Open research questions in Congenital Heart Disease Studies

What the literature leaves open

• Despite the international uptake of POS, there is still no consensus regarding the most appropriate screening algorithm, although several have been described.

  Pulse Oximetry Screening in the Newborn: Can Modifications to the Screening Algorithm Improve Detection? · 2026 · DOI

• Future research is warranted to evaluate the clinical usefulness, cost–benefit ratio, and optimal strategies for implementing CCHD screening across different healthcare settings, particularly where prenatal detec- tion is limited or unavailable.

  Neonatal screening for critical congenital heart disease: five-year experience of a tertiary hospital · 2026 · DOI

• BackgroundGaps in care (GIC) among patients with congenital heart disease (CHD) are associated with adverse outcomes, yet the specific social and healthcare-related factors contributing to GIC and the clinical consequences of delayed re-engagement in care remain poorly characterized.

  Gaps in Congenital Heart Disease Care: Social Drivers and Clinical Consequences · 2026 · DOI

• sections of patent ductus arteriosus, heart failure and cyanosis. What is new is that the patients will benefit now care at ACHD centers where specialists will provide guidelines-directed care and work with multidisciplinary teams. For example, patients with moderate ACHD before undergoing cardiac or noncardiac procedures should be consulted by ACHD specialist who will guide care during and after procedures. Again, pregnant women with ACHD can undergo vaginal delivery with proper monitoring and risk stratification. Patients with repaired tetralogy of Fallot after should be referred for pulmonary valve replacement, if right ventricular (RV) end-systolic volume is >80 ml/m2; also these patients can undergo and new ablation approaches arrhythmia management. Patients with secundum atrial septal defect, pulmonary hypertension, significant left-to right shunt, and pulmonary vascular resistance of 2 Woods units or >2 less than 5 Wood units should undergo closure of defect. In patients with complex ACHD as systemic RV and Fontan circulation with atrial arrhythmias, rhythm control is preferred strategy over rate control. Guideline –directed medical therapy for HF treatment is indicated in patients with systemic right or left ventricle and the pacing strategies should be sought for patients with systemic RV and Fontan circulation. Patients with Eisenmenger syndrome can be as pulmonary treated phosphodiesterase -5 inhibitors or endothelin receptor antagonist as initial strategy. Patients with Fontan tachycardia recommended ventricular are vasodilators with for for circulation should undergo screening for liver disease annually. Guidelines on APE management (7) presents a new clinical classification of APE based on clinical categories (5 categories A-E) and subcategories to guide prognosis and treatment decision –making. Asymptomatic patients with ACC/AHA APE category A can be discharged from emergency room and do not need hospitalization. Symptomatic patients in category B with low severity score can be discharged early and patients with APE and higher severity score with increased biomarkers and RV dysfunction (category C), emergent cardiopulmonary failure (category D) and those with accompanying above symptoms persistent hypotension (category E) should be hospitalized to optimize treatment. In patients with APE category E1, advanced therapies as systemic or catheter-based thrombolysis, mechanical or surgical embolectomy are reasonable strategies. These therapies could be considered in D1-2 category of patients. In APE patients who require unfractionated heparin, low molecular weight heparin is recommended over heparin. Patients eligible for oral are anticoagulation, recommended over vitamin K antagonists to prevent venous thromboembolism and reduce major bleeding. Patient with first APE and those with persistent risk is factors, anticoagulation beyond 3-6 months recommended. Patients should be monitored at least 1year for development of chronic thromboembolic pulmonary disease. To improve care, formation of PE response teams is recommended.

  From Editor-in-Chief: On current issue, acknowledging the best in 2025, new guidelines and statements · 2026 · DOI

• The study is limited by the relatively small cohort size and by the lower number of girls and women than boys and men. As it was not possible to recruit healthy children for this study, patients who had been referred to CMR and who had cardiovascular and non-cardiovascular disorders that were unlikely to affect the size and anatomy of the pulmonary arteries were included. However, it cannot be ruled out that the size and anatomy of the pulmonary arteries in our cohort differ from normal. Additionally, the radial QISS method is not available everywhere, which may limit the broader clinical applicability of our results.

