Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
Showing 11 appraisals
RMD open
Anakinra for intravenous immunoglobulin-resistant Kawasaki disease: a systematic literature review
BACKGROUND: Approximately 10%-20% of patients with Kawasaki disease (KD) are resistant to intravenous immunoglobulins (IVIG) and are at increased risk of developing coronary artery aneurysms (CAA). A potential therapeutic role of anakinra (ANK) in refractory KD has been suggested. The aim of this work is to systematically review and critically appraise the available clinical evidence on the use of ANK in the treatment of IVIG-resistant KD, focusing on treatment indications, timing, dosage, efficacy on fever, inflammation, CAA and safety. METHODS: A systematic literature search was conducted across PubMed, Embase, Web of Science, Cochrane Library, Emcare, Academic Search Premier and Google Scholar from inception to 9 October 2025, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Eligible studies included all study designs reporting outcomes of patients with KD treated with ANK. RESULTS: Thirty-two publications (31 identified through database search and one by cross-referencing) describing 81 patients were included. Most reports were single cases or small series, with two early-phase clinical trials. Treatment with ANK was associated with resolution of fever and systemic inflammation in 94.9% of patients. Complete CAA resolution was reported in 32% and stabilisation/dimensional reduction in 56.3%. No serious safety concerns were identified. However, these findings derive from heterogeneous and low-quality evidence and should be interpreted with caution. CONCLUSIONS: In IVIG-resistant KD, ANK was effective in controlling systemic inflammation, although more data are needed to assess its efficacy on coronary outcomes. While these findings are encouraging in supporting consideration of ANK for refractory KD, larger randomised clinical studies are warranted to define optimal ANK timing of introduction and dosing, and to evaluate its long-term efficacy on cardiac outcomes. PROSPERO REGISTRATION NUMBER: CRD420252129435.
31 July 2026
Read appraisal →JMIR mHealth and uHealth
mHealth Technologies for the Care of Children With Congenital Heart Disease: Scoping Review
BACKGROUND: Mobile information technology (IT) is increasingly being used in the health care sector, and it can play a critical role in both the care of children with congenital heart disease (CHD) and the quality of life of their families. OBJECTIVE: This study aimed to conduct a scoping review of the application of mobile health (mHealth) technologies in the care of children with CHD. We summarized the forms of mHealth interventions and effects on CHD to provide a reference for future research in this field. METHODS: We searched PubMed; Embase; Web of Science; the Cochrane Library; CINAHL; China National Knowledge Infrastructure; Wanfang Data; the Chinese Biomedical Database; VIP Chinese Science and Technology Journal Database; National Guideline Clearinghouse of the United States; the website of the Registered Nurses' Association of Ontario, Canada; the Guidelines International Network; the American Heart Association; and the American Association of Cardiovascular and Pulmonary Rehabilitation. The search period was from the establishment of the databases to June 12, 2025. The retrieved literature was screened and analyzed. RESULTS: A total of 519 Chinese- and English-language articles were identified, with 44 (8.5%) studies meeting the inclusion criteria. The primary forms of mHealth interventions for patients with CHD included mobile apps, wearable devices, and remote monitoring equipment. The findings indicated that mHealth technologies could improve exercise capacity, nutritional status, psychological well-being, and quality of life in children with CHD. CONCLUSIONS: The application of mHealth in the care of children with CHD is feasible and demonstrates positive effects. Future research should emphasize peer education and patient privacy protection while further exploring remote education and health management based on theoretical frameworks and intelligent ITs to enhance quality of life for both children with CHD and their parents.
