The widely used antihistamine mepyramine causes topical pain relief through direct blockade of nociceptor sodium channels.

Mepyramine, a first-generation antihistamine targeting the histamine H(1) receptor, was extensively prescribed to patients suffering from allergic reactions and urticaria. Serious adverse effects, especially in case of overdose, were frequently reported, including drowsiness, impaired thinking, convulsion, and coma. Many of these side effects were associated with the blockade of histaminergic or cholinergic receptors. Here we show that mepyramine directly inhibits a variety of voltage-gated sodium channels, including the Tetrodotoxin-sensitive isoforms and the main isoforms (Nav1.7, Nav1.8, and Nav1.9) of nociceptors. Estimated IC50 were within the range of drug concentrations detected in poisoned patients. Mepyramine inhibited sodium channels through fast- or slow-inactivated state preference depending on the isoform. Moreover, mepyramine inhibited the firing responses of C- and Aß-type nerve fibers in ex vivo skin-nerve preparations. Locally applied mepyramine had analgesic effects on the scorpion toxin-induced excruciating pain and produced pain relief in acute, inflammatory, and chronic pain models. Collectively, these data provide evidence that mepyramine has the potential to be developed as a topical analgesic agent.

Outcomes of Newborns with Prenatal Ventricular Asymmetry not Requiring Neonatal Surgical Intervention: a 22-Year Retrospective Single-Center Study.

To assess the outcomes of neonates prenatally diagnosed with ventricular asymmetry and not operated on within the neonatal period and to determine the risk factors for left heart obstruction occurrence at follow-up. All neonates with prenatal asymmetry of the ventricles, diagnosed from August 1993 to July 2015, not operated on within the neonatal period, were retrospectively included in the study. Left heart echocardiographic measurements at birth and at last follow-up were collected and compared. Left heart anomaly included isthmus and/or aortic valve and/or mitral valve obstruction. There were a total of 34 newborns included in the study. The median follow-up was 2 years. There was no death. Eleven patients were operated on at a median age of three months; seven of them had an obstruction of the left heart (five coarctations of the aorta, one sub-aortic and aortic valve stenosis, and one mitral stenosis). Estimated freedom of left heart surgery was 80% at 6 months and 75% at 10 years. The main risk factor for progression to a left heart anomaly was a hypoplasia of the aortic isthmus (p = 0.0003), while the presence of a left superior vena cava was more frequent in these patients although the difference was not significant. Patients with an aortic isthmus z-score below - 2 at the closure of arterial duct are at risk of later coarctation and therefore follow-up should be extended to at least 3 months. Furthermore, the prenatal ventricular asymmetry does not only identify patients at risk of coarctation but also of other left heart anomalies. This last point should be a better approach with future parents to improve prenatal counseling on a more complex postnatal diagnostic than a simple isolated coarctation.

Incomplete Timothy syndrome secondary to a mosaic mutation of the CACNA1C gene diagnosed using next-generation sequencing.

Autosomal dominant genetic diseases can occur de novo and in the form of somatic mosaicism, which can give rise to a less severe phenotype, and make diagnosis more difficult given the sensitivity limits of the methods used. We report the case of female child with a history of surgery for syndactyly of the hands and feet, who was admitted at 6 years of age to a pediatric intensive care unit following cardiac arrest. The electrocardiogram (ECG) showed a long QT interval that on occasions reached 500 ms. Despite the absence of facial dysmorphism and the presence of normal psychomotor development, a diagnosis of Timothy syndrome was made given the association of syndactyly and the ECG features. Sanger sequencing of the CACNA1C gene, followed by sequencing of the genes KCNQ1, KCNH2, KCNE1, KCNE2, were negative. The subsequent analysis of a panel of genes responsible for hereditary cardiac rhythm disorders using Haloplex technology revealed a recurrent mosaic p.Gly406Arg missense mutation of the CACNA1C gene in 18% of the cells. This mosaicism can explain the negative Sanger analysis and the less complete phenotype in this patient. Given the other cases in the literature, mosaic mutations in Timothy syndrome appear more common than previously thought. This case demonstrates the importance of using next-generation sequencing to identify mosaic mutations when the clinical picture supports a specific mutation that is not identified using conventional testing. © 2016 Wiley Periodicals, Inc.

Transduction and encoding sensory information by skin mechanoreceptors.

