Laura J. Collins

Cardioversion of Nonrheumatic Atrial Fibrillation: Reduced Thromboembolic Complications With 4 Weeks of Precardioversion Anticoagulation Are Related to Atrial Thrombus Resolution

BACKGROUND The use of warfarin anticoagulation for several weeks before cardioversion results in a 90% reduction in the incidence of cardioversion-related thromboembolism. The mechanism of this benefit, however, is unknown; it has been widely attributed to organization and adherence of atrial thrombi, a finding observed among pathological studies of patients with rheumatic valvular disease. METHODS AND RESULTS Serial transesophageal echocardiography was performed in 14 patients with nonrheumatic atrial fibrillation after identification of atrial thrombi on initial transesophageal study. All patients received warfarin anticoagulation and were followed clinically for signs of thromboembolism. Eighteen atrial thrombi were identified on initial transesophageal study, including 14 thrombi confined to the left atrial appendage, 2 in the body of the left atrium, 1 in the right atrial appendage, and 1 in the body of the right atrium. Thrombus size varied from 5 to 20 mm, and 6 were considered mobile. After a median of 4 weeks of warfarin, 16 of 18 atrial thrombi (89%; 95% CI, 73% to 100%) had completely resolved on transesophageal echocardiographic study. In addition, no new thrombi were identified on follow-up study, and no patient had a clinical thromboembolic event between studies. CONCLUSIONS These data strongly support the hypothesis that among patients with nonrheumatic atrial fibrillation, the mechanism of clinical benefit with 3 to 4 weeks of warfarin before cardioversion is related to thrombus resolution and prevention of new thrombus formation rather than thrombus organization.

Adiponectin gene ADIPOQ SNP associations with serum adiponectin in two female populations and effects of SNPs on promoter activity

AbstractAdiponectin is an insulin sensitiser in muscle and liver, and low serum levels characterise obesity and insulin resistance. Eight tagging single nucleotide polymorphisms (tSNPs) in the ADIPOQ gene and promoter were selected, and association with serum adiponectin was tested, in two independent samples of Caucasian women: the Chingford Study (n = 808, mean age 62.8 ± 5.9 years) and Twins UK (n = 2,718, mean age 47.4 ± 12.6 years). In the Chingford cohort, −11391 G/A, −10066 G/A (rs182052), −7734 C/A (rs16861209), +276 G/T (rs1501299) and +3228 C/T (rs1063537) were significantly associated with fasting serum adiponectin (Ps = 1.00 × 10−4 to 1.40 × 10−2). Associations with all except +3228 C/T were replicated in the Twins UK cohort (Ps = 3.19 × 10−9 to 6.00 × 10−3). In Chingford subjects, the 12 most common 8-SNP haplotypes (frequency 1.90%) explained 2.85% (p = 5.00 × 10−2) and in Twins UK subjects, the four most common 5-SNP haplotypes (frequency > 5.00%) explained 1.66% of the variance (p = 5.83 × 10−7). To investigate effects of −11391 G/A (rs17300539) and −11377 C/G (rs266729) on promoter activity, 1.2 kb of the ADIPOQ promoter region was cloned in a luciferase reporter plasmid, and the four haplotypes were transfected in differentiated 3T3-L1 adipocytes. No significant allelic effects on promoter activity were found.

CD36 Gene Promoter Polymorphisms Are Associated With Low Density Lipoprotein-Cholesterol in Normal Twins and After a Low-Calorie Diet in Obese Subjects

Common polymorphisms of the CD36 fatty acid transporter gene have been associated with lipid metabolism and cardiovascular disease. Association of a CD36 promoter single nucleotide polymorphism genotype with anthropometry and serum lipids was investigated in normal subjects, and in obese subjects during an 8-week low calorie diet and 6-month weight-maintenance period. 2728 normal female Twins UK subjects (mean body mass index 24.8 +/- 4.4 kg/m2; age 47.3 +/- 12.5 y) and 183 obese male and female Spanish subjects (mean body mass index 30.6 +/- 3.0 kg/m2; age 35.0 +/- 5.0 y) were genotyped for the CD36-22674 T/C (rs2151916) promoter single nucleotide polymorphism. In the Twins UK full cohort, the C-allele was associated with lower low density lipoprotein-cholesterol (p = .02, N = 2396). No associations were found in the obese Spanish subjects at baseline, but 6 months after the end of the low-calorie diet, the C-allele was associated with lower total- (p = .03) and low density lipoprotein-cholesterol (p = .01) and higher high density lipoprotein-cholesterol (p = .01). Intake of saturated fatty acids was lower in carriers of the C-allele at baseline, but not significantly so (p = .11). However, 6 months after the end of the low-calorie diet, elements of the lipid profile were correlated with saturated fatty acid intake: total cholesterol r = .21, p = .060; low density lipoprotein-cholesterol: r = .25, p = .043; high density lipoprotein-cholesterol: r = -.26, p = .007. CD36 promoter SNP allele -22674C is therefore associated with lower serum low-density lipoprotein-cholesterol in normal female twins and with improved lipid profile during weight loss and maintenance in obese subjects.