19 July 2026
Read appraisal →BMC cardiovascular disorders
Clinical spectrum, cardiac phenotypes, and outcomes of FHL1-related cardiomyopathies: a systematic review
BACKGROUND: Mutations in the Four-and-a-Half LIM Domains 1 (FHL1) gene are increasingly recognized as a rare cause of inherited cardiomyopathies, often associated with skeletal myopathy and adverse cardiac outcomes. The phenotypic spectrum and clinical implications of FHL1 variants remain poorly defined. OBJECTIVE: To systematically review published cases of FHL1-related cardiomyopathy and characterize the clinical, genetic, and pathological features. METHODS: We conducted a systematic literature search in PubMed and EMBASE up to July 2025 using predefined criteria to identify studies reporting clinical cases of patients with FHL1 mutations and cardiac involvement. Data on genotype, phenotype, cardiac and neuromuscular features, and clinical outcomes were extracted and synthesized. RESULTS: Twenty-two studies were included, comprising 114 patients with pathogenic or likely pathogenic FHL1 mutations. Most patients were male (69%), with a median age of onset of 18 (IQR 10-26) years. Cardiac involvement consisted in left ventricular hypertrophy (56%), followed by arrhythmias (51%), and conduction abnormalities (8%). The incidence of sudden cardiac death was 7%, and heart transplantation was reported in 5% of patients. Skeletal muscle involvement was present in 75%, ranging from mild contractures to more severe myopathic phenotypes with functional impairment. Creatine kinase levels were variably elevated. Truncating variants were reported in several severe cardiac presentations in young males, while isolated cardiac disease occurred with selected variants. CONCLUSIONS: FHL1-related cardiomyopathy is a rare but important diagnosis. Genetic testing should be considered in patients with cardiac hypertrophy and neuromuscular features. Further research is needed to define prognostic markers and guide management.
19 June 2026
Read appraisal →Open heart
Impact of three-dimensional heart models on surgical planning and outcomes in congenital heart disease: a systematic review and meta-analysis
BACKGROUND: Congenital heart disease surgery includes intricate structures that are perhaps hard to completely understand by traditional two-dimensional shapes. Individualised, centre-based three-dimensional (3D) heart models may enhance structural imaging and surgical preparation, while data on their medical effect continue to be unpredictable and uneven. This systematic review and meta-analysis assessed the impact of 3D heart simulations on surgical preparation and outcomes in congenital cardiac disease. OBJECTIVE: To assess the successful outcomes of patient-centred 3D cardiac simulations in medical preparation, intraoperative execution and surgical results in patients experiencing operation for congenital cardiac disease. OBJECTIVE: To evaluate the impact of patient-specific 3D heart models on surgical planning precision and preoperative outcomes in congenital heart disease surgery. METHODS: A systematic review and meta-analysis were performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 standards and prospectively registered in PROSPERO (CRD42024211985). PubMed, Embase, Scopus and Cochrane CENTRAL were searched through March 2025 for comparative studies evaluating 3D-printed or virtual heart models versus conventional imaging. Outcomes were harmonised and pooled as risk ratios (RRs), mean differences (MDs) or standardised MDs (SMDs) with 95% CIs using random-effects models. RESULTS: 32 studies (n=1842) met inclusion criteria. The use of 3D models was associated with more frequent surgical plan modification (RR 1.42; 95% CI 1.21 to 1.67), reduced operative time (MD -18.4 min; 95% CI -27.6 to -9.2), lower postoperative complications (RR 0.74; 95% CI 0.56 to 0.98) and reduced re-operation (RR 0.52; 95% CI 0.31 to 0.86). Hospital stay was shortened (MD: 1.8 days; 95% CI -3.0 to -0.6), and surgeon confidence improved (SMD 0.88; 95% CI 0.60 to 1.15). The confidence of indication extended from modest to small because of non-experimental research and variability. CONCLUSION: Individualised-centred 3D heart stimulation improves structural imaging and medical preparation in congenital cardiac disease, chiefly for intricate lacerations and can increase preoperative competence, while statistics for conclusive diagnosis results continue to be restricted and mainly experiential. Upcoming potential, large-scale investigator-led research with consistent result events are required to ratify their medical success.
