V současné době nejsou známa rozmezí normálních hodnot QT intervalu pro konkrétní věkové skupiny v dětství a pubertě. V rámci tohoto projektu budou u dětí a adolescentů provedeny kontinuální 12-svodové elektrokardiografické záznamy v průběhu standardizovaných posturálních autonomních provokačních testů. V těchto záznamech bude provedena analýza již dříve ověřeného souboru ukazatelů a charakteristik morfologie a heterogenity repolarizace. Tak budou stanoveny věkově a pohlavně specifické normy pro QT/RR závislost a související korekční matematické vzorce s cílem zpřesnění časné diagnózy abnormalit QT intervalu a dalších souvisejících repolarizačních patologií.; Presently, sex-specific normality limits of QT interval are not known for different age-groups of children and adolescents. In this project continuous, 12-lead electrocardiographic monitoring will be performed in children and adolescents during standardised postural autonomic provocations. A previously verified battery of repolarization morphology indices and of repolarization heterogeneity characteristics will be investigated. The project will establish age- and sex-related normative QT/RR patterns and corresponding heart rate correction formulae to serve more accurate early diagnosis of QT interval abnormalities and of repolarization-related pathologies.

• Klíčová slova
• děti, children, adolescenti, adolescents, repolarizace, pohlavně závislé rozdíly, QT interval, repolarization, sex-related differences, QT interval,

• NLK Publikační typ
• závěrečné zprávy o řešení grantu AZV MZ ČR

Three-dimensional angle between the QRS complex and T wave vectors is a known powerful cardiovascular risk predictor. Nevertheless, several physiological properties of the angle are unknown or poorly understood. These include, among others, intra-subject profiles and stability of the angle relationship to heart rate, characteristics of angle/heart-rate hysteresis, and the changes of these characteristics with different modes of QRS-T angle calculation. These characteristics were investigated in long-term 12-lead Holter recordings of 523 healthy volunteers (259 females). Three different algorithmic methods for the angle computation were based on maximal vector magnitude of QRS and T wave loops, areas under the QRS complex and T wave curvatures in orthogonal leads, and weighted integration of all QRS and T wave vectors moving around the respective 3-dimensional loops. These methods were applied to orthogonal leads derived either by a uniform conversion matrix or by singular value decomposition (SVD) of the original 12-lead ECG, giving 6 possible ways of expressing the angle. Heart rate hysteresis was assessed using the exponential decay models. All these methods were used to measure the angle in 659,313 representative waveforms of individual 10-s ECG samples and in 7,350,733 individual beats contained in the same 10-s samples. With all measurement methods, the measured angles fitted second-degree polynomial regressions to the underlying heart rate. Independent of the measurement method, the angles were found significantly narrower in females (p < 0.00001) with the differences to males between 10o and 20o, suggesting that in future risk-assessment studies, different angle dichotomies are needed for both sexes. The integrative method combined with SVD leads showed the highest intra-subject reproducibility (p < 0.00001). No reproducible delay between heart rate changes and QRS-T angle changes was found. This was interpreted as a suggestion that the measurement of QRS-T angle might offer direct assessment of cardiac autonomic responsiveness at the ventricular level.

• Publikační typ
• časopisecké články MeSH

Monitoring of QTc interval is mandated in different clinical conditions. Nevertheless, intra-subject variability of QTc intervals reduces the clinical utility of QTc monitoring strategies. Since this variability is partly related to QT heart rate correction, 10 different heart rate corrections (Bazett, Fridericia, Dmitrienko, Framingham, Schlamowitz, Hodges, Ashman, Rautaharju, Sarma, and Rabkin) were applied to 452,440 ECG measurements made in 539 healthy volunteers (259 females, mean age 33.3 ± 8.4 years). For each correction formula, the short term (5-min time-points) and long-term (day-time hours) variability of rate corrected QT values (QTc) was investigated together with the comparisons of the QTc values with individually corrected QTcI values obtained by subject-specific modelling of the QT/RR relationship and hysteresis. The results showed that (a) both in terms of short-term and long-term QTc variability, Bazett correction led to QTc values that were more variable than the results of other corrections (p < 0.00001 for all), (b) the QTc variability by Fridericia and Framingham corrections were not systematically different from each other but were lower than the results of other corrections (p-value between 0.033 and < 0.00001), and (c) on average, Bazett QTc values departed from QTcI intervals more than the QTc values of other corrections. The study concludes that (a) previous suggestions that Bazett correction should no longer be used in clinical practice are fully justified, (b) replacing Bazett correction with Fridericia and/or Framingham corrections would improve clinical QTc monitoring, (c) heart rate stability is needed for valid QTc assessment, and (d) development of further QTc corrections for day-to-day use is not warranted.

