Lamia Ait-Ali

Cumulative Patient Effective Dose and Acute Radiation-Induced Chromosomal DNA Damage in Children with Congenital Heart Disease

Background The seventh Committee on “Biological Effects of Ionizing Radiation” (BEIR VII, 2006) underlines “the need of studies of infants who are exposed to diagnostic radiation because catheters have been placed in their hearts”. Objective To determine the lifetime attributable risk (LAR) of cancer associated with the estimated cumulative radiological dose in 59 children (42 male, age 2.8±3.2 years) with complex congenital heart disease, and to assess chromosomal DNA damage after cardiac catheterisation procedures. Methods In all patients, the cumulative exposure was estimated as effective dose in milliSievert (mSv), and LAR cancer was determined from the BEIR VII report. In a subset of 18 patients (13 male, age 5.2±5.7 years) micronucleus as a biomarker of DNA damage and long-term risk predictor of cancer was assayed before and 2 h after catheterisation procedures. Dose–area product (Gy cm2) was assessed as a measure of patient dose. Results The median life time cumulative effective dose was 7.7 mSv per patient (range 4.6–41.2). Cardiac catheterisation procedures and CT were responsible for 95% of the total effective dose. For a 1-year-old child, the LAR cancer was 1 in 382 (25th to 75th centiles: 1 in 531 to 1 in 187) and 1 in 156 (25th to 75th centiles: 1 in 239 to 1 in 83) for male and female patients, respectively. Median micronucleus values increased significantly after the procedure in comparison with baseline (before 6‰ vs after 9‰, p=0.02). The median dose–area product value was 20 Gy cm2 (range 1–277). Conclusion Children with congenital heart disease are exposed to a significant cumulative dose. Indirect cancer risk estimations and direct DNA data both emphasise the need for strict radiation dose optimisation in children.

Prothrombotic Mutations as Risk Factors for Cryptogenic Ischemic Cerebrovascular Events in Young Subjects With Patent Foramen Ovale

Background and Purpose— Patent foramen ovale (PFO) has been identified as a potential risk factor for cerebrovascular ischemia. Procoagulant mutations may increase the risk and impact the choice of appropriate therapy for secondary prevention. We evaluated the prevalence of the 2 most common genetic risk factors for thromboembolism, factor V Leiden (G1691A) and prothrombin G20210A, in young PFO patients who were referred for percutaneous transcatheter closure of their PFO. Methods— Ninety-seven patients (50 men; mean±SD age, 40.9±10.0 years) with first-ever cerebrovascular events before the age of 55 years and 160 age-matched control subjects (69 men; mean±SD age, 40.4±10.5 years) were recruited into the study. Factor V Leiden and prothrombin G20210A mutations were detected by using a multiplex allele-specific polymerase chain reaction assay. Results— The prevalence of subjects carrying at least 1 prothrombotic genotype was significantly higher in the group of PFO patients than in the group of controls (10.3% vs 2.5%; &khgr;2=7.2, P=0.008). Two patients (2.1%) versus 1 control subject (0.6%) and 8 cases (8.2%) versus 3 controls (1.9%) were carriers for factor V Leiden and prothrombin G20210A mutations, respectively. After adjustment for other vascular risk factors, the combination of either factor V Leiden or prothrombin G20210A and PFO was associated with a 4.7-fold (95% CI=1.4 to 16.1; P=0.008) increased risk of cerebral ischemia in young patients. Conclusions— Our results indicate that prothrombotic mutations are important risk factors for cerebral ischemia in young patients with PFO. Screening for thrombotic mutations should be considered in young patients with PFO-related ischemic events.

