Bożena Werner

Interaction Between Heart Rate Variability and Heart Rate in Pediatric Population

Background: Heart rate variability (HRV) is primarily heart rate (HR) dependent, and therefore, different HR may exert different impact on HRV. The objectives of the study were to evaluate the effect of HR on HRV in children and to determine whether HRV indices normalized to HR are sex- and age-related. Methods: Short-term ECG recordings were performed in 346 healthy children. Standard time and frequency domain HRV parameters and HR were analyzed in four age subgroups (6–7, 8–9, 10–11, and 12–13 years old). To investigate the HR impact on HRV, standard HRV parameters were normalized to prevailing HR. Results: Standard HRV measures did not differ between age subgroups, however, HR significantly decreased with subjects age and turned out to be the strongest determinant of HRV. The normalization of HRV to prevailing HR allowed to show that sex-related differences in standard HRV resulted from differences in HR between boys and girls. The normalized HRV significantly decreased with age—before the normalization this effect was masked by age-related HR alterations. Conclusions: HR significantly impacts HRV in pediatric population and turns out to be the strongest determinant of all standard HRV indices. The differences in standard HRV between boys and girls result from differences in their HR. The normalized HRV is decreasing with age in healthy children and it is accompanied by the reduction of HR—as a net result, the standard HRV is constant in children at different ages. This may reflect the maturation of the autonomic nervous system.

Evidence for troponin C (TNNC1) as a gene for autosomal recessive restrictive cardiomyopathy with fatal outcome in infancy.

Restrictive cardiomyopathy is a rare form of pediatric cardiac disease, for which the known genes include MYH7, TNNT2, TNNI3, ACTC1, and DES. We describe a pediatric proband with fatal restrictive cardiomyopathy associated with septal hypertrophy and compound heterozygosity for TNNC1 mutations (NM_003280: p.A8V [c.C23T] and p.D145E [c.C435A]). This association between restrictive cardiomyopathy and TNNC1 mutations was strengthened by prospective observations on the second pregnancy in the family which revealed, in the presence of the same TNNC1 genotype, prenatally diagnosed hypertrophic cardiomyopathy which evolved into restrictive cardiomyopathy, heart failure and death at the age of 9 months. Contrary to previous reports, family and population analyses showed that each of the TNNC1 variants was not pathogenic when present alone. Our results (i) confirm that genetic backgrounds of hypertrophic cardiomyopathy and restrictive cardiomyopathy overlap and (ii) indicate that TNNC1 is a likely novel gene for autosomal recessive restrictive cardiomyopathy.

SETD5 loss‐of‐function mutation as a likely cause of a familial syndromic intellectual disability with variable phenotypic expression

Loss‐of‐function de novo mutations in the SETD5 gene, encoding a putative methyltransferase, are an important cause of moderate/severe intellectual disability as evidenced by the results of sequencing large patient cohorts. We present the first familial case of a SETD5 mutation contributing to a phenotype of congenital heart defects and dysmorphic features, with variable expression, in two siblings and their father. Interestingly, the father demonstrated only mild intellectual impairment. Family based exome sequencing combined to careful parental phenotyping may reveal a more complex clinical picture in newly recognized syndromes.

Ultrasonography of the brain, abdomen, and heart in neonates born to liver or renal transplant recipient mothers.

BACKGROUND Pregnancies in graft recipients are associated with increased risk of a number of pathologies. The aim of the study was to analyze results of brain and abdominal ultrasonography and echocardiography (ECHO) in neonates born to liver (LTx) or renal recipients (RTx). MATERIAL/METHODS The study group consisted of 82 neonates born to transplanted women (46 neonates of liver recipients and 36 neonates of renal recipients), enrolled in a retrospective study. The control group consisted of 74 neonates from the general population. Sonographic examination of the brain was performed to check for the presence of intra-/periventricular hemorrhage (IVH/PVH) according to Papile, and periventricular leukomalacia (PVL).The results of abdominal ultrasonography and 2-dimensional echocardiography (ECHO) were compared between the groups. The immunosuppressive therapy used during pregnancy was also analyzed. RESULTS No significant differences were observed between the frequency of IVH in LTx and RTx groups and LTx, RTx, and control groups. Abdominal ultrasonography revealed 1 case of suprarenal hemorrhage, 1 case of cystic kidney, and 3 cases of pyelocalyceal system dilatation in the study group. There were no abnormalities in the echocardiography in 97.8% of children born to mothers after LTx and in 94.4% after RTx. There were significant differences in the immunosuppressive therapy between the pregnant women after LTx and RTx. CONCLUSIONS The risk was not increased in intra-/periventricular hemorrhage and congenital abnormalities of the gastrointestinal tract and heart in neonates of mothers after organ transplantation, regardless of the immunotherapy used, and risk was similar to that of the general population.

