BibTex RIS Cite

Evaluation of Doxorubicin Cardiomyopathy by Signal Averaged Electrocardiography

Year 2013, Volume: 38 Issue: 2, 241 - 249, 01.06.2013

Abstract

BACKGROUND: Signal-averaged electrocardiography detects low-amplitude signals designated as late potentials which are strongly related to myocardial damage. We aimed to search for the possible relation between the myocardial effects of doxorubicin and signal-averaged electrocardiographic parameters. METHODS: Fortyeight patients who received doxorubicin included chemotherapy were enrolled. Signal-averaged electrocardiographic parameters were detected by using 3 parameters; filtered QRS (fQRS), the square root of the voltage obtained during the last 40 milliseconds of the duration of fQRS (RMS40), the duration starting from the last 40 miliseconds of fQRS till the decrease of voltage under 40 microvolts. (HFLA40). Ejection fractions of the patients were measured by echocardiographic evaluation. RESULTS: Median age was 44 (27-70) years. Mean cumulative doxorubicin dosage was 475.56±98.45 mg. Mean values of the measured signal-averaged electrocardiographic parameters were as follows; fQRS: 78.27±10.74 miliseconds, RMS40:115.10±50.23 and HFLA was 21.95±8.39 microvolts . The doses of doxorubicin showed a positive correlation with fQRS (r=0.28, p=0.02) and a negative correlation with RMS40 (r=-.31,p=0.03). There was no correlation between the doxorubicin dosage and the ejection fraction of the patients (r=.18, p=0.22). CONCLUSION: Our results suggested that significant correlations are present between fQRS and RMS40 and cumulative doxorubicin dosages. Therefore, signal-averaged electrocardiographic parameters may be of value for predicting the prognosis of the patients who have received doxorubicin included chemotherapy.