  Pulmonary Artery Diameters in Children, Teenagers and Young Adults Derived from Quiescent Interval Slice Selective (QISS) Magnetic Resonance Angiography · 2026 · DOI

• 1 Pathogenesis and clinical rarity the fusion scarce, and specific pathogenesis Complete absence of the mitral chordae tendineae with concomitant papillary muscle is an extremely rare congenital cardiac malformation, for which clinical reports are exceedingly remains incompletely elucidated.

  Case Report: Transthoracic echocardiographic diagnosis of agenesis of mitral chordae tendineae with papillary muscle fusion · 2026 · DOI

• Abstract Background Turner syndrome (TS) is associated with cardiovascular abnormalities and metabolic risk, but karyotype-specific phenotypes remain incompletely defined, particularly in pediatric and adolescent cohorts assessed by transthoracic echocardiography (TTE).

  Karyotype-specific cardiovascular and metabolic profiles in Turner syndrome: a retrospective echocardiographic study · 2026 · DOI

• Importance Despite widespread adoption and investment of resources nationally, the pediatric acute care cardiology (ACC) model of care has not been previously evaluated prospectively.

  Adoption of a Pediatric Acute Care Cardiology Inpatient Model · 2026 · DOI

• inability inflammatory Like many pediatric studies in congenital heart disease, our study was limited by a relatively small sample size and incomplete imaging datasets, precluding multivariable analyses. As a result, the observed associations may reflect shared hemodynamic influences rather than independent predictors. The heterogeneous cohort and to stratify by diagnosis or ventricular morphology may have further masked subgroup-specific effects. The wide range in PE duration, may reflect additional unmeasured risk factors such as lymphatic dysfunction, postoperative management differences, or responses, which were not systematically assessed in this study. Image quality constraints, particularly in 3D echocardiography and MRI, led to exclusion of several datasets and limited completeness of analysis. Acquisition of high-quality 3D datasets in young children is technically challenging due to high heart rates, motion, and limitations of ECG-gated multi- beat imaging, increasing the risk of stitching and tracking artefacts (23). Invasive validation of APC flow was not performed, and MRI flow analysis was conducted by a single non-blinded observer without formal assessment of inter- or intra-observer variability, which may introduce measurement bias. Postoperative outcomes may also have been influenced by clinical management factors, as chest tube removal was not protocolized, and data on pleural effusion volume, postoperative medications, and other contributors such as pulmonary artery anatomy or diaphragmatic function were not available. Mesenteric resistance indices are influenced by multiple physiological factors that were not controlled for in this study. Several established determinants of prolonged pleural effusion after TCPC, such as pulmonary vascular resistance, Fontan pressure, ventricular diastolic function, atrioventricular valve regurgitation, lymphatic abnormalities, and nutritional status, were not systematically assessed. Therefore, the observed associations between APC flow, GLS, SMA resistance index, and pleural effusion duration may partly reflect overall hemodynamic severity of single-ventricle physiology rather than a specific causal relationship and should be interpreted as exploratory rather than predictive or mechanistic.

  Preoperative myocardial strain, mesenteric resistance, and aortopulmonary collateral flow are associated with pleural effusion duration after fontan completion · 2026 · DOI

• The current study has its limitations that must be taken into account during the interpretation of the results. The study was limited to a single tertiary care center, which may restrict the generalizability of the findings to larger and more diverse populations. The study involved only healthy term newborns, not preterm or low- birth-weight infants, and thus, not all babies who might need early screening were represented. The sample size was also insufficient to establish definitive sensitivity, specificity, positive predictive value, or negative predictive value for early pulse oximetry screening. Because CCHD is relatively uncommon, the present study was not adequately powered to detect rarer CCHD variants or to reliably estimate the risk of false- negative screening results. Also, no long-term follow-up of newborns whose screening was found to be normal was performed, and this could have resulted in missed cases that became clinically apparent after discharge. Future studies should be multicentric and include larger sample sizes to confirm the applicability of early pulse oximetry screening in different healthcare environments. Such studies should be adequately powered to assess diagnostic accuracy, including sensitivity, specificity, false-positive rates, and false-negative rates for both common and rare forms of CCHD. This should also include high-risk newborn groups, such as preterm babies and low-birth-weight infants. Employing long-term follow-up and cost-effectiveness analyses of early screening protocols would assist in formulating standard protocols to be adopted in universal neonatal care practice.

