Assessing autonomic activity and prognostic risk factors comparing multisystem inflammatory syndrome and isolated viral myocarditis/myopericarditis.

INTRODUCTION AND AIM: In pediatric multisystem inflammatory syndrome and isolated viral myocarditis/myopericarditis, autonomic nervous system function can be evaluated by a non-invasive method called heart rate variability. This study aims to evaluate heart rate variability in these two groups by comparing them with each other. This is the first study assessing these values in these two groups of patients. METHOD: Patients who are diagnosed with multisystem inflammatory syndrome in children and isolated viral myocarditis/myopericarditis at a university hospital from September 2021 to February 2023 are screened by electrocardiography, echocardiography, and 24-hour Holter monitoring. A healthy control group, compatible in age and gender with the patient groups, was selected from healthy subjects that applied to the hospital for palpitation, murmur, and/or chest pain. Heart rate variability parameters and related laboratory markers were analyzed and compared among the three groups. RESULTS: There were 30 patients with multisystem inflammatory syndrome in children, 43 patients with isolated viral myocarditis/myopericarditis, and 109 participants in the healthy control group. Statistically significant differences were found in most of the heart rate variability parameters: standard deviation of normal to normal intervals (SDNN), the mean of the 5- minute RR interval standard deviations (SDNNI), the standard deviation of 5-minute R wave to R wave(RR) interval means (SDANN), the root mean square of successive RR interval differences (RMSSD), and the percentage of the beats with a consecutive RR interval difference of more than 50 ms (pNN50%), very low frequency, high frequency, low frequency, triangular index, and low frequency/high-frequency ratio. Multisystem inflammatory syndrome in children patients had impaired and declined heart rate variability values compared to the other two groups. In patients with myocarditis/myopericarditis, we couldn't find a significant difference in these parameters with the control group. CONCLUSION: Heart rate variability can be used as an important non-invasive autonomic function parameter in determining prognosis and treatment plans, especially in patients diagnosed with multisystem inflammatory syndrome in children. This impairment of autonomic activity could be more prominent in patients with decreased left ventricular systolic functions.

Autonomic activity and cardiovascular system risk assessment in pediatric patients with hemolytic uremic syndrome.

In pediatric patients with hemolytic uremic syndrome (HUS), cardiac involvement and autonomic nervous system function can be evaluated by a non-invasive method called heart rate variability (HRV). This study aims to evaluate heart rate variability and electrocardiography findings in patients with HUS by comparing a healthy group. Patients who are diagnosed with HUS at a university hospital from December 2020 to June 2022 are screened by electrocardiography (ECG), echocardiography, and 24-h Holter ECG. A healthy control group, compatible in age and gender with the patient group, was selected from healthy subjects. HRV parameters, laboratory values, and ECG findings were analyzed and compared with the healthy group and each other. There were 25 patients with HUS and 51 participants in the healthy control group. Statistically significant differences were found in some HRV parameters: standard deviation of normal to normal intervals, the mean of the 5-min RR interval standard deviations, the standard deviation of 5-min RR interval means, the triangular interpolation of normal to normal interval, and very-low-frequency power. HUS patients had impaired and declined HRV values compared to the healthy group. There was a significant decrease in the PR distance, while a significant increase in the corrected QT and QT dispersion values was detected in the electrocardiographic findings of the patient group. HRV values impaired as renal failure parameters increased.  Conclusion: Patients with HUS may have autonomic nervous system dysfunction. HRV measurement is a non-invasive method that can evaluate this. It can be thought that there may be an increased risk of cardiovascular events and arrhythmias in some patients with HUS. ECG should be also considered to detect arrhythmia. What is Known: • Hemolytic uremic syndrome (HUS) primarily effects the hematologic parameters and kidney. • Secondary cardiomyopathy with hypertension and renal failure could be observed in these patients. • Rhythm problems are not expected primarily in these patients. • There is very limited data in evaluating autonomic function and arrhythmia risk for these patients. What is New: • Patients with HUS may have autonomic nervous system dysfunction. • HRV measurement is a non-invasive method that can evaluate this. • Cardiovascular events and arrhythmias due to the deterioration of the balance between the sympathetic and parasympathetic systems could manifest in patients with HUS. • An ECG and screening patients for cardiac events, and monitoring them closely should be considered.