Fostering Critical Thinking, Reasoning, and Argumentation Skills through Bioethics Education

Developing a position on a socio-scientific issue and defending it using a well-reasoned justification involves complex cognitive skills that are challenging to both teach and assess. Our work centers on instructional strategies for fostering critical thinking skills in high school students using bioethical case studies, decision-making frameworks, and structured analysis tools to scaffold student argumentation. In this study, we examined the effects of our teacher professional development and curricular materials on the ability of high school students to analyze a bioethical case study and develop a strong position. We focused on student ability to identify an ethical question, consider stakeholders and their values, incorporate relevant scientific facts and content, address ethical principles, and consider the strengths and weaknesses of alternate solutions. 431 students and 12 teachers participated in a research study using teacher cohorts for comparison purposes. The first cohort received professional development and used the curriculum with their students; the second did not receive professional development until after their participation in the study and did not use the curriculum. In order to assess the acquisition of higher-order justification skills, students were asked to analyze a case study and develop a well-reasoned written position. We evaluated statements using a scoring rubric and found highly significant differences (p<0.001) between students exposed to the curriculum strategies and those who were not. Students also showed highly significant gains (p<0.001) in self-reported interest in science content, ability to analyze socio-scientific issues, awareness of ethical issues, ability to listen to and discuss viewpoints different from their own, and understanding of the relationship between science and society. Our results demonstrate that incorporating ethical dilemmas into the classroom is one strategy for increasing student motivation and engagement with science content, while promoting reasoning and justification skills that help prepare an informed citizenry.

Association of Common JAK2 Variants With Body Fat, Insulin Sensitivity and Lipid Profile

The leptin signal is transduced via the JAK2‐STAT3 (Janus kinase 2‐signal transducer and activator of transcription‐3) pathway at the leptin receptor. JAK2 also phosphorylates insulin receptor substrate, integral to insulin and leptin action and is required for optimum adenosine triphosphate–binding cassette transporter A1 (ABCA1)‐dependent transport of lipids from cells to apolipoprotein A‐1 (apoA‐I). We hypothesized that common variation in the JAK2 gene may be associated with body fat, insulin sensitivity, and modulation of the serum lipid profile in the general population. Ten tagging single‐nucleotide polymorphisms (SNPs) spanning the gene were genotyped in 2,760 white female twin subjects (mean age 47.3 ± 12.6 years) from the St Thomas’ UK Adult Twin Registry. Minor allele frequencies were between 0.170 and 0.464. The major allele of rs7849191 was associated with higher central fat (P = 0.030), percentage of central fat (P = 0.014) and waist circumference (P = 0.027) the major allele of rs3780378 with higher serum apoA (P = 0.026), total cholesterol (P = 0.014), low‐density lipoprotein (LDL) cholesterol (P = 0.012) and lower triglyceride (P = 0.023). However, no associations were significant at a level which took account of multiple testing. Although JAK2 is a critical element in leptin and insulin signaling and has a role in cellular cholesterol transport, we failed to establish associations of common SNPs with relevant phenotypes in this human study.

Ranolazine for the treatment of refractory angina in a veterans population.

BACKGROUND Pivotal ranolazine trials did not require optimization of conventional medical therapy including coronary revascularization and antianginal drug therapy prior to ranolazine use. This case series describes the use of ranolazine for the treatment of chronic stable angina refractory to maximal medical treatment in a veterans population. RESULTS A total of 18 patients with a median age of 66 years were identified. All patients had prior percutaneous coronary intervention and/or coronary artery bypass graft surgery; 83% had three-vessel coronary artery disease, with left main disease present in 39% of patients. Prior to initiating ranolazine, antianginal use consisted of beta blockers (94%), long-acting nitrates (83%) and calcium channel blockers (61%). Median blood pressure (116.2/61.8 mmHg) and pulse (65 beats per min) were controlled. Median preranolazine angina episodes and sublingual nitroglycerin (SLNTG) doses per week were 14 and 10, respectively, with a Canadian Cardiovascular Society (CCS) angina grade of III-IV in 67% of patients. After initiation of ranolazine, median angina episodes per week and SLNTG doses used per week decreased to 0.7 and 0, respectively, with CCS grade of III-IV declining to 17%. Of the 18 subjects enrolled, 44% had complete resolution of angina episodes. CONCLUSION The addition of ranolazine to maximally tolerated conventional antianginal drug therapy post coronary revascularization was associated with decreases in angina episodes and SLNTG utilization and improvement in CCS angina grades. Ranolazine may provide an effective treatment option for revascularized patients with refractory angina.

Mechanical valve dysfunction after percutaneous perimitral leak closure: salvage by percutaneous occluder retrieval.

Percutaneous closure of perivalvular regurgitation may be complicated by prosthetic valve impingement and dysfunction. We describe a patient with two perimitral defects who developed severe mitral stenosis due to mitral leaflet impingement after percutaneous implantation of three amplatzer muscular ventricular septal defect occluder devices. The largest amplatzer occluder device was successfully snared with restoration of normal prosthetic valve motion.

