An Issue Waiting to be Clarified: Effects of the QT Prolonging Drugs on Tp-e Interval

Omer Yiginer Mehmet Dogan Emrah Erdal About the authors

Keywords
Psychotropic /drugs therapeutic; Electrocardiography; Cardiovascular Diseases; Torsades de Pointes; Ventricular Fibrillation; Death, Sudden

We read the article ‘Impact of Psychotropic Drugs on QT Interval Dispersion in Adult Patients’ by Claudio et al. with great interest1Claudio B de Q, Costa MA, Penna F, Konder MT, Celoria BM, Souza LL, et al. Impact of psychotropic drugs on QT interval dispersion in adult patients. Arq Bras Cardiol. 2014;102(5):465-72.. They investigated in this study the effects of psychotropic drugs on QT interval (QTI), corrected QT interval (QTc), and QT dispersion (QTd). They concluded that psychotropic drugs increased QTd and QTc interval.

QTd is the most frequently used non-invasive method to quantify electrical myocardial heterogeneity. However, there are variable results in studies related to QTI due to the technical limitations in measurements2Malik M, Batchvarov VN. Measurement, interpretation and clinical potential of QT dispersion [Review]. J Am Coll Cardiol. 2000;36(6):1749-66.. It is well-known that the reproducibility of QTI measurements is low both in manual and automatic measurements2Malik M, Batchvarov VN. Measurement, interpretation and clinical potential of QT dispersion [Review]. J Am Coll Cardiol. 2000;36(6):1749-66.. In this study, the measurements were performed digitally by four cardiologists using the Preview software with a magnification of 300%. We appreciated the method used in this study in order to obtain more accurate data. It is recommended that measurements be done digitally at least by two cardiologists2Malik M, Batchvarov VN. Measurement, interpretation and clinical potential of QT dispersion [Review]. J Am Coll Cardiol. 2000;36(6):1749-66..

Quantifying electrical myocardial heterogeneity and transmural dispersion of repolarization (TDR) was introduced in the beginning of 2000’s3Gupta P, Patel C, Patel H, Narayanaswamy S, Malhotra B, Green JT, et al. T(p-e)/QT ratio as an index of arrhythmogenesis. J Electrocardiol. 2008;41(6):567-74.. The myocardium comprises 3 distinct myocyte types - namely, endocardial, epicardial, and midmyocardial M cells3Gupta P, Patel C, Patel H, Narayanaswamy S, Malhotra B, Green JT, et al. T(p-e)/QT ratio as an index of arrhythmogenesis. J Electrocardiol. 2008;41(6):567-74.. Although these myocytes are morphologically similar, they exhibit different electrophysiological characteristics. M cells have typically the longest action potential. Furthermore, when myocardium is exposed to conditions prolonging the repolarization phase, such as bradycardia or agents, the action potential duration of the M cells are more prolonged than in the other cells3Gupta P, Patel C, Patel H, Narayanaswamy S, Malhotra B, Green JT, et al. T(p-e)/QT ratio as an index of arrhythmogenesis. J Electrocardiol. 2008;41(6):567-74.. While repolarization of the epicardial region ends at the peak of T-wave, repolarization phase of M cells ends at the end of T wave3Gupta P, Patel C, Patel H, Narayanaswamy S, Malhotra B, Green JT, et al. T(p-e)/QT ratio as an index of arrhythmogenesis. J Electrocardiol. 2008;41(6):567-74.. Therefore, the time between the peak and end of the T wave is called Tp-e interval, as an index of TDR.

The role of the TDR in the prediction of possible life‑threatening arrhythmic events has been demonstrated in the Brugada, short-QT and long-QT syndromes and coronary artery disease3Gupta P, Patel C, Patel H, Narayanaswamy S, Malhotra B, Green JT, et al. T(p-e)/QT ratio as an index of arrhythmogenesis. J Electrocardiol. 2008;41(6):567-74.. Previously, we showed that TDR was increased in patients with obstructive sleep apnea and chronic arsenic exposure4Kilicaslan F, Tokatli A, Ozdag F, Uzun M, Uz O, Isilak Z, et al. Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio are prolonged in patients with moderate and severe obstructive sleep apnea. Pacing Clin Electrophysiol. 2012; 35(8):966-72.,5Yildiz A, Karaca M, Biceroglu S, Nalbantcilar MT, Coskun U, Arik F, et al. Effect of chronic arsenic exposure from drinking waters on the QT interval and transmural dispersion of repolarization. J Int Med Res. 2008;36(3):471-8.. However, there is no study investigating the effects of QT prolonging drugs on TDR. The repolarization phase of myocytes in midmyocardial and endocardial layers may be more influenced by the drugs. In this context, psychotropic drugs may be increasing QT interval duration via Tp-e interval prolongation. In conclusion, it seems that adding the data related to Tp-e interval to the study results might have completely illuminated the effects of psychotropic drugs on electrical heterogeneity of myocardium in many respects.

