The TANGO2 disease and the therapeutic challenge of acute arrhythmia management: a case report.

Background: TANGO2-related metabolic encephalopathy and arrhythmia are a rare, newly recognized, and likely under-diagnosed condition. First described in 2016, it is characterized by developmental delay and recurrent metabolic crisis. During these episodes, patients may present QTc prolongation and ventricular arrhythmias. Case summary: A 13-year-old female, with developmental delay, presented with severe rhabdomyolysis and an initially normal electrocardiogram (ECG). Due to the worsening of rhabdomyolysis, QTc prolongation was identified (QTc 570 ms) and oral ß-blocker therapy started. A non-sustained ventricular tachycardia developed, initially managed with magnesium and lidocaine. After a short period, an arrhythmic storm of polymorphic ventricular extrasystoles induced Torsade de Pointes (TdP) was triggered. A temporary percutaneous pacing lead was placed and esmolol infusion started. The electrical instability ran in parallel with the increasing severity of rhabdomyolysis and systolic ventricular function decline. Genetic testing identified a pathogenic variant in homozygosity in the TANGO2 gene. A stable sinus rhythm was achieved with metabolic and serum electrolytes optimization. ECG showed normalization of the QTc interval. Discussion: The full TANGO2-related phenotype emerges over time and the prognosis is linked to the appearance of ECG abnormalities. QT interval prolongation can lead to life-threatening ventricular tachycardias. The arrhythmia mechanism seems to be secondary to metabolite build-up in cardiomyocytes, which can explain the cardiac phenotype during the crisis which subsides after their resolution. In these patients, avoiding bradycardia is fundamental, since long QT-related TdP seems to be triggered by bradycardia and short-long-short ventricular premature beats (VPB). During an acute metabolic crisis, the management of arrhythmias relies on metabolic control.

Mechanical circulatory support in children: Strategies, challenges and future directions.

INTRODUCTION: The use of mechanical circulatory support (MCS) in the pediatric population has evolved significantly in the past 20 years, but its management still poses several challenges. We aim to describe patient characteristics, outcomes, and morbidity associated with different modalities of MCS, in a tertiary center. METHODS: Retrospective analysis of data from all the children who underwent MCS between 2002 and 2018 at a pediatric cardiology unit. RESULTS: Between 2002 and 2018, 22 devices were implanted in 20 patients. Patients were divided into three groups: Group A (n=11) extracorporeal membrane oxygenator (ECMO); Group B (n=8) pulsatile paracorporeal ventricular assist device (VAD) and group C (n=3) paracorporeal continuous flow VAD. The median age was similar in groups A and B (18 and 23 months, respectively), and higher in group C (13 years). ECMO patients were cannulated mainly as a bridge to recovery (post cardiotomy- 8) while group B and C patients were bridged to transplantation. The most frequent complications were bleeding (group A - 36%, group C - 66.6%) and thromboembolic events (group B - 50%, group C - 33.3%). As for outcomes, in group A the majority of patients (54.5%) were weaned and 27.3% died. Half of group B and all of group C patients underwent transplantation. CONCLUSION: Bleeding and thromboembolic events were the main complications observed. Group B showed the highest mortality, probably related to the low weight of the patients. Overall, outcomes and complications are related to the type of device and patient status and characteristics.

Campylobacter coli Myocarditis: a case report.

We report the case of a 14-year-old male presented with raised myocardial injury biomarkers, on the workout, Campylobacter coli was identified on stool culture, treated with antibiotics with total resolution. Cardiac magnetic resonance showed interventricular septum and lateral wall hypokinesia and subepicardial delayed enhancement, with preserved ventricular systolic function. To our knowledge, this is the first report linking Campylobacter coli to myopericarditis in children.

Paediatric giant cell myocarditis: a case report.

A previously healthy 15-year-old teenage boy was admitted for fever and heart failure. Myocarditis was suspected, and endomyocardial biopsy revealed giant cell myocarditis. Immunosuppressive treatment was initiated, with excellent response. A plausible link to previous leptospirosis was identified. At 18-month follow-up, left ventricular function is normal. Only one other reported case of paediatric giant cell myocarditis had such a favourable outcome.

Protocol-based cardiotoxicity monitoring in hydroxychloroquine medicated COVID-19 pediatric patients.

