Autosomal dominant inheritance of left ventricular outflow tract obstruction

Most nonsyndromic congenital heart malformations (CHMs) in humans are multifactorial in origin, although an increasing number of monogenic cases have been reported recently. We describe here four new families with presumed autosomal dominant inheritance of left ventricular outflow tract obstruction (LVOTO), consisting of hypoplastic left heart (HLHS) or left ventricle (HLV), aortic valve stenosis (AS) and bicuspid aortic valve (BAV), hypoplastic aortic arch (HAA), and coarctation of the aorta (CoA). LVOTO in these families shows a wide clinical spectrum with some family members having severe anomalies such as hypoplastic left heart, and others only minor anomalies such as mild aortic valve stenosis. This supports the suggestion that all anomalies of the LVOTO spectrum are developmentally related and can be caused by a single gene defect.     

Novel membrane frizzled‐related protein gene mutation as cause of posterior microphthalmia resulting in high hyperopia with macular folds

Purpose: We present a genetic and clinical analysis of two sisters, 3 and 4 years of age, with nanophthalmos and macular folds. Methods: Ophthalmological examination, general paediatric examination and molecular genetic analysis of the MFRP gene were performed in both affected siblings. Results: Clinical analysis showed high hyperopia (+11 D and +12 D), short axial lengths (15 mm) and the presence of macular folds and optic nerve head drusen. Autofluorescence of the retina was generally normal with subtle macular abnormalities. Sequence analysis showed compound heterozygosity for severe MFRP mutations in both sisters: a previously reported p.Asn167fs (c.498dupC) and a novel stop codon mutation p.Gln91X (c.271C>T). Conclusion: These are the youngest nanophthalmos patients in the literature identified with severe loss of MFRP function, showing already the known structural abnormalities for this disease. Adult patients affected by homozygous or compound heterozygous MFRP mutations generally show signs of retinal dystrophy, with ERG disturbances and RPE abnormalities on autofluorescence imaging. ERG examination could not be performed in these children, but extensive RPE abnormalities were not seen at this young age.     

Outcome of pregnancy in patients after repair of aortic coarctation.

AIMS: Nowadays, most women born with aortic coarctation reach childbearing age. However, data on outcome of pregnancy in women after repair of aortic coarctation are scarce. The aim of this study was to report on maternal and neonatal outcome of pregnancy in women after aortic coarctation repair. METHODS AND RESULTS: The CONCOR national registry on congenital heart disease in The Netherlands was reviewed for women of childbearing age (> or =18 years old) with a history of aortic coarctation repair. Medical history and maternal, obstetrical, and neonatal outcome were determined. Fifty-four of the 100 women included had a history of pregnancy. The 54 women had 126 pregnancies resulting in 98 successful pregnancies, 22 miscarriages, and six abortions. The success rate was estimated as 0.778 (SE 0.002) including abortions and 0.817 (SE 0.002) excluding abortions. There were 85 vaginal deliveries, seven vaginal deliveries with epidural analgesia, and six caesarean sections. There were two neonatal deaths. A total of 26 pregnancies were complicated by a hypertensive disorder of pregnancy. There were 21 pregnancies in 14 women complicated by hypertension and five pregnancies in four women complicated by pre-eclampsia. The hypertension- and pre-eclampsia-probabilities were estimated as 0.183 (SE 0.285) and 0.061 (SE 0.211), respectively. During pregnancy, five patients had an increase > or =15 mmHg across the site of repair at echocardiography, but only one patient required reintervention for recoarctation after delivery. Four of the 98 children (4%) had a congenital heart defect. CONCLUSION: Pregnancy is well tolerated in women after repair of aortic coarctation. However, an excess of miscarriages and hypertensive disorders of pregnancy were found.     

Postinfectious onset in functional dyspepsia is a risk factor for weight loss

Journal of Gastroenterology - Functional dyspepsia (FD) is differentiated into two subgroups: the postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS). Acute gastroenteritis and...     