Maternal and Paternal Environmental Risk Factors, Metabolizing GSTM1 and GSTT1 Polymorphisms, and Congenital Heart Disease

Congenital heart defects (CHDs) are the most prevalent of all birth malformations arising from the complex interplay of environmental exposures and genes. Modifiable environmental risk factors are still largely unknown, especially for paternal exposure. The aim of the present study was to examine the association between the environmental exposures of both parents and CHD risk and to explore the modification effect of metabolizing gene polymorphisms in children who lack the genetic capacity to produce the glutathione S-transferase (GST) GSTM1 and GSTT1 enzymes. A total of 330 parents of a child with CHD and 330 parents of a child without any congenital malformations were compared in terms of lifestyle habits and toxicant exposure. GST gene polymorphisms were investigated in 180 patients with CHD (104 males, age 4.9 ± 5.8 years). Paternal smoking (≥15 cigarettes/day) was significantly associated with CHD risk (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.3 to 3.5, p = 0.002). Both maternal (OR 2.6, 95% CI 1.6 to 4.2, p <0.0001) and paternal (OR 2.5, 95% CI 1.6 to 3.8, p <0.0001) occupational/environmental exposures increased the risk of CHD. Also, a significant additive risk (OR 4.5, 95% CI 2.5 to 8.3, p <0.0001) was found when both parents were exposed to toxicants. Both maternal (OR 3.6, 95% CI 1.1 to 11.2, p = 0.03) and paternal (OR 3.3, 95% CI 1.0 to 10.8, p = 0.03) exposure to toxicants increased the CHD risk in children who carried the combined null GST genotypes. The effect for the combined null GST genotypes was also stronger (OR 6.5, 95% CI 1.5 to 28.0) when both parents were exposed. In conclusion, paternal smoking and exposure to toxicants for both parents affect the risk of children with CHD. Polymorphisms in GST genes can modify a persons risk of toxicant exposure-induced disease.

Elastic Properties of Aortic Wall in Patients With Bicuspid Aortic Valve by Magnetic Resonance Imaging

Bicuspid aortic valve (BAV) is frequently associated with aortic wall abnormalities, including dilation of the ascending aorta and even dissection. We propose 2 new indexes of aortic wall biophysical properties, the maximum rates of systolic distension and diastolic recoil (MRSD and MRDR, respectively), in patients with BAV and matched control subjects. We evaluated 53 consecutive young patients with BAV (36 males, mean age 16 ± 4 years) with mild aortic valve disease and a control group of 22 age- and gender-matched healthy volunteers. All subjects underwent a cardiac magnetic resonance imaging study that included phase velocity mapping and cine acquisition at several aortic levels. The MRSD and MRDR were measured in the ascending aorta in both patients with BAV and controls. Of the 53 patients with BAV, 26 had enlarged ascending aortas (dilated BAV), and 27 had a normal aortic diameter (nondilated BAV). Compared to controls, the MRSD was significantly lower in the whole BAV group (4.37 ± 1.1 vs 9.1 ± 2.1), in patients with dilated BAV (4.5 ± 1.1 p <0.0001), and in those with nondilated BAV (4.3 ± 1.0, p <0.0001). The MRDR was greater in the whole BAV group (-4 ± 1.2 vs -7.6 ± 2.7, p <0.0001), in the dilated BAV group (-3.9 ± 1.3, p <0.0001), and in the nondilated BAV group (-4.1 ± 1.2, p <0.0001). A receiver operating characteristic curve analysis of MRSD distinguished BAV from controls with 100% sensitivity and 95% specificity. In conclusion, MRSD and MRDR were slower in the patients with BAV than in the controls, regardless of the dimensions of the ascending aorta.

Age-dependent changes in elastic properties of thoracic aorta evaluated by magnetic resonance in normal subjects

OBJECTIVES Aortic stiffness is an independent cardiovascular risk factor. Cardiac magnetic resonance (CMR) allows evaluation of aortic elastic properties by different indexes such as distensibility, the maximum rate of systolic distension (MRSD) and pulse wave velocity (PWV). We sought to define age-dependent changes of indexes of elastic properties of the thoracic aorta in healthy subjects. METHODS We enrolled 85 healthy subjects (53 males) free of overt cardiovascular disease subdivided into 6 classes of age (from 15 to >60 years). Distensibility, MRSD and PWV were measured by the analysis of CMR images acquired using a 1.5 T clinical scanner. RESULTS MRSD and distensibility decreased progressively through the classes of age (P < 0.001) after an initial plateau between 20 and 30 years in males and 15 and 20 years in females. Pulse wave velocity increased progressively with the age (P < 0.001). Distensibility was related to body mass index (P = 0.002), surface area (P < 0.005), weight (P = 0.005) and to left ventricular parameters such as mass index (P < 0.001) and end-diastolic volume index (P = 0.002). MRSD was related to end-diastolic volume index (P < 0.001) but not to body parameters. PWV was not related to body and ventricular parameters. CONCLUSIONS This study confirmed that physiological ageing is associated with a progressive impairment of the elastic properties of the aortic wall. Results of this study may be useful for the early identification of subjects with impaired aortic wall properties providing referral values of elasticity indexes assessed by CMR in different classes of age.