The Role of RARG rs2229774, SLC28A3 rs7853758, and UGT1A6*4 rs17863783 Single-nucleotide Polymorphisms in the Doxorubicin-induced Cardiotoxicity in Solid Childhood Tumors.

BACKGROUND: The objective of our study was to determine the role of retinoic acid receptor gamma (RARG) rs2229774, SLC28A3 rs7853758, and UGT1A6*4 rs17863783 single-nucleotide polymorphisms in identifying the risk of doxorubicin-induced cardiotoxicity in pediatric solid tumors. METHODS: A total of 60 pediatric patients who had completed their treatment at least 2 years ago and 50 healthy children matched for age and sex were included in the study. All patients were evaluated for cardiotoxicity by echocardiography. The blood samples were analyzed for RARG rs2229774, SLC28A3 rs7853758, and UGT1A6*4 rs17863783 polymorphisms. Demographic characteristics, echocardiographic parameters, and genetic results of both groups were evaluated. RESULTS: In our study, the RARG rs2229774 AA genotype was associated with cardiotoxicity ( P =0.017). The SLC28A3 rs7853758 AA+GA genotype was detected more frequently in patients who did not develop cardiotoxicity ( P <0.023). Furthermore, the frequency of the SLC28A3 rs7853758 A allele was significantly lower in the cardiotoxicity group ( P <0.025). CONCLUSIONS: This is the first study in the Turkish population to investigate the correlation between the cardiotoxicity risk and 3 marker genes, which are recommended in the pharmacogenetic guideline for risk assessment in pediatric doxorubicin patients. The gene polymorphism that we investigated in this study was useful for the early prediction of cardiotoxicity risk.

Electrocardiography (ECG) analysis and a new feature extraction method using wavelet transform with scalogram analysis.

Electrocardiography (ECG) signals and the information obtained through the analysis of these signals constitute the main source of diagnosis for many cardiovascular system diseases. Therefore, accurate analyses of ECG signals are very important for correct diagnosis. In this study, an ECG analysis toolbox together with a user-friendly graphical user interface, which contains the all ECG analysis steps between the recording unit and the statistical investigation, is developed. Furthermore, a new feature calculation methodology is proposed for ECG analysis, which carries distinct information than amplitudes and durations of ECG main waves and can be used in artificial intelligence studies. Developed toolbox is tested using both Massachusetts Institute of Technology-Beth Israel Hospital (MIT-BIH) Arrhythmia ECG Database and an experimentally collected dataset for performance evaluation. The results show that ECG analysis toolbox presented in this study increases the accuracy and reliability of the ECG main wave detection analysis, highly fasten the process duration compared to manual ones and the new feature set can be used as a new parameter for decision support systems about ECG based on artificial intelligence.

Evaluation of T-wave alternans in pediatric patients with chronic renal failure.

