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Olanzapin Kullanımı QT İntervali Normal Ölçülen Hastalarda T Dalga Tepe- T Dalga Sonlanım Noktaları İntervalini Uzatır

Year 2014, Volume: 11 Issue: 3, 237 - 241, 15.12.2014

Abstract

Amaç: Antipsikotik ilaçların QT intervalini uzatarak ani kardiyak ölüme yol açabildikleri uzun süredir
bilinmektedir. İkinci nesil antipsikotikler, düşük aritmik etkileri nedeniyle birinci nesilden daha güvenli
olarak değerlendirilmektedir. Olanzapin en sık kullanılan ikinci nesil antipsikotiklerden birisidir ancak QT
intervaline olan etkisi için çelişkili veriler mevcuttur. Yapılan çalışmalar, 12-kanal elektrokardiyogramda T
dalga tepe noktasından sonlanım noktasına kadar ölçülen intervalin (Tp-e) uzamasının ventriküler
aritmogenezin belirteci olduğunu göstermektedir. Çalışmamızın amacı, olanzapin tedavisi altındaki
hastaların ventriküler repolarizasyon anormalliklerini Tp-e, Qt ve QTc intervalleri ve Tp-e/QT oranı
kullanarak değerlendirmektir.
Materyal ve Metot: Hasta kayıtları retrospektif olarak incelendi. En az 3 aydır olanzapin kullanmakta olan
şizofreni hastalarının EKG'leri incelendi.Yaş ve cinsiyet uyumlu kontrol grubu da karşılaştırma için gruba
dahil edildi. Yüzeyel EKG'lerin dijital ortamda bilgisayar programıyla QT, QTc ve Tp-e intervalleri ölçüldü.
Bulgular: Her iki grubun demografik özellikleri benzerdi. Hastaların kullandığı Ortalama günlük olanzapin
dozu 20,3±7 mg idi. Her iki grup QT (371,8±55,4 vs. 362,61±34,7; p=0,440) ve QTc (455,98±49,3 vs.
434,48±43,724; p=0,077) intervalleri açısından farksızdı. Ancak Tp-e intervali olanzapin kullanan
hastalarda anlamlı olarak uzamış bulundu (89,5±31,8 vs. 76,4±9,8; p=0,039).
Sonuç: T dalgası tepe noktası-sonlanım noktası intervali, sol ventrikül transmural repolarizasyon
dispersiyonunun göstergesi ve ventriküler aritmogenez belirteci olarak kabul edilmektedir. Tp-e/QT ise
daha yeni bir parametre olup aynı defektlere işaret etmektedir. Bulgularımız, yalnızca olanzapin tedavisi
alan hastalarda sağlıklı bireylere göre uzamış Tp-e intervali ve daha yüksek Tp-e/QT (p=0,041)
göstermiştir. Antipsikotikler QT intervalini uzatmayabilir, ancak sadece Tp-e segmentindeki uzama da
repolarizasyon heterojenitesine işaret edebilir. Tp-e ve Tp-e/QT ölçümlerinin antipsikotik olanzapin kullanan hastalarda ventriküler aritmi riskinin belirteci olabileceğini düşünüyoruz.