INTRODUCTION/OBJECTIVES: By May 2020, SARS-CoV-2 had caused more than 400 000 deaths worldwide. Initially, hydroxychloroquine was a treatment option for COVID-19. More recent studies have questioned its safety and efficacy and, until stronger evidence is available, it was suspended from therapy protocols. We describe our experience treating COVID-19 Portuguese pediatric patients with hydroxychloroquine, having applied a protocol for monitoring cardiac toxicity. METHODS: An observational retrospective study of COVID-19 pediatric patients, admitted from March to April 2020 and treated with hydroxychloroquine. Cardiotoxicity was assessed using ECG recordings and corrected QT-time (QTc). Patients were classified into risk-groups depending on QTc value: normal, slightly elevated or severely elevated (>500 ms). RESULTS: Total of 14 patients, with a median age of 10 years [four months; 17 years], treated with hydroxychloroquine for a median of five days. Hydroxychloroquine was used in monotherapy in six patients (mainly mild disease with comorbidities), and in association with lopinavir/ritonavir (3) and azithromycin (5) in moderate to severe disease. Other QT-prolonging therapies were used in five patients: oseltamivir (3), omeprazole (1), morphine (1) and ketamine (1). At 48 hours of treatment, two patients temporarily suspended hydroxychloroquine due to QTc prolongation (>500 ms). All patients completed the whole treatment. No other side effects or deaths occurred. CONCLUSION: Clinical trials are evolving to define hydroxychloroquine effectivity and safety. Our considerable pediatric population supports the need for cardiotoxicity monitoring during therapy but suggest its use seems to be safe in COVID-19 pediatric patients, even in association with other QT-prolonging therapies.

INTRODUÇÃO/OBJETIVO: A hidroxicloroquina foi inicialmente uma das opções terapêuticas na Covid-19. Descreve-se o tratamento com hidroxicloroquina em doentes Covid-19 pediátricos, tendo aplicado um protocolo de monitoração cardíaca pelo seu potencial arritmogénico. MÉTODOS: Estudo observacional retrospetivo de doentes pediátricos com Covid-19, internados de março a abril 2020, medicados com hidroxicloroquina. A monitoração cardíaca foi realizada por eletrocardiogramas regulares e cálculo do intervalo QT corrigido durante o tratamento. Os doentes foram classificados consoante o valor de QTc: normal, moderadamente aumentado ou muito aumentado (>500 msg). RESULTADOS: Total de 14 doentes, com mediana de 10 anos [4 meses; 17 anos], medicados com HCQ durante uma mediana de 5 dias em doentes com pneumonia ou comorbilidades. A monoterapia foi realizada em 6 doentes, 4 com fatores de risco, e em associação com lopinavir/ritonavir (3) e azitromicina (5) na doença grave e moderada. Foram ainda usados fármacos capazes de prolongar o intervalo QT: oseltamivir (3), omeprazol (1), cetamina e morfina (1) em 5 doentes. Após 48 horas de terapêutica, dois doentes apresentaram intervalo QTc muito aumentado, condicionando suspensão temporária do fármaco. Todos os doentes concluíram o tratamento sem outros efeitos adversos. CONCLUSÃO: A HCQ permanece em ensaios clínicos para avaliação da sua efetividade e segurança. A nossa amostra considerável em doentes pediátricos apoia a necessidade de monitoração de toxicidade cardíaca, mas sugere na população estudada, mesmo na associação com outros fármacos que prolongam o intervalo QT, a segurança de sua utilização.

Quality of life among adults with repaired tetralogy of fallot: A literature review.

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect. Survival into adulthood is currently expected following surgical repair, leading to a growing population of adults with repaired TOF. In this literature review, we aim to summarize the current state of knowledge on the quality of life of adults with repaired TOF. A search was conducted on PubMed and results were reviewed for articles published between January of 2010 and June of 2020. Search terms included "Tetralogy of Fallot", "repaired", "adults" and "quality of life". For the subjective health status evaluation, most published studies used Short-Form-36. Most studies agree that physical complex status is poorer for adult patients with repaired TOF than for controls. Mental complex status was also lower. Patients reported similar satisfaction with their lives and levels of social participation. Most patients had a college or university degree. Higher education, male gender and having a partner were positively associated with being employed. Studies found no difference in the proportion of patients that are married or living with a partner, compared to control groups. Patients operated for TOF have a lower reproduction rate compared with the background population. A consistent finding of these studies is abnormal physical parameters compared to psychosocial issues. The diverse needs of adults with repaired TOF require a multidisciplinary care, that takes into consideration all aspects that affect their quality of life. Despite abnormal physical functional status, it is reassuring that most adult patients with TOF lead independent and productive lives.

