Effect of anti-TNFα treatment on Tp-e interval and Tp-e/QT ratio in patients with ankylosing spondylitis: A case-control study

Abstract

Aim: Ankylosing spondylitis (AS) is an axial spondyloarthropathy with multisystemic involvement. Anti-TNFα agents play a significant role in treatment options of this disease. In the literature, there is contradictory data about the effects of AS disease and anti-TNFα therapy on ventricular repolarization parameters. In this present study, we examined whether electrocardiographic parameters which reflect ventricular repolarization like QT, QTc, Tp-e, Tp-e/QT and Tp-e/QTc are different in AS patients than the control group and the effect of anti-TNFα agents on these parameters.
Methods: Sixty patients diagnosed with AS (33 patients treated with anti-TNFα, 27 patients treated with non-anti-TNFα) and 60 healthy subjects were included in the study. Demographic, biochemical, electrocardiographic, and echocardiographic parameters of the study and control groups were compared. Tp-e interval was measured as the time interval between the T wave’s peak point and down slope tangent intersecting with the isoelectric line.
Results: Heart rate, QT, QTc, and QRS were similar in both groups (P=0.232, P=0.660, P=0.220, and P=0.846, respectively); Tp-e (P=0.013), Tp-e/QT (P=0.006), and Tp-e/QTc (P=0.041) values were higher in the study group. Comparison analysis performed between groups treated with anti-TNFα and non-anti-TNFα showed no statistically significant difference in terms of heart rate, QT, QTc, QRS, Tp-e, Tpe/QT, and Tp-e/QTc values (P=0.916, P=0.655, P=0.335, P=0.999, P=0.731, P=0.848, and P=0.901, respectively).
Conclusion: Although QT and QTc values were similar between AS patients and the control group, Tp-e, Tp-e/QT, and Tp-e/QTc values were higher in AS patients. Additionally, anti-TNFα treatment had a neutral effect on these parameters.

Keywords

• Ankylosing spondylitis,T peak-to-end,Tp-e/QT,Anti-TNFα treatment

Ankilozan spondilit hastalarında anti-TNFα tedavinin Tp-e mesafesi ve Tp-e/QT oranı üzerine etkisi: Bir vaka-kontrol çalışması

Öz

Amaç: Ankilozan spondilit (AS) multisistemik tutulumla seyredebilen bir aksiyal spondiloartropatidir. Anti-TNFα ajanlar bu hastalığın tedavisinde önemli bir rol oynarlar. Literatürde AS hastalığı ve anti-TNFα tedavinin ventriküler repolarizasyon parametreleri üzerine etkileri hakkında çelişkili veriler mevcuttur. Sunulan bu çalışmada, QT, QTc, Tp-e, Tp-e/QT ve Tp-e/QTc gibi ventriküler repolarizasyonu gösteren elektrokardiyografik parametrelerin AS hastalarında, kontrol grubuna göre farklı olup olmadığını ve anti-TNFα ajanların bu parametreler üzerinde etkili olup olmadığını araştırdık.
Yöntemler: AS tanılı 60 hasta (anti-TNFα ile tedavi edilen 33 hasta, non-anti-TNFα ile tedai edilen 27 hasta) ve 60 sağlıklı gönüllü çalışmaya dahil edildi. Çalışma ve kontrol grubunun demografik, biyokimyasal, elektrokardiyografik ve ekokardiyografik parametreleri karşılaştırıldı. Tp-e aralığı, T dalgasının tepe noktası ile izoelektrik çizgiyle kesişen aşağı eğim teğeti arasındaki zaman aralığı olarak ölçüldü.
Bulgular: Kalp hızı, QT, QTc ve QRS her iki grupta benzer iken (P=0,232, P=0,660, P=0,220 ve P=0,846, sırasıyla); Tp-e (P=0,013), Tp-e/QT (P=0,006) ve Tp-e/QTc (P=0,041) değerleri çalışma grubunda istatistiksel anlamlı olarak daha yüksekti. Anti-TNFα ajanlar ile tedavi edilen ve non-anti-TNFα ajanlar ile tedavi edilen gruplar arasında karşılaştırma analizi yapıldığında ise, kalp hızı, QT, QTc, QRS, Tp-e, Tp-e/QT ve Tp-e/QTc değerlerinde istatistiksel anlamlı farklılık izlenmedi (P=0,916, P=0,655, P=0,335, P=0,999, P=0,731, P=0,848 ve P=0,901, sırasıyla).
Sonuç: QT ve QTc değerleri AS hastaları ile kontrol grubu arasında benzer iken; Tp-e, Tp-e/QT ve Tp-e/QTc değerleri çalışma grubunda daha yüksek idi. Ek olarak, anti-TNFα ajanlar bu parametreler üzerine nötral etkiliydi.