References

  • Shan K., Lincoff AM, Young, J.B. Anthracycline-induced cardiotoxicity. Ann Intern Med. 1996; 1251: 47-58.
  • Lipshultz SE, Colan SD, Gelber RD, Perez-Atayde AR, Sallan SE, Sanders SP. Late cardiac effects of doxorubicin therapy for acute lymphoblastic leukemia in childhood. N Engl J Med. 1991; 324: 808-15.
  • Yeung ST, Yoong C, Spink J, Galbraith A, Smith PJ. Functional myocardial impairment in children treated with anthracyclines for cancer. Lancet. 1991; 337: 816
  • Ferreira AL, MatsubaraLS, Matsubara BB. Anthracycline-induced cardiotoxicity. Cardiovasc Hematol Agents Med Chem. 2008; 6:278-81, Rajagopalan S, Politi PM, Sinha BK, Myers CE. Adriamycin-induced free radical formation in the perfused rat heart: implications for cardiotoxicity. Cancer Res. 1988; 48:4766-9.
  • Schimmel KJ, Richel DJ, van den Brink RB, Guchelaar HJ. Cardiotoxicity of cytotoxic drugs. Cancer Treat Rev. 2004; 30:181-91.
  • Bristow MR, MasonJW, Billingham ME, Daniels JR. Doxorubicin cardiomyopathy: evaluation by phonocardiography, endomyocardial biopsy, and cardiac catheterization. Ann Intern Med. 1978;88:168-75.
  • Corapcioglu F, Sarper N, Berk F, Sahin T, Zengin E, Demir H. Evaluation of anthracycline-induced early left ventricular dysfunction in children with cancer: a comparative study with echocardiography and multigated radionuclide angiography. Pediatr Hematol Oncol 2006;23:71-80.
  • Simson M. Use of signals in the terminal QRS complex to identify patients with ventricular tachycardia after myocardial infarction. Circulation. 1981;64: 235-242.
  • Isner JM, Ferrans VJ, Cohen SR, Witkind BG, Virmani R, Beck JR. Clinical and morphologic cardiac findings after anthracycline chemotherapy: Analysis of 64 patients studied at necropsy. The American Journal of Cardiology. 1983;51: 1167-74.
  • Mortensen SA, Olsen HS, Baandrup U. Chronic anthracycline cardiotoxicity: haemodynamic and histopathological manifestations suggesting a restrictive endomyocardial disease. Br Heart J. 1986;55:274-82.
  • Gardner P, Ursell P, Fenoglio J Jr, Wit, A. Electrophysiologic and anatomic basis for fractionated electrograms recorded from healed myocardial infarcts. Circulation. 1985; 72:596-611.
  • Simson MB, Untereker WJ, Spielman SR, Horowitz LN, Marcus NH, Falcone RA. Relation between late potentials on the body surface and directly recorded fragmented electrograms in patients with ventricular tachycardia. The American Journal of Cardiology. 1983;51:105-12.
  • Bender R S. ECG left ventricular Hypertrophy Detection and Prognosis, in Topics in Structural Heart Disease, L.B.B. Basson T.C, Editor. p. 54. Gomes JA, Cain, ME, Buxton AE, Josephson ME, Lee KL, Hafley GE. Prediction of long-term outcomes by signal-averaged electrocardiography in patients with unsustained ventricular tachycardia, coronary artery disease, and left ventricular dysfunction. Circulation. 2001; 104:436-41.
  • Fauchier L, Babuty D, Cosnay P, Poret P, Rouesnel P, Fauchier JP. Long-term prognostic value of time domain analysis of signal-averaged electrocardiography in idiopathic dilated cardiomyopathy. Am J Cardiol. 2000;85: 618-23.
  • Larsen RL, Jakacki RI, Vetter VL, Meadows AT, Silber JH, Barber G. Electrocardiographic changes and arrhythmias after cancer therapy in children and young adults. Am J Cardiol. 1992;70: 73-7.
  • Steinherz LJ, Steinherz PG, and Tan C. Cardiac failure and dysrhythmias 6-19 years after anthracycline therapy: a series of 15 patients. Med Pediatr Oncol. 1995;24: 352-61.
  • Michaelides AP, Dilaveris PE, Psomadaki ZD, Richter DJ, Andrikopoulos GK, Pitsilides N, et al. QRS prolongation on the signal-averaged electrocardiogram versus ST-segment changes on the 12-lead electrocardiogram: which is the most sensitive electrocardiographic marker of myocardial ischemia? Clin Cardiol. 1999;22: 403-8.
