bims-hylehe Biomed News
on Hypoplastic left heart syndrome
Issue of 2020‒04‒26
fifteen papers selected by
Richard James
University of Pennsylvania
  1. Trajectories of care in congenital heart disease - the long arm of disease in the womb.
  2. Insertion of the total artificial heart in the Fontan circulation.
  3. Coping with Caregiving Stress in Families of Children with Congenital Heart Disease: A Qualitative Study.
  4. Good at heart: Developing a tertiary perinatal cardiac service; the first eight years of experience.
  5. Environmental and Socioeconomic Factors Influence the Live-Born Incidence of Congenital Heart Disease: A Population-Based Study in California.
  6. Maternal Obesity and Diabetes Mellitus as Risk Factors for Congenital Heart Disease in the Offspring.
  7. Developmental Care of Hospitalized Neonates Outside of the Neonatal Intensive Care Unit: Beyond Surviving But Thriving.
  8. Current status of pediatric mechanical circulatory support.
  9. The cost-effectiveness of prenatal congenital heart defect screening methods in IVF pregnancies.
  10. The total artificial heart in patients with congenital heart disease.
  11. The total artificial heart in pediatrics: outcomes in an evolving field.
  12. A hybrid heart for heart failure - how much remains to be done? An interview with Jolanda Kluin.
  13. Identification and Evaluation of Controlled Trials in Pediatric Cardiology: Crowdsourced Scoping Review and Creation of Accessible Searchable Database.
  14. COVID-19 FAQ's in Pediatric Cardiac Surgery.
  15. Differences in morbidity and mortality in Down syndrome are related to the type of congenital heart defect.
  1. J Intern Med. 2020 Apr 22.
    Trajectories of care in congenital heart disease - the long arm of disease in the womb.
    Marelli A.
      Our understanding of the development of congenital heart disease (CHD) across the lifespan has evolved. These include the evidence for the change in demographics of CHD, the observations that lifelong complications of CHD result in CHD as a lifespan disease, and the concept of long windows of exposure to risk that start in foetal life and magnify the expression of risk in adulthood. These observations set the stage for trajectories as an emerging construct to target health-service interventions. The lifelong cardiovascular and systemic complications of CHD make the long-term care of these patients challenging for cardiologists and internists alike. A life-course approach is thus required to facilitate our understanding of the natural history and to orient our clinical efforts. Three specific examples are illustrated: neurocognition; cancer resulting from exposure to low-dose ionizing radiation; and cardiovascular disease acquired in ageing adults. As patients grow, they do not just want to live longer, they want to live well. With the need to move beyond the mortality outcome, a shift in paradigm is needed. A life-course health development framework is developed for CHD. Trajectories are used as a complex construct to illustrate the patient's healthcare journey. There is a need to define disease trajectories, wellness trajectories and ageing trajectories in this population. Disease trajectories for repaired tetralogy of Fallot, transposition of the great arteries and the Fontan operation are hypothetically constructed. For clinicians, the life-course horizon helps to frame the patient's history and plan for the future. For researchers, life-course epidemiology offers a framework that will help increase the relevance of clinical enquiry and improve study design and analyses. A health-service policy framework is proposed for a growing number of conditions that start in the before birth and extend as long as contemporary survival now permits. Ultimately, the goal is the precision delivery of health services that enables lifelong health management, organization of developmental health services, and integration of vertical and horizontal health-service delivery.
    Keywords:  cardiology; congenital heart disease
    DOI:  https://doi.org/10.1111/joim.13048
  2. Ann Cardiothorac Surg. 2020 Mar;9(2): 134-140
    Insertion of the total artificial heart in the Fontan circulation.
    Jaquiss RDB, Woods RK.
      Though the Fontan circulation provides long-term palliation for patients with univentricular hearts, failure of the circulation may ensue, leaving heart transplantation as the only definitive treatment. For Fontan patients awaiting transplant, both "right-sided" and "left-sided" symptoms may be present and severe, hence, biventricular mechanical circulatory support may be indicated. This can be provided by implantation of the total artificial heart (TAH), a procedure which is performed slightly differently than in patients with biventricular hearts. In this article, the unique aspects of implantation of this device in a patient with a Fontan operation are reviewed, with specific attention to the most commonly encountered anatomic variants of importance to the implanting surgeon.
