Compensation for interventional cardiologists varies substantially by patient population and practice setting, yet no prior study has compared lifetime, discounted earnings between pediatric and adult interventional cardiology. Understanding these differences is essential for workforce sustainability and equitable access to congenital heart interventions. We conducted an economic evaluation using benchmark compensation and productivity data from pediatric academic, adult academic, and adult private. Lifetime earnings were estimated using a net present value (NPV) framework over a 32-year career (age 35-67) at a 3% discount rate (2025 USD). Models incorporated academic promotion scenarios, private-practice fixed and ramp-up structures, and a 10,000-iteration Monte Carlo simulation varying salary percentile, career length, and promotion timing. Productivity was assessed using daily relative value unit (RVU) and NPV per career RVU. At the 50th percentile, lifetime NPVs were $8.03 million for pediatric academic, $10.45 million for adult academic, and $15.73 million for adult private practice-gaps of 30% and 96% relative to pediatrics. Median Monte Carlo NPVs were similar ($7.81 million, $10.29 million, and $15.01 million, respectively). Pediatric interventionalists generated fewer daily RVUs (20.6) than adult academic (41.0) and adult private (43.0) cardiologists, whereas compensation per RVU was comparable. These disparities reflect lower achievable procedural throughput and occur within an RVU framework that has repeatedly under-recognized the time and intensity of congenital work. Limited private-practice opportunities in pediatrics further widen earnings gaps. Pediatric interventional cardiologists experience pronounced lifetime earnings disadvantages compared with adult counterparts because of throughput constraints, RVU valuation shortcomings, and labor-market structure. Addressing these systemic inequities will be essential to sustaining the congenital interventional workforce and ensuring equitable access to advanced cardiovascular care for children.
The Kahramanmaraş-centered earthquakes of February 6, 2023 severely disrupted healthcare services, with children-one of the most vulnerable groups-being at particular risk for trauma, infections, and interruptions in chronic disease management. This study evaluated the demographic and clinical characteristics of pediatric inpatients in 2 hospitals in Hatay (Defne State Hospital and Mustafa Kemal University Hospital) by comparing pre- and post-earthquake periods. This retrospective cross-sectional study included pediatric patients admitted between December 2020-March 2022 (pre-earthquake) and December 2023-March 2024 (post-earthquake). Medical records were reviewed for demographic data, diagnoses, length of hospital stay, and discharge outcomes. A total of 920 patients were included (313 pre-earthquake, 607 post-earthquake). After the earthquake, children admitted were younger (mean age 3.6 ± 4.3 years), had shorter hospital stays (2.6 ± 2.1 days), and were less often foreign nationals compared to the pre-earthquake cohort. Respiratory system infections were the leading diagnosis overall (61.7%), with a notable increase in the post-earthquake period (75.9%). Pediatric neurology and nephrology wards were entirely closed, while endocrinology admissions nearly disappeared. Most patients (90.1%) were discharged in good condition, and referral rates to higher-level centers remained low. Respiratory infections emerged as the leading cause of pediatric hospitalizations after the earthquake. The rapid re-establishment of pediatric inpatient services allowed most cases to be treated locally, yet the closure of pediatric subspecialty wards underscores long-term challenges. Disaster preparedness must therefore encompass not only acute trauma care but also sustained management of pediatric infections and chronic diseases.
