Infection

, Volume 45, Issue 5, pp 659–667 | Cite as

Prolongation of the QTc interval in HIV-infected individuals compared to the general population

  • Nico Reinsch
  • Marina Arendt
  • Marie Henrike Geisel
  • Christina Schulze
  • Volker Holzendorf
  • Anna Warnke
  • Till Neumann
  • Norbert H. Brockmeyer
  • Dirk Schadendorf
  • Lewin Eisele
  • Raimund Erbel
  • Susanne Moebus
  • Karl-Heinz Jöckel
  • Stefan Esser
  • On behalf of HIV HEART Study Group and the Heinz Nixdorf Recall Investigative Group
Original Paper
  • 156 Downloads

Abstract

Objectives

Prolonged QT interval is associated with arrhythmias and sudden death. An increased prevalence of QT interval prolongation in human immunodeficiency virus-infected (HIV) subjects was previously described. The impact of different medications and HIV infection itself on the QT interval is rarely investigated in large HIV+ cohorts.

Methods

We compared QT interval measurement in 496 HIV(+) patients of the HIV-HEART study (HIVH) and 992 sex- and age-matched controls of the population-based German Heinz Nixdorf Recall study (HNR). QT corrected for heart rate (QTc) >440 ms in male and >460 ms in female was considered pathological. We analysed the impact of HIV status and HIV medication on QTc prolongation in the HIVH subjects.

Results

We observed longer QTc in HIVH subjects compared with HNR controls: 424.1 ms ± 23.3 vs. 411.3 ± 15.3 ms for male and 435.5 ms ± 19.6 vs. 416.4 ms ± 17.3 for female subjects (p < 0.0001 for both sexes). Adjusting for QT prolonging medication the mean differences in QTc between the two studies remained significant with 12.6 ms (95% CI 10.5–14.8; p value <0.0001) for male and 19.3 ms (95% CI 14.5–24.2; p value <0.0001) for female subjects. Prolongation of QTc was pathologic in 22.8 vs. 3.9% of HIV(+) and non-infected males and in 12.1 vs. 1.8% of the females [OR of 7.9 (5.0–12.6) and OR of 6.7 (1.8–24.2), respectively]. Smoking behaviour was an independent factor to lengthen QTc in HIV(+) patients. Diabetes mellitus was not a risk factor itself, but might be associated with medication which was associated with LQT. We could not observe any influence of the HIV status, ART, or any co-medication on the QTc.

Conclusions

Our study showed that HIV(+) patients had significantly longer QTc intervals compared to the general population. The number of patients with pathologic QTc prolongation was significantly increased in HIV(+) population.

Keywords

QTc prolongation HIV Electrocardiogram ART 

Notes

Acknowledgements

The authors give their respect and thanks to all participating and supporting persons of the present study, including the staff of the recruiting centers, i.e. the team of Dr. Hower (Dortmund).