INTRODUCTION: Microvolt T-wave alternans (TWA) is known to be useful in prediction of ischemia and sudden death in high-risk populations and there are no studies in children with chronic renal failure (CRF). Cardiac problems seem to be responsible for an important part of death in children and young adults with CRF. The aim of this study is to evaluate Holter microvolts TWA measurements in children with CRF comparing to the control group. METHODS: This prospective study included 40 patients with CRF and 48 healthy controls. The history, echocardiography and microvolt TWA values based on 24-hour ECG recordings of the patients were evaluated. Analysis of microvolt TWA was considered on the basis of three leads (V5, V1 and AVF). RESULTS: Compared with the controls, the mean systolic and diastolic blood pressure values and average heart rates were significantly higher in the children with CRF (p = 0.001 and p = 0.026, respectively). Also, the values of left ventricular internal dimensions at end diastole and end-diastolic volume were significantly higher in CRF group (p = 0.01 and p = 0.049, respectively) and couplet ventricular extrasystole was detected in 2 patients with CRF. Consequently, all TWA values in three leads were increased in CRF group than the control group but the only increase in V5 lead was statistically significant (p = 0.028). CONCLUSIONS: This study has demonstrated that microvolt TWA values increased in pediatric patients with CRF. TWA might be used for early risk assessment in pediatric patients with CRF in the future.

MicroRNA values in children with rheumatic carditis: a preliminary study.

MicroRNAs (miRNAs) are fine regulators of gene expression which participate in the regulation of almost every phase of cell physiology, including development of immune cells and adjustment of immune response. In the studies with in vitro/in vivo model systems, specific miRNAs are revealed to have various roles in cardiovascular development and physiological functions. Furthermore, some studies have been done to understand the role of miRNAs about myocarditis, heart failure and coronary artery diseases. miRNAs crucial role in the pathogenesis of other rheumatic diseases have been investigated, however rheumatic carditis was not studied. The aim of this study is to assess values of miRNAs in children with rheumatic carditis and compare them with healthy children. This study included 36 children with rheumatic carditis (mean aged 12.1 ± 2.1 years) and age-gender matched 35 healthy controls (mean aged 11.1 ± 2.3 years). Conventional echocardiography was performed to all subjects. Using real-time polymerase chain reaction, the expression of some miRNAs (hsamiR-16-5p, hsa-miR-221-3p, hsa-miR-223-3p, hsa-miR-10a-5p, hsa-miR-24-3p, hsamiR-92a-3p, hsa-iR-320a, hsa-miR-21-5p, hsa-miR-155-5p, hsa-miR-132-3p, hsamiR-146a-5p, hsa-miR-499a-5p, hsa-miR-1, hsa-miR-125, hsa-miR-196a-5p, hsa-miR-130b-3p, hsa-miR-133b, hsa-miR150-5p,hsa-miR-204-5p, hsa-miR-203a) were analyzed. hsa-miR-16-5p(-1.46 fold, p < 0.01), hsa-miR-223-3p(-1.46 fold, p < 0.01), and hsa-miR-92a-3p(-1.27 fold, p < 0.05) expressions in the patients were lower than those of controls, whereas other examined miRNAs did not differently express between the groups. Results of the study demonstrated that significant downregulation of hsa-miR-16-5p, hsa-miR-223-3p and hsa-miR-92a-3p in children with rheumatic carditis. Since, this is the first study in children with rheumatic carditis, further studies are needed for lightening whether these miRNAs might be helpful as biomarkers.

Increased microvolt T-wave alternans in children and adolescents with Eisenmenger syndrome.

OBJECTIVE: To determine the values of microvolt T-wave alternans (MTWA) in children and adolescents with Eisenmenger syndrome (ES) and controls. METHODS: Thirteen were included in the study. After analyzing the 24-h ECG recordings, MTWA was considered using three leads (V5, V1, and aVF). Right heart catheterization and 6-minute walk test (6-MWD) were applied to the patients and pro-brain natriuretic peptide levels were assessed; echocardiographic parameters were obtained from both the groups and the results were compared. RESULTS: The MTWA value in lead V5 was 81.08±10.73 µV in the patient group (63.50±18.78 µV in the control group), in lead V1 was 75.00±16.86 µV (73.94±16.77 µV in the control group), and in lead aVF was 73.77±17.81 µV (72.61±16.21 µV in the control group). Comparison of MTWA values between patients and controls revealed that only lead V5 values were statistically different in the ES group. The 6-MWD scores significantly correlated with lead V5. Right atrial volume and right ventricular fractional area change were significantly correlated with lead V1. The Tei index was significantly correlated with lead aVF. CONCLUSION: The MTWA lead V5 value was significantly higher in children with ES than in controls and was also correlated with decreased exercise tolerance.

