Pediatric takotsubo cardiomyopathy: A review and insights from a National Multicentric Registry.

Takotsubo syndrome (TTS) in the pediatric population is an infrequent but relevant cause of morbidity and mortality, with limited studies addressing its clinical course and prognosis. We aimed to analyze the clinical features and prognosis of pediatric TTS in a nation-wide multicenter registry and considering the published literature. We included a total of 54 patients from 4 different hospitals in Spain, as well as pediatric TTS patients from the published literature. Comparisons between groups were performed in order to assess for statistically and clinically relevant prognostic differences between pediatric and adult population features. Patients with pediatric TTS are more commonly male and exhibit a higher prevalence of physical triggers. The left ventricular ejection fraction (LVEF) was significantly lower in the pediatric population (30.5 + 10.4 vs 36.9 + 16.9, p < 0.05), resulting in more than fivefold rates of cardiogenic shock on admission compared to the general adult TTS population (Killip IV 74.1% vs 10.5%, p < 0.001) with similar rates of death and recurrence between groups. TTS in the pediatric population presents a distinctive clinical profile, with higher prevalence of atypical symptoms and physical triggers, as well as higher rates of cardiogenic shock on admission and similar mortality and recurrence rates than those of the adult population. This study provides valuable insights into understanding pediatric TTS and underscores the necessity for further research in this age group.

The relevance of electrocardiogram filtering in the differential diagnosis of Brugada syndrome: An illustrative case report.

We present a clinical case of a teenager in whom a Brugada syndrome electrical pattern was found which was finally diagnosed as a Brugada phenocopy due to a wrong setup of the high-pass filter on the electrocardiogram.

Lipomatous atrial septal hypertrophy associated with adrenocorticotropin hormone administration in an infant with West syndrome.

We present the rare case of lipomatous atrial septal hypertrophy associated with adrenocorticotropin hormone therapy in an infant with West syndrome, highlighting their relatively benign nature and good prognosis in children, and the relevance of the differential diagnosis with more dangerous cardiac masses in order to avoid aggressive diagnostic and therapeutic interventions.

New onset severe right ventricular failure associated with COVID-19 in a young infant without previous heart disease.

We present our recent experience with a 6-month-old infant with a personal history of short bowel syndrome that presented with fever, cyanosis, and cardiogenic shock secondary to severe pulmonary hypertension and right ventricular failure without pulmonary thromboembolism. He did not present signs of toxin-mediated disease or Kawasaki disease. He was finally diagnosed with SARS-CoV-2 infection. If this presentation is confirmed in future research, the severe cardiovascular impairment in children with COVID-19 could be also attributable to the primary pulmonary infection, not only to a multisystem inflammatory syndrome but also in children without heart disease.

Role of the Renin-Angiotensin-Aldosterone System in Dystrophin-Deficient Cardiomyopathy.

Dystrophin-deficient cardiomyopathy (DDC) is currently the leading cause of death in patients with dystrophinopathies. Targeting myocardial fibrosis (MF) has become a major therapeutic goal in order to prevent the occurrence of DDC. We aimed to review and summarize the current evidence about the role of the renin-angiotensin-aldosterone system (RAAS) in the development and perpetuation of MF in DCC. We conducted a comprehensive search of peer-reviewed English literature on PubMed about this subject. We found increasing preclinical evidence from studies in animal models during the last 20 years pointing out a central role of RAAS in the development of MF in DDC. Local tissue RAAS acts directly mainly through its main fibrotic component angiotensin II (ANG2) and its transducer receptor (AT1R) and downstream TGF-b pathway. Additionally, it modulates the actions of most of the remaining pro-fibrotic factors involved in DDC. Despite limited clinical evidence, RAAS blockade constitutes the most studied, available and promising therapeutic strategy against MF and DDC. Conclusion: Based on the evidence reviewed, it would be recommendable to start RAAS blockade therapy through angiotensin converter enzyme inhibitors (ACEI) or AT1R blockers (ARBs) alone or in combination with mineralocorticoid receptor antagonists (MRa) at the youngest age after the diagnosis of dystrophinopathies, in order to delay the occurrence or slow the progression of MF, even before the detection of any cardiovascular alteration.