Compliance with ethical standards

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

References

  1. 1.
    Roden DM. Drug-induced prolongation of the QT interval. N Engl J Med. 2004;350:1013–22.CrossRefPubMedGoogle Scholar
  2. 2.
    Trinkley KE, Page RL, Lien H, Yamanouye K, Tisdale JE. QT interval prolongation and the risk of torsades de pointes: essentials for clinicians. Curr Med Res Opin. 2013;29:1719–26.CrossRefPubMedGoogle Scholar
  3. 3.
    Niemeijer MN, van den Berg ME, Deckers JW, Franco OH, Hofman A, Kors JA, Stricker BH, Rijnbeek PR, Eijgelsheim M. Consistency of heart rate–QTc prolongation consistency and sudden cardiac death: the Rotterdam Study. Heart Rhythm. 2015;12:2078–85.CrossRefPubMedGoogle Scholar
  4. 4.
    Kocheril AG, Bokhari SA, Batsford WP, Sinusas AJ. Long QTc and torsades de pointes in human immunodeficiency virus disease. Pacing Clin Electrophysiol. 1997;20:2810–6.CrossRefPubMedGoogle Scholar
  5. 5.
    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.CrossRefPubMedGoogle Scholar
  6. 6.
    Ogunmola OJ, Oladosu YO, Olamoyegun MA. QTC interval prolongation in HIV-negative versus HIV-positive subjects with or without antiretroviral drugs. Ann Afr Med. 2015;14:169–76.CrossRefPubMedGoogle Scholar
  7. 7.
    Sani MU, Okeahialam BN. QTc interval prolongation in patients with HIV and AIDS. J Natl Med Assoc. 2005;97:1657–61.PubMedPubMedCentralGoogle Scholar
  8. 8.
    Villa A, Foresti V, Confalonieri F. Autonomic neuropathy and prolongation of QT interval in human immunodeficiency virus infection. Clin Auton Res. 1995;5:48–52.CrossRefPubMedGoogle Scholar
  9. 9.
    Tseng ZH, Secemsky EA, Dowdy D, Vittinghoff E, Moyers B, Wong JK, Havlir DV, Hsue PY. Sudden cardiac death in patients with human immunodeficiency virus infection. J Am Coll Cardiol. 2012;59:1891–6.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Neumann T, Esser S, Potthoff A, Pankuweit S, Neumann A, Breuckmann F, Neuhaus K, Kondratieva J, Buck T, Muller-Tasch T, Wachter R, Prettin C, Gelbrich G, Herzog W, Pieske B, Rauchhaus M, Loffler M, Maisch B, Mugge A, Wasem J, Gerken G, Brockmeyer NH, Erbel R. Prevalence and natural history of heart failure in outpatient HIV-infected subjects: rationale and design of the HIV-HEART study. Eur J Med Res. 2007;12:243–8.PubMedGoogle Scholar
  11. 11.
    Schmermund A, Mohlenkamp S, Stang A, Gronemeyer D, Seibel R, Hirche H, Mann K, Siffert W, Lauterbach K, Siegrist J, Jockel KH, Erbel R. Assessment of clinically silent atherosclerotic disease and established and novel risk factors for predicting myocardial infarction and cardiac death in healthy middle-aged subjects: rationale and design of the Heinz Nixdorf RECALL Study. Risk factors, evaluation of coronary calcium and lifestyle. Am Heart J. 2002;144:212–8.CrossRefPubMedGoogle Scholar
  12. 12.
    Willems JL, Abreu-Lima C, Arnaud P, van Bemmel JH, Brohet C, Degani R, Denis B, Gehring J, Graham I, van Herpen G, et al. The diagnostic performance of computer programs for the interpretation of electrocardiograms. N Engl J Med. 1991;325:1767–73.CrossRefPubMedGoogle Scholar
  13. 13.
    Robbins J, Nelson JC, Rautaharju PM, Gottdiener JS. The association between the length of the QT interval and mortality in the Cardiovascular Health Study. Am J Med. 2003;115:689–94.CrossRefPubMedGoogle Scholar
  14. 14.
    Algra A, Tijssen JG, Roelandt JR, Pool J, Lubsen J. QTc prolongation measured by standard 12-lead electrocardiography is an independent risk factor for sudden death due to cardiac arrest. Circulation. 1991;83:1888–94.CrossRefPubMedGoogle Scholar
  15. 15.
