Congenital Heart Disease
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Laura M. Wienecke ◽  
Sarah Cohen ◽  
Johann Bauersachs ◽  
Alexandre Mebazaa ◽  
Benjamin G. Chousterman

AbstractAlthough more than 90% of children born with congenital heart disease (CHD) survive into adulthood, patients face significantly higher and premature morbidity and mortality. Heart failure as well as non-cardiac comorbidities represent a striking and life-limiting problem with need for new treatment options. Systemic chronic inflammation and immune activation have been identified as crucial drivers of disease causes and progression in various cardiovascular disorders and are promising therapeutic targets. Accumulating evidence indicates an inflammatory state and immune alterations in children and adults with CHD. In this review, we highlight the implications of chronic inflammation, immunity, and immune senescence in CHD. In this context, we summarize the impact of infant open-heart surgery with subsequent thymectomy on the immune system later in life and discuss the potential role of comorbidities and underlying genetic alterations. How an altered immunity and chronic inflammation in CHD influence patient outcomes facing SARS-CoV-2 infection is unclear, but requires special attention, as CHD could represent a population particularly at risk during the COVID-19 pandemic. Concluding remarks address possible clinical implications of immune changes in CHD and consider future immunomodulatory therapies.

2021 ◽  
Yuhan Xie ◽  
Wei Jiang ◽  
Weilai Dong ◽  
Hongyu Li ◽  
Sheng Chih Jin ◽  

De novo variants (DNVs) with deleterious effects have proved informative in identifying risk genes for early-onset diseases such as congenital heart disease (CHD). A number of statistical methods have been proposed for family-based studies or case/control studies to identify risk genes by screening genes with more DNVs than expected by chance in Whole Exome Sequencing (WES) studies. However, the statistical power is still limited for cohorts with thousands of subjects. Under the hypothesis that connected genes in protein-protein interaction (PPI) networks are more likely to share similar disease association status, we develop a Markov Random Field model that can leverage information from publicly available PPI databases to increase power in identifying risk genes. We identified 46 candidate genes with at least 1 DNV in the CHD study cohort, including 18 known human CHD genes and 35 highly expressed genes in mouse developing heart. Our results may shed new insight on the shared protein functionality among risk genes for CHD.

2021 ◽  
Vol 8 ◽  
Jef Van den Eynde ◽  
Cedric Manlhiot ◽  
Alexander Van De Bruaene ◽  
Gerhard-Paul Diller ◽  
Alejandro F. Frangi ◽  

Built on the foundation of the randomized controlled trial (RCT), Evidence Based Medicine (EBM) is at its best when optimizing outcomes for homogeneous cohorts of patients like those participating in an RCT. Its weakness is a failure to resolve a clinical quandary: patients appear for care individually, each may differ in important ways from an RCT cohort, and the physician will wonder each time if following EBM will provide best guidance for this unique patient. In an effort to overcome this weakness, and promote higher quality care through a more personalized approach, a new framework has been proposed: Medicine-Based Evidence (MBE). In this approach, big data and deep learning techniques are embraced to interrogate treatment responses among patients in real-world clinical practice. Such statistical models are then integrated with mechanistic disease models to construct a “digital twin,” which serves as the real-time digital counterpart of a patient. MBE is thereby capable of dynamically modeling the effects of various treatment decisions in the context of an individual's specific characteristics. In this article, we discuss how MBE could benefit patients with congenital heart disease, a field where RCTs are difficult to conduct and often fail to provide definitive solutions because of a small number of subjects, their clinical complexity, and heterogeneity. We will also highlight the challenges that must be addressed before MBE can be embraced in clinical practice and its full potential can be realized.

2021 ◽  
Vol 21 (1) ◽  
Rediet Woldesenbet ◽  
Rajalakshmi Murugan ◽  
Feven Mulugeta ◽  
Tamirat Moges

