Terapia anticancerígena y repolarización ventricular
Texto completo:
PDFResumen
Varios fármacos anticancerígenos tienen efectos proarrítmicos al inducir prolongación del intervalo QT (IQT), con riesgo potencial de generar torsión de puntas (TP). Los trastornos de la repolarización ventricular se producen, generalmente, por la interacción de la droga con los canales iónicos de la membrana celular. La marcada prolongación del IQT (> 500 milisegundos) es más frecuente en la terapia molecular dirigida y los reportes de TP y/o muerte súbita arrítmica por prolongación del IQT son escasos. Las alteraciones genéticas, el desbalance hidroelectrolítico, la presencia de cardiopatía estructural y el uso concomitante de otras drogas, tienen efecto coadyuvante en la génesis de la TP. Este artículo revisa, en la terapia anticancerígena, las bases electrofisiológicas de los trastornos de la repolarización ventricular y de la TP, las consideraciones para medir y corregir el IQT, el valor de otras variables electrocardiográficas para evaluar la repolarización ventricular, así como, los fármacos anticancerígenos que con mayor frecuencia prologan el IQT y el seguimiento de los pacientes con estas terapias.
Palabras clave
Referencias
- Chang HM, Okwuosa TM, Scarabelli T, Moudgil R, Yeh ET. Cardiovascular complications of cancer therapy: Best practices in diagnosis, prevention, and management: Part 1. Journal of the American College of Cardiology. 2017;70: 2536–51.
- Livingston RB, Carter SK. Daunomycin (NSC-82151). In: Chemotherapy Fact Sheet. Bethesda, MD: Program Analysis Branch. Chemotherapy, National Cancer Institute. 1970:12–13.
- Guglin M, Aljayeh M, Saiyad S, Ali R, Curtis AB. Introducing a new entity: chemotherapy-induced arrhythmia. Europace. 2009;11:1579–86.
- Buza V, Rajagopalan B, Curtis AB. Cancer treatment-induced arrhythmias: Focus on chemotherapy and targeted therapies. Circulation. Arrhythmia and Electrophysiology. 2017;10. DOI: 10.1161/CIRCEP.117.005443.
- Fradley MG, Moslehi J. QT Prolongation and Oncology Drug Development. Card Electrophysiol Clin. 2015;7: 341–55.
- Coppola C, Rienzo A, Piscopo G, Barbieri A, Arra C, Maurea N. Management of QT prolongation induced by anticancer drugs: target therapy and old agents. Different algorithms for different drugs. Cancer Treat Rev. 2018;63:135-43.
- Roden DM. Predicting drug-induced QT prolongation and torsades de pointes. J Physiol. 2016;594:2459–68.
- Antzelevitch C. Cardiac repolarization. The long and short of it. Europace. 2005;7(Supl 2):S3-9.
- Coronel R, Wilms-Schopman FJ, Opthof T, Janse MJ. Dispersion of repolarization and arrhythmogenesis. Heart Rhythm. 2009;6:537-43.
- Alemán A, Dorantes M. Marcadores electrocardiográficos de arritmias ventriculares malignas. Revista Cubana de Cardiología y Cirugía Cardiovascular. 2012;18:66-71
- Grant AO. Cardiac ion channels. Circ Arrhythm Electrophysiol. 2009;2:185–94.
- Katz AM: Cardiac ion channels. In Katz AM, editor: Physiology of the heart, ed 5, Philadelphia: Lippincott Williams & Wilkins;2011.p.343–68.
- McCauley M, Vallabhajosyula S, Darbar D. Proarrhythmic and Torsadogenic effects of potassium channel blockers in patients. Card Electrophysiol Clin. 2016;8:481–93.
- Vandenberg JI, Perry MD, Perrin MJ, Mann SA, Ke Y, Hill AP. hERG K (+) channels: structure, function, and clinical significance. Physiol Rev. 2012;92:1393–478.
- Buza V, Rajagopalau B, Curtis AB. Cancer treatment induced arrhythmias focus on chemotherapy and targeted therapies. Circ Arrhythm Electrophysiol. 2017;10: e005443. DOI: 10.1161/CIRCEP.117.005443.
- Alexandre J, Molsehi JJ, Bersell KR, Funck-Brentano C, Roden DM, Salemc JE. Anticancer drug-induced cardiac rhythm disorders: Current knowledge and basic underlying mechanisms. Pharmacology Therapeutics. 2018;189:89-103.
- Saenen JB, Vrints CJ. Molecular aspects of the congenital and acquired long QT syndrome: clinical implications, J Mol Cell. 2008;44:633–46.