Importance of plasma endothelin-1 level in the evaluation of heart failure severity in infants with ventricular septal defect

BACKGROUND Haemodynamic disturbances due to ventricular septal defect (VSD) can lead to heart failure (HF) and cause neurohormonal activation. Endothelin-1 (ET-1) clearance takes place mainly in the pulmonary circulation. We hypothesized that increased pulmonary blood flow in children with VSD could influence ET-1 level and reflect haemodynamic disturbances in these patients. AIM To analyse usefulness of plasma ET-1 level in the evaluation of HF severity in infants with VSD without pulmonary hypertension. METHODS The study group included 34 children (aged 38-338 days, mean 130 ± 81 days) with VSD. Evaluation included history, physical examination, ET-1 level measurement, standard 12-lead electrocardiogram, chest X-ray, and transthoracic echocardiography in all children. The control group consisted of 31 healthy children. RESULTS Mean plasma ET-1 level was significantly (p < 0.01) higher in the study group compared to the control group. We found no significant difference (p > 0.05) in mean plasma ET-1 level between children with or without HF. No significant correlation was found between plasma ET-1 level and the severity of HF. CONCLUSIONS Infants with VSD show higher ET-1 level compared to healthy children. Plasma ET-1 level does not reflect the severity of HF in infants with VSD.

Right ventricular function assessment using tissue Doppler imaging and speckle tracking echocardiography

Modern echocardiographic techniques, i.e. tissue Doppler imaging and speckle tracking echocardiography, allow for an assessment of global and regional right ventricular function. The right ventricular myocardial performance index and tricuspid annulus motion are used in the assessment of global right ventricular function, whereas duration of the cardiac cycle phases and myocardial velocities are used in the assessment of regional function. Strain and strain rate allow for an evaluation of both regional and global myocardial function. Literature reports provide data on the usefulness of these methods in patients with pressure and volume overload as well as with direct myocardial damage involving the right ventricle. In pulmonary hypertension, S’ wave assessment may be used for therapeutic efficacy evaluation. Longitudinal strain reduction indicates an increased risk of vascular events, while an increased value of myocardial performance index is a predictor for a survival in pulmonary hypertension. A decreased S’ wave velocity is associated with limited pulmonary vascular flow in patients with pulmonary embolism. In patients after atrial baffle repair for transposition of the great arteries, decreased longitudinal strain was an independent predictor for heart failure. A statistically significant decrease in both the S’ wave as well as acceleration during isovolumic contraction were observed in arrhythmogenic right ventricular cardiomyopathy. S’ wave and global right ventricular longitudinal strain values were lower in patients in the acute phase of myocardial infarction involving the right ventricle compared to the corresponding parameters in healthy individuals. In the case of tetralogy of Fallot correction, the evaluation of S’ wave velocity may prove useful in identifying patients with reduced cardiac systolic reserve; a good correlation was also found between the global right ventricular longitudinal strain and right ventricular ejection fraction in MRI.

Bland-White-Garland syndrome – a rare and serious cause of failure to thrive

Patient: Male, 0 Final Diagnosis: Bland-White-Garland syndrome Symptoms: Cardiomegaly, feeding problems Medication: — Clinical Procedure: Reimplantation of the left coronary artery to the aorta Specialty: Pediatrics and Neonatology Objective: Rare disease Background: Bland-White-Garland syndrome (BWGS) is a very rare disease characterized by anomalous origin of the left coronary artery from the pulmonary trunk (ALCAPA). WBGS affects 1 in every 300 000 live births. Children typically present with dyspnea, pallor, and failure to thrive. Without surgical repair, most of these children die during the first months of life. Case Report: This case report describes 3-month-old boy admitted to the hospital because of feeding problems. The boy was born at term, with birth weight 3200 g, and was 10 points in Apgar score. He was breast-fed from birth. From the seventh week of age, his mother observed his increasing difficulties with feeding. Physical examination revealed pale skin, diminished heart sounds, tachycardia, cardiomegaly, and hepatomegaly. Results of urine and blood tests and ultrasonography of the central nervous system and abdomen were normal. The chest radiography showed cardiomegaly and electrocardiogram revealed anterolateral myocardial infarction. On echocardiography, an anomalous left coronary artery arising from the pulmonary artery was found. The life-saving treatment of choice was immediate surgical reimplantation of the left coronary artery to the aorta. Conclusions: Children with congenital heart disease are often prone to malnutrition, but in rare cases failure to thrive and breast-feeding problems can be the first symptoms of life-threatening diseases like myocardial infarction secondary to Bland-White-Garland syndrome (BWGS).

Assessment of right atrial and right ventricular size in children after percutaneous closure of secundum atrial septal defect with Amplatzer septal occluder.