Common STAT3 Variants Are Not Associated With Obesity or Insulin Resistance in Female Twins

In animal models, STAT3 action in the hypothalamus and liver appears essential for normal body weight and glucose homeostasis in response to insulin. We hypothesized that variation in the STAT3 gene may be associated with body fat and/or insulin resistance in the general population. Five tagging SNPs spanning the STAT3 gene, rs8074524, rs2293152, rs2306580, rs6503695, and rs7211777 were genotyped in 2776 white female twins (mean age, 47.4 ± 12.5 yrs) from the St Thomas’ United Kingdom Adult Twin Registry (Twins UK). Minor allele frequencies were as follows: rs8074524 (0.19), rs2293152 (0.37), rs2306580 (0.06), rs6503695 (0.35), and rs7211777 (0.34). The minor allele of rs2293152 was associated with higher homeostasis model assessment index of insulin resistance (p = 0.013) in the full cohort and confirmed in sib‐transmission/disequilibrium test (TDT): (p = 0.015; n = 60). However, there were no associations with fasting serum insulin or glucose or with obesity variables. Although defective STAT3 action results in obesity and insulin resistance in animal models, we failed to establish any indicative associations with common SNPs in this human study.

Outcomes after atrioventricular node ablation and biventricular pacing in patients with refractory atrial fibrillation and heart failure: a comparison between non-ischaemic and ischaemic cardiomyopathy.

AIMS Atrioventricular junction ablation (AVJA) combined with biventricular (BiV) pacing (AVJA/BiV) is an effective treatment for refractory atrial fibrillation (AF) and rapid ventricular response (RVR) associated with heart failure (HF). This study compared the outcomes between patients with non-ischaemic (DCM) and ischaemic cardiomyopathy (ICM) following AVJA/BiV for AF/RVR. METHODS AND RESULTS This was a retrospective study of 45 patients, comparing the response to AVJA/BiV in patients with ICM to those with DCM. The study compared (a) the change in echocardiographic parameters of HF (ejection fraction (EF) and left ventricular dimensions) prior to, and at least 6 months post AVJA/BiV; and (b) HF hospitalizations (HFH) and appropriate implantable cardioverter defibrillator (ICD) therapies occurring post-procedure. Ejection fraction improved significantly in the DCM group (ΔEF 11.2% ± 11.9; P< 0.01); however, EF remained unchanged (ΔEF 0.5% ± 9.9; P = NS) in the ICM group post-AVJA/BiV. Post-procedurely, HFH were significantly more common (15/18 vs. 4/25; P < 0.0001), and there were significantly more appropriate ICD therapies (9.4 ± 12.3 vs. 2.3 ± 6.1; P = 0.01) in the ICM compared with the DCM group. CONCLUSION After AVJA/BiV, there was significantly less post-procedural echocardiographic reverse remodelling, and more HFH in the ICM compared with the DCM group. In addition, significantly more appropriate ICD therapies occurred in ICM patients post-procedure. These differences may be due to the presence of more extensive discrete myocardial scar in patients with ICM. Furthermore, it is possible that tachycardia-induced cardiomyopathy plays more of a causative role in HF in patients with AF and DCM than those with ICM.

The Predictors of Diet Quality among Australian Children Aged 3.5 Years

BACKGROUND It is critical to promote healthy eating early in life. OBJECTIVE The aim of this study was to examine diet quality and its predictors among Australian preschool-aged children. DESIGN Diet was assessed at age 3.5 years using multiple 24-hour recalls. Diet quality was assessed using an adapted version of the Revised Childrens Diet Quality Index (RC-DQI). Potential predictors of diet quality were from questionnaires at age 3, 9, and 18 months and informed by the ecologic model of childhood overweight. Potential predictors included childs sex, age of introduction to solid foods, breastfeeding status, food acceptance, maternal nutrition knowledge, modeling of healthy eating, self-efficacy, education, and home food availability. PARTICIPANTS Data from 244 children participating in the Melbourne Infant Feeding, Activity, and Nutrition Trial in 2008-2010 and follow-up data collection in 2011-2013 were examined. MAIN OUTCOME MEASURES Diet quality at age 3.5 years. STATISTICAL ANALYSES PERFORMED Bivariate logistic regression was performed to assess the relationship between diet quality and each predictor. A multivariable logistic regression model accounting for influences of covariates, treatment arm, and clustering by group tested associations between diet quality and significant predictors from bivariate analyses. RESULTS RC-DQI scores had a mean±standard deviation score of 62.8±8.3 points out of a maximum of 85 points. Breastfeeding status (odds ratio [OR] 2.34, 95% CI 1.33 to 4.10) and maternal modeling of healthy eating (OR 1.75, 95% CI 1.01 to 3.03) were positively associated with RC-DQI scores. Both breastfeeding status (OR 3.09, 95% CI 1.63 to 5.85) and modeling (OR 2.01, 95% CI 1.04 to 3.88) remained positively associated with diet quality after adjustment for child age, body mass index z score, energy intake, treatment arm, and clustering. CONCLUSIONS Breastfeeding status and modeling of healthy eating were independently associated with childrens diet quality. Early intervention could assist mothers to practice these behaviors to provide support for improving child diet quality.