26 May 2026
Read appraisal →Circulation journal : official journal of the Japanese Circulation Society
Smaller Right Ventricle Results in Poorer Exercise Performance in Young Patients With Repaired Tetralogy of Fallot
BACKGROUND: Severe right ventricular (RV) dilatation and exercise intolerance are considered indications for pulmonary valve replacement in surgically repaired tetralogy of Fallot (rTOF). METHODS AND RESULTS: Cardiopulmonary exercise testing (CPET) and cardiac magnetic resonance (CMR) were performed in rTOF patients with pulmonary insufficiency (PI). Oxygen pulse (OP), calculated as oxygen consumption (V̇O2)/heart rate, was used as a surrogate of stroke volume (SV). Correlations between CPET and CMR measures were investigated. In all, 37 patients (mean [±SD] age 17±5 years; 14 males) were examined. Peak V̇O2/kg was approximately 70% of predicted value. The pulmonary regurgitant fraction (PRF) was 28.3±13.4%. Body surface area (BSA)-indexed RV end-diastolic volume (RVEDVi) and RVSV (RVSVi) were 127±28 and 65±16 mL/m2, respectively. RV and left ventricular (LV) ejection fractions were 50.3±7.8% and 59.1±6.1%, respectively. A strong positive correlation was noted between RV end-diastolic volume and RVSV (P<0.0001), RVSV and LVSV (P<0.0001), and RVEDVi and peak OP/BSA (P=0.0004). Larger RVEDVi was correlated with better exercise performance, whereas smaller RVEDVi was correlated with worse exercise performance. RVEDVi was larger in male than female rTOF patients despite comparable PRF, RVSVi, LVEDVi, and BSA-indexed LVSV. CONCLUSIONS: A smaller RV was associated with worse exercise performance, indicating exercise intolerance is independent of RV dilatation in young rTOF with PI and represents a unique pathological entity responsible for reduced exercise performance.
25 May 2026
Read appraisal →JMIR research protocols
A Large, Diverse, Urban Cardiovascular Health e-Cohort in Childhood and Adolescence: Protocol for the Young Hearts Study
BACKGROUND: Cardiovascular health (CVH), defined as a composite of 8 health factors and behaviors ranging from body composition to sleep duration, is strongly associated with the risk for future cardiovascular events in adults. However, there is little data on CVH among contemporary, diverse cohorts of children and adolescents. OBJECTIVE: This protocol describes the completed recruitment of a diverse pediatric e-cohort based in Chicago. We include details about ongoing longitudinal data collection for CVH behaviors, as well as neighborhood and environment-based socioeconomic factors, and linkage to electronic health records (EHRs) for direct capture of CVH factors. METHODS: Young Hearts (YH) uses a longitudinal cohort design, linking participant responses to annual electronic surveys to EHRs. Parents/guardians of children aged 0-17 years and adolescents aged 18 years are asked to complete surveys at 3 e-visits, completed annually in consecutive years. Adolescents aged 12-17 years are invited to complete surveys at each e-visit to provide self-reports of their data in addition to their parents/guardians. As adolescents reach the age of majority, they re-consent and complete their remaining e-visit data. Participants' clinical data are abstracted from EHRs at 6 health systems in Chicago and linked to their survey data. The main study outcome is the CVH score, adapted from the Life's Essential Eight framework for use in pediatric populations. We will also study component CVH behaviors and factors, each assessed using developmentally-appropriate measures, including body mass index, blood pressure, lipids, glycemic control, diet, physical activity, sleep, and smoking exposure. Our innovative study design will allow us to model trajectories of pediatric CVH from birth through 20 years of age. Funding for this study was provided by the National Heart, Lung, and Blood Institute (R01HL155864). RESULTS: The YH study, funded in March 2021, recruited, enrolled, and consented 7114 children and adolescents aged 0-18 years between April 2022 and February 2025. Baseline surveys have been completed by 6651 participants, of whom 3259 (49%) were female, and the mean age was 7.4 (SD 5.4) years. Data collection is still in progress, with completion anticipated in February 2027. We aim to publish results beginning in 2026. CONCLUSIONS: This study will define the epidemiology of cardiovascular risk factors in a diverse, contemporary cohort of US children and adolescents and identify behavioral and structural individual- and area-level economic, psychosocial, and lifestyle factors associated with identified disparities. We anticipate that the YH cohort will become an ongoing resource for pediatric CVH research.