    Keywords:  Fontan takedown; Total artificial heart (TAH); failing Fontan; univentricular support
    DOI:  https://doi.org/10.21037/acs.2020.03.11
  3. Int J Community Based Nurs Midwifery. 2020 Apr;8(2): 127-139
    Coping with Caregiving Stress in Families of Children with Congenital Heart Disease: A Qualitative Study.
    Dalir Z, Heydari A, Kareshki H, Manzari ZS.
      Background: The families of children with congenital heart disease experience significant stress as to the care of the child and need to cope with stress. Accordingly, understanding of how families cope and use coping strategies is more important to help them better cope with stressful situations caused by caregiving. This study aimed to explore coping strategies used by families in the face of caregiving stress.Methods: This qualitative study was conducted on 40 eligible participants from the families of children with congenital heart disease. They were recruited through a purposive sampling method from those referred to hospitals in Mashhad, Iran. In-depth and semi-structured interviews were used for data collection from November 2017 to December 2018. The data were analyzed using conventional content analysis, and MAXQDA software (Ver.2010) was used to manage the data encoding process.
    Results: According to the results, effort to maintain well-being emerged as the main theme which included five categories: "spirituality in caregiving", "acceptance and adjustment", "optimism and hopefulness", "self-control and patience", and " management of psychological needs".
    Conclusion: Families used various coping strategies including spirituality, acceptance, optimism, patience, and management of psychological needs based on their beliefs, attitudes, abilities, and available resources for coping with caregiving stress. The results can help the nurses and health care professionals to develop appropriate educational, supportive, and psychological interventions based on the family's needs to cope effectively with caregiving stress.
    Keywords:   Child; Congenital heart defects; Coping; Family; Stress
    DOI:  https://doi.org/10.30476/IJCBNM.2020.83029.1113
  4. Aust N Z J Obstet Gynaecol. 2020 Apr 23.
    Good at heart: Developing a tertiary perinatal cardiac service; the first eight years of experience.
    Heland S, de Chellis A, Rieder W, Sleeman M, Johns J, Lancefield T, Robinson A, Fung A, Walker S.
      BACKGROUND: Maternal cardiac disease is the most common cause of indirect maternal death, and women with pre-existing cardiac disease have complex medical, obstetric and anaesthetic requirements. Our hospital commenced a multidisciplinary perinatal cardiac service in 2009 to optimise outcomes in women with cardiac disease.AIM: To assess the maternal and perinatal outcomes of women referred to the clinic to evaluate clinical practice and inform future service provision.
    MATERIALS AND METHODS: This is a single-centre retrospective study of women referred to the perinatal cardiac service between 2009-2016. Data collected included: demographic details; cardiac diagnosis; pregnancy outcomes, including anaesthetic and delivery complications, and admission to intensive care unit (ICU)/high dependency unit (HDU).
    RESULTS: One hundred and fifty-two women were referred for care in 165 pregnancies. Congenital heart disease was the most common indication for referral (35%), followed by maternal cardiac arrhythmia (26%) and valvular disease (18%). The perinatal mortality rate was 2%, median gestational age at delivery was 38 weeks 4 days, fetal growth restriction (customised birthweight <10th centile) was 9% although 25 (17%) pregnancies resulted in preterm birth, 36% of which were spontaneous and 64% were iatrogenic. Maternal outcomes were favourable and there were no maternal deaths. However, 51% of women required a caesarean section, and 23% who achieved a live birth required ICU/HDU admission.
    CONCLUSION: This study confirmed that women with cardiac disease are at increased risk of preterm birth, and high acuity in the peripartum period but otherwise good maternal and perinatal outcomes. An integrated multidisciplinary perinatal cardiac service can optimise perinatal outcomes in these women.
    Keywords:  cardiac disease; cardiology; maternal disease; perinatal; pregnancy
    DOI:  https://doi.org/10.1111/ajo.13160
  5. J Am Heart Assoc. 2020 Apr 21. 9(8): e015255
    Environmental and Socioeconomic Factors Influence the Live-Born Incidence of Congenital Heart Disease: A Population-Based Study in California.
    Peyvandi S, Baer RJ, Chambers CD, Norton ME, Rajagopal S, Ryckman KK, Moon-Grady A, Jelliffe-Pawlowski LL, Steurer MA.
