AIMS: Fragmented QRS complex with visible notching on standard 12-lead electrocardiogram (ECG) is understood to represent depolarization abnormalities and to signify risk of cardiac events. Depolarization abnormalities with similar prognostic implications likely exist beyond visual recognition but no technology is presently suitable for quantification of such invisible ECG abnormalities. We present such a technology. METHODS AND RESULTS: A signal processing method projects all ECG leads of the QRS complex into optimized three perpendicular dimensions, reconstructs the ECG back from this three-dimensional projection, and quantifies the difference (QRS 'micro'-fragmentation, QRS-μf) between the original and reconstructed signals. QRS 'micro'-fragmentation was assessed in three different populations: cardiac patients with automatic implantable cardioverter-defibrillators, cardiac patients with severe abnormalities, and general public. The predictive value of QRS-μf for mortality was investigated both univariably and in multivariable comparisons with other risk factors including visible QRS 'macro'-fragmentation, QRS-Mf. The analysis was made in a total of 7779 subjects of whom 504 have not survived the first 5 years of follow-up. In all three populations, QRS-μf was strongly predictive of survival (P < 0.001 univariably, and P < 0.001 to P = 0.024 in multivariable regression analyses). A similar strong association with outcome was found when dichotomizing QRS-μf prospectively at 3.5%. When QRS-μf was used in multivariable analyses, QRS-Mf and QRS duration lost their predictive value. CONCLUSION: In three populations with different clinical characteristics, QRS-μf was a powerful mortality risk factor independent of several previously established risk indices. Electrophysiologic abnormalities that contribute to increased QRS-μf values are likely responsible for the predictive power of visible QRS-Mf.

• Klíčová slova
• Electrocardiogram, Fragmentation, Mortality prediction, QRS complex,
• MeSH
• elektrokardiografie * metody   MeSH
• lidé MeSH
• prediktivní hodnota testů MeSH
• prognóza MeSH
• rizikové faktory MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

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.

• Klíčová slova
• ECG measurements, healthy volunteers, heart rate, heart rate hysteresis, long-term ECG, polynomial regression, sex differences, spatial QRS-T angle,
• Publikační typ
• časopisecké články MeSH

Increases in beat-to-beat variability of electrocardiographic QT interval duration have repeatedly been associated with increased risk of cardiovascular events and complications. The measurements of QT variability are frequently normalized for the underlying RR interval variability. Such normalization supports the concept of the so-called immediate RR effect which relates each QT interval to the preceding RR interval. The validity of this concept was investigated in the present study together with the analysis of the influence of electrocardiographic morphological stability on QT variability measurements. The analyses involved QT and RR measurements in 6,114,562 individual beats of 642,708 separate 10-s ECG samples recorded in 523 healthy volunteers (259 females). Only beats with high morphology correlation (r > 0.99) with representative waveforms of the 10-s ECG samples were analyzed, assuring that only good quality recordings were included. In addition to these high correlations, SDs of the ECG signal difference between representative waveforms and individual beats expressed morphological instability and ECG noise. In the intra-subject analyses of both individual beats and of 10-s averages, QT interval variability was substantially more strongly related to the ECG noise than to the underlying RR variability. In approximately one-third of the analyzed ECG beats, the prolongation or shortening of the preceding RR interval was followed by the opposite change of the QT interval. In linear regression analyses, underlying RR variability within each 10-s ECG sample explained only 5.7 and 11.1% of QT interval variability in females and males, respectively. On the contrary, the underlying ECG noise contents of the 10-s samples explained 56.5 and 60.1% of the QT interval variability in females and males, respectively. The study concludes that the concept of stable and uniform immediate RR interval effect on the duration of subsequent QT interval duration is highly questionable. Even if only stable beat-to-beat measurements of QT interval are used, the QT interval variability is still substantially influenced by morphological variability and noise pollution of the source ECG recordings. Even when good quality recordings are used, noise contents of the electrocardiograms should be objectively examined in future studies of QT interval variability.