Abstract Background Children with congenital heart disease are at risk for poor growth and under-nutrition compared with healthy children. The aim of this study was to assess the nutritional status of children with congenital heart disease and associated factors in selected governmental hospitals and cardiac center Addis Ababa, Ethiopia. Method Institutional based cross sectional study among 373 children aged under15 years was conducted from February to March; 2021G.c. Data was collected using structured questionnaire and chart review. Z-scores based on WHO reference ranges were used. Anthropometric z-scores based on WHO 2007 reference ranges were generated for each child. Weight-for-age z-scores for children 0–10 years and height-for-age and BMI-for-age z-scores for all children. Binary logistic regression was used for associated factors. Result A total of 373 children were participated in this study. The prevalence of wasting and stunting was 144(38.6%) and 134(35.9%) respectively. The prevalence of underweight and malnutrition in children under 10 years was 143(43.1%). Most of the children were diagnosed with VSD (36.7%). Children age group of 13 months-5 years were associated with wasting and underweight [AOR = 0.434, 95%CI: (0.231, 0.816)] and [AOR = 0.360, 95%CI: (0.183, 0.711)] respectively. Children diagnosed with PAH were 1.885 times more likely to be underweight [AOR = 1.885, 95%CI: (1.094, 3.246)]. When the hemoglobin level increases by every unit per g/dl the chance to be wasting and underweight decreases by 13.1 and 18.6%[AOR = 0.869, 95%CI: (0.792, 0.955)] and [AOR = 0.869, 95%CI: (0.792, 0.955)] respectively. The level of SPO2 is associated with stunting and underweight [AOR = 0.970, 95%CI: (0.943, 0.998)] and [AOR = 0.970, 95%CI: (0.943, 0.998)] respectively. Conclusion The prevalence of malnutrition in children with CHD is pretty high. Decreased level of hemoglobin and SPO2 was found to be associated factors for malnutrition in this case. There need to be a new strategy about including different health professional while care giving.

2021 ◽  
Vol 73 (12) ◽  
pp. 808-814
Atipotsawee Tungsupreechameth ◽  
Klaita Srisingh

Objective: To determine the factors associated with severe ALRTI from RSV in children.Materials and Methods: A retrospective study of children aged 1-60 months were conducted from 2014 to 2018. Out of 269 patients diagnosed with RSV ALRTI, 100 children were enrolled in the study, 20 had severe RSV ALRTI, while 80 had non-severe RSV ALRTI as identified by the ReSVinet scale. A multivariable logistic model was conducted to select significant variables.Results: During the study period, 269 patients were diagnosed with RSV ALRTI. Mean age was 10.45 ± 3.53 months. Clinical manifestations of severe RSV ALRTI group had significant difference in abnormal general condition (P < 0.001), tachypnea (P < 0.001), SpO2 < 85% (P < 0.001), poor air entry in lungs (P < 0.001), and retraction (P < 0.001). The factors associated with severe RSV ALRTI group, were underlying congenital heart disease [aOR32.45; 95% CI 3.38-311.87, P = 0.003] and duration of hospital stay >5 days [aOR 19.56; 95% CI 1.81-212.05, P = 0.014].Conclusion: Factors associated with severe RSV ALRTI in children were underlying congenital heart disease andduration of hospital stay >5 days.

Rebecca Spillmann ◽  
Susanne Polentarutti ◽  
Melanie Ehrler ◽  
Oliver Kretschmar ◽  
Flavia M. Wehrle ◽  

Abstract Background Children with congenital heart disease (CHD) are at risk for neurodevelopmental deficits. This study aimed to investigate the impact of cognitive deficits on educational outcome and participation in leisure activities. Methods A prospective cohort of 134 children with CHD who underwent cardiopulmonary bypass surgery (CPB) was examined at 10 years of age. IQ was assessed with the WISC-IV and executive functions with the BRIEF (parent- and teacher-report). Parents reported on type and level of education and educational support, and leisure activity participation. Ordinal regression analyses assessed the association between cognitive deficits and educational outcome and participation. Results Total IQ (P = 0.023), working memory (P < 0.001), processing speed (P = 0.008), and teacher-reported metacognition (P = 0.022) were lower than norms. Regular school was attended by 82.4% of children with CHD compared to 97% of the general Swiss population (P < 0.001). Seventy-five percent of children participated in leisure activities. Lower total IQ and teacher-rated global executive functions were associated with more educational support and lower IQ was associated with less participation. Conclusion As school-aged children with CHD experience cognitive deficits, follow-up is required to provide optimal support with regard to educational outcome and participation in leisure activities. Impact Contemporary cohorts of children with congenital heart disease undergoing cardiopulmonary bypass surgery remain at increased risk for cognitive deficits. Cognitive deficits affect educational outcome and leisure activities. These findings underline the importance of early detection of cognitive deficits and recommend support with respect to cognitive functioning.

2021 ◽  
Vol 78 (23) ◽  
pp. 2312-2322 ◽  
Gregor O. Dovjak ◽  
Tim Zalewski ◽  
Elisabeth Seidl-Mlczoch ◽  
Patricia A. Ulm ◽  
Vanessa Berger-Kulemann ◽  

2021 ◽  
Vol Publish Ahead of Print ◽  
Lu-Chi Hsiao ◽  
Shuenn-Nan Chiu ◽  
Ling-Yin Chang ◽  
Chia-Ching Wang ◽  
Wen-Chin Weng ◽  

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