Anahtar Kelimeler

• Ankilozan spondilit,Tp-e,Tp-e/QT,Anti-TNFα tedavi

Kaynakça

1. 1. Stolwijk C, Essers I, van Tubergen A, Boonen A, Bazelier MT, De Bruin ML, et al. The epidemiology of extra-articular manifestations in ankylosing spondylitis: a population-based matched cohort study. Ann Rheum Dis. 2015 Jul;74(7):1373-8.
2. 2. Bakland G, Gran JT, Nossent JC. Increased mortality in ankylosing spondylitis is related to disease activity. Ann Rheum Dis. 2011;70:1921–5.
3. 3. Moyssakis I, Gialafos E, Vassiliou VA, Boki K, Votteas V, Sfikakis PP, et al. Myocardial performance and aortic elasticity are impaired in patients with ankylosing spondylitis. Scand J Rheumatol. 2009;38(3):216-21.
4. 4. Ozkan Y. Cardiac Involvement in Ankylosing Spondylitis. J Clin Med Res. 2016 Jun;8(6):427-30.
5. 5. Longo B, Kirchner LA, Simioni J, Campos APB, Skare TL. Electrocardiographic changes in spondyloarthritis and use of anti-TNF-α drugs: a retrospective study with 100 patients. Einstein (Sao Paulo). 2019 Apr 1;17(2):eAO4539. doi: 10.31744/einstein_journal/2019AO4539.
6. 6. Acar G, Yorgun H, Inci MF, Akkoyun M, Bakan B, Nacar AB, et al. Evaluation of Tp-e interval and Tp-e/QT ratio in patients with ankylosing spondylitis. Mod Rheumatol. 2014 Mar;24(2):327-30.
7. 7. Yildirir A, Aksoyek S, Calguneri M, Aytemir K, Kabakci G, Ovunc K, et al. QT dispersion as a predictor of arrhythmic events in patients with ankylosing spondylitis. Rheumatology (Oxford). 2000 Aug;39(8):875-9.
8. 8. Mota LM, Cruz BA, Brenol CV, Pollak DF, Pinheiro GR, Laurindo IM, et al. Segurança do uso de terapias biológicas para o tratamento de artrite reumatoide e espondiloartrites. Rev Bras Reumatol. 2015;55(3):281-309.

