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Ventricular repolarization
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Journal of Electrocardiology 44 (2011) 299 – 300 www.jecgonline.com
Editorial
Ventricular repolarization Characterization of physiologic processes involved in ventricular repolarization and the diagnosis of repolarization abnormalities are significant tasks faced by contemporary electrocardiology. The repolarization processes are perhaps reasonably understood at the level of isolated myocytes. A multitude of ion channels have been identified, including their genetic coding, which is responsible for transmembrane currents active during different phases of the action potentials of individual myocytes.1,2 The understanding of how individual cells influence each other during the repolarization process of the ventricular muscle is much less advanced. It is well known that different ventricular regions have different repolarization properties. Gradients in the duration of action potentials exist across the ventricular wall between the endocardium and epicardium, along the long cardiac axis between the apex and base, as well as between the left and right ventricles.3,4 In isolated sections of animal hearts, detailed investigations have studied the intramyocardial distributions of action potential durations. In canine wedge preparations, a distinct middle layer was observed showing substantially prolonged repolarization duration compared with both the endocardial and epicardial regions.5 This led to speculations that this middle layer might be responsible for forming the T-wave patterns on surface electrocardiograms (ECG). Although this might be a reasonable explanation of signals recorded from an isolated segment of myocardial tissue, the situation with whole hearts is clearly much more complicated. It is not even obvious whether any distinct layers of special repolarization properties exist in human hearts in situ.6 The synchrony of ventricular repolarization must be maintained not only at a border between separate myocardial layers but also at the level of electronic interactions within each cluster of neighboring cells. Such localized manifestations of electronic interactions are bound to create a recursive process spanning across the whole ventricular muscle. Under physiologic conditions, localized repolarization differences are likely smoothed by the electronic interactions that keep closely coupled cells in synchrony. Under pathologic conditions, regardless of whether congenital or acquired, the strength of electronic coupling might be lost either because of anatomical or histological barriers or because of an abnormal function of repolarization transmembrane ion currents. In such a case, even small local disparities between neighboring cells might spread, occasionally creating a substrate for serious arrhythmias such as ventricular fibrillation or Torsade de Pointes tachycardia. 0022-0736/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.jelectrocard.2011.02.004
The complex interplay between individual myocytes within the complete 3-dimensional structure of the ventricular myocardial mass is clearly beyond the capabilities of our imagination. This is one of the reasons why investigations of ventricular repolarization pose such a challenge to present electrocardiology. It is, therefore, pleasing that several contributions were accepted to the Journal, all devoted to different aspects of ventricular repolarization, so that forming a dedicated issue was possible. The Editor-in-Chief asked me to write this introductory note. Although the articles in this issue are devoted to broad ranging facets of ventricular repolarization, some of the texts deserve specific comments. The simplest characterization of ventricular repolarization in the surface ECG is based on the measurement of the QT interval duration. The QT interval measurement is certainly not problem-free, especially when dealing with ECGs showing pathologic T-wave shapes or influenced by highlevel noise and/or recording artifacts. Two articles of this issue are devoted to the advances in computerized QT measurement. Zhou and Wei7 report on a new algorithmic possibility, whereas Tyl et al8 compared selected methods for the measurement. Even elementary methods for QT interval measurement are providing acceptable results if dealing with good quality physiologic signals. It is, therefore, regrettable that in the articles presented here, similar to other publications of this kind, the character and quality of the clinical data in which the tests and comparisons were performed is not explicitly described. This is likely because no broadly accepted technologies and methods exist for expressing the quality and normality of standard ECGs. Objective measurement of the noise in the signals is possible but objective characterization of T-wave shape peculiarities is still missing. Further development of such techniques would surely help to advance the technology of ECG processing by providing difficult but standardized benchmarks. The ECG community would clearly benefit from such a universally acceptable standard. Kusuki et al9 report on an interesting collection of data in small children in whom the measurements of QT interval variability were performed, mainly using the previously researched technique of QT variability index. Although the observations that in small children, heart rate decreases with age (and, thus, the uncorrected QT interval increases with age) are known and do not offer further insight, the observations that the QT variability reaches equilibrium
