treated with aminoguanidine (AG), an inhibitor of AGE formation, and novel glycomimetic compounds in order to determine their anti-calcification potential in vitro using qPCR, ELISA, Alkaline phosphatase (ALP) activity and Alizarin red staining. Gly-LDL (10 µg/ml) and CML (2.5nM) increased the level of calcification observed compared to the I²-GP (5 mM) positive control after 21 days (p In summary, we conclude that gly-LDL and CML are potent inducers of calcification compared with I²-GP, and that their osteogenic potential can be modulated by both AG and novel glycomimetic compounds.

Endothelial microparticles (EMPs) are complex structures with pleiotropic properties and are emerging as an index of endothelial damage; however, further work to determine the effect of EMPs on vascular smooth muscle cells (VSMC) is needed. We have shown that elevated EMPs are detected in Systemic Lupus Erythematosus (SLE) and carotid artery disease patients, who present accelerated vascular ageing and calcification. This study aims to investigate the molecular components of EMPs and whether they modulate vascular calcification and osteogenic differentiation of VSMCs in vitro. EMPs were generated in vitro using human aortic endothelial cells (AoEMPs) by serum starvation (24 h) followed by TNF-alpha stimulation (10 ng/ml; 24 h), isolated by ultracentrifugation and quantified using flow cytometry. Human coronary artery smooth muscle cells (HCASMCs) were incubated with 106 AoEMPs/ml in osteoinductive media (5 mM BGP and 2.6 mM CaCl2) for 21 days. Calcification was assessed by alizarin red staining and calcium deposition assays. Conditioned media was collected at 7, 14 and 21 days to identify markers of bone metabolism using Bioplex array technology and ELISA. AoEMPs were also subjected to proteomic and miR screening to identify relevant molecules and pathways. AoEMP-treated HCASMCs showed enhanced calcification after 21 days, by both alizarin red staining (p We conclude that AoEMPs enhance calcification and the reprogramming of HCASMCs to an osteogenic pathway in vitro, which may be in part, linked with HGF and miR-3148, supporting their role in vascular calcification in SLE and carotid artery disease. Further studies are required to determine how AoEMPs contribute to pathophysiological mechanisms in vivo and whether the circulating property of AoEMPs may represent a new biomarker in vascular calcification.

Background Endothelial dysfunction is a key player in cardiovascular disease (CVD) complications and novel drugs are required to treat this pathological process. Glycosaminoglycans (GAGs) are key molecules that regulate signalling in many biological processes and drugs that mimic their structure could be a novel source of therapeutics to target specific CVD pathways. Purpose We have synthesised a set of four glycomimetic compounds and our objective was to determine whether they could activate protective pathways in endothelial cells subjected to fatty acid-induced endothelial dysfunction. Methods Glycomimetics, C1-C4, were synthesised by the stepwise transformation of 2,5-dihydroxybenzoic acid to a range of 2,5-substituted benzoic acid derivatives, incorporating the key sulphate groups to mimic heparan sulphate. Human Umbilical Vein Endothelial Cells (HUVECs) were treated with glycomimetics (1µM) in the presence or absence of the free fatty acid, palmitate. DAF-2 and H2DCF-DA assays were used to determine NO and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity ssays were also carried out. RT-PCR and western blotting were utilised to measure Akt, eNOS, Nrf-2, NQO-1 and HO-1 expression. Endothelial function was determined ex vivo using acetylcholine-induced endothelium-dependent relaxation in mouse thoracic aortic rings by wire myography. Results All four glycomimetics protected against palmitate-induced oxidative stress and enhanced NO production in vitro via upregulation of Akt/eNOS signalling, activation of the Nrf2/ARE pathway and down-regulation of ROS-induced lipid peroxidation. Under palmitate-induced oxidative stress, ex vivo endothelium-dependent relaxation was significantly enhanced by all four glycomimetics. Furthermore, the glycomimetics did not induce HUVEC activation, as determined by lack of ICAM-1 protein. Conclusion We have developed a new set of small molecule glycomimetics that do not activate ECs and protect against free fatty acid-induced endothelial dysfunction both in vitro and ex vivo. Future work will focus on developing the glycomimetics into drug-like therapies that target endothelial damage.