• MeSH
• algoritmy MeSH
• dospělí MeSH
• elektrokardiografie metody   MeSH
• kardiologie metody   normy   MeSH
• lidé středního věku MeSH
• lidé MeSH
• počítačové zpracování signálu MeSH
• reprodukovatelnost výsledků MeSH
• srdeční frekvence fyziologie   MeSH
• syndrom dlouhého QT diagnóza   patofyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

While it is now well-understood that the extent of QT interval changes due to underlying heart rate differences (i.e., the QT/RR adaptation) needs to be distinguished from the speed with which the QT interval reacts to heart rate changes (i.e., the so-called QT/RR hysteresis), gaps still exist in the physiologic understanding of QT/RR hysteresis processes. This study was designed to address the questions of whether the speed of QT adaptation to heart rate changes is driven by time or by number of cardiac cycles; whether QT interval adaptation speed is the same when heart rate accelerates and decelerates; and whether the characteristics of QT/RR hysteresis are related to age and sex. The study evaluated 897,570 measurements of QT intervals together with their 5-min histories of preceding RR intervals, all recorded in 751 healthy volunteers (336 females) aged 34.3 ± 9.5 years. Three different QT/RR adaptation models were combined with exponential decay models that distinguished time-based and interval-based QT/RR hysteresis. In each subject and for each modelling combination, a best-fit combination of modelling parameters was obtained by seeking minimal regression residuals. The results showed that the response of QT/RR hysteresis appears to be driven by absolute time rather than by the number of cardiac cycles. The speed of QT/RR hysteresis was found decreasing with increasing age whilst the duration of individually rate corrected QTc interval was found increasing with increasing age. Contrary to the longer QTc intervals, QT/RR hysteresis speed was faster in females. QT/RR hysteresis differences between heart rate acceleration and deceleration were not found to be physiologically systematic (i.e., they differed among different healthy subjects), but on average, QT/RR hysteresis speed was found slower after heart rate acceleration than after rate deceleration.

• Publikační typ
• časopisecké články MeSH

QT interval variability, mostly expressed by QT variability index (QTVi), has repeatedly been used in risk diagnostics. Physiologic correlates of QT variability expressions have been little researched especially when measured in short 10-second electrocardiograms (ECGs). This study investigated different QT variability indices, including QTVi and the standard deviation of QT interval durations (SDQT) in 657,287 10-second ECGs recorded in 523 healthy subjects (259 females). The indices were related to the underlying heart rate and to the 10-second standard deviation of RR intervals (SDRR). The analyses showed that both QTVi and SDQT (as well as other QT variability indices) were highly statistically significantly (p < 0.00001) influenced by heart rate and that QTVi showed poor intra-subject reproducibility (coefficient of variance approaching 200%). Furthermore, sequential analysis of regression variance showed that SDQT was more strongly related to the underlying heart rate than to SDRR, and that QTVi was influenced by the underlying heart rate and SDRR more strongly than by SDQT (p < 0.00001 for these comparisons of regression dependency). The study concludes that instead of QTVi, simpler expressions of QT interval variability, such as SDQT, appear preferable for future applications especially if multivariable combination with the underlying heart rate is used.

• Publikační typ
• časopisecké články MeSH

The electrocardiographic (ECG) assessment of the T peak-T end (Tpe) intervals has been used in many clinical studies, but several related physiological aspects have not been reported. Specifically, the sources of the Tpe differences between different ECG leads have not been systematically researched, the relationship of Tpe duration to underlying heart rate has not been firmly established, and little is known about the mutual correspondence of Tpe intervals measured in different ECG leads. This study evaluated 796,620 10-s 12-lead ECGs obtained from long-term Holters recorded in 639 healthy subjects (311 female) aged 33.8 ± 9.4 years. For each ECG, transformation to orthogonal XYZ lead was used to measure Tpe in the orthogonal vector magnitude (used as a reference for lead-to-lead comparisons) and to construct a three-dimensional T wave loop. The loop roundness was expressed by a ratio between its circumference and length. These ratios were significantly related to the standard deviation of Tpe durations in different ECG leads. At the underlying heart rate of 60 beats per minute, Tpe intervals were shorter in female than in male individuals (82.5 ± 5.6 vs 90.0 ± 6.5 ms, p < 0.0001). When studying linear slopes between Tpe intervals measured in different leads and the underlying heart rate, we found only minimal heart rate dependency, which was not systematic across the ECG leads and/or across the population. For any ECG lead, positive Tpe/RR slope was found in some subjects (e.g., 79 and 25% of subjects for V2 and V4 measurements, respectively) and a negative Tpe/RR slope in other subjects (e.g., 40 and 65% for V6 and V5, respectively). The steepest positive and negative Tpe/RR slopes were found for measurements in lead V2 and V4, respectively. In all leads, the Tpe/RR slope values were close to zero, indicating, on average, Tpe changes well below 2 ms for RR interval changes of 100 ms. On average, longest Tpe intervals were measured in lead V2, the shortest in lead III. The study concludes that the Tpe intervals measured in different leads cannot be combined. Irrespective of the measured ECG lead, the Tpe interval is not systematically heart rate dependent, and no heart rate correction should be used in clinical Tpe investigations.

• Publikační typ
• časopisecké články MeSH

BACKGROUND: Bazett formula is frequently used in paediatric screening for the long QT syndrome (LQTS) and proposals exist that using standing rather than supine electrocardiograms (ECG) improves the sensitivity of LQTS diagnosis. Nevertheless, compared to adults, children have higher heart rates (especially during postural provocations) and Bazett correction is also known to lead to artificially prolonged QTc values at increased heart rates. This study assessed the incidence of erroneously increased QTc values in normal children without QT abnormalities. METHODS: Continuous 12-lead ECGs were recorded in 332 healthy children (166 girls) aged 10.7 ± 2.6 years while they performed postural manoeuvring consisting of episodes (in the following order) of supine, sitting, standing, supine, standing, sitting, and supine positions, each lasting 10 min. Detailed analyses of QT/RR profiles confirmed the absence of prolonged individually corrected QTc interval in each child. Heart rate and QT intervals were measured in 10-s ECG segments and in each segment, QTc intervals were obtained using Bazett, Fridericia, and Framingham formulas. In each child, the heart rates and QTc values obtained during supine, sitting and standing positions were averaged. QTc durations by the three formulas were classified to < 440 ms, 440-460 ms, 460-480 ms, and > 480 ms. RESULTS: At supine position, averaged heart rate was 77.5 ± 10.5 beat per minute (bpm) and Bazett, Fridericia and Framingham QTc intervals were 425.3 ± 15.8, 407.8 ± 13.9, and 408.2 ± 13.1 ms, respectively. At sitting and standing, averaged heart rate increased to 90.9 ± 10.1 and 100.9 ± 10.5 bpm, respectively. While Fridericia and Framingham formulas showed only minimal QTc changes, Bazett correction led to QTc increases to 435 ± 15.1 and 444.9 ± 15.9 ms at sitting and standing, respectively. At sitting, Bazett correction identified 51, 4, and 0 children as having the QTc intervals 440-460, 460-480, and > 480 ms, respectively. At sitting, these numbers increased to 118, 11, and 1, while on standing these numbers were 151, 45, and 5, respectively. Irrespective of the postural position, Fridericia and Framingham formulas identified only a small number (< 7) of children with QT interval between 440 and 460 ms and no children with longer QTc. CONCLUSION: During screening for LQTS in children, the use of Bazett formula leads to a high number of false positive cases especially if the heart rates are increased (e.g. by postural manoeuvring). The use of Fridericia formula can be recommended to replace the Bazett correction not only for adult but also for paediatric ECGs.

• MeSH
• dítě MeSH
• dospělí MeSH
• elektrokardiografie MeSH
• lidé MeSH
• mladiství MeSH
• rodina MeSH
• srdeční frekvence MeSH
• syndrom dlouhého QT * diagnóza   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Accurate evaluation of the appearance of QTc sex differences during childhood and adolescence is intricate. Inter-subject differences of individual QT/RR patterns make generic heart rate corrections inaccurate because of fast resting heart rates in children. The study investigated 527 healthy children and adolescents aged 4-19 years (268 females, 50.9%). All underwent continuous ECG 12-lead monitoring while performing postural changes during a 70-min investigative protocol to obtain QT interval measurements at different heart rates. On average, more than 1200 ECG measurements (QT interval and its 5-min history of preceding RR intervals) were made in each subject. Curvilinear QT/RR regression involving intra-individual correction for QT/RR hysteresis were calculated in each subject. The projection of the QT/RR regressions to the heart rate of 60 beats per minute defined individually corrected QTc intervals. In males, gradual QTc shortening by about 15 ms appeared during the ages of 13-19 years synchronously with the incidence of secondary sex signs (p = 0.016). On the contrary, whilst gradual QTc prolongation by about 10 ms appeared in females, it occurred only during ages 16-19 years and was not related to the incidence of secondary sex signs (p = 0.18). The study also showed that in children and adolescents, linear QT/RR models fit the intra-subject data significantly more closely than the log-linear models (p < 0.001). The study speculates that hormonal shifts during puberty might be directly responsible for the QTc shortening in males but that QTc prolongation in females is likely more complex since it was noted to follow the appearance of secondary sex signs only after a considerable delay.