  • Redfield MM, Rodeheffer RJ, Jacobsen SJ, Mahoney DW, Bailey KR, Burnett JC Jr. Plasma brain natriuretic peptide concentration: impact of age and gender. J Am Coll Cardiol. 2002;40: 976-82.
  • Wang TJ, Larson MG, Levy D, Leip EP, Benjamin EJ, Wilson PW, et al. Impact of age and sex on plasma natriuretic peptide levels in healthy adults. The American journal of cardiology. 2002;90: 254-58.
  • Mehra MR, Uber PA, Park MH, Scott RL, Ventura HO, Harris BC, et al. Obesity and suppressed B-type natriuretic peptide levels in heart failure. J Am Coll Cardiol. 2004;43: 1590-5.
  • O'Hanlon R, O'Shea P, Ledwidge M, O'Loughlin C, Lange S, Conlon C, et al. The Biologic Variability of BType Natriuretic Peptide and N-Terminal Pro-B-Type Natriuretic Peptide in Stable Heart Failure Patients. Journal of cardiac failure. 2007;13: 50-5.
  • Nousiainen T, Jantunen E, Vanninen E, Remes J, Vuolteenaho O, Hartikainen J. Natriuretic peptides as markers of cardiotoxicity during doxorubicin treatment for non-Hodgkin's lymphoma. Eur J Haematol. 1999;62:135-41.
  • Kremer LC, Bastiaansen BA, Offringa M, Lam J, van Straalen JP, de Winter RJ, et al. Troponin T in the first 24 hours after the administration of chemotherapy and the detection of myocardial damage in children. Eur J Cancer. 2002;38:686-9.
  • Fink FM, Genser N, Fink C, Falk M, Mair J, MaurerDengg K, et al. Cardiac troponin T and creatine kinase MB mass concentrations in children receiving anthracycline chemotherapy. Med Pediatr Oncol. 1995;25: 185-9.
  • Wu AH and Lane P. Metaanalysis in clinical chemistry: validation of cardiac troponin T as a marker for ischemic heart diseases. Clin Chem. 1995;41:1228-33.
  • Friedman MA, Bozdech MJ, Billingham ME, Rider AK. Doxorubicin cardiotoxicity. Serial endomyocardial biopsies and systolic time intervals. JAMA. 1978;240:1603-6.
  • Sorensen K, Levitt GA, Bull C, Dorup I, Sullivan ID. Late anthracycline cardiotoxicity after childhood cancer: a prospective longitudinal study. Cancer. 2003;97:1991
  • Limat S, Demesmay K, Voillat L, Bernard Y, Deconinck E, Brion A, et al. Early cardiotoxicity of the CHOP regimen in aggressive non-Hodgkin's lymphoma. Ann Oncol. 2003;14: 277-81.
  • Lipshultz SE, Lipsitz SR, Mone SM, Goorin AM, Sallan SE, Sanders SP, et al. Female sex and drug dose as risk factors for late cardiotoxic effects of doxorubicin therapy for childhood cancer. N Engl J Med. 1995;332: 1738Von Hoff DD, Layard MW, Basa P, Davis HL Jr, Von
  • Hoff AL, Rozencweig M, et al. Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med. 1979;91:710-7.
  • Henderson IC, Allegra JC, Woodcock T, Wolff S, Bryan S, Cartwright K, et al. Randomized clinical trial comparing mitoxantrone with doxorubicin in previously treated patients with metastatic breast cancer. J Clin Oncol. 1989;7: 560-71.
  • Ewer MS, Ali MK, Mackay B, Wallace S, Valdivieso M, Legha SS, et al. A comparison of cardiac biopsy grades and ejection fraction estimations in patients receiving Adriamycin. J Clin Oncol. 1984;2: 112-7.
  • Mason JW, Bristow MR, Billingham ME, Daniels JR. Invasive and noninvasive methods of assessing adriamycin cardiotoxic effects in man: superiority of histopathologic assessment using endomyocardial biopsy. Cancer Treat Rep. 1978;62: 857-64.
  • Bristow MR, Mason JW, Billingham ME, Daniels JR. Dose-effect and structure-function relationships in doxorubicin cardiomyopathy. Am Heart J. 1981;102:709
  • Torti FM, Bristow MR, Howes AE, Aston D, Stockdale FE, Carter SK, et al. Reduced cardiotoxicity of doxorubicin delivered on a weekly schedule. Assessment by endomyocardial biopsy. Ann Intern Med. 1983;99: 745-9.
  • Yazışma Adresi / Address for Correspondence: Dr. Didem Arslan Taş Adana Numune Training and Research Hospital İnternal Medicine and Rheumatology Department ADANA e-mail: arslan_didem@yahoo.com Tel: 00 90 554 7547364 Fax: 00 90 322 3386373 geliş tarihi/received :09.08.2012 kabul tarihi/accepted:05.10.2012 .

