Clinical implementation of first trimester screening for congenital heart defects.

OBJECTIVE: To examine the feasibility and performance of implementing a standardized fetal cardiac scan at the time of a routine first-trimester ultrasound scan. METHOD: A retrospective, single-center study in an unselected population between March 2021 and July 2022. A standardized cardiac scan protocol consisting of a four-chamber and 3-vessel trachea view with color Doppler was implemented as part of the routine first-trimester scan. Sonographers were asked to categorize the fetal heart anatomy. Data were stratified into two groups based on the possibility of evaluating the fetal heart. The influence of maternal and fetal characteristics and the detection of major congenital heart disease were investigated. RESULTS: A total of 5083 fetuses were included. The fetal heart evaluation was completed in 84.9%. The proportion of successful scans increased throughout the study period from 76% in the first month to 92% in the last month. High maternal body mass index and early gestational age at scan significantly decreased the feasibility. The first-trimester detection of major congenital heart defects was 7/16, of which four cases were identified by the cardiac scan protocol with no false-positive cases. CONCLUSION: First-trimester evaluation of the fetal heart by a standardized scan protocol is feasible to implement in daily practice. It can contribute to the earlier detection of congenital heart defects at a very low false positive rate.

A novel algorithm for classification of interatrial communications within the oval fossa in the newborn.

BACKGROUND: An interatrial communication is present in most neonates. The majority are considered the "normal" patency of the oval foramen, while a minority are abnormal atrial septal defects. Differentiation between the two with transthoracic echocardiography may be challenging, and no generally accepted method of classification is presently available. We aimed to develop and determine the reliability of a new classification of interatrial communications in newborns. METHODS AND RESULTS: An algorithm was developed based on echocardiographic criteria from 495 newborns (median age 11[8;13] days, 51.5% females). The algorithm defines three main categories: patency of the oval foramen, atrial septal defect, and no interatrial communication as well as several subtypes. We found an interatrial communication in 414 (83.6%) newborns. Of these, 386 (93.2%) were categorised as patency of the oval foramen and 28 (6.8%) as atrial septal defects.Echocardiograms from another 50 newborns (median age 11[8;13] days, 36.0% female), reviewed by eight experts in paediatric echocardiography, were used to assess the inter- and intraobserver variation of classification of interatrial communications into patency of the oval foramen and atrial septal defect, with and without the use of the algorithm. Review with the algorithm gave a substantial interobserver agreement (kappa = 0.66), and an almost perfect intraobserver agreement (kappa = 0.82). Without the use of the algorithm, the interobserver agreement between experienced paediatric cardiologists was low (kappa = 0.20). CONCLUSION: A new algorithm for echocardiographic classification of interatrial communications in newborns produced almost perfect intraobserver and substantial interobserver agreement. The algorithm may prove useful in both research and clinical practice.

Copenhagen Baby Heart Study: a population study of newborns with prenatal inclusion.

Congenital heart diseases (CHDs) are reported in 0.8% of newborns. Numerous factors influence cardiovascular development and CHD prevalence, and possibly also development of cardiovascular disease later in life. However, known factors explain the probable etiology in only a fraction of patients. Past large-scale population-based studies have made invaluable contributions to the understanding of cardiac disease, but none recruited participants prenatally and focused on the neonatal period. The Copenhagen Baby Heart Study (CBHS) is a population-based study of the prevalence, spectrum, and prognosis of structural and functional cardiac abnormalities. The CBHS will also establish normal values for neonatal cardiac parameters and biomarkers, and study prenatal and early childhood factors potentially affecting later cardiovascular disease risk. The CBHS is an ongoing multicenter, prospective study recruiting from second trimester pregnancy (gestational weeks 18-20) (expected n = 25,000). Information on parents, pregnancy, and delivery are collected. After birth, umbilical cord blood is collected for biochemical analysis, DNA purification, and biobank storage. An echocardiographic examination, electrocardiography, and post-ductal pulse oximetry are performed shortly after birth. Infants diagnosed with significant CHD are referred to a specialist or admitted to hospital, depending on CHD severity. CBHS participants will be followed prospectively as part of specific research projects or regular clinical follow-up for CHD. CBHS design and methodology are described. The CBHS aims to identify new mechanisms underlying cardiovascular disease development and new targets for prevention, early detection, and management of CHD and other cardiac diseases presenting at birth or developing later in life.