Plasmatic NT-proBNP could help to select cases for screening echocardiography in healthy infants with Respiratory Syncytial Virus infection.

In Respiratory Syncytial Virus infection, the early identification of infants at risk for severe disease in order to potentially decrease morbidity could be considered a major goal. Current guidelines recommend only clinical observation for this purpose in infants without known comorbidities. However, recent evidence shows that the presence of pulmonary hypertension in this population is a relevant risk factor for the development of a severe illness, even in healthy infants. The determination of plasmatic NT-proBNP levels could help to identify those cases that benefit of echocardiographic screening to detect pulmonary hypertension in this population during hospitalization.

Anakinra as rescue therapy for steroid-dependent idiopathic recurrent pericarditis in children: case report and literature review.

In approximately 5% of patients with idiopathic recurrent pericarditis, the disease usually follows a chronic relapsing course, and children can develop dependence and side effects of prolonged high-dose corticosteroid regimens. In this setting anakinra, a recombinant human interleukin-1 competitive receptor antagonist that blocks the biologic effects of interleukin-1, thereby reducing systemic inflammatory responses, appears to be one of the most promising strategies. We report an adolescent with steroid-dependent idiopathic recurrent pericarditis that was successfully treated with anakinra, highlighting that this therapeutic option seems to be an effective, rapidly acting, steroid-sparing, and relatively safe agent for the treatment of this entity in children.

Coronary artery spasm due to intravenous atropine infusion in a child: possible Kounis syndrome.

Coronary vasospasm can result from silent myocardial ischaemia to sudden death. There are many precipitant factors including different pharmacological agents. Kounis syndrome is defined by acute coronary syndromes associated with anaphylactic or anaphylactoid reactions. We report, to the best of our knowledge, the first paediatric case of Kounis syndrome due to intravenous atropine.

Atypical Presentation of Incomplete Kawasaki Disease: A Peripheral Facial Nerve Palsy.

BACKGROUND: Kawasaki disease (KD) is a multisystem vasculitic disease. Coronary artery aneurysms (CAAs) are the most important and life-threatening complication of KD. Various neurologic complications have been described to occur in 1-30% of patients with KD, but peripheral facial nerve palsy (FNP) is rare (0.9%). CASE REPORT: We describe a 5-month-old male infant who presented to us with unilateral left infranuclear FNP in the convalescent phase (day 18 of illness) of incomplete KD. The initial diagnosis was not made during the first 10 days of illness (therapeutic window for immunoglobulin treatment) as he was suspected to have hand-mouth-foot disease. We believe that both the delay in diagnosis and treatment of an atypical presentation of KD, combined with the more severe vasculitis and inflammatory burden reported in these cases, contributed to the development of CAA in our patient. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case highlights the importance of considering KD diagnosis in children with prolonged unexplained fever, even with incomplete diagnostic features, as well as the need to be aware of unusual manifestations, such as FNP. Atypical cases like this may be at increased risk of CAA because of delayed diagnosis and a higher inflammatory burden; therefore, a more aggressive treatment approach may be necessary.

Inferior Vena Cava Aneurysm in Children: A Case Report.

The presence of aneurysms in the territory of the inferior vena cava (IVC) is an extremely rare finding in children and few cases have been reported in the literature. Etiology is unknown and some authors have hypothesized that it can be related to a congenital defect. Most cases present as incidental radiologic findings in asymptomatic patients, but can appear as life-threatening massive thrombosis. Clinical presentation is very heterogeneous and it should be included in the differential diagnosis of patients with retroperitoneal masses. Owing to the rarity of this condition, little is known about the natural history; thus, there is no consensus about the treatment and follow-up of inferior vena cava aneurysms.