      BACKGROUND The development of congenital heart disease (CHD) is multifactorial with genetic and environmental influences. We sought to determine the relationship between socioeconomic and environmental factors with the incidence of CHD among live-born infants in California and to determine whether maternal comorbidities are in the causal pathway. METHODS AND RESULTS This was a population-based cohort study in California (2007-2012). The primary outcome was having significant CHD. Predictors included socioeconomic status and environmental exposure to pollutants determined by U.S. Census data. A social deprivation index and environmental exposure index was assigned based on neighborhood socioeconomic variables, categorized into 4 quartiles. Quartile 1 was the best with the least exposure to pollutants and social deprivation, and quartile 4 was the worst. Multivariate logistic regression and mediation analyses were performed. Among 2 419 651 live-born infants, the incidence of CHD was 3.2 per 1000 live births. The incidence of CHD was significantly higher among those in quartile 4 compared with quartile 1 (social deprivation index: 0.35% versus 0.29%; odds ratio [OR], 1.31; 95% CI, 1.21-1.41; environmental exposure index: 0.35% versus 0.29%; OR, 1.23; 95% CI, 1.15-1.31) after adjusting for maternal race/ethnicity and age and accounting for the relationship between the 2 primary predictors. Maternal comorbidities explained 13% (95% CI, 10%-20%) of the relationship between social deprivation index and environmental exposure index with the incidence of CHD. CONCLUSIONS Increased social deprivation and exposure to environmental pollutants are associated with the incidence of live-born CHD in California. Maternal comorbidities explain some, but not all, of this relationship. These findings identify targets for social policy initiatives to minimize health disparities.
    Keywords:  congenital cardiac defect; environment; health disparities; socioeconomic position
    DOI:  https://doi.org/10.1161/JAHA.119.015255
  6. J Am Heart Assoc. 2020 Apr 21. 9(8): e011541
    Maternal Obesity and Diabetes Mellitus as Risk Factors for Congenital Heart Disease in the Offspring.
    Helle E, Priest JR.
      Congenital heart disease (CHD) is the most common anatomical malformation occurring live-born infants and an increasing cause of morbidity and mortality across the lifespan and throughout the world. Population-based observations have long described associations between maternal cardiometabolic disorders and the risk of CHD in the offspring. Here we review the epidemiological evidence and clinical observations relating maternal obesity and diabetes mellitus to the risk of CHD offspring with particular attention to mechanistic models of maternal-fetal risk transmission and first trimester disturbances of fetal cardiac development. A deeper understanding of maternal risk factors holds the potential to improve both prenatal detection of CHD by identifying at-risk pregnancies, along with primary prevention of disease by improving preconception and prenatal treatment of at-risk mothers.
    Keywords:  cardiometabolic; congenital heart disease; maternal diabetes mellitus; maternal obesity
    DOI:  https://doi.org/10.1161/JAHA.119.011541
  7. J Perinat Neonatal Nurs. 2020 Apr/Jun;34(2):34(2): 106-107
    Developmental Care of Hospitalized Neonates Outside of the Neonatal Intensive Care Unit: Beyond Surviving But Thriving.
    Broge MJ, Steurer LM.
      
    DOI:  https://doi.org/10.1097/JPN.0000000000000481
  8. Curr Opin Organ Transplant. 2020 Apr 16.
    Current status of pediatric mechanical circulatory support.
    Spigel ZA, Cho J, Adachi I.
      PURPOSE OF REVIEW: The field of pediatric mechanical circulatory support has experienced exponential evolution in recent decades. With favorable complication profiles, implantable continuous-flow ventricular assist devices (VADs) have become a standard option in children, as has been seen in the adult counterpart. Nevertheless, there still exists room for further advances, not just for survival, but throughout the whole trajectory of treatment courses. With reviewing the current state of pediatric VAD support, including existing challenges, we aim to highlight the targets clinicians should focus on for further improvement of pediatric VAD support.RECENT FINDINGS: The field of pediatric VAD has been steadily growing, as evidenced by an increasing number of total VAD implants, particularly with continuous-flow VAD. Currently, HeartWare HVAD (Medtronic Inc., Mounds View, MN) is the most widely used continuous-flow VAD in children with excellent performance. However, only half of the children with HVAD are discharged home, which is drastically different from adult patients, suggesting that the pediatric field is still in the process of maturation. Additionally, outcomes of VAD support for complex congenital heart defect, particularly single ventricle physiology, remain suboptimal, despite an increasing number of such patients.