Background Circulating endothelial progenitor cells (EPCs) are thought to play a pivotal role in endothelial repair. Clinical trials utilising EPCs to promote therapeutic angiogenesis are already underway Previous reports suggest a reduced EPC number and impaired functional activity in patients with type 2 diabetes mellitus. However, the actual identity of the cell type involved and the functional role played in the repair process needs to be further defined before EPCs can be successfully utilised in the clinic. In the present study, we assessed the functional capacity of circulating late out-growth endothelial progenitor cells (OECs) to further assess the contribution of the diabetic environment to diminished OEC function in the context of wound healing. Methods and results OECs were isolated from 7 diabetic patients, presenting with ulcers ranging in size from 60 mm 3 –2500 mm 3 . OECs were characterised as CD34 + , CD31 + , vWF+, positive for AcLDL and UEA uptake and negative for the hematopoietic marker CD45 by immunohistochemistry. Migration of CD34 + OECs, evaluated by a scratch assay, demonstrated that migration is impaired in diabetic OECs compared to healthy control OECs, with 40–42% closure vs 100% over 24 h respectively. In addition, achemotaxis transwell migration assay showed a decreased response to SDF-1 by diabetic cells vs healthy OECs. An angiogenesis tube formation assay also established a reduced capacity of the diabetic OECs to form an endothelial network as compared to healthy OECs (p Conclusion OECs from diabetic patients show an impaired migration and response to chemotactic agents in vitro compared to OECs isolated from healthy controls. In addition, the reduced nitric oxide bioavailability found by diabetic cells may contribute to OEC dysfunction in diabetes. Future work will focus on assessing the secretome of healthy vs diabetic OECs.

Seventy three infants who underwent neonatal anatomical correction for transposition of the great arteries with or without a ventricular septal defect were reviewed for evidence of conduction and rhythm abnormalities on preoperative and postoperative 12 lead electrocardiograms and during 24 hour Holter monitoring. There was a partial right bundle branch block pattern in 47% (29/62) of all patients and in 60% (24/40) of those with simple transposition. Complete right bundle branch block was noted in 21% including 5% with simple transposition. Holter monitoring showed sinus rhythm in all patients except three: one had episodes of supraventricular tachycardia, another an intermittent second degree heart block, and a third a complete heart block. Atrial extrasystoles were noted in 47% (29/62) of patients but were frequent in only three patients. Occasional unifocal ventricular extrasystoles were encountered in 37% (23/62) of patients and were frequent in a further 3% (2/62). Only one patient (2%) developed multifocal ventricular extrasystoles. The frequency of important cardiac arrhythmias after neonatal anatomical correction of transposition of the great arteries was 5%, significantly less than that reported after atrial inflow diversion for the same malformation.

It is well established that vascular calcification is a common complication in diabetes and recent studies suggest that glycation may play a pathogenic role in this process. The aim of this study was to investigate the role of glycation in the induction of calcification in vascular smooth muscle cells (SMCs), and the potential inhibitory effects of the anti-diabetic agent, Momordica Charantia. Vascular SMCs were incubated with native or glycated LDL in the presence of osteogenic media and mineral deposition was determined using alizarin red staining and alkaline phosphatase (ALP) activity. We found that SMCs incubated in osteogenic media exhibited mineralisation after 7 days. This calcification was significantly increased following treatment with glycated-LDL, but not by native LDL. Furthermore, we found that ALP activity was significantly elevated at day 4 in glycated-LDL treated cells, compared to those incubated in native LDL. The vascular SMCs were exposed to increasing concentrations of Momordica Charantia extract in the presence of osteogenic media. ALP activity was reduced in treated cells, compared to osteogenic controls. Furthermore, we found that Momordica Charantia reduced gene expression of a range of biomarkers linked with vascular calcification after 4 days in a dose-dependent manner, including osteocalcin and BMP-2. In conclusion, we have shown that glycated LDL promotes osteogenic differentiation of vascular SMCs. Momordica Charantia extract shows promise as a potential therapeutic agent to reduce vascular calcification. Future work will identify the active ingredient responsible for calcification inhibitory effects, and establish whether it links to the pathological glycation-induced osteogenesis.