Physical contact with the external world occurs through specialized neural structures called mechanoreceptors. Cutaneous mechanoreceptors provide information to the central nervous system (CNS) about touch, pressure, vibration, and skin stretch. The physiological function of these mechanoreceptors is to convert physical forces into neuronal signals. Key questions concern the molecular identity of the mechanoelectric transducer channels and the mechanisms by which the physical parameters of the mechanical stimulus are encoded into patterns of action potentials (APs). Compelling data indicate that the biophysical traits of mechanosensitive channels combined with the collection of voltage-gated channels are essential to describe the nature of the stimulus. Recent research also points to a critical role of the auxiliary cell-nerve ending communication in encoding stimulus properties. This review describes the characteristics of ion channels responsible for translating mechanical stimuli into the neural codes that underlie touch perception and pain.

Population pharmacokinetic model of free and total ropivacaine after transversus abdominis plane nerve block in patients undergoing liver resection.

AIMS: The aim of this study was to develop a pharmacokinetic model in order to characterize the free and total ropivacaine concentrations after transversus abdominis plane block in a population of patients undergoing liver resection surgery. In particular, we evaluated the impact of the size of liver resection on ropivacaine pharmacokinetics. METHODS: This work is based on a single-centre, double-blinded, randomized, placebo-controlled study. Among the 39 patients included, 19 patients were randomized to the ropivacaine group. The free and total ropivacaine concentrations were measured in nine or 10 blood samples per patient. A pharmacokinetic model was built using a nonlinear mixed-effect modelling approach. RESULTS: The free ropivacaine concentrations remained under the previously published toxic threshold. A one-compartment model, including protein binding site with a first-order absorption, best described the data. The protein binding site concentration was considered as a latent variable. Bodyweight, the number of resected liver segments and postoperative fibrinogen evolution were, respectively, included in the calculation of the volume of distribution, clearance and binding site production rate. The resection of three or more liver segments was associated with a 53% decrease in the free ropivacaine clearance. CONCLUSIONS: Although large liver resections were associated with lower free ropivacaine clearance, the ropivacaine pharmacokinetic profile remained within the safe range after this type of surgery.

Activation of lysosomal iron triggers ferroptosis in cancer.

Iron catalyses the oxidation of lipids in biological membranes and promotes a form of cell death referred to as ferroptosis1-3. Identifying where this chemistry takes place in the cell can inform the design of drugs capable of inducing or inhibiting ferroptosis in various disease-relevant settings. Whereas genetic approaches have revealed underlying mechanisms of lipid peroxide detoxification1,4,5, small molecules can provide unparalleled spatiotemporal control of the chemistry at work6. Here, we show that the ferroptosis inhibitor liproxstatin-1 (Lip-1) exerts a protective activity by inactivating iron in lysosomes. Based on this, we designed the bifunctional compound fentomycin that targets phospholipids at the plasma membrane and activates iron in lysosomes upon endocytosis, promoting oxidative degradation of phospholipids and ferroptosis. Fentomycin effectively kills primary sarcoma and pancreatic ductal adenocarcinoma cells. It acts as a lipolysis-targeting chimera (LIPTAC), preferentially targeting iron-rich CD44high cell-subpopulations7,8 associated with the metastatic disease and drug resistance9,10. Furthermore, we demonstrate that fentomycin also depletes CD44high cells in vivo and reduces intranodal tumour growth in an immunocompetent murine model of breast cancer metastasis. These data demonstrate that lysosomal iron triggers ferroptosis and that lysosomal iron redox chemistry can be exploited for therapeutic benefits.

Parental electrocardiographic screening identifies a high degree of inheritance for congenital and childhood nonimmune isolated atrioventricular block.