Hypertensive blood pressure (BP) response to exercise is a risk factor for the development of cardiovascular disease. Normative pediatric treadmill-based cardiopulmonary exercise test (CPET) BPs are not well established. We aimed to establish reference standards for CPET-derived BP response in children with structurally normal hearts. Retrospective analysis of 2,043 maximal effort Bruce protocol CPETs from patients ages 6-18 years without heart disease. Age- and sex-specific statistical analyses performed to determine BP percentile at peak exercise. A normal systolic blood pressure response (SBP) response to exercise was defined as < 90th percentile, elevated 90th-<95th percentile, and hypertensive ≥ 95th percentile for age- and sex-specific groups. Analysis of variance was performed to analyze differences between BP groups. Maximal exercise SBP percentile data were determined for age and sex specific groups. Peak exercise SBP is similar for males and females during childhood. In adolescence, males have higher peak SBP. Comparison amongst normal, elevated, and hypertensive CPET responses showed that patients with elevated and hypertensive responses to exercise had higher BMI and higher resting SBP. No significant differences in maximal heart rate or aerobic capacity based on peak exercise SBP. This study provides reference standards for BP response to peak exercise in pediatric and adolescent patients with structurally normal hearts using the Bruce protocol. The results help define pediatric BP responses to peak exercise and lay groundwork for future studies on prognostic significance of a pediatric hypertensive response to exercise.
Pulmonary arteriovenous malformations (PAVMs) are rare vascular anomalies that can present with profound hypoxemia in children. While transcatheter embolization is the treatment of choice, extreme hypoxemia may preclude safe intervention. Extracorporeal membrane oxygenation (ECMO) can provide temporary stabilization in such scenarios, though its use as a bridge in pediatric PAVM is seldom reported. We describe a 12-year-old girl with no prior comorbidities who presented with severe hypoxemia refractory to maximal ventilatory support. Imaging revealed multiple bilateral PAVMs. Due to worsening desaturation to 60-70% despite high-flow oxygen and intubation, venovenous ECMO was initiated, resulting in improved oxygenation and hemodynamic stability. Once stabilized, she underwent successful staged transcatheter embolization using multiple vascular plugs. ECMO was weaned within 12 hours post-procedure, and the patient was extubated the following day. At follow-up, she remained stable with oxygen saturations of 88-90% on room air and no sequelae from ECMO. This case highlights ECMO as a life-saving bridge to intervention in pediatric PAVM with refractory hypoxemia. Multidisciplinary coordination enabled safe transport, comprehensive imaging, and definitive embolization. Literature review confirms that pediatric reports of ECMO use in PAVM are scarce, with most confined to infancy. Our case underscores the role of ECMO in expanding therapeutic options for older children with severe shunt physiology. In children with life-threatening PAVM and critical hypoxemia, ECMO should be considered as a bridging strategy to transcatheter embolization. Early recognition and coordinated multidisciplinary management are essential for favorable outcomes.
Accurate blood pressure reference values are crucial for detecting hypertension in children. However, international guidelines, with reference values based on multiethnic US cohorts, may not be fully applicable in other populations. This study primarily aimed to develop percentile-based population-specific oscillometric blood pressure reference values for Danish children and, secondly, to compare these to existing percentile-based international reference values. A cross-sectional study was conducted using data from the Lolland-Falster Health Study (2016-2020), including 1771 children aged 4-15 years. A reference model was developed based on 1512 children of normal weight, excluding those with chronic conditions, blood pressure-altering medications, or a country of origin other than Denmark. Quantile regression models estimated sex- and age-specific 5th to 95th percentile for systolic and diastolic blood pressure. Reference values were compared in reclassification tables. The novel Danish reference model provides percentile-based age- and sex-specific oscillometric office blood pressure reference values. Excluding height from the model had minimal impact on explanatory power. Applying international reference values identified 27% to 69% of the Danish children with blood pressure at or above the 95th percentile, when using the novel Danish reference values as an internal comparative benchmark.  This study provided percentile-based reference values for oscillometric office blood pressure screening in children and adolescents of Danish origin and demonstrated that applying international reference values across different pediatric populations and measurement modalities may carry risk of misclassification. These findings suggest a need for population-tailored reference values in improving the diagnosis and management of hypertension in children and adolescents. • Current international pediatric blood pressure guidelines are based on percentile-based reference values derived from US multiethnic cohorts. • These reference values may not accurately reflect other populations, leading to potential misclassification. • The novel Danish age- and sex-specific reference values, provided in this study, can be used in the assessment of oscillometric blood pressure measurements for screening purposes. • The novel oscillometric reference values are easy to apply and might reduce the risk of underdiagnosis.
