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BACKGROUND: Patients with ≥2 ventricular arrhythmia (VA) events within 3 months (clustered VA) have increased risk for mortality. OBJECTIVES: The aim of this study was to examine the association of risk factors including scar characteristics on cardiovascular magnetic resonance imaging with clustered VA and VA cycle length in nonischemic cardiomyopathy (NICM) and ischemic cardiomyopathy (ICM). METHODS: Data from 329 primary prevention implantable cardioverter-defibrillator recipients (mean age 57 years, 26% women) were analyzed from the Left Ventricular Structural Predictors of Sudden Cardiac Death study. RESULTS: Twenty-one patients developed clustered VA (median time 2.7 years after implantable cardioverter-defibrillator placement). Men had the greatest risk for recurrent VA. Patients with NICM and scar had the highest incidence rate of clustered VA. In patients with NICM, each 1-g increase in core scar correlated with greater clustered VA risk (HR: 1.19; 95% CI: 1.07–1.32). Gray scar was similar among subgroups. Patients with NICM with clustered VA had the longest mean VA cycle length (297 ± 40 milliseconds). Higher core scar burden correlated with longer VA cycle length in patients with NICM (P = 0.002), and higher body mass index correlated with shorter VA cycle length in those with ICM (P = 0.02). Type of VA was similar between cardiomyopathy subgroups, and no scar pattern predominated. CONCLUSIONS: Clustered VA was most common in patients with NICM and scar, with greatest risk among those with larger core scar. Core scar correlated with slower VA in patients with NICM, and higher body mass index correlated with faster VA in those with ICM. Type of VA was similar by cardiomyopathy etiology, and no dominant scar pattern was associated with clustered VA. (J Am Coll Cardiol EP 2022;8:957–966) © 2022 by the American College of Cardiology Foundation.

A healthy 41-year-old man sustained cardiac arrest secondary to ventricular fibrillation. An extensive ischemic, structural, and genetic evaluation did not identify an attributable pathologic condition. Electrocardiograms were notable for early repolarization pattern. Here we review the diagnosis, prevalence, and prognostic significance of the early repolarization syndrome on sudden cardiac death. (Level of Difficulty: Intermediate.), Central Illustration

Introduction Five decades ago, Fredrickson, Levy, and Lees (FLL) qualitatively characterized clinical dyslipidemias with specific implications for cardiovascular and non-cardiovascular morbidity and mortality. They separated disorders of elevated cholesterol and triglycerides into five phenotypes (types I–V) based on their lipoprotein profile. Although clinicians generally consider them rare entities, modern FLL prevalence may be greater than previously reported. Material and methods We performed a cross-sectional analysis in 5,272 participants from the 2011–2014 National Health and Nutrition Examination Survey and 128,506 participants from the Very Large Database of Lipids study with complete, fasting lipid profiles. We used a validated algorithm to define FLL phenotypes employing apolipoprotein B, total cholesterol, and triglycerides. Results Overall prevalence of FLL phenotypes was 33.9%. FLL prevalence in the general population versus clinical lipid database was: type I (0.05 vs. 0.02%), type IIa (3.2 vs. 3.9%), type IIb (8.0 vs. 10.3%), type III (2.0 vs. 1.7%), type IV (20.5 vs. 24.1%), and type V (0.15 vs. 0.13%). Those aged 40–74 years had a higher overall prevalence compared to other age groups (p < 0.001) and men had overall higher prevalence than women (p < 0.001). Those with diabetes (51.6%) or obese BMI (49.0%) had higher prevalence of FLL phenotypes compared to those without diabetes (31.3%; p < 0.001) and normal BMI (18.3%; p < 0.001). Conclusions FLL phenotypes are likely far more prevalent than appreciated in clinical practice, in part due to diabetes and obesity epidemics. Given the prognostic and therapeutic importance of these phenotypes, their identification becomes increasingly important in the era of precision medicine.