BACKGROUND: The origin of congenital or childhood nonimmune isolated atrioventricular (AV) block remains unknown. We hypothesized that this conduction abnormality in the young may be a heritable disease. METHODS AND RESULTS: A multicenter retrospective study (13 French referral centers, from 1980-2009) included 141 children with AV block diagnosed in utero, at birth, or before 15 years of age without structural heart abnormalities and without maternal antibodies. Parents and matched control subjects were investigated for family history and for ECG screening. In parents, a family history of sudden death or progressive cardiac conduction defect was found in 1.4% and 11.1%, respectively. Screening ECGs from 130 parents (mean age 42.0 ± 6.8 years, 57 couples) were compared with those of 130 matched healthy control subjects. All parents were asymptomatic and in sinus rhythm, except for 1 with undetected complete AV block. Conduction abnormalities were more frequent in parents than in control subjects, found in 50.8% versus 4.6%, respectively (P<0.001). A long PR interval was found in 18.5% of the parents but never in control subjects (P<0.0001). Complete or incomplete right bundle-branch block was observed in 39.2% of the parents and 1.5% of the control subjects (P<0.0001). Complete or incomplete left bundle-branch block was found in 15.4% of the parents and 3.1% of the control subjects (P<0.0006). Estimated heritability for isolated conduction disturbances was 91% (95% confidence interval, 80%-100%). SCN5A mutation screening identified 2 mutations in 2 patients among 97 children. CONCLUSIONS: ECG screening in parents of children affected by idiopathic AV block revealed a high prevalence of conduction abnormalities. These results support the hypothesis of an inheritable trait in congenital and childhood nonimmune isolated AV block.

Characteristics and long-term outcome of non-immune isolated atrioventricular block diagnosed in utero or early childhood: a multicentre study.

AIMS: The natural history of congenital or childhood non-immune, isolated atrioventricular (AV) block is poorly defined. METHODS AND RESULTS: We retrospectively studied 141 children with isolated, non-immune AV block diagnosed in utero, or up to 15 years of age, at 13 French medical centres, between 1980 and 2009. Patients with structural heart disease or maternal antibodies were excluded. Atrioventricular block was asymptomatic in 119 (84.4%) and complete in 100 (70.9%) patients. There was progression to complete AV block in 29/41 (70.7%) patients with incomplete AV block over 2.8 ± 3.4 years (1-155 months), but all patients with incomplete AV block may not have been included in the study. Narrow QRS complex was present in 18 of 26 patients (69.2%) with congenital, and 106 of 115 (92.2%) with childhood AV block. Pacemakers were implanted in 112 children (79.4%), during the first year of life in 18 (16.1%) and before 10 years of age in 90 (80.4%). The mean interval between diagnosis of AV block and pacemaker implants was 2.6 ± 3.9 years (0-300 months). The pacing indication was prophylactic in 70 children (62.5%). During a mean follow-up of 11.6 ± 6.7 years (1-32 years), no patient died or developed dilated cardiomyopathy (DCM). The long-term follow-up was uncomplicated in 127 children (90.1%). CONCLUSION: In this large multicentre study, the long-term outcome of congenital or childhood non-immune, isolated AV block was favourable, regardless of the patient's age at the time of diagnosis. No patient died or developed DCM, and pacemaker-related complications were few.

Regulation of different phases of AMPA receptor intracellular transport by 4.1N and SAP97.

Changes in the number of synaptic AMPA receptors underlie many forms of synaptic plasticity. These variations are controlled by an interplay between their intracellular transport (IT), export to the plasma membrane (PM), stabilization at synapses, and recycling. The cytosolic C-terminal domain of the AMPAR GluA1 subunit is specifically associated with 4.1 N and SAP97. We analyze how interactions between GluA1 and 4.1N or SAP97 regulate IT and exocytosis in basal conditions and after cLTP induction. The down-regulation of 4.1N or SAP97 decreases GluA1 IT properties and export to the PM. The total deletion of its C-terminal fully suppresses its IT. Our results demonstrate that during basal transmission, the binding of 4.1N to GluA1 allows their exocytosis whereas the interaction with SAP97 is essential for GluA1 IT. During cLTP, the interaction of 4.1N with GluA1 allows its IT and exocytosis. Our results identify the differential roles of 4.1N and SAP97 in the control of various phases of GluA1 IT.

Collaborative work in a complex case of Fontan for treating intra-atrial reentrant tachycardia and severe aortic stenosis: a case report.

