A MYH7 variant in a five-generation-family with hypertrophic cardiomyopathy.

Background: Hypertrophic cardiomyopathy (HCM) is a genetic condition with a prevalence of 1:500-1:3 000. Variants in genes encoding sarcomeric proteins are mainly responsible for the disease. MYH7 gene encoding a myosin heavy chain beta, together with MYPBC3 gene are the two most commonly affected genes. The clinical presentation of this disease varies widely between individuals. This study aims to report a variant of MYH7 responsible for HCM in a five-generation family with a history of cardiac problems. Methods: The diagnosis was established according to the European Society of Cardiology HCM criteria based on two-dimensional Doppler echocardiography or cardiovascular magnetic resonance. Genetic analysis was performed using next-generation-sequencing and Sanger method. Results: The medical history of the presented family began with a prenatal diagnosis of HCM in the first child of a family with previously healthy parents. Five generations of the family had a long history of sudden cardiac death and cardiac problems. A NM_000257.4:c.2342T>A (p.Leu781Gln) variant was detected in the MYH7 gene. It was heterozygous in the proband and in all affected individuals in a large family. The variant was present in 10 affected members of the family, and was absent in 7 members. The clinical course of the disease was severe in several members of the family: three family members died of sudden cardiac death, one patient required heart transplantation, three underwent septal myectomy, and three required implantable cardioverter defibrillator (ICD) implantation. Conclusion: Herein, we report a MYH7 variant responsible for HCM. Familial HCM is inherited primarily in autosomal dominant mode, which is in accordance with our study. However, the presented family showed a broad clinical spectrum of HCM. Out of 10 family members with positive genetic testing 8 had severe presentation of the disease and 2 had a mild phenotype. This suggests that the severity of the disease may depend on other factors, most likely genetic.

Diastolic function evaluation in children with ventricular arrhythmia.

Premature ventricular contractions (PVC) are frequently seen in children. We evaluated left ventricular diastolic function in PVC children with normal left ventricular systolic function to detect whether diastolic function disturbances affect physical performance. The study group consisted of 36 PVC children, and the control group comprised 33 healthy volunteers. Echocardiographic diastolic function parameters such as left atrial volume index (LAVI), left atrial strains (AC-R, AC-CT, AC-CD), E wave, E deceleration time (Edt), E/E' ratio, and isovolumic relaxation time (IVRT) were measured. In the cardiopulmonary exercise test (CPET), oxygen uptake (VO2 max) was registered. Evaluation of diastolic function parameters revealed statically significant differences between the patients and controls regarding Edt (176.58 ± 54.8 ms vs. 136.94 ± 27.8 ms, p < 0.01), E/E' (12.6 ± 3.0 vs. 6.7 ± 1.0, p < 0.01), and IVRT (96.6 ± 19.09 ms. vs. 72.86 ± 13.67 ms, p < 0.01). Left atrial function was impaired in the study group compared to controls: LAVI (25.3 ± 8.2 ml/m2 vs. 19.2 ± 7.5 ml/m2, p < 0.01), AC-CT (34.8 ± 8.6% vs. 44.8 ± 11.8%, p < 0.01), and AC-R-(6.0 ± 4.9% vs. -11.5 ± 3.5%, p < 0.01), respectively. VO2 max in the study group reached 33.1 ± 6.2 ml/min/kg. A statistically significant, moderate, negative correlation between VO2 max and E/E' (r = -0.33, p = 0.02) was found. Left ventricular diastolic function is impaired and deteriorates with the arrhythmia burden increase in PVC children. Ventricular arrhythmia in young individuals may be related to the filling pressure elevation and drive to exercise capacity deterioration.

Cardiopulmonary capacity is reduced in children with ventricular arrhythmia.

