Bicuspid Aortic Valve Disease With Early Onset Complications: Characteristics And Aortic Outcomes.

Bicuspid aortic valve (BAV) is the most common congenital heart malformation in adults but can also cause childhood-onset complications. In multicenter study, we found that adults who experience significant complications of BAV disease before age 30 are distinguished from the majority of BAV cases that manifest after age 50 by a relatively severe clinical course, with higher rates of surgical interventions, more frequent second interventions, and a greater burden of congenital heart malformations. These observations highlight the need for prompt recognition, regular lifelong surveillance, and targeted interventions to address the significant health burdens of patients with early onset BAV complications.

New-onset heart failure in infants: when the aetiological diagnosis becomes a challenge.

This study aimed to report the findings of cardiac magnetic resonance imaging (CMR) with quantitative mappings in infants presenting with new-onset heart failure, as well as to assess the capabilities of endomyocardial biopsy (EMB) and CMR in detecting inflammatory cardiomyopathies and determining their etiology. In a prospective analysis of infants who underwent CMR with tissue mappings, EMB, and genetic testing, the sample was categorized into two groups: those with inflammatory cardiomyopathy and negative genetics (indicative of possible myocarditis) and those with positive genetics (indicative of possible dilated cardiomyopathy). All patients exhibited similar clinical presentations, echocardiographic dysfunction, and elevated troponins and NT-proBNP levels. Additionally, they all met the diagnostic criteria for inflammatory cardiomyopathy based on EMB findings (≥14 mononuclear cells, ≥7 T-lymphocytes/mm2). EMB results unveiled significant differences in the presence of inflammation and edema between the two groups, with higher troponin levels correlating with increased inflammation. Notably, when focusing on CMR, neither the classic criteria nor the 2018 Lake Louise criteria (LLC) could effectively differentiate between the two groups. Only late gadolinium enhancement (LGE) appeared to be associated with myocarditis in this cohort, while other LLC and tissue mappings did not exhibit a similar correlation. Importantly, there was no observed correlation between the inflammation detected through EMB and CMR. CONCLUSIONS: The onset of heart dysfunction in infants can result from either inherited factors or viral infections, both of which may involve inflammation. However, the precise role of EMB and CMR in determining the etiology of such cases remains poorly defined. While CMR demonstrates high sensitivity in detecting inflammation, our experience suggests that it may not effectively differentiate between these two groups. A comprehensive diagnostic approach is essential when addressing this challenge, which includes considering EMB (with attention to the number of T-lymphocytes and the presence of oedema), specific CMR criteria, notably LGE and tissue mappings, as well as the identification of viral agents in cardiac tissue and troponin levels. Additionally, genetic tests should be conducted when evaluating these patients. WHAT IS KNOWN: • EMB is the gold standard diagnostic test for myocarditis but it is not universally accepted. • The diagnostic value of the 2018-LLC in pediatric patients is still undefined. WHAT IS NEW: • Both EMB and CMR may show inflammation in infants with new-onset heart failure of any aetiology. • A global approach should be used when facing this diagnostic challenge, including the EMB (number of T-lymphocytes and oedema), some CMR criteria, specially LGE and mappings, the detection of viral agents in cardiac tissue and troponins. Genetic tests should also be performed when studying these patients.

Rare Genomic Copy Number Variants Implicate New Candidate Genes for Bicuspid Aortic Valve.

Bicuspid aortic valve (BAV), the most common congenital heart defect, is a major cause of aortic valve disease requiring valve interventions and thoracic aortic aneurysms predisposing to acute aortic dissections. The spectrum of BAV ranges from early onset valve and aortic complications (EBAV) to sporadic late onset disease. Rare genomic copy number variants (CNVs) have previously been implicated in the development of BAV and thoracic aortic aneurysms. We determined the frequency and gene content of rare CNVs in EBAV probands (n = 272) using genome-wide SNP microarray analysis and three complementary CNV detection algorithms (cnvPartition, PennCNV, and QuantiSNP). Unselected control genotypes from the Database of Genotypes and Phenotypes were analyzed using identical methods. We filtered the data to select large genic CNVs that were detected by multiple algorithms. Findings were replicated in cohorts with late onset sporadic disease (n = 5040). We identified 34 large and rare (< 1:1000 in controls) CNVs in EBAV probands. The burden of CNVs intersecting with genes known to cause BAV when mutated was increased in case-control analysis. CNVs intersecting with GATA4 and DSCAM were enriched in cases, recurrent in other datasets, and segregated with disease in families. In total, we identified potentially pathogenic CNVs in 8% of EBAV cases, implicating alterations of candidate genes at these loci in the pathogenesis of BAV.

