Isolated hemihyperplasia (IHH) is a rare congenital condition characterized by asymmetric overgrowth of body parts, often associated with increased risk of embryonal tumors. While syndromic forms are well-documented, idiopathic IHH without dysmorphic features remains underrecognized. Tetralogy of Fallot (TOF), a common cyanotic congenital heart defect, and brain abscesses are known complications in cyanotic heart disease, but their co-occurrence with IHH is exceedingly rare. We report a 3-year-old boy presenting with fever, irritability, and limb asymmetry. Clinical examination revealed right-sided hemihyperplasia, cyanosis, and clubbing. Echocardiography confirmed TOF. Neuroimaging identified a left frontoparietal brain abscess. Syndromic causes of hemihyperplasia were excluded based on clinical features. The child responded well to intravenous antibiotics and supportive care. Tumor surveillance was initiated, and cardiac surgical planning was underway. This case highlights a rare triad of IHH, TOF, and brain abscess, not previously reported in the literature. It underscores the importance of thorough phenotypic assessment, tumor surveillance, and multidisciplinary management in complex pediatric presentations.
Transfusion-dependent thalassemia (TDT) is a major health problem across the thalassemia belt. Although regular transfusions extend survival, they cause cardiac iron overload (CIO). Cardiac magnetic resonance imaging T2-star (MRI T2*) is the gold standard for detecting myocardial siderosis, but it remains costly and has limited availability. QT and corrected QT (QTc) intervals have been proposed as simple, inexpensive alternatives, yet pediatric evidence is limited. This systematic review aims to assess the association between QT and QTc prolongation and CIO in pediatric TDT. We conducted a systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020 guidelines (PROSPERO ID: CRD420251051029). Searches were performed in PubMed, EBSCO, Scopus, ProQuest, ScienceDirect, and Google Scholar for studies published between January 2015 and January 2025. Keywords included "β-thalassemia," "transfusion-dependent thalassemia," "pediatric,", "iron overload," "QT interval," "QTc interval," "cardiac MRI T2*," and "serum ferritin." Eligible studies reported QT/QTc intervals in pediatric TDT with CIO confirmed by MRI T2* and/or serum ferritin. Study quality was evaluated using the Newcastle-Ottawa Scale. Data were pooled using a random-effects model, with subgroup and sensitivity analyses. Seven studies involving 619 children were included; six provided data for meta-analysis. Both QT (mean difference [MD] 18.23 ms; 95% confidence interval [CI] 12.05-24.41; P < 0.00001) and QTc intervals (MD 21.15 ms; 95% CI 15.88-26.42; P < 0.00001) were significantly prolonged in the CIO group. Subgroup analyses confirmed consistent findings with low heterogeneity. QT and QTc prolongation are strongly associated with CIO in pediatric TDT.
Pediatric heart failure (PHF), most commonly resulting from cardiomyopathies, congenital heart disease, or acquired cardiac disorders, remains a major cause of childhood morbidity and mortality. The 2025 International Society for Heart and Lung Transplantation (ISHLT) guidelines provide the most comprehensive update in over a decade, offering a contemporary framework for pharmacologic management when underscoring persistent gaps in pediatric-specific evidence. This narrative review synthesizes the 2025 ISHLT Guidelines alongside contemporary pediatric and adult HF guidance, emphasizing pharmacologic recommendations, areas of extrapolation from adult trials, and persistent evidence gaps across diverse PHF phenotypes. The updated guideline introduces an ejection fraction (EF)-based classification system and refines pharmacologic recommendations for acute and chronic PHF. It reaffirms Class I support for foundational neurohormonal therapies in PHF with reduced EF, incorporates randomized control trial-based recommendations for sacubitril-valsartan and ivabradine, and offers limited, extrapolated recommendations for agents such as sodium-glucose cotransporter-2 inhibitors, mineralocorticosteroid receptor antagonists, and soluble guanylate cyclase stimulators. The guideline also outlines phenotype-specific considerations for high-risk groups, including congenital heart disease and cancer therapy-related cardiomyopathy. Persistent unmet needs include the absence of disease-modifying therapies for PHF with preserved EF and insufficient evidence to guide management of complex congenital and syndromic conditions. The 2025 ISHLT Guidelines provide a structured, contemporary approach to pharmacologic therapy in PHF when clearly delineating areas where evidence remains limited. Addressing these limitations will require coordinated multicenter research, real-world data integration, and learning health systems capable of translating emerging therapies into evidence-based pediatric practice.
With over 260,000 yearly mortality, 87% from low socio-economic countries, congenital heart disease (CHD) stands as a major global health crisis. Echocardiography, the current diagnostic standardized approach, often delays diagnosis due to interpretation variability and limited availability in low socioeconomic countries. Hence, exploring alternative screening approaches is crucial. The deep learning (DL) method coupled with heart sound analysis is a promising diagnostic approach for early CHD detection. This study focuses on the innovation of DL-based heart sound analysis in enhancing the diagnosis of CHD patients. The outcomes of interest of the study were the sensitivity, specificity, and area under the curve (AUC) of various diagnostic tools and DL methods used in diagnosing CHD. Quality appraisal was done using Quality Assessment of Diagnostic Accuracy Studies 2, while the diagnostic meta-analysis used Stata MP 17. A comprehensive search across seven databases yielded 19 articles for analysis. Among these, 13 were deemed low-risk and six unclear-risk of bias. The results were observed through meta-analysis with sensitivity at 91% (95% confidence interval [CI] = 0.85-0.94, P = 0.001), specificity at 92% (95% CI = 0.86-0.95, P = 0.001), and an AUC of 96% (95% CI = 0.94-0.98). The adoption of DL-based heart sound analysis for CHD diagnosis shows promise, demonstrating good diagnostic accuracy and potential as an adjunctive tool to support triage or pre-screening, although further validation is required before it can be considered alongside echocardiography.
Pulmonary artery hypertension associated with left-to-right intracardiac shunts adversely affects outcomes. Studies are limited to guide the decision to operate or not in patients presenting late with a left-to-right shunt and PAH. This study aimed to assess clinical and investigative parameters, including acute vasodilator testing (AVT) using oxygen, to predict operability decisions and outcomes. We conducted a retrospective analysis of patients who underwent cardiac catheterization for operability assessment over 5 years, excluding those with left-heart obstructive disease or residual postoperative lesions. A total of 157 patients (mean age: 12.8 ± 12.6 years; 83 males) were included, with the majority having post-tricuspid shunt lesions (132/157, 84%). Multiple logistic regression identified predictors of inoperability on AVT, including age >2 years, absence of cardiomegaly, bidirectional or predominantly right-to-left shunting across the defect, and absence of left ventricular volume overload on echocardiography. These variables formed a scoring system with 80% specificity and 60% sensitivity for predicting inoperability. Of the 157 patients, 60 underwent surgical correction, with six experiencing right heart failure or death post-operatively, and three facing adverse outcomes during further follow-up. Univariate analysis indicated that age >2 years, hemoglobin levels, single or narrowly split second heart sound, cyanosis, and a postoxygen Qp: Qs ratio <0.9 were significantly associated with unfavorable outcomes among patients who underwent surgery. In the multivariate analysis, none of the parameters predicted an unfavorable surgical outcome. This study highlights the importance of simple clinical and non-invasive parameters in assessing operability among patients with left-to-right intracardiac shunts and severe PAH. However, none of the parameters were independently predictive of operative outcome. A simple AIIMS operability score based on clinical and noninvasive parameters can predict inoperability with acceptable sensitivity and specificity. However, the score should be validated in larger prospective studies.
