Cardiac complications relating to pregnancy and recurrence of disease in the offspring of women with atrioventricular septal defects

Aims In most pregnancy reports, atrioventricular septal defects (AVSD) are not differentiated from more simple septal defects, thus underestimating the risks of pregnancy. To investigate the magnitude and determinants of risk during pregnancy in female patients with balanced AVSD. Methods and results Using a nation-wide registry (CONCOR), 79 female patients with balanced/isolated AVSD were identified. A total of 29 patients had 62 pregnancies, including 12 miscarriages (19%) and two elective abortions. Detailed recordings of each completed (greater-than 20 weeks gestation) pregnancy (n=48, 26 women) were obtained. Cardiovascular events complicated almost 40% of the completed pregnancies. In particular, post-partum persistence of pregnancy-related New York Heart Association (NYHA) class deterioration [23% mainly patients with residual atrial septal defects (ASD)] and deterioration of pre-existing left AV-valvular regurgitation (17%) were frequently recorded. Additional cardiac complications were arrhythmias (19%) and symptomatic heart failure (2%). Congenital heart disease (CHD) recurred in six children (12%): AVSD (n=4, three with left-sided hypoplasia), patent ductus arteriosus (n=1), and ASD (n=1). Three children died including two children with left-sided hypoplasia. Conclusion Pregnancy is not always well tolerated in women with AVSD, predominantly due to NYHA class deterioration and worsening of pre-existing AV-valvular regurgitation. Offspring mortality is high (6.3%), primarily due to recurrence of complex CHD

Explaining the world heritage list: an empirical study

The UNESCO World Heritage List is designed to protect the global heritage. We show that, with respect to countries and continents, the existing World Heritage List is highly imbalanced. Major econometric determinants of this imbalance are historical GDP, historical population, area in square kilometers of a country, and number of years of high civilization. Surprisingly, economic and political factors, such as membership on the UN Security Council, which should be unrelated to the value of a country’s heritage and therefore should have no impact, are shown to have a systematic impact on the composition of the World Heritage List

Large-scale gene-centric analysis identifies novel variants for coronary artery disease

Coronary artery disease (CAD) has a significant genetic contribution that is incompletely characterized. To complement genome-wide association (GWA) studies, we conducted a large and systematic candidate gene study of CAD susceptibility, including analysis of many uncommon and functional variants. We examined 49,094 genetic variants in ~2,100 genes of cardiovascular relevance, using a customised gene array in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733 controls of European descent; 4,394 cases and 4,259 controls of South Asian origin). We attempted to replicate putative novel associations in an additional 17,121 CAD cases and 40,473 controls. Potential mechanisms through which the novel variants could affect CAD risk were explored through association tests with vascular risk factors and gene expression. We confirmed associations of several previously known CAD susceptibility loci (eg, 9p21.3:p<10; LPA:p<10; 1p13.3:p<10) as well as three recently discovered loci (COL4A1/COL4A2, ZC3HC1, CYP17A1:p<5×10). However, we found essentially null results for most previously suggested CAD candidate genes. In our replication study of 24 promising common variants, we identified novel associations of variants in or near LIPA, IL5, TRIB1, and ABCG5/ABCG8, with per-allele odds ratios for CAD risk with each of the novel variants ranging from 1.06-1.09. Associations with variants at LIPA, TRIB1, and ABCG5/ABCG8 were supported by gene expression data or effects on lipid levels. Apart from the previously reported variants in LPA, none of the other ~4,500 low frequency and functional variants showed a strong effect. Associations in South Asians did not differ appreciably from those in Europeans, except for 9p21.3 (per-allele odds ratio: 1.14 versus 1.27 respectively; P for heterogeneity = 0.003). This large-scale gene-centric analysis has identified several novel genes for CAD that relate to diverse biochemical and cellular functions and clarified the literature with regard to many previously suggested genes. © 2011 Butterworth et al