• Publikační typ
• časopisecké články MeSH

BACKGROUND: Classic symptoms of long QT syndrome (LQTS) include prolongation of QT interval on electrocardiograph, syncope, and cardiac arrest due to a distinctive form of polymorphic ventricular tachycardia, known as Torsade de Pointes. We assessed occurrence of LQTS signs in individuals from 30 Czech families with mutations in KCNQ1 and KCNH2 genes. METHODS AND RESULTS: One hundred five individuals from 30 Czech families with LQTS were genotyped for KCNQ1 and KCNH2. The occurrence of typical LQTS signs (pathologic prolongation of QT interval; syncope; cardiac arrest; Torsade de Pointes) was clinically assessed by exercise test with QT interval analysis. Family history of sudden cardiac death was taken. Statistical analysis was performed to determine correlation of clinical results and mutation status. KCNQ1 gene mutations were found in 23 families, and KCNH2 gene mutations in eight families. Only 46 (70%) of the 66 mutation carriers had at least two of the typical LQTS signs. The others were minimally or asymptomatic. From 39 noncarrier individuals, only 1 fulfilled the clinical criteria of LQTS diagnosis, another 4 had an intermediate probability of diagnosis. The exercise test had 92% sensitivity and 93% specificity for LQTS diagnosis. CONCLUSIONS: Incidence of classical signs of LQTS was not high in Czech carriers of KCNQ1 and KCNH2 mutations. Therefore, proper diagnosis relies on detection of symptoms at presentation. The exercise test may be beneficial owing to its high sensitivity and specificity for LQTS diagnosis.

• MeSH
• dospělí MeSH
• draslíkové kanály ether-a-go-go genetika   MeSH
• elektrokardiografie statistika a číselné údaje   MeSH
• genetická predispozice k nemoci epidemiologie   genetika   MeSH
• hodnocení rizik MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• lidé MeSH
• mutace genetika   MeSH
• prevalence MeSH
• reprodukovatelnost výsledků MeSH
• RNA dlouhá nekódující genetika   MeSH
• senzitivita a specificita MeSH
• syndrom dlouhého QT diagnóza   epidemiologie   genetika   MeSH
• zátěžový test statistika a číselné údaje   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

Introduction Mutations of RyR2 gene encoding calcium channel of sarcoplazmatic reticulum are the cause of congenital catecholaminergic polymorphic ventricular tachycardia. The aim of this study was to test the hypothesis that RyR2 variants can increase occurrence of malignant arrhythmias in patients with structural heart diseases. Methods The investigated group consisted of 36 patients with structural heart diseases with ICD implanted who suffered arrhythmic storm. In the control group there were 141 patients with coronary artery disease who were hospitalized at our department owing to an acute coronary event and they were alive at least 3 years after the index event. Thus, they could be considered as a group with a low risk of sudden cardiac death. In all of them mutation analysis of RyR2 gene was performed. Results We detected 16 different sequence changes of RyR2 gene in both groups. None of the found nucleotide polymorphisms led to amino acid changes, were located close to splice sites or had any similarity to known splicing enhancer motifs. The occurrence of these variants was not different in both groups. Conclusions The prevalence of RyR2 gene variants was not different in cases versus controls suggesting a limited role of this gene in the arrhythmogenesis in structural heart disease patients.

• MeSH
• defibrilátory implantabilní využití   MeSH
• dilatační kardiomyopatie genetika   komplikace   MeSH
• fibrilace komor etiologie   genetika   MeSH
• financování organizované MeSH
• flutter komor etiologie   genetika   MeSH
• funkce levé komory srdeční genetika   MeSH
• genetická predispozice k nemoci genetika   MeSH
• genetické techniky využití   MeSH
• ischemická choroba srdeční genetika   komplikace   MeSH
• lidé MeSH
• metaanalýza jako téma MeSH
• mutační analýza DNA MeSH
• náhlá srdeční smrt etiologie   patologie   prevence a kontrola   MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• ryanodinový receptor vápníkového kanálu genetika   MeSH
• srdeční arytmie etiologie   genetika   klasifikace   MeSH
• statistika jako téma MeSH
• Check Tag
• lidé MeSH