Correlation of Calcification on Excised Aortic Valves by Micro-Computed Tomography with Severity of Aortic Stenosis

Background and aim of the study: The quantification of incidentally found aortic valve calcification on computed tomography (CT) is not performed routinely, as data relating to the accuracy of aortic valve calcium for estimating the severity of aortic stenosis (AS) is neither consistent nor validated. As aortic valve calcium quantification by CT is confounded by wall and coronary ostial calcification, as well as motion artifact, the ex-vivo micro-computed tomography (micro-CT) of stenotic aortic valves allows a precise measurement of the amounts of calcium present. The study aim, using excised aortic valves from patients with confirmed AS, was to determine if the amount of calcium on micro-CT correlated with the severity of AS. Methods: Each of 35 aortic valves that had been excised from patients during surgical valve replacement were examined using micro-CT imaging. The amount of calcium present was determined by absolute and proportional values of calcium volume in the specimen. Subsequently, the correlation between calcium volume and preoperative mean aortic valve gradient (MAVG), peak transaortic velocity (V-max), and aortic valve area (AVA) on echocardiography, was evaluated. Results: The mean calcium volume across all valves was 603.2 +/- 398.5 mm(3), and the mean ratio of calcium volume to total valve volume was 0.36 +/- 0.16. The mean aortic valve gradient correlated positively with both calcium volume and ratio (r = 0.72, p <0.001). V-max also correlated positively with the calcium volume and ratio (r = 0.69 and 0.76 respectively; p <0.001). A logarithmic curvilinear model proved to be the best fit to the correlation. A calcium volume of 480 mm(3) showed sensitivity and specificity of 0.76 and 0.83, respectively, for a diagnosis of severe AS, while a calcium ratio of 0.37 yielded sensitivity and specificity of 0.82 and 0.94, respectively. Conclusion: A radiological estimation of calcium amount by volume, and its proportion to the total valve volume, were shown to serve as good predictive parameters for severe AS. An estimation of the calcium volume may serve as a complementary measure for determining the severity of AS when aortic valve calcification is identified on CT imaging. The Journal of Heart Valve Disease 2012;21:320-327

Whole exome sequencing in an Indian family links Coats plus syndrome and dextrocardia with a homozygous novel CTC1 and a rare HES7 variation

Background: Coats plus syndrome is an autosomal recessive, pleiotropic, multisystem disorder characterized by retinal telangiectasia and exudates, intracranial calcification with leukoencephalopathy and brain cysts, osteopenia with predisposition to fractures, bone marrow suppression, gastrointestinal bleeding and portal hypertension. It is caused by compound heterozygous mutations in the CTC1 gene. Case presentation: We encountered a case of an eight-year old boy from an Indian family with manifestations of Coats plus syndrome along with an unusual occurrence of dextrocardia and situs inversus. Targeted resequencing of the CTC1 gene as well as whole exome sequencing (WES) were conducted in this family to identify the causal variations. The identified candidate variations were screened in ethnicity matched healthy controls. The effect of CTC1 variation on telomere length was assessed using Southern blot. A novel homozygous missense mutation c.1451A > C (p.H484P) in exon 9 of the CTC1 gene and a rare 3'UTR known dbSNP variation (c.*556 T > C) in HES7 were identified as the plausible candidates associated with this complex phenotype of Coats plus and dextrocardia. This CTC1 variation was absent in the controls and we also observed a reduced telomere length in the affected individual's DNA, suggesting its likely pathogenic nature. The reported p.H484P mutation is located in the N-terminal 700 amino acid regionthat is important for the binding of CTC1 to ssDNA through its two OB domains. WES data also showed a rare homozygous missense variation in the TEK gene in the affected individual. Both HES7 and TEK are targets of the Notch signaling pathway. Conclusions: This is the first report of a genetically confirmed case of Coats plus syndrome from India. By means of WES, the genetic variations in this family with unique and rare complex phenotype could be traced effectively. We speculate the important role of Notch signaling in this complex phenotypic presentation of Coats plus syndrome and dextrocardia. The present finding will be useful for genetic diagnosis and carrier detection in the family and for other patients with similar disease manifestations.

Isotopic disequilibrium in Globigerina bulloides and carbon isotope response to productivity increase in Southern Ocean

Oxygen and carbon isotope ratios in planktonic foraminifera Globigerina bulloides collected from tow samples along a transect from the equatorial Indian ocean to the Southern Ocean (45 degrees E and 80 degrees E and 10 degrees N to 53 degrees S) were analysed and compared with the equilibrium delta O-18 and delta C-13 values of calcite calculated using the temperature and isotopic composition of the water column. The results agree within similar to 0.25% for the region between 10 degrees N and 40 degrees S and 75-200 m water depth which is considered to be the habitat of Globigerina bulloides. Further south (from 40 degrees S to 55 degrees S), however, the measured delta O-18 and delta C-13 values are higher than the expected values by similar to 2% and similar to 1% respectively. These enrichments can be attributed to either a `vital effect' or a higher calcification rate. An interesting pattern of increase in the delta C-13(DIC) value of the surface water with latitude is observed between 35 degrees S and similar to 60 degrees S, with a peak at similar to 42 degrees S. This can be caused by increased organic matter production and associated removal. A simple model accounting for the increase in the delta C-13(DIC) values is proposed which fits well with the observed chlorophyll abundance as a function of latitude.