• Klíčová slova
• ECG noise contents, QT variability, RR variability, healthy volunteers, immediate RR interval effect, long-term ECG, regression-based correction, short-term ECG measurements,
• 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

The normal physiologic range of QRS complex duration spans between 80 and 125 ms with known differences between females and males which cannot be explained by the anatomical variations of heart sizes. To investigate the reasons for the sex differences as well as for the wide range of normal values, a technology is proposed based on the singular value decomposition and on the separation of different orthogonal components of the QRS complex. This allows classification of the proportions of different components representing the 3-dimensional representation of the electrocardiographic signal as well as classification of components that go beyond the 3-dimensional representation and that correspond to the degree of intricate convolutions of the depolarisation sequence. The technology was applied to 382,019 individual 10-s ECG samples recorded in 639 healthy subjects (311 females and 328 males) aged 33.8 ± 9.4 years. The analyses showed that QRS duration was mainly influenced by the proportions of the first two orthogonal components of the QRS complex. The first component demonstrated statistically significantly larger proportion of the total QRS power (expressed by the absolute area of the complex in all independent ECG leads) in females than in males (64.2 ± 11.6% vs 59.7 ± 11.9%, p < 0.00001-measured at resting heart rate of 60 beats per minute) while the second component demonstrated larger proportion of the QRS power in males compared to females (33.1 ± 11.9% vs 29.6 ± 11.4%, p < 0.001). The analysis also showed that the components attributable to localised depolarisation sequence abnormalities were significantly larger in males compared to females (2.85 ± 1.08% vs 2.42 ± 0.87%, p < 0.00001). In addition to the demonstration of the technology, the study concludes that the detailed convolution of the depolarisation waveform is individual, and that smoother and less intricate depolarisation propagation is the mechanism likely responsible for shorter QRS duration in females.

• MeSH
• algoritmy MeSH
• analýza dat MeSH
• biologická variabilita populace MeSH
• dospělí MeSH
• elektrofyziologické jevy * účinky léků   MeSH
• elektrokardiografie * metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• sexuální faktory MeSH
• srdce účinky léků   fyziologie   MeSH
• výpočetní biologie metody   MeSH
• zdraví dobrovolníci pro lékařské studie 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.

• Klíčová slova
• QT/RR adaptation, QT/RR hysteresis, age influence, best-fit models, healthy subjects, non-linear regression modelling, sex differences,
• 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.

• Klíčová slova
• QT variability, QT variability index, RR variability, sequential analysis of regression variance, underlying heart rate,
• 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.

• Klíčová slova
• ECG lead comparison, T wave peak, T wave spatial loop, heart rate dependency, sex differences,
• 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.

• Klíčová slova
• Bazett correction, Framingham correction, Fridericia correction, Long QT screening, QTc prolongation in children,
• 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

Sex differences are known in several facets of cardiac electrophysiology, mostly concerning myocardial repolarisation. In this study, heart rate and heart rate variability (HRV) responses to postural provocations were compared in 175 and 176 healthy females and males, respectively (aged 33.1 ± 9.1 years). Two different postural provocative tests with position changes supine→sitting→standing→supine and supine→standing→sitting→supine (15-min standing, 10-min other positions) were performed up to 4 times in each subject. Heart rate and heart rate variability spectral indices were measured in 5-min windows before positional changes. At supine position, females had averaged heart rate approximately 5 beats per minute (bpm) faster than males and this sex difference was practically constant during the postural changes. In both sexes, change supine→sitting and supine→standing increased heart rate by approximately 10 and 30 bpm, respectively, with no statistical differences between the sex groups. At supine baseline, females had normalised high frequency components (nHF) of HRV approximately 7% larger compared to males (p < 0.001). While the same difference in nHF was found at sitting, the change to standing position lead to significantly larger nHF reduction in females compared to males (mean changes 22.5 vs 17.2%, p < 0.001). This shows that despite similar heart rate increase, females respond to standing by more substantial shifts in cardiac sympatho-vagal modulations. This makes it plausible to speculate that the differences in autonomic reactions to stress contribute to the known sex-differences in psychosocial responses to stressful situations and to the known difference in susceptibility to ventricular fibrillation between females and males.

• Klíčová slova
• Autonomic modulations, Autonomic responsiveness, Heart rate, Heart rate variability, Postural changes, Responses to stress, Sex differences,
• MeSH
• autonomní nervový systém fyziologie   MeSH
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• postura těla fyziologie   MeSH
• referenční hodnoty MeSH
• sexuální faktory MeSH
• srdeční frekvence fyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH