Akut koroner sendromlu hastalarda 12 ledli elektrokardiyografi yeni parametreleri kullanılarak klaritromisinin aritmik etkilerinin değerlendirilmesi

Year 2019, , 324 - 328, 30.09.2019

Hakan Göçer Erdem Türkyılmaz Ahmet Ünlü Ahmet Barış Durukan

https://doi.org/10.18663/tjcl.559313

Cited By: 1

Abstract

Amaç: Klaritromisin yaygın
olarak kullanılan kardiyak aritmik etkileri olan, QT uzaması ile torsade de
point’ e sebep olan mikrolit antibiyotiktir. Eskiden akut koroner sendrom
tedavisinde de kullanılmıştır. Bu çalışmanın amacı akut koroner sendromlu hastalarda
kısa dönem klaritromisin kullanımının aritmik riski gösteren yeni EKG parametreleri
üzerine olan etkisinin gösterilmesidir.

Gereç ve Yöntemler: 2002
yılında yürütülen akut koroner sendromu hastalarda 1000 mg/gün bir hafta
klaritromisin tedavisinin endotel disfonksiyonu ve QT dispersiyonu üzerine olan
etkilerinin gösterildiği çalışmanın EKG’leri geriye dönük olarak yeniden yeni
EKG parametreleri için analiz edilmiştir. Atriyal ve ventriküler artmış aritmi
riskini gösteren bu yeni EKG parametreleri; Tp–e interval, Tp-e/QTc oranı,
maximum QTc, minimum QTc, QTc dispersionu, P-maximum, P-minimum ve P dalga
dispersiyonu incelenmiştir.

Bulgular: 40 hasta çalışmaya
dahil edilmiştir.  20 hasta klaritromisin
tedavisi almış yirmisi almamıştır. 
Klaritromisin tedavisi alan gurupta ortalama yaş 53,2 ± 8,0’dır. Kontrol
gurubunda 58,9 ± 11,6’dır. Demografik karakterler ve tedavi öncesi EKG
parametreleri her iki gurup için benzerdir ve karşılaştırılabilir. Fakat tedavi
sonrası max QTc, min QTc, QTc dispersiyonu, Tp-e interval, TP-e/QTc, Pmax, Pmin
ve P dalga dispersiyonu istatistiksel olarak anlamlı bir şekilde klaritromisin
ile tedavi edilen gurupta kontrol gurubuna göre yüksektir (p<0.05, her bir
parametre için).

Sonuç:  Klaritromisin tedavisi QT parametreleri yanı
sıra yeni EKG parametreleri olan ve artmış ventriküler aritmi riskini gösteren Tp–e interval ve Tp-e/QTc oranını etkiler. Bununla
birlikte atrial fibrilasyon artmış risk faktörü olan P-dalga parametreleri ve
dispersiyonunu da etkiler. Tüm bu sonuçlardan akut koroner sendromlarda
klaritromisin tedavisinin ventriküler ve atriyal aritmik riski arttırdığı
çıkarılabilir.

Keywords

klaritromisin, aritmiler, kardiyak, akut koroner sendrom

Evaluation of arrhythmic effects of clarithromycin usage in patients with acute coronary syndrome via new parameters of 12 lead electrocardiography

Abstract

Aim: Clarithromycin is a widely used
macrolide antibiotic with arrhythmic effects causing torsade de pointes by
elongating QT interval. Clarithromycin was used to treat acute coronary syndrome. we aimed to determine the
acute effects of short-term clarithromycin treatment on novel ECG parameters in
patients with acute coronary syndrome.

Material and Methods: The study we conducted in
2002 evaluated the effects of clarithromycin on endothelial functions and QTdispersion.
We recently analyzed these patients’ ECGs performed before and one week after
of 1000 mg/day clarithromycin treatment. We analyzed newly recognized parameters; Tp–e interval, Tp-e/QTc ratio,
maximum QTc, minimum QTc, QTc dispersion values, P-maximum, P-minimum and P-wave
dispersion to indicate the
risk of atrial and ventricular arrhythmias.

Results: There were 40 patients included where 20 were treated with
clarithromycin and 20 not. In the clarithromycin group, mean age of the
patients was 53.2±8.0 and in control group 58.9±11.6. Demographic characteristics of patients were
similar. All ECG parameters were comparable prior to clarithromycin treatment.
However, following therapy, all parameters including max QTc, min QTc, QTc
dispersion, Tp-e interval, TP-e/QTc, Pmax, Pmin, and P-wave dispersion were
statistically significantly higher in clarithromycin treated group (p<0.05
for each).

Conclusion:Clarithromycin treatment not only affects QT
parameters but also novel ECG parameters Tp–e interval and Tp-e/QTc
ratio showing the
risk of ventricular arrhythmias. It also affects P-wave parameters and dispersion
that shows risk of atrial arrhythmias. We may conclude that clarithromycin
treatment increases both ventricular and atrial arrhythmic risk during acute
coronary syndromes.