ROSS SURGERY: OUR EXPERIENCE.

OBJECTIVES: At Santa Marta Hospital, Ross Surgery was performed for the first time in 1999. Twenty years later, we feel it is desirable to evaluate the mid and long-term results of our experience, as well as estimate the future of this procedure. METHODS: Between March 1999 and June 2016, 23 Ross procedures were performed at our institution. We did a retrospective analysis of the patients´ data, results of the surgery, complications, freedom from reoperation and mortality. RESULTS: The majority (36,4%) of the patients had aortic stenosis, 22,7% had aortic regurgitation and 27,3% had aortic stenosis and regurgitation. Sub-valvular stenosis was present in 13,6% of patients. The mean follow-up is 15 years. The overall mortality was 9%, without early mortality. In our series, 83% of the patients are free from reoperation. Eighty percent (n=16) of the survivors are in NYHA class I, with the remaining 20% (n=4) in class II. CONCLUSION: Ross surgery has strict indications and in this group of patients the advantages are undeniable and the outcomes, according to our results (with 83% of patients free from reoperation, at a mean follow-up of 15 years), are positive and encouraging.

Pericarditis - Clinical presentation and characteristics of a pediatric population. / Pericardite ­ apresentação e características numa população pediátrica.

INTRODUCTION: Pericarditis is an inflammation of the pericardium. It may be infectious or secondary to a systemic disease. The aim of this study was to analyze the clinical findings, course, treatment and follow-up of children diagnosed with pericarditis at our center. METHODS: We performed a retrospective analysis of all children admitted to our pediatric cardiology unit with pericarditis between 2003 and 2015. Patient characteristics were summarized using frequencies and percentages for categorical variables and medians with percentiles for continuous variables. RESULTS: Fifty patients were analyzed (40 male, 10 female) with a median age of 14 years. The most common diagnosis was acute pericarditis (80%). Thirty-five patients (70%) presented with chest pain and 26% reported fever. Cardiomegaly was identified on chest X-ray in 11 patients (22%), 30 patients (60%) had an abnormal ECG and 44 patients (80%) had alterations on the transthoracic echocardiogram. In 17 cases (34%) there was myocardial involvement. Forty-eight percent of patients presented with infectious pericarditis and the pathologic agent was identified in half of them. Postpericardiotomy syndrome was diagnosed in five cases. The first-line therapy was aspirin in 50% of cases. Pericardiocentesis was performed in 12 patients. The median length of stay was nine days. There was symptom recurrence in seven children. CONCLUSIONS: In this study, acute infectious pericarditis was the most common presentation and about one third of patients also had myocarditis. The symptom recurrence rate was not negligible and is probably related to the type of therapy employed.

Clinical and genetic diagnosis of familial hypertrophic cardiomyopathy: Results in pediatric cardiology. / Diagnóstico clínico e genético de miocardiopatia hipertrófica familiar: resultados em cardiologia pediátrica.

INTRODUCTION: Hypertrophic cardiomyopathy (HCM) is most often of autosomal dominant inheritance with incomplete penetrance and variable expression. The main purpose of family screening is to identify relatives with unrecognized HCM and to monitor those at risk for disease, in order to minimize complications and to assess risk of sudden cardiac death. The ESC and ACCF/AHA guidelines on the diagnosis and management of HCM recommend the screening of child relatives from the age of 10-12 years. OBJECTIVES: We studied the outcome of clinical screening and genetic testing of child probands and relatives (<18 years of age) from families with HCM and assessed the age-related penetrance of HCM during the follow-up of these young relatives. METHODS AND RESULTS: Twenty patients from ten families were included between 2004 and 2013, consisting of three probands and 17 first-degree relatives (80% male; median age 10 years). Fourteen child relatives were mutation carriers (70%; median age eight years). Seven (50%) of the 14 mutation carriers were diagnosed with HCM at initial assessment. At-risk child relatives were defined as those with a positive mutation but a negative phenotype at enrollment. After 3.5±0.8 years of follow-up, two of the phenotype-negative mutation carriers developed HCM at 10 and 15 years of age (28% penetrance rate). CONCLUSIONS: The penetrance of HCM in phenotype-negative child relatives was 28% after 3.5 years of follow-up. This underlines the need for long-term monitoring of mutation carriers irrespective of the presence of a positive phenotype.