9. 9. Senel S, Cobankara V, Taskoylu O, Guclu A, Evrengul H, Kaya MG. Effect of infliximab treatment on QT intervals in patients with ankylosing spondylitis. J Investig Med. 2011 Dec;59(8):1273-5.
10. 10. Regel A, Sepriano A, Baraliakos X, van der Heijde D, Braun J, Landewé R, et al. Efficacy and safety of non-pharmacological and non-biological pharmacological treatment: a systematic literature review informing the 2016 update of the ASAS/EULAR recommendations for the management of axial spondyloarthritis. RMD Open. 2017 Jan 27;3(1):e000397.
11. 11. Zochling J. Measures of symptoms and disease status in ankylosing spondylitis: Ankylosing Spondylitis Disease Activity Score (ASDAS), Ankylosing Spondylitis Quality of Life Scale (ASQoL), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Global Score (BAS-G), Bath Ankylosing Spondylitis Metrology Index (BASMI), Dougados Functional Index (DFI), and Health Assessment Questionnaire for the Spondylarthropathies (HAQ-S). Arthritis Care Res (Hoboken). 2011 Nov;63 Suppl 11:S47-58.
12. 12. Castro-Torres Y, Carmona-Puerta R, Katholi RE. Ventricular repolarization markers for predicting malignant arrhythmias in clinical practice. World J Clin Cases. 2015;3:705–20.
13. 13. Haarmark C, Graff C, Andersen MP, Hardahl T, Struijk JJ, Toft E, et al. Reference values of electrocardiogram repolarization variables in a healthy population. J Electrocardiol. 2010;43:31–9.
14. 14. Goldenberg I, Moss AJ, Zareba W. QT interval: how to measure it and what is "normal". J Cardiovasc Electrophysiol. 2006;17:333-6.
15. 15. Smetana P, Schmidt A, Zabel M, Hnatkova K, Franz M, Huber K, Malik M. Assessment of repolarization heterogeneity for prediction of mortality in cardiovascular disease: peak to the end of the T wave interval and nondipolar repolarization components. J Electrocardiol. 2011 May-Jun;44(3):301-8.
16. 16. Panikkath R, Reinier K, Uy-Evanado A, Teodorescu C, Hattenhauer J, Mariani R, et al. Prolonged Tpeak-to-tend interval on the resting ECG is associated with increased risk of sudden cardiac death. Circ Arrhythm Electrophysiol. 2011;4:441-7.
17. 17. Divecha H, Sattar N, Rumley A, Cherry L, Lowe GD, Sturrock R. Cardiovascular risk parameters in men with ankylosing spondylitis in comparison with non-inflammatory control subjects: relevance of systemic inflammation. Clin Sci. 2005;109(2):171–176.
18. 18. Amaya-Amaya J, Montoya-Sánchez L, Rojas-Villarraga A. Cardiovascular involvement in autoimmune diseases. Biomed Res Int. 2014;2014:367359.
19. 19. Sinagra E, Perricone G, Romano C, Cottone M. Heart failure and anti tumor necrosis factor-alpha in systemic chronic inflammatory diseases. Eur J Intern Med. 2013;24:385–92.
20. 20. Dik VK, Peters MJ, Dijkmans PA, Van der Weijden MA, De Vries MK, Dijkmans BA, et al. The relationship between disease-related characteristics and conduction disturbances in ankylosing spondylitis. Scand J Rheumatol. 2010;39(1):38-41.
21. 21. Bergfeldt L, Allebeck P, Edhag O. Mortality in pacemaker- treated patients. A follow-up study of the impact of HLA B27 and associated rheumatic disorders. Acta Med Scand. 1987;222(4):293-9.
22. 22. Aksoy H, Okutucu S, Sayin BY, Ercan EA, Kaya EB, Ozdemir O, et al. Assessment of cardiac arrhythmias in patients with ankylosing spondylitis by signal-averaged P wave duration and P wave dispersion. Eur Rev Med Pharmacol Sci. 2016;20(6):1123-9.
23. 23. Thomsen NH, Horslev-Peterson K, Beyer JM. Ambulatory 24-hour continuous electrocardiographic monitoring in 54 patients with ankylosing spondylitis. Eur Heart J. 7:240-246:1986.
24. 24. Kazmierczak J, Peregud-Pogorzelska M, Biernawska J, Przepiera-Bedzak H, Goracy J, Brzosko I, et al. Cardiac arrhythmias and conduction disturbances in patients with ankylosing spondylitis. Angiology. 2007 Dec-2008 Jan;58(6):751-6.
25. 25. Antzelevitch C, Sicouri S, Di Diego JM, Burashnikov A, Viskin S, Shimizu W, et al. Does Tpeak-Tend provide an index of transmural dispersion of repolarization? Heart Rhythm. 2007:4:1114–6.
26. 26. Gupta P, Patel C, Patel H, Narayanaswamy S, Malhotra B, Green JT, et al. T(p-e)/QT ratio as an index of arrhythmogenesis. J Electrocardiol. 2008 Nov-Dec;41(6):567-74.
27. 27. Sieper J, Lenaerts J, Wollenhaupt J, Rudwaleit M, Mazurov VI, Myasoutova L, et al. Maintenance of biologic-free remission with naproxen or no treatment in patients with early, active axial spondyloarthritis: results from a 6-month, randomised, open-label follow-up study, INFAST part 2. Ann Rheum Dis. 2014;73:108–13.
28. 28. Sieper J, Lenaerts J, Wollenhaupt J, Rudwaleit M, Mazurov VI, Myasoutova L, et al. Efficacy and safety of infliximab plus naproxen versus naproxen alone in patients with early, active axial spondyloarthritis: results from the double-blind, placebo-controlled INFAST study, part 1. Ann Rheum Dis. 2014;73:101–7.
29. 29. Ntusi NAB, Francis JM, Sever E, Liu A, Piechnik SK, Ferreira VM, et al. Anti-TNF modulation reduces myocardial inflammation and improves cardiovascular function in systemic rheumatic diseases. Int J Cardiol. 2018 Nov 1;270:253-9.
30. 30. DI Franco M, Paradiso M, Ceccarelli F, Scrivo R, Spinelli FR, Iannuccelli C, et al. Biological drug treatment of rheumatoid arthritis and spondyloarthritis: effects on QT interval and QT dispersion. J Rheumatol. 2012 Jan;39(1):41-5.