Doksorubisin Kardiyotoksisitesinin Sinyal Ortalamali Elektrokardiyografi İle Değerlendirilmesi

Year 2013, Volume: 38 Issue: 2, 241 - 249, 01.06.2013

Abstract

AMAÇ: Sinyal ortalamalı elektrokardiyografi miyokardiyal hasarla oldukça ilişkili olan geç potansiyeller olarak adlandırlan düşük amplitüdlü sinyalleri saptar. Bu çalışmadaki amacımız, doksorubisinin miyokardiyal yan etkileri ile sinyal ortalamalı elektrokardiyogram arasındaki potansiyel ilişkiyi araştırmaktır. YÖNTEM: Doksorubisin içeren kemoterapi alan 48 hasta çalışmaya dahil edildi. Sinyal ortalamalı elektrokardiyografi, 3 parametre kullanılarak ölçüldü: filtrelenmiş QRS (fQRS), fQRS süresinin son 40 milisaniyesi boyunca saptanan voltajın karekökü (RMS40), fQRS in son 40 milisaniyesinden başlayarak 40μV altına düştükten sonraki geçen süre (HFLA40). Hastaların ejeksiyon fraksiyonları, ekokardiyografi ile ölçüldü. SONUÇLAR: Ortalama yaş 44 (27-70) yıl idi. Ortalama kümülatif doksorubisin dozu 475.56±98.45 mg idi. Ölçülen sinyal ortalamalı elektrokardiyografik parametrelerin ortalama süreleri şöyleydi: fQRS:78.27±10.74 milisaniye, RMS40: 115.10±50.23 ve HFLA: 21.95±8.39 mikrovolt idi. Doksorubisin dozu ile fQRS arasında pozitif korelasyon saptanırken (r=0.28, p=0.02), RMS40 arasında negatif korelasyon mevcuttu (r=-.31,p=0.03). Doksorubisin dozu ile ejeksiyon fraksiyonları arasında korelasyon saptanmadı (r=.18, p=0.22). TARTIŞMA: Bulgularımız, kümülatif doksorubisin dozları ile fQRS ve RMS40 arasında anlamlı korelasyon olduğunu düşündürmektedir. Bu yüzden sinyal ortalamalı elektrokardiyografik parametreler doksorubisin içeren tedaviler alan hastalarının prognozunu belirlemede değerli olabilir.