BACKGROUND: Premature ventricular contractions (PVCs) are frequently seen in children and are considered benign. A substantial group of adolescents with PVCs complain about a broad range of clinical symptoms, including low exertion tolerance. OBJECTIVE: The purpose of this study was to evaluate prospectively whether ventricular arrhythmia affects physical performance in adolescents with normal left ventricular function, using a cardiopulmonary exercise test (CPET) and evaluating the electrocardiographic (ECG) characteristics of patients with PVCs with regard to exercise capacity. METHODS: The study group consisted of 49 children with PVCs and normal left ventricular function. The control group consisted of 36 healthy volunteers. Standard ECG, 24-hour Holter ECG, and CPET were performed. PVCs were analyzed for QRS duration, bundle branch block pattern, QRS axis, and coupling interval (CInt). For CPET, heart rate (HR), oxygen uptake (VO2max), predicted VO2max, and VO2max expressed as a percentage of the predicted value (%VO2) were measured. RESULTS: In 37 patients (76%), arrhythmia subsided during exercise. Patients achieved lower VO2max (32.9 ± 6.3 mL/min/kg) than controls (40.4 ± 6.7 mL/min/kg; P <.01). %VO2 was 71.0 ± 13.7 in patients and 79.3 ± 12.2 in controls (P <.01). Exercise HR at which PVCs subsided correlated with VO2max (r = 0.3; P = .07). Patients with persisting arrhythmia performed worse than those in whom arrhythmia subsided during exercise (VO2max, P <.01; %VO2,P <.01). No correlation between QRS and CInt parameters and VO2max was observed. CONCLUSION: Patients with PVCs have lower aerobic capacity than their healthy peers. Further worsening of exercise capacity is present when PVCs are preserved during effort.

Electrocardiograms in school-aged healthy Polish children - an observational study.

BACKGROUND: Electrocardiographic (ECG) examination has long been used to assess cardiovascular function in clinical practice. Age-related ECG changes are observed as the cardiovascular system matures from the neonatal period to adolescence. AIM: This study aimed to evaluate effects of sex and age on ECG parameters in healthy schoolchildren. METHODS: The study included 336 healthy participants aged 5-12 years from the Masovian voivodeship. Children were divided into age groups of 5-8 and 9-12 years. Values for heart rate (HR), time intervals and amplitudes of P and QRS waves, and QRS axis for pediatric ECGs were estimated. RESULTS: Significant differences between boys and girls aged 5-8 years old were discovered for such parameters as PR interval, R-wave, S-wave, and the R/S ratio. Age-related decline in HR, Q-wave in V5 and V6, R-wave in V1-V4, and increase in QRS duration were noted. Girls presented a higher HR and shorter QRS than boys. HR, QRS axis, P wave amplitude in lead II, and amplitude of R and S in the precordial leads were different in our population than those previously reported. CONCLUSIONS: Pediatric ECG tracings were estimated for the first time for healthy Polish schoolchildren. Sex-related differences in selected ECG parameters in the younger age group were noticed. Several parameters differed from those previously reported in other ethnic populations. These findings are clinically significant and suggest that diagnostic criteria for pediatric ECG should be revised to establish if they are justifiable for the entire population.

Assessment of the physical performance in children with asymptomatic pre-excitation.

AIMS: Pre-excitation syndrome can lead to recurrent supraventricular tachycardias (SVTs) and carries a risk of sudden cardiac death (SCD). However, an underestimated consequence of antegrade conduction through an accessory pathway is fusion of intrinsic and accessory conduction that causes asynchronous activation and myocardial contraction that could be a cause for cardiac dysfunction and dilation. It is not known to what extent pre-excitation affects myocardial and physical performance in those patients. The aim of the study was to assess to what degree ventricular pre-excitation affects physical performance in children, using cardio-pulmonary exercise testing (CPET). METHODS AND RESULTS: The study group consisted of 30 asymptomatic children, aged 8-17 years, with pre-excitation and no history or documentation of SVT compared to 31 healthy controls matched according to sex and age. All patients underwent routine cardiology assessment and then CPET. Echocardiography showed there were no differences in the left ventricular size and function between the study and control group. During the CPET both, patients and controls achieved maximal effort. Patients in the study group showed significantly lower values of VO2max and anaerobic threshold when compared to controls. The most affected subgroup was patients with persistent pre-excitation throughout the exercise. CONCLUSIONS: Physical performance is affected in children with pre-excitation. This effect is stronger in patients with persistent delta wave observed throughout the exercise.

Intracardiac atrial overdrive pacing as an alternative to extracorporeal membrane oxygenation in the treatment of cardiogenic shock due to drug refractory and incessant persistent junctional reciprocating tachycardia in a 7-month-old infant.