Increased anxiety and depression in Danish cardiac patients with a type D personality: cross-validation of the Type D Scale (DS14).

BACKGROUND: Type D personality is an emerging risk factor in cardiovascular disease. We examined the psychometric properties of the Danish version of the Type D Scale (DS14) and the impact of Type D on anxiety and depression in cardiac patients. METHOD: Cardiac patients (n = 707) completed the DS14, the Hospital Anxiety and Depression Scale, and the Eysenck Personality Questionnaire. A subgroup (n = 318) also completed the DS14 at 3 or 12 weeks. RESULTS: The two-factor structure of the DS14 was confirmed; the subscales negative affectivity and social inhibition were shown to be valid, internally consistent (Cronbach's alpha = 0.87/0.91; mean inter-item correlations = 0.49/0.59), and stable over 3 and 12 weeks (r = 0.85/0.78; 0.83/0.79; ps < 0.01). Type D was an independent associate of anxiety (beta, 0.49; p < 0.01) and depression (beta, 0.47; p < 0.01) in univariable linear regression analysis and remained a significant independent associate of anxiety (beta, 0.26; p < 0.01) and depression (beta, 0.17; p < 0.01) in adjusted analyses. CONCLUSIONS: The Danish DS14 was shown to be a valid and reliable measure associated with increased symptoms of anxiety and depression independent of socio-demographic and clinical risk factors. The DS14 may be used in research and clinical practice to identify high-risk patients.

Familial hypercholesterolaemia reduces the quality of life of patients not reaching treatment targets.

INTRODUCTION: Familial hypercholesterolaemia (FH) is the most common monogenic disorder associated with premature cardiovascular disease. If untreated, life expectancy in heterozygous FH patients is shortened by 20-30 years compared with the general population. Nevertheless, treatment goals are only met in approximately 50% of patients. This comparative study examined the quality of life (QoL) impact of FH in patients who had and had not reached the target of treatment. METHODS: Two qualitative focus group interviews were carried out with a total of ten FH patients. A semi-structured interview guide included questions identified in a preceding literature study. The data were analysed using a medical anthropological approach. RESULTS: While having FH did not have much impact on well-treated patients' QoL, patients who had not reached the treatment target had markedly more concerns. They had experienced severe side-effects and worried about their own and their relatives' health. They were concerned about the long-term impact of not being effectively treated including the risk that coronary heart disease could cause their premature death or disability and inability to care for their children, in particular. The women had issues with stigma and self-efficacy. CONCLUSIONS: The QoL impact of FH is related to treatment efficacy. These findings need to be addressed in the management of FH patients. Particular attention should be paid to those who are not presently reaching the target of treatment. FUNDING: The study was funded by a research grant from Amgen. TRIAL REGISTRATION: not relevant.

Good long-term survival after paediatric heart transplantation.

INTRODUCTION: The brain-death criterion was introduced in Denmark in 1990. The first Danish paediatric heart transplantation (HTx) was performed at Copenhagen University Hospital, Rigshospitalet, in Copenhagen in 1991. We describe our experiences during the first 20 years with paediatric HTx. MATERIAL AND METHODS: This was a retrospective study of 37 paediatric patients (<18 years) who were listed for HTx from 1991 to 2011. RESULTS: A total of 26 of the 37 children listed underwent HTx, nine due to congenital heart disease (CHD) and 17 due to cardiomyopathy (CM). Ten patients died while being on the waiting list. One patient was withdrawn from the list due to spontaneous improvement. A total of 21 patients remain alive. Survival was 92% after five years and 82% after ten years. We had two early (CHD) and three late (CM) deaths. Complications were few, but significant. Early acute rejection occurred in seven patients, whereas one patient with repeated late episodes of acute rejection died from graft failure 5.5 years after HTx. We found a time-related progressive deterioration in renal function. Two patients underwent renal Tx, two others died while being on dialysis. Cardiac allograft vasculopathy occurred in three patients, two of whom died. The third remains alive today, 19 years after HTx. CONCLUSION: Our paediatric HTx results are comparable with those of larger international centres and consistent with true long-term survival. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

Positive affect and negative affect correlate differently with distress and health-related quality of life in patients with cardiac conditions: validation of the Danish Global Mood Scale.