Pediatric acute myocarditis presents with a heterogeneous clinical spectrum. The primary aim of this study was to identify early clinical and laboratory predictors of severe disease requiring intensive care unit (ICU) admission. A secondary aim was to describe the clinical characteristics of cases diagnosed in the postpandemic context. We conducted a retrospective cohort study of children admitted to a tertiary center with acute myocarditis between 2012 and 2024. Patients requiring ICU admission were compared with those managed in standard wards to identify risk factors for severity. Data were analyzed using descriptive statistics, nonparametric tests, and effect size calculations. Thirty-eight cases were identified, with 76% of diagnoses occurring after 2020. The median age was 12.5 years. Two distinct clinical phenotypes emerged: patients with chest pain (59%) and those with cardiogenic shock (15%). Admission to the ICU was strongly associated with hemodynamic instability (P < 0.001), lower left ventricular ejection fraction (P < 0.001), and the absence of reported chest pain (P < 0.001). Among biomarkers, higher levels of NT-pro-BNP (P = 0.005) and elevated Procalcitonin (P = 0.02) were associated with severe disease. Parvovirus B19 was the most frequently detected pathogen in the recent period. In our cohort, pediatric myocarditis presented with increased frequency in the postpandemic years. Risk stratification remains crucial: "infarct-like" chest pain was associated with a milder course in older children. Conversely, severe cases, often occurring in younger patients unable to report pain, were identified by hemodynamic stress (shock, elevated NT-pro-BNP) and systemic inflammation (procalcitonin).
ABO-incompatible (ABOi) heart transplantation, first performed in infants by West and colleagues in 1996, transformed pediatric heart allocation by challenging longstanding immunologic constraints. Early success of this approach leveraged the developmental immaturity of the neonatal immune system and has since shown comparable short- and long-term outcomes to ABO-compatible (ABOc) transplantation. Over three decades, increasing clinical experience and policy evolution, including broader ABOi eligibility criteria and relaxed titer thresholds, have expanded access to donor hearts and reduced waitlist mortality, particularly among blood group ABO-O candidates. Despite these advances, marked variability persists among centers in the measurement, interpretation, and reporting of ABO antibody titers, directly influencing candidate selection, perioperative management, and post-transplant surveillance. Most assays rely on manual hemagglutination techniques that are subject to significant inter-laboratory and intra-laboratory variability. Emerging single-antigen bead-based methods utilizing the Luminex™ platform may provide an opportunity for standardized, semi-quantitative assessment of graft-relevant anti-A and -B antibody levels. Perioperative strategies are individualized according to ABO antibody titer, with intraoperative plasma exchange or immunoadsorption typically employed when titers exceed a center-specific level. Standard immunosuppression regimens are generally sufficient, with anti-B cell therapies (e.g., rituximab) reserved for elevated or rebound titers. Long-term outcomes remain excellent, with most patients not producing donor-specific ABO antibodies after ABOi transplant. Most centers perform surveillance biopsies only when rising titers, an uncommon occurrence, are accompanied by graft dysfunction or biopsy-proven antibody-mediated rejection, managed with combinations of plasmapheresis, IVIG, and anti-B cell therapies as indicated. Future multicenter collaborations incorporating standardized reporting and longitudinal follow-up will be critical to optimize candidate selection, refine management algorithms, and further improve utilization and outcomes of ABOi heart transplantation.
Arrhythmogenic cardiomyopathy (ACM) is an inherited disorder characterized by fibrofatty replacement of cardiomyocytes. The inflammatory episodes of ACM, known as the "hot phase", can mimic acute myocarditis. It was seldom observed in a DES-associated ACM as a "hot-phase" presentation. The proband, a 13-year-old female, initially presented with a series of clinical manifestations of fulminant myocarditis. Although recommendation-guided anti-immunotherapy had been provided, this patient still developed into an aggressive cardiomyopathy with biventricular dilation and severe systolic heart failure. Additionally, cardiac magnetic resonance demonstrated circumferential late gadolinium enhancement in left ventricular myocardium with diffuse fibrosis. Whole-exon sequencing identified a de novo missense variant, as c.335T>A (p.L112Q) of the DES gene, resulting in protein dysfunction. And a diagnosis of ACM due to a DES variant had been identified. Finally, this patient received heart transplantation, and biventricular fibrofatty infiltration was confirmed by pathological analysis. This case presented a de novo genetic variant that can induce severe and aggressive heart failure. This finding emphasizes the importance of comprehensive genetic analysis in patients suspected of having fulminant myocarditis, which would greatly benefit the precise clinical management and outcomes.
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American Indian/Alaska Native (AI/AN) people face numerous health disparities, including alarming rates of cardiovascular morbidity and mortality. These inequities are closely tied to unique social, political, and economic circumstances due to the ongoing consequences of systemic racism. Although poorly described, these cardiovascular inequities extend to adult and pediatric interventional cardiology. AI/AN adults are less likely to undergo cardiac catheterization and are more likely to experience complications. There are no published studies on pediatric interventional cardiology outcomes in AI/AN children. The scarcity of available data underscores the need for novel studies to investigate the epidemiology, sociodemographic associations, and outcomes of AI/AN adults and children who require cardiac catheterization. Additionally, interventions addressing the geographic and social barriers to care require thoughtfulness and cultural sensitivity. Equity in interventional cardiology for AI/AN people may be best achieved through partnerships among tribes, health care providers, industry, health systems, and regulatory bodies, as well as accurate data collection. A concerted effort is required to meet the needs of this vulnerable population.
Hypertensionis one of the leading causes of cardiovascular disease and premature death worldwide, affecting more than 1.2 billion adults, with a significant part living in low- and middle-income countries. Pediatric hypertension is also a growing concern, with an estimated 4.5% of children in the United States affected. The 2024 European Society of Cardiology guidelines provide updated protocols for diagnosing and treating hypertension in adults, while pediatrics diagnosis is based on age and weight-specific percentiles. The renin-angiotensin-aldosterone system plays a crucial role in blood pressure (BP) regulation, with 2 pathways: classical pathway and alternative pathway. classical pathway increases BP and fluid retention, while alternative pathway counteracts these effects. Neuropeptides such as Nesfatin-1 (Nes-1) and Galanin (Gal), along with the endocannabinoid system, also influence BP regulation. The study focused on adolescents with hypertension, obesity, or combination. From the hospital, 128 patients were recruited to the study. Plasma samples were analyzed for Nes-1, Gal, anandamide (AEA), and 2-arachidonoylglycerol levels. The results showed significantly lower levels of Nes-1 and Gal in the obese hypertensive patients (P = .005 and P = .022 respectively) and obesity groups (P = .022 and P = .035 respectively) compared to the controls. AEA levels did not show significant differences, while 2-arachidonoylglycerol levels were tendential to higher concentration in hypertensive patients. The lower concentration of Nes-1 and Gal can be considered as predictive factors of hypertension in obese patients, with Nes-1 negatively correlated with systolic pressure. Endocannabinoid system, through cannabinoid receptors 1, may also influence BP, though its role requires further research. Understanding these systems could improve the management of hypertension, particularly in pediatric populations.