Maternal and fetal mortality in patients with congenital heart disease-associated pulmonary artery hypertension (CHD-PAH) is reported to be quite high. Sildenafil is the standard of care in PAH. Studies on sildenafil in maternal and fetal clinical outcomes are few. This study aimed to determine the effect of oral sildenafil on the clinical outcomes of mothers and fetuses with CHD-PAH. This study was an observational study with a retrospective cohort method. Patient data were taken from the hospital registry and medical records of patients who met the research criteria from August 2015 to August 2022. Based on sildenafil treatment, subjects were divided into two groups: subjects with oral sildenafil and those without sildenafil. The research outcome was maternal mortality and a composite of fetal adverse outcomes, defined as fetal mortality, oligohydramnios, intrauterine growth retardation (IUGR), and small for gestational age. There were 68 pregnant women who met research criteria, consisting of subjects with sildenafil (n = 32) and without sildenafil (n = 36). A composite of maternal and fetal adverse outcomes occurred in 24 subjects (35.3%). Subjects with oral sildenafil therapy were not associated with maternal mortality. Subjects with oral sildenafil therapy had a lower incidence of fetal adverse outcomes (n = 7, 21.9%) as compared to those without sildenafil (n = 25, 56.8%), P = 0.029. In the multivariate analysis, oral sildenafil therapy had a neutral impact on maternal mortality and fetal adverse outcomes. Other PAH therapy use was a significant independent predictor of maternal mortality. The PVR value was a significant independent predictor of fetal adverse outcomes. Oral sildenafil therapy was safe for pregnant CHD-associated PAH patients. Oral sildenafil therapy reduced fetal adverse outcomes, namely fetal mortality, oligohydramnios, fetal growth restriction, and small for gestational age infants, in patients with CHD-associated PAH. PAH severity had a significant impact on pregnancy outcome.
Reoperation for dysfunctional mitral bioprostheses carries substantial risk. Endovascular valve-in-valve (V-in-V) implantation is an alternative, but pediatric experience is scarce. We report the feasibility of the Melody valve V-in-V with elective extracorporeal membrane oxygenation (ECMO) support in an inoperable pediatric patient. A transvenous antegrade, transesophageal echocardiography-guided procedure was performed with venoarterial ECMO. The transmitral gradient fell from 30 to 8 mmHg without paravalvular leak or left-ventricular outflow obstruction. ECMO was discontinued within 24 h. At 3-year follow-up, valve function remains preserved, and the patient is stable. Melody V-in-V with elective ECMO is a viable rescue strategy for high-risk pediatric candidates.
Adults with repaired tetralogy of Fallot (rTOF) remain at increased risk for major adverse cardiac events (MACEs). Cardiopulmonary exercise testing (CPET) is increasingly used for risk stratification, though prognostic data beyond peak oxygen consumption (VO2) are limited in this population. We evaluated the prognostic significance of CPET-derived variables for predicting MACE in adults with rTOF. Clinical and CPET data from 47 adults with rTOF who underwent symptom-limited CPET were retrospectively analyzed. MACE was defined as cardiac-related hospitalization, device implantation, surgical intervention, or death. Associations between CPET variables and MACE were assessed using multivariable Cox regression adjusted for age, sex, and body mass index. Discriminative performance was evaluated using receiver operating characteristic (ROC) analysis. Over a mean follow-up of 20.8 months, 9 patients (19.1%) experienced MACE. Peak VO2, oxygen uptake efficiency slope (OUES), and circulatory power (CircP) were significantly lower in patients with New York Heart Association functional class III and in those who developed MACE. CircP was positively associated with peak VO2 (r = 0.899), OUES (r = 0.503), ventilatory anaerobic threshold (r = 0.537), and rate-pressure product (r = 0.673). On multivariable analysis, peak VO2 (adjusted hazard ratio [aHR]: 0.80; P = 0.002), CircP (aHR: 0.99; P = 0.012), and OUES (aHR: 0.99; P = 0.015) were independently associated with MACE. ROC analysis demonstrated comparable discriminative performance among these variables, with CircP showing the highest sensitivity, specificity, and predictive values. Kaplan-Meier analyses confirmed significantly higher event rates below identified thresholds. Peak VO2, CircP, and OUES are significant predictors for adverse outcomes in adults with rTOF. CircP demonstrated relatively strong overall prognostic performance, supporting its potential role in clinical risk stratification. Larger studies are warranted to validate these findings.