  Role of Pulse Oximetry Screening for Term Healthy Newborns During Transitional Period to Detect Critical Congenital Heart Disease (CCHD): A Prospective Observational Study in a Tertiary Care Hospital · 2026 · DOI

• is consistent across multiple versus parallel circulation) when titrating, and engage sensitivity analyses, and the GRADE certainty for the families in shared decision-making about the timing of apnoea and fever outcomes is moderate to low, definitive intervention.

  Prostaglandin E1 Dose and Duration as Determinants of Adverse Outcomes in Neonates with Duct-Dependent Congenital Heart Disease: A Systematic Review and Meta-Analysis · 2026 · DOI

• This study has several limitations. First, this study is limited by the single-arm, retrospective, real-world setup, and the anatomical and surgical heterogeneity inherent to the Fontan population. Linear mixed models were used to account for within-patient correlations and unbalanced data, with data from the year before starting SGLT2i serving as the patients’ control data. While randomized controlled trials remain the gold standard, real-world registries provide essential evidence that advances clinical care in the Fontan population. Second, the lack of (exercise) catheterization data in the registry prevented detailed stratification of the underlying hemodynamic mechanisms of FCF. The dichotomization of patients into FCFrEF and FCFpEF oversimplifies the complex phenotypes of FCF, and future studies should aim to evaluate the benefits of SGLT2i for different underlying causes. Third, although all patients had preserved renal there was no function at baseline and deterioration after SGLT2i, creatinine-based eGFR estimation is influenced by skeletal muscle and may overestimate actual renal function in the Fontan population, which is known to be subject to sarcopenia. Twenty-four-hour urine creatinine clearance would have provided a more accurate estimate of renal function.

  Real-world experience with sodium-glucose cotransporter 2 inhibitors in adults with Fontan circulatory failure · 2026 · DOI

• Although the study proposes a potential skeletal muscle testing bundle for clinical application in SV patients, the validity and clinical utility of this bundle relative to health outcomes has not been established. Validation studies relating the skeletal muscle testing bundle metrics to long-term cardiac and functional outcomes are required.

  Protocol for non-invasive assessment of skeletal muscle structure and function in adolescents with single ventricle heart disease: a cross-sectional, case-control study · 2026 · DOI

• The study aims to generate hypotheses supporting future exercise intervention trials (aerobic activation, strength training, hypertrophy) in the SV population, but no randomized controlled trials testing specific exercise interventions on skeletal muscle outcomes in SV adolescents have been designed or conducted.

  Protocol for non-invasive assessment of skeletal muscle structure and function in adolescents with single ventricle heart disease: a cross-sectional, case-control study · 2026 · DOI

• Different SV morphologies are included in the analysis, which may dilute morphology-specific effects on skeletal muscle structure and function. Future studies should stratify analyses by specific single ventricle morphology (e.g., hypoplastic left heart syndrome, pulmonary atresia) to identify domain-specific skeletal muscle impairments.

  Protocol for non-invasive assessment of skeletal muscle structure and function in adolescents with single ventricle heart disease: a cross-sectional, case-control study · 2026 · DOI

• The current study design is cross-sectional and prohibits identification of causality between skeletal muscle deficits and adverse outcomes in SV patients. Longitudinal studies tracking skeletal muscle structure and function changes over time in adolescents with single ventricle physiology are needed to establish causal relationships.

  Protocol for non-invasive assessment of skeletal muscle structure and function in adolescents with single ventricle heart disease: a cross-sectional, case-control study · 2026 · DOI

• Mitochondrial oxidative capacity, motor unit neural activation, and muscle quality in single ventricle patients have been poorly studied. This study represents the first comprehensive evaluation of all skeletal muscle domains in SV adolescents, but future studies must isolate and characterize mitochondrial function using specific oxidative capacity assays in this population.

