QTc  prolongation in methadone maintenance – the role of HCV infection

Najibulah Gholami; Lukas Boesch; Luis Falcato; Rudolf Stohler; Philip Bruggmann

doi:10.4414/smw.2013.13852

Original article

Vol. 143 No. 3536 (2013)

QTc prolongation in methadone maintenance – the role of HCV infection

Najibulah Gholami
Lukas Boesch
Luis Falcato
Rudolf Stohler
Philip Bruggmann

DOI: https://doi.org/10.4414/smw.2013.13852
Cite this as:: Swiss Med Wkly. 2013;143:w13852
Published: 25.08.2013

Summary

OBJECTIVES: Several studies have reported prolonged QTc intervals in patients under methadone maintenance treatment, including development of torsade-de-pointes arrhythmia and death. It is still not clear why some patients develop critical QTc extensions while others do not.

METHODS: ECG findings in a convenience sample of 210 methadone-maintained heroin-dependent patients, taking HCV-infection status and methadone dosage into account simultaneously by means of a multiple linear regression model with QTc-interval as the dependent variable.

RESULTS: Prolonged QTc-time is associated with hepatitis C infections (p = 0.005) and higher doses of racemic methadone (p = 0.012).

CONCLUSION: Infection with hepatitis C increases the likelihood of critical QTc prolongation in patients in methadone maintenance treatment.

References

Mattick RP, Breen C, Kimber J, Davoli M. Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. Cochrane Database Syst Rev 2009; CD002209.
Toombs JD, Kral LA. Methadone treatment for pain states. Am Fam Physician. 2005;71:1353–8.
Eap CB, Crettol S, Rougier JS, Schläpfer J, Sintra Grilo L, Déglon JJ, et al. Stereoselective block of hERG channel by (S)- methadone and QT interval prolongation in CYP2B6 slow metabolizers. Clin Pharmacol Ther. 2007;81:719–28.
Katchman AN, McGroary KA, Kilborn MJ, Kornick CA, Manfredi PL, Woosley RL, et al. Influence of opioid agonists on cardiac human ether-a-go-go-related gene K(+) currents. J Pharmacol Exp Ther. 2002;303:688–94.
Krantz MJ, Lewkowiez L, Hays H, Woodroffe MA, Robertson AD, Mehler PS. Torsade de pointes associated with very-high-dose methadone. Ann Intern Med. 2002;137:501–4.
Krantz MJ, Kutinsky IB, Robertson AD, Mehler PS. Dose-related effects of methadone on QT prolongation in a series of patients with torsade de pointes. Pharmacotherapy. 2003;23:802–5.
Anchersen K, Clausen T, Gossop M, Hansteen V, Waal H. Prevalence and clinical relevance of corrected QT interval prolongation during methadone and buprenorphine treatment: a mortality assessment study. Addiction. 2009;104:993–9.
Athanasos P, Farquharson AL, Compton P, Psaltis P, Hay J. Electrocardiogram characteristics of methadone and buprenorphine maintained subjects. J Addict Dis. 2008;27:31–5.
Fonseca F, Marti-Almor J, Pastor A, Cladellas M, Farré M, de la Torre R, et al. Prevalence of long QTc interval in methadone maintenance patients. Drug Alcohol Depend. 2009;99:327–32.
Krantz MJ, Baker WA, Schmittner J. Cocaine and methadone: parallel effects on the QTc interval. Am J Cardiol. 2006;98:1121.
Peles E, Bodner G, Kreek MJ, Rados V, Adelson M. Corrected-QT intervals as related to methadone dose and serum level in methadone maintenance treatment (MMT) patients: a cross-sectional study. Addiction. 2007;102:289–300.
Roy A, McCarthy C, Kiernan G, McGorrian C, Keenan E, Mahon NG, et al. Increased incidence of QT interval prolongation in a population receiving lower doses of methadone maintenance therapy. Addiction. 2012:1132–9.
Alter MJ. Prevention of spread of hepatitis C. Hepatology. 2002;36:S93–8.
Trepo C, Pradat P. Hepatitis C virus infection in Western Europe. J Hepatol. 1999;31(Suppl 1):80–3.
Matsumori A. Detection of viral genomes in myocarditis. Rinsho Byori. 1995;43:358–64.
Okabe M, Fukuda K, Arakawa K, Kikuchi M. Chronic variant of myocarditis associated with hepatitis C virus infection. Circulation. 1997;96:22–4.
Matsumori A. Hepatitis C virus and cardiomyopathy. Herz. 2000;25:249–54.
Matsumori A. Hepatitis C virus infection and cardiomyopathies. Circ Res. 2005;96:144–7.
Nordin C, Kohli A, Beca S, Zaharia V, Grant T, Leider J, Marantz P. Importance of hepatitis C coinfection in the development of QT prolongation in HIV-infected patients. J Electrocardiol. 2006;39:199–205.
Bernardi M, Calandra S, Colantoni A, Trevisani F, Raimondo ML, Sica G, et al. Q-T interval prolongation in cirrhosis: prevalence, relationship with severity, and etiology of the disease and possible pathogenetic factors. Hepatology. 1998;27:28–34.
Ehret GB, Voide C, Gex-Fabry M, Chabert J, Shah D, Broers B, et al. Drug-induced long QT syndrome in injection drug users receiving methadone: high frequency in hospitalized patients and risk factors. Arch Intern Med. 2006;166:1280–7.
Goldenberg I, Moss AJ, Zareba W. QT interval: how to measure it and what is “normal.” J Cardiovasc Electrophysiol. 2006;17:333–6.
Funck-Brentano C, Jaillon P. Rate-corrected QT interval: techniques and limitations. Am J Cardiol. 1993;72:17B–22B.
Kornick CA, Kilborn MJ, Santiago-Palma J, Schulman G, Thaler HT, Keefe DL, et al. QTc interval prolongation associated with intravenous methadone. Pain. 2003;105:499–506.
Maremmani I, Pacini M, Cesaroni C, Lovrecic M, Perugi G, Tagliamonte A. QTc interval prolongation in patients on long-term methadone maintenance therapy. Eur Addict Res. 2005;11:44–9.
Krantz MJ, Mehler PS. Methadone and QT prolongation: a dose-dependent effect? Am J Cardiol. 2004;93:952.
Martell BA, Arnsten JH, Krantz MJ, Gourevitch MN. Impact of methadone treatment on cardiac repolarization and conduction in opioid users. Am J Cardiol. 2005;95:915–8.
Pearson EC, Woosley RL. QT prolongation and torsades de pointes among methadone users: reports to the FDA spontaneous reporting system. Pharmacoepidemiol Drug Saf. 2005;14:747–53.