This study aimed to determine the levels of e-health literacy and quality of life in adolescents with Congenital Heart Disease (CHD), to examine associated factors, and to explore the relationship between e-health literacy and quality of life. This descriptive cross-sectional study was conducted between June and November 2024 in the pediatric cardiovascular surgery and cardiology outpatient clinics of a hospital in Istanbul, Türkiye. The sample consisted of 93 adolescents with CHD. Data were collected using a Descriptive Information Form, the E-Health Literacy Scale for Adolescents, and the Pediatric Quality of Life Inventory (ages 13-18). Data were analyzed using t-tests, ANOVA, Mann-Whitney U tests, Kruskal-Wallis tests, and Pearson correlation analysis. The mean e-health literacy score was 29.31 ± 7.51, and the mean quality of life score was 36.72 ± 12.72. Significant differences were found between e-health literacy scores and age and emotional status, and between quality of life scores and sex, health perception, and emotional status (p < 0.05). No significant correlation was found between total and subscale scores of e-health literacy and quality of life. E-health literacy and quality of life levels differed according to certain sociodemographic characteristics; however, e-health literacy alone was not associated with quality of life in adolescents with CHD. These findings suggest that nursing-led, structured digital health education and psychosocial support interventions may be necessary to improve quality of life beyond increasing access to online health information.
Ventricular electrical storm is a life-threatening emergency, especially in pediatric settings. The condition is largely mediated by heightened cardiac adrenergic tone and may be triggered by acquired conditions, while therapeutic options remain limited. We report the case of a 15-year-old male adolescent with profound functional impairment and congenital long QT syndrome admitted to a tertiary pediatric cardiology referral center in Southern Brazil for the treatment of aspiration pneumonia, who subsequently presented with refractory ventricular electrical storm during hospitalization. Despite optimized medical therapy in the intensive care unit, the patient became severely hemodynamically unstable and was deemed unsuitable for immediate definitive cardiac sympathectomy. A temporary autonomic modulation strategy using right stellate ganglion blockade was proposed. The intervention was successful in suppressing the electric storm, promoting hemodynamic stabilization, and serving as a bridging therapy until sympathectomy could be safely performed under more stable clinical conditions.
This study aimed to evaluate the clinicopathological features and survival outcomes of head and neck mucoepidermoid carcinoma (MEC) in children, with a focus on identifying significant clinical factors affecting prognosis. We analyzed pediatric patients aged ≤19 years diagnosed with head and neck MEC between 2000 and 2022 in the SEER database. Descriptive statistics, Kaplan-Meier survival analysis, and multivariate Cox regression models were employed to examine patient demographics, tumor characteristics, treatment modalities, and overall survival (OS). A nomogram was developed to predict OS based on significant predictors. Of the 323 patients, parotid gland being the most common tumor site (55.7%), followed by the palate (including both hard and soft palate) (27.6%). The majority of tumors were localized (70.9%) and of lower grade (Grade I-II, 67.2%). Surgery was performed in 95.6% of cases. Multivariate analysis identified age, tumor site, and grade as independent predictors of OS. Patients aged 0-14 years, those tumors located in palate, or those with Grade I-II tumors had better prognosis. The nomogram developed demonstrated good accuracy, with AUC values of 0.715, 0.617, and 0.58 for 1-, 5-, and 10-year survival, respectively. Our findings suggest that younger age, palate site, and lower grade tumors are associated with improved survival in pediatric HNMEC. The developed nomogram provides a valuable tool for predicting survival outcomes. Further validation of the model is warranted to enhance clinical decision-making.
BackgroundThe role of corticosteroids in the management of severe community-acquired pneumonia (CAP) in children remains controversial, with limited pediatric evidence. Recent studies have suggested that the effect of corticosteroids varies among subgroups, particularly according to cardiovascular status. The present study thus evaluated the effect of corticosteroids on in-hospital mortality in children with severe CAP and described subgroup differences by concomitant organ failure, age, and the microbial diagnosis.MethodsThis retrospective cohort study used a national inpatient database in Japan to identify children under 20 years old admitted with pneumonia between July 2010 and March 2022 who received ventilatory support within the first 2 days of admission. We performed one-to-one nearest-neighbor propensity score matching to compare children who received corticosteroids within 2 days of admission and continued for ≥3 days (steroid group) with those who did not (non-steroid group). The primary outcome was in-hospital mortality, assessed in matched pairs with subgroup analyses.ResultsOf the 11,427 children with severe CAP, propensity score matching yielded 3,081 matched pairs. In-hospital mortality was 1.6% in the steroid group and 1.7% in the non-steroid group (odds ratio, 0.94; 95% confidence interval [CI]: 0.68-1.31; p = 0.72). Among 359 children with cardiovascular compromise, corticosteroid use was associated with a reduced in-hospital mortality (odds ratio: 0.47; 95% CI: 0.26-0.87), whereas among 5,803 children without cardiovascular compromise, it was not (odds ratio: 1.64; 95% CI: 0.99-2.74). Other subgroup analyses showed no significant differences between the groups.ConclusionsCorticosteroid use did not significantly affect in-hospital mortality in children with severe CAP except in those with cardiovascular compromise. These findings suggest caution in the routine use of corticosteroids in this pediatric cohort, especially in those without cardiovascular compromise.