  Protocol for non-invasive assessment of skeletal muscle structure and function in adolescents with single ventricle heart disease: a cross-sectional, case-control study · 2026 · DOI

• A total of 1,350 2D ultrasound fetal heart images (collected in four years, 2021–2024) were collected in accordance with ethical considerations based on both private and web-based sources. Preprocessing is done in noise removal and optimal ROI segmentation by the EZOO algorithm. STA is used to improve feature extraction, and IWO algorithm that was concerned with the data dimensionality to select features. In VSD Optimal prenatal diagnosis model for fetal heart ventricular septal defect detection using hybrid deep…1 3 177 Page 14 of 19 m h t i r o g l a O W I g n i s u n o i t c e l e s e r u t a e F e r u s a e m - F 5. 0 @ P A m l l a c e R n o i s i c e r P e r u s a e m - F 5. 0 @ P A m n o i t c e l e s e r u t a e f t u o h t i W l l a c e R n o i s i c e r P 0 5 9. 0 3 4 9. 0 8 4 9. 0 5 4 9. 0 7 4 9. 0 5 5 9. 0 8 4 9. 0 2 5 9. 0 9 4 9. 0 2 5 9. 0 3 6 9. 0 6 5 9. 0 0 6 9. 0 6 5 9. 0 1 6 9. 0 9 6 9. 0 1 6 9. 0 5 6 9. 0 2 6 9. 0 5 6 9. 0 0 6 9. 0 3 5 9. 0 7 5 9. 0 4 5 9. 0 8 5 9. 0 7 6 9. 0 1 6 9. 0 4 6 9. 0 2 6 9. 0 3 6 9. 0 1 7 9. 0 5 6 9. 0 8 6 9. 0 6 6 9. 0 7 6 9. 0 8 7 9. 0 3 7 9. 0 6 7 9. 0 3 7 9. 0 5 7 9. 0 2 8 9. 0 7 7 9. 0 0 8 9. 0 8 7 9. 0 9 7 9. 0 6 7 9. 0 0 7 9. 0 4 7 9. 0 2 7 9. 0 3 7 9. 0 6 5 9. 0 9 4 9. 0 4 5 9. 0 1 5 9. 0 3 5 9. 0 0 6 9. 0 3 5 9. 0 7 5 9. 0 5 5 9. 0 8 5 9. 0 8 6 9. 0 1 6 9. 0 5 6 9. 0 2 6 9. 0 6 6 9. 0 3 7 9. 0 6 6 9. 0 0 7 9. 0 7 6 9. 0 0 7 9. 0 5 6 9. 0 8 5 9. 0 2 6 9. 0 0 6 9. 0 3 6 9. 0 5 4 9. 0 8 3 9. 0 2 4 9. 0 9 3 9. 0 1 4 9. 0 0 5 9. 0 2 4 9. 0 6 4 9. 0 3 4 9. 0 7 4 9. 0 8 5 9. 0 1 5 9. 0 5 5 9. 0 1 5 9. 0 6 5 9. 0 4 6 9. 0 6 5 9. 0 1 6 9. 0 7 5 9. 0 0 6 9. 0 5 5 9. 0 8 4 9. 0 2 5 9. 0 9 4 9. 0 3 5 9. 0 9 1 9. 0 1 1 9. 0 7 1 9. 0 2 1 9. 0 6 1 9. 0 3 2 9. 0 4 1 9. 0 0 2 9. 0 6 1 9. 0 1 2 9. 0 1 3 9. 0 0 2 9. 0 6 2 9. 0 0 2 9. 0 5 2 9. 0 5 3 9. 0 3 2 9. 0 9 2 9. 0 3 2 9. 0 8 2 9. 0 6 2 9. 0 6 1 9. 0 3 2 9. 0 8 1 9. 0 2 2 9. 0 5 4 9. 0 9 3 9. 0 3 4 9. 0 0 4 9. 0 2 4 9. 0 0 5 9. 0 2 4 9. 0 7 4 9. 0 3 4 9. 0 6 4 9. 0 5 5 9. 0 9 4 9. 0 2 5 9. 0 8 4 9. 0 1 5 9. 0 0 6 9. 0 4 5 9. 0 7 5 9. 0 3 5 9. 0 6 5 9. 0 1 5 9. 0 6 4 9. 0 0 5 9. 0 5 4 9. 0 9 4 9. 0 6 2 9. 0 8 1 9. 0 5 2 9. 0 0 2 9. 0 4 2 9. 0 9 2 9. 0 1 2 9. 0 7 2 9. 0 3 2 9. 0 8 2 9. 0 8 3 9. 0 7 2 9. 0 3 3 9. 0 7 2 9. 0 2 3 9. 0 2 4 9. 0 0 3 9. 0 6 3 9. 0 0 3 9. 0 5 3 9. 0 3 3 9. 0 4 2 9. 0 0 3 9. 0 5 2 9. 0 9 2 9. 0 2 1 9. 0 4 0 9. 0 0 1 9. 0 5 0 9. 0 9 0 9. 0 8 1 9. 0 7 0 9. 0 3 1 9. 0 9 0 9. 0 4 1 9. 0 4 2 9. 0 2 1 9. 0 9 1 9. 0 3 1 9. 0 8 1 9. 0 9 2 9. 0 6 1 9. 0 2 2 9. 0 6 1 9. 0 1 2 9. 0 0 2 9. 0 9 0 9. 0 6 1 9. 0 1 1 9. 0 5 1 9. 0 n o i t c e t e d D S V t r a e h l a t e f f o s t l u s e R 6 e l b a T s s a l C d l o F l a m r o N 1 d l o F D S V s u o n a r b m e m i r e P D S V l a t s i r c a r p u S D S V r a l u c s u M D S V t e l n I D S V s u o n a r b m e m i r e P D S V l a t s i r c a r p u S D S V r a l u c s u M D S V t e l n I D S V s u o n a r b m e m i r e P D S V l a t s i r c a r p u S D S V r a l u c s u M D S V t e l n I D S V s u o n a r b m e m i r e P D S V l a t s i r c a r p u S D S V r a l u c s u M D S V t e l n I D S V s u o n a r b m e m i r e P D S V l a t s i r c a r p u S D S V r a l u c s u M D S V t e l n I l a m r o N 3 d l o F l a m r o N 4 d l o F l a m r o N 5 d l o F l a m r o N 2 d l o F R. Mittal, M. Bhushan1 3 Page 15 of 19 177 Fig.