    Priori SG, Schwartz PJ, Napolitano C, Bloise R, Ronchetti E, Grillo M, Vicentini A, Spazzolini C, Nastoli J, Bottelli G, Folli R, Cappelletti D. Risk stratification in the long-QT syndrome. N Engl J Med. 2003;348:1866–74.CrossRefPubMedGoogle Scholar
  16. 16.
    Zareba W, Moss AJ, Schwartz PJ, Vincent GM, Robinson JL, Priori SG, Benhorin J, Locati EH, Towbin JA, Keating MT, Lehmann MH, Hall WJ. Influence of genotype on the clinical course of the long-QT syndrome. International Long-QT Syndrome Registry Research Group. N Engl J Med. 1998;339:960–5.CrossRefPubMedGoogle Scholar
  17. 17.
    Moss AJ. Measurement of the QT interval and the risk associated with QTc interval prolongation: a review. Am J Cardiol. 1993;72:23B–5B.CrossRefPubMedGoogle Scholar
  18. 18.
    Mohlenkamp S, Schmermund A, Lehmann N, Roggenbuck U, Dragano N, Stang A, Moebus S, Beck EM, Schluter C, Sack S, Meinertz T, Taylor A, Jockel KH, Erbel R. Subclinical coronary atherosclerosis and resting ECG abnormalities in an unselected general population. Atherosclerosis. 2008;196:786–94.CrossRefPubMedGoogle Scholar
  19. 19.
    Isbister GK, Page CB. Drug induced QT prolongation: the measurement and assessment of the QT interval in clinical practice. Br J Clin Pharmacol. 2013;76:48–57.CrossRefPubMedGoogle Scholar
  20. 20.
    Reinsch N, Buhr C, Krings P, Kaelsch H, Neuhaus K, Wieneke H, Erbel R, Neumann T. Prevalence and risk factors of prolonged QTc interval in HIV-infected patients: results of the HIV-HEART study. HIV Clin Trials. 2009;10:261–8.CrossRefPubMedGoogle Scholar
  21. 21.
    Anson BD, Weaver JG, Ackerman MJ, Akinsete O, Henry K, January CT, Badley AD. Blockade of HERG channels by HIV protease inhibitors. Lancet. 2005;365:682–6.CrossRefPubMedGoogle Scholar
  22. 22.
    Zhou S, Yung Chan S, Cher Goh B, Chan E, Duan W, Huang M, McLeod HL. Mechanism-based inhibition of cytochrome P450 3A4 by therapeutic drugs. Clin Pharmacokinet. 2005;44:279–304.CrossRefPubMedGoogle Scholar
  23. 23.
    Castillo R, Pedalino RP, El-Sherif N, Turitto G. Efavirenz-associated QT prolongation and Torsade de Pointes arrhythmia. Ann Pharmacother. 2002;36:1006–8.CrossRefPubMedGoogle Scholar
  24. 24.
    Hrovatin E, Zardo F, Brieda M, Dametto E, Piazza R, Antonini-Canterin F, Cassin M, Meneguzzo N, Viel E, Lestuzzi C, Di Gennaro G, Nicolosi GL. Long QT and torsade de pointes in a patient with acquired human immunodeficiency virus infection in multitherapy with drugs affecting cytochrome P450. Ital Heart J Suppl. 2004;5:735–40.PubMedGoogle Scholar
  25. 25.
    Ly T, Ruiz ME. Prolonged QT interval and torsades de pointes associated with atazanavir therapy. Clin Infect Dis. 2007;44:e67–8.CrossRefPubMedGoogle Scholar
  26. 26.
    Szabados E, Fischer GM, Toth K, Csete B, Nemeti B, Trombitas K, Habon T, Endrei D, Sumegi B. Role of reactive oxygen species and poly-ADP-ribose polymerase in the development of AZT-induced cardiomyopathy in rat. Free Radic Biol Med. 1999;26:309–17.CrossRefPubMedGoogle Scholar
  27. 27.
    Vallecillo G, Mojal S, Roquer A, Martinez D, Rossi P, Fonseca F, Muga R, Torrens M. Risk of QTc prolongation in a cohort of opioid-dependent HIV-infected patients on methadone maintenance therapy. Clin Infect Dis. 2013;57:1189–94.CrossRefPubMedGoogle Scholar
  28. 28.
    Soliman EZ, Lundgren JD, Roediger MP, Duprez DA, Temesgen Z, Bickel M, Shlay JC, Somboonwit C, Reiss P, Stein JH, Neaton JD, INSIGHT SMART Study Group. Boosted protease inhibitors and the electrocardiographic measures of QT and PR durations. AIDS. 2011;25:367–77.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Malik M, Camm AJ. Evaluation of drug-induced QT interval prolongation: implications for drug approval and labelling. Drug Saf. 2001;24:323–51.CrossRefPubMedGoogle Scholar
  30. 30.