How to Cite

1.

Gholami N, Boesch L, Falcato L, Stohler R, Bruggmann P. QTc prolongation in methadone maintenance – the role of HCV infection. Swiss Med Wkly [Internet]. 2013 Aug. 25 [cited 2024 Jul. 22];143(3536):w13852. Available from: https://smw.ch/index.php/smw/article/view/1743

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

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1 2 > >>

[1] Mattick RP, Breen C, Kimber J, Davoli M. Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. Cochrane Database Syst Rev 2009; CD002209.

[2] Toombs JD, Kral LA. Methadone treatment for pain states. Am Fam Physician. 2005;71:1353–8.

[3] Eap CB, Crettol S, Rougier JS, Schläpfer J, Sintra Grilo L, Déglon JJ, et al. Stereoselective block of hERG channel by (S)- methadone and QT interval prolongation in CYP2B6 slow metabolizers. Clin Pharmacol Ther. 2007;81:719–28.

[4] Katchman AN, McGroary KA, Kilborn MJ, Kornick CA, Manfredi PL, Woosley RL, et al. Influence of opioid agonists on cardiac human ether-a-go-go-related gene K(+) currents. J Pharmacol Exp Ther. 2002;303:688–94.

[5] Krantz MJ, Lewkowiez L, Hays H, Woodroffe MA, Robertson AD, Mehler PS. Torsade de pointes associated with very-high-dose methadone. Ann Intern Med. 2002;137:501–4.

[6] Krantz MJ, Kutinsky IB, Robertson AD, Mehler PS. Dose-related effects of methadone on QT prolongation in a series of patients with torsade de pointes. Pharmacotherapy. 2003;23:802–5.