Major aortopulmonary collateral arteries (MAPCAs) in the setting of d-transposition of the great arteries (d-TGA) are a rare and occult finding, as they are often asymptomatic and difficult to detect in preoperative imaging. Consequences of undiagnosed MAPCAs in d-TGA are varied. Rarely, they lead to a catastrophic perioperative bronchial bleeding. Early identification and coiling are crucial. We report the case of a male neonate with d-TGA and ventricular septal defect (VSD) who experienced intrabronchial bleeding by the end of the arterial switch and VSD closure procedure, leading to inability to adequately ventilate and perioperative extracorporeal membrane oxygenation. Early identification and coil embolization were critical in identifying and managing the bleeding collaterals. This case underscores the need for employing emergent cath-angiography to diagnose previously unknown MAPCAs and thus salvaging the child from a dreadful but treatable cause. To our knowledge, this is one of the very few successfully treated cases of arterial switch operation complicated with MAPCA-induced perioperative bronchial bleeding.
Fetal cardiac rhabdomyoma is the most common prenatal cardiac tumor and is frequently associated with tuberous sclerosis complex (TSC). Everolimus, a mammalian target of rapamycin inhibitor, is an established postnatal therapy for TSC-related tumors, but its prenatal use remains rare. A 27-year-old primigravida was referred at 21 weeks' gestation for evaluation of a left ventricular mass. Given the rapid, severe progression of tumor size, maternal oral everolimus therapy was initiated at 28 weeks, with dose titration to achieve drug levels of 3-8 ng/ml. At 32 weeks, the tumor size regressed significantly. Neonatal serum everolimus on day 1 was 5.2 ng/mL, confirming transplacental transfer. Therapy was resumed postnatally, and at 5 months, the tumor had completely resolved, with normal neurodevelopment and no seizures. While short-term safety and efficacy of prenatal everolimus therapy are promising, further studies are needed to establish standardized dosing, safety profiles, and long-term developmental outcomes.
Transcatheter or surgical treatment of coarctation of the aorta (CoA) and recoarctation is the gold standard in adults and children. However, in some cases, both approaches are challenging and require a tailored strategy. A female child affected by Moyamoya and PHACE syndrome presented with a diagnosis of CoA with significant posterior arch hypoplasia. At 3 years of age, she underwent surgical aortic arch reconstruction. Nine months after the procedure, the patient developed a significant recoarctation and underwent an unsuccessful percutaneous aortic angioplasty. The recoarctation was treated with a Valeo® balloon-expandable vascular stent. At 8 years of age, the patient developed restenosis due to multiple stent fractures. The implantation of the covered stent was postponed, since the femoral artery could not accept an appropriately sized sheath. A conservative medical strategy was adopted. At 14 years, the femoral artery diameter was adequate, and a covered Cheatham Platinum stent (39 mm) was crimped onto a semi-compliant balloon (16 mm) and implanted. This case emphasizes the critical need for highly personalized strategies in managing CoA and recoarctation in children.
Pulmonary hypertension (PH) is a rare and usually irreversible disease, eventually leading to right heart failure (RHF). There are multiple PH registries in adults with PH, but very few pediatric PH registries, especially from developing countries. All children (aged 3 months-18 years) diagnosed with PH were enrolled in the study. PH was defined by standard echocardiographic and cardiac catheterization criteria. We excluded patients with transient or reversible PH, including hyperkinetic PH associated with congenital heart defects (CHDs). Our registry included 100 children from June 2019 to January 2024, with an equal gender ratio (male: female = 1:1). Easy fatigability, syncope, and RHF were the most common presenting features. Only 15% of children were classified as idiopathic pulmonary artery hypertension (IPH). The majority (81%) of children belonged to the CHD-pulmonary artery hypertension (CHD-PAH) group (49% Eisenmenger syndrome, 26% CHD with systemic to pulmonary shunt and severe PAH falling in the inoperable category, and 6% had post-operative residual PH). All patients in the IPH group and 42 patients (48.2%) in other PH were on pulmonary vasodilators. The median follow-up duration was 13 months (range: 4-56 months). Overall, there were 5 deaths (5% mortality), with 3 deaths in the IPH (20%) group. Children with CHD-PAH had better functional class, and no patient in this group died. The underlying etiology and prognosis in children with PH may differ in the Indian context compared to the Western world. Different centers across India may still face a higher proportion of unoperated CHD due to late referral, a limited number of specialized centers, and financial constraints. Children with IPH have poor long-term outcomes and a high risk of mortality. Multicenter PH registries may provide actual statistics and further insights into the disease.
We report a child with massive, chronic idiopathic pericardial effusion (PE), initially detected incidentally and asymptomatically. Despite multiple treatment attempts, including Nonsteroidal anti-inflammatory drugs, corticosteroids, colchicine, and repeated pericardiocentesis, the effusion persisted and recurred. Advanced imaging revealed a stable but severe PE over the years, with no hemodynamic compromise. Cytokine analysis of the pericardial fluid showed markedly elevated interleukin (IL)-6 levels, suggesting an underlying inflammatory process despite the absence of classic clinical signs. Based on this finding, the patient was successfully treated with anakinra, an IL-1 receptor antagonist, resulting in sustained remission for 24 months. This case highlights the potential role of biologic therapy in selected pediatric patients with chronic idiopathic PE, even when traditional markers of inflammation are absent. Cytokine profiling may help identify candidates for anti-IL-1 treatment, providing a valuable therapeutic option where standard approaches fail.
Hypertrophic cardiomyopathy (HCM) remains widely underdiagnosed in both adult and pediatric population. The ECGVision HCM© model leverages artificial intelligence deep learning to identify HCM and has been validated in an adult population. We aimed to assess the efficacy of this tool in identifying HCM in a high-risk adolescent population. In our 119 patients (average age 14.2 years), the model had 100% sensitivity, 96.51% specificity, a positive predictive value of 66.67%, and a negative predictive value of 100%. Our study demonstrates the efficacy of the ECGVision HCM© algorithm in an adolescent population and suggests that it may serve as a valuable screening tool.
Absent pulmonary valve syndrome (APVS) is a rare congenital cardiac anomaly, commonly associated with tetralogy of Fallot (TOF). Non-TOF variant, APVS with intact ventricular septum (IVS) and patent ductus arteriosus (PDA) are infrequently reported. While airway compression is a well-known complication, hemodynamic compromise with circular shunting is extremely rare. A full-term neonate with prenatally diagnosed APVS and IVS presented with severe pulmonary stenosis, pulmonary regurgitation (PR), tricuspid regurgitation (TR), and a large PDA. On the 3rd day of life, the infant developed respiratory distress and systemic hypoperfusion. Echocardiography revealed a circular shunt comprising severe PR and TR, right-to-left shunting at the atrial level, and left-to-right ductal flow. Emergent PDA ligation resulted in rapid hemodynamic recovery. The infant remained well at the 8-month follow-up. This appears to be the first reported case of circular shunting in APVS and intact IVS, emphasizing the need for vigilance and timely surgical intervention.
Infective endocarditis (IE) can cause extensive cardiac tissue destruction, often requiring surgical reconstruction with pericardial patches. The compromised integrity of necrotic tissue increases the risk of pseudoaneurysm formation. Redo surgical repair of pseudoaneurysms is associated with high morbidity; thus, catheter-based interventions may be preferable in select cases. Percutaneous transapical access provides a direct route to left ventricular pseudoaneurysms but demands thorough preprocedural planning and intra-procedural imaging. We report the successful transapical device closure of a large left ventricular pseudoaneurysm following a Ross procedure for aortic valve IE.