    SUMMARY: With the ongoing advancement, the field of pediatric VAD support is undergoing a rapid maturation process. This will eventually lead to further paradigm changes, including the use of VAD as permanent therapy.
    DOI:  https://doi.org/10.1097/MOT.0000000000000761
  9. Ultrasound Obstet Gynecol. 2020 Apr 18.
    The cost-effectiveness of prenatal congenital heart defect screening methods in IVF pregnancies.
    Chung EH, Lim SL, Havrilesky LJ, Steiner AZ, Dotters-Katz S.
      OBJECTIVES: To determine if a policy of universal fetal echocardiography (echo) for IVF pregnancies is cost-effective as a screening strategy for congenital heart defects (CHDs) and to examine the cost-effectiveness of various CHD screening strategies in IVF pregnancies.STUDY DESIGN: A decision-analysis model was designed from a societal perspective with respect to the obstetric patient, to compare the cost-effectiveness of three screening strategies: (1) Anatomic-US: selective fetal echo following an abnormal detailed anatomic survey; (2) ICSI-Only: fetal echo for all pregnancies following IVF with ICSI; (3) All-IVF: fetal echo for all IVF pregnancies. The model initiated at conception and had a time horizon of 1 year post-delivery. Sensitivities and specificities for each strategy, probabilities of major and minor CHDs, and all other clinical estimates were derived from the literature. Costs, including imaging, consults, surgeries, caregiver productivity losses, were derived from the literature and Medicare databases. Effectiveness was quantified as quality-adjusted life years (QALYs) based on how the strategies would affect the quality of life of the obstetric patient. Secondary effectiveness was quantified as cases of CHD and, specifically, cases of major CHD detected.
    RESULTS: The average base case cost of each strategy was: Anatomic-US $8,119, ICSI-Only $8,408, and All-IVF $8,560. The effectiveness of each strategy was: Anatomic-US 1.74487 QALYs, ICSI-Only 1.74497 QALYs, and All-IVF 1.74499 QALYs. ICSI-Only had an incremental cost effectiveness ratio (ICER) of $2,840,494/QALY when compared to Anatomic-US; All-IVF had an ICER of $5,962,457/QALY when compared to ICSI-Only. Both ICERs considerably exceed the standard willingness-to-pay threshold of $50,000 to $100,000 per QALY. In a secondary analysis, ICSI-Only had an ICER of $527,562 per additional case of major CHD detected when compared to Anatomic-US. All-IVF had an ICER of $790,510 per case of major CHD detected when compared to ICSI-Only. It was determined that it costs society 5 times more to detect one additional major CHD through intensive screening of all IVF pregnancies than to pay for the neonate's first year of care.
    CONCLUSION: The most cost-effective screening method for CHDs in pregnancies following IVF either with or without ICSI is to obtain a fetal echo only when abnormal cardiac findings are noted on detailed anatomy scans. Routine fetal echo for all IVF pregnancies is not cost-effective. This article is protected by copyright. All rights reserved.
    Keywords:  ICSI; IVF; congenital heart defects; cost-effectiveness; fetal echo; prenatal screening
    DOI:  https://doi.org/10.1002/uog.22048
  10. Ann Cardiothorac Surg. 2020 Mar;9(2): 89-97
    The total artificial heart in patients with congenital heart disease.
    Thangappan K, Ashfaq A, Villa C, Morales DLS.
      Background: While ventricular assist devices (VADs) remain the cornerstone of mechanical circulatory support (MCS), the total artificial heart (TAH-t) has gained popularity for certain patients in whom VAD support is not ideal. Congenital heart disease (CHD) patients often have barriers to VAD placement due to anatomic and physiological variation and thus can benefit from the TAH-t. The purpose of this study is to analyze the differences in TAH application and outcomes in patients with and without CHD.Methods: The SynCardia Department of Clinical Research provided data upon request for all TAH-t implantations worldwide from December 1985 to October 2019. These patients were divided into two groups by pre-implantation diagnosis of CHD and non-CHD.