We evaluate the association between pre-extracorporeal membrane oxygenation (ECMO) markers of impaired oxygen delivery, as quantified by the impaired oxygen delivery index (iDo2; Etiometry, Boston, MA) and neurologic outcomes in infants supported on ECMO. A single-center retrospective cohort study using demographic and clinical data along with iDo2 metrics calculated at 120-minute intervals before ECMO initiation. Primary outcomes included mortality, electroencephalography abnormalities, and head imaging findings. The secondary outcomes included brain MRI abnormalities and Functional Status Score (FSS) at discharge. Pediatric ECMO center in North America. We included infants younger than 1 year old who were supported on ECMO between 2013 and 2017. We excluded cases with congenital diaphragmatic hernia or postcardiac surgery ECMO. None. We identified 47 infants meeting the inclusion criteria. Median (interquartile range [IQR]) age and weight at ECMO initiation were 16 days (IQR, 6-112 d) and 3.3 kg (IQR, 2.8-4.8 kg). The overall mortality was 26 of 47 (55% [95% CI, 41-69%]). Nonsurvival compared with survival was associated with a greater proportion of patients with congenital heart disease (p = 0.03) and pre-ECMO cardiac arrest (p = 0.006). Time spent above iDo2 thresholds of 25%, 50%, and 75% increased closer to ECMO initiation. Higher iDo2 dose correlated with adverse neurologic outcomes, including electroencephalography abnormalities and abnormal imaging. Last, a logistic regression model for poor outcome (composite of death and FSS), including the time spent above the three iDo2 thresholds at the three time intervals pre-ECMO, showed classification model performance with an area under the receiver operating characteristic curve 0.81 (95% CI, 0.7-0.92; p = 0.0002). Markers of impaired oxygen delivery, such as iDo2 in the 6 hours before ECMO are associated with subsequent outcome. Incorporation of these metrics into clinical decision-support systems need to be prospectively tested and evaluated.
Right ventricle-to-pulmonary artery (RV-PA) conduits are crucial to establishing or restoring RV-PA continuity in children with complex congenital heart disease. Progressive conduit obstruction is common, particularly in growing patients, and may necessitate transcatheter dilation and stenting. One of the major procedural concerns in these cases is the risk of coronary artery compression during stent implantation. This study evaluated the technical feasibility and clinical utility of patient-specific three-dimensional (3D) reconstruction and virtual reality (VR) modeling to enhance pre-procedural planning and coronary risk assessment. This retrospective bi-center feasibility analysis of pediatric patients who underwent evaluation for RV-PA conduit dilation and stenting was conducted at the Sheba and Wolfson Medical Centers, Israel, between January 2018 and September 2022. For 19 eligible patients, cardiac CT datasets were processed to generate high-fidelity 3D VR models. Two independent cardiologists assessed the models, quantified the distances between the conduit and the major coronary arteries before and after simulated balloon expansion, and provided structured qualitative feedback on VR usability. VR-based anatomical measurements demonstrated strong inter-operator agreement (intraclass correlation coefficient >0.7 across most parameters). Both cardiologists rated VR significantly superior to CT alone for delineating coronary trajectories and assessing compression risk (mean score 4.58 vs. 3.78, p < 0.0001). VR model generation was technically successful in all cases, with intuitive user interface performance and rapid rendering times. Patient-specific 3D VR modeling is technically feasible and provides clinically meaningful advantages for planning RV-PA conduit interventions. VR enhances visualization of complex coronary anatomy beyond what is achievable with standard CT imaging and may support more accurate risk stratification, improved procedural planning, and potentially reduce catheterization-associated complications. These preliminary findings support further prospective evaluation for the integration of VR tools into routine congenital cardiac practice.