[Acute kidney injury after pediatric cardiac surgery: risk factors and outcomes. Proposal for a predictive model]. / Insuficiência renal aguda no contexto de cirurgia cardíaca pediátrica: fatores de risco e prognóstico. Proposta de um modelo preditivo.

OBJECTIVES: To characterize the epidemiology and risk factors for acute kidney injury (AKI) after pediatric cardiac surgery in our center, to determine its association with poor short-term outcomes, and to develop a logistic regression model that will predict the risk of AKI for the study population. METHODS: This single-center, retrospective study included consecutive pediatric patients with congenital heart disease who underwent cardiac surgery between January 2010 and December 2012. Exclusion criteria were a history of renal disease, dialysis or renal transplantation. RESULTS: Of the 325 patients included, median age three years (1 day-18 years), AKI occurred in 40 (12.3%) on the first postoperative day. Overall mortality was 13 (4%), nine of whom were in the AKI group. AKI was significantly associated with length of intensive care unit stay, length of mechanical ventilation and in-hospital death (p<0.01). Patients' age and postoperative serum creatinine, blood urea nitrogen and lactate levels were included in the logistic regression model as predictor variables. The model accurately predicted AKI in this population, with a maximum combined sensitivity of 82.1% and specificity of 75.4%. CONCLUSIONS: AKI is common and is associated with poor short-term outcomes in this setting. Younger age and higher postoperative serum creatinine, blood urea nitrogen and lactate levels were powerful predictors of renal injury in this population. The proposed model could be a useful tool for risk stratification of these patients.

The hybrid approach for palliation of hypoplastic left heart syndrome: Intermediate results of a single-center experience.

INTRODUCTION: Hypoplastic left heart syndrome (HLHS) is a major cause of cardiac death during the first week of life. The hybrid approach is a reliable, reproducible treatment option for patients with HLHS. Herein we report our results using this approach, focusing on its efficacy, safety and late outcome. METHODS: We reviewed prospectively collected data on patients treated for HLHS using a hybrid approach between July 2007 and September 2014. RESULTS: Nine patients had a stage 1 hybrid procedure, with seven undergoing a comprehensive stage 2 procedure. One patient completed the Fontan procedure. Five patients underwent balloon atrial septostomy after the hybrid procedure; in three patients, a stent was placed across the atrial septum. There were three deaths: two early after the hybrid procedure and one early after stage two palliation. Overall survival was 66%. CONCLUSIONS: In our single-center series, the hybrid approach for HLHS yields intermediate results comparable to those of the Norwood strategy. The existence of dedicated teams for the diagnosis and management of these patients, preferably in high-volume centers, is of major importance in this condition.

Successful catheter ablation of a left anterior accessory pathway from the non-coronary cusp of the aortic valve.

Left anterior accessory pathways are considered to be rare findings. Catheter ablation of accessory pathways in this location remains a challenging target, and few reports about successful ablation of these accessory pathways are available. We describe our experience regarding a case of a manifest left anterior accessory pathway ablation using radiofrequency energy at the junction of the left coronary cusp with the non-coronary cusp.

An insight into the autonomic and haemodynamic mechanisms underlying reflex syncope in children and adolescents: a multiparametric analysis.

Around 15% of children and adolescents experience at least one episode of syncope until adulthood. Excluding cardiac disease, the majority of syncopes are of reflex origin and benign in nature. In this situation, a tilt test is conducted to reproduce symptoms and to evaluate cardiovascular adaptations to orthostatism, but its mechanisms are not yet well defined. Here, we investigated haemodynamics and autonomic activity during tilt in young patients. Patients (n=113) with unexplained syncope were enrolled. Tilt followed a standard protocol without provocative agents. A positive response (fainters) was defined as a sudden development of syncope or presyncope associated with hypotension, bradycardia, or both. Haemodynamic parameters, autonomic activity, and baroreflex sensibility were evaluated. Data were analysed on baseline; immediately after tilting; on tilt adaptation; before fainting or before tilt-down for non-fainters; and on tilt-down. A total of 45 patients experienced syncope after a mean time of 18 minutes. During tilting up, fainters showed lower blood pressure and peripheral resistance values, which decreased progressively with time together with baroreflex sensibility. Sympathetic tone increased massively along time till syncope. No changes in cardiac output and heart rate were observed. Results show a strong effort of the autonomic nervous system to adapt to orthostatic stress through different magnitudes of sympathetic output, which was maximal before syncope without apparent modifications of parasympathetic tone. These changes suggest an imbalance between both branches of the autonomic nervous system, not enabling a time-progressive adaptation and leading the subject to faint.