300
Editorial / Journal of Electrocardiology 44 (2011) 299–300
during the preschool years is of physiologic interest. Unfortunately, the very small children investigated in the study have to be tranquilized, thus potentially creating a confounding factor in the reported data. It would also be interesting to extend investigations of this kind into adolescents in whom the sex differences in QT interval duration are known to appear around puberty. Future investigation of that kind might advance our understanding of the sex differences in ventricular repolarization further. Torbey et al10 report on an interesting clinical case of a patient who repeatedly exhibited clinical signs of repolarization abnormality due to ginseng consumption. Although some inconsistent reports exist in the literature of whether ginseng consumption leads to a delayed repolarization,11 the case report is interesting in providing another example of a patient in whom an unusual chemical leads to severe arrhythmic problems. In isolated cases of this kind, it is very difficult to differentiate between the overall repolarization toxicity of a drug or chemical and the highly specific individual repolarization abnormality that makes the subject uniquely sensitive to a particular compound. Indeed, examples exist of Torsade de Pointes tachycardia reproducibly induced by drugs that are generally very safe and without any repolarization involvement in the broad population.12 Zhao et al13 report on QT interval restitution during exercise-induced heart rate increases in women. Unfortunately, the topic of the so-called QT restitution is highly controversial. Because the QT interval adaptation to heart rate changes is not instantaneous because of the QT/R-R interval hysteresis, relating the QT interval to the preceding or following R-R interval is nonsensical in the presence of heart rate changes. Unfortunately, the sum of the QT and TQ intervals equals to the R-R interval of the given cycle, and thus, any studies of the so-called QT restitution are hugely dependent on the speed of heart rate changes. With a slower speed of heart rate increases, the gap between the QT interval duration and the instantaneously measured heart rate (and, thus, also TQ intervals) becomes small compared with the fast occurring heart rate increases. This all influences the expressions of the so-called restitution
beyond any reasonable experimental control. Hence, unfortunately, the report by Zhao et al is an example of a study that should be actively discouraged. Marek Malik, PhD, MD St Paul's Cardiac Electrophysiology and St George's University of London, London, England E-mail address: [email protected] References 1. Conrath CE, Opthof T. Ventricular repolarization: an overview of (patho)physiology, sympathetic effects and genetic aspects. Prog Biophys Mol Biol 2006;92:269. 2. Abbott GW, Xu X, Roepke TK. Impact of ancillary subunits on ventricular repolarization. J Electrocardiol 2007;40(6 Suppl):S42. 3. Noble D, Cohen I. The interpretation of the T wave of the electrocardiogram. Cardiovasc Res 1978;12:13. 4. Janse MJ, Sosunov EA, Coronel R, et al. Repolarization gradients in the canine left ventricle before and after induction of short-term cardiac memory. Circulation 2005;112:1711. 5. Antzelevitch C, Shimizu W, Yan GX, et al. The M cell: its contribution to the ECG and to normal and abnormal electrical function of the heart. J Cardiovasc Electrophysiol 1999;10:1124. 6. Morgan JM, Cunningham D, Rowland E. Dispersion of monophasic action potential duration: demonstrable in humans after premature ventricular extrastimulation but not in steady state. J Am Coll Cardiol 1992;19:1244. 7. Zhou X, Wei D. A multidifferentiator-based approach to the reliable determination of T-wave offset in electrocardiograms. J Electrocardiol 2011;44:330. 8. Tyl B, Azzam S, Blanco N, Wheeler W. Improvement and limitation of the reliability of automated QT measurement by recent algorithms. J Electrocardiol 2011;44:320. 9. Kusuki H, Kuriki M, Horio K, et al. Beat-to-beat QT interval variability in children: normal and physiologic data. J Electrocardiol 2011;44:326. 10. Torbey E, Rafeh NA, Khoueiry G, Kowalski M, Bekheit S. Ginseng: a potential cause of long QT. J Electrocardiol 2011;44:357. 11. Caron MF, Hotsko AL, Robertson S, Mandybur L, Kluger J, White CM. Electrocardiographic and hemodynamic effects of Panax ginseng. Ann Pharmacother 2002;36:758. 12. Pinto YM, van Gelder IC, Heeringa M, Crijns HJ. QT lengthening and life-threatening arrhythmias associated with fexofenadine. Lancet 1999;353:980. 13. Zhao D, Wang Y, Wei Y, Tang K, Yu X, Xu Y. QT restitution properties of middle-aged women with different exercise capacities. J Electrocardiol 2011;44:340.