Arterial tortuosity syndrome: Phenotypic features and cardiovascular manifestations in 4 newly identified patients.

Arterial tortuosity syndrome (ATS) is an autosomal recessive connective tissue disease caused by biallelic variants in the SLC2A10 gene (NG_016284.1) and characterised by tortuosity and elongation of the aorta and medium-sized arteries. It is considered an extremely rare disease; only 106 individuals with genetically confirmed ATS have been identified to date. Four cases of ATS from two families are described, contributing to the clinical delineation of this condition. A patient with microcephaly and a complex uropathy and two cases with diaphragmatic hernia are noticed. Regarding the vascular involvement, a predominant supra-aortic involvement stands out and only 1 patient with significant arterial stenoses was described. All presented severe tortuosity of the intracranial arteries. To reduce hemodynamic stress on the arterial wall, beta-adrenergic blocking treatment was prescribed. A not previously described variant (NM_030777.4:c.899T>G (p.Leu300Trp)) was detected in a proband; it has an allegedly deleterious effect in compound heterozygous state with the pathogenic variant c.417T>A (p.Tyr139Ter). The other 3 patients, siblings born to healthy consanguineous parents, had a variant in homozygous state: c.510G>A (p.Trp170Ter).

Characteristics and outcomes of the Spanish registry for pediatric patients with bicuspid aortic valve (REVAB).

INTRODUCTION AND OBJECTIVES: Bicuspid aortic valve (BAV) disorder is the most common congenital heart disease. The aim of this study was to describe the characteristics of 0- to 18-year olds with BAV in a population-based registry. METHODS: Data from all pediatric patients were obtained from the Spanish registry for pediatric patients with bicuspid aortic valve (REVAB) (< 18 years). For data analysis, patients with BAV were divided into 2 groups by their features: isolated BAV and BAV with associated congenital heart disease. RESULTS: We included 1681 patients from 33 hospitals. Males accounted for 69.6% (n = 1158). Valve morphology was horizontal in 63.4% (n = 1012) and pure (Sievers type 0) in 28.4% (n=469). Isolated BAV was present in 63.7% (n=1060), and concomitant left-sided obstructive lesions in 23.4% (n=390). Interventions were required in 8.6% (n=145). CONCLUSION: These data represent the first large, population-based description of the clinical presentations and outcomes of patients enrolled in the Spanish registry for pediatric patients with bicuspid aortic valve.

Myocardial tissue characterization by cardiovascular magnetic resonance T1 mapping and pericardial fat quantification in adolescents with morbid obesity. Cardiac dimorphism by gender.

PURPOSE: Changes in the myocardial extracellular matrix (ECM) identified using T1 mapping cardiovascular magnetic resonance (CMR) have been only reported in obese adults, but with opposite conclusions. The objectives are to assess the composition of the myocardial ECM in an obese pediatric population without type 2 diabetes by quantifying native T1 time, and to quantify the pericardial fat index (PFI) and their relationship with cardiovascular risk factors. METHODS: Observational case-control research of 25 morbidly obese adolescents and 13 normal-weight adolescents. Native T1 and T2 times (ms), left ventricular (LV) geometry and function, PFI (g/ht3) and hepatic fat fraction (HFF, %) were calculated by 1.5-T CMR. RESULTS: No differences were noticed in native T1 between obese and non-obese adolescents (1000.0 vs. 990.5 ms, p0.73), despite showing higher LV mass values (28.3 vs. 22.9 g/ht3, p0.01). However, the T1 mapping values were significantly higher in females (1012.7 vs. 980.7 ms, p < 0.01) while in males, native T1 was better correlated with obesity parameters, particularly with triponderal mass index (TMI) (r = 0.51), and inflammatory cells. Similarly, the PFI was correlated with insulin resistance (r = 0.56), highly sensitive C-reactive protein (r = 0.54) and TMI (r = 0.77). CONCLUSION: Female adolescents possess myocardium peculiarities associated with higher mapping values. In males, who are commonly more exposed to future non-communicable diseases, TMI may serve as a useful predictor of native T1 and pericardial fat increases. Furthermore, HFF and PFI appear to be markers of adipose tissue infiltration closely related with hypertension, insulin resistance and inflammation.

