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Cardiac autonomic functions in children with familial Mediterranean fever

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Abstract

Familial Mediterranean fever (FMF) is the most common inherited autoinflammatory disease in the world. The long-term effects of subclinical inflammation in FMF are not well recognized. Some studies have suggested that FMF is associated with cardiac autonomic dysfunction in adult FMF patients. The objective of this study was to investigate the cardiac autonomic functions in pediatric FMF patients by using several autonomic tests. Thirty-five patients with FMF and 35 healthy controls were enrolled in this cross-sectional study. Demographic data, disease-specific data, and orthostatic symptoms were recorded. In all participants, 12-lead electrocardiography (ECG), 24 h ambulatory electrocardiographic monitoring, transthoracic echocardiography, treadmill exercise test, and head upright tilt-table (HUTT) test were performed. The heart rate recovery (HRR) indices of the two groups were similar. Also, chronotropic response was similar in both groups. The time-domain parameters of heart rate variability (HRV) were similar in both groups, except mean RR (p = 0.024). Frequencies of ventricular and supraventricular ectopic stimuli were similar in both groups. There were no statistically significant differences between the groups in average QT and average corrected QT interval length, average QT interval dispersion, and average QT corrected dispersion. There was no significant difference between the two groups regarding the ratio of clinical dysautonomic reactions on HUTT. However, we observed a significantly higher rate of dysautonomic reactions on HUTT in patients with exertional leg pain than that in patients without (p = 0.013). When the fractal dimension of time curves were compared, FMF patients exhibited significantly lower diastolic blood pressure parameters than controls in response to HUTT. Cardiovascular autonomic dysfunction in children with FMF is not prominent. Particularly, patients with exertional leg pain are more prone to have dysautonomic features. Further studies are needed to elucidate the exact mechanisms leading to impaired cardiac autonomic functions in FMF.

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References

  1. Samuels J, Ozen S (2006) Familial Mediterranean fever and the other autoinflammatory syndromes: evaluation of the patient with recurrent fever. Curr Opin Rheumatol 18:108–117

    Article  PubMed  Google Scholar 

  2. Balow JE Jr, Shelton DA, Orsborn A et al (1997) A high-resolution genetic map of the familial Mediterranean fever candidate region allows identification of haplotype-sharing among ethnic groups. Genomics 44:280–291

    Article  CAS  PubMed  Google Scholar 

  3. Zemer D, Pras M, Sohar E et al (1986) Colchicine in the prevention and treatment of the amyloidosis of familial Mediterranean fever. N Engl J Med 314:1001–1005

    Article  CAS  PubMed  Google Scholar 

  4. Zemer D, Revach M, Pras M et al (1974) A controlled trial of colchicine in preventing attacks of familial Mediterranean fever. N Engl J Med 291:932–934

    Article  CAS  PubMed  Google Scholar 

  5. Ludomirsky A, Passwell J, Boichis H (1981) Amyloidosis in children with familial Mediterranean fever. Arch Dis Child 56:464–467

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Oner A, Erdoğan O, Demircin G et al (2003) Efficacy of colchicine therapy in amyloid nephropathy of familial Mediterranean fever. Pediatr Nephrol 18:521–526

    PubMed  Google Scholar 