Journal of Electrocardiology 44 (2011) 299 – 300 www.jecgonline.com
Editorial
Ventricular repolarization Characterization of physiologic processes involved in ventricular repolarization and the diagnosis of repolarization abnormalities are significant tasks faced by contemporary electrocardiology. The repolarization processes are perhaps reasonably understood at the level of isolated myocytes. A multitude of ion channels have been identified, including their genetic coding, which is responsible for transmembrane currents active during different phases of the action potentials of individual myocytes.1,2 The understanding of how individual cells influence each other during the repolarization process of the ventricular muscle is much less advanced. It is well known that different ventricular regions have different repolarization properties. Gradients in the duration of action potentials exist across the ventricular wall between the endocardium and epicardium, along the long cardiac axis between the apex and base, as well as between the left and right ventricles.3,4 In isolated sections of animal hearts, detailed investigations have studied the intramyocardial distributions of action potential durations. In canine wedge preparations, a distinct middle layer was observed showing substantially prolonged repolarization duration compared with both the endocardial and epicardial regions.5 This led to speculations that this middle layer might be responsible for forming the T-wave patterns on surface electrocardiograms (ECG). Although this might be a reasonable explanation of signals recorded from an isolated segment of myocardial tissue, the situation with whole hearts is clearly much more complicated. It is not even obvious whether any distinct layers of special repolarization properties exist in human hearts in situ.6 The synchrony of ventricular repolarization must be maintained not only at a border between separate myocardial layers but also at the level of electronic interactions within each cluster of neighboring cells. Such localized manifestations of electronic interactions are bound to create a recursive process spanning across the whole ventricular muscle. Under physiologic conditions, localized repolarization differences are likely smoothed by the electronic interactions that keep closely coupled cells in synchrony. Under pathologic conditions, regardless of whether congenital or acquired, the strength of electronic coupling might be lost either because of anatomical or histological barriers or because of an abnormal function of repolarization transmembrane ion currents. In such a case, even small local disparities between neighboring cells might spread, occasionally creating a substrate for serious arrhythmias such as ventricular fibrillation or Torsade de Pointes tachycardia. 0022-0736/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.jelectrocard.2011.02.004
The complex interplay between individual myocytes within the complete 3-dimensional structure of the ventricular myocardial mass is clearly beyond the capabilities of our imagination. This is one of the reasons why investigations of ventricular repolarization pose such a challenge to present electrocardiology. It is, therefore, pleasing that several contributions were accepted to the Journal, all devoted to different aspects of ventricular repolarization, so that forming a dedicated issue was possible. The Editor-in-Chief asked me to write this introductory note. Although the articles in this issue are devoted to broad ranging facets of ventricular repolarization, some of the texts deserve specific comments. The simplest characterization of ventricular repolarization in the surface ECG is based on the measurement of the QT interval duration. The QT interval measurement is certainly not problem-free, especially when dealing with ECGs showing pathologic T-wave shapes or influenced by highlevel noise and/or recording artifacts. Two articles of this issue are devoted to the advances in computerized QT measurement. Zhou and Wei7 report on a new algorithmic possibility, whereas Tyl et al8 compared selected methods for the measurement. Even elementary methods for QT interval measurement are providing acceptable results if dealing with good quality physiologic signals. It is, therefore, regrettable that in the articles presented here, similar to other publications of this kind, the character and quality of the clinical data in which the tests and comparisons were performed is not explicitly described. This is likely because no broadly accepted technologies and methods exist for expressing the quality and normality of standard ECGs. Objective measurement of the noise in the signals is possible but objective characterization of T-wave shape peculiarities is still missing. Further development of such techniques would surely help to advance the technology of ECG processing by providing difficult but standardized benchmarks. The ECG community would clearly benefit from such a universally acceptable standard. Kusuki et al9 report on an interesting collection of data in small children in whom the measurements of QT interval variability were performed, mainly using the previously researched technique of QT variability index. Although the observations that in small children, heart rate decreases with age (and, thus, the uncorrected QT interval increases with age) are known and do not offer further insight, the observations that the QT variability reaches equilibrium