Different profiles of lipoprotein particles associate various degrees of cardiac involvement in adolescents with morbid obesity.

Introduction: Dyslipidemia secondary to obesity is a risk factor related to cardiovascular disease events, however a pathological conventional lipid profile (CLP) is infrequently found in obese children. The objective is to evaluate the advanced lipoprotein testing (ALT) and its relationship with cardiac changes, metabolic syndrome (MS) and inflammatory markers in a population of morbidly obese adolescents with normal CLP and without type 2 diabetes mellitus, the most common scenario in obese adolescents. Methods: Prospective case-control research of 42 morbidly obese adolescents and 25 normal-weight adolescents, whose left ventricle (LV) morphology and function had been assessed. The ALT was obtained by proton nuclear magnetic resonance spectroscopy, and the results were compared according to the degree of cardiac involvement - normal heart, mild LV changes, and severe LV changes (specifically LV remodeling and systolic dysfunction) - and related to inflammation markers [highly-sensitive C-reactive protein and glycoprotein A (GlycA)] and insulin-resistance [homeostatic model assessment for insulin-resistance (HOMA-IR)]. A second analysis was performed to compare our results with the predominant ALT when only body mass index and metabolic syndrome criteria were considered. Results: The three cardiac involvement groups showed significant increases in HOMA-IR, inflammatory markers and ALT ratio LDL-P/HDL-P (40.0 vs. 43.9 vs. 47.1, p 0.012). When only cardiac change groups were considered, differences in small LDL-P (565.0 vs. 625.1 nmol/L, p 0.070), VLDL size and GlycA demonstrated better utility than just traditional risk factors to predict which subjects could present severe LV changes [AUC: 0.79 (95% CI: 0.54-1)]. In the second analysis, an atherosclerotic ALT was detected in morbidly obese subjects, characterized by a significant increase in large VLDL-P, small LDL-P, ratio LDL-P/HDL-P and ratio HDL-TG/HDL-C. Subjects with criteria for MS presented overall worse ALT (specially in triglyceride-enriched particles) and remnant cholesterol values. Conclusions: ALT parameters and GlycA appear to be more reliable indicators of cardiac change severity than traditional CV risk factors. Particularly, the overage of LDL-P compared to HDL-P and the increase in small LDL-P with cholesterol-depleted LDL particles appear to be the key ALT's parameters involved in LV changes. Morbidly obese adolescents show an atherosclerotic ALT and those with MS present worse ALT values.

Arrhythmia and impaired myocardial function in heritable thoracic aortic disease: An international retrospective cohort study.

BACKGROUND: Heritable thoracic aortic diseases (HTAD), typically entailing aortic complications, can be caused by pathogenic variants or likely pathogenic variants (PV/LPVs) in several genes, including fibrillin1 (FBN1), Actin Alpha2 (ACTA2) and genes encoding components of the transforming growth factor (TGF)-ß signaling pathway. In addition to aortic complications, non-aortic cardiac disease such as impaired myocardial function and/or arrhythmia have been increasingly reported, mainly in Marfan syndrome with underlying FBN1 PV/LPVs and are acknowledged as additional causes of morbidity and mortality. The prevalence of these manifestations in the various HTAD entities is largely unknown. METHODS: This international multicentre retrospective study collected data on patients with HTAD presenting non-aortic cardiac disease. A total of 9 centers from 7 different countries participated. Patients 12 years or older carrying a PV/LPV in one of the following genes: FBN1, TGFBR1, TGFBR2, TGFB2, TGFB3, SMAD3 and ACTA2 were screened. Non-aortic cardiac disease included impaired myocardial function and/or arrhythmia. Impaired myocardial function was defined as (a)symptomatic reduced ejection fraction (EF<50%). Arrhythmias included atrial fibrillation (AF), atrial flutter (AFL), ventricular tachycardia (VT), ventricular fibrillation (VF) and (aborted) sudden cardiac death (presumed arrhythmogenic) (SCD). RESULTS: Medical records of 3219 patients with HTAD were screened (2761, 385 and 73 carrying a PV/LPV in FBN1, in a TGF-ß signaling gene and in ACTA2 respectively). Non-aortic cardiac disease was reported 142 times in 101 patients (3.1%) (age 37 [range 12-77] years, 39% female): 88 patients carrying an FBN1 PV/LPV and 13 carrying a PV/LPV in one of the TGF-ß signaling genes. Neither impaired myocardial function nor arrhythmia was reported in screened patients carrying a PV/LPV in ACTA2. Among the 142 reported non-aortic cardiac diseases, 68 (48%) were impaired myocardial function, 47 (33%) were AF/AFL and 27 (19%) were VT/VF/SCD. Among the patients with non-aortic cardiac disease, prior cardiac surgery was noted in 80% and severe valvular disease (valvular surgery or severe valvular regurgitation) in 58%, while 18% of the patients developed non-aortic cardiac disease in the absence of any of the latter. CONCLUSIONS: In patients with HTAD, arrhythmia and impaired myocardial function was reported in patients with PV/LPVs in FBN1 and in the TGF-ß signaling genes and not in patients harboring PV/LPVs in ACTA2. Though infrequent, non-aortic cardiac disease should be acknowledged as potentially severe, also occurring in young patients with no underlying significant valvular or aortic disease.