  Optimal prenatal diagnosis model for fetal heart ventricular septal defect detection using hybrid deep learning · 2026 · DOI

• Acknowledgments A potential drawback of LVOT stenting is its impact on subsequent surgical repair. The rigid stent may distort the geometry of the subpulmonary region or the pulmonary valve, thereby complicating later intracardiac rerouting procedures. In addition, stent struts may embed within the endocardium or fibrose into surrounding tissue, requiring surgical excision or necessitating modifications. These factors can increase operative complexity and risk.

  Left ventricular outflow tract stenting in late presenting transposition physiology with ventricular shunt and pulmonary stenosis: a case series · 2026 · DOI

• Further research into the molecular genetics and pathogenesis of CTD holds promise for early risk stratification and personalised management in children with CHD.

  CONGENITAL HEART DEFECTS AND THEIR ASSOCIATION WITH CONNECTIVE TISSUE DYSPLASIA IN CHILDREN (REVIEW) · 2025 · DOI

• Dilated cardiomyopathy (DCM) in children remains the most frequent type of cardiomyopathy, representing an important cause of death in the first 2 years of life, and its impact at neonatal age is not fully understood, due to the low number of studies regarding its real incidence.

  New approaches to pediatric dilated cardiomyopathy in current practice · 2020 · DOI

• Conclusion: Echo has a diagnostic advantage and in general, CMR and Echo findings overlap in cases with valve dysfunctions, ventricular wall motion disorders, and hypertrophy, whereas we found that Echo findings were insufficient for diagnosis of congenital heart pathologies.

  Comparison of cardiac magnetic resonance and cardiac ultrasound imaging findings in congenital and acquired heart diseases · 2020 · DOI

• Despite the need for lifelong care due for residual symptoms, only a few studies have explored cardiac-related HRQOL but none in lower middle-income countries (LMIC).