Congenital heart disease (CHD) is a leading cause of pediatric morbidity and mortality worldwide. The genetics of CHD in African populations is not well understood, although it has been shown in other settings that a genetic diagnosis can have implications for patient management and risk stratification. In this study, we aimed to identify pathogenic and likely pathogenic (P/LP) variants in a cohort of patients with CHD from Southern Africa. Exome sequencing was used to screen 356 patients with diverse cardiac phenotypes from South Africa and Namibia. A P/LP variant was identified in 28 patients (7.9%). Analysis of 11 parent-child trios revealed a further LP variant in MYLK in 1 patient, bringing the overall yield to 8.1%. Variants of uncertain significance with high pathogenic potential were found in 30 additional patients. NOTCH1, MYH11, and MYH6 had the most recurrent variants in this cohort. Our data expand on the phenotypic spectrum of many established CHD genes, including the overlap between syndromic CHD genes and nonsyndromic presentation, and a potential link between aortopathy genes and conotruncal anomalies such as Tetralogy of Fallot. Variants were identified across the spectrum of CHD subtypes, with an increased yield in patients with atrioventricular septal defects and syndromic CHD, and a slight enrichment of P/LP variants in patients who died after CHD surgery. There were significantly fewer P/LP variants in patients who were of mixed ancestry. Together, these data confirm a role for rare deleterious variation in nonsyndromic CHD and demonstrate that a P/LP variant can be identified in 8% of patients from Southern Africa.
Heterozygous TBX4 variants are the second most common genetic cause of pediatric pulmonary hypertension (PH), yet mechanisms underlying TBX4-related lung disease remain poorly understood. This study developed a lung mesenchyme-specific Tbx4 loss-of-function (Tbx4cKO) mouse model that bypasses embryonic lethality to investigate this condition. Adult Tbx4cKO mice demonstrated significantly impaired pulmonary flow acceleration consistent with PH. Three-dimensional analysis of embryonic lungs revealed reduced lobe volumes and decreased distance between pleural edges and muscularized vessels. In adult Tbx4cKO lungs, we identified extensive vascular remodeling characterized by medial thickening and the extension of muscularized arteries into normally non-muscularized subpleural parenchymal zones. Contrary to previous reports suggesting vascular simplification, three-dimensional analysis demonstrated an elaborated pulmonary artery (PA) tree in addition to pathologic wall muscularization. Depletion of a single Tbx5 allele in addition to both Tbx4 alleles exacerbated histologic phenotypes with worsened right ventricular dilation. This model also demonstrated dysregulated airway smooth muscle patterning and prominent subpleural smooth muscle bands, similar to those in human TBX4 syndrome. We identify TBX4 as a critical regulator of smooth muscle differentiation and patterning across multiple lung compartments. Our model recapitulates key features of human TBX4 syndrome and identifies dysregulated smooth muscle differentiation as a potential future therapeutic target.
This review is based on interviews with internationally recognized female leaders in congenital cardiac interventions. The discussions explore diverse career pathways and professional experiences across different health care systems. The interviews are structured around 8 core themes: entry into the field, training, key turning points, leadership and professional survival, science and recognition, mentoring and legacy, the "Water or Warrior" paradigm, and messages for the future. Together, these perspectives offer a global view of shared challenges, career development, and the evolving role of women in congenital interventional cardiology.