Summary Background Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear. Methods We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10 195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106 353 patients with established coronary heart disease and 19 332 deaths in 22 studies or cohorts. Findings The median follow-up was 9·9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio [HR] 1·44, 95% CI 1·14–1·83) and the presence of either LPA SNP (1·88, 1·40–2·53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0·95, 0·81–1·11 and either LPA SNP 1·10, 0·92–1·31) or cardiovascular mortality (0·99, 0·81–1·2 and 1·13, 0·90–1·40, respectively) or in the validation studies. Interpretation In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and genetic variants showed no associations with mortality. We conclude that these variables are not useful risk factors to measure to predict progression to death after coronary heart disease is established. Funding Seventh Framework Programme for Research and Technical Development (AtheroRemo and RiskyCAD), INTERREG IV Oberrhein Programme, Deutsche Nierenstiftung, Else-Kroener Fresenius Foundation, Deutsche Stiftung für Herzforschung, Deutsche Forschungsgemeinschaft, Saarland University, German Federal Ministry of Education and Research, Willy Robert Pitzer Foundation, and Waldburg-Zeil Clinics Isny.
The clinical utility of routine electroencephalography (EEG) after a first unprovoked seizure remains uncertain. Its diagnostic accuracy in identifying adults and children with new onset epilepsy was examined. A systematic review and meta-analysis of studies examining individuals who underwent routine EEG after a first unprovoked seizure and were followed for seizure recurrence for at least 1 year was performed. A 'positive' test was defined by the presence of epileptiform discharges (ED). Pooled sensitivity and specificity estimates were calculated using a bivariate random effects regression model. In all, 3096 records were reviewed, from which 15 studies were extracted with a total of 1799 participants. Amongst adult studies, the sensitivity and specificity (95% confidence interval) of routine EEG were 17.3% (7.9, 33.8) and 94.7% (73.7, 99.1), respectively. Amongst child studies, the pooled sensitivity and specificity were 57.8% (49.7, 65.6) and 69.6% (57.5, 79.5), respectively. Based upon our positive likelihood ratios, and assuming a pre-test probability of 50%, an adult with ED on routine EEG after a first unprovoked seizure has a 77% probability of having a second seizure, whilst a child with similar findings has a 66% probability. Further studies are required to examine the impact of patient characteristics and EEG features on the diagnostic accuracy of routine EEG for new onset epilepsy.
ObjectiveOur goal was to perform a systematic review of the literature to demonstrate the prevalence of cardiac abnormalities identified using cardiac investigations in patients with mitochondrial myopathy (MM).MethodsThis systematic review surveys the available evidence for cardiac investigations in MM from a total of 21 studies including 825 participants. Data were stratified by genetic mutation and clinical syndrome.ResultsWe identified echocardiogram and ECG as the principal screening modalities that identify cardiac structural (29%) and conduction abnormalities (39%) in various MM syndromes. ECG abnormalities were more prevalent in patients with m.3243A>G mutations than other gene defects, and patients with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) had a higher prevalence of ECG abnormalities than patients with other clinical syndromes. Echocardiogram abnormalities were significantly more prevalent in patients with m.3243A>G or m.8344A>G mutations compared with other genetic mutations. Similarly, MELAS and MERRF had a higher prevalence compared with other syndromes. We observed a descriptive finding of an increased prevalence of ECG abnormalities in pediatric patients compared with adults.ConclusionsThis analysis supports the presence of a more severe cardiac phenotype in MELAS and myoclonic epilepsy with ragged red fibres syndromes and with their commonly associated genetic mutations (m.3243A>G and m.8344A>G). This provides the first evidence basis on which to provide more intensive cardiac screening for patients with certain clinical syndromes and genetic mutations. However, the data are based on a small number of studies. We recommend further studies of natural history, therapeutic response, pediatric participants, and cardiac MRI as areas for future investigation.
Aims Bipolar electrogram (Bi EGM )-based substrate maps are heavily influenced by direction of a wavefront to the mapping bipole. In this study, we evaluate high-resolution, orientation-independent peak-to-peak voltage (Vpp) maps obtained with an equi-spaced electrode array and omnipolar EGMs (OT EGMs ), measure its beat-to-beat consistency, and assess its ability to delineate diseased areas within the myocardium compared against traditional Bi EGMs on two orientations: along (AL) and across (AC) array splines. Methods and results The endocardium of the left ventricle of 10 pigs (three healthy and seven infarcted) were each mapped using an Advisor™ HD grid with a research EnSite Precision™ system. Cardiac magnetic resonance images with late gadolinium enhancement were registered with electroanatomical maps and were used for gross scar delineation. Over healthy areas, OT EGM Vpp values are larger than AL bipoles by 27% and AC bipoles by 26%, and over infarcted areas OT EGM Vpp values are 23% larger than AL bipoles and 27% larger than AC bipoles ( P < 0.05). Omnipolar EGM voltage maps were 37% denser than Bi EGM maps. In addition, OT EGM Vpp values are more consistent than bipolar Vpps showing less beat-by-beat variation than Bi EGM by 39% and 47% over both infarcted and healthy areas, respectively ( P < 0.01). Omnipolar EGM better delineate infarcted areas than traditional Bi EGMs from both orientations. Conclusion An equi-spaced electrode grid when combined with omnipolar methodology yielded the largest detectable bipolar-like voltage and is void of directional influences, providing reliable voltage assessment within infarcted and non-infarcted regions of the heart.
Background Limited evidence exists regarding the utility of genetic risk scores (GRS) in predicting recurrent cardiovascular events after acute coronary syndrome (ACS). We sought to determine whether a GRS would predict early recurrent cardiovascular events within 1 year of ACS. Methods & Results Participants admitted with acute coronary syndromes from the RISCA, PRAXY, and TRIUMPH cohorts, were genotyped for 30 single nucleotide polymorphisms (SNPs) associated with coronary artery disease (CAD) or myocardial infarction (MI) in prior genome wide association studies. A 30 SNP CAD/MI GRS was constructed. The primary endpoint was defined as all-cause mortality, recurrent ACS or cardiac re-hospitalization within 1 year of ACS admission. Results across all cohorts for the 30 SNP CAD/MI GRS were pooled using a random-effects model. There were 1040 patients from the RISCA cohort, 691 patients from the PRAXY cohort, and 1772 patients from the TRIUMPH cohort included in the analysis and 389 occurrences of the primary endpoint of recurrent events at 1-year post-ACS. In unadjusted and fully adjusted analyses, a 30 SNP GRS was not significantly associated with recurrent events (HR per allele 0.97 (95%CI 0.91–1.03) for RISCA, HR 0.99 (95%CI 0.93–1.05) for PRAXY, 0.98 (95%CI 0.94–1.02) for TRIUMPH, and 0.98 (95%CI 0.95–1.01) for the pooled analysis). Addition of this GRS to the GRACE risk model did not significantly improve risk prediction. Conclusion The 30 MI SNP GRS was not associated with recurrent events 1-year post ACS in pooled analyses across cohorts and did not improve risk discrimination or reclassification indices. Our results suggest that the genetic etiology of early events post-ACS may differ from later events.
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