- Kallergis EM, Goudis CA, Simantirakis EN, Kochiadakis GE, Vardas PE. Mechanisms, risk factors, and management of acquired long QT syndrome: a comprehensive review. Sci World J. 2012;212178. doi:10.1100/2012/212178
- Dorantes M, Bazán M. Repolarización ventricular en la terapia oncológica. CorSalud 2019;11:146-52.
- Moss AJ, Schwartz PJ, Crampton RS, Tzivoni D, Locati EH, MacCluer J et al. The long QT syndrome. Prospective longitudinal study of 328 families. Circulation. 1991;84:1136–44.
- Duan J, Tao J, Zhai M, Li Ch, Zhou N, Lv J. Anticancer drugs-related QTc prolongation, torsade de pointes and sudden death: current evidence and future research perspectives. Oncotarget. 2018; (39): 25738-49.
- Parvez B, Darbar D. Novel ECG markers for ventricular repolarization: is the QT interval obsolete? Heart Rhythm. 2011;8:1044-5.
- Postema PG, De Jong JS, Van der Bilt IA, et al. Accurate electrocardiographic assessment of the QT interval: teach the tangent. Heart Rhythm 2008; 5:1015–8.
- Rautaharju PM, Surawicz B, Gettes LS. AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram: part IV: the ST segment, T and U waves, and the QT interval: a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society: endorsed by the International Society for Computerized Electrocardiology. Circulation 2009;119:e241–50.
- Al-Khatib SM, LaPointe NM, Kramer JM, et al. What clinicians should know about the QT interval. JAMA 2003;289:2120–7.
- Viskin S, Rosovski U, Sands AJ, et al. Inaccurate electrocardiographic interpretation of long QT: the majority of physicians cannot recognize a long QT when they see one. Heart Rhythm 2005;2:569–74.
- Luo S, Michler K, Johnston P, Macfarlane PW. A comparison of commonly used QT correction formulae: the effect of heart rate on the QTc of normal ECGs. J Electrocardiol. 2004;37(spl):S81–90.
- Bogossian H, Frommeyer G, Ninios I, Hasan F, Nguyen QS, Karosiene Z et al. New formula for evaluation of the QT interval in patients with left bundle branch block. Heart Rhythm. 2014;11:2273–7.
- Porta-Sanchez A, Gilbert C, Spears D, Amir E, Chan J, Nanthakumar K et al. Incidence, Diagnosis, and Management of QT Prolongation Induced by Cancer Therapies: A Systematic Review. J Am Heart Assoc.2017;6:e007724. DOI: 10.1161/JAHA.117.007724.
- Goldenberg I, Moss AJ, Zareba W. QT interval: how to measure it and what is “normal”. J Cardiovasc Electrophysiol. 2006;17:333–36.
- Laksman ZW, Krahn AD. Fast and spurious: correcting the QT interval. Heart Rhythm. 2016;13: 536-7.
- Kentta TV, Nearing BD, Porthan K, Tikkanen JT, Vitasalo M, Nieminen MS, et al. Prediction of sudden cardiac death with automated high-through-put analysis of heterogeneity in standard resting 12-lead electrocardiograms. Heart Rhythm. 2016;13:713-20.
- Batchvarov V, Camm AJ. QT dispersion: Clinical applications. Uptpdate.2017;1:1-10. DOI: https://somepomed.org/_articulos/contents/mobipreview.htm?23/23/23921
- Antzelevitch C, Di Diego JM, Argenziano M. Tpeak-Tend as a predictor of ventricular arrhythmogenesis. International Journal of Cardiology. 2017;249:75–6.
- Kirchhof P, Franz MR, Bardai A, Wilde AM. Giant T-U waves precede torsades de pointes in long QT syndrome. A systematic electrocardiographic analysis in patient with acquired and congenital QT prolongation. J Am Coll Cardiol. 2009;54: 143-9.
- Verrier RL, Huikuri H. Tracking interlead hetero-geneity of R-and T-wave morphology to disclose latent risk for sudden cardiac death. Heart Rhythm. 2017;14:1466-75.
- Soignet SL, Frankel SR, Douer D, Tallman MS, Kantarjian H, Calleja E et al. United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia. J Clin Oncol. 2001;19:3852–60.
- Lu HR, Vlaminckx E, Cools F, Gallacher DJ. Direct effects of arsenic trioxide on action potentials in isolated cardiac tissues: importance of the choice of species, type of cardiac tissue and perfusion time. J Pharmacol Toxicol Methods. 2012;66:135–44.
- Chu W, Li C, Qu X, Zhao D, Wang X, Yu X et al. Arsenic induced interstitial myocardial fibrosis reveals a new insight into drug-induced long QT syndrome. Cardiovasc Res. 2012;96:90–98.