References

  • Shan K., Lincoff AM, Young, J.B. Anthracycline-induced cardiotoxicity. Ann Intern Med. 1996; 1251: 47-58.
  • Lipshultz SE, Colan SD, Gelber RD, Perez-Atayde AR, Sallan SE, Sanders SP. Late cardiac effects of doxorubicin therapy for acute lymphoblastic leukemia in childhood. N Engl J Med. 1991; 324: 808-15.
  • Yeung ST, Yoong C, Spink J, Galbraith A, Smith PJ. Functional myocardial impairment in children treated with anthracyclines for cancer. Lancet. 1991; 337: 816
  • Ferreira AL, MatsubaraLS, Matsubara BB. Anthracycline-induced cardiotoxicity. Cardiovasc Hematol Agents Med Chem. 2008; 6:278-81, Rajagopalan S, Politi PM, Sinha BK, Myers CE. Adriamycin-induced free radical formation in the perfused rat heart: implications for cardiotoxicity. Cancer Res. 1988; 48:4766-9.
  • Schimmel KJ, Richel DJ, van den Brink RB, Guchelaar HJ. Cardiotoxicity of cytotoxic drugs. Cancer Treat Rev. 2004; 30:181-91.
  • Bristow MR, MasonJW, Billingham ME, Daniels JR. Doxorubicin cardiomyopathy: evaluation by phonocardiography, endomyocardial biopsy, and cardiac catheterization. Ann Intern Med. 1978;88:168-75.
  • Corapcioglu F, Sarper N, Berk F, Sahin T, Zengin E, Demir H. Evaluation of anthracycline-induced early left ventricular dysfunction in children with cancer: a comparative study with echocardiography and multigated radionuclide angiography. Pediatr Hematol Oncol 2006;23:71-80.
  • Simson M. Use of signals in the terminal QRS complex to identify patients with ventricular tachycardia after myocardial infarction. Circulation. 1981;64: 235-242.
  • Isner JM, Ferrans VJ, Cohen SR, Witkind BG, Virmani R, Beck JR. Clinical and morphologic cardiac findings after anthracycline chemotherapy: Analysis of 64 patients studied at necropsy. The American Journal of Cardiology. 1983;51: 1167-74.
  • Mortensen SA, Olsen HS, Baandrup U. Chronic anthracycline cardiotoxicity: haemodynamic and histopathological manifestations suggesting a restrictive endomyocardial disease. Br Heart J. 1986;55:274-82.
  • Gardner P, Ursell P, Fenoglio J Jr, Wit, A. Electrophysiologic and anatomic basis for fractionated electrograms recorded from healed myocardial infarcts. Circulation. 1985; 72:596-611.
  • Simson MB, Untereker WJ, Spielman SR, Horowitz LN, Marcus NH, Falcone RA. Relation between late potentials on the body surface and directly recorded fragmented electrograms in patients with ventricular tachycardia. The American Journal of Cardiology. 1983;51:105-12.
  • Bender R S. ECG left ventricular Hypertrophy Detection and Prognosis, in Topics in Structural Heart Disease, L.B.B. Basson T.C, Editor. p. 54. Gomes JA, Cain, ME, Buxton AE, Josephson ME, Lee KL, Hafley GE. Prediction of long-term outcomes by signal-averaged electrocardiography in patients with unsustained ventricular tachycardia, coronary artery disease, and left ventricular dysfunction. Circulation. 2001; 104:436-41.
  • Fauchier L, Babuty D, Cosnay P, Poret P, Rouesnel P, Fauchier JP. Long-term prognostic value of time domain analysis of signal-averaged electrocardiography in idiopathic dilated cardiomyopathy. Am J Cardiol. 2000;85: 618-23.
  • Larsen RL, Jakacki RI, Vetter VL, Meadows AT, Silber JH, Barber G. Electrocardiographic changes and arrhythmias after cancer therapy in children and young adults. Am J Cardiol. 1992;70: 73-7.
  • Steinherz LJ, Steinherz PG, and Tan C. Cardiac failure and dysrhythmias 6-19 years after anthracycline therapy: a series of 15 patients. Med Pediatr Oncol. 1995;24: 352-61.
  • Michaelides AP, Dilaveris PE, Psomadaki ZD, Richter DJ, Andrikopoulos GK, Pitsilides N, et al. QRS prolongation on the signal-averaged electrocardiogram versus ST-segment changes on the 12-lead electrocardiogram: which is the most sensitive electrocardiographic marker of myocardial ischemia? Clin Cardiol. 1999;22: 403-8.
  • Redfield MM, Rodeheffer RJ, Jacobsen SJ, Mahoney DW, Bailey KR, Burnett JC Jr. Plasma brain natriuretic peptide concentration: impact of age and gender. J Am Coll Cardiol. 2002;40: 976-82.
  • Wang TJ, Larson MG, Levy D, Leip EP, Benjamin EJ, Wilson PW, et al. Impact of age and sex on plasma natriuretic peptide levels in healthy adults. The American journal of cardiology. 2002;90: 254-58.
