Prospective examination of Tp-e interval and Tp-e/QT ratio in breast cancer patients receiving radiation therapy

Year 2023, Volume: 4 Issue: 4, 362 - 367, 30.08.2023

Necla Gürdal , Gizem Cosgun Binnur Donmez Yılmaz Ahmet Gurdal

https://doi.org/10.47582/jompac.1302914

Abstract

Aims: The aim of this prospective study was to investigate ventricular repolarization using the Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio in breast cancer patients treated with adjuvant radiotherapy(RT) following systemic chemotherapy.
Methods: The study was designed as a national, single-center prospective study. According to the treatment protocol, electrocardiograms (ECGs) were taken from all patients on their first and last days of RT. Tp-e intervals, Tp-e/QT ratios, and Tp-e/QTc ratios were calculated based on the ECG recordings. The heart doses due to radiation exposure were examined with mean heart dose, V5, V10,V20, and V30 values.
Results: 51 postsurgical patients, who were all treated with AC followed by weekly paclitaxel and had an indication for adjuvant RT, were included in the study. The mean heart dose was observed as median 205 cGy, and the V30 value was 0.01%. When ECG measurements were analyzed, statistically significant increases were observed in Tp-e interval (p<0.001), QT interval (p=0.007), Tp-e/QT ratio (p<0.001), and Tp-e/QTc ratio (p<0.001) at the end of RT. Additionally, positive correlations were observed between mean heart dose and post RT Tp-e (r= 0.770,p<0.01) and Tp-e/QTc ratio (r = 0.778,p<0.01)
Conclusion: When compared to before RT, statistically significant prolongation of Tp-e interval and QT interval and increases in Tp-e/QT ratio and Tp-e/QTc ratio were detected which are thought to be predictive for ventricular repolarization process and ventricular rhythm disorders. In addition, the mean heart dose was positively correlated with Tp-e interval and Tp-e/QTc ratio.

Keywords

Radiotherapy, cardiac toxicity, breast cancer, Tp-e interval, Tp-e/QT ratio, Tp-e/QTc ratio

Supporting Institution

none

Project Number

none

Thanks

none

Meme kanseri nedeniyle radyoterapi uygulanan hastalarda Tp-e aralığı ve Tp-e/QT oranının prospektif olarak incelenmesi

Abstract

Amaç:
Prospektif olarak dizayn edilen bu çalışmada amacımız sistemik kemoterapiyi takiben adjuvan radyoterapi (RT) ile tedavi edilen meme kanseri hastalarında Tp-e aralığı, Tp-e/QT oranı ve Tp-e/QTc oranını kullanarak ventriküler repolarizasyonu araştırmaktır.
Metod:
Çalışma ulusal, tek merkezli prospektif bir çalışma olarak tasarlandı. Tedavi protokolüne göre tüm hastalardan RT'nin ilk ve son günlerinde elektrokardiyogramlar (EKG) çekildi. EKG kayıtlarından Tp-e aralıkları, Tp-e/QT oranları ve Tp-e/QTc oranları hesaplandı. Radyasyon maruziyetine bağlı kalp dozları kalp mean doz, V5, V10,V20 ve V30 değerleri ile incelendi.
Bulgular:
Postoperatif sistemik tedavi sonrası adjuvan RT endikasyonu olan 51 hasta çalışmaya dahil edildi. Ortalama kalp dozu ortanca 205 cGy olarak gözlendi ve V30 değeri %0,01 idi. EKG ölçümleri incelendiğinde RT öncesine göre Tp-e aralığı (p<0,001), QT aralığı (p=0,007), Tp-e/QT oranı (p<0,001) ve Tp-e/QTc oranında (p<0,001) istatistiksel olarak anlamlı artışlar gözlendi. Ek olarak, ortalama kalp dozu ile RT sonrası Tp-e (r= 0.770,p<0.01) ve Tp-e/QTc oranı (r= 0.778,p<0.01) arasında pozitif korelasyonlar gözlendi.
Sonuç:
Ventriküler repolarizasyon süreci ve ventriküler ritim bozuklukları için prediktif olduğu düşünülen Tp-e intervali ve QT intervalinde RT öncesine göre istatistiksel olarak anlamlı uzama ve Tp-e/QT oranı ve Tp-e/QTc oranında artış saptandı. Ek olarak, ortalama kalp dozu ile Tp-e aralığı ve Tp-e/QTc oranı arasında pozitif korelasyon gözlendi.