Relationship between mean platelet volume-to-lymphocyte ratio and coronary artery abnormalities in Kawasaki disease.

OBJECTIVES: Recently, mean platelet volume-to-lymphocyte ratio has emerged as a novel parameter of inflammation. No study has investigated the role of mean platelet volume-to-lymphocyte ratio in children with Kawasaki disease. We aimed to evaluate the relationship between mean platelet volume-to-lymphocyte ratio and coronary artery abnormalities in Kawasaki disease. METHODS: Between January 2008 and January 2017, a total of 58 children with Kawasaki disease and 42 healthy subjects matched for sex and age were enrolled. Before the treatment, transthoracic echocardiography for all children was performed. Clinical and laboratory results including mean platelet volume, platelet distribution width, red blood cell distribution width, and counts of platelets, neutrophils, lymphocytes, and white blood cells, erythrocyte sedimentation rate, and C-reactive protein levels were measured. Mean platelet volume-to-lymphocyte ratio was calculated as mean platelet volume divided by lymphocyte count. RESULTS: Compared with healthy controls, mean platelet volume-to-lymphocyte ratio was significantly lower in the children with Kawasaki disease (p<0.01). A total of 14 patients (24.1%) had incomplete Kawasaki disease and 15 (25.8%) children with Kawasaki disease had coronary involvement. Mean platelet volume-to-lymphocyte ratio was significantly lower in patients with coronary artery abnormalities (p<0.01). According to receiver operating characteristic curve analysis performed for the prediction of coronary artery abnormalities, the best cut-off point for mean platelet volume-to-lymphocyte ratio was 2.5 (area under curve=0.593, sensitivity 53.3%, specificity 51.1%). CONCLUSION: It was first shown that the children with Kawasaki disease have lower mean platelet volume-to-lymphocyte ratio compared with control subjects. Mean platelet volume-to-lymphocyte ratio may be helpful in predicting coronary artery lesions in patients with Kawasaki disease.

A Rare Cause of Abdominal Pain in Childhood: Cardiac Angiosarcoma.

Cardiac angiosarcomas are extremely rare in childhood, they are rapidly progressive tumours that often present themselves as diagnostic dilemmas, resulting in delayed diagnosis. Also, extracardiac manifestations, including abdominal pain, are extremely rare in patients with intracardiac tumors. We herein present the case of a 15-year-old girl who presented with abdominal pain. Echocardiography and thoracic computed tomography showed right atrial mass. The patient underwent surgery, chemotherapy, and radiotherapy. Eight months after treatment, abdominal recurrence was detected. The abdominal mass was resected, and radiotherapy and new chemotherapy protocol were given. The present case illustrates a rare case of primary cardiac angiosarcoma posing a diagnostic dilemma in an adolescent girl.

A rare cause of abdominal pain in childhood: cardiac angiosarcoma

Abstract Cardiac angiosarcomas are extremely rare in childhood, they are rapidly progressive tumours that often present themselves as diagnostic dilemmas, resulting in delayed diagnosis. Also, extracardiac manifestations, including abdominal pain, are extremely rare in patients with intracardiac tumors. We herein present the case of a 15-year-old girl who presented with abdominal pain. Echocardiography and thoracic computed tomography showed right atrial mass. The patient underwent surgery, chemotherapy, and radiotherapy. Eight months after treatment, abdominal recurrence was detected. The abdominal mass was resected, and radiotherapy and new chemotherapy protocol were given. The present case illustrates a rare case of primary cardiac angiosarcoma posing a diagnostic dilemma in an adolescent girl.

Prognostic markers in congenital diaphragmatic hernia: Left ventricular diameter and pulmonary hypertension.

