Narrow QRS complex tachycardia with long RP-interval: what is the mechanism?

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Benefit of a wearable cardioverter defibrillator for detection and therapy of arrhythmias in patients with myocarditis

Aims: Myocarditis may lead to malignant arrhythmias and sudden cardiac death. As of today, there are no reliable predictors to identify individuals at risk for these catastrophic events. The aim of this study was to evaluate if a wearable cardioverter defibrillator (WCD) may detect and treat such arrhythmias adequately in the peracute setting of myocarditis. Methods and results: In this observational, retrospective, single centre study, we reviewed patients presenting to the Charite Hospital from 2009 to 2017, who were provided with a WCD for the diagnosis of myocarditis with reduced ejection fraction (<50%) and/or arrhythmias. Amongst 259 patients receiving a WCD, 59 patients (23%) were diagnosed with myocarditis by histology. The mean age was 46 +/- 14 years, and 11 patients were women (19%). The mean WCD wearing time was 86 +/- 63 days, and the mean daily use was 20 +/- 5 h. During that time, two patients (3%) had episodes of sustained ventricular tachycardia (VT; four total) corresponding to a rate of 28 sustained VT episodes per 100 patient-years. Consequently, one of these patients underwent rhythm stabilization through intravenous amiodarone, while the other patient received an implantable cardioverter defibrillator. Two patients (3.4%) were found to have non-sustained VT. Conclusions: Using a WCD after acute myocarditis led to the detection of sustained VT in 2/59 patients (3%). While a WCD may prevent sudden cardiac death after myocarditis, our data suggest that WCD may have impact on clinical management through monitoring and arrhythmia detection

Assessment of gene-by-sex interaction effect on bone mineral density

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.Sexual dimorphism in various bone phenotypes, including bone mineral density (BMD), is widely observed; however, the extent to which genes explain these sex differences is unclear. To identify variants with different effects by sex, we examined gene-by-sex autosomal interactions genome-wide, and performed expression quantitative trait loci (eQTL) analysis and bioinformatics network analysis. We conducted an autosomal genome-wide meta-analysis of gene-by-sex interaction on lumbar spine (LS) and femoral neck (FN) BMD in 25,353 individuals from 8 cohorts. In a second stage, we followed up the 12 top single-nucleotide polymorphisms (SNPs; p < 1 × 10(-5) ) in an additional set of 24,763 individuals. Gene-by-sex interaction and sex-specific effects were examined in these 12 SNPs. We detected one novel genome-wide significant interaction associated with LS-BMD at the Chr3p26.1-p25.1 locus, near the GRM7 gene (male effect = 0.02 and p = 3.0 × 10(-5) ; female effect = -0.007 and p = 3.3 × 10(-2) ), and 11 suggestive loci associated with either FN- or LS-BMD in discovery cohorts. However, there was no evidence for genome-wide significant (p < 5 × 10(-8) ) gene-by-sex interaction in the joint analysis of discovery and replication cohorts. Despite the large collaborative effort, no genome-wide significant evidence for gene-by-sex interaction was found to influence BMD variation in this screen of autosomal markers. If they exist, gene-by-sex interactions for BMD probably have weak effects, accounting for less than 0.08% of the variation in these traits per implicated SNP. © 2012 American Society for Bone and Mineral Research.Medtronic NIH R01 AG18728 R01HL088119 R01AR046838 U01 HL084756 R01 AR43351 P01-HL45522 R01-MH-078111 R01-MH-083824 Nutrition and Obesity Research Center of Maryland P30DK072488 NIAMS/NIH F32AR059469 Instituto de Salud Carlos III-FIS (Spanish Health Ministry) PI 06/0034 PI08/0183 Canadian Institutes of Health Research (CIHR) NHLBI HHSN268201200036C N01-HC-85239 N01-HC-85079 N01-HC-85086 N01-HC-35129 N01 HC15103 N01 HC-55222 N01-HC-75150 N01-HC-45133 HL080295 HL087652 HL105756 NIA AG-023629 AG-15928 AG-20098 AG-027058 N01AG62101 N01AG62103 N01AG62106 1R01AG032098-01A1 National Center of Advancing Translational Technologies CTSI UL1TR000124 National Institute of Diabetes and Digestive and Kidney Diseases DK063491 EUROSPAN (European Special Populations Research Network) European Commission FP6 STRP grant 018947 LSHG-CT-2006-01947 Netherlands Organisation for Scientific Research Erasmus MC Centre for Medical Systems Biology (CMSB) Netherlands Brain Foundation (HersenStichting Nederland) US National Institute for Arthritis, Musculoskeletal and Skin Diseases National Institute on Aging R01 AR/AG41398 R01 AR050066 R21 AR056405 National Heart, Lung, and Blood Institute's Framingham Heart Study N01-HC-25195 Affymetrix, Inc. N02-HL-6-4278 Canadian Institutes of Health Research from Institute of Aging 165446 Institute of Genetics 179433 Institute of Musculoskeletal health 221765 Intramural Research Program of the NIH, National Institute on Aging National Institutes of Health HHSN268200782096C Hong Kong Research Grant Council HKU 768610M Bone Health Fund of HKU Foundation KC Wong Education Foundation Small Project Funding 201007176237 Matching Grant CRCG Grant Osteoporosis and Endocrine Research Fund Genomics Strategic Research Theme of The University of Hong Kong Netherlands Organisation of Scientific Research NWO Investments 175.010.2005.011 911-03-012 Research Institute for Diseases in the Elderly 014-93-015 Netherlands Genomics Initiative (NGI)/Netherlands Consortium for Healthy Aging (NCHA) 050-060-810 Erasmus Medical Center and Erasmus University, Rotterdam Netherlands Organization for the Health Research and Development (ZonMw) Research Institute for Diseases in the Elderly (RIDE) Ministry of Education, Culture and Science Ministry for Health, Welfare and Sports European Commission (DG XII) Municipality of Rotterdam German Bundesministerium fur Forschung und Technology 01 AK 803 A-H 01 IG 07015

Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci.

Bone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. We used a novel genetic pleiotropy-informed conditional False Discovery Rate (FDR) method to identify single nucleotide polymorphisms (SNPs) associated with BMD by leveraging cardiovascular disease (CVD) associated disorders and metabolic traits. By conditioning on SNPs associated with the CVD-related phenotypes, type 1 diabetes, type 2 diabetes, systolic blood pressure, diastolic blood pressure, high density lipoprotein, low density lipoprotein, triglycerides and waist hip ratio, we identified 65 novel independent BMD loci (26 with femoral neck BMD and 47 with lumbar spine BMD) at conditional FDR < 0.01. Many of the loci were confirmed in genetic expression studies. Genes validated at the mRNA levels were characteristic for the osteoblast/osteocyte lineage, Wnt signaling pathway and bone metabolism. The results provide new insight into genetic mechanisms of variability in BMD, and a better understanding of the genetic underpinnings of clinical comorbidity

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Velocity characteristics of atrial fibrillation sources determined by electrographic flow mapping before and after catheter ablation

Background: Electrographic-Flow-(EGF)-Mapping is a novel method to identify Atrial Fibrillation (AF) drivers. Sources of excitation during AF can be characterized and monitored. Objective: The aim of this study was to evaluate the correlation between velocity of EGF around a respective AF source and its spatial variability (SV) and stability (SST). Methods: 25 patients with AF were included in this study (persistent: n = 24, long-standing persistent: n = 1; mean age 70 +/- 8.3 years, male: n = 17). Focal impulse and Rotor-Mapping (FIRM) was performed in addition to pulmonary vein isolation. One-minute epochs of unipolar electrograms recorded via a 64-pole basket catheter in both atria were re-analyzed with EGF-Mapping. SST was calculated as the percentage of time in which a source was detected. Results: AF sources identified with EGF-Mapping show a wide range of SV during 1 min covering between 0.12% and 38% of the recorded basket-catheter surface. The 12 atria where the sources showed highest temporal stability (TS; between 34% and 97% of 1 min recorded) and those 12 with the lowest TS (between 11 and 20%) differed significantly in their velocities (17.8 el/s vs 12.2 el/s; p < 0.01). In 11 atria ablation caused an average decrease of TS by 47% and of velocity by 27% while SV more than doubled. Conclusion: Less stable AF-sources with high spatial variability showed reduced excitation propagation velocity while stable AF sources displayed a high average velocity in their vicinity. Importantly, catheter ablation reduced stability of sources and velocity suggesting a role of these parameters in guidance of ablation. Condensed abstract: Electrographic Flow(EGF)-Mapping is a novel method to identify Atrial Fibrillation (AF) drivers based on modeling of an electrical potential surface and subsequent flow analysis. Sources of excitation during AF can be characterized and monitored. The aim of this study was to evaluate the correlation between velocity of EGF around a respective AF source and its spatial variability and stability. Less stable AF sources with high spatial variability showed reduced excitation propagation velocity while very stable AF sources displayed a high average velocity in their vicinity. Catheter ablation reduced stability of sources and velocity. Crown Copyright (C) 2019 Published by Elsevier B.V. All rights reserved

Protected risk stratification with the wearable cardioverter-defibrillator: results from the WEARIT-II-EUROPE registry

Background!#!The prospective WEARIT-II-EUROPE registry aimed to assess the value of the wearable cardioverter-defibrillator (WCD) prior to potential ICD implantation in patients with heart failure and reduced ejection fraction considered at risk of sudden arrhythmic death.!##!Methods and results!#!781 patients (77% men; mean age 59.3 ± 13.4 years) with heart failure and reduced left ventricular ejection fraction (LVEF) were consecutively enrolled. All patients received a WCD. Follow-up time for all patients was 12 months. Mean baseline LVEF was 26.9%. Mean WCD wearing time was 75 ± 47.7 days, mean daily WCD use 20.3 ± 4.6 h. WCD shocks terminated 13 VT/VF events in ten patients (1.3%). Two patients died during WCD prescription of non-arrhythmic cause. Mean LVEF increased from 26.9 to 36.3% at the end of WCD prescription (p &amp;lt; 0.01). After WCD use, ICDs were implanted in only 289 patients (37%). Forty patients (5.1%) died during follow-up. Five patients (1.7%) died with ICDs implanted, 33 patients (7%) had no ICD (no information on ICD in two patients). The majority of patients (75%) with the follow-up of 12 months after WCD prescription died from heart failure (15 patients) and non-cardiac death (15 patients). Only three patients (7%) died suddenly. In seven patients, the cause of death remained unknown.!##!Conclusions!#!Mortality after WCD prescription was mainly driven by heart failure and non-cardiovascular death. In patients with HFrEF and a potential risk of sudden arrhythmic death, WCD protected observation of LVEF progression and appraisal of competing risks of potential non-arrhythmic death may enable improved selection for beneficial ICD implantation