[7] Anchersen K, Clausen T, Gossop M, Hansteen V, Waal H. Prevalence and clinical relevance of corrected QT interval prolongation during methadone and buprenorphine treatment: a mortality assessment study. Addiction. 2009;104:993–9.

[8] Athanasos P, Farquharson AL, Compton P, Psaltis P, Hay J. Electrocardiogram characteristics of methadone and buprenorphine maintained subjects. J Addict Dis. 2008;27:31–5.

[9] Fonseca F, Marti-Almor J, Pastor A, Cladellas M, Farré M, de la Torre R, et al. Prevalence of long QTc interval in methadone maintenance patients. Drug Alcohol Depend. 2009;99:327–32.

[10] Krantz MJ, Baker WA, Schmittner J. Cocaine and methadone: parallel effects on the QTc interval. Am J Cardiol. 2006;98:1121.

[11] Peles E, Bodner G, Kreek MJ, Rados V, Adelson M. Corrected-QT intervals as related to methadone dose and serum level in methadone maintenance treatment (MMT) patients: a cross-sectional study. Addiction. 2007;102:289–300.

[12] Roy A, McCarthy C, Kiernan G, McGorrian C, Keenan E, Mahon NG, et al. Increased incidence of QT interval prolongation in a population receiving lower doses of methadone maintenance therapy. Addiction. 2012:1132–9.

[13] Alter MJ. Prevention of spread of hepatitis C. Hepatology. 2002;36:S93–8.

[14] Trepo C, Pradat P. Hepatitis C virus infection in Western Europe. J Hepatol. 1999;31(Suppl 1):80–3.

[15] Matsumori A. Detection of viral genomes in myocarditis. Rinsho Byori. 1995;43:358–64.

[16] Okabe M, Fukuda K, Arakawa K, Kikuchi M. Chronic variant of myocarditis associated with hepatitis C virus infection. Circulation. 1997;96:22–4.

[17] Matsumori A. Hepatitis C virus and cardiomyopathy. Herz. 2000;25:249–54.

[18] Matsumori A. Hepatitis C virus infection and cardiomyopathies. Circ Res. 2005;96:144–7.

[19] Nordin C, Kohli A, Beca S, Zaharia V, Grant T, Leider J, Marantz P. Importance of hepatitis C coinfection in the development of QT prolongation in HIV-infected patients. J Electrocardiol. 2006;39:199–205.

[20] Bernardi M, Calandra S, Colantoni A, Trevisani F, Raimondo ML, Sica G, et al. Q-T interval prolongation in cirrhosis: prevalence, relationship with severity, and etiology of the disease and possible pathogenetic factors. Hepatology. 1998;27:28–34.

[21] Ehret GB, Voide C, Gex-Fabry M, Chabert J, Shah D, Broers B, et al. Drug-induced long QT syndrome in injection drug users receiving methadone: high frequency in hospitalized patients and risk factors. Arch Intern Med. 2006;166:1280–7.

[22] Goldenberg I, Moss AJ, Zareba W. QT interval: how to measure it and what is “normal.” J Cardiovasc Electrophysiol. 2006;17:333–6.

[23] Funck-Brentano C, Jaillon P. Rate-corrected QT interval: techniques and limitations. Am J Cardiol. 1993;72:17B–22B.

[24] Kornick CA, Kilborn MJ, Santiago-Palma J, Schulman G, Thaler HT, Keefe DL, et al. QTc interval prolongation associated with intravenous methadone. Pain. 2003;105:499–506.

[25] Maremmani I, Pacini M, Cesaroni C, Lovrecic M, Perugi G, Tagliamonte A. QTc interval prolongation in patients on long-term methadone maintenance therapy. Eur Addict Res. 2005;11:44–9.

[26] Krantz MJ, Mehler PS. Methadone and QT prolongation: a dose-dependent effect? Am J Cardiol. 2004;93:952.

[27] Martell BA, Arnsten JH, Krantz MJ, Gourevitch MN. Impact of methadone treatment on cardiac repolarization and conduction in opioid users. Am J Cardiol. 2005;95:915–8.

[28] Pearson EC, Woosley RL. QT prolongation and torsades de pointes among methadone users: reports to the FDA spontaneous reporting system. Pharmacoepidemiol Drug Saf. 2005;14:747–53.