References

  • 1) Hennekens CH, Hennekens AR, Hollar D, et al. Schizophrenia and increased risks of cardiovascular disease. AmHeart J. 2005;150:1115–1121. 2) Casey DE, Hansen TE. Excessive morbidity and mortality in schizophrenia. In: Meyer JM, Nasrallah HA, eds. Medical Illness and Schizophrenia. Washington, DC: AmericanPsychiatric. Pub.; 2006;210–222. 3) Hennessy S, Bilker WB, Knauss JS, et al. Cardiac arrest and ventricular arrhythmia in patients taking antipsychotic drugs: cohort study using administrative data. BMJ. 2002;325:1070. 4) Bar KJ, Letzsch A, Jochum T, et al. Loss of efferent vagal activity in acute schizophrenia. J PsychiatrRes. 2005;39:519–527. 5) Toichi M, Kubota Y, Murai T, et al. The influence of psychoticstates on the autonomic nervous system in schizophrenia. Int J Psychophysiol. 1999;31:147–154. 6) Haarmark C, Hansen PR, Vedel-Larsen E, et al. The prognostic value of the Tpeak-Tend interval in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. J Electrocardiol. 2009; 42:555–560. 7) Castro Hevia J, Antzelevitch C, TornésBárzaga F,et al. Tpeak-Tend and Tpeak-Tend dispersion as risk factors for ventricular tachycardia/ventricular fibrillation in patients with the Brugada syndrome. J Am CollCardiol. 2006;47(9):1828-34 8) Savelieva I, Yap YG, Yi G, et al. Comparative reproducibility of QT, QT peak, and T peak–T end intervals and dispersion in normal subjects, patients with myocardial infarction, and patients with hypertrophic c a r d i o m y o p a t h y . P a c i n g C l i n Electrophysiol1998;21:2376. 9) Tran PV, Hamilton SH, Kuntz AJ, et al. Doubleblindcomparison of olanzapine versus risperidone in thetreatment of schizophrenia and other psychotic disorders. J Clin Psychopharmacol.1997;17:407Y418. 10) Conley RR, Mahmoud R. Arandomized double-blind study of risperidone and olanzapine in the treatment of schizophrenia or schizoaffective disorder. Am J Psychiatry.2001;158:765Y774. 11) Harrigan EP, Miceli JJ, Anziano R, et al. A randomized evaluation of the effects of six antipsychotic agents on QTc, in the absence and presence of metabolic inhibition. J Clin Psychopharmacol. 2004;24:62-69. 12) Bazett JC. An analysis of time relations of electrocardiograms.Heart. 1920;7:353-367. 13) Bär KJ, Koschke M, Berger S, et al. Influence of olanzapine on QT variability and complexity measures of he a rt r a t e in pa ti ents with s chi zophr eni a .J ClinPsychopharmacol. 2008 Dec;28(6):694-8. 14) Erikssen G, Liestøl K, Gullestad L, Haugaa KH, Bendz B, Amlie JP. The terminal part of the QT interval (T peak to T end): a predictor of mortality after acute myocardial infarction. Ann Noninvasive Electrocardiol. 2012;17:85- 94. 15) Morissette P, Hreiche R, Mallet L, Vo D, Knaus EE, Turgeon J. Olanzapine prolongs cardiac repolarization by blocking the rapid component of the delayed rectifier potassium current. J Psychopharmacol. 2007 Sep;21(7):735-41. Epub 2006 Nov 8. 16) Piccirillo G, Moscucci F, D'Alessandro G, et al. Myocardial repolarization dispersion and autonomic nerve activity in a canine experimental acute myocardial infarction model. Heart Rhythm. 2014 Jan;11(1):110-8.

Olanzapıne Usage Prolongs T Wave Peak To T Wave End Segment In Patıents Wıth Normal QT Interval

Year 2014, Volume: 11 Issue: 3, 237 - 241, 15.12.2014

Abstract

Background: Antipsychotic drugs are long known to cause prolongation in QTinterval which is a marker of
increased risk for sudden cardiac death. Studies indicate that prolongation of the interval between the peak
and end of the T wave (Tpeak to Tend, Tp-e) on the 12-lead ECG, is a marker of ventricular
arrhythmogenesis. The aim of this study was to assess ventricular repolarization in patients who are on
antipsychotic therapy by using Tp-e, QTand QTc interval and Tp-e/QTratio.
Material and Method: Patient records were retrospectively analyzed. Electrocardiogram of 31 patients,
who were on antipsychotic drug therapy (olanzapine) at least 3 months, were obtained and scanned. T wave
peak to end interval, QT and corrected QT (QTc) intervals and some other ECG intervals were measured.
Electrocardiograms of age and sex matched 31 healthy control individuals were also analyzed for
comparison. Patients with critical coronary stenosis, moderate or severe valve disease, left and/or right heart
failure, left and/or right ventricle hypertrophy, atrial fibrillation, right or left bundle block or patients who got
pacemaker or ICD implanted were excluded.
Results: Both groups' baseline characteristics were similar. Mean olanzapine dose for patients was 20,3±7
mg. Both groups did not differ in QT (371,8±55,4 vs. 362,61±34,7; p=0,440) and QTc (455,98±49,3 vs.
434,48±43,724; p=0,077) interval measurements. However, patients who were on olanzapine had
significantly longer Tp-e (89,5±31,8 vs. 76,4±9,8; p=0,039) than controls.
Discussion: T wave peak to end interval is a measure of transmural dispersion of repolarization in the left
ventricle and accepted as a surrogate for increased ventricular arrhythmogenesis risk. Tp-e/QTis a relatively
new marker which also indicates repolarization defects. Antipsychotic drugs are claimed to be responsible
for QT prolongation and increase risk for Torsades de pointes. Our findings show that patients who are on
olanzapine treatment alone, have significantly longer Tp-e and higher Tp-e/QT(0,23 vs. 0,21; p=0,041) than
healthy controls. Antipsychotics may not prolong QT interval, however; may cause repolarization
heterogeneity and lengthen the Tp-e segment of whole QT interval. Tp-e and Tp-e/QT are suggestive
surrogates of ventricular arrhythmogenesis risk in patients who are on antipsychotic drugs. 