Correlation between urinary and serum NT-proBNP in acute bronchiolitis: A pilot study.

BACKGROUND AND AIMS: We aimed to analyze the correlation of urinary with serum N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations and its association with severity in acute bronchiolitis. MATERIAL AND METHODS: A pilot observational study was conducted between October 1, 2021 and March 31, 2022 including acute bronchiolitis cases who attended our institution. Serum and urinary NT-proBNP concentrations were determined using the Alere i NT-proBNP assay in time-matched urine and blood samples. The Mann-Whitney U test, Spearman's correlations, and simple linear regression were utilized to analyze the association of urine NT-proBNP levels with serum NT-proBNP and with variables indicative of severe bronchiolitis. RESULTS: Seventeen infants (median age 68 [IQR: 36-91] days) with 36 time-matched samples were included. The urine NT-proBNP was positively and strongly correlated with the serum NT-proBNP concentrations (Spearman's ρ = 0.81 & R2  coefficient = 0.751; p < 0.001), and increased with higher C-reactive protein, (p = 0.004), procalcitonin (p = 0.001), and pCO2 (p = 0.029) levels. The initial urinary NT-proBNP concentrations were higher in those infants that required ventilatory support compared with those without this outcome (1.85 [IQR: 1.16-2.44] vs. 0.63 [IQR: 0.45-0.84] pg/mg); p < 0.001); and resulted positively and strongly correlated with the duration of the ventilatory support (Spearman's ρ = 0.76; p < 0.001) and the length of stay hospitalization (Spearman's ρ = 0.84; p < 0.001). CONCLUSION: The urinary NT-proBNP concentrations could be a reliable surrogate for serum NT-proBNP levels and resulted elevated in cases of acute bronchiolitis with complicated evolution, suggesting a potential as a noninvasive tool to assess severity in this setting.

Age-adjusted NT-proBNP could help in the early identification and follow-up of children at risk for severe multisystem inflammatory syndrome associated with COVID-19 (MIS-C).

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) has emerged as a new disease associated with COVID-19 that presents in acute critically ill children with acute cardiovascular dysfunction. AIM: To determine whether the age-adjusted N-terminal pro-brain natriuretic peptide (NT-proBNP) value (Z-log-NT-proBNP) is associated with severe MIS-C and myocardial dysfunction. METHODS: A retrospective study was conducted which included children with MIS-C managed at our institution between April 1, 2020, and February 28, 2022. We divided the population into groups depending on severity based on pediatric intensive care unit (PICU) admission. We compared Z-log-NT-proBNP values across these groups and analyzed Z-log-NT-proBNP dynamics during the one-month follow-up. RESULTS: We included 17 participants [median age 3 (2-9) years] and seven (41%) required PICU admission. All (100%) of these cases presented very high (Z-log > 4) levels of NT-proBNP at the time of admission compared to only 5 (50%) patients with non-severe MIS-C (P = 0.025). NT-proBNP was significantly correlated with high-sensitive Troponin I levels (P = 0.045), Ross modified score (P = 0.003) and left ventricle ejection fraction (P = 0.021). CONCLUSION: Raised NT-proBNP, specifically very high values (Z-log-NT-proBNP > 4) could help in the early identification of MIS-C patients with myocardial dysfunction requiring inotropic support and PICU admission.

