Exercise-induced shift in right ventricular contraction pattern: novel marker of athlete's heart?

Data about the functional adaptation of the right ventricle (RV) to intense exercise are limited. Our aim was to characterize the RV mechanical pattern in top-level athletes using three-dimensional echocardiography. A total of 60 elite water polo athletes (19 ± 4 yr, 17 ± 6 h of training/wk, 50% women and 50% men) and 40 healthy sedentary control subjects were enrolled. We measured the RV end-diastolic volume index (RVEDVi) and ejection fraction (RVEF) using dedicated software. Furthermore, we determined RV global longitudinal (RV GLS) and circumferential strain (RV GCS) and the relative contribution of longitudinal ejection fraction (LEF) and radial ejection fraction (REF) to RVEF using the ReVISION method. Athletes also underwent cardiopulmonary exercise testing [O2 consumption (V̇o2)/kg]. Athletes had significantly higher RVEDVi compared with control subjects (athletes vs. control subjects, 88 ± 11 vs. 65 ± 10 ml/m2, P < 0.001); however, they also demonstrated lower RVEF (56 ± 4% vs. 61 ± 5%, P < 0.001). RV GLS was comparable between the two groups (-22 ± 5% vs. -23 ± 5%, P = 0.24), whereas RV GCS was significantly lower in athletes (-21 ± 4% vs. -26 ± 7%, P < 0.001). Athletes had higher LEF and lower REF contribution to RVEF (LEF/RVEF: 0.50 ± 0.07 vs. 0.42 ± 0.07, P < 0.001; REF/RVEF: 0.33 ± 0.08 vs. 0.45 ± 0.08, P < 0.001). Moreover, the pattern of RV functional shift correlated with V̇o2/kg (LEF/RVEF: r = 0.30, P < 0.05; REF/RVEF: r = -0.27, P < 0.05). RV mechanical adaptation to long-term intense exercise implies a functional shift; the relative contribution of longitudinal motion to global function was increased, whereas the radial shortening was significantly decreased, in athletes. Moreover, this functional pattern correlates with aerobic exercise performance, representing a potential new resting marker of an athlete's heart. NEW & NOTEWORTHY Intensive regular physical exercise results in significant changes of right ventricular morphology and function. By separate quantification of the right ventricular longitudinal and radial function, a relative dominance of longitudinal motion and a decrease in radial motion can be observed compared with sedentary controls. Moreover, this contraction pattern correlates with cardiopulmonary fitness. According to these results, this functional shift of the right ventricle may represent a novel marker of an athlete's heart.

Detection of mitochondrial haplogroups in a small avar-slavic population from the eigth-ninth century AD.

OBJECTIVES: In the sixth century AD, Avars came to Central Europe from middle Eurasian steppes and founded a strong Empire called the Avar Khagante (568-799/803 AD) in the Pannonian basin. During the existence of this empire, they undertook many military and pugnacious campaigns. In the seventh century, they conquered the northern territory inhabited by Slavs, who were further recruited in Avar military and were commissioned with obtaining food supplies. During almost 200 years of Avar domination, a significant influence by the Avar culture (especially on the burial rite) and assimilation with indigenous population (occurrence of "East Asian"cranial features) could be noticed in this mixed area, which is supported by achaeological and anthropologcal research. Therefore we expected higher incidence of east Eurasian haplogroups (introduced by Avars) than the frequencies detected in present-day central European populations. MATERIALS AND METHODS: Mitochondrial DNA from 62 human skeletal remains excavated from the Avar-Slavic burial site Cífer-Pác (Slovakia) dated to the eighth and ninth century was analyzed by the sequencing of hypervariable region I and selected parts of coding region. Obtained haplotypes were compared with other present-day and historical populations and genetic distances were calculated using standard statistical method. RESULTS AND DISCUSSION: In total, the detection of mitochondrial haplogroups was possible in 46 individuals. Our results prooved a higher frequency of east Eurasian haplogroups in our analyzed population (6.52%) than in present-day central European populations. However, it is almost three times lower than the frequency of east Eurasian haplogroups detected in other medieval Avar populations. The statistical analysis showed a greater similarity and the lowest genetic distances between the Avar-Slavic burial site Cifer-Pac and medieval European populations than the South Siberian, East and Central Asian populations. CONCLUSION: Our results indicate that the transfer of Avar genetic variation through their mtDNA was rather weak in the analyzed mixed population.

Analysis of Leucine-rich repeat kinase 2 (LRRK2) and Parkinson protein 2 (parkin, PARK2) genes mutations in Slovak Parkinson disease patients.

Parkinson disease (PD) is a chronic neurodegenerative movement disorder characterized by selective loss of nigrostriatal dopaminergic neurons and formation of Lewy bodies. Clinical manifestations include motor impairments involving tremor, bradykinesia, postural instability and rigidity. Using dHPLC method we screened exons 31, 35, 41, 48 of the Leucine-rich repeat kinase 2 (LRRK2) gene and exons 2, 6 and 7 of Parkinson protein 2 (parkin, PARK2) genes in a cohort of 216 consecutive, unrelated Slovak patients with familial or sporadic PD, including early and late onset. By this means we aimed to detect the most common pathogenic mutations within LRRK2 (Arg1441Cys, Arg1441Gly, Arg1628Pro, Tyr1699Cys, Gly2019Ser, Ile2020Thr, Gly2385Arg) and parkin genes responsible for late and early onset forms of disease, respectively. However, none of these mutations was identified in our cohort. Heterozygous point mutation p.Arg275Trp in exon 7 of parkin gene was identified in one patient with age at onset 61 years. Furthermore, we observed the presence of one exonic (LRRK2 ex 48: 7155A>G) and eight intronic polymorphisms (in LRRK2: IVS35+23T>A, IVS47-91insGCCAT, IVS47-91insGCAT, IVS47-41A>G, IVS47-9delT, IVS47-20C>T, IVS47-90A>G, in parkin: IVS2+25T>C), three of which were novel.

Clinical manifestation of CDKL5 deficiency disorder and identified mutations in a cohort of Slovak patients.

CDKL5 deficiency disorder (CDD) is an independent clinical entity associated with early-onset encephalopathy, which is often considered the type of epileptic encephalopathy with CDKL5 mutation also found in children diagnosed with early-onset seizure (Hanefeld) type of Rett syndrome, epileptic spasms, West syndrome, Lennox-Gastaut syndrome, or autism. Since early seizure onset is a prominent feature, in this study, a cohort of 54 unrelated patients consisting of 26 males and 28 females was selected for CDKL5 screening, with seizures presented before 12 months of age being the only clinical criterion. Five patients were found to have pathogenic or likely pathogenic variants in CDKL5 while 1 was found to have a variant of uncertain significance (p.L522V). Although CDKL5 variants are more frequently identified in female patients, we identified three male and three female patients (11.1 %, 6/54) in this study. Missense variant with unknown inheritance (p.L522V), de novo missense variant (p.E60 K), two de novo splicing (IVS15 + 1G > A, IVS16 + 2 T > A), and one de novo nonsense variant p.W125* were identified using Sanger sequencing. Whole exome analysis approach revealed de novo frameshift variant c.1247_1248delAG in a mosaic form in one of the males. Patient clinical features are reviewed and compared to those previously described in related literature. Variable clinical features were presented in CDKL5 positive patients characterised in this study. In addition to more common features, such as early epileptic seizures, severe intellectual disability, and gross motor impairment, inappropriate laughing/screaming spells and hypotonia appeared at the age of 1 year in all patients, regardless of the type of CDKL5 mutation or sex. All three CDKL5 positive males from our cohort were initially diagnosed with West syndrome, which suggests that the CDKL5 gene mutations are a significant cause of West syndrome phenotype, and also indicate the overlapping characteristics of these two clinical entities.

Characterisation of Non-Pathogenic Premutation-Range Myotonic Dystrophy Type 2 Alleles.

Myotonic dystrophy type 2 (DM2) is caused by expansion of a (CCTG)n repeat in the cellular retroviral nucleic acid-binding protein (CNBP) gene. The sequence of the repeat is most commonly interrupted and is stably inherited in the general population. Although expanded alleles, premutation range and, in rare cases, also non-disease associated alleles containing uninterrupted CCTG tracts have been described, the threshold between these categories is poorly characterised. Here, we describe four families with members reporting neuromuscular complaints, in whom we identified altogether nine ambiguous CNBP alleles containing uninterrupted CCTG repeats in the range between 32 and 42 repeats. While these grey-zone alleles are most likely not pathogenic themselves, since other pathogenic mutations were identified and particular family structures did not support their pathogenic role, they were found to be unstable during intergenerational transmission. On the other hand, there was no observable general microsatellite instability in the genome of the carriers of these alleles. Our results further refine the division of CNBP CCTG repeat alleles into two major groups, i.e., interrupted and uninterrupted alleles. Both interrupted and uninterrupted alleles with up to approximately 30 CCTG repeats were shown to be generally stable during intergenerational transmission, while intergenerational as well as somatic instability seems to gradually increase in uninterrupted alleles with tract length growing above this threshold.

Significance of extended sports cardiology screening of elite handball referees.