References

  • 1) Hennekens CH, Hennekens AR, Hollar D, et al. Schizophrenia and increased risks of cardiovascular disease. AmHeart J. 2005;150:1115–1121. 2) Casey DE, Hansen TE. Excessive morbidity and mortality in schizophrenia. In: Meyer JM, Nasrallah HA, eds. Medical Illness and Schizophrenia. Washington, DC: AmericanPsychiatric. Pub.; 2006;210–222. 3) Hennessy S, Bilker WB, Knauss JS, et al. Cardiac arrest and ventricular arrhythmia in patients taking antipsychotic drugs: cohort study using administrative data. BMJ. 2002;325:1070. 4) Bar KJ, Letzsch A, Jochum T, et al. Loss of efferent vagal activity in acute schizophrenia. J PsychiatrRes. 2005;39:519–527. 5) Toichi M, Kubota Y, Murai T, et al. The influence of psychoticstates on the autonomic nervous system in schizophrenia. Int J Psychophysiol. 1999;31:147–154. 6) Haarmark C, Hansen PR, Vedel-Larsen E, et al. The prognostic value of the Tpeak-Tend interval in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. J Electrocardiol. 2009; 42:555–560. 7) Castro Hevia J, Antzelevitch C, TornésBárzaga F,et al. Tpeak-Tend and Tpeak-Tend dispersion as risk factors for ventricular tachycardia/ventricular fibrillation in patients with the Brugada syndrome. J Am CollCardiol. 2006;47(9):1828-34 8) Savelieva I, Yap YG, Yi G, et al. Comparative reproducibility of QT, QT peak, and T peak–T end intervals and dispersion in normal subjects, patients with myocardial infarction, and patients with hypertrophic c a r d i o m y o p a t h y . P a c i n g C l i n Electrophysiol1998;21:2376. 9) Tran PV, Hamilton SH, Kuntz AJ, et al. Doubleblindcomparison of olanzapine versus risperidone in thetreatment of schizophrenia and other psychotic disorders. J Clin Psychopharmacol.1997;17:407Y418. 10) Conley RR, Mahmoud R. Arandomized double-blind study of risperidone and olanzapine in the treatment of schizophrenia or schizoaffective disorder. Am J Psychiatry.2001;158:765Y774. 11) Harrigan EP, Miceli JJ, Anziano R, et al. A randomized evaluation of the effects of six antipsychotic agents on QTc, in the absence and presence of metabolic inhibition. J Clin Psychopharmacol. 2004;24:62-69. 12) Bazett JC. An analysis of time relations of electrocardiograms.Heart. 1920;7:353-367. 13) Bär KJ, Koschke M, Berger S, et al. Influence of olanzapine on QT variability and complexity measures of he a rt r a t e in pa ti ents with s chi zophr eni a .J ClinPsychopharmacol. 2008 Dec;28(6):694-8. 14) Erikssen G, Liestøl K, Gullestad L, Haugaa KH, Bendz B, Amlie JP. The terminal part of the QT interval (T peak to T end): a predictor of mortality after acute myocardial infarction. Ann Noninvasive Electrocardiol. 2012;17:85- 94. 15) Morissette P, Hreiche R, Mallet L, Vo D, Knaus EE, Turgeon J. Olanzapine prolongs cardiac repolarization by blocking the rapid component of the delayed rectifier potassium current. J Psychopharmacol. 2007 Sep;21(7):735-41. Epub 2006 Nov 8. 16) Piccirillo G, Moscucci F, D'Alessandro G, et al. Myocardial repolarization dispersion and autonomic nerve activity in a canine experimental acute myocardial infarction model. Heart Rhythm. 2014 Jan;11(1):110-8.
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Details

Primary Language Turkish
Journal Section Research Article
Authors

Osman Can Yontar

Gözde Yontar This is me

Ahmet Tütüncü This is me

Kemal Karaağaç

Erhan Tenekecioğlu This is me

Alper Karakuş This is me

Mehmet Melek This is me

Publication Date December 15, 2014
Submission Date June 5, 2014
Acceptance Date July 9, 2014
Published in Issue Year 2014 Volume: 11 Issue: 3

Cite

Vancouver Yontar OC, Yontar G, Tütüncü A, Karaağaç K, Tenekecioğlu E, Karakuş A, Melek M. Olanzapin Kullanımı QT İntervali Normal Ölçülen Hastalarda T Dalga Tepe- T Dalga Sonlanım Noktaları İntervalini Uzatır. Harran Üniversitesi Tıp Fakültesi Dergisi. 2014;11(3):237-41.

Harran Üniversitesi Tıp Fakültesi Dergisi  / Journal of Harran University Medical Faculty