Introduction Dysbetalipoproteinaemia (HLP3) is a disorder characterized by excess cholesterol-enriched, triglyceride-rich lipoprotein remnants in genetically predisposed individuals that powerfully promote premature cardiovascular disease if untreated. The current prevalence of HLP3 is largely unknown. Material and methods We performed cross-sectional analysis of 128,485 U.S. adults from the Very Large Database of Lipids (VLDbL), using four algorithms to diagnose HLP3 employing three Vertical Auto Profile ultracentrifugation (UC) criteria and a previously described apolipoprotein B (apoB) method. We evaluated 4,926 participants from the 2011-2014 National Health and Nutrition Examination Survey (NHANES) with the apoB method. We examined demographic and lipid characteristics stratified by presence of HLP3 and evaluated lipid characteristics in those with HLP3 phenotype discordance and concordance as determined by apoB and originally defined UC criteria 1. Results In U.S. adults in VLDbL and NHANES, a 1.7-2.0% prevalence is observed for HLP3 with the novel apoB method as compared to 0.2-0.8% prevalence in VLDbL via UC criteria 1-3. Participants who were both apoB and UC criteria HLP3 positive had higher remnant particles as well as more elevated triglyceride/apoB and total cholesterol/apoB ratios (all p < 0.001) than those who were apoB method positive and UC criteria 1 negative. Conclusions HLP3 may be more prevalent than historically and clinically appreciated. The apoB method increases HLP3 identification via inclusion of milder phenotypes. Further work should evaluate the clinical implications of HLP3 diagnosis at various lipid algorithm cut-points to evaluate the ideal standard in the modern era.

Summary Self-weighing is an evidence-based weight management strategy, which requires patients to have a home scale. For clinicians to effectively counsel patients on self-weighing, they should be aware of the costs and features available in typical home scales. Our objective was to describe the cost and features of the top bathroom scales available online. We performed content analysis of top 100 scales listed on a popular online retailer. Two coders independently extracted price and scale features (i.e., digital connectivity, body mass index [BMI] calculation, maximum weight accommodated). We used t-tests and ANOVA, as appropriate, to examine the relationships between price and features. Among the 97 scales included, mean scale price was $28.99 (SD $21.06; range $7.20–$139.95). Of the advanced features, 20.6% of scales had digital connectivity and 28.9% calculated BMI. Scales with advanced features cost significantly more than scales without (digital connectivity: $49.18 vs. $23.74, P < 0.001; BMI calculation: $42.92 vs. $23.33, P < 0.001). Most scales (76.2%) had a maximum weight of 351–400 lbs, and only 17.5% could accommodate >400 lbs. Price was higher for scales with a higher maximum weight (P = 0.002). No scale with maximum weight > 500 lbs had advanced features. Scales that have digital connectivity for telemedicine or can accommodate higher weights are less commonly available online and their costs may be prohibitive for some patients who need these features. Future research might consider testing whether insurance coverage for scales improves scale access and patient weight management outcomes.

Objective To characterize weight-loss claims and disclaimers present on websites for commercial weight-loss programs and compare them with results from published randomized controlled trials (RCTs). Methods A content analysis of all home pages and testimonials available on the websites of 24 randomly selected programs was performed. Two team members independently reviewed each page and abstracted information from text and images to capture relevant content, including demographics, weight loss, and disclaimers. A systematic review was performed to evaluate the efficacy of these programs by searching MEDLINE and the Cochrane Database of Systematic Reviews, and the mean weight change from each RCT included was abstracted. Results Overall, the amount of weight loss portrayed in the testimonials was extreme across all programs examined (range median weight loss 10.7-49.5 kg). Only 10 out of the 24 programs had eligible RCTs. Median weight losses reported in testimonials exceeded that achieved by trial participants. Most programs with RCTs (78%) provided disclaimers stating that the testimonial's results were nontypical and/or gave a range of typical weight loss. Conclusions Weight-loss claims within testimonials were higher than results from RCTs. Future studies should examine whether commercial programs' advertising practices influence patients' expectations or satisfaction with modest weight-loss results.

SummaryObjective We examined the glycemic benefits of commercial weight loss programmes as compared with control/education or counselling among overweight and obese adults with and without type 2 diabetes mellitus (T2DM). Methods We searched MEDLINE, Cochrane Database of Systematic Reviews, and references cited by individual programmes. We included randomized controlled trials of ≥12 weeks duration. Two reviewers extracted information on study design, population characteristics, interventions, and mean changes in haemoglobin A1c and glucose. Results We included 18 randomized controlled trials. Few trials occurred among individuals with T2DM. In this population, Jenny Craig reduced A1c at least 0.4% more than counselling at 12 months, Nutrisystem significantly reduced A1c 0.3% more than counselling at 6 months, and OPTIFAST reduced A1c 0.3% more than counselling at 6 months. Among individuals without T2DM, few studies evaluated glycemic outcomes, and when reported, most did not show substantial reductions. Discussion Few trials have examined whether commercial weight loss programmes result in glycemic benefits for their participants, particularly among overweight and obese individuals without T2DM. Jenny Craig, Nutrisystem and OPTIFAST show promising glycemic lowering benefits for patients with T2DM, although additional studies are needed to confirm these conclusions. © 2016 World Obesity