300
Editorial / Journal of Electrocardiology 44 (2011) 299–300
during the preschool years is of physiologic interest. Unfortunately, the very small children investigated in the study have to be tranquilized, thus potentially creating a confounding factor in the reported data. It would also be interesting to extend investigations of this kind into adolescents in whom the sex differences in QT interval duration are known to appear around puberty. Future investigation of that kind might advance our understanding of the sex differences in ventricular repolarization further. Torbey et al10 report on an interesting clinical case of a patient who repeatedly exhibited clinical signs of repolarization abnormality due to ginseng consumption. Although some inconsistent reports exist in the literature of whether ginseng consumption leads to a delayed repolarization,11 the case report is interesting in providing another example of a patient in whom an unusual chemical leads to severe arrhythmic problems. In isolated cases of this kind, it is very difficult to differentiate between the overall repolarization toxicity of a drug or chemical and the highly specific individual repolarization abnormality that makes the subject uniquely sensitive to a particular compound. Indeed, examples exist of Torsade de Pointes tachycardia reproducibly induced by drugs that are generally very safe and without any repolarization involvement in the broad population.12 Zhao et al13 report on QT interval restitution during exercise-induced heart rate increases in women. Unfortunately, the topic of the so-called QT restitution is highly controversial. Because the QT interval adaptation to heart rate changes is not instantaneous because of the QT/R-R interval hysteresis, relating the QT interval to the preceding or following R-R interval is nonsensical in the presence of heart rate changes. Unfortunately, the sum of the QT and TQ intervals equals to the R-R interval of the given cycle, and thus, any studies of the so-called QT restitution are hugely dependent on the speed of heart rate changes. With a slower speed of heart rate increases, the gap between the QT interval duration and the instantaneously measured heart rate (and, thus, also TQ intervals) becomes small compared with the fast occurring heart rate increases. This all influences the expressions of the so-called restitution
beyond any reasonable experimental control. Hence, unfortunately, the report by Zhao et al is an example of a study that should be actively discouraged. Marek Malik, PhD, MD St Paul's Cardiac Electrophysiology and St George's University of London, London, England E-mail address: [email protected] References 1. Conrath CE, Opthof T. Ventricular repolarization: an overview of (patho)physiology, sympathetic effects and genetic aspects. Prog Biophys Mol Biol 2006;92:269. 2. Abbott GW, Xu X, Roepke TK. Impact of ancillary subunits on ventricular repolarization. J Electrocardiol 2007;40(6 Suppl):S42. 3. Noble D, Cohen I. The interpretation of the T wave of the electrocardiogram. Cardiovasc Res 1978;12:13. 4. Janse MJ, Sosunov EA, Coronel R, et al. Repolarization gradients in the canine left ventricle before and after induction of short-term cardiac memory. Circulation 2005;112:1711. 5. Antzelevitch C, Shimizu W, Yan GX, et al. The M cell: its contribution to the ECG and to normal and abnormal electrical function of the heart. J Cardiovasc Electrophysiol 1999;10:1124. 6. Morgan JM, Cunningham D, Rowland E. Dispersion of monophasic action potential duration: demonstrable in humans after premature ventricular extrastimulation but not in steady state. J Am Coll Cardiol 1992;19:1244. 7. Zhou X, Wei D. A multidifferentiator-based approach to the reliable determination of T-wave offset in electrocardiograms. J Electrocardiol 2011;44:330. 8. Tyl B, Azzam S, Blanco N, Wheeler W. Improvement and limitation of the reliability of automated QT measurement by recent algorithms. J Electrocardiol 2011;44:320. 9. Kusuki H, Kuriki M, Horio K, et al. Beat-to-beat QT interval variability in children: normal and physiologic data. J Electrocardiol 2011;44:326. 10. Torbey E, Rafeh NA, Khoueiry G, Kowalski M, Bekheit S. Ginseng: a potential cause of long QT. J Electrocardiol 2011;44:357. 11. Caron MF, Hotsko AL, Robertson S, Mandybur L, Kluger J, White CM. Electrocardiographic and hemodynamic effects of Panax ginseng. Ann Pharmacother 2002;36:758. 12. Pinto YM, van Gelder IC, Heeringa M, Crijns HJ. QT lengthening and life-threatening arrhythmias associated with fexofenadine. Lancet 1999;353:980. 13. Zhao D, Wang Y, Wei Y, Tang K, Yu X, Xu Y. QT restitution properties of middle-aged women with different exercise capacities. J Electrocardiol 2011;44:340.