Evolución del intervalo QTc en pacientes con infección SARS-CoV-2 tratados con fármacos antivirales / QTc interval prolongation in patients infected with SARS-CoV-2 and treated with antiviral drugs

Introducción: Muchos antivirales, como la hidroxicloroquina, se han utilizado para el tratamiento de COVID-19. La prolongación del QTc es un efecto adverso preocupante, escasamente estudiado en pediatría. Pacientes y métodos: Los pacientes pediátricos con COVID-19 que recibieron tratamiento antiviral se emparejaron (1:2) con controles no infectados ni expuestos al tratamiento. Se analizaron prospectivamente los electrocardiogramas basales, en las primeras 72 horas de tratamiento y posterior a 72 horas. Resultados: Once (22,9%) de 48 pacientes pediátricos ingresados por COVID-19 (marzo a julio del 2020) recibieron terapia antiviral. Todos presentaban patologías de base; destacando cardiopatías (4/11; 36,4%) e inmunosupresión (3/11; 27,3%); 5/11 (45,5%) recibían tratamiento de base con potencial efecto sobre el QTc. No hubo diferencias en el QTc basal entre casos y controles: 414,8 ms (49,2) vs. 416,5 ms (29,4) (p = 0,716). Se observó QTc prolongado basal en 2/11 casos y 2/22 controles. De los casos, 10/11 (90,9%) recibieron hidroxicloroquina, principalmente asociada a azitromicina (8/11; 72,7%); tres recibieron lopinavir/ritonavir, uno remdesivir. La mediana de incremento del QTc tras 72 horas fue de 28,9 ms (IQR 48,7) (p = 0,062); 4/11 (36,4%) presentaron un QTc largo, de los cuales en tres ≥ 500 ms. En uno se paró el tratamiento (QTc 510 ms) pero no se documentaron arritmias ventriculares. Conclusiones: El uso de fármacos antivirales causó un incremento del QTc tras 72 horas de tratamiento, considerándose un QTc largo en el 36,4% de los pacientes, aunque no se objetivaron eventos arrítmicos. El uso de hidroxicloroquina y antivirales requiere monitorización activa del QTc y se recomienda suspender el tratamiento si el QTc > 500 ms. (AU)

Introduction: Many antiviral agents, such as hydroxychloroquine, have been used to treat COVID-19, without being broadly accepted. QTc prolongation is a worrisome adverse effect, scarcely studied in pediatrics. Patients and methods: Pediatric patients affected from COVID-19 who received antivirals were matched (1:2) with controls not infected nor exposed. Electrocardiograms were prospectively analyzed at baseline, during the first 72 h in treatment and after 72 h. Results: Eleven (22.9%) out of 48 patients admitted due to COVID-19 (March–July 2020) received antiviral therapy. All had underlying diseases: congenital heart disease (4/11; 36.4%) and immunosuppression (3/11; 27.3%) stand out. 5/11 (45.5%) received treatment at baseline with a potential effect on QTc. There where no differences observed in the baseline QTc between cases and controls: 414.8 ms (49.2) vs. 416.5 ms (29.4) (p = 0.716). Baseline long QT was observed in 2/11 cases and 2/22. Among cases, 10/11 (90.9%) received hydroxychloroquine, mainly associated with azithromycin (8/11; 72.7%), 3 received lopinavir/ritonavir and one remdesivir. The median increase in QTc after 72 h under treatment was 28.9 ms (IQR 48.7) (p = 0.062). 4/11 (36.4%) patients had a long QTc at 72 h, resulting in 3 patients ≥500 ms; treatment was stopped in one (QTc 510 ms) but ventricular arrhythmias were not documented. Conclusions: The use of antivirals caused an increase on the QTc interval after 72 h of treatment, being the QTc long in 36.3% of the patients, although no arrhythmic events were observed. The use of hydroxychloroquine and antivirals requires active QTc monitoring and it is recommended to discontinue treatment if QTc >500 ms. (AU)

