Evaluation of Cardiac Arrhythmia Susceptibility in Pediatric Familial Mediterranean Fever Patients

Year 2023, Volume: 13 Issue: 1, 100 - 106, 31.01.2023

Vildan Güngörer , Ahmet Sert , Şükrü  Arslan

https://doi.org/10.16899/jcm.1232293

Abstract

Aim: Familial Mediterranean fever is an autoinflammatory disease characterized by attacks of inflammation. Despite treatment, there is evidence of subclinical persistence of inflammation with normal laboratory values. This study was conducted to investigate the cardiac effects of continued subclinical inflammation in children and the predisposition towards arrhythmia in familial Mediterranean fever.
Materials and Methods: Age and sex-matched familial Mediterranean fever patients and healthy controls were compared in terms of demographic, laboratory, echocardiographic and electrocardiographic data. The patients with familial Mediterranean fever were grouped according to disease severity scores and compared in terms of electrocardiographic data that could indicate arrhythmogenesis. Correlation analysis was used to examine the relationship between the electrocardiographic measurements and the clinical and laboratory data.
Results: In the comparison of the two groups, no significant difference was found in the echocardiographic measurements in terms of left ventricular systolic and diastolic functions. According to these data, QT and Tp-e intervals were significantly longer in those with familial Mediterranean fever (p=0.002, p=0.046, respectively). When the patients were classified according to the 3 separate disease severity scores, QT dispersion in the moderate-severe disease group was significantly longer than in the mild disease group (p<0.001, p=0.002, p=0.013, respectively). In correlation analysis, weak correlations were found between and QT dispersion, disease duration and P wave dispersion, and frequency of attacks and QT dispersion.
Conclusion: Our study results indicate that the predisposition to ventricular arrhythmia is greater in children with familial Mediterranean fever and that this can be associated with the severity of the disease.

Keywords

Arrhythmia, electrocardiography, familial Mediterranean fever

Pediatrik Ailevi Akdeniz Ateşi Hastalarında Kardiyak Aritmi Yatkınlığının Değerlendirilmesi

Abstract

Amaç: Ailevi Akdeniz ateşi inflamasyon atakları ile karakterize otoinflamatuar bir hastalıktır. Tedaviye rağmen, normal laboratuvar değerleri ile subklinik inflamasyonun devam ettiğine dair kanıtlar vardır. Bu çalışma, çocuklarda devam eden subklinik inflamasyonun kardiyak etkilerini ve ailesel Akdeniz ateşinde aritmiye yatkınlığı araştırmak için yapılmıştır.
Gereç ve Yöntem: Yaş ve cinsiyet açısından eşleştirilmiş ailevi Akdeniz ateşi hastaları ve sağlıklı kontroller demografik, laboratuvar, ekokardiyografik ve elektrokardiyografik veriler açısından karşılaştırıldı. Ailevi Akdeniz ateşi hastaları hastalık şiddeti skorlarına göre gruplandırıldı ve aritmogenezi gösterebilecek elektrokardiyografik veriler açısından karşılaştırıldı. Elektrokardiyografik ölçümler ile klinik ve laboratuvar verileri arasındaki ilişkiyi incelemek için korelasyon analizi kullanıldı.
Bulgular: İki grup karşılaştırıldığında, ekokardiyografik ölçümlerde sol ventrikül sistolik ve diyastolik fonksiyonları açısından anlamlı bir fark bulunmadı. Bu verilere göre QT ve Tp-e intervalleri ailesel Akdeniz ateşi olanlarda anlamlı olarak daha uzundu (sırasıyla p=0.002, p=0.046). Hastalar 3 ayrı hastalık şiddeti skoruna göre sınıflandırıldığında, orta-şiddetli hastalık grubunda QT dispersiyonu hafif hastalık grubuna göre anlamlı olarak daha uzundu (sırasıyla p<0.001, p=0.002, p=0.013). Korelasyon analizinde, QT dispersiyonu ile QT dispersiyonu, hastalık süresi ile P dalga dispersiyonu ve atak sıklığı ile QT dispersiyonu arasında zayıf korelasyonlar bulunmuştur.
Sonuç: Çalışma sonuçlarımız ailevi Akdeniz ateşi olan çocuklarda ventriküler aritmiye yatkınlığın daha fazla olduğunu ve bunun hastalığın şiddeti ile ilişkili olabileceğini göstermektedir