In the case of prolonged, undiagnosed persistent junctional reciprocating tachycardia in infants, compensatory mechanisms are exhausted leading to heart failure. However, when cardioverted to sinus rhythm patients often deteriorate due to cardiac output dependency on the higher rates. Extracorporeal membrane oxygenation (ECMO) is often used to stabilize their hemodynamic status. A 7-month-old female infant was admitted in cardiogenic shock due to drug refractory supraventricular tachycardia (SVT). Pharmacological cardioversion to sinus rhythm with heart rate (HR) of 90 bpm was achieved but resulted in hemodynamic deterioration and early recurrence of arrhythmia. Right atrial overdrive pacing (ODP) wire was introduced through femoral vein and allowed to override the tachycardia with 2:1 A:V block and HR of 160 bpm. ODP was continued for 24 h allowing to wean off the inotropic support. We postulate that ODP can be a safe and less invasive alternative to ECMO in stabilizing infants with cardiogenic shock due to intractable SVTs.

Evaluation of Galectin-3 Plasma Concentration in Adolescents with Ventricular Arrhythmia.

Galectin-3 (G3) is a biomarker known as an inflammatory state exponent. The aim of this paper was to analyze the G3 in adolescents with ventricular arrhythmia (VES) in order to evaluate its impact on myocardial tissue preservation. The study group (SG) consisted of 25 VES adolescents. The control group (CG) was 21 healthy children. G3 was assessed in the SG and CG. In the SG electrocardiography, Holter monitoring, echocardiography and CMR were performed. The G3 in SG was 13.45 ± 11.4 ng/mL and in CG 7.2 ± 2.0 ng/mL, p < 0.001. Moderate positive correlation between the G3 and z-score of the left ventricular diameter (r = 0.47, p = 0.041) and moderate negative correlation between the G3 and the left ventricular ejection fraction in cardiac magnetic resonance (CMR EF) (-0.49, p = 0.032) were found. According to the multiple linear regression analysis, CMR EF and VES were independent predictors for G3 elevation. Conclusion: Galectin-3 plasma concentration is elevated and correlates with the chosen left ventricular dysfunction parameters in adolescents suffering from ventricular arrhythmia. Further investigation is necessary to establish if elevated G3 is a useful biomarker for screening young individuals with ventricular arrhythmia who are at risk of structural cardiovascular pathology.

Recommendations from the Association for European Paediatric and Congenital Cardiology for training in diagnostic and interventional electrophysiology.

The field of electrophysiology (EP) in paediatric cardiology patients and adults with congenital heart disease is complex and rapidly growing. The current recommendations for diagnostic and invasive electrophysiology of the working group for Cardiac Dysrhythmias and Electrophysiology of the Association for European Paediatric and Congenital Cardiology acknowledges the diveristy of European countries and centers. These training recommendations can be fulfilled in a manageable period of time, without compromising the quality of training required to become an expert in the field of paediatric and congenital EP and are for trainees undergoing or having completed accredited paediatric cardiologist fellowship. Three levels of expertise, the training for General paediatric cardiology EP, for non-invasive EP and invasive EP have been defined. This Association for European EP curriculum describes the theoretical and practicsal knowledge in clinical EP; catheter ablation, cardiac implantable electronic devices, inherited arrhythmias and arrhythmias in adults with congenital heart defects for the 3 levels of expertise.

Management of Young Athletes with Asymptomatic Preexcitation-A Review of the Literature.