QTc interval prolongation in patients infected with SARS-CoV-2 and treated with antiviral drugs.

INTRODUCTION: Many antiviral agents, such as hydroxychloroquine, have been used to treat COVID-19, without being broadly accepted. QTc prolongation is a worrisome adverse effect, scarcely studied in pediatrics. PATIENTS AND METHODS: Paediatric patients affected from COVID-19 who received antivirals were matched (1:2) with controls not infected nor exposed. Electrocardiograms were prospectively analyzed at baseline, during the first 72 h of treatment and after 72 h. RESULTS: Eleven (22.9%) out of 48 patients admitted due to COVID-19 (March-July 2020) received antiviral therapy. All had underlying diseases: congenital heart disease (4/11; 36.4%) and immunosuppression (3/11; 27.3%) stand out. 5/11 (45.5%) received treatment at baseline with a potential effect on QTc. There where no differences observed in the baseline QTc between cases and controls: 414.8 ms (49.2) vs 416.5 ms (29.4), (P = .716). Baseline long QT was observed in 2/11 cases and 2/22. Among cases, 10/11 (90.9%) received hydroxychloroquine, mainly associated with azithromycin (8/11; 72.7%), 3 received lopinavir/ritonavir and one remdesivir. The median increase in QTc after 72 h under treatment was 28.9 ms [IQR 48.7] (P = .062). 4/11 (36.4%) patients had a long QTc at 72 h, resulting in 3 patients ≥500 ms; treatment was stopped in one (QTc 510 ms) but ventricular arrhythmias were not documented. CONCLUSIONS: The use of antivirals caused an increase on the QTc interval after 72 h of treatment, being the QTc long in 36.3% of the patients, although no arrhythmic events were observed. The use of hydroxychloroquine and antivirals requires active QTc monitoring and it is recommended to discontinue treatment if QTc > 500 ms.

Differences between genetic dilated cardiomyopathy and myocarditis in children presenting with severe cardiac dysfunction.

Acute myocarditis is an inflammatory disease of the myocardium, and it can present as severe heart failure in children. Differential diagnosis with genetic cardiomyopathy can be difficult. The objective of this study is to identify patterns of clinical presentation and to assess invasive and non-invasive measures to differentiate patients with acute myocarditis from patients with dilated genetic cardiomyopathy. We performed a retrospective descriptive study of all paediatric patients (0-16 years old) that presented with new-onset heart failure with left ventricle ejection fraction < 35% in whom we performed an endomyocardial biopsy (EMB) during the period from April 2007 to December 2020. The patients were classified into two groups: Group 1 included 18 patients with myocarditis. Group 2 included 9 patients with genetic cardiomyopathy. Findings favouring a diagnosis of myocarditis included a fulminant or acute presentation (77.8% vs 33.3%, p = 0.01), higher degree of cardiac enzyme elevation (p = 0.011), lower left ventricular dimension z-score (2.2 vs 5.4, p = 0.03) increase of ventricular wall thickness (88.8% vs 33.3%, p = 0.03) and oedema in the EMB. Seven (77.8%) patients with genetic cardiomyopathy had inflammation in the endomyocardial biopsy fulfilling the diagnostic criteria of inflammatory cardiomyopathy.Conclusion: Differentiating patients with a myocarditis from those with genetic cardiomyopathy can be challenging, even performing an EMB. Some patients with genetic cardiomyopathy fulfil the diagnostic criteria of inflammatory cardiomyopathy. Using invasive and non-invasive measures may be useful to develop a predictive model to differentiate myocarditis from genetic cardiomyopathy. What is Known: • Acute myocarditis could present with cardiogenic shock in paediatric patients. • Parvovirus B19 is the main cause of myocarditis in this population. What is New: • Current diagnostic criteria for myocarditis have limited use in paediatric patients presenting with new-onset heart failure. • Some patients with a genetic cardiomyopathy and a new-onset heart failure fulfill the diagnostic criteria of inflammatory cardiomyopathy.