Keywords

Arrhythmia, electrocardiography, familial Mediterranean fever

References

• 1. Masters SL, Simon A, Aksentijevich I, Kastner DL. Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease. Annu Rev Immunol 2009; 27: 621-668
• 2. Ben-Zvi I, Livneh A. Chronic inflammation in FMF: markers, risk factors, outcomes and therapy. Nat Rev Rheumatology. 2011; 7(2): 105.
• 3. Lachmann H. Clinical immunology review series: an approach to the patient with a periodic fever syndrome. Clin Exp Immunol. 2011; 165(3): 301-309.
• 4. Akcay A, Acar G, Sayarlioglu M et al. QT dispersion and transmural dispersion of repolarization in patients with familial Mediterranean fever. Mod Rheumatol. 2009; 19(5): 550-555.
• 5. Nussinovitch U, Livneh A. Late ventricular potentials in familial Mediterranean fever with and without AA amyloidosis. Eur J Rheumatol. 2017; 4(3): 184-188.
• 6. Nussinovitch U, Shoenfeld Y. Autoimmunity and heart diseases: pathogenesis and diagnostic criteria. Arch Immunol Ther Exp. 2009; 57(2): 95-104.
• 7. Polachek A, Touma Z, Anderson M, Eder L. Risk of cardiovascular morbidity in patients with psoriatic arthritis: a meta‐analysis of observational studies. Arthritis Care Res 2017; 69(1): 67-74.
• 8. Kaya EB, Yorgun H, Akdogan A, et al. Heart-rate recovery index is impaired in Behçet's disease. Tex Heart Inst J. 2009;36(4):282-6.
• 9. Rozenbaum M, Naschitz JE, Yudashkin M, et al. Cardiovascular autonomic dysfunction in familial Mediterranean fever. J Rheumatol. 2002; 29(5): 987-9.
• 10. Ocal AG, Ocal L, Kup A, Eren H, Tezcan ME. Colchicine's Effects on Electrocardiographic Parameters in Newly Diagnosed Familial Mediterranean Fever Patients : Colchicine may have Favorable Effects on Parameters Related to Ventricular Arrhythmias in New Diagnosed Familial Mediterranean Fever. Z Rheumatol. 2020; 79(2): 210-215.
• 11. Arslan D, Oran B, Yazılıtas F, Peru H, Cimen D, Vatansev H. P-wave duration and dispersion in children with uncomplicated familial Mediterranean fever. Mod Rheumatol. 2013; 23(6): 1166-1171.
• 12. Antzelevitch C, Shimizu W, Yan G-X, Sicouri S. Cellular basis for QT dispersion. J Electrocardiol. 1998; 30: 168-175.
• 13. Kors JA, Ritsema van Eck HJ, van Herpen G. The meaning of the Tp-Te interval and its diagnostic value. J Electrocardiol. 2008; 41(6): 575-580.
• 14. Ahbap E, Sakaci T, Kara E, et al. Familial Mediterranean Fever is associated with abnormal ventricular repolarization indices. Rev Med Chil. 2015; 143(12): 1560-8. doi: 10.4067/S0034-98872015001200009.
• 15. Karaman K, Karayakali M, Erken E, et al. Assessment of myocardial repolarisation parameters in patients with familial Mediterranean fever. Cardiovasc J Afr. 2017; 28(3): 154-158. doi: 10.5830/CVJA-2016-074.
• 16. Fidancı MK, Kilic A, Gülgün M, et al. QT and JT dispersion in children with familial Mediterranean fever. Arch Rheumatol. 2015; 30(4): 343-348.