- Barbey JT, Pezzullo JC, Soignet SL. Effect of arsenic trioxide on QT interval in patients with advanced malignancies. J Clin Oncol. 2003;21:3609–15.
- Naito K, Kobayashi M, Sahara N, Shigeno K, Nakamura S, Shinjo K et al. Two cases of acute promyelocytic leukemia complicated by torsade de pointes during arsenic trioxide therapy. Int J Hematol. 2006;83:318–23.
- Unnikrishnan D, Dutcher JP, Varshneya N, Lucariello R, Api M, Garl S, Wiernik PH, Chiaramida S. Torsades de pointes in 3 patients with leukemia treated with arsenic trioxide. Blood. 2001;97:1514–16.
- Kishi S, Yoshida A, Yamauchi T, Tsutani H, Lee JD, Nakamura T et al. Torsade de pointes associated with hypokalemia after anthracycline treatment in a patient with acute lymphocytic leukemia. Int J Hematol. 2000;71:172–9.
- Arbel Y, Swartzon M, Justo D. QT prolongation and Torsades de Pointes in patients previously treated with anthracyclines. Anticancer Drugs. 2007;18:493–98.
- Simůnek T, Stérba M, Popelová O, Adamcová M, Hrdina R, Gersl V. Anthracycline-induced cardiotoxicity: overview of studies examining the roles of oxidative stress and free cellular iron. Pharmacol Rep. 2009;61:154–71.
- Milberg P, Fleischer D, Stypmann J, Osada N, Mönnig G, Engelen MA et al. Reduced repolarization reserve due to anthracycline therapy facilitates torsade de pointes induced by IKr blockers. Basic Res Cardiol. 2007;102:42–51.
- Hanna AD, Lam A, Tham S, Dulhunty A F. Adverse effects of doxorubicin and its metabolic product on cardiac RyR2 and SERCA2A. Molecular Pharmacology. 2014;86:438–49.
- Horacek JM, Jakl M, Horackova J, Pudil R, Jebavy L, Maly J. Assessment of anthracycline-induced cardiotoxicity with electrocardiography. Exp Oncol. 2009;31:115–7.
- Galetta F, Franzoni F, Cervetti G, Cecconi N, Carpi A, Petrini M et al. Effect of epirubicin-based chemotherapy and dexrazoxane supplementation on QT dispersion in non-Hodgkin lymphoma patients. Biomed Pharmacother. 2005;59:541–4.
- Oztop I, Gencer M, Okan T, Yaren A, Altekin E, Turker S et al. Evaluation of cardiotoxicity of a combined bolus plus infusional 5-fluorouracil/folinic acid treatment by echocardiography, plasma troponin I level, QT interval and dispersion in patients with gastrointestinal system cancers. Jpn J Clin Oncol. 2004;34:262–8.
- Koca D, Salman T, Unek IT, Oztop I, Ellidokuz H, Eren M et al. Clinical and electrocardiography changes in patients treated with capecitabine. Chemotherapy. 2011;57:381–7.
- Kim HJ, An SH, Cho YH, Kim SY, Lee HG, Yoon SY. Oxaliplatin-induced Torsades de pointes and long QT syndrome in a patient with gastric cancer. Acta Oncol. 2013;52:1223–24.
- Adelsberger H, Quasthoff S, Grosskreutz J, Lepier A, Eckel F, Lersch C. The chemotherapeutic oxaliplatin alters voltage-gated Na (+) channel kinetics on rat sensory neurons. Eur J Pharmacol. 2000;406:25–32.
- El Gebeily G, Fiset C. 4-Hydroxytamoxifen inhibits K (+) currents in mouse ventricular myocytes. Eur J Pharmacol. 2010;629:96–103.
- Asp ML, Martindale JJ, Metzger JM. Direct, differential effects of tamoxifen, 4-hydroxytamoxifen, and raloxifene on cardiac myocyte contractility and calcium handling. PLoS One. 2013;8:e78768.doi:10.1371/journal.pone.0078768
- Kamineni P, Prakasa K, Hasan SP, Akula R, Dawkins F. Cardiotoxicities of paclitaxel in African Americans. J Natl Med Assoc. 2003;95:977–81.
- Yavas O, Yazici M, Eren O, Oyan B. The acute effect of trastuzumab infusion on ECG parameters in metastatic breast cancer patients. Swiss Med Wkly. 2007;137:556–8.
- Tanriverdi O, Meydan N, Barutca S. Long-term effect of trastuzumab on QT dispersion in adjuvant treatment for patients with Her2 receptor positive breast cancer: a pilot study. Med Oncol. 2012;29:3265–71.
- Shah, RR, Morganroth, J. Update on cardiovascular safety of tyrosine kinase inhibitors: With a special focus on QT interval, left ventricular dysfunction and overall risk/benefit. Drug Safety. 2015;38:693–710.