Most reports on surgical strategies for anomalous origin of the right pulmonary artery from the ascending aorta (AORPA) describe one-stage repairs, and there are few reports on staged repairs. We report a case of bilateral pulmonary artery banding of an AORPA and coarctation of the aorta, with a good result.
The long-term structural integrity of expanded polytetrafluoroethylene (ePTFE) conduits used for extracardiac total cavopulmonary connection (EC-TCPC) is not well established. Although conduit calcification has been reported, quantitative data remain limited. We retrospectively analyzed 20 EC-TCPC patients who underwent computed tomography more than 5 years after Fontan completion (median: 13.7 years). Cross-sectional area (CSA) was measured at five sites and expressed as a percentage of the original CSA (%CSA), and calcification volume was indexed to body surface area. Median values of mean and minimum %CSA were 74.0% and 65.5%, respectively. %CSA correlated inversely with calcification volume index (ρ = -0.47, P = 0.04). Calcification was greater along the lesser curvature than the greater curvature (0.66 vs. 0.20 mm3/m2, P < 0.001). These findings suggest curvature-specific vulnerability in ePTFE conduits and support the importance of long-term structural surveillance in Fontan patients.
Chronic mucocutaneous candidiasis (CMC) is a condition characterized by persistent or recurrent infections caused by candida species. Gain-of-function (GOF) mutations in signal transducer and activator of transcription-1 (STAT1) have been identified as a major cause of CMC and are linked to a broad clinical spectrum, including increased susceptibility to infections and vascular abnormalities. We present the case of aortic calcification in a patient with a STAT1 GOF mutation. The 8-year-old male patient had recurrent oral ulcers, upper respiratory tract infections, and pneumonia, and was found to have calcifications in the aortic arch and branches. Treatment with ruxolitinib led to significant clinical improvement, although no regression in aortic calcification was observed. STAT1 GOF mutations may enhance a pro-osteogenic environment through sustained activation of the Janus Kinase (JAK)-STAT pathway. This case highlights the potential link between STAT1 GOF mutations and vascular calcification and underscores the need for further investigation into the long-term vascular impact of JAK inhibition.
Acute rheumatic fever and rheumatic heart disease (RHD) are serious complications of untreated Group A Streptococcal infections. Given that India bears the highest global burden of RHD, optimizing secondary prophylaxis is a public health priority. Concerns regarding the adequacy of the current 3-weekly benzathine penicillin G (BPG) regimen and the lack of pharmacokinetic data in Indian children prompted this study. The objective of the study was to quantify serum penicillin levels in Indian children (aged 5-18 years) with RHD receiving 3-weekly BPG prophylaxis. Children (n = 23) with confirmed RHD and compliant with BPG prophylaxis for at least 6 months were enrolled. Intramuscular BPG was administered on day 0, and blood samples were collected at baseline, at 48 h, on day 6, and on day 14 postinjection. Serum penicillin concentrations were measured using a validated assay. A one-compartment pharmacokinetic model was used to estimate concentration-time profiles and duration of protective drug levels. The mean age of participants was 12.87 ± 2.1 years; 52.2% were female. Mean serum penicillin concentrations were 5.21 ± 6.41 ng/mL (day 0), 22.16 ± 22.62 ng/mL (day 2), 20.22 ± 18.11 ng/mL (day 6), and 10.15 ± 7.26 ng/mL (day 14). Levels were significantly higher at all postinjection time points compared to baseline (P < 0.05). However, only 1/3 of patients maintained serum concentrations above the protective threshold (20 ng/mL) on days 2 and 6, and just one patient (6.2%) did so by day 14. No patient maintained therapeutic levels throughout the 21-day interval. Median duration above 20 ng/mL was 144 h (6 days), and above 10 ng/mL was 336 h (14 days). Most Indian children receiving 3-weekly BPG prophylaxis for RHD do not maintain therapeutic serum penicillin concentrations for >1 week postinjection. These findings highlight the limitations of the current prophylaxis strategy and underscore the need to reassess injection intervals.