OBJECTIVE: The Global Mood Scale (GMS), assessing negative affect (NA) and positive affect (PA), is sensitive to tapping treatment-related changes in patients with cardiac conditions. We examined the psychometric properties of the Danish GMS and the influence of NA and PA on distress and health-related quality of life (HRQL). METHOD: A mixed group of patients with cardiac conditions (n=502) completed the GMS, the Hospital Anxiety and Depression Scale, the Type D Scale, and the 36-item Short-Form Health Survey. RESULTS: The two-factor model of the Danish GMS was confirmed, and the scale was shown to be valid, internally consistent (Cronbach's alpha NA/PA=.93/.85), and stable over 3 weeks (Pearson's r NA/PA=.82/.80). Unadjusted multiple linear regression analyses showed NA (beta=0.67, P<.001), PA (beta=-0.17, P=.001), and the interaction effect NA x PA (beta=-0.17, P=.015) to be associated with anxiety and depressive symptoms (NA:beta=0.99, P<.001; PA:beta=-0.12, P=.004; NA x PA:beta=-0.43, P<.001), as well as with physical HRQL (NA:beta=-0.37, P<.001; PA:beta=0.17, P=.001; NA x PA: beta=-0.27, P<.001) and mental HRQL (NA:beta=-0.72, P<.001; PA:beta=0.27, P=.004; NA x PA:beta=0.23, P<.001). When adjusting for demographic and clinical characteristics, only NA (beta=0.26, P=.003) was associated with anxiety, whereas NA (beta=0.75, P<.001) and NA x PA (beta=-0.34, P=.002) were associated with depressive symptoms. For physical HRQL, PA (beta=0.21, P=.03) and NA x PA (beta=-0.36, P=.005) remained significant, whereas NA (beta=-0.38, P<.001) and PA (beta=0.21, P=.002) remained significant for mental HRQL. CONCLUSION: The Danish GMS is a psychometrically sound measure of affect in patients with cardiac conditions. Future studies should examine changes in both PA and NA and their impact on health outcomes.

Functional significance of metastasis-inducing S100A4(Mts1) in tumor-stroma interplay.

Causal implication of S100A4 in inducing metastases was convincingly shown previously. However, the mechanisms that associate S100A4 with tumor progression are not well understood. S100A4 protein, as a typical member of the S100 family, exhibits dual, intracellular and extracellular, functions. This work is focused on the extracellular function of S100A4, in particular its involvement in tumor-stroma interplay in VMR (mouse adenocarcinoma cell line) tumor cells, which exhibit stroma-dependent metastatic phenotype. We demonstrated the reciprocal influence of tumor and stroma cells where tumor cells stimulate S100A4 secretion from fibroblasts in culture. In turn, extracellular S100A4 modifies the cytoskeleton and focal adhesions and triggers several other events in tumor cells. We found stabilization of the tumor suppressor protein p53 and modulation of its function. In particular, extracellular S100A4 down-regulates the pro-apoptotic bax and the angiogenesis inhibitor thrombospondin-1 genes. For the first time, we demonstrate here that the S100A4 protein added to the extracellular space strongly stimulates proteolytic activity of VMR cells. This activity most probably is associated with matrix metalloproteinases and, in particular, with matrix metalloproteinase-13. Finally, the application of the recombinant S100A4 protein confers stroma-independent metastatic phenotype on VMR tumor cells. In conclusion, our results indicate that metastasis-inducing S100A4 protein plays a pivotal role in the tumor-stroma environment. S100A4 released either by tumor or stroma cells triggers pro-metastatic cascades in tumor cells.