Background: Intra-atrial reentrant tachycardia (IART) is a frequent arrhythmia in patients with Fontan circulation. Although its supraventricular origin, such arrhythmia can be poorly tolerated as it leads to haemodynamic impairment. Concomitant assessment of pressure/volume overload of cardiac chambers due to valvular disease or residual shunts is necessary. Case summary: We report the case of a 33-year-old male with Fontan extracardiac conduit, suffering from IART with initial poor haemodynamic tolerance. He had a medical history of pulmonary atresia with intact ventricular septum and Type 0 bicuspid aortic valve, with a total of four cardiac surgeries. Echocardiography demonstrated a severe impairment of the univentricular ejection fraction and a critical aortic stenosis. Given the limited medical treatment options of the arrhythmia and the risks of another heart surgery, both IART ablation and transcatheter aortic valve replacement (TAVR) were performed during the same procedure. The IART critical isthmus located in the antero-lateral region of the extracardiac conduit was effectively treated with radiofrequency. Rapid pacing during TAVR was provided by a catheter placed in the unique ventricle via a transconduit puncture. The aortic valve was deployed with minimal para-valvular regurgitation and a satisfactory transvalvular gradient. At follow-up, the univentricular ejection fraction normalized and no arrhythmic episode was recorded in absence of anti-arrhythmic drugs. Discussion: This case highlights the need of a collaborative approach for treating complex cases of adult congenital heart disease, suffering from both electrophysiological and haemodynamic disorders. This combination offered an elegant and safest solution for treating concomitantly a life-threatening arrhythmia and an aortic stenosis.

The tetraspanin TSPAN5 regulates AMPAR exocytosis by interacting with the AP4 complex.

Intracellular trafficking of AMPA receptors is a tightly regulated process which involves several adaptor proteins, and is crucial for the activity of excitatory synapses both in basal conditions and during synaptic plasticity. We found that, in rat hippocampal neurons, an intracellular pool of the tetraspanin TSPAN5 promotes exocytosis of AMPA receptors without affecting their internalisation. TSPAN5 mediates this function by interacting with the adaptor protein complex AP4 and Stargazin and possibly using recycling endosomes as a delivery route. This work highlights TSPAN5 as a new adaptor regulating AMPA receptor trafficking.

Monitoring of Hemodynamics With Right Heart Catheterization in Children With Pulmonary Arterial Hypertension.

Background Right heart catheterization (RHC) is a high-risk procedure in children with pulmonary arterial hypertension without clear guidelines for the indications and targets of invasive reassessment. Our objectives are to define the aims of repeated RHC and evaluate the correlation between noninvasive criteria and hemodynamic parameters. Methods and Results Clinical and hemodynamic characteristics from 71 incident treatment-naïve children (median age 6.2 years) with pulmonary arterial hypertension who had a baseline and reevaluation RHC were analyzed. Correlations between noninvasive predictors and hemodynamic parameters were tested. Adverse outcomes were defined as death, lung transplantation, or Potts shunt. At baseline, pulmonary vascular resistance index (hazard ratio [HR] 1.07 per 1 WU·m2 increase [95% CI, 1.02-1.12], P=0.002), stroke volume index (HR 0.95 per 1 L·min-1·m-2 increase [95% CI, 0.91-0.99], P=0.012), pulmonary artery compliance index (HR 0.16 per 1 mL·mm Hg-1·m-2 increase [95% CI, 0.051-0.52], P=0.002), and right atrial pressure (HR, 1.31 per 1 mm Hg increase [95% CI, 1.01-1.71], P=0.043) were associated with adverse outcomes. Pulmonary vascular resistance index, pulmonary artery compliance index, and right atrial pressure were still associated with a worse outcome at second RHC. Noninvasive criteria accurately predicted hemodynamic evolution; however, 70% of the patients who had improved based on noninvasive criteria still presented at least 1 "at risk" hemodynamics at second RHC. Conclusions Pulmonary vascular resistance index, pulmonary artery compliance index, and right atrial pressure are solid predictors of adverse outcomes in pediatric pulmonary arterial hypertension and potential therapeutic targets. Noninvasive criteria accurately predict the evolution of hemodynamic parameters, but insufficiently. Repeated RHC are helpful to identify children with persistent higher risk after treatment introduction.

Familial Recurrence Patterns in Congenitally Corrected Transposition of the Great Arteries: An International Study.