The role of propranolol in the treatment of infantile hemangioma.

INTRODUCTION: Infantile hemangioma (IH) is one of the most common childhood tumors. There are various medical or surgical therapeutic options, all with suboptimal results. Recently, the successful use of propranolol for involution of IH was described. We report the results of a single-center experience with this therapeutic option. OBJECTIVE: To prospectively assess the efficacy and safety of propranolol in children with infantile hemangioma. METHODS: We performed a prospective analysis of clinical data of all patients with IH referred to a pediatric cardiology center for baseline cardiovascular assessment prior to propranolol therapy. Propranolol was given at a starting dose of 1 mg/kg/day and titrated to a target dose of 2-3 mg/kg/day according to clinical response. Efficacy was assessed through a photograph-based severity scoring scale. Safety was assessed by collecting data regarding significant side effects. RESULTS: Starting in 2010, 30 patients (15 female) were referred for propranolol treatment of IH, at a median age of six months (1-63 months). The mean target propranolol dose was 2.8 mg/kg/day, with a mean duration of therapy of 12 months. All patients experienced significant reduction of IH size and volume. There were no side effects. CONCLUSIONS: In our experience propranolol appears to be a useful and safe treatment option for severe or complicated IH, achieving a rapid and significant reduction in their size. No adverse effects were observed, although until larger clinical trials are completed, potential adverse events should be borne in mind and consultation with local specialists is recommended prior to initiating treatment.

Dual etiology of dilated cardiomyopathy: the synergistic role of vitamin D deficiency.

Dilated cardiomyopathy is the commonest form of cardiomyopathy in pediatric patients. Various causal factors have been identified, including ionic imbalance. Calcium ions play an essential role in regulating myocardial contractile function, and the harmful role of hypocalcemia as a coadjuvant or even precipitating factor of worsening heart failure has been described in rare case reports. Multiple causative factors may occasionally be present. We describe the first case, to our knowledge, of dilated cardiomyopathy in an infant with severe hypocalcemia and viral myocarditis.

Mitro-aortic aneurysms in children: single-centre experience and review of the literature.

OBJECTIVES: This publication aims to report the cases of four children with pseudoaneurysm of the mitral-aortic intervalvular fibrosa and carry out a review of the literature. BACKGROUND: Pseudoaneurysm of the mitral-aortic intervalvular fibrosa is a very rare anomaly in children. It can be either congenital or acquired, namely, after bacterial endocarditis or cardiac trauma. This pathology does not usually cause specific symptoms but its outcome may be potentially fatal. METHODS: We report the cases of four patients presenting with pseudoaneurysm of the mitral-aortic intervalvular fibrosa, referred for treatment in a paediatric cardiology clinic. Patient clinical notes were retrospectively reviewed for aetiology, clinical presentation, diagnostic work-up, surgical treatment, and follow-up. Literature on the subject was extensively reviewed. RESULTS: In three patients, pseudoaneurysm of the mitral-aortic intervalvular fibrosa was acquired, being secondary to bacterial endocarditis in two cases and establishing after mitral surgery in another case. The remaining patient had a "congenital" aetiology - no other cause could be traced. The diagnosis was achieved by transthoracic echocardiography for all patients, and confirmed in all by trans-oesophageal echocardiography, to better define morphological details and to access flow into the aneurysmal formation. All patients were submitted to corrective cardiac surgery. Of the patients, three survived and were cured by surgery, staying asymptomatic, and one died after repeated interventions, for persistent endocarditis. CONCLUSIONS: Pseudoaneurysm of the mitral-aortic intervalvular fibrosa is a rare but potentially fatal anomaly. In our experience, surgical cure was achieved for the majority of the cases, except for a case for which infection could not be locally eradicated, leading to multiple reinterventions.

Partial anomalous pulmonary venous connections: surgical management.

Partial anomalous pulmonary venous connections (PAPVCs) are a heterogeneous group of congenital heart lesions in which at least one pulmonary vein will drain into the systemic venous system. The consequences are a variable left-to-right hemodynamic shunt and more rarely pulmonary artery hypertension. Often, PAPVC occurs in association with other congenital cardiac malformations. Surgical correction is most often advisable and is generally straightforward and simple to achieve. Historically, some repairs have included incision across the junction of the superior vena cava with the right atrium, which can lead to late arrhythmias. The Warden technique avoids incision across the atriocaval junction. Neonates and infants with Scimitar syndrome represent the most challenging subset of patients with PAPVC.