Glycomimetics are molecules that mimic the structure of carbohydrates involved in important biological processes. Small molecule glycomimetics are an untapped source of novel therapies for endothelial dysfunction, a hallmark of cardiovascular complications associated with diabetes. The current study aims to investigate the possible protective effects of newly synthesised small molecule glycomimetics against lipid-induced endothelial dysfunction, with an emphasis on nitric oxide (NO) and induced oxidative stress. Glycomimetics were synthesised by the stepwise transformation of 2,5-dihydroxybenzoic acid to a range of 2,5-substituted benzoic acid derivatives incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Acetylcholine-induced endothelium-dependent relaxation in mouse thoracic aortic rings was measured using wire myography, and human umbilical vein endothelial cells (HUVECs) function was assessed in the presence or absence of palmitate, with or without the test glycomimetics. NO and reactive oxygen species (ROS) production was measured using DAF-2 and H2DCF-DA, respectively. Colorimetric assays were used to determine lipid peroxidation and activity of the antioxidant enzymes. Expression of Akt, eNOS, Nrf-2, NQO-1 and HO-1 were assessed using RT-PCR and western blotting. At 1 µM concentration, the synthesised glycomimetics significantly improved endothelium-dependent relaxation ex vivo and protected HUVECs against palmitate-induced oxidative stress and reduced NO production. Pre-incubation of HUVECs with all compounds upregulated Akt/eNOS signalling, activated Nrf2/ARE pathway, and suppressed ROS-induced lipid peroxidation. In conclusion, our newly synthesised small molecule glycomimetics protect against lipid-induced endothelial dysfunction. These novel cytoprotective effects open the door to a new class of therapeutic drugs to target endothelial dysfunction.

Endothelial microparticles (EMPs) are complex structures with pleiotropic properties and are emerging as an index of endothelial damage. Previous studies have shown elevated circulating EMP levels in inflammatory disorders, which raises the question about their physiological role. This study aims to investigate the autocrine effects of EMPs on TNFα-mediated EMP release, as well as on endothelial cell activation and migration. Two groups of EMPs were generated in vitro from TNF-stimulated human umbilical vein endothelial cells (HUVECs; sEMPs) or untreated HUVECs (uEMPs) and collected by ultracentrifugation. HUVECs were incubated with either 106 sEMPs or uEMPs/ml in the presence or absence of TNFα (10 ng/ml) for 24 h. EMP levels were enumerated by flow cytometry; RT-PCR and functional scratch assays were also carried out. HUVECs treated with either sEMP or uEMP showed increased ICAM-1 mRNA abundance (p

Endothelial dysfunction is an early event in the pathogenesis of diabetes mellitus and its associated cardiovascular morbidities. Endothelial microparticles (EMPs) are endothelium-derived sub-micron vesicles that are released in response to diverse stimuli. Our study aims to investigate the effect of EMPs on endothelial cell function/dysfunction focusing on the Akt/eNOS signalling pathway and lipid-induced oxidative stress. EMPs were generated in vitro using TNFα-stimulated human umbilical vein endothelial cells (HUVECs). Flow cytometry was used to quantify the generated EMPs. HUVECs were cultured in M199 and treated with and without 100 µM palmitate in the presence or absence of 10 5 and 10 6 EMPs. Nitric oxide bioavailability in EMPs and HUVECs was measured using DAF-2. H 2 DCF-DA was used to quantify reactive oxygen species (ROS). Lipid peroxidation and activity of superoxide dismutase and catalase were determined by colorimetric assays, while RT-PCR and western blotting were used to assess eNOS, Akt and NOX4 expression. Analysis of the NO production suggests that EMPs carry a functional eNOS. Palmitate stimulation evoked oxidative stress and reduced activity of the antioxidant enzymes as well as A23187-stimulated NO production in HUVECs. RT-PCR and western blotting demonstrated a marked decrease in eNOS and Akt and increased NOX4 expression in palmitate-treated endothelial cells. EMPs protected against the palmitate-induced endothelial dysfunction through attenuation of oxidative stress and positive regulation of Akt/eNOS signalling, leading to an increased NO production. In conclusion, our data strongly suggest that EMPs express a functional eNOS and are effective in protecting endothelial cells against lipid-induced dysfunction.