INTRODUCTION: The management of young athletes with asymptomatic preexcitation remains a challenge, regardless of the progress we have made in understanding the basis of condition and developing catheter ablation procedures. The risk of sudden death, however small, yet definite, being the first symptom is determining our approach. The aim of the study was to establish the current state of knowledge regarding the management of young athletes diagnosed with asymptomatic preexcitation, by conducting a literature review. MATERIAL AND METHODS: A comprehensive literature review was completed in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search was limited to English language publications using the following search terms: "asymptomatic" or "incidental" and "pre-excitation" or "Wolff-Parkinson-White" or "delta wave" and "athlete" or "sport". The search was supplemented by hand review of the bibliographies of previous relevant systematic reviews. RESULTS: The search resulted in 85 of abstracts, and the manual search of the bibliographies resulted in 24 additional papers. After careful analysis 10 publications were included in the review. In all but one of the presented papers, the authors used non-invasive methods and then either trans-esophageal or invasive EPS as a way to risk stratify asymptomatic patients. Evidence of rapid conduction through the accessory pathway was considered high risk and prompted sport disqualification. In the analysed reports there were combined: 142 episodes of the life-threatening events (LTE)/sudden death (SCD), of which 56 were reported to occur at rest, 61 during activity and no data were available for 25. CONCLUSIONS: athletic activity may impose an increased risk of life-threatening arrhythmias in patients with asymptomatic preexcitation; hence, a separate approach could be considered, especially in patients willing to engage in high-intensity, endurance and competitive sports.

Chromosome instabilities in resynthesized Brassica napus revealed by FISH.

Brassica napus is an allopolyploid plant, derived from spontaneous hybridization between Brassica rapa and Brassica oleracea. Intensive breeding has led to a significant reduction in genetic and phenotypic diversity within this species. Newly resynthesized hybrids from progenitor species may restore some diversity in B. napus, but they often are chromosomally and phenotypically unstable. Using fluorescence in situ hybridization, we tested chromosome constitutions in a range of new allopolyploids resynthesized from various parental species. A majority of these allopolyploids were euploid, with the expected chromosome numbers and constitutions, but deviations were also identified. We detected a low level of intergenomic rearrangements in analyzed hybrids and a high level of changes in rDNA loci. Our study revealed a significant effect of maternal cross combination on loss of 35S rDNA loci, especially when B. rapa was the maternal parent. The studied lines were characterized by diversified of pollen viability. In the analyzed hybrids, the erucic acid level in the seed oil ranged from 0 to 43.4% and total glucosinolate content in seeds ranged from 24.3 to 119.2 µmol g-1. Our study shows that cytogenetic analysis of B. napus resynthesized hybrids would be useful in breeding for the selection of lines with important agricultural characters and genetically stable stock seed production.

Cytogenetic and molecular genotyping in the allotetraploid Festuca pratensis × Lolium perenne hybrids.

BACKGROUND: Species of the Festuca and Lolium genera, as well as intergeneric Festuca × Lolium (Festulolium) hybrids, are valuable fodder and turf grasses for agricultural and amenity purposes worldwide. Festulolium hybrids can merge in their genomes agronomically important characteristics. However, in polyploid plants, especially in allopolyploids, the hybridization of divergent genomes could contribute to various abnormalities, such as variability in chromosome number, structural rearrangements, and/or disorders in inheritance patterns. Here we studied these issues in allotetraploid Festuca pratensis × Lolium perenne hybrids. RESULTS: Cytogenetic procedures, including fluorescent in situ hybridization, genomic in situ hybridization, and molecular markers - inter-simple sequence repeats (ISSR) were exploited. This cytogenetic approach indicated the dynamics in the number and distribution of ribosomal RNA genes and structural rearrangements for both parental genomes (Festuca and Lolium) in hybrid karyotypes. The separate analysis of F. pratensis and L. perenne chromosomes in hybrid plants (F2-F3 generations of F. pratensis × L. perenne) revealed the asymmetrical level of rearrangements. Recognized structural changes were mainly located in the distal part of chromosome arms, and in chromosomes bearing ribosomal DNA, they were more frequently mapped in arms without this sequence. Based on the ISSR markers distribution, we found that the tetrasomic type of inheritance was characteristic for the majority of ISSR loci, but the disomic type was also observed. Nonetheless, no preference in the transmission of either Festuca or Lolium alleles to the following generations of allotetraploid F. pratensis × L. perenne hybrid was observed. CONCLUSION: Our study reports cytogenetic and molecular genotyping of the F. pratensis × L. perenne hybrid and its following F2-F3 progenies. The analysis of 137 allotetraploid F. pratensis × L. perenne hybrids revealed the higher level of recombination in chromosomes derived from F. pratensis genome. The results of ISSR markers indicated a mixed model of inheritance, which may be characteristic for these hybrids.

Normative Values for Heart Rate Variability Parameters in School-Aged Children: Simple Approach Considering Differences in Average Heart Rate.