• 17. Shimizu M, Ino H, Okeie K, et al. T-peak to T-end interval may be a better predictor of high-risk patients with hypertrophic cardiomyopathy associated with a cardiac troponin I mutation than QT dispersion. Clin Cardiol. 2002; 25(7): 335-9. doi: 10.1002/clc.4950250706.
• 18. Yalçinkaya F, Ozen S, Ozçakar ZB, et al. A new set of criteria for the diagnosis of familial Mediterranean fever in childhood. Rheumatology (Oxford). 2009; 48(4): 395-8. doi: 10.1093/rheumatology/ken509.
• 19. Pras E, Livneh A, Balow JE Jr, et al. Clinical differences between North African and Iraqi Jews with familial Mediterranean fever. Am J Med Genet. 1998; 75(2): 216-9.
• 20. Mor A, Shinar Y, Zaks N, et al. Evaluation of disease severity in familial Mediterranean fever. Semin Arthritis Rheum. 2005; 35(1): 57-64. doi: 10.1016/j.semarthrit.2005.02.002.
• 21. Demirkaya E, Acikel C, Hashkes P, et al; FMF Arthritis Vasculitis and Orphan disease Research in pediatric rheumatology (FAVOR). Development and initial validation of international severity scoring system for familial Mediterranean fever (ISSF). Ann Rheum Dis. 2016; 75(6): 1051-6. doi: 10.1136/annrheumdis-2015-208671.
• 22. Mitchell C, Rahko PS, Blauwet LA, et al. Guidelines for Performing a Comprehensive Transthoracic Echocardiographic Examination in Adults: Recommendations from the American Society of Echocardiography. J Am Soc Echocardiogr. 2019; 32(1): 1-64. doi: 10.1016/j.echo.2018.06.004.
• 23. Alp H, Baysal T, Altın H, Karataş Z, Karaarslan S. QT and P-wave dispersions in rheumatic heart disease: prospective long-term follow up. Pediatr Int. 2014; 56(5): 681-688. doi:10.1111/ped.12328
• 24. Kittnar O, Lechmanová M. Disperze QT intervalu [QT interval dispersion]. Cesk Fysiol. 2001; 50(3): 125-133. 25. Ben-Chetrit E, Levy M. Familial Mediterranean fever. The Lancet. 1998; 351(9103): 659-664.
• 26. Uslu AU, Deveci K, Korkmaz S, et al. Is neutrophil/lymphocyte ratio associated with subclinical inflammation and amyloidosis in patients with familial Mediterranean fever? Biomed Res Int. 2013; 2013: 185317. doi: 10.1155/2013/185317.
• 27. Lachmann HJ, Sengül B, Yavuzşen TU, et al. Clinical and subclinical inflammation in patients with familial Mediterranean fever and in heterozygous carriers of MEFV mutations. Rheumatology (Oxford). 2006; 45(6): 746-50. doi: 10.1093/rheumatology/kei279.
• 28. Marzouk H, Mostafa N, Khalifa I, et al. Red Cell Distribution Width (RDW) as a Marker of Subclinical Inflammation in Children with Familial Mediterranean Fever. Curr Rheumatol Rev. 2020; 16(4): 298-303. doi:10.2174/1573397116666200312142709
• 29. Özer S, Yılmaz R, Sönmezgöz E, et al. Simple markers for subclinical inflammation in patients with Familial Mediterranean Fever. Med Sci Monit. 2015; 21: 298-303. doi: 10.12659/MSM.892289.
• 30. Shoenfeld Y, Gerli R, Doria A, et al. Accelerated atherosclerosis in autoimmune rheumatic diseases. Circulation. 2005; 112(21): 3337-47. doi: 10.1161/CIRCULATIONAHA.104.507996.