Introduction It is well established that glyc-LDL is elevated in the serum of diabetic patients compared to healthy subjects, and that vascular calcification is common in diabetes. Furthermore, recent studies suggest that advanced glycation end products may play a pathogenic role in vascular calcification. We hypothesise that glyc-LDL promotes the osteogenic differentiation of vascular smooth muscle cells in vitro . Methods LDL was isolated from human serum by sequential density gradient ultracentrifugation and incubated at 37°C with a range of glucose concentrations at different time points to determine the optimum glycation conditions. The glyc-LDL was measured using an in-house ELISA method. Bovine Aortic Smooth Muscle Cells (BAoSMCs) were incubated with native or glycated LDL in the presence of osteogenic media and mineral deposition was determined using alizarin red staining and alkaline phosphatase (ALP) activity, which is an early marker of osteogenesis. Results The optimum conditions for LDL glycation was determined as 80mM glucose for 7 days, so these conditions were used for the production of glycated LDL throughout the study. BAoSMCs incubated in osteogenic media exhibited mineralisation after 7 days as determined by alizarin red staining. This calcification was significantly enhanced by treatment with glyc-LDL, but not by native LDL. Furthermore, we found that ALP activity was significantly elevated as early as day 4 in glyc-LDL treated cells, compared to those incubated in native LDL. The glyc-LDL-induced mineralisation was not attenuated in the presence of osteoprotegrin (OPG) nor in the presence of two novel small RAGE antagonist peptides, which were designed to prevent RAGE binding with several of its most important ligands, including HMGB-1, S100P and S1004A. Conclusion We have shown that human-derived glyc-LDL accelerates vascular calcification in vitro . This process does not appear to be attenuated by the addition of OPG, suggesting AGE-induced accelerated calcification occurs through a pathway independent of the RANKL/OPG signalling activity. Further studies with a range of RAGE inhibitors should allow the identification of the molecular pathways implicated in glyc-LDL induced calcification to enable the development of therapeutic peptides effective in blocking of RAGE-ligand interaction, which is prevalent in many pathologies.

There is a clinical need to develop novel biomarkers to identify patients at risk of stroke. We aim to establish a systemic signature and microparticle profile of asymptomatic patients with unstable carotid disease, for improved selection of patients for interventional surgery and stroke prevention. Blood samples were taken from 70 patients (51 symptomatic; 19 asymptomatic), undergoing carotid endarterectomy, and 20 healthy controls. Circulating endothelial microparticles (EMPs; CD31+/Annexin V+/CD42b−), together with inflammatory markers were measured using flow cytometry and Bioplex assays respectively. Carotid plaques were graded and analysed using immunohistochemistry. EMPs were elevated in asymptomatic and symptomatic patients, compared to healthy controls (p= These data could aid in the development of a diagnostic tool whereby EMPs, together with macrophage activity markers, could identify those patients with vulnerable plaques and stroke susceptibility.