References

  • 1
    Claudio B de Q, Costa MA, Penna F, Konder MT, Celoria BM, Souza LL, et al. Impact of psychotropic drugs on QT interval dispersion in adult patients. Arq Bras Cardiol. 2014;102(5):465-72.
  • 2
    Malik M, Batchvarov VN. Measurement, interpretation and clinical potential of QT dispersion [Review]. J Am Coll Cardiol. 2000;36(6):1749-66.
  • 3
    Gupta P, Patel C, Patel H, Narayanaswamy S, Malhotra B, Green JT, et al. T(p-e)/QT ratio as an index of arrhythmogenesis. J Electrocardiol. 2008;41(6):567-74.
  • 4
    Kilicaslan F, Tokatli A, Ozdag F, Uzun M, Uz O, Isilak Z, et al. Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio are prolonged in patients with moderate and severe obstructive sleep apnea. Pacing Clin Electrophysiol. 2012; 35(8):966-72.
  • 5
    Yildiz A, Karaca M, Biceroglu S, Nalbantcilar MT, Coskun U, Arik F, et al. Effect of chronic arsenic exposure from drinking waters on the QT interval and transmural dispersion of repolarization. J Int Med Res. 2008;36(3):471-8.

Publication Dates

  • Publication in this collection
    June 2015

History

  • Received
    11 Nov 2014
  • Reviewed
    11 Nov 2014
  • Accepted
    19 Jan 2015

Answer to Letter to Editor

Bruno de Queiroz Claudio

We appreciate the authors’ interest in our study and the valuable contributions on the subject.

The spatial dispersion of ventricular repolarization can occur in the transmural, trans-septal or apical-basal direction.1Antzelevitch C. The role of spatial dispersion of repolarization in inherited and acquired sudden cardiac death syndromes. Am J Physiol Heart Circ Physiol. 2007;293(4):H2024-38.,2Restivo M, Caref EB, Kozhevnikov DO, El-Sherif N. Spatial dispersion of repolarization is a key factor in the arrythmogenicity of long QT syndrome. J Cardiovasc Electrophysiol. 2004;15(3):323-31.. A large number of publications has been dedicated to the study of cell diversity of the human myocardium and its heterogenic response to pharmacological agents.

Researchers such as Antzelevitch et al.3Antzelevitch C, Shimizu W, Yan GX, Sicouri S, Weissenburger J, Nesterenko VV, 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(8):1124-52. and Luo e Rudy4Luo CH, Rudy Y. A dynamic model of the cardiac ventricular action potential. I. Simulations of ionic currents and concentration changes. Circ Res. 1994;74(6):1071-96. have tested several models in normal hearts and individuals with congenital long-QT syndrome, concluding that the properties of the M cell action potential critically participate on QT interval dispersion, mainly in the presence of drugs with binding capacity in the IKr and IKs channels1Antzelevitch C. The role of spatial dispersion of repolarization in inherited and acquired sudden cardiac death syndromes. Am J Physiol Heart Circ Physiol. 2007;293(4):H2024-38.,5Antzelevitch C, Shimizu W. Cellular mechanisms underlying the long QT syndrome. Curr Opin Cardiol. 2002;17(1):43-51..

Under this idea, in fact, the measurement of Tp-e is conceptually an electrocardiographic correlation truthful to the abovementioned concepts. In a recent article, in the coronary artery disease model, Karaman et al.6Karaman K1, Altunkas F, Cetin M, Karayakali M, Arisoy A, Akar I, Zencir C, Aygüç B, Celik A. New Markers for Ventricular Repolarization in Coronary Slow Flow: Tp-e Interval, Tp-e/QT Ratio, and Tp-e/QTc Ratio. Ann Noninvasive Electrocardiol. 2014 Sep 30. [Epub ahead of print] found an association between increased QT dispersion and the Tp-e interval with slowed coronary flow in coronary angiography (TIMI 1) in patients with acute coronary syndrome, when compared to the control group (TIMI 3)6Karaman K1, Altunkas F, Cetin M, Karayakali M, Arisoy A, Akar I, Zencir C, Aygüç B, Celik A. New Markers for Ventricular Repolarization in Coronary Slow Flow: Tp-e Interval, Tp-e/QT Ratio, and Tp-e/QTc Ratio. Ann Noninvasive Electrocardiol. 2014 Sep 30. [Epub ahead of print].

In our study, we chose to measure the QT dispersion, as it is a powerful tool that can be fully incorporated by general practitioners that prescribes psychotropic drugs in the routine monitoring of a potentially fatal complication of their patients7. However, we expect the Tp-e interval, considering its solid results in the literature, also to become a routine tool in the increasingly frequent use of these drugs.

Sincerely,

Bruno de Queiroz Claudio

References

  • 1
    Antzelevitch C. The role of spatial dispersion of repolarization in inherited and acquired sudden cardiac death syndromes. Am J Physiol Heart Circ Physiol. 2007;293(4):H2024-38.
  • 2
    Restivo M, Caref EB, Kozhevnikov DO, El-Sherif N. Spatial dispersion of repolarization is a key factor in the arrythmogenicity of long QT syndrome. J Cardiovasc Electrophysiol. 2004;15(3):323-31.
  • 3
    Antzelevitch C, Shimizu W, Yan GX, Sicouri S, Weissenburger J, Nesterenko VV, 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(8):1124-52.
  • 4
    Luo CH, Rudy Y. A dynamic model of the cardiac ventricular action potential. I. Simulations of ionic currents and concentration changes. Circ Res. 1994;74(6):1071-96.
  • 5
    Antzelevitch C, Shimizu W. Cellular mechanisms underlying the long QT syndrome. Curr Opin Cardiol. 2002;17(1):43-51.
  • 6
    Karaman K1, Altunkas F, Cetin M, Karayakali M, Arisoy A, Akar I, Zencir C, Aygüç B, Celik A. New Markers for Ventricular Repolarization in Coronary Slow Flow: Tp-e Interval, Tp-e/QT Ratio, and Tp-e/QTc Ratio. Ann Noninvasive Electrocardiol. 2014 Sep 30. [Epub ahead of print]
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