- Lu Z, Wu CY, Jiang YP, et al. Suppression of phosphoinositide 3-kinase signaling and alteration of multiple ion currents in drug-induced long QT syndrome. Sci Transl Med 2012;4:131-50.
- Alexandre J, Salem JE, Funck-Brentano C, Milliez P. Ibrutinib and short coupled variant of torsade de pointes. Blood 2017. doi.org/10.1016/j.pharmthera.2018.04.009.
- Fujii Y, Itoh H, Ohno S, Murayama T, Kurebayashi N, Aok H et al. A type 2 ryanodine receptor variant associated with reduced Ca (2+) release and short coupled torsades de pointes ventricular arrhythmia. Heart Rhythm 2017;14:98–107.
- Shah RR, Morganroth J, Shah DR. Cardiovascular safety of tyrosine kinase inhibitors: with a special focus on cardiac repolarization (QT interval). Drug Saf 2013;36:295–316.
- Ou SH, Tang Y, Polli A, Wilner KD, Schnell P. Factors associated with sinus bradycardia during crizotinib treatment: a retrospective analysis of two large-scale multinational trials (PROFILE 1005 and 1007). Cancer Med. 2016;5:617–22.
- Holkova B, Supko JG, Ames MM, Reid JM, Shapiro GI, Perkins EB et al. A phase I trial of vorinostat and alvocidib in patients with relapsed, refractory, or poor prognosis acute leukemia, or refractory anemia with excess blasts-2. Clin Cancer Res. 2013;19:1873–83.
- O’Connor OA, Horwitz S, Masszi T, Van Hoof A, Brown P, Doorduijn J, Hess G et al. Belinostat in patients with relapsed or refractory peripheral T-cell lymphoma: results of the pivotal phase II BELIEF (CLN-19) study. J Clin Oncol. 2015;33:2492–9.
- Sharma S, Witteveen PO, Lolkema MP, Hess D, Gelderblom H, Hussain SA et al. A phase I, open-label, multicenter study to evaluate the pharmacokinetics and safety of oral panobinostat in patients with advanced solid tumors and varying degrees of renal function. Cancer Chemother Pharmacol. 2015;75:87–95.
- Whittaker SJ, Demierre MF, Kim EJ, Rook AH, Lerner A, Duvic M et al. Final results from a multicenter, international, pivotal study of romidepsin in refractory cutaneous T-cell lymphoma. J Clin Oncol. 2010;28:4485–91.
- Dahut WL, Madan RA, Karakunnel JJ, Adelberg D, Gulley JL, Turkbey IB et al. Phase II clinical trial of cediranib in patients with metastatic castration-resistant prostate cancer. BJU Int. 2013;111:1269–80.
- McKeage MJ, Fong P, Jeffery M, Baguley BC, Kestell P, Ravic M et al. 5,6-dimethylxanthenone-4-acetic acid in the treatment of refractory tumors: a phase I safety study of a vascular disrupting agent. Clin Cancer Res. 2006;12:1776–84.
- Ibrahim MA, Do DV, Sepah YJ, Shah SM, Van Anden E, Hafiz G et al. Vascular disrupting agent for neovascular age related macular degeneration: a pilot study of the safety and efficacy of intravenous combretastatin A-4 phosphate. BMC Pharmacol Toxicol. 2013;14:7.
- Cooney MM, Radivoyevitch T, Dowlati A, Overmoyer B, Levitan N, Robertson K et al. Cardiovascular safety profile of combretastatin a4 phosphate in a single-dose phase I study in patients with advanced cancer. Clin Cancer Res. 2004;10:96–100.
- Borad MJ, Soman AD, Benjamin M, Casa D, Tembe WD, Piper BF et al. Effect of selection of QTc formula on eligibility of cancer patients for phase I clinical trials. Invest New Drugs. 2013;31:1056–65.
- Weissler-Snir A, Gollob MH, Chauhan V, Care M, Spears DA. Evaluation of prolonged QT interval: structural heart disease mimicking long QT syndrome. Pacing Clin Electrophysiol. 2017;40:417–24.
- Tisdale JE. Drug-induced QT interval prolongation and torsades de pointes: role of the pharmacist in risk assessment, prevention and management. Can Pharm J (Ott). 2016;149:139–52.
Enlaces refback
- No hay ningún enlace refback.
Copyright (c) 2020 Marleny Cruz Cardentey, Alain Gutierrez Lopez, Ana Mengana Betancourt
![Licencia de Creative Commons](https://i.creativecommons.org/l/by-nc/4.0/88x31.png)
Esta obra está bajo una licencia de Creative Commons Reconocimiento-NoComercial 4.0 Internacional.