    Results: A total of 1,876 patients were identified. Eighty (4%) of these patients also carried a diagnosis of CHD. There was a higher proportion of children in the CHD cohort (16.3% vs. 2.1%, P<0.001) and this translated into a lower average age amongst the two groups (34±13 vs. 49±13 years, P<0.001). There were also significantly more females in the CHD group (22.8% vs. 12.8%, P=0.010). CHD patients were more likely to be supported with a 50 cc TAH-t (11.3% vs. 4.5%, P=0.005) while all other support characteristics, including duration of support, were similar between the groups. All measured outcomes were similar between CHD and non-CHD patients including positive outcome (alive on device or transplanted), 1-month conditional survival, and rate of Freedom Driver use.
    Conclusions: TAH-t is an effective means to support patients with CHD. Patients with CHD had similar survival, support characteristics, and frequency of discharge compared to patients without CHD. As MCS continues to grow, its indications broadened, and its contraindications narrowed, more patient populations will see the benefit of the TAH's continuously developing technology.
    Keywords:  Total artificial heart (TAH); congenital heart disease (CHD); heart failure; heart transplantation
    DOI:  https://doi.org/10.21037/acs.2020.02.08
  11. Ann Cardiothorac Surg. 2020 Mar;9(2): 104-109
    The total artificial heart in pediatrics: outcomes in an evolving field.
    Villa CR, Moore RA, Morales DL, Lorts A.
      Background: The use of the SynCardia temporary total artificial heart (TAH-t) in adults has increased with time. The development of the smaller, 50 cc TAH-t has expanded the potential applications of the device in children. We sought to describe the evolving use of the TAH-t over time and describe outcomes in the current era.Methods: The SynCardia database was queried to identify all pediatric patients ≤18 years of age implanted with the device between December 1985 and October 2019. Patient demographics, clinical outcome and support characteristics collected.
    Results: Fifty-one children were supported, 36 with the 70 cc TAH-t and 15 with the 50 cc TAH-t with a total support time of 6,243 days. The number of implants has increased with time (19 between 2015 and 2019). A total of 13 patients have been converted to Freedom Driver support, seven 50 cc TAH-t and six 70 cc TAH-t. The majority of implants in the last 5 years (15/19, 79%) have been with the 50 cc TAH-t. The most common diagnosis was dilated cardiomyopathy [24 (47%)] and the average age at the time of implant was 16±2 years old. Overall survival for the patient cohort was 71%.
    Conclusions: The use of the SynCardia TAH-t to support children with end-stage heart failure has increased over time. Clinical outcomes with both the 50 cc and 70 cc TAH-t are similar to reported outcomes in adults who require TAH-t or other methods of biventricular support.
    Keywords:  Total artificial heart; congenital heart disease; pediatrics
    DOI:  https://doi.org/10.21037/acs.2020.02.15
  12. Future Cardiol. 2020 Apr 23.
    A hybrid heart for heart failure - how much remains to be done? An interview with Jolanda Kluin.
    Kluin J.
      Jolanda Kluin speaks to Julia Titova, Commissioning Editor at Future Cardiology Jolanda Kluin started her medical training at the Erasmus University Rotterdam in 1989 and obtained her medical degree cum laude in 1996. Thereafter, she worked as a PhD student on the project: "Photodynamic therapy for Barrett's esophagus with use of 5-aminolevulinic acid", receiving her PhD degree cum laude in 1999. In 2006 she finished her residency in cardiothoracic surgery. From 2006 to 2014 she worked as a staff cardiothoracic surgeon at the Department of Cardiothoracic Surgery of the University Medical Center Utrecht and since 2015 she works at the Academic Medical Center, Amsterdam as congenital cardiac surgeon. In 2018 she became a professor in translational cardiothoracic surgery at the University of Amsterdam. Her main interests are grown ups with congenital heart disease cardiac surgery, mitral valve surgery, and reconstructive surgery of the aortic valve and the thoracic aorta. Alongside her clinical tasks, she has started a new line of research in translational cardiothoracic surgery, including tissue engineering of heart valves, valve pathophysiology and the development of a hybrid soft robotic total artificial heart. She is the current chair of the EACTS Women in Cardiothoracic Surgery Committee.
    Keywords:  artificial heart; congenital heart disease; heart failure
    DOI:  https://doi.org/10.2217/fca-2020-0041
  13. Can J Cardiol. 2020 Feb 15. pii: S0828-282X(20)30174-4. [Epub ahead of print]
    Identification and Evaluation of Controlled Trials in Pediatric Cardiology: Crowdsourced Scoping Review and Creation of Accessible Searchable Database.