23 May 2026
Read appraisal →Physiological measurement
Machine learning-based information flow analysis of ECG signals for long QT syndrome
Objective. Cardiovascular diseases remain the leading cause of death worldwide, highlighting the need for non-invasive and cost-effective risk assessment tools. Biological systems, including the heart, exhibit complex nonlinear dynamics arising from interactions between their subsystems. Information-theoretic measures, particularly entropy-based methods, provide a framework to quantify these interactions. Using ECG recordings, we investigate information flow between heart rhythm and ventricular repolarization to identify potential markers of pathological alterations in cardiac electrical activity.Approach. Entropy-based measures of information transfer were derived from beat-to-beat ECG time series using a window-based approach and subsequently averaged at the subject level. These features were used as inputs to supervised machine learning models to discriminate patients with congenital long QT syndrome (LQTS) from healthy controls. Model performance was evaluated using repeated stratified train-test splits, and classification robustness was assessed across multiple runs using standard performance metrics, including the area under the receiver operating characteristic curve. The explainable artificial intelligence techniques were applied. SHapley Additive exPlanations were used to quantify the contribution of entropy-based features to the model predictions. This post-hoc explainability analysis enabled systematic assessment of feature importance while preserving the predictive performance of the models.Results. The proposed approach achieved high and stable classification performance across repeated validation runs. Both random forest (RF) and support vector machine (SVM) classifiers demonstrated high discrimination between LQTS patients and healthy controls, with consistently high area under the curve. For RF a mean accuracy of 95.9%, mean sensitivity of 95.9%, and mean specificity of 92.9% were achieved across repeated runs. For SVM the corresponding mean values were 93.1%, 93.1%, and 92.0%, respectively.Conclusions.Explainability analysis revealed a dominant contribution of multivariate and conditional information flow features compared with single-source entropy measures, highlighting the relevance of joint and conditional interactions in the classification patterns.
19 May 2026
Read appraisal →European heart journal
Digital profile of children's hearts: automated echocardiogram strain analysis facilitates earlier detection of cardiac dysfunction
BACKGROUND AND AIMS: Paediatric myocardial strain analysis through echocardiography is often characterized by high variance and limited precision, highlighting the need for a standardized and vendor-agnostic approach applicable for diverse image qualities and populations, which could enhance cardiac function evaluation and enable early detection of cardiac impairment. METHODS: The Motion-Echo system was proposed, a semi-supervised deep learning framework built on 11 096 paediatric and 11 297 adult echocardiograms spanning diverse image qualities and vendors. It integrated context compensation and motion estimation modules for temporally coherent segmentation, myocardial motion estimation, and global strain assessment with minimal manual annotations. Clinical utility was further evaluated through downstream applications. RESULTS: Motion-Echo achieved mean absolute errors of 2.099% [95% confidence interval (CI) 1.803-2.401] and 2.665% (95% CI 2.339-3.026) for global longitudinal and circumferential strain assessments, with Pearson correlation coefficients of 0.799 (95% CI 0.715-0.871) and 0.781 (95% CI 0.687-0.844), respectively. To validate the clinical utility, automated strain values achieved an area under the curve (AUC) of 0.906 (95% CI 0.816-0.981) for cancer therapy-related cardiac dysfunction risk prediction. For late gadolinium enhancement detection, automated global longitudinal strain reached an AUC of 0.782 (95% CI 0.666-0.885). For left ventricular ejection fraction decline forecasting, the system outperformed manual strain values (DeLong P < .001). In addition, incorporating estimated motion flows yielded a remarkable AUC improvement to 0.952 (95% CI 0.917-0.980) for myocardial infarction detection. CONCLUSIONS: Leveraging a large-scale paediatric dataset, Motion-Echo provided a reliable and generalizable framework for myocardial strain analysis, demonstrating potential to facilitate earlier detection of cardiac dysfunction and generate digital cardiac function profiles of children.