Keywords

clarithromycin, arrhythmias, cardiac, acute coronary syndrome

References

• 1. Gysel M, Vieweg W, Hasnain M, Hancox J, Kunanithy V, Baranchuk A. Torsades de pointesfollowing clarithromycin treatment. Expert Rev Cardiovascular Ther 2013; 11: 1485-93.
• 2. Kaab S, Crawford D, Sinner M et al. A large candidate gene survey identifies the KCNE1 D85N polymorphism as a possible modulator of drug-induced torsades de pointes . Circ Cardiovasc Genet 2012; 5: 91-99.
• 3. Hancox J, McPate M, El Harchi A, Zhang Y. The hERG potassium channel and hERG screening for drug-induced torsades de pointes. Pharmacol Ther 2008; 119: 118-32.
• 4. Abbott G, Sesti F, Splawski I et al. MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia. Cell 1999; 97: 175-87.
• 5. Göçer H, Şekuri, C, Bayturan Ö al. Akut Koroner Sendromlarda Kısa Süreli Klaritromisin Tedavisinin Akıma Bağlı Vazodilatasyon ve QT Dispersiyonu Üzerine Ektisi. Hipokrat Kardiyoloji Dergisi 2004; 31: 113- 17.
• 6. Vieweg W, Hancox J, Hasnain M, Koneru J, Gysel M, Baranchuk A. Clarithromycin, QTc interval prolongation and torsades de pointes: the need to study case reports. Ther Adv Infect Dis 2013; 1: 121-38.
• 7. Bril F, Gonzalez C, Di Girolamo G. Antimicrobial agents-associated with QT interval prolongation. Curr Drug Saf 2010; 5: 85-92.
• 8. Kirbas A, Kirbas O, Daglar K et al. Novel indexes of arrhythmogenesis in preeclampsia:QT dispersion, Tp-e interval, and Tp-e/QT ratio. Pregnancy Hypertens 2016; 6: 38-41.
• 9. Tukek T, Yildiz P, Akkaya V et al. Factors associated with the development of atrial fibrillation in COPD patients: the role of P-wave dispersion. Ann Noninvasive Electrocardiol 2002; 7: 222–27.
• 10. Kose S, Aytemir K, Sade E et al. Detection of patients with hypertrophic cardiomyopathy at risk for paroxysmal atrial fibrillation during sinus rhythm by P-wave dispersion. Clin Cardiol 2003; 26: 431- 34.
• 11. Malik M, Batchvarov VN. Measurement, interpretation and clinical potential of QT dispersion. J Am Coll Cardiol 2000; 36: 1749-66.
• 12. Castro Hevia J, Antzelevitch C, Tornes Barzaga 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 Coll Cardiol 2006; 47: 1828-34.
• 13. Braschi A, Abrignani MG, Francavilla VC, Abrignani V, Francavilla G. Age- and sex-based reference ranges for non-invasive ventricular repolarisation parameters. Int J Clin Pract 2017; 71: 12949.
• 14. Lin L, Horigome H, Nishigami N, Ohno S, Horie M, Sumazaki R. Drug-induced QT-interval prolongation and recurrent torsade de pointes in a child with heterotaxy syndrome and KCNE1 D85N polymorphism. J Electrocardiol 2012; 45: 770-73.
• 15.Li DQ, Kim R, McArthur E et al. Risk of adverse events among older adults following co-prescription of clarithromycin and statins not metabolized by cytochrome P450 3A4. CMAJ 2015; 187: 174-80.
• 16.Wong AYS, Root A, Douglas IJ, Chui CS, Chan EW, Ghebremichael-Weldeselassie Yet al. Cardiovascular outcomes associated with use ofclarithromycin: population based study. BMJ 2016; 352.
• 17. Chou HW, Wang JL, Chang CH, Lai CL, Lai MS, Chan KA. Risks of cardiac arrhythmia and mortality among patients using new‐generation macrolides, fluoroquinolones, and beta‐lactam/beta‐lactamase inhibitors: a Taiwanese nationwide study. Clin Infect Dis 2015; 60: 566-77.
• 18. Trac MH, McArthur E, Jandoc R et al. Macrolide antibiotics and the risk of ventricular arrhythmia in older adults. Can Med Assoc J 2016; 188: 120–29.
• 19. Elming H, Holm E, Jun L et al. The prognostic value of the QT interval and QT interval dispersion in all-cause and cardiac mortality and morbidity in a population of Danish citizens. Eur Heart J 1998; 19: 1391-400.
• 20. Castro Hevia J, Antzelevitch C, Tornes Barzaga F et al. TpeakTend and Tpeak-Tend dispersion as risk factors for ventricular tachycardia/ventricular fibrillation in patients with the Brugada syndrome. J Am Coll Cardiol 2006; 47: 1828-34.
• 21. Castro-Torres Y, Carmona-Puerta R, Katholi RE. Ventricular repolarization markers for predicting malignant arrhythmias in clinical practice. World J Clin Cases 2015; 3: 705-20.
• 22. Dilaveris PE, Gialafos JE. P-wave dispersion: a novel predictor of paroxysmal atrial fibrillation. Ann Noninvasive Electrocardiol 2001; 6: 159-65.
• 23.Cercek B, Shah PK, Noc M et al. Effect of short-term treatment with azithromycin on recurrent ischaemic events in patients with acute coronary syndrome in the Azithromycin in Acute Coronary Syndrome (AZACS) trial: a randomised controlled trial. Lancet 2003; 361: 809-13.
• 24. Kutlin A, Roblin MP, Hammerschla, Dunne M et al. Azithromycin for the secondary prevention of coronary heart disease events. The WIZARD study: A randomized controlled trial. JAMA 2003; 290: 1459-66.
• 25. Gurfinkel E, Bozovich G, Beck E, Testa E, Livellara B, Mautner B. Treatment with the antibiotic roxithromycin in patients with acute non-Q-wave coronary syndromes. The final report of the ROXIS study. Eur Heart J 1999; 20: 121-27.