New developments in adult congenital heart disease

Contains fulltext : 225482.pdf (Publisher’s version ) (Open Access)Congenital heart disease (CHD) affects 0.8% of live births and over the past decades technical improvements and large-scale repair has led to increased survival into adulthood of over 95% of the new-born. A new group of patients, those who survived their congenital heart defect, has emerged but late complications including heart failure, pulmonary hypertension (PH), arrhythmias, aneurysms and endocarditis appeared numerous, with a huge impact on mortality and morbidity. However, innovations over the past years have changed the landscape of adult CHD dramatically. In the diagnostic process important improvements have been made in the use of MRI, biomarkers, e‑health concepts and 3D visualisation of anatomy. Care is now concentrated in specialised centres, with a continuous emphasis on education and the introduction of weekly multidisciplinary consultations on diagnosis and intervention. Surgery and percutaneous intervention have been refined and new concepts applied, further reducing the burden of the congenital malformations. Research has matured from case series to global networks. Currently, adults with CHD are still facing high risks of early mortality and morbidity. By global collaboration and continuous education and development and innovation of our diagnostic and therapeutic arsenal, we will improve the perspectives of these young patients

Reduced right ventricular function on cardiovascular magnetic resonance imaging is associated with uteroplacental impairment in tetralogy of Fallot

Background: Maternal right ventricular (RV) dysfunction (measured by echocardiography) is associated with impaired uteroplacental circulation, however echocardiography has important limitations in the assessment of RV function. We therefore aimed to investigate the association of pre-pregnancy RV and left ventricular (LV) function measured by cardiovascular magnetic resonance with uteroplacental Doppler flow parameters in pregnant women with repaired Tetralogy of Fallot (ToF). Methods: Women with repaired ToF were examined, who had been enrolled in a prospective multicenter study of pregnant women with congenital heart disease. Clinical data and CMR evaluation before pregnancy were compared with uteroplacental Doppler parameters at 20 and 32 weeks gestation. In particular, pulsatility index (PI) of uterine and umbilical artery were studied. Results: We studied 31 women; mean age 30 years, operated at early age. Univariable analyses showed that reduced RV ejection fraction (RVEF; P = 0.037 and P = 0.001), higher RV end-systolic volume (P = 0.004) and higher LV end-diastolic and end-systolic volume (P = 0.001 and P = 0.003, respectively) were associated with higher uterine or umbilical artery PI. With multivariable analyses (corrected for maternal age and body mass index), reduced RVEF before pregnancy remained associated with higher umbilical artery PI at 32 weeks (P = 0.002). RVEF was lower in women with high PI compared to women with normal PI during pregnancy (44% vs. 53%, p = 0.022). LV ejection fraction was not associated with uterine or umbilical artery PI. Conclusions: Reduced RV function before pregnancy is associated with abnormal uteroplacental Doppler flow parameters. It could be postulated that reduced RV function on pre-pregnancy CMR (≤2 years) is a predisposing factor for impaired placental function in women with repaired ToF.</p

Social interaction patterns, therapist responsiveness, and outcome in treatments for borderline personality disorder.

Inflexible social interaction patterns are defining features of borderline personality disorder (BPD). Specific beliefs about the self and others may be activated across interaction situations, often leading to instable relationships. It may be pivotal to address these difficulties in early treatment phases, through appropriate therapist responsiveness, which means an adaptation of therapist's activity to their client's behaviours using emerging information in the process (Stiles, 2009, Clinical Psychology: Science and Practice, 16, 86). In this process-outcome study, responsiveness is operationalized by the motive-oriented therapeutic relationship (Caspar, 2007, Handbook of psychotherapeutic case formulations, 2nd ed., 251-289, Guilford), based on the Plan analysis case formulation. The present study assesses the interplay between social interaction problems and therapist responsiveness, explaining symptoms at discharge and the therapeutic alliance. In total, N = 50 clients with BPD entered the study, and standard and responsive treatments were compared. Social interaction patterns were assessed by the newly developed Borderline Interaction Patterns Scale (BIPS), applied to recorded material of three sessions per therapy. Outcome was measured by general symptoms (OQ-45), borderline symptoms (BSL-23), interpersonal problems (IIP), and the therapeutic alliance (WAI). Results suggest that in standard treatment, social interaction patterns are neither related to outcome nor the therapeutic alliance. In responsive treatment, more activation of social interaction patterns predicted better outcome on IIP and lower therapist ratings of the alliance. The conclusions seem promising for specific effectiveness of responsive treatments in particular in the interpersonal problem area of BPD. Identifying social interaction patterns early in treatment may be a crucial pathway to change for BPD. Responsive therapy activating social interaction patterns may be crucial for better outcome. Future research should focus on mechanisms of change in early treatment phases for BPD. New scale for assessing social interaction patterns specific to borderline personality disorder