Left Ventricular Hypertrophy in Patients with X-Linked Hypophosphataemia

X-linked hypophosphatemia (XLH) is a rare genetic disorder with X-linked dominant inheritance. Mutations in the PHEX gene increase fibroblast growth factor 23 (FGF23) concentrations, causing loss of phosphorus at the proximal tubule. Most pediatric patients debut in the first two years with short stature and bowed legs. Conventional treatment consists of oral supplements with phosphorus and calcitriol. Since 2018, burosumab has been approved as a novel therapeutic option for XLH, with promising results. The purpose of this study was to share our experience with two cases of XLH treated with burosumab. These patients presented with a broad phenotypical differences. One had the most severe radiological phenotype and developed left ventricular hypertrophy (LVH) and left ventricular dysfunction with preserved ejection fraction. Treatment with burosumab was well-tolerated and was followed by radiological stability and a striking improvement in both blood biochemistry and quality of life. The LVH was stable and left ventricular function normalized in the patient with cardiac involvement. In recent years many studies have been carried out to explain the role of FGF23 in cardiovascular damage, but the exact pathophysiological mechanisms are as yet unclear. The most intensively studied populations are patients with XLH or chronic kidney disease, as both are associated with high levels of FGF23. To date, cardiovascular involvement in XLH has been described in patients treated with conventional treatment, so it would be of interest to investigate if early use of burosumab at the time of diagnosis of XLH would prevent the occurrence of cardiovascular manifestations.

Characterization of Cardiopulmonary Interactions and Exploring Their Prognostic Value in Acute Bronchiolitis: A Prospective Cardiopulmonary Ultrasound Study.

We aimed to delineate cardiopulmonary interactions in acute bronchiolitis and to evaluate the capacity of a combined cardiopulmonary ultrasonography to predict the need for respiratory support. This was a prospective observational single-center study that includes infants <12 month of age admitted to a hospital due to acute bronchiolitis. All the included patients underwent clinical, laboratory and cardiopulmonary ultrasonographic evaluation at the same time point within 24 h of hospital admission. The existence of significant correlation between cardiac and respiratory parameters was the primary outcome. The association of different cardiopulmonary variables with the need of respiratory support higher than O2, the length of stay hospitalization, the PICU stay and the duration of respiratory support were a secondary outcome. We enrolled 112 infants (median age 1 (0.5-3) months; 62% males) hospitalized with acute bronchiolitis. Increased values of the pulmonary variables (BROSJOD score, pCO2 and LUS) showed moderate correlations with NT-proBNP and all echocardiographic parameters indicative of pulmonary hypertension and myocardial dysfunction (Tei index). Up to 36 (32%) infants required respiratory support during the hospitalization. This group presented with higher lung ultrasound score (p < 0.001) and increased values of NT-proBNP (p < 0.001), the Tei index (p < 0.001) and pulmonary artery pressures (p < 0.001). All the analyzed respiratory and cardiac variables showed moderate-to-strong correlations with the LOS of hospitalization and the time of respiratory support. Lung ultrasound and echocardiography showed a moderate-to-strong predictive accuracy for the need of respiratory support in the ROC analysis, with the AUC varying from 0.74 to 0.87. Those cases of bronchiolitis with a worse pulmonary status presented with a more impaired cardiac status. Cardiopulmonary ultrasonography could be a useful tool to easily identify high-risk populations for complicated acute bronchiolitis hospitalization.

Routine laboratory test to assess the need of respiratory support in acute bronchiolitis.

BACKGROUND AND OBJECTIVES: Accurate and readily available biomarkers to predict the clinical course of bronchiolitis would enable enhanced decision-making in this setting. We explored the relationship of several biochemical parameters available at the pediatric emergency care setting with the need of advanced respiratory support (ARS): continuous positive airway pressure (CPAP), biphasic positive airway pressure (BiPAP), or invasive mechanical ventilation (MV) in bronchiolitis. METHODS: Single-center, prospective, observational, including infants aged less than 12 months diagnosed with acute bronchiolitis at the Pediatric Emergency Department. Determination of plasmatic values of several laboratory tests was performed at the time of hospital admission. Multivariate logistic analysis identified independent predictors for need of ARS. RESULTS: From October 1, 2018 to May 1, 2020, we recruited 149 infants (58% males; median age of 1 [0.5-2.5] month). Thirty-seven (25%) cases required ARS. After adjusting by age, bacterial superinfection, and comorbidities in the multivariate analysis, only higher levels of glycemia (p = 0.001), C-reactive protein (CRP) (p = 0.028), CRP/albumin ratio (p = 0.032), and NT-proBNP (p = 0.001) remained independently associated with ARS. These biomarkers reached moderate prediction accuracy with area under the curve of receiver operator curve curves ranging from 0.701 to 0.830 (p = 0.001). All they presented relatively high specificity (0.75-0.84) and negative predictive values (0.77-0.89) with low sensitivity and positive predictive values. They also correlated significantly with length of stay hospitalization (p = 0.001). CONCLUSION: Increased plasmatic levels of CRP, CRP/albumin ratio, glycemia, and NT-proBNP at hospital admission are associated with the need for ARS in infants with acute bronchiolitis.