    Ashkanase J, Nama N, Sandarage RV, Penslar J, Gupta R, Ly S, Wan M, Tsang P, Nantsios A, Jacques E, Yang HY, Tsang CI, Mazhar H, Xu G, Rodriguez M, Gerber S, Laird LM, Sampson M, Wong DT, McNally JD.
      Cardiac disease in children is associated with significant morbidity and mortality as well as increased health resource utilisation. There is a perception that there is a paucity of high-quality studies, particularly randomised controlled trials (RCTs), in the field of pediatric cardiology. We sought to identify, examine, and map the range of RCTs conducted in children with cardiac conditions, including the development of a searchable open-access database. A literature search was conducted encompassing MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from inception to 2018. All English-language RCTs enrolling children (age 0-21 years) with cardiac conditions were included. Data extraction and risk of bias assessments were performed in duplicate via crowdsourcing for each eligible study and entered into an online database. A total of 933 RCTs met eligibility criteria. Median trial recruitment was 49 patients (interquartile range 30-86) with 18.9% of studies (n = 176) including > 100 patients. A wide variety of populations and interventions were encompassed with congenital heart disease (79.8% of RCTs) and medications (63.3% of RCTs) often studied. Just over one-half of the trials (53.4%) clearly identified a primary outcome, and fewer than half (46.6%) fully documented a robust randomisation process. Trials were summarised in a searchable online database (https://pediatrics.knack.com/cardiology-rct-database#cardiology-rcts/). Contrary to a commonly held perception, there are nearly 1,000 published RCTs in pediatric cardiology. The open-access database created as part of this project provides a resource that facilitates an efficient comprehensive review of the literature for clinicians and researchers caring for children with cardiac issues.
    DOI:  https://doi.org/10.1016/j.cjca.2020.01.028
  14. World J Pediatr Congenit Heart Surg. 2020 Apr 21. 2150135120924653
    COVID-19 FAQ's in Pediatric Cardiac Surgery.
    Levy E, Blumenthal J, Chiotos K, Dearani JA.
      
    Keywords:  COVID-19; congenital heart disease; education; frequently asked questions
    DOI:  https://doi.org/10.1177/2150135120924653
  15. Am J Med Genet A. 2020 Apr 22.
    Differences in morbidity and mortality in Down syndrome are related to the type of congenital heart defect.
    Baban A, Olivini N, Cantarutti N, Calì F, Vitello C, Valentini D, Adorisio R, Calcagni G, Alesi V, Di Mambro C, Villani A, Dallapiccola B, Digilio MC, Marino B, Carotti A, Drago F.
      Morbidity and mortality in Down syndrome (DS) are mainly related to congenital heart defects (CHDs). While CHDs with high prevalence in DS (typical CHDs), such as endocardial cushion defects, have been extensively described, little is known about the impact of less common CHDs (atypical CHDs), such as aortic coarctation and univentricular hearts. In our single-center study, we analyzed, in observational, retrospective manner, data regarding cardiac features, surgical management, and outcomes of a cohort of DS patients. Literature review was performed to investigate previously reported studies on atypical CHDs in DS. Patients with CHDs were subclassified as having typical or atypical CHDs. Statistical analysis was performed for comparison between the groups. The study population encompassed 859 DS patients, 72.2% with CHDs, of which 4.7% were atypical. Statistical analysis showed a significant excess in multiple surgeries, all-cause mortality and cardiac mortality in patients with atypical CHDs (p = .0067, p = .0038, p = .0001, respectively). According to the Kaplan-Meier method, survival at 10 and 40 years was significantly higher in typical CHDs (99 and 98% vs. 91 and 84%, log rank <0.05). Among atypical CHDs, it seems that particularly multiple complex defects in univentricular physiology associate with a worse outcome. This may be due to the surgical difficulty in managing univentricular hearts with multiple defects concurring to the clinical picture or to the severity of associated defects themselves. Further studies need to address this specific issue, also considering the higher pulmonary pressures, infective complications, and potential comorbidities in DS patients.
    Keywords:  Down syndrome; atrioventricular septal defects; congenital heart defects; left-sided congenital heart defects; univentricular physiology
    DOI:  https://doi.org/10.1002/ajmg.a.61586
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