BACKGROUND: Congenitally corrected transposition of the great arteries (ccTGA) is a rare disease of unknown cause. We aimed to better understand familial recurrence patterns. METHODS: An international, multicentre, retrospective cohort study was conducted in 29 tertiary hospitals in 6 countries between 1990 and 2018, entailing investigation of 1043 unrelated ccTGA probands. RESULTS: Laterality defects and atrioventricular block at diagnosis were observed in 29.9% and 9.3%, respectively. ccTGA was associated with primary ciliary dyskinesia in 11 patients. Parental consanguinity was noted in 3.4% cases. A congenital heart defect was diagnosed in 81 relatives from 69 families, 58% of them being first-degree relatives, including 28 siblings. The most prevalent defects in relatives were dextro-transposition of the great arteries (28.4%), laterality defects (13.6%), and ccTGA (11.1%); 36 new familial clusters were described, including 8 pedigrees with concordant familial aggregation of ccTGA, 19 pedigrees with familial co-segregation of ccTGA and dextro-transposition of the great arteries, and 9 familial co-segregation of ccTGA and laterality defects. In one family co-segregation of ccTGA, dextro-transposition of the great arteries and heterotaxy syndrome in 3 distinct relatives was found. In another family, twins both displayed ccTGA and primary ciliary dyskinesia. CONCLUSIONS: ccTGA is not always a sporadic congenital heart defect. Familial clusters as well as evidence of an association between ccTGA, dextro-transposition of the great arteries, laterality defects and in some cases primary ciliary dyskinesia, strongly suggest a common pathogenetic pathway involving laterality genes in the pathophysiology of ccTGA.

Value of preoperative echocardiography for the diagnosis of coronary artery patterns in neonates with transposition of the great arteries.

BACKGROUND: Abnormal coronary pattern may complicate coronary transfer during arterial switch operation. OBJECTIVE: To evaluate the accuracy of echocardiography in assessing the anatomy of coronary arteries in neonates with transposition of the great arteries, and determine impact on outcomes. METHODS: We conducted a retrospective analysis of data in neonates with transposition of the great arteries. Preoperative echocardiographic coronary artery pattern and surgical intraoperative reports were compared. Mismatch between transthoracic echocardiography and surgical intraoperative reports and the impact on perioperative outcome were assessed. Coronary patterns were classified into four groups: type 1 (normal); type 2 (risk of coronary with intramural course); type 3 (coronary loop); and type 2+3. RESULTS: Overall, 108 neonates who underwent an arterial switch operation were included: 68 were classified as type 1; seven as type 2; 32 as type 3; and one as type 2+3. Overall, 10 adverse events occurred. Five patients died, three from coronary causes. Survival was 96% at 1 month. Transthoracic echocardiography and surgical intraoperative reports differed in 17.6% of cases. Mortality was 15.8% in case of inappropriate diagnosis and 2.2% for appropriate diagnosis (P=0.01). Mortality in type 2 was 66.7% in case of discordance versus 0% when concordant. Multivariable analysis found that inappropriate preoperative transthoracic echocardiography diagnosis of coronary pattern was the only significant risk factor for mortality (P=0.04). CONCLUSIONS: Echocardiography can assess coronary artery anatomy in neonates with transposition of the great arteries. Intramural coronary course is often misdiagnosed. Preoperative misdiagnosis of coronary artery anomaly may impact perioperative mortality. However, this assessment will have to be confirmed by further larger studies.

Maladaptive activation of Nav1.9 channels by nitric oxide causes triptan-induced medication overuse headache.

Medication-overuse headaches (MOH) occur with both over-the-counter and pain-relief medicines, including paracetamol, opioids and combination analgesics. The mechanisms that lead to MOH are still uncertain. Here, we show that abnormal activation of Nav1.9 channels by Nitric Oxide (NO) is responsible for MOH induced by triptan migraine medicine. Deletion of the Scn11a gene in MOH mice abrogates NO-mediated symptoms, including cephalic and extracephalic allodynia, photophobia and phonophobia. NO strongly activates Nav1.9 in dural afferent neurons from MOH but not normal mice. Abnormal activation of Nav1.9 triggers CGRP secretion, causing artery dilatation and degranulation of mast cells. In turn, released mast cell mediators potentiates Nav1.9 in meningeal nociceptors, exacerbating inflammation and pain signal. Analysis of signaling networks indicates that PKA is downregulated in trigeminal neurons from MOH mice, relieving its inhibitory action on NO-Nav1.9 coupling. Thus, anomalous activation of Nav1.9 channels by NO, as a result of chronic medication, promotes MOH.

Dominant variants in the splicing factor PUF60 cause a recognizable syndrome with intellectual disability, heart defects and short stature.