[QTc interval prolongation in patients infected with SARS-CoV-2 and treated with antiviral drugs]. / Evolución del intervalo QTc en pacientes con infección SARS-CoV-2 tratados con fármacos antivirales.

Introduction: Many antiviral agents, such as hydroxychloroquine, have been used to treat COVID-19, without being broadly accepted. QTc prolongation is a worrisome adverse effect, scarcely studied in pediatrics. Patients and methods: Pediatric patients affected from COVID-19 who received antivirals were matched (1:2) with controls not infected nor exposed. Electrocardiograms were prospectively analyzed at baseline, during the first 72 h in treatment and after 72 h. Results: Eleven (22.9%) out of 48 patients admitted due to COVID-19 (March-July 2020) received antiviral therapy. All had underlying diseases: congenital heart disease (4/11; 36.4%) and immunosuppression (3/11; 27.3%) stand out. 5/11 (45.5%) received treatment at baseline with a potential effect on QTc. There where no differences observed in the baseline QTc between cases and controls: 414.8 ms (49.2) vs. 416.5 ms (29.4) (p = 0.716). Baseline long QT was observed in 2/11 cases and 2/22. Among cases, 10/11 (90.9%) received hydroxychloroquine, mainly associated with azithromycin (8/11; 72.7%), 3 received lopinavir/ritonavir and one remdesivir. The median increase in QTc after 72 h under treatment was 28.9 ms (IQR 48.7) (p = 0.062). 4/11 (36.4%) patients had a long QTc at 72 h, resulting in 3 patients ≥500 ms; treatment was stopped in one (QTc 510 ms) but ventricular arrhythmias were not documented. Conclusions: The use of antivirals caused an increase on the QTc interval after 72 h of treatment, being the QTc long in 36.3% of the patients, although no arrhythmic events were observed. The use of hydroxychloroquine and antivirals requires active QTc monitoring and it is recommended to discontinue treatment if QTc >500 ms.

Are Aortic Root and Ascending Aorta Diameters Measured by the Pediatric versus the Adult American Society of Echocardiography Guidelines Interchangeable?

Ascending aorta diameters have important clinical value in the diagnosis, follow-up, and surgical indication of many aortic diseases. However, there is no uniformity among experts regarding ascending aorta diameter quantification by echocardiography. The aim of this study was to compare maximum aortic root and ascending aorta diameters determined by the diastolic leading edge (DLE) and the systolic inner edge (SIE) conventions in adult and pediatric patients with inherited cardiovascular diseases. Transthoracic echocardiograms were performed in 328 consecutive patients (260 adults and 68 children). Aorta diameters were measured twice at the root and ascending aorta by the DLE convention following the 2015 American Society of Echocardiography (ASE) adult guidelines and the SIE convention following the 2010 ASE pediatric guidelines. Comparison of the diameters measured by the two conventions in the overall population showed a non-significant underestimation of the diameter measured by the SIE convention at root level of 0.28 mm (CI -1.36; 1.93) and at tubular ascending aorta level of 0.17 mm (CI -1.69; 2.03). Intraobserver and interobserver variability were excellent. Maximum aorta diameter measured by the leading edge convention in end-diastole and the inner edge convention in mid-systole had similar values to a mild non-significant underestimation of the inner-to-inner method that permits them to be interchangeable when used in clinical practice.

Myocardial Geometry and Dysfunction in Morbidly Obese Adolescents (BMI 35-40 kg/m2).

