Papillary muscle traction in mitral valve prolapse: Quantitation by two-dimensional echocardiography

Previous angiographic observations in patients with mitral valve prolapse have suggested that superior leaflet displacement results in abnormal superior tension on the papillary muscle tips that causes their superior traction or displacement. It has further been postulated that such tension can potentially affect the mechanical and electrophysiologic function of the left ventricle. The purpose of this study was to confirm and quantitate this phenomenon noninvasively by using two-dimensional echocardiography to determine whether superior displacement of the papillary muscle tips occurs and its relation to the degree of mitral leaflet displacement.Directed echocardiographic examination of the papillary muscles and mitral anulus was carried out in a series of patients with classic mitral valve prolapse and results were compared with those in a group of normal control subjects. Distance from the anulus to the papillary muscle tip was measured both in early and at peak ventricular systole. In normal subjects, this distance did not change significantly through systole, whereas in the patient group it decreased, corresponding to a superior displacement of the papillary muscle tips toward the anulus in systole (8.5 ± 2.6 vs. 0.8 ± 0.7 mm; p < 0.0001). This superior papillary muscle motion paralleled the superior displacement of the leaflets in individual patients (y = l.0x + 0.8; r = 0.93) and followed a similar time course. The systolic motion of the mitral anulus toward the apex, assessed with respect to a fixed external reference, was not significantly different in the patients and control groups (14.3 ± 4 vs. 15.5 ± 4.4 mm; p = 0.4) and therefore could not explain the superior papillary muscle tip motion relative to the anulus in the patients with mitral valve prolapse.These results demonstrate that normal mechanisms maintain a relatively constant distance between the papillary muscle tips and the mitral anulus during systole. In classic mitral valve prolapse, superior leaflet displacement is paralleled by superior displacement of the papillary muscles that is consistent with superiorly directed forces causing their traction. Two-dimensional echocardiography can therefore be used to measure these relations and test hypotheses as to their clinical correlates in patients with mitral valve prolapse

Genome-wide analyses identify 68 new loci associated with intraocular pressure and improve risk prediction for primary open-angle glaucoma.

Glaucoma is the leading cause of irreversible blindness globally 1 . Despite its gravity, the disease is frequently undiagnosed in the community 2 . Raised intraocular pressure (IOP) is the most important risk factor for primary open-angle glaucoma (POAG)3,4. Here we present a meta-analysis of 139,555 European participants, which identified 112 genomic loci associated with IOP, 68 of which are novel. These loci suggest a strong role for angiopoietin-receptor tyrosine kinase signaling, lipid metabolism, mitochondrial function and developmental processes underlying risk for elevated IOP. In addition, 48 of these loci were nominally associated with glaucoma in an independent cohort, 14 of which were significant at a Bonferroni-corrected threshold. Regression-based glaucoma-prediction models had an area under the receiver operating characteristic curve (AUROC) of 0.76 in US NEIGHBORHOOD study participants and 0.74 in independent glaucoma cases from the UK Biobank. Genetic-prediction models for POAG offer an opportunity to target screening and timely therapy to individuals most at risk

Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process

Glaucoma is characterized by irreversible optic nerve degeneration and is the most frequent cause of irreversible blindness worldwide. Here, the International Glaucoma Genetics Consortium conducts a meta-analysis of genome-wide association studies of vertical cup-disc ratio (VCDR), an important disease-related optic nerve parameter. In 21,094 individuals of European ancestry and 6,784 individuals of Asian ancestry, we identify 10 new loci associated with variation in VCDR. In a separate risk-score analysis of five case-control studies, Caucasians in the highest quintile have a 2.5-fold increased risk of primary open-angle glaucoma as compared with those in the lowest quintile. This study has more than doubled the known loci associated with optic disc cupping and will allow greater understanding of mechanisms involved in this common blinding condition

New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics

Primary open-angle glaucoma (POAG), the most common optic neuropathy, is a highly heritable disease (h2 = 0.42 ± 0.09). Siblings of POAG cases have a ten-fold increase risk of developing the disease. Intraocular pressure (IOP) and optic nerve head characteristics are used clinically to predict POAG risk. We conducted a genome-wide association meta-analysis of IOP and optic disc parameters and validated our findings in multiple sets of POAG cases and controls. Using imputation to the 1000 genomes (1000G) reference set, we identified 9 new genomic regions associated with vertical cup disc ratio (VCDR) and 1 new region associated with IOP. Additionally, we found 5 novel loci for optic nerve cup area and 6 for disc area. Previously it was assumed that genetic variation influenced POAG either through IOP or via changes to the optic nerve head; here we present evidence that some genomic regions affect both IOP and the disc parameters. We characterized the effect of the novel loci through pathway analysis and found that pathways involved are not entirely distinct as assumed. Further, we identified a novel association between CDKN1A and POAG. Using a zebrafish model we show that six6b (associated with POAG and optic nerve head variation) alters the expression of cdkn1a. In summary, we have identified several novel genes influencing the major clinical risk predictors of POAG and showed that genetic variation in CDKN1A is important in POAG ris

Implementing an Oxygen Supplementation and Monitoring Protocol on Inpatient Pediatric Bronchiolitis: An Exercise in Deimplementation

Aim. Our goal in this study is to evaluate the effectiveness of our oxygen (O2) protocol to reduce length of stay (LOS) for children hospitalized with bronchiolitis. Methods. In this retrospective cohort study, the outcomes of children ≤ 24 months old that were admitted with bronchiolitis and placed on the O2 protocol were compared to historical controls. The primary outcome was hospital length of stay. Secondary outcomes were duration of O2 supplementation, rates of pediatric intensive care unit transfer, and readmission. Results. Groups were not significantly different in age, gender, and rates of respiratory distress score assessment. Significantly more severely ill patients were in the O2 protocol group. There were no significant differences between control and O2 protocol groups with regard to mean LOS, rates of pediatric intensive care unit transfer, or seven-day readmission rates. By multiple regression analysis, the use of the O2 protocol was associated with a nearly 20% significant decrease in the length of hospitalization (p=0.030). Conclusion. Use of O2 supplementation protocol increased LOS in the more ill patients with bronchiolitis but decreased overall LOS by having a profound effect on patients with mild bronchiolitis