Endothelial microparticles (EMPs) are complex structures with pleiotropic properties and are emerging as an index of endothelial damage. We demonstrate their levels can be modulated by anti-inflammatory treatment and their existence in the circulation raises the question about their physiological role. Our studies aim to investigate the molecular components of EMPs, and whether EMPs modulate matrix mineralisation. Flow cytometry was used to quantify circulating EMPs (AnnexinV+/CD31+/CD42b−) in lupus patients, pre- and post- anti-inflammatory treatment. EMPs were generated in vitro using TNF-activation of human aortic endothelial cells and used for proteomic analysis and to treat human vascular smooth muscle cells (HVSMC). Alizarin Red staining was used to quantify levels of mineralisation using an in vitro model of calcification. We show that EMP levels are significantly elevated in lupus patients compared to healthy subjects (p We conclude that EMPs may prevent the reprogramming of SMCs to an osteogenic pathway in vitro, which may be, in part linked with PTX3. Further studies are required to determine how MPs contribute to pathophysiological mechanisms in vivo and whether the circulating property of MPs may represent a new biomarker in vascular calcification.

Introduction Endothelial microparticles (EMPs) are released from dysfunctional endothelial cells. We hypothesised that patients with unstable carotid plaque have higher levels of circulating microparticles compared to patients with stable plaques which could be related to a specific cytokine profile. Methods Circulating EMPs and inflammatory cytokine levels were measured in seventy patients with significant carotid disease undergoing carotid endarterectomy and 20 healthy controls. Fifty one (73%) patients had symptomatic disease whilst 19 (27%) were asymptomatic. EMPs (CD31 + / Annexin V + CD42b - ) were quantified using flow cytometry. Immunohistological analysis of carotid plaques for CD68 + , CD206 + macrophages, TNF-α smooth muscle actin and osteopontin was performed, together with Alizarin red staining for detection of calcific deposits. Bioplex assays were used for cytokine analysis. Plaques were graded according to the American Heart Association plaque scoring system. Results Significantly higher EMP levels were observed in symptomatic patients compared to controls, p = 0.01, while no differences were noted in EMP levels in asymptomatic vs controls p = 0.11. The higher EMP levels appeared to associate with the unstable plaques which also had a significantly higher level of CD68 + macrophages compared to stable plaques (AHA I-IV) and higher circulating levels of Chemokine ligand-9 (CXCL-9) (p Conclusion Circulatory EMP and specific inflammatory cytokine levels are raised in patients with unstable plaques, while MIF, a potentially protective factor was elevated in serum of patients with stable plaques. These data could have major implications for the development of a diagnostic tool whereby EMPs together with markers of macrophage activity could act in a combined manner as biomarkers of plaque vulnerability and stroke susceptibility.

Aortic coarctation is a common abnormality comprising about 6% of congenital heart diseases. The narrowing of the aorta and consequent increased peak systolic stress is a potent stimulus for the development of left ventricular (LV) hypertrophy before repair. Clinically, however, the degree of hypertrophy and the progression to dilation and failure is variable. The extent of remodelling after successful repair is also difficult to predict, and persistence of hypertrophy has been demonstrated. Angiotensin converting enzyme (ACE) is responsible for the hydrolisation of angiotensin Ι into angiotensin ΙΙ, which is the principal circulating hormone of the renin–angiotensin system. It was shown that angiotensin ΙΙ stimulates myocardial growth by a direct effect on cardiac myocytes (increasing the fractional rate of protein synthesis), and also by indirect effects (increasing total peripheral vascular resistance). A single polymorphism of the ACE gene is described as follows: the insertion/larger allele, I, and the deletion/shorter allele, D, as well as a heterozygous form, ID, were located in intron 16 of chromosome 17q23. DD was associated with an increased plasma ACE activity and a high concentration of plasma angiotensin ΙΙ.1 ACE gene polymorphism has been implicated in the pathogenesis of various cardiovascular diseases. DD has been associated with LV hypertrophy, ischaemic and idiopathic cardiomyopathy, and an increased risk of sudden death in hypertrophic cardiomyopathy.1,2 This association between increased LV mass and ACE gene polymorphism might be expected to modify the responses to …