Integrated analysis of DNA copy number and gene expression microarray data using gene sets

Background: Genes that play an important role in tumorigenesis are expected to show association between DNA copy number and RNA expression. Optimal power to find such associations can only be achieved if analysing copy number and gene expression jointly. Furthermore, some copy number changes extend over larger chromosomal regions affecting the expression levels of multiple resident genes.

Review of the Mental Health and Well-being Benefits of Biodiversity

Little is known about the contribution that biodiversity has on mental health and well-being. To date, only one systematic review has investigated the health and well-being benefits from contact with biodiversity (Lovell et al. J Toxicol Environ Health B Crit Rev 17(1):1–20, 2014). The number of research studies investigating the health and well-being effects of biodiversity has increased since this publication. Here, we provide an update, focusing on the impact of biodiversity on mental health and well-being. Our objectives are to: (i) identify and describe the literature published after 2012; and (ii) synthesise all results from Lovell et al. (J Toxicol Environ Health B Crit Rev 17(1):1–20, 2014) and the more recently published literature to assess whether biodiversity influences mental health and well-being. Sixteen recently published studies met the inclusion criteria. The literature is varied with different study designs, measures of biodiversity, mental health and well-being. The synthesis of results was drawn from 24 studies: nine from Lovell et al. (J Toxicol Environ Health B Crit Rev 17(1):1–20, 2014) and 15 identified by this chapter. There is some evidence to suggest that biodiversity promotes better mental health and well-being. However, more studies reported non-significant results. The evidence is not yet of the extent necessary to characterise the role of biodiversity in relation to mental health or well-being. Future interdisciplinary research directions are discussed

Common genetic variants contribute to risk of transposition of the great arteries

Rationale: Dextro-transposition of the great arteries (D-TGA) is a severe congenital heart defect which affects approximately 1 in 4,000 live births. While there are several reports of D-TGA patients with rare variants in individual genes, the majority of D-TGA cases remain genetically elusive. Familial recurrence patterns and the observation that most cases with D-TGA are sporadic suggest a polygenic inheritance for the disorder, yet this remains unexplored. Objective: We sought to study the role of common single nucleotide polymorphisms (SNPs) in risk for D-TGA. Methods and Results: We conducted a genome-wide association study in an international set of 1,237 patients with D-TGA and identified a genome-wide significant susceptibility locus on chromosome 3p14.3, which was subsequently replicated in an independent case-control set (rs56219800, meta-analysis P=8.6x10-10, OR=0.69 per C allele). SNP-based heritability analysis showed that 25% of variance in susceptibility to D-TGA may be explained by common variants. A genome-wide polygenic risk score derived from the discovery set was significantly associated to D-TGA in the replication set (P=4x10-5). The genome-wide significant locus (3p14.3) co-localizes with a putative regulatory element that interacts with the promoter of WNT5A, which encodes the Wnt Family Member 5A protein known for its role in cardiac development in mice. We show that this element drives reporter gene activity in the developing heart of mice and zebrafish and is bound by the developmental transcription factor TBX20. We further demonstrate that TBX20 attenuates Wnt5a expression levels in the developing mouse heart. Conclusions: This work provides support for a polygenic architecture in D-TGA and identifies a susceptibility locus on chromosome 3p14.3 near WNT5A. Genomic and functional data support a causal role of WNT5A at the locus