Vitamin D Levels and Cardiopulmonary Status in Infants with Acute Bronchiolitis.

BACKGROUND: To assess association of Vitamin D deficiency with cardiac and pulmonary status in infants with acute bronchiolitis. METHODS: Infants hospitalized with acute bronchiolitis were enrolled and classified as those with serum 25 hydroxyvitamin D (25-OHD) below or equal and above 20 ng/mL. The primary outcomes were cardiopulmonary involvement defined by elevation of NT-ProBNP, alteration of echocardiographic parameters and respiratory support requirements. The secondary outcomes were the need for PICU admission and duration of hospitalization. RESULTS: Ninety two (50 males) infants with median (IQR) age 1 (0.5 - 3) months were included with median (IQR) serum 25 - OHD level 27.4 (11.4 - 40.3) ng/mL. Forty-three (47%) patients had serum below 20 ng/mL with left ventricle dysfunction (P=0.008), right ventricle dysfunction (P=0.008) and pulmonary hypertension (P=0.007) on echocardiography than those with serum 25 - OHD > 20 ng/mL. The median (IQR) serum NT - ProBNP levels were higher in those with low 25 - OHD levels than normal 25 - OHD levels [2232.2 (461.4 - 4313.3) and 830.4 (312.7 - 2579.5)], respectively; P=0.003. Low 25-OHD levels were associated with increased risk for PICU admission (OR 3.9 (95% CI 1.5-10.1); P=0.004), higher rates of non-invasive ventilation, (P= 0.048), mechanical ventilation (P=0.005), and longer duration of hospitalization (P=0.015). CONCLUSION: Low serum vitamin D level was associated with clinical severity and impaired cardiac and pulmonary status in infants with acute bronchiolitis.

Different Phenotypes of Schimke Immuno-Osseous Dysplasia (SIOD) in Two Sisters with the Same Mutation in the SMARCAL1 Gene.

BACKGROUND: Schimke immuno-osseous dysplasia (SIOD) is a very rare autosomal recessive genetic disease caused by mutations in the SMARCAL1 gene. It is characterized by spondyloepiphyseal dysplasia, T-cell immunodeficiency, hypercromic nevi, hypercholestero-lemia, and steroid-resistant nephrotic syndrome with progressive renal failure to end-stage kidney disease. CASE PRESENTATION: We report two cases of SIOD in sisters, diagnosed after the debut of nephrotic syndrome. Both had a personal history of short stature, acetabular hip dysplasia, and hypercholesterolemia. The first case, a 6-year-old girl, presented peripheral refractory edema, severe arterial hypertension, and progressive decrease of the glomerular filtration rate. Steroid-resistance of nephrotic syndrome was confirmed, treated with tacrolimus without response. Renal function worsened over the following 4 months, so haemodialysis was started. Her sister, a 5-year-old girl, had the steroid-resistant nephrotic syndrome and normal blood pressure and renal function under enalapril treatment. In view of the suspicion of SIOD, genetic studies were carried out, revealing the same mutation in homozygosis. CONCLUSION: SIOD has a variable expression with multi-systemic involvement with a short life expectancy. Early diagnosis is important, which can encourage the early start of treatment and anticipation of complications that may be life-threatening.