To the Editor: Increasing concerns about the potential for atrioventricular (AV) block after transcatheter closure of perimembranous ventricular septal defect (VSD) were emphasised by Ian Sullivan in a recent issue of Heart .1 This complication has been highlighted in a clinical series published by Walsh et al .2 Their patients developed heart block after closure of perimembranous VSD (pmVSD) within 10 days of the procedure. Because of two instances of very late onset of complete atrioventricular block (cAVB) 24 …

Three patients developed protein-losing enteropathy caused by intra-atrial obstruction of the systemic venous return after Mustard's operation. The enteropathy resolved in one case after reoperation and in the others after balloon dilatation of the stenosed caval pathways. Protein-losing enteropathy may occur as a complication of Mustard's operation. Balloon dilatation of the obstructed baffle is an effective alternative to reoperation.

We have reviewed data on all patients born between 1960 and 1969 and registered in the Liverpool Registry of Congenital Malformations as having congenital heart disease. There were 385 with a ventricular septal defect as their sole or main cardiac lesion. Analysis of the available follow-up data showed that 50 of these were subsequently assigned in other diagnostic categories and a further 41 failed to fulfil our diagnostic criteria for a ventricular septal defect, leaving 294 patients for study. In view of the high incidence of small defects in asymptomatic infants and children not subjected to cardiac catheterisation, clinical criteria for the acceptance of the diagnosis were defined and 190 patients were included on these grounds alone. The clinical course, associated cardiac and non-cardiac defects, and surgical implications were analysed. The majority of defects were small and 31% closed spontaneously. Fifty per cent of the deaths in infancy were unrelated to the ventricular septal defect. We estimate that by present criteria only 15% of an unselected population of patients with a ventricular septal defect are likely to require surgical treatment.

Anatomical studies were made on 114 necropsy specimens of atrioventricular defects with atrioventricular concordance. The malformation is characterised by disproportion between the ventricular inlet and outlet dimensions and a malorientation of the aortic valve relative to the atrioventricular valve or valves. Associated with this there is a characteristic 'scopped-out' appearance of the muscular ventricular septum, gross abnormalities of the membranous components of the septum as compared with the normal heart, and narrowing of the aortic outflow tract. Hearts with these anatomical features can be divided into partial and complete forms depending on the morphology of the atrioventricular annuli. In the partial form the septal leaflets are conjoined to give separate mitral and tricuspid orifices, the conjoined leaflets being displaced into the ventricles and usually attached to the crest of the septum. In the complete form, anterior and posterior components of the 'septal' leaflets are separate, so that a single valve orifice connects the atrial to the ventricular chambers. Further subdivision of the complete form, apart from the morphology of the anterior leaflet, is dependent upon the presence or absence of an ostium primum atrial septal defect.

Among 160 480 children born alive between 1960 and 1969 in Liverpool, 884 patients with structural congenital heart disease were identified. Data on these patients have been reviewed in order to estimate the number likely to need cardiac surgery during childhood and adolescence. Though only 33.9% of patients had surgery, we estimate that if current policies for management were followed, 475 (53.7%) patients would not require surgery. Extrapolation of this data suggests that each year in England and Wales approximately 830 infants (1383 per million livebirths) will require cardiac surgery within the first year of life and a further 1424 operations (2374 per million livebirths) will be required in later childhood or adolescence. No attempt has been made to estimate the number of operations for congenital heart disease which may prove necessary in adult life.

Two cases are described of a most unusual variant of two-chambered right ventricle. In both the ventricular septal defect was between the distal chamber of the right ventricle and the left ventricle. However the extensive dividing 'septum' between proximal and distal parts of the right ventricle converted the latter, haemodynamically, into part of the left ventricle. In the first case the distal chamber supported the aorta in the left anterior position, the pulmonary artery arising from the proximal part of the right ventricle. In the second the pulmonary artery arose from the distal chamber and the aorta from the proximal chamber. Though in both the ventriculoarterial connection was double outlet right ventricle, functionally there was arterial concordance in case 1 and discordance in case 2. A further disconcerting feature was the resemblance of the distal right ventricular chamber to the rudimentary chamber of a univentricular heart of left ventricular type.