BACKGROUND: The aim of this study was to investigate whether the outcome of congenital diaphragmatic hernia (CDH) in newborns can be predicted using left ventricular (LV) diameter and estimated pulmonary artery pressure. METHODS: Patients in the newborn unit in 2012-2016 were screened retrospectively. Echocardiographic measurements of 35 patients with isolated left lateral CDH and 27 healthy newborns were compared in the first 24 h of life. RESULTS: Mean LV end-diastolic diameter (LVEDD) and end-systolic diameter (LVESD), and LV ejection fraction were significantly lower in the CDH group. Moreover, tricuspid regurgitation (TR) and pulmonary regurgitation (PR) were significantly higher than in the controls (P < 0.001). Six CDH patients died within the next 40 days after birth. Mean LVEDD and LVESD were significantly lower in the CHD patients who died compared with those who were discharged (P < 0.001, P = 0.016). Also, mean TR and PR (P < 0.001) and the frequency of pulmonary hypertension (PH; P = 0.001) were significantly higher in these patients. On receiver operating characteristic analysis of the CDH non-survivors, LVEDD < 11 mm (sensitivity, 100%; 95%CI: 87.9-100; specificity, 100%; 95%CI: 54.1-100) and TR > 3.5 m/s (sensitivity, 89.66%; 95%CI: 72.6-97.7; specificity, 100%; 95%CI: 54.1-100) were associated with poor prognosis. CONCLUSIONS: Decrease in LVEDD and presence of PH are associated with poor prognosis. Also, PH was associated with mortality in CDH patients. Thus, outcome may be predicted on careful echocardiographic evaluation of the LV diameters and pulmonary pressure.

Familial hypertrophic cardiomyopathy: A case with a new mutation in the MYBPC3 gene.

Familial hypertrophic cardiomyopathy is a genetically heterogeneous disease with variable clinical features that is inherited as autosomal dominant with variable penetrance. Recent developments in genetics of hereditary cardiomyopathy have not only enlightened many points about pathogenesis, but have also provided great benefit to diagnostic approaches of clinicians. Heterozygous mutation of c3691-3692insTTCA in MYBPC3 gene was identified in a pediatric patient with diagnosis of hypertrophic cardiomyopathy at clinic. Hypertrophy was observed in sister and father of the patient in echocardiography screening, and it was subsequently determined that they also had same mutation. This mutation has not previously been defined and reported previously in the literature as cause of hypertrophic cardiomyopathy.

Can whole-blood parameters be used in follow-up of children with rheumatic valvular heart disease?

OBJECTIVES: The aim of the present study was to investigate the relationships between red blood cell distribution width, platelet distribution width, and mean platelet volume and the presence and severity of valvular involvement in patients with rheumatic heart disease. METHODS: Between April, 2012 and December, 2015, 151 patients who were admitted to the Pediatric Cardiology Unit with diagnosis of rheumatic heart disease and 148 healthy children were included to our study. Transthoracic echocardiography for all children was performed, and the values of red blood cell distribution width, platelet distribution width, and mean platelet volume, besides other blood count parameters, erythrocyte sedimentation rate, and C-reactive protein levels were recorded. RESULTS: Red blood cell distribution width, platelet distribution width, mean platelet volume, and C-reactive protein levels were significantly higher in patients with rheumatic heart disease when compared with healthy controls (p0.05). CONCLUSION: This is the first study in children with rheumatic heart disease that demonstrated significantly increased red blood cell distribution width, platelet distribution width, and mean platelet volume levels, as well as evaluated all three parameters together. Furthermore, red blood cell distribution width values in the chronical period of acute rheumatic fever, due to the positive correlation with the other chronic inflammatory markers, may help make the diagnosis in children.

The effect of metilpheniydate, risperidone and combination therapy on ECG in children with attention-deficit hyperactivity disorder.

