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  • 1
    Publication Date: 2012-06-20
    Description: Background— The occurrence of a congenital heart defect has long been thought to have a multifactorial basis, but the evidence is indirect. Complex trait analysis could provide a more nuanced understanding of congenital heart disease. Methods and Results— We assessed the role of genetic and environmental factors on the incidence of ventricular septal defects (VSDs) caused by a heterozygous Nkx2-5 knockout mutation. We phenotyped 〉3100 hearts from a second-generation intercross of the inbred mouse strains C57BL/6 and FVB/N. Genetic linkage analysis mapped loci with lod scores of 5 to 7 on chromosomes 6, 8, and 10 that influence the susceptibility to membranous VSDs in Nkx2-5 +/– animals. The chromosome 6 locus overlaps one for muscular VSD susceptibility. Multiple logistic regression analysis for environmental variables revealed that maternal age is correlated with the risk of membranous and muscular VSD in Nkx2-5 +/– but not wild-type animals. The maternal age effect is unrelated to aneuploidy or a genetic polymorphism in the affected individuals. The risk of a VSD is not only complex but dynamic. Whereas the effect of genetic modifiers on risk remains constant, the effect of maternal aging increases over time. Conclusions— Enumerable factors contribute to the presentation of a congenital heart defect. The factors that modify rather than cause congenital heart disease substantially affect risk in predisposed individuals. Their characterization in a mouse model offers the potential to narrow the search space in human studies and to develop alternative strategies for prevention.
    Keywords: Animal models of human disease, Pediatric and congenital heart disease, including cardiovascular surgery, Cardiac development, Genetics of cardiovascular disease
    Print ISSN: 1942-325X
    Electronic ISSN: 1942-3268
    Topics: Medicine
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  • 2
    Publication Date: 2013-01-16
    Description: Background— Patterns of noninvasive stress test (ST) and invasive coronary angiography (CA) utilization after percutaneous coronary intervention (PCI) are not well described in older populations. Methods and Results— We linked National Cardiovascular Data Registry CathPCI Registry data with longitudinal Medicare claims data for 250 350 patients undergoing PCI from 2005 to 2007 and described subsequent testing and outcomes. Between 60 days post-PCI and end of follow-up (median 24 months), 49% (n=122 894) received ST first, 10% (n=25 512) underwent invasive CA first, and 41% (n=101 944) had no testing. Several clinical risk factors at time of index PCI were associated with decreased likelihood of downstream testing (ST or CA, P 〈0.05 for all), including older age (hazard ratio [HR] 0.784 per 10-year increase), male sex (HR 0.946), heart failure (HR 0.925), diabetes mellitus (HR 0.954), smoking (HR 0.804), and renal failure (HR 0.880). Fifteen percent of patients with ST first proceeded to subsequent CA within 90 days of testing (n=18 472/101 884); of these, 48% (n=8831) underwent revascularization within 90 days, compared with 53% (n=13 316) of CA first patients ( P 〈0.0001). Conclusions— In this descriptive analysis, ST and invasive CA were common in older patients after PCI. Paradoxically, patients with higher risk features at baseline were less likely to undergo post-PCI testing. The revascularization yield was low on patients referred for ST after PCI, with only 9% undergoing revascularization within 90 days.
    Keywords: Health policy and outcome research
    Print ISSN: 1941-9651
    Electronic ISSN: 1942-0080
    Topics: Medicine
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  • 3
    Publication Date: 2014-08-26
    Description: Background and Purpose— Intraventricular hemorrhage is associated with high mortality and poor functional outcome. The use of intraventricular fibrinolytic (IVF) therapy as an intervention in intraventricular hemorrhage is an evolving therapy with conflicting reports in the literature. The goal of this study is to investigate the impact of IVF on mortality, functional outcome, ventriculitis, shunt dependence, and rehemorrhage. Methods— During March and April 2014, a systematic literature search was performed identifying 1359 articles. Of these, 24 met inclusion criteria. A random effects meta-analysis was performed using both pooled and subset analysis based on study type. Results— Our meta-analysis demonstrated that IVF reduced mortality in intraventricular hemorrhage by nearly half (relative risk [RR], 0.55; 95% confidence interval [CI], 0.42–0.71; P 〈0.00001), increased the likelihood of good functional outcome by 66% (RR, 1.66; 95% CI, 1.27–2.19; P =0.0003), and also decreased the rate of shunt dependence (RR, 0.62; 95% CI, 0.42–0.93; P =0.02). IVF was not found to be associated with increased rates of ventriculitis (RR=1.46; 95% CI, 0.77–2.76; P =0.25) or rehemorrhage (RR=1.06; 95% CI, 0.66–1.70; P =0.80). We detected no evidence of publication bias. Conclusions— Our meta-analysis showed that IVF is safe and could be an effective strategy for the treatment of intraventricular hemorrhage. It may reduce mortality, improve functional outcome, and diminish the need for permanent ventricular shunting, while not increasing the risk of ventriculitis or rehemorrhage.
    Keywords: Acute Cerebral Hemorrhage, Emergency treatment of Stroke, Other Stroke Treatment - Medical
    Print ISSN: 0039-2499
    Electronic ISSN: 1524-4628
    Topics: Medicine
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