• 31. Karaman K, Karayakalı M, Sağlam E, et al . Evaluation of Tp-e Interval and Tp-e/QT Ratio in Patients with Familial Mediterranean Fever. Am J Cardiol. 2016; 117: 90-91.
• 32. Giese A, Ornek A, Kurucay M, et al. P wave dispersion and QT dispersion in adult Turkish migrants with familial mediterranean fever living in Germany. Int J Med Sci. 2014; 11(11): 1140-6. doi: 10.7150/ijms.9444.
• 33. Caliskan M, Gullu H, Yilmaz S, et al. Impaired coronary microvascular function in familial Mediterranean fever. Atherosclerosis. 2007; 195(2): 161-7. doi: 10.1016/j.atherosclerosis.2007.06.014.
• 34. Coronel R, Wilders R, Verkerk AO, Wiegerinck RF, Benoist D, Bernus O. Electrophysiological changes in heart failure and their implications for arrhythmogenesis. Biochim Biophys Acta Mol Basis Dis. 2013; 1832(12): 2432-2441.
• 35. Antzelevitch C, Sicouri S, Di Diego JM, et al. Does Tpeak-Tend provide an index of transmural dispersion of repolarization? Heart Rhythm. 2007; 4(8): 1114-6; author reply 1116-9. doi: 10.1016/j.hrthm.2007.05.028.
• 36. Sicouri S, Antzelevitch C. A subpopulation of cells with unique electrophysiological properties in the deep subepicardium of the canine ventricle. The M cell. Circ res. 1991; 68(6): 1729-1741.
• 37. Yan G-X, Wu Y, Liu T, Wang J, Marinchak RA, Kowey PR. Phase 2 early afterdepolarization as a trigger of polymorphic ventricular tachycardia in acquired long-QT syndrome: direct evidence from intracellular recordings in the intact left ventricular wall. Circulation. 2001; 103(23): 2851-2856.
• 38. Gupta P, Patel C, Patel H, et al. Tp-e/QT ratio as an index of arrhythmogenesis. J Electrocardiol. 2008; 41(6): 567-574.
• 39. Yamaguchi M, Shimizu M, Ino H, et al. T wave peak-to-end interval and QT dispersion in acquired long QT syndrome: a new index for arrhythmogenicity. Clin Sci (Lond). 2003; 105(6): 671-6. doi: 10.1042/CS20030010.
• 40. Acar GR, Akkoyun M, Nacar AB, et al. Evaluation of Tp-e interval and Tp-e/QT ratio in patients with rheumatoid arthritis. Turk Kardiyol Dern Ars. 2014; 42(1): 29-34. doi: 10.5543/tkda.2014.52959.
• 41. Avci A, Demir K, Altunkeser BB, et al. Assessment of inhomogeneities of repolarization in patients with systemic lupus erythematosus. Ann Noninvasive Electrocardiol. 2014; 19(4): 374-82. doi: 10.1111/anec.12145.
• 42. Bazoukis G, Yeung C, Wui Hang Ho R, et al. Association of QT dispersion with mortality and arrhythmic events-A meta-analysis of observational studies. J Arrhythm. 2019; 36(1): 105-115. doi: 10.1002/joa3.12253.
• 43. Koca B, Kasapçopur O, Bakari S, et al. QT dispersion and cardiac involvement in children with Familial Mediterranean fever. Cardiol Young. 2012; 22(4): 404-9. doi: 10.1017/S1047951111001867.
• 44. Okutucu S, Aytemir K, Oto A. P-wave dispersion: What we know till now?. JRSM Cardiovasc Dis. 2016; 5: 2048004016639443. doi:10.1177/2048004016639443
• 45. Boos CJ, Anderson RA and Lip GY. Is atrial fibrillation an inflammatory disorder? Eur Heart J 2006; 27: 136–149.