Background: Longitudinal increases in metabolic syndrome (MS) components are associated with increased heart failure (HF) risk, but the association of MS change over time with subclinical myocardial injury is unknown. Hypothesis: Greater progression and duration of MS is associated with subclinical myocardial injury, as reflected by high-sensitivity cardiac troponin T (hs-cTnT). Methods: We studied 8,170 participants (mean age 63, 59% female) without coronary heart disease, HF or diabetes at ARIC Visit 4 (1996-1998) with available data on MS components from the first four ARIC visits and hs-cTnT data at Visit 4. We defined MS using AHA/NHLBI criteria for high waist circumference (WC), hyperglycemia, elevated blood pressure (BP), low HDL-C and hypertriglyceridemia, with a diagnosis of MS made by ≥ 3 components. Using data on MS components from Visit 1 (1987-89) through 4, we used logistic regression models adjusted for demographics and cardiovascular risk factors to evaluate associations of changes in MS components over time and duration of MS with elevated hs-cTnT (≥ 14 ng/L) at Visit 4. Results: 3,644 (45%) of Visit 4 participants had MS. Greater number of MS components at Visit 4 was associated with a higher likelihood of elevated hs-cTnT, with the highest odds seen for those with 5 MS components (OR 2.32; 95%CI: 1.39-3.87) compared to those with none. Among MS components, the strongest associations were seen for elevated BP and high WC. Among participants without MS at V1, those with no MS components at both Visits 1 and 4 had the lowest odds of elevated hs-cTnT (reference), with progressively higher likelihood of elevated hs-cTnT for those increasing to 1-2 (OR 1.12; 95%CI 0.61-2.06), 3 (OR 1.90; 95%CI 1.04-3.45) and 4-5 (OR 2.64; 95%CI 1.41-4.92) MS components by Visit 4. MS duration was also significantly associated with elevated hs-cTnT, with an OR of 1.08 (95%CI: 1.06-1.11) per year of MS duration. Conclusions: Greater MS severity and progression, and longer duration of MS, are associated with a higher likelihood of subclinical myocardial injury. This may have mechanistic implications for the association between MS and HF, and underscores the need to refine strategies to prevent MS onset and progression.

The Friedewald equation for estimation of low-density lipoprotein cholesterol (LDL-C) was published in 1972 as an alternative to direct assessment by preparative ultracentrifugation. In this equation, very low-density lipoprotein is estimated by dividing triglycerides by a fixed factor (5 in mg/dL or 2.2 in mmol/L) and subtracting this term from non-high-density lipoprotein cholesterol (non-HDL-C). This method was derived in fasting samples from a small cohort of patients with primarily genetic dyslipidemias followed at the NIH. The method served well as the global standard for LDL-C estimation for decades, but is not well suited to modern clinical practice because it tends to underestimate LDL-C at low LDL-C and high triglyceride levels. The concern is that underestimation could lead to undertreatment in high-risk patients. Derived from big data and now validated around the world, a novel LDL-C equation created at Johns Hopkins replaces the fixed factor seen in the classic equation with a patient-specific variable based on triglyceride and non-HDL-C levels. Given its superior accuracy in fasting and non-fasting populations alike, the novel equation is now the preferred method for LDL-C estimation and is being incorporated by leading clinical laboratories.

BACKGROUND Commercial and proprietary weight-loss programs are popular obesity treatment options, but their efficacy is unclear. PURPOSE To compare weight loss, adherence, and harms of commercial or proprietary weight-loss programs versus control/education (no intervention, printed materials only, health education curriculum, or

Background As the size of the known human interactome grows, biologists increasingly rely on computational tools to identify patterns that represent protein complexes and pathways. Previous studies have shown that densely connected network components frequently correspond to community structure and functionally related modules. In this work, we present a novel method to identify densely connected and bipartite network modules based on a log odds score for shared neighbours. Results To evaluate the performance of our method (NeMo), we compare it to other widely used tools for community detection including kMetis, MCODE, and spectral clustering. We test these methods on a collection of synthetically constructed networks and the set of MIPS human complexes. We apply our method to the CXC chemokine pathway and find a high scoring functional module of 12 disconnected phospholipase isoforms. Conclusion We present a novel method that combines a unique neighbour-sharing score with hierarchical agglomerative clustering to identify diverse network communities. The approach is unique in that we identify both dense network and dense bipartite network structures in a single approach. Our results suggest that the performance of NeMo is better than or competitive with leading approaches on both real and synthetic datasets. We minimize model complexity and generalization error in the Bayesian spirit by integrating out nuisance parameters. An implementation of our method is freely available for download as a plugin to Cytoscape through our website and through Cytoscape itself.