Age-Related Prevalence of Open Ductus Arteriosus in Full-Term Newborns

BACKGROUND: The ductus arteriosus is part of the fetal circulation. Normally, the vessel closes during the cardiac transition. Delayed closure is associated with complications. The aim of this study was to evaluate the age-related prevalence of open ductus arteriosus in full-term neonates.METHODS: Echocardiograms were collected in the population study, the Copenhagen Baby Heart Study. The present study included full-term neonates with an echocardiogram performed within 28 days after birth. All echocardiograms were reviewed to assess ductus arteriosus patency.RESULTS: A total of 21,649 neonates were included. In neonates examined at day zero and day seven, an open ductus arteriosus was found in 36% and 0.6%, respectively. Beyond day seven, the prevalence remained stable at 0.6%.CONCLUSION: More than one-third of full-term neonates had an open ductus arteriosus on the first day of life, declining rapidly within the first week and stabilizing below 1% after day seven.</p

Maternal autoimmune systemic connective tissue disease and vasculitis and electrocardiographic findings in the offspring

Introduction: Maternal autoimmune systemic connective tissue diseases (CTDs) and their related antibodies have been associated with adverse fetal outcomes, including complete heart block. In this study, we assessed the association between maternal CTD or vasculitis and neonatal electrocardiographic (ECG) parameters. Methods: Our study population was drawn from the Copenhagen Baby Heart Study (CBHS), a prospective, population-based cohort study open to all neonates born in the Copenhagen area. All CBHS neonates born to mothers with CTD or vasculitis were matched 1:3 to neonates born to mothers without these diseases on sex, gestational age, age and weight at time of examination, and maternal age at delivery. Maternal CTD and vasculitis diagnoses were validated through medical record review. Our primary analyses compared ECG parameters for exposed and unexposed neonates overall. Where numbers allowed, subanalyses were then conducted by specific CTD diagnoses and autoantibody types. Results: Among 17,862 CBHS neonates with an available ECG, 40 neonates of mothers with CTDs or vasculitis (50 % males, median age 12 [interquartile range 8–16] days) were matched to unexposed neonates. Overall, no significant differences in heart rate, PR interval, QRS axis, QRS duration, QT/QTc interval, or R- or S-wave amplitudes were found when comparing exposed and unexposed neonates (all p &gt; 0.05). Similarly, separate analyses of the 10 neonates with anti-Ro/SSA-positive mothers and their matched comparators revealed no significant between-group differences. However, neonates born to mothers with antiphospholipid syndrome (n = 15) had a significantly longer QRS duration (median 56 ms vs. 52 ms, p = 0.02) and corrected QT interval (median QTcBaz 430 ms vs. 414 ms, p = 0.01), compared with matched unexposed neonates. Conclusion: In this population-based study, no significant overall differences in ECG parameters were found between neonates exposed to maternal CTD or vasculitis and unexposed neonates. However, neonates exposed to maternal antiphospholipid syndrome had significantly longer QRS- and QTc intervals than unexposed neonates. The potential clinical implications of these findings are unknown and, combined with the limitations of this study, warrant further investigation in larger cohorts.</p

Cholesterol not particle concentration mediates the atherogenic risk conferred by apolipoprotein B particles: a Mendelian randomization analysis