The significance of cardiology screening of referees is not well established. Cardiovascular risk factors and diseases were examined in asymptomatic Hungarian elite handball referees undergoing extended screening: personal/family history, physical examination, 12-lead ECG, laboratory tests, body-composition analysis, echocardiography, and cardiopulmonary exercise testing. Holter-ECG (n = 8), blood pressure monitorization (n = 10), cardiac magnetic resonance imaging (CMR; n = 27) and computer tomography (CCT; n = 4) were also carried out if needed. We examined 100 referees (age: 29.6±7.9years, male: 64, training: 4.3±2.0 hours/week), cardiovascular risk factors were: positive medical history: 24%, overweight: 10%, obesity: 3%, dyslipidaemia: 41%. Elevated resting blood pressure was measured in 38%. Stress-ECG was positive due to ECG-changes in 16%, due to elevated exercise blood pressure in 8%. Echocardiography and/or CMR identified abnormalities in 19%. A significant number of premature ventricular contractions was found on the Holter-ECG in two cases. The CCT showed myocardial bridge or coronary plaques in one-one case. We recommended lifestyle changes in 58%, new/modified antihypertensive or lipid-lowering therapy in 5%, iron-supplementation in 22%. By our results, a high percentage of elite Hungarian handball referees had cardiovascular risk factors or diseases, which, combined with physical and psychological stress, could increase the possibility of cardiovascular events. Our study draws attention to the importance of cardiac screening in elite handball referees.

Role of duties related to COVID-19 suspected, probable and confirmed fatality cases / [Elhunytakkal kapcsolatos teendok COVID­19-gyanús, valószínusített és megerosített esetekben]

The outbreak caused by SARS-CoV-2 beta-coronavirus, first identified in Wuhan, China, was declared a pandemic by the World Health Organization on 11th March, 2020. In Hungary, the first confirmed COVID-19 case was reported on 4th March, 2020, and on 15th March, the first fatality related to the infection was announced. At the moment of the latter event, there was no central, standardized guideline, which could explain the necessary precautions, and provide an unequivocal description on how to handle the dead body. The procedure of transportation, storage, occurent autopsy or final disposition of the deceased raise a lot of questions, especially on how to carry out these tasks. Legislation related to infectious diseases and decedent management in general do not provide enough information on how to perform duties in a COVID-19 fatality case. The chief medical officer suspended the execution of autopsies, except in cases of unnatural death, since 19th March, however, the transportation and storage of fatalities can still be a problem. The Department of Pathology of the Healthcare Professional College of the Ministry of Human capacities published a procedure on recommended post-mortem duties on 21st March, but the suggested protocols only represent a narrow spectrum of international recommendations. Therefore supplementation may be necessary. Sadly, post-mortem protocols, in spite of their importance, are also underrepresented in the international literature. A further problem, wich makes adoptability difficult, is that available foreign guidelines and algorithms are optimized for different legislation, and organisations, resources not available in our country. In this article, besides providing a summary of literature, we would also like to make practical recommendations which may increase the safety of healthcare providers participating in the treatment or pathological duties with COVID-19 suspected, probable and confirmed cases. Orv Hetil. 2020; 161(17): 713­722.

Relationship between Cardiac Remodeling and Exercise Capacity in Elite Athletes: Incremental Value of Left Atrial Morphology and Function Assessed by Three-Dimensional Echocardiography.

BACKGROUND: Data are scarce regarding left atrial (LA) adaptation to regular physical exercise. The aim of this study was to examine left ventricular (LV) and also LA morphologic and functional remodeling in elite athletes using three-dimensional (3D) echocardiography. METHODS: In this retrospective analysis, the study group consisted of 138 elite athletes (mean age, 20 ± 4 years; 62% men) and 50 sedentary control subjects. Electrocardiographically gated full-volume 3D data sets were obtained for offline analysis using dedicated software for 3D LA and LV measurements. Body surface area-indexed LA maximal volume (LAVmax) and LV end-diastolic volume were determined. LA total emptying fraction, LA passive and LA active emptying fraction, and LV global longitudinal strain were also calculated. Athletes also underwent cardiopulmonary exercise testing to determine peak oxygen uptake. RESULTS: Athletes demonstrated higher 3D LAVmax (32 ± 6 vs 26 ± 8 mL/m2) and indexed LV end-diastolic volume (85 ± 12 vs 62 ± 10 mL/m2) compared with control subjects (P < .001 for both). Functional measures of the left ventricle and left atrium, such as the absolute value of 3D LV global longitudinal strain (19 ± 2% vs 22 ± 2%), LA total emptying fraction (58 ± 6% vs 64 ± 6%), and active emptying fraction (24 ± 10% vs 32 ± 10%) were lower in athletes (P < .001 for all). Male athletes had higher indexed LV end-diastolic volume compared with female athletes (89 ± 13 vs 80 ± 8 mL/m2, P < .001), but LAVmax did not differ between genders (32 ± 6 vs 33 ± 5 mL/m2, P = .18). Besides heart rate, gender, and body surface area, 3D LAVmax, LV global longitudinal strain, and LA passive emptying fraction were independent predictors of peak oxygen uptake. CONCLUSIONS: Regular physical exercise results in marked LA and LV remodeling with considerable gender differences as explored by 3D echocardiography. In contrast with various cardiovascular diseases, more pronounced LA dilation and lower resting functional measures are associated with better exercise performance.