  • Mehra MR, Uber PA, Park MH, Scott RL, Ventura HO, Harris BC, et al. Obesity and suppressed B-type natriuretic peptide levels in heart failure. J Am Coll Cardiol. 2004;43: 1590-5.
  • O'Hanlon R, O'Shea P, Ledwidge M, O'Loughlin C, Lange S, Conlon C, et al. The Biologic Variability of BType Natriuretic Peptide and N-Terminal Pro-B-Type Natriuretic Peptide in Stable Heart Failure Patients. Journal of cardiac failure. 2007;13: 50-5.
  • Nousiainen T, Jantunen E, Vanninen E, Remes J, Vuolteenaho O, Hartikainen J. Natriuretic peptides as markers of cardiotoxicity during doxorubicin treatment for non-Hodgkin's lymphoma. Eur J Haematol. 1999;62:135-41.
  • Kremer LC, Bastiaansen BA, Offringa M, Lam J, van Straalen JP, de Winter RJ, et al. Troponin T in the first 24 hours after the administration of chemotherapy and the detection of myocardial damage in children. Eur J Cancer. 2002;38:686-9.
  • Fink FM, Genser N, Fink C, Falk M, Mair J, MaurerDengg K, et al. Cardiac troponin T and creatine kinase MB mass concentrations in children receiving anthracycline chemotherapy. Med Pediatr Oncol. 1995;25: 185-9.
  • Wu AH and Lane P. Metaanalysis in clinical chemistry: validation of cardiac troponin T as a marker for ischemic heart diseases. Clin Chem. 1995;41:1228-33.
  • Friedman MA, Bozdech MJ, Billingham ME, Rider AK. Doxorubicin cardiotoxicity. Serial endomyocardial biopsies and systolic time intervals. JAMA. 1978;240:1603-6.
  • Sorensen K, Levitt GA, Bull C, Dorup I, Sullivan ID. Late anthracycline cardiotoxicity after childhood cancer: a prospective longitudinal study. Cancer. 2003;97:1991
  • Limat S, Demesmay K, Voillat L, Bernard Y, Deconinck E, Brion A, et al. Early cardiotoxicity of the CHOP regimen in aggressive non-Hodgkin's lymphoma. Ann Oncol. 2003;14: 277-81.
  • Lipshultz SE, Lipsitz SR, Mone SM, Goorin AM, Sallan SE, Sanders SP, et al. Female sex and drug dose as risk factors for late cardiotoxic effects of doxorubicin therapy for childhood cancer. N Engl J Med. 1995;332: 1738Von Hoff DD, Layard MW, Basa P, Davis HL Jr, Von
  • Hoff AL, Rozencweig M, et al. Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med. 1979;91:710-7.
  • Henderson IC, Allegra JC, Woodcock T, Wolff S, Bryan S, Cartwright K, et al. Randomized clinical trial comparing mitoxantrone with doxorubicin in previously treated patients with metastatic breast cancer. J Clin Oncol. 1989;7: 560-71.
  • Ewer MS, Ali MK, Mackay B, Wallace S, Valdivieso M, Legha SS, et al. A comparison of cardiac biopsy grades and ejection fraction estimations in patients receiving Adriamycin. J Clin Oncol. 1984;2: 112-7.
  • Mason JW, Bristow MR, Billingham ME, Daniels JR. Invasive and noninvasive methods of assessing adriamycin cardiotoxic effects in man: superiority of histopathologic assessment using endomyocardial biopsy. Cancer Treat Rep. 1978;62: 857-64.
  • Bristow MR, Mason JW, Billingham ME, Daniels JR. Dose-effect and structure-function relationships in doxorubicin cardiomyopathy. Am Heart J. 1981;102:709
  • Torti FM, Bristow MR, Howes AE, Aston D, Stockdale FE, Carter SK, et al. Reduced cardiotoxicity of doxorubicin delivered on a weekly schedule. Assessment by endomyocardial biopsy. Ann Intern Med. 1983;99: 745-9.
  • Yazışma Adresi / Address for Correspondence: Dr. Didem Arslan Taş Adana Numune Training and Research Hospital İnternal Medicine and Rheumatology Department ADANA e-mail: arslan_didem@yahoo.com Tel: 00 90 554 7547364 Fax: 00 90 322 3386373 geliş tarihi/received :09.08.2012 kabul tarihi/accepted:05.10.2012 .
There are 36 citations in total.

Details

Primary Language Turkish
Journal Section Research
Authors

Hakan Sakallı This is me

Didem Arslan Tas This is me

Osman Karaarslan This is me

Huseyin Mertsoylu This is me

Bahattin Yılmaz This is me

Abdullah Canataroglu This is me

Publication Date June 1, 2013
Published in Issue Year 2013 Volume: 38 Issue: 2

Cite

MLA Sakallı, Hakan et al. “Doksorubisin Kardiyotoksisitesinin Sinyal Ortalamali Elektrokardiyografi İle Değerlendirilmesi”. Cukurova Medical Journal, vol. 38, no. 2, 2013, pp. 241-9.