Introduction The aim of this study was to evaluate the right atrial (RA) and right ventricular (RV) size, and the speed of their normalization, in children after percutaneous closure of secundum atrial septal defect with the Amplatzer septal occluder. Material and methods The study group consisted of 42 children, aged 4.5 to 18.5 years. The following measurements (indexed to body surface area) were performed using 2D echocardiography: longitudinal, transverse axis and area of RA, RV inflow dimensions at one-third, and halfway between the tricuspid annulus and the apex (in the apical 4-chamber view), short axis and M-mode RV diastolic dimensions. All measurements were obtained 24 h and 1, 3 and 12 months after the procedure, then annually over 4 years of follow-up, and compared with the values obtained from the control groups. Results A significant decrease in all RA and RV values was observed after 24 h. Right ventricular transverse dimension normalized after 1 month, the RA longitudinal axis and area and the RV inflow dimensions after 3 months, and the RA transverse axis and M-mode RV diastolic dimension after 2 years, but the ratio of transverse to longitudinal RA axis remained significantly higher. Conclusions Right atrial and right ventricular measurements decrease rapidly during the first 24 h, and most of them normalize within a 3-month period. M-mode RV diastolic dimension does not capture the real RV changes. Amplatzer septal occluder closure of ASD influences the RA geometry, which is reflected by the higher transverse to longitudinal RA axis ratio.

Postsystolic Shortening Is Associated with Altered Right Ventricular Function in Children after Tetralogy of Fallot Surgical Repair

The aim of the study was to determine whether segmental interactions, as expressed by postsystolic shortening (PSS), affects RV mechanics and are connected with impaired systolic and diastolic function in rTOF children. Patients and Methods: 55 rTOF adolescent (study group), and 34 healthy volunteers (control group) were examined using classical Doppler flow (Doppler), Tissue Doppler Imaging (TDI) and Speckle Tracking Echocardiography (STE). PSS was found to occur when time to peak (TTP) was longer than pulmonary valve closure time (PVCT). TTP and strain were derived from RV lateral segments—basal (BL), medial (ML) and apical (AL) in STE. PVCT was measured from the beginning of QRS complex in the ECG to the termination of Doppler flow at the pulmonary valve. TDI was obtained at the lateral tricuspid annulus site and the systolic (S′), early (E′) and late diastolic (A’) peak velocities were measured along with isovolumic contraction (IVCT), and relaxation (IVRT) time. PW was used to measure early tricuspid inflow velocity (E) for calculating the E/E’ ratio. The TDI data in patients with PSS presence (TTP>PVCT) and those in whom it did not occur (TTP≤PVCT) were compared. Results: PSS in BL, ML and AL were observed respectively in: 27(51,9%), 9 (18%), and 8 (16,7%) patients. Mean values of TTP in BL, ML, and AL were respectively: 420.6±55.5ms, 389.8±50.0ms and 366.7±59.0ms. PVCT mean value was 396.6±33.5ms. In the study group, the mean E’ in TTP>PVCT was significantly lower (4.8±1.8 cm/s) compared to mean E’ in TTP≤PVCT (8.4±2.6 cm/s), p<0.01. The average E/E’ was significantly higher in TTP>PCVT than in TTP≤PVCT, respectively 21.6±7.3 vs 12.2±5.1, p<0.05. IVRT was significantly prolonged in TTP>PVCT compared to IVRT in TTP≤PVCT, respectively 95.9±38.7 vs 77.0±35.1, p<0.05. Furthermore, in TTP>PVCT, significantly higher strain in BL (-28.8±8.7%) was observed when compared to that parameter in TTP≤PVCT (-35.3±13.1%), p <0.05. Conclusions: Tissue Doppler Echocardiography and Speckle Tracking Echocardiography are useful techniques for detecting regional systolic and diastolic dysfunction in children after Tetralogy of Fallot surgical repair. Postsystolic shortening in the basal lateral segment is commonly seen in children after the Tetralogy of Fallot surgical repair, and is associated with altered right ventricular systolic and diastolic function.

Study design and rationale for biomedical shirt-based electrocardiography monitoring in relevant clinical situations: ECG-shirt study

BACKGROUND Today, the main challenge for researchers is to develop new technologies which may help to improve the diagnoses of cardiovascular disease (CVD), thereby reducing healthcare costs and improving the quality of life for patients. This study aims to show the utility of biomedical shirt-based electrocardiography (ECG) monitoring of patients with CVD in different clinical situations using the Nuubo® ECG (nECG) system. METHODS An investigator-initiated, multicenter, prospective observational study was carried out in a cardiology (adult and pediatric) and cardiac rehabilitation wards. ECG monitoring was used with the biomedical shirt in the following four independent groups of patients: 1) 30 patients after pulmonary vein isolation (PVI), 2) 30 cardiac resynchronization therapy (CRT) recipients, 3) 120 patients during cardiac rehabilitation after myocardial infarction, and 4) 40 pediatric patients with supraventricular tachycardia (SVT) before electrophysiology study. Approval for all study groups was obtained from the institutional review board. The biomedical shirt captures the electrocardiographic signal via textile electrodes integrated into a garment. The software allows the visualization and analysis of data such as ECG, heart rate, arrhythmia detecting algorithm and relative position of the body is captured by an electronic device. DISCUSSION The major advantages of the nECG system are continuous ECG monitoring during daily activities, high quality of ECG recordings, as well as assurance of a proper adherence due to adequate comfort while wearing the shirt. There are only a few studies that have examined wearable systems, especially in pediatric populations. TRIAL REGISTRATION This study is registered in ClinicalTrials.gov: Identifier NCT03068169. (Cardiol J 2018; 25, 1: 52-59).