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.
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On standard electrocardiogram (ECG) PQ interval is known to be moderately heart rate dependent, but no physiologic details of this dependency have been established. At the same time, PQ dynamics is a ...clear candidate for non-invasive assessment of atrial abnormalities including the risk of atrial fibrillation. We studied PQ heart rate dependency in 599 healthy subjects (aged 33.5 ± 9.3 years, 288 females) in whom drug-free day-time 12-lead ECG Holters were available. Of these, 752,517 ECG samples were selected (1256 ± 244 per subject) to measure PQ and QT intervals and P wave durations. For each measured ECG sample, 5-minute history of preceding cardiac cycles was also obtained. Although less rate dependent than the QT intervals (36 ± 19% of linear slopes), PQ intervals were found to be dependent on underlying cycle length in a highly curvilinear fashion with the dependency significantly more curved in females compared to males. The PQ interval also responded to the heart rate changes with a delay which was highly sex dependent (95% adaptation in females and males after 114.9 ± 81.1 vs 65.4 ± 64.3 seconds, respectively, p < 0.00001). P wave duration was even less rate dependent than the PQ interval (9 ± 10% of linear QT/RR slopes). Rate corrected P wave duration was marginally but significantly shorter in females than in males (106.8 ± 8.4 vs 110.2 ± 7.9 ms, p < 0.00001). In addition to establishing physiologic standards, the study suggests that the curvatures and adaptation delay of the PQ/cycle-length dependency should be included in future non-invasive studies of atrial depolarizations.
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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.
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Abstract Aim Cardiac arrest centers have been associated with improved outcome for patients after cardiac arrest. Aim of this study was to investigate the effect on outcome depending on admission to ...high-, medium- or low volume centers. Methods Analysis from a prospective, multicenter registry for out of hospital cardiac arrest patients treated by the emergency medical service of Vienna, Austria. The frequency of cardiac arrest patients admitted per center/year (low <50; medium 50–100; high >100) was correlated to favorable outcome (30-day survival with cerebral performance category of 1 or 2). Results Out of 2238 patients (years 2013–2015) with emergency medical service resuscitation, 861 (32% female, age 64 (51;73) years) were admitted to 7 different centers. Favorable outcome was achieved in 267 patients (31%). Survivors were younger (58 vs. 66 years; p < 0.001), showed shockable initial heart rhythm more frequently (72 vs. 35%; p < 0.001), had shorter CPR durations (22 vs. 29 min; p < 0.001) and were more likely to be treated in a high frequency center (OR 1.6; CI: 1.2–2.1; p = 0.001). In multivariate analysis, age below 65 years (OR 15; CI: 3.3–271.4; p = 0.001), shockable initial heart rhythm (OR 10.1; CI: 2.4–42.6; p = 0.002), immediate bystander or emergency medical service CPR (OR 11.2; CI: 1.4–93.3; p = 0.025) and admission to a center with a frequency of >100 OHCA patients/year (OR 5.2; CI: 1.2–21.7; p = 0.025) was associated with favorable outcome. Conclusions High frequency of post-cardiac arrest treatment in a specialized center seems to be an independent predictor for favorable outcome in an unselected population of patients after out of hospital cardiac arrest.
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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 10
o
and 20
o
, 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.
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,
< 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.
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.
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 (
> 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.
Abstract Background In the canine wedge preparation, the interval from the peak to the end of the T wave (TpTe) reflects transwedge heterogeneities. Increase of ventricular dispersion of action ...potential durations has been repeatedly shown to be arrhythmogenic; thus, prolonged TpTe intervals were assumed to reflect increased risk. However, despite attempted extrapolation to clinical electrocardiograms, the appropriateness of this assumption has not been investigated in a large population. In another animal model, nondipolar components of the descending T-wave limb (TWRd) have been shown to correlate with TpTe interval. Although total T-wave nondipolar components (TWRt), believed to reflect heterogeneities during total repolarization, were shown associated with worse outcome of cardiac patients, this has not been investigated for TWRd. Methods and Results Male cardiovascular patients (n = 813) had digital 12-lead electrocardiograms recorded between 1984 and 1991 and were followed until 2000. Using commercial and previously validated technology, QT intervals, TpTe intervals, TWRd, and TWRt were calculated, heart rate corrected, and compared between survivors and nonsurvivors. Their predictive power was also compared with established markers of mortality risk. In contrast to former reports, TpTec intervals were significantly shorter in nonsurvivors (98.76 ± 20.63 milliseconds vs 103.14 ± 20.87 milliseconds, P = .016) and not predictive of outcome. Although TWRdc was significantly higher in nonsurvivors (0.007% ± 0.02% vs 0.005% ± 0.08%, P = .03), it was also not predictive of outcome. Only increased TWRtc , increased heart rate, and increased age were predictive of death. Conclusions The findings challenge the concept that prolongation of TpTe corresponds to higher risk of death from any cause in every population. Further investigations are needed to confirm that clinically measured TpTe reflects transmural repolarization heterogeneity in all clinical populations and indeed is a useful risk marker.
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To facilitate the precision of clinical electrocardiographic studies of J-to-Tpeak (JTp) and Tpeak-to-Tend (Tpe) intervals, the study investigated their differences between healthy females and males, ...and between subjects of African and Caucasian origin. In 523 healthy subjects (254 females; 236 subjects of African origin), repeated Holter recordings were used to measure QT, JT, JTp, and Tpe intervals preceded by both stable and variable heart rates. Subject-specific curvilinear regression models were used to obtain individual QTc, JTc, JTpc and Tpec intervals. Rate hysteresis, i.e., the speed with which the intervals adapted after heart rate changes, was also investigated. In all sex-race groups, Tpe intervals were not systematically heart rate dependent. Similar to QTc intervals, women had JTc, and JTpc intervals longer than males (difference 20-30 ms, p < 0.001). However, women had Tpec intervals (and rate uncorrected Tpe intervals) shorter by approximately 10 ms compared to males (p < 0.001). Subjects of African origin had significantly shorter QTc intervals than Caucasians (p < 0.001). Gradually diminishing race-difference was found for JTc, JTpc and Tpec intervals. JTc and JTpc were moderately increasing with age but Tpe/Tpec were not. Rate hysteresis of JTp was approximately 10% longer compared to that of JT (p < 0.001). In future clinical studies, Tpe interval should not be systematically corrected for heart rate and similar to the QT interval, the differences in JT, JTp and Tpe intervals should be corrected for sex. The differences in QT and JT, and JTp intervals should also be corrected for race.
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