Background and aims The causal contribution of apolipoprotein B (apoB) particles to coronary artery disease (CAD) is established. We examined whether this atherogenic contribution is better reflected by non-high-density lipoprotein cholesterol (non-HDL-C) or apoB particle concentration. Method and results We performed Mendelian randomization (MR) analysis using 235 variants as genetic instruments; testing the relationship between their effects on the exposures, non-HDL-C and apoB, and on the outcome CAD using weighted regression. Variant effect estimates on the exposures came from the UK Biobank (N = 376 336) and on the outcome from a meta-analysis of five CAD datasets (187 451 cases and 793 315 controls). Subsequently, we carried out sensitivity and replication analyses. In univariate MR analysis, both exposures associated with CAD (beta(non-HDL-C) = 0.40, P = 2.8 x 10(-48) and beta(apoB) = 0.38, P = 1.3 x 10(-44)). Adding effects on non-HDL-C into a model that already included those on apoB significantly improved the genetically predicted CAD effects (P = 3.9 x 10(-5)), while adding apoB into the model including non-HDL-C did not (P = 0.69). Thirty-five per cent (82/235) of the variants used as genetic instruments had discordant effects on the exposures, associating with non-HDL-C/apoB ratio at P &lt; 2.1 x 10(-4) (0.05/235). Fifty-one variants associated at genome-wide significance. Conclusion Many sequence variants have discordant effects on non-HDL-C and apoB. These variants allowed us to show that the causal mechanism underlying the relationship between apolipoprotein B particles and CAD is more associated with non-HDL-C than apoB particle concentration.Background The causal contribution of apolipoprotein B (apoB) particles to coronary artery disease (CAD) is established. We exam- and aims ined whether this atherogenic contribution is better reflected by non-high-density lipoprotein cholesterol (non-HDL-C) or apoB particle concentration. Method We performed Mendelian randomization (MR) analysis using 235 variants as genetic instruments; testing the relationship be- and results tween their effects on the exposures, non-HDL-C and apoB, and on the outcome CAD using weighted regression. Variant effect estimates on the exposures came from the UK Biobank (N= 376 336) and on the outcome from a meta-analysis of five CAD datasets (187 451 cases and 793 315 controls). Subsequently, we carried out sensitivity and replication analyses. In univariate MR analysis, both exposures associated with CAD (β non-HDL-C = 0.40, P= 2.8 × 10 −48 and β apoB = 0.38, P= 1.3 × 10 −44). Adding effects on non-HDL-C into a model that already included those on apoB significantly improved the genetically predicted CAD effects (P= 3.9 × 10 −5), while adding apoB into the model including non-HDL-C did not (P= 0.69). Thirty-five per cent (82/235) of the variants used as genetic instruments had discordant effects on the exposures, associating with non-HDL-C/apoB ratio at P&lt; 2.1 × 10 −4 (0.05/235). Fifty-one variants associated at genome-wide significance. Conclusion Many sequence variants have discordant effects on non-HDL-C and apoB. These variants allowed us to show that the causal mechanism underlying the relationship between apolipoprotein B particles and CAD is more associated with non-HDL-C than apoB particle concentration.</p

Genome-wide association analysis provides insights into the molecular etiology of dilated cardiomyopathy

Dilated cardiomyopathy (DCM) is a leading cause of heart failure and cardiac transplantation. We report a genome-wide association study and multi-trait analysis of DCM (14,256 cases) and three left ventricular traits (36,203 UK Biobank participants). We identified 80 genomic risk loci and prioritized 62 putative effector genes, including several with rare variant DCM associations (MAP3K7, NEDD4L and SSPN). Using single-nucleus transcriptomics, we identify cellular states, biological pathways, and intracellular communications that drive pathogenesis. We demonstrate that polygenic scores predict DCM in the general population and modify penetrance in carriers of rare DCM variants. Our findings may inform the design of genetic testing strategies that incorporate polygenic background. They also provide insights into the molecular etiology of DCM that may facilitate the development of targeted therapeutics

Genome-wide association study meta-analysis provides insights into the etiology of heart failure and its subtypes

Heart failure (HF) is a major contributor to global morbidity and mortality. While distinct clinical subtypes, defined by etiology and left ventricular ejection fraction, are well recognized, their genetic determinants remain inadequately understood. In this study, we report a genome-wide association study of HF and its subtypes in a sample of 1.9 million individuals. A total of 153,174 individuals had HF, of whom 44,012 had a nonischemic etiology (ni-HF). A subset of patients with ni-HF were stratified based on left ventricular systolic function, where data were available, identifying 5,406 individuals with reduced ejection fraction and 3,841 with preserved ejection fraction. We identify 66 genetic loci associated with HF and its subtypes, 37 of which have not previously been reported. Using functionally informed gene prioritization methods, we predict effector genes for each identified locus, and map these to etiologic disease clusters through phenome-wide association analysis, network analysis and colocalization. Through heritability enrichment analysis, we highlight the role of extracardiac tissues in disease etiology. We then examine the differential associations of upstream risk factors with HF subtypes using Mendelian randomization. These findings extend our understanding of the mechanisms underlying HF etiology and may inform future approaches to prevention and treatment

Genome-wide association analysis provides insights into the molecular etiology of dilated cardiomyopathy

Dilated cardiomyopathy (DCM) is a leading cause of heart failure and cardiac transplantation. We report a genome-wide association study and multi-trait analysis of DCM (14,256 cases) and three left ventricular traits (36,203 UK Biobank participants). We identified 80 genomic risk loci and prioritized 62 putative effector genes, including several with rare variant DCM associations (MAP3K7, NEDD4L and SSPN). Using single-nucleus transcriptomics, we identify cellular states, biological pathways, and intracellular communications that drive pathogenesis. We demonstrate that polygenic scores predict DCM in the general population and modify penetrance in carriers of rare DCM variants. Our findings may inform the design of genetic testing strategies that incorporate polygenic background. They also provide insights into the molecular etiology of DCM that may facilitate the development of targeted therapeutics.</p

Genome-wide association study meta-analysis provides insights into the etiology of heart failure and its subtypes

Heart failure (HF) is a major contributor to global morbidity and mortality. While distinct clinical subtypes, defined by etiology and left ventricular ejection fraction, are well recognized, their genetic determinants remain inadequately understood. In this study, we report a genome-wide association study of HF and its subtypes in a sample of 1.9 million individuals. A total of 153,174 individuals had HF, of whom 44,012 had a nonischemic etiology (ni-HF). A subset of patients with ni-HF were stratified based on left ventricular systolic function, where data were available, identifying 5,406 individuals with reduced ejection fraction and 3,841 with preserved ejection fraction. We identify 66 genetic loci associated with HF and its subtypes, 37 of which have not previously been reported. Using functionally informed gene prioritization methods, we predict effector genes for each identified locus, and map these to etiologic disease clusters through phenome-wide association analysis, network analysis and colocalization. Through heritability enrichment analysis, we highlight the role of extracardiac tissues in disease etiology. We then examine the differential associations of upstream risk factors with HF subtypes using Mendelian randomization. These findings extend our understanding of the mechanisms underlying HF etiology and may inform future approaches to prevention and treatment.</p

Genome-wide association analysis provides insights into the molecular etiology of dilated cardiomyopathy

Dilated cardiomyopathy (DCM) is a leading cause of heart failure and cardiac transplantation. We report a genome-wide association study and multi-trait analysis of DCM (14,256 cases) and three left ventricular traits (36,203 UK Biobank participants). We identified 80 genomic risk loci and prioritized 62 putative effector genes, including several with rare variant DCM associations (MAP3K7, NEDD4L and SSPN). Using single-nucleus transcriptomics, we identify cellular states, biological pathways, and intracellular communications that drive pathogenesis. We demonstrate that polygenic scores predict DCM in the general population and modify penetrance in carriers of rare DCM variants. Our findings may inform the design of genetic testing strategies that incorporate polygenic background. They also provide insights into the molecular etiology of DCM that may facilitate the development of targeted therapeutics

Genome-wide association analysis provides insights into the molecular etiology of dilated cardiomyopathy

Dilated cardiomyopathy (DCM) is a leading cause of heart failure and cardiac transplantation. We report a genome-wide association study and multi-trait analysis of DCM (14,256 cases) and three left ventricular traits (36,203 UK Biobank participants). We identified 80 genomic risk loci and prioritized 62 putative effector genes, including several with rare variant DCM associations (MAP3K7, NEDD4L and SSPN). Using single-nucleus transcriptomics, we identify cellular states, biological pathways, and intracellular communications that drive pathogenesis. We demonstrate that polygenic scores predict DCM in the general population and modify penetrance in carriers of rare DCM variants. Our findings may inform the design of genetic testing strategies that incorporate polygenic background. They also provide insights into the molecular etiology of DCM that may facilitate the development of targeted therapeutics.</p