    Gili S, Mancone M, Ballocca F, Grosso Marra W, Calcagno A, D’Ettorre G, Cannillo M, D’Ascenzo F, Orofino G, Marruncheddu L, Lonni E, Cinque A, Vullo F, Ceccarelli G, Vilardi I, Sardella G, Vullo V, Moretti C, Fedele F, Bonora S, Gaita F. Prevalence and predictors of long corrected QT interval in HIV-positive patients: a multicenter study. J Cardiovasc Med (Hagerstown). 2017;18:539–44.CrossRefGoogle Scholar
  31. 31.
    Patel N, Veve M, Kwon S, McNutt LA, Fish D, Miller CD. Frequency of electrocardiogram testing among HIV-infected patients at risk for medication-induced QTc prolongation. HIV Med. 2013;14:463–71.CrossRefPubMedGoogle Scholar
  32. 32.
    Owens RCJ, Nolin TD. Antimicrobial-associated QT interval prolongation: pointes of interest. Clin Infect Dis. 2006;43:1603–11.CrossRefPubMedGoogle Scholar
  33. 33.
    Becker K, Gorlach I, Frieling T, Haussinger D. Characterization and natural course of cardiac autonomic nervous dysfunction in HIV-infected patients. AIDS. 1997;11:751–7.CrossRefPubMedGoogle Scholar
  34. 34.
    Mittal CM, Wig N, Mishra S, Deepak KK. Heart rate variability in human immunodeficiency virus-positive individuals. Int J Cardiol. 2004;94:1–6.CrossRefPubMedGoogle Scholar
  35. 35.
    Lehmann MH, Timothy KW, Frankovich D, Fromm BS, Keating M, Locati EH, Taggart RT, Towbin JA, Moss AJ, Schwartz PJ, Vincent GM. Age-gender influence on the rate-corrected QT interval and the QT-heart rate relation in families with genotypically characterized long QT syndrome. J Am Coll Cardiol. 1997;29:93–9.CrossRefPubMedGoogle Scholar
  36. 36.
    Locati EH, Zareba W, Moss AJ, Schwartz PJ, Vincent GM, Lehmann MH, Towbin JA, Priori SG, Napolitano C, Robinson JL, Andrews M, Timothy K, Hall WJ. Age- and sex-related differences in clinical manifestations in patients with congenital long-QT syndrome: findings from the International LQTS Registry. Circulation. 1998;97:2237–44.CrossRefPubMedGoogle Scholar
  37. 37.
    Bidoggia H, Maciel JP, Capalozza N, Mosca S, Blaksley EJ, Valverde E, Bertran G, Arini P, Biagetti MO, Quinteiro RA. Sex differences on the electrocardiographic pattern of cardiac repolarization: possible role of testosterone. Am Heart J. 2000;140:678–83.CrossRefPubMedGoogle Scholar
  38. 38.
    Abi-Gerges N, Philp K, Pollard C, Wakefield I, Hammond TG, Valentin JP. Sex differences in ventricular repolarization: from cardiac electrophysiology to Torsades de Pointes. Fundam Clin Pharmacol. 2004;18:139–51.CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Nico Reinsch
    • 1
    • 2
  • Marina Arendt
    • 3
  • Marie Henrike Geisel
    • 3
  • Christina Schulze
    • 4
  • Volker Holzendorf
    • 5
  • Anna Warnke
    • 4
  • Till Neumann
    • 6
  • Norbert H. Brockmeyer
    • 7
  • Dirk Schadendorf
    • 4
  • Lewin Eisele
    • 3
  • Raimund Erbel
    • 3
  • Susanne Moebus
    • 3
  • Karl-Heinz Jöckel
    • 3
  • Stefan Esser
    • 4
  • On behalf of HIV HEART Study Group and the Heinz Nixdorf Recall Investigative Group
  1. 1.Department of Internal Medicine I and Cardiology, Division of ElectrophysiologyAlfried Krupp von Bohlen and Halbach HospitalEssenGermany
  2. 2.Department of CardiologyWitten/Herdecke UniversityWittenGermany
  3. 3.Institute for Medical Informatics, Biometry and Epidemiology (IMIBE)University Hospital EssenEssenGermany
  4. 4.Clinic of Dermatology, Department of VenerologyUniversity Hospital EssenEssenGermany
  5. 5.Clinical Trial Centre Leipzig-Coordination Centre for Clinical Trials (ZKS Leipzig-KKS)University LeipzigLeipzigGermany
  6. 6.Out-Patient-Clinic StaubachBochumGermany
  7. 7.Clinic of Dermatology, Venerology and AllergologyRuhr University BochumBochumGermany

Personalised recommendations