Background: Heart rate variability (HRV) analysis is a clinical tool frequently used to characterize cardiac autonomic status. The aim of this study was to establish normative values for short-term HRV parameters by considering their main determinants in school-aged children. Methods: Five-minute electrocardiograms were taken from 312 non-athlete children (153 boys) at age of 6 to 13 years for computation of conventional time- and frequency-domain HRV parameters. Heart rate (HR), respiratory rate, age, body mass index, and sex were considered as their potential determinants. Multiple regression analysis revealed that HR was the principal predictor of all standard HRV indices. To develop their universal normative limits, standard HRV parameters were corrected for prevailing HR. Results: The HRV correction for HR yielded the parameters which became independent on both sex and HR, and only poorly dependent on age (with small effect size). Normal ranges were calculated for both time- and frequency-domain indices (the latter computed with either fast Fourier transform and autoregressive method). To facilitate recalculation of standard HRV parameters into corrected ones, a calculator was created and attached as a Supplementary Material that can be downloaded and used for both research and clinical purposes. Conclusion: This study provides HRV normative values for school-aged children which have been developed independently of their major determinants. The calculator accessible in the Supplementary Material can considerably simplify determination if HRV parameters accommodate within normal limits.

Initial experience of catheter ablation for cardiac arrhythmias in children and adolescents at a newly built ablation centre.

BACKGROUND: Catheter ablation (CA) therapy is the first-choice treatment in adults with heart rhythm disturbances. Arrhythmias in adults are mainly conditioned by coronary artery disease. Aetiology of arrhythmias in children is mostly associated with inherited heart disorders. According to the current guidelines, CA is widely used in children, indicating the need to make it more achievable in the paediatric population. AIM: To assess the efficacy and safety of CA in children with different types of arrhythmias on the initial learning curve at a newly built Ablation Centre in the Independent Paediatric Hospital of the Medical University of Warsaw, Poland. METHODS: The study population comprised 32 children with supraventricular tachycardias, asymptomatic pre-excitation syndrome, or ventricular ectopic beats undergoing CA. The mean age of the study population was 14.1 ± 2.4 years. In all patients, electrophysiological study (EPS) and CA were performed. Analysis with respect to procedure duration, fluoroscopy exposure duration, location of accessory pathways (AP), success rate, recurrences, and complications was performed. RESULTS: The mean procedure duration was 105.4 ± 41.4 min (range 40-175 min). The mean fluoroscopy duration was 8:34 ± 5:01 min (range 1:28-21:01). The mean exposure to ionising radiation was 4.7 ± 3.2 mcG/kg. EPS revealed significantly more frequent presence of AP in the left side (57.1%). The radiofrequency ablation procedure was successful in 26 of 32 (81.3%) children, and cryoablation was successful in two of four patients. In two (6.3%) children minor complications occurred. CONCLUSIONS: Catheter ablation may be effectively performed without major complications in the initial phase of the learning curve if a reasonable approach with a gradual increase of the procedural complexity is taken.

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).

Exploiting repetitive sequences and BAC clones in Festuca pratensis karyotyping.

The Festuca genus is thought to be the most numerous genus of the Poaceae family. One of the most agronomically important forage grasses, Festuca pratensis Huds. is treated as a model plant to study the molecular mechanisms associated with tolerance to winter stresses, including frost. However, the precise mapping of the genes governing stress tolerance in this species is difficult as its karyotype remains unrecognized. Only two F. pratensis chromosomes with 35S and 5S rDNA sequences can be easily identified, but its remaining chromosomes have not been distinguished to date. Here, two libraries derived from F. pratensis nuclear DNA with various contents of repetitive DNA sequences were used as sources of molecular probes for fluorescent in situ hybridisation (FISH), a BAC library and a library representing sequences most frequently present in the F. pratensis genome. Using FISH, six groups of DNA sequences were revealed in chromosomes on the basis of their signal position, including dispersed-like sequences, chromosome painting-like sequences, centromeric-like sequences, knob-like sequences, a group without hybridization signals, and single locus-like sequences. The last group was exploited to develop cytogenetic maps of diploid and tetraploid F. pratensis, which are presented here for the first time and provide a remarkable progress in karyotype characterization.