16 May 2026
Read appraisal →BMJ paediatrics open
Prevalence of dysglycemia following paediatric cardiac surgery: a systematic review and meta-analysis
BACKGROUND: Postoperative dysglycemia is a common but under-recognised complication in paediatric cardiac surgery, driven by physiologic stress, hormonal changes and cardiopulmonary bypass. Reported prevalence varies widely, and no meta-analysis has synthesised the evidence. Therefore, this study aimed to estimate the pooled prevalence of postoperative dysglycaemia and describe associated postoperative outcomes, such as intensive care unit (ICU) stay and mechanical ventilation duration. METHODS: We conducted a systematic review and meta-analysis following PRISMA 2020 guidelines and the Joanna Briggs Institute (JBI) methodology for prevalence studies. Eligible studies included paediatric patients (≤18 years) undergoing cardiac surgery reporting postoperative dysglycaemia (hyperglycaemia or hypoglycaemia). A random-effects model was used to calculate pooled prevalence and 95%CIs, with logit transformation applied to prevalence proportions and heterogeneity assessed using I² statistics. Subgroup analyses were performed by region/continent, study design, age group and glycaemic threshold. All included studies were critically appraised using the Newcastle-Ottawa Scale for observational studies and the Cochrane Risk of Bias 2 tool for randomised trials. The protocol was registered with PROSPERO (CRD420251161893). RESULTS: 22 studies involving 3864 patients were included. The pooled prevalence of postoperative dysglycemia was 68.6% (95% CI 52.8 to 81.0), with hyperglycaemia accounting for most cases (71.2%) and hypoglycaemia observed in 8.1%. Prevalence was higher in Asia and North America (~75%) than in Europe (45.2%), though not statistically significant. Studies using lower hyperglycaemia thresholds (126-139 mg/dL) reported significantly the highest prevalence (82.3%, p<0.032). The pooled mean ICU stay among dysglycemic patients was 180.3 hours (95% CI 82.3 to 279.3), and mean mechanical ventilation duration was 94.6 hours (95% CI 5.2 to 184.1). Sensitivity analyses showed that no single study disproportionately influenced the overall pooled estimates, and no publication bias was detected. The certainty of evidence assessed using the GRADE approach was moderate for overall dysglycemia prevalence. CONCLUSION: Dysglycaemia is highly prevalent following paediatric cardiac surgery, particularly hyperglycaemia, with prolonged ICU and mechanical ventilation times observed among affected patients. These findings underscore the need for vigilant perioperative glucose monitoring, standardised definitions of dysglycaemia, and evidence-based glycaemic management protocols. Future multicentre studies are warranted to establish optimal glycaemic thresholds and evaluate targeted interventions to improve postoperative outcomes in this vulnerable population.