Verheij syndrome, also called 8q24.3 microdeletion syndrome, is a rare condition characterized by ante- and postnatal growth retardation, microcephaly, vertebral anomalies, joint laxity/dislocation, developmental delay (DD), cardiac and renal defects and dysmorphic features. Recently, PUF60 (Poly-U Binding Splicing Factor 60 kDa), which encodes a component of the spliceosome, has been discussed as the best candidate gene for the Verheij syndrome phenotype, regarding the cardiac and short stature phenotype. To date, only one patient has been reported with a de novo variant in PUF60 that probably affects function (c.505C>T leading to p.(His169Tyr)) associated with DD, microcephaly, craniofacial and cardiac defects. Additional patients were required to confirm the pathogenesis of this association and further delineate the clinical spectrum. Here we report five patients with de novo heterozygous variants in PUF60 identified using whole exome sequencing. Variants included a splice-site variant (c.24+1G>C), a frameshift variant (p.(Ile136Thrfs*31)), two nonsense variants (p.(Arg448*) and p.(Lys301*)) and a missense change (p.(Val483Ala)). All six patients with a PUF60 variant (the five patients of the present study and the unique reported patient) have the same core facial gestalt as 8q24.3 microdeletions patients, associated with DD. Other findings include feeding difficulties (3/6), cardiac defects (5/6), short stature (5/6), joint laxity and/or dislocation (5/6), vertebral anomalies (3/6), bilateral microphthalmia and irido-retinal coloboma (1/6), bilateral optic nerve hypoplasia (2/6), renal anomalies (2/6) and branchial arch defects (2/6). These results confirm that PUF60 is a major driver for the developmental, craniofacial, skeletal and cardiac phenotypes associated with the 8q24.3 microdeletion.

Off-pump replacement of the pulmonary valve in large right ventricular outflow tracts: a hybrid approach.

BACKGROUND: Percutaneous pulmonary valve replacement has recently been introduced and is under investigation in humans. This technique is, however, limited to patients with a right ventricular outflow tract that does not exceed 22 mm in diameter. We report our experience of off-pump pulmonary valve replacement using a hybrid approach in animals with large right ventricular outflow tracts. METHODS: Eight ewes were included in the protocol and were equally divided into 2 groups. A left thoracotomy was first performed, and the main pulmonary artery was banded by using 2 radiopaque rings with a diameter of 18 mm that allowed for further pulmonary valve replacement. We then intended to implant a valved stent either percutaneously (group 1) or through a transventricular approach (group 2). All animals were killed after valve implantation. The operation allowed the pulmonary diameter to be reduced from 30 to 17.6 mm. RESULTS: The right ventricular pressure did not significantly increase after reduction of the pulmonary artery diameter (25 vs 36 mm Hg). Subsequent pulmonary valve replacement through a percutaneous or a transventricular approach was always possible without any requirement for extracorporeal circulation. All devices were successfully delivered inside the pulmonary artery banding and were functioning perfectly at early evaluation. CONCLUSIONS: Implantation of a pulmonary valve is possible in ewes through a hybrid approach when the right ventricular outflow tract exceeds 22 mm in diameter. This involves both surgeons and interventionists and allows for a staged procedure in which the valvulation is performed percutaneously or, for a combined hybrid approach, in which the valve is implanted off pump transventricularly during the same operation.

Usefulness of MRI in the follow-up of patients with repaired aortic coarctation and bicuspid aortic valve.

BACKGROUND: The long-term outcome of repaired aortic coarctation may be complicated by dilatation of the ascending aorta notably in patients with bicuspid aortic valve. Magnetic resonance imaging was used to compare the size of the ascending aorta in patients with bicuspid or tricuspid aortic valve. METHODS: In 50 patients with a repair of aortic coarctation, the size of the ascending aorta was measured in a bicuspid aortic valve group (n=11) and a tricuspid aortic valve group (n=39). The aortic diameter was measured at the level of the sinus of Valsalva and at the widest part of the ascending aorta using magnetic resonance imaging. RESULTS: The mean age of patients at surgical repair was respectively 2.2+/-3.3 years for the bicuspid aortic valve group and 2.5+/-3.5 years for the tricuspid aortic valve group (p=NS) and the mean age at the time of the magnetic resonance imaging was 10.2+/-4.7 years and 9.3+/-5.9 years (p=NS) respectively. A significant difference in the aortic diameter was found between the bicuspid aortic valve group and the tricuspid aortic group both at the level of sinus of Valsalva (34.8+/-8.2 mm, 19.5+/-4.4 mm, respectively, p<0.01) and at the level of the ascending aorta (36.8+/-7.2 mm, 16.9+/-3.4 mm, respectively, p<0.01). CONCLUSIONS: The occurrence of ascending aortic dilatation is significantly associated with the presence of a bicuspid aortic valve. This requires long-term follow-up, which can be effectively performed by magnetic resonance imaging.