This study evaluated the preclinical effect of obesity on the ventricular remodeling in adolescents with morbid obesity, and determined if subjects labelled as metabolically healthy obesity (MHO) presented better heart index than those with metabolically unhealthy obesity (MUO). Prospective case-control research of 45 adolescents (14-year-old) with morbid obesity and 25 normal weight adolescents' gender- and age-matched with Tanner stage 4-5. Left ventricle (LV) was evaluated by conventional Doppler echocardiography, tissue Doppler imaging and two-dimensional speckle tracking echocardiography. Compared to normal-weight subjects, adolescents with morbid obesity presented a high percentage of pathological LV geometry (87%; p<0.01), and systolic and diastolic dysfunctions only detected by E/A ratio (2.0 vs 1.7, p<0.01), global longitudinal strain (-21.0% vs -16.5%, p<0.01), and early diastolic strain rate (3.2 vs 2.2, p<0.01). A correlation was found between impaired cardiac index and body mass index (BMI), high blood pressure, hyperglycemia, low HDL-cholesterol and hypertriglyceridemia. BMI and HDL-cholesterol were the most significant independent variables. No significant differences were found in structural and functional cardiac index when MHO and MUO subjects were compared (global longitudinal strain: -17.0% vs -16.4%, p0.79). Morbidly obese adolescents have an abnormal LV geometry, closely related to BMI, and systolic and diastolic LV dysfunctions. Adolescents labelled as MHO, despite exhibiting better BMI and insulin-resistance values, present the same pathological heart changes as MUO.

[QTc interval prolongation in patients infected with SARS-CoV-2 and treated with antiviral drugs]. / Evolución del intervalo QTc en pacientes con infección SARS-CoV-2 tratados con fármacos antivirales.

INTRODUCTION: Many antiviral agents, such as hydroxychloroquine, have been used to treat COVID-19, without being broadly accepted. QTc prolongation is a worrisome adverse effect, scarcely studied in pediatrics. PATIENTS AND METHODS: Pediatric patients affected from COVID-19 who received antivirals were matched (1:2) with controls not infected nor exposed. Electrocardiograms were prospectively analyzed at baseline, during the first 72 h in treatment and after 72 h. RESULTS: Eleven (22.9%) out of 48 patients admitted due to COVID-19 (March-July 2020) received antiviral therapy. All had underlying diseases: congenital heart disease (4/11; 36.4%) and immunosuppression (3/11; 27.3%) stand out. 5/11 (45.5%) received treatment at baseline with a potential effect on QTc. There where no differences observed in the baseline QTc between cases and controls: 414.8 ms (49.2) vs. 416.5 ms (29.4) (p = 0.716). Baseline long QT was observed in 2/11 cases and 2/22. Among cases, 10/11 (90.9%) received hydroxychloroquine, mainly associated with azithromycin (8/11; 72.7%), 3 received lopinavir/ritonavir and one remdesivir. The median increase in QTc after 72 h under treatment was 28.9 ms (IQR 48.7) (p = 0.062). 4/11 (36.4%) patients had a long QTc at 72 h, resulting in 3 patients ≥500 ms; treatment was stopped in one (QTc 510 ms) but ventricular arrhythmias were not documented. CONCLUSIONS: The use of antivirals caused an increase on the QTc interval after 72 h of treatment, being the QTc long in 36.3% of the patients, although no arrhythmic events were observed. The use of hydroxychloroquine and antivirals requires active QTc monitoring and it is recommended to discontinue treatment if QTc >500 ms.

Adolescents with bicuspid aortic valve: Which criteria should we use for aortic dilatation?

BACKGROUND: Criteria to define aortic dilatation in bicuspid aortic valve (BAV) patients are different for children and adults. The objective of this study was to find the best reference tool to define dilation of the aortic root (AR) and the ascending aorta (AA) in BAV adolescents with an adult body surface area (BSA). METHODS: Patients recruited were ≥10-years-old with a BSA ≥1.5 m2. Three measurements of the AR and AA were compared: z-score, the BSA-indexed value (BSA-IV) and the absolute value (AV), with thresholds in +2/+3, 21 mm/m2 and 40 mm, respectively. RESULTS: 231 subjects were collected from the Pediatric REVAB database, with a median age and BSA of 14-year-old and 1.67 m2. Significant differences were reported in the AA: 109 (47%) patients had a z-score ≥2 and 67 (29%) a Z ≥ 3, but only 9 (3%) a BSA-IV ≥21 mm/m2 (p < 0.01 and p < 0.01) and 2 (0.9%) an AV ≥40 mm (p = 0.22 and p = 0.08). CONCLUSION: Our results indicate that in the AA there are a significant number of patients in which it would be recommendable changing to BSA-IV when children are older than 10-year-old and BSA ≥1.5 m2. Regarding the AR, criteria for dilatation seems not to be influenced by the reference chosen.