Right Ventricular Function After Acute Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention:(from the Glycometabolic Intervention as Adjunct toPrimary Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction III Trial)

Right ventricular (RV) dysfunction is a powerful risk marker after acute myocardial infarction (MI). Primary percutaneous coronary intervention (PCI) has markedly reduced myocardial damage of the left ventricle, but reliable data on RV damage using cardiac magnetic resonance imaging (MRI) are scarce. In a recent trial of patients with acute MI treated with primary PCI, in which the primary end point was left ventricular (LV) ejection fraction after 4 months measured with MRI, we conducted a prospectively defined substudy in which we examined RV function. RV ejection fraction (RVEF) and RV scar size were measured with MRI at 4 months. Tricuspid annular plane systolic excursion (TAPSE) and RV free wall longitudinal strain (FWLS) were assessed using echocardiography before discharge and at 4 months. We studied 258 patients without diabetes mellitus; their mean age was 58 ± 11 years, 79% men and mean LV ejection fraction was 54 ± 8%. Before discharge, 5.2% of patients had TAPSE <17 mm, 32% had FWLS > -20% and 11% had FWLS > -15%. During 4 months, TAPSE increased from 22.8 ± 3.6 to 25.1 ± 3.9 mm (p <0.001) and FWLS increased from -22.6 ± 5.8 to -25.9 ± 4.7% (p <0.001). After 4 months, mean RVEF on MRI was 64.1 ± 5.2% and RV scar was detected in 5 patients (2%). There was no correlation between LV scar size and RVEF (p = 0.9), TAPSE (p = 0.1), or RV FWLS (p = 0.9). In conclusion, RV dysfunction is reversible in most patients and permanent RV ischemic injury is very uncommon 4 months after acute MI treated with primary PCI

Surgery in Adults With Congenital Heart Disease

Background-A significant proportion of patients with congenital heart disease require surgery in adulthood. We aimed to give an overview of the prevalence, distribution, and outcome of cardiovascular surgery for congenital heart disease. We specifically questioned whether the effects of surgical treatment on subsequent long-term survival depend on sex. Methods and Results-From the Dutch Congenital Corvitia (CONCOR) registry for adults with congenital heart disease, we identified 10 300 patients; their median age was 33.1 years. Logistic and Cox regression models were used to assess the association of surgery in adulthood with sex and with long-term survival. In total, 2015 patients (20%) underwent surgery for congenital heart disease in adulthood during a median follow-up period of 15.1 years; in 812 patients (40%), it was a reoperation. Overall, both first operations and reoperations in adulthood were performed significantly more often in men compared with women (adjusted odds ratio = 1.4 [95% confidence interval, 1.2-1.6] and 1.2 [95% confidence interval, 1.0-1.4], respectively). Patients with their third and fourth or more surgery in adulthood had a 2- and 3-times-higher risk of death compared with patients never operated on (adjusted hazard ratio = 1.9 [95% confidence interval, 1.0-3.6] and 2.7 [95% confidence interval, 1.1-6.3], respectively). Men with a reoperation in adulthood had a 2-times-higher risk of death than women (adjusted hazard ratio = 1.9; 95% confidence interval, 1.0-3.5). Conclusions-Of predominantly young adults with congenital heart disease, one fifth required cardiovascular surgery during a 15-year period; in 40%, the surgery was a reoperation. Men with congenital heart disease have a higher chance of undergoing surgery in adulthood and have a consistently worse long-term survival after reoperations in adulthood compared with women. (Circulation. 2011;124:2195-2201.

Improving Genetic Prediction by Leveraging Genetic Correlations Among Human Diseases and Traits

Genomic prediction has the potential to contribute to precision medicine. However, to date, the utility of such predictors is limited due to low accuracy for most traits. Here theory and simulation study are used to demonstrate that widespread pleiotropy among phenotypes can be utilised to improve genomic risk prediction. We show how a genetic predictor can be created as a weighted index that combines published genome-wide association study (GWAS) summary statistics across many different traits. We apply this framework to predict risk of schizophrenia and bipolar disorder in the Psychiatric Genomics consortium data, finding substantial heterogeneity in prediction accuracy increases across cohorts. For six additional phenotypes in the UK Biobank data, we find increases in prediction accuracy ranging from 0.7 for height to 47 for type 2 diabetes, when using a multi-trait predictor that combines published summary statistics from multiple traits, as compared to a predictor based only on one trait. © 2018 The Author(s)

Age at first birth in women is genetically associated with increased risk of schizophrenia

Prof. Paunio on PGC:n jäsenPrevious studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is -0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.Peer reviewe