15 May 2026
Read appraisal →BMJ open
Multimodal personalised executive function intervention (E-Fit) for school-aged children with complex congenital heart disease in Switzerland: a randomised controlled feasibility study
OBJECTIVE: To explore the feasibility of a novel multimodal executive function intervention in school-aged children with complex congenital heart disease (cCHD). DESIGN: Single-centre, single-blinded, randomised-controlled 8-week multimodal personalised executive function intervention (E-Fit) study. Outcomes were measured throughout the intervention, post-intervention (T1) and at 4-month follow-up (T2). SETTING: Tertiary care centre between May 2022 and May 2024. PARTICIPANTS: Children 10 to 12 years (M=11.0, SD=0.9) with cCHD without a genetic diagnosis with infant open-heart surgery and reported difficulties (T-scores ≥60) on any of the summary scales of the parent- or teacher-reported Behavior Rating Inventory for Executive Function (BRIEF). INTERVENTIONS: Children with cCHD were randomly assigned to one of two groups: the intervention or the control group. The 8-week intervention was multimodal including three modalities: (1) computerised executive function (EF) training 3×20 min/week with CogniFit; (2) a weekly, remote standardised 1:1 individual EF strategy coaching; (3) analogue games played at convenience. The control group completed activity logs. FEASIBILITY MEASURES: Acceptability: Acceptance and Feasibility Scale (AFS) and coach-rated engagement during coaching sessions. Demand: Number of completed computerised training, strategy coaching and analogue game sessions. IMPLEMENTATION: E-Fit Fidelity Measurement System, assessing adherence to core components. Practicality: Retention rate. Integration: AFS integration items. Exploratory efficacy: BRIEF, neuropsychological EF testing and psychosocial variables at baseline, post-intervention (8 weeks) and at 4-month follow-up. RESULTS: We recruited 42 participants (Nfemale=20). Acceptability: The intervention was acceptable, with moderate observed engagement. Demand: median number of computerised training sessions completed was 16 of 24 sessions (67%, (IQR; 6 to 19)), all children attended all scheduled coaching sessions, analogue games were played in total a median of 9 times (IQR 4 to 14). IMPLEMENTATION: Coaching sessions could be implemented by the coaches as intended. Practicality: Overall retention rate was 90%. Integration: E-Fit was well integrable into the home setting. Exploratory efficacy favoured the intervention group with improvements in the parent-rated Behavioral Regulation Index of the BRIEF (adjusted Hedge's (gA1) = -0.408 to -0.903) and in social responsiveness (gA1 = -0.427 to -0.521) at T1 and at T2. CONCLUSIONS: E-Fit is a feasible intervention suggesting EF and social responsiveness improvements in children with cCHD. Motivational strategies to improve adherence to computerised training should be refined before a full-scale efficacy trial. TRIAL REGISTRATION NUMBER: NCT05198583.
12 May 2026
Read appraisal →Journal of the American Heart Association
Ex Vivo Effect of Apixaban on Hemostatic Biomarkers in Children With Heart Disease: A SAXOPHONE Trial Substudy
BACKGROUND: The SAXOPHONE (Safety of Apixaban on Pediatric Heart Disease on the Prevention of Embolism) trial demonstrated the safety of apixaban for thromboprophylaxis in children with heart disease. Included a priori in the trial design was an exploratory biomarker substudy to evaluate the effects of apixaban on surrogate biomarkers of efficacy, thrombin generation capacity, and hemostatic proteins. The study assessed changes in d-dimer, thrombin generation assay parameters, factor VIII, fibrinogen, protein C, and protein S in children receiving apixaban compared with standard-of-care vitamin K antagonists (VKAs) or low-molecular-weight heparin. METHODS: SAXOPHONE participants aged >1 year (n=182) had blood samples for biomarkers collected at baseline, week 2, or month 6. Participants were randomized to apixaban (n=123) or standard of care (VKA or low-molecular-weight heparin; n=59). Subgroup analyses accounted for prior VKA exposure. RESULTS: d-dimer levels decreased at month 6 in all treatment groups and remained stable during VKA-to-apixaban bridging. Apixaban significantly prolonged thrombin generation assay lag time and time to peak compared with VKAs and decreased peak thrombin similarly to VKAs in anticoagulant-naïve participants. Apixaban was associated with decreased fibrinogen and factor VIII at month 6, with no effect on protein C or S. Prior VKA exposure produced carryover effects, suppressing baseline d-dimer, thrombin generation assay parameters, and proteins C and S. CONCLUSIONS: Apixaban reduced hypercoagulability, as shown by decreased d-dimer levels and prolonged lag time, and preserved endogenous thrombin potential in thrombin generation assay, changes consistent with adult data. These findings align with SAXOPHONE's primary outcomes, supporting apixaban's favorable risk-benefit profile as a thromboprophylaxis option in children with heart disease.
8 Apr 2026
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