  Health-related quality of life in surgical children and adolescents with congenital heart disease compared with their age-matched healthy sibling: a cross-sectional study from a lower middle-income country, Pakistan · 2018 · DOI

• Although percutaneous transcatheter atrial septal defect (ASD) closure (TCC) has been performed on adults for a long time there is limited data about the effects of the procedure in the literature and the majority of studies have been performed on children.

  Effects of the transcatheter closure of atrial septal defect on electrocardiographic and echocardiographic parameters six months after the closure · 2016 · DOI

• Conclusions The evidence remains inconsistent and limited by heterogeneity, absence of theoretical foundations, risk of bias, and high dropout rates; further refinement is thus needed.

  Effectiveness of eHealth Interventions for Adolescents and Young Adults With Congenital Heart Disease: Systematic Review · 2026 · DOI

Most-cited papers in Congenital Heart Disease Studies

• Incidence, Causes, and Outcomes of Dilated Cardiomyopathy in Children · JAMA · 2006 · 869 citations
• Necrotizing Enterocolitis in Neonates With Congenital Heart Disease: Risk Factors and Outcomes · PEDIATRICS · 2000 · 376 citations
• Epidemiology of Idiopathic Cardiomyopathies in Children and Adolescents: A Nationwide Study in Finland · American Journal of Epidemiology · 1997 · 219 citations
• Infant mortality and congenital anomalies from 1950 to 1994: an international perspective · Journal of Epidemiology & Community Health · 2000 · 216 citations
• Neurodevelopmental Outcomes for Individuals With Congenital Heart Disease: Updates in Neuroprotection, Risk-Stratification, Evaluation, and Management: A Scientific Statement From the American Heart Association · Circulation · 2024 · 178 citations
• Cardiovascular abnormalities in Down's syndrome: spectrum, management and survival over 22 years · Archives of Disease in Childhood · 2011 · 122 citations
• Association of maternal chronic disease with risk of congenital heart disease in offspring · Canadian Medical Association Journal · 2016 · 81 citations
• Ethnic and socioeconomic variation in incidence of congenital heart defects · Archives of Disease in Childhood · 2016 · 77 citations
• Health-related quality of life in congenital heart disease surgery in children and young adults: a systematic review and meta-analysis · Archives of Disease in Childhood · 2018 · 71 citations
• Evaluation and Management of Chronic Heart Failure in Children and Adolescents With Congenital Heart Disease: A Scientific Statement From the American Heart Association · Circulation · 2024 · 68 citations

Most recent work

• Prevalence of Cerebral Abnormalities in Children With Congenital Heart Disease: A Systematic Review and Meta-Analysis · PEDIATRICS · 2026
• Case Report: Cor triatriatum sinister presenting as acute decompensated heart failure in an adolescent · Frontiers in Cardiovascular Medicine · 2026
• Left ventricular outflow tract stenting in late presenting transposition physiology with ventricular shunt and pulmonary stenosis: a case series · Frontiers in Cardiovascular Medicine · 2026
• Optimal prenatal diagnosis model for fetal heart ventricular septal defect detection using hybrid deep learning · Applied Intelligence · 2026
• Real-time deep learning interpretation of echocardiographic video for automated detection of anatomical features associated with tetralogy of fallot in pediatric patients : a feasibility study · Scientific Reports · 2026
• Protocol for non-invasive assessment of skeletal muscle structure and function in adolescents with single ventricle heart disease: a cross-sectional, case-control study · Frontiers in Cardiovascular Medicine · 2026
• 3D Virtual reality assessment of right ventricle-pulmonary artery conduit dilation and coronary compression risk: a retrospective bi-center feasibility study · Frontiers in Cardiovascular Medicine · 2026
• Twenty Years' Experience of Congenital Heart Disease Characterization in Thammasat University Hospital · Asian Medical Journal and Alternative Medicine · 2026
• <scp>5D</scp> Flow <scp>MRI</scp> Reveals Respiration‐Driven Changes in Blood Flow Energetics in Congenital Heart Disease · Magnetic Resonance in Medicine · 2026
• Case Report: Transthoracic echocardiographic diagnosis of agenesis of mitral chordae tendineae with papillary muscle fusion · Frontiers in Cardiovascular Medicine · 2026

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