INTRODUCTION: This study is to investigate ventricular repolarization on electrocardiogram (ECG) in a pediatric population receiving methylphenidate (MPH), risperidone (RIS) and combined therapy. METHODS: A total of 215 patients between 6 and 12years with ADHD/conduct disorder receiving methylphenidate, risperidone and combined therapy for minimum 3months and an untreated ADHD group (n=76) was consecutively included in the study. Twelve lead ECG parameters including mean QT, QTc, T-peak to T-end (TpTe) intervals, TpTe dispersion and TpTe/QT ratio were compared. RESULTS: QT interval, and QTc, TpTe interval, TpTe dispersion and TpTe/QTc ratio values for groups receiving RIS, MPH and combined therapy were found to be significantly higher than other groups. Moreover, in the combined therapy group TpTe and TpTe/QTc values were higher than the single drug administration groups (p<0.05). TpTe and TpTe/QT ratio was significantly higher in the RIS group compared to that of the MPH group. CONCLUSION: These results suggested that combined therapy of these drugs had a more prominent impact on the T wave and RIS could be strongly associated with it.

Effects of Acute Carbon Monoxide Poisoning on ECG and Echocardiographic Parameters in Children.

The aim of the current study is to investigate the effects of CO (carbon monoxide) on the cardiovascular system via electrocardiographic, echocardiographic and biochemical findings in children. This prospective study included 22 children with CO poisoning and 24 healthy children as a control group. The CO-intoxicated children were evaluated via electrocardiography and echocardiography 1 h after admission to the emergency department and daily until their discharge from the hospital. Blood gasses, complete blood account, troponin I and creatinine kinase-MB(CK-MB) were assessed daily. Tpeak-end (p:0.001), QTc durations (p:0.02), Tpeak-end dispersion (p:0.001) and Tpeak-end/QT ratio (p:0.001) of CO-intoxicated patients were significantly higher than those in the control group. Mitral E duration (p:0.001), mitral E/A ratio (p:0.001) and left ventricle contractile fraction (p:0.023) at admission were significantly lower, and left ventricle myocardial performance index was higher (p:0.001) in the CO poisoning group. Troponin I and CK-MB levels were higher at admission in 6 (27 %) and 4 (18 %) patients, respectively. The heart is the most critical organ in pediatric CO poisoning. These children present subclinical systolic and diastolic left ventricle dysfunction even in mild cases. Although, in children with acute CO-intoxication ventricular repolarization is impaired, it seems to be reversible like other findings.

Evaluation of Neurodevelopment Using Bayley-III in Children with Cyanotic or Hemodynamically Impaired Congenital Heart Disease.

OBJECTIVE: The purpose of this study was to compare neurological development of children with cyanotic or hemodynamically impaired congenital heart disease (CHD) and healthy controls by using "Bayley Scales of Infant and Toddler Development Screening Test, Third Edition" (Bayley-III). PATIENTS: Children with CHD (n = 37) and healthy controls (n = 24) aged between 1 and 41 months who were admitted to the Department of Pediatric Cardiology at our university hospital were included. The participants were assessed using Bayley-III test. All patients had cyanotic or hemodynamically impaired CHD. Weight, height, body mass index (BMI), mid-arm circumference (MAC), triceps skinfold thickness (TSF), and head circumference (HC) were measured and standard deviation scores (SDSs) were determined. RESULTS: SDS values of weight, height, BMI, MAC, and TSF of the patients as well as HC values were significantly lower than the control group (P < .001). Compared with controls, the patients had significantly lower mean scores in all Bayley-III subscales (P < .001). We observed similar results in Bayley-III scores including the mean values of cognitive, language, and global motor scores for the CHD patients with and without cardiac surgery (P > .05). CONCLUSION: This study demonstrated that children with cyanotic or hemodynamically impaired CHD have delayed neurodevelopmental outcomes compared with healthy children as assessed using Bayley-III.