Communication between human mast cells and CD4+ T cells through antigen‐dependent interactions

Mast cells (MCs) are immune cells residing in tissues where pathogens are first encountered. It has been indicated that MCs might also be involved in setting the outcome of T‐cell responses. However, little is known about the capacity of human MCs to express MHC class II and/or to capture and present antigens to CD4⁺ T cells. To study the T‐cell stimulatory potential of human MCs, CD34⁺ stem cell derived MCs were generated. These cells expressed HLA‐DR when stimulated with IFN‐γ, and, importantly, presented peptide and protein for activation of antigen‐specific CD4⁺ T cells. The interplay between MC and T cell led to increased HLA‐DR expression on MCs. MCs were present in close proximity to T cells in tonsil and expressed HLA‐DR and CD80, indicating their ability to present antigens to CD4⁺ T cells in T‐cell areas of human LNs. Our data show that MCs can present native antigens to human CD4⁺ T cells and that HLA‐DR expressing MCs are present in tonsil tissue, indicating that human MCs can directly activate T cells and provide a rationale to study the potential of MCs to prime and/or skew human T‐cell responses.     

A qualitative participatory study to identify experiences of coronary heart disease patients to support the development of online self-management services

ObjectiveWeb-based self-management services remain underutilized in current practice. Our aim was to gain insight into disease and self-management experiences of patients in early and progressive stages of coronary heart disease (CHD), to understand moderating effects of daily life experiences on the utilization of web-based self-management services and preconditions for use.MethodsWe applied generative research techniques, which stem from the field of product design and are characterized by the use of creative processes. Three groups of patients with CHD received a sensitizing package to document and reflect on their health, and were subsequently either interviewed or participated in a focus group session.ResultsIn total, 23 patients participated in this study. Emerging themes were (1) fear for recurrent events, (2) experiences with professional care, (3) the perceived inability to prevent disease progression, (4) the desire to go on living without thinking about the disease every day, (5) the social environment as a barrier to or facilitator for self-management, and (6) the need for information tailored to personal preferences.ConclusionHow patients experience their disease varies between stable and post-acute stages, as well as between early and progressive stages of CHD. Patients in post-acute stages of the disease seem to be most amenable to support, while patients in stable stages want to live their life without being reminded of their disease. In the context of self-management, web-based services should be adapted to the variation in needs that occur in the different stages of CHD and new strategies to fit such services to these needs should be developed. Furthermore, they should be tailored to patients’ individual health situation and preferences, support patient empowerment, and manage expectations regarding the progression of their disease.     

Effect of Spironolactone on Atrial Fibrillation in Patients with Heart Failure with Preserved Ejection Fraction: Post-Hoc Analysis of the Randomized,Placebo-Controlled TOPCAT Trial

Mineralocorticoid receptor antagonists (MRAs) reduce the risk of atrial fibrillation (AF) in patients with heart failure (HF) and a reduced ejection fraction. The efficacy of MRAs for AF prevention in patients with HF and a preserved ejection fraction (HFpEF) is unclear. We performed a secondary analysis of a randomized placebo-controlled trial to determine the efficacy of spironolactone in reducing new-onset AF and recurrence of AF in 2733 patients with symptomatic HFpEF. Patients with and without prevalent AF at baseline were included, and those with permanent AF were excluded. Patients were randomized 1:1 to spironolactone or placebo. The risk of new-onset AF or the recurrence of AF was quantified using hazard ratios (HRs) with corresponding 95% confidence intervals (CIs). At baseline, 2228 (64.7%) patients had no history of AF (spironolactone, n = 1111; placebo, n = 1117), whereas 505 (18.4%) patients had prevalent AF (spironolactone, n = 260; placebo, n = 245). During a median follow-up of 3.1 years (interquartile range [IQR] 2.0–4.9), the incidence of new-onset AF was similar in both treatment arms: spironolactone 5.2% (n = 58) versus placebo 4.4% (n = 49); p = 0.41. The risk of new-onset AF was similar in both treatment arms: HR 1.19; 95% CI 0.81–1.74; p = 0.38. AF recurrence was also similar in both treatment arms during a median follow-up of 3.3 years (IQR 1.9–4.7): spironolactone 11.5% (n = 30) versus placebo 11.8% (n = 29); p = 1.00. The risk of recurrence of AF did not differ per treatment arm: HR 0.94; 95% CI 0.57–1.58; p = 0.83. Spironolactone does not reduce the risk of new-onset AF or AF recurrence in patients with HFpEF. This is in contrast to results in cohorts of patients with HF and a reduced ejection fraction. ClinicalTrials.gov identifier no. NCT00094302 (TOPCAT).