Keywords

Meme Kanseri, Radyoterapi, Tp-e Aralığı, Kardiyak toksisite, Tp-e/QT Oranı

Project Number

none

References

• Yeboa DN, Evans SB. Contemporary breast radiotherapy and cardiac toxicity. Semin Radiat Oncol. 2016;26(1):71-78. doi: 10.1016/j.semradonc.2015.09.003
• Demissei BG, Finkelman BS, Hubbard RA, et al. Cardiovascular function phenotypes in response to cardiotoxic breast cancer therapy. J Am Coll Cardiol. 2019;73(2):248-249. doi: 10.1016/jjacc.2018.10.057
• Coleman CN. International Conference on Translational Research and Preclinical Strategies in Radio-Oncology (ICTR)--conference summary. Int J Radiat Oncol Biol Phys. 2001;49(2):301-309. doi: 10.1016/s0360-3016(00)01521-2
• Munro TR. The relative radiosensitivity of the nucleus and cytoplasm of Chinese hamster fibroblasts. Radiat Res. 1970 Jun;42(3):451-470.
• Dewey WC, Ling CC, Meyn RE. Radiation-induced apoptosis: relevance to radiotherapy. Int J Radiat Oncol Biol Phys. 1995;33(4):781-796. doi: 10.1016/0360-3016(95)00214-8
• Castro-Torres Y, Carmona-Puerta R, Katholi RE. Ventricular repolarization markers for predicting malignant arrhythmias in clinical practice. World J Clin Cases. 2015;3(8):705-720. doi: 10.12998/ wjcc.v3.i8.705.
• 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;10:1124-1152. doi: 10.1111/j.1540-8167.1999.tb00287.x
• Xia Y, Liang Y, Kongstad O, et al. Tpeak-Tend interval as an index of global dispersion of ventricular repolarization: evaluations using monophasic action potential mapping of the epi- and endocardium in swine. J Interv Card Electrophysiol. 2005;14: 9-87. doi: 10.1007/s 10840-005-4592-4
• Errahmani MY, Locquet M, Spoor D, et al. association between cardiac radiation exposure and the risk of arrhythmia in breast cancer patients treated with radiotherapy: a case–control study. Front Oncol. 12:892882. doi: 10.3389/fonc.2022.892882
• Kors Jan A, Henk J. Ritsema van Eck, Gerard van Herpen. The meaning of the Tp-Te interval and its diagnostic value. J Electrocardiol. 2008;41(6):575-580.
• Castro Hevia J, Antzelevitch C, Tornés Bárzaga 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(9):1828-1834.
• Demirtas D, Sumbul HE, Bulut A, et al. Tp-e interval, Tp-e/QT and Tp-e/QTc ratio in hypertensive patients with primary aldosteronism. Clin Exp Hypertens. 2020;42(1):93-98. doi: 10.1080/ 10641963.2019.1632341
• Kongstad O, Xia Y, Liang Y, et al. Epicardial and endocardial dispersion of ventricular repolarization. A study of monophasic action potential mapping in healthy pigs. Scand Cardiovasc J. 2005;39(6):342-347. doi: 10.1080/14017430500188744
• Gheorghe ACD, Ciobanu A, Hodorogea AS, et al. Evolution of electrocardiographic repolarization parameters during antiandrogen therapy in patients with prostate cancer and hypogonadism. Cardiovasc Toxicol. 2020;20(4):390-400. doi: 10.1007/s12012-020-09566-6
• Lee MS, Liu DW, Hung SK, et al. Emerging challenges of radiation-associated cardiovascular dysfunction (RACVD) in modern radiation oncology: clinical practice, bench investigation, and multidisciplinary care. Front Cardiovasc Med. 2020;7:16. doi: 10.3389/fcvm.2020.00016
• Darby SC, Ewertz M, McGale P, et al. Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med. 2013;368(11):987-98. doi: 10.1056/ NEJMoa1209825
• Wright, Jean L. Toxicities of radiation treatment for breast cancer: risks and management strategies. Springer, 2019.
• Taylor CW, Kirby AM. Cardiac Side-effects from breast cancer radiotherapy. Clin Oncol (R Coll Radiol). 2015;27(11):621-629. doi: 10.1016/j.clon.2015.06.007
• Tse G, Gong M, Wong WT, et al. The Tpeak - Tend interval as an electrocardiographic risk marker of arrhythmic and mortality outcomes: a systematic review and meta-analysis. Heart Rhythm. 2017;14(8):1131-1137. doi: 10.1016/j.hrthm.2017.05.031
• Larsen RL, Jakacki RI, Vetter VL, et al. Electrocardiographic changes and arrhythmias after cancer therapy in children and young adults. Am J Cardiol. 1992;70(1):73-77. doi: 10.1016/0002-9149(92)91393-i
• Herrmann J. Adverse cardiac effects of cancer therapies: cardiotoxicity and arrhythmia. Nat Rev Cardiol. 2020;17(8):474-502. doi: 10.1038/s41569-020-0348-1
• Chen C, Heusch A, Donner B, et al. Present risk of anthracycline or radiation-induced cardiac sequelae following therapy of malignancies in children and adolescents. Klin Padiatr. 2009; 221(3):162-166. doi: 10.1055/s-0029-120722
• Teng AE, Noor B, Ajijola OA, Yang EH. Chemotherapy and radiation-associated cardiac autonomic dysfunction. Curr Oncol Rep. 2021;23(2):14. doi: 10.1007/s11912-020-01013-7
• Gomez DR, Yusuf SW, Munsell MF, et al. Prospective exploratory analysis of cardiac biomarkers and electrocardiogram abnormalities in patients receiving thoracic radiation therapy with high-dose heart exposure. J Thorac Oncol. 2014;9(10):1554-1460. doi: 10.1097/JTO.0000000000000306
• Zamorano JL, Lancellotti P, Rodriguez Muñoz D, et al. ESC Scientific Document Group. 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines:  The Task Force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC). Eur Heart J. 2016;37(36):2768-2801. doi: 10.1093/eurheartj/ehw211
• Caron J, Nohria A. Cardiac toxicity from breast cancer treatment: can we avoid this? Curr Oncol Rep. 2018;20(8):61. doi: 10.1007/s11912-018-0710-1