A New Simple Method to Estimate Pulmonary Regurgitation by Echocardiography in Operated Fallot: Comparison With Magnetic Resonance Imaging and Performance Test Evaluation

BACKGROUND The aim of this study was to assess a novel transthoracic echocardiographic method to estimate the severity of pulmonary regurgitation (PR) in patients with surgically repaired tetralogy of Fallot. METHOD In 63 patients with operated tetralogy of Fallot, PR was evaluated by vena contracta width, jet deceleration, PR index, pressure half-time, and a new index, referred to as Pulmonary Regurgitation Index by M-mode echocardiography (PRIME), which is the systolic-to-diastolic variation in right pulmonary artery diameter. The results were matched to PR fraction (PRF) assessed by cardiovascular magnetic resonance imaging. PRIME cutoff values for selecting patients with mild, moderate, and severe PR were identified by maximizing PRIME sensitivity and specificity. Nonlinear regression by 3-parameter logistic function was used to estimate PRF by PRIME. RESULTS The sensitivity and specificity of PRIME were high for all diagnostic targets: PRF > or =15% versus <15%, PRF > or =25% versus <25%, and PRF >40% versus < or =40%. The nonlinear regression model showed a good correlation between PRF and PRIME (R(2) = 0.95). CONCLUSION PRIME is a simple and accurate method to estimate PR by transthoracic echocardiography in patients with operated tetralogy of Fallot.

Ascending aortic aneurysm in a patient with bicuspid aortic valve, positive history of systemic autoimmune diseases and common genetic factors: a case report

The bicuspid aortic valve (BAV) and specific systemic autoimmune diseases are associated with cardiovascular manifestation, including aortic aneurysm. We reported a case of 64 year-old patient with BAV and a history of ankylosing spondylitis (AS) and systemic lupus erythematosus (SLE), and who developed ascending thoracic aortic aneurysm. The patient presented also the homozygosity for genetic variants of MMP9, ACE, MTHFR and PAI-1 genes. Gene-environmental interactions may represent an additional pathogenetic dimension in the still challenging management of the abnormalities of the aortic wall, including dilatation, aneurysm and dissection.

Smoking and congenital heart disease: the epidemiological and biological link.

Cigarette smoking is a powerful human germ cell mutagen and teratogen. Congenital heart defects (CHD) is the most prevalent of all birth defects and leading cause of death in the first year of life. The purpose of this article is to review the epidemiology of the impact of cigarette smoking on CHD risk as well as to discuss the potential biological mechanisms of smoking-mediated abnormal cardiac development. Although epidemiological studies of association between parental smoking and CHD are limited, biological evidence support the concept that cigarette smoking may substantially contribute to the aetiology of CHD through induction of either male and female germ-cell mutation or interference with epigenetic pathways. Further research is needed to better define the relationship between parental smoking and the risk of heart defects as well as to assess parental-fetal gene-smoking interactions.

Computational fluid dynamics in a model of the total cavopulmonary connection reconstructed using magnetic resonance images.

The recent developments in imaging techniques have created new opportunities to give an accurate description of the three-dimensional morphology of vessels. Such three-dimensional reconstruction of anatomical structures from medical images has achieved importance in several applications, such as the reconstruction of human bones, spine portions, and vascular districts.

Myocardial infarction and arterial thrombosis in identical newborn twins with homozygosity for the PAI-1 4 G/5 G polymorphism

Myocardial infarction in the perinatal period, in the absence of congenital heart disease or coronary artery lesions, is rare. The most common etiology described are the thromboembolism and perinatal asphyxia. We report a case of monozygotic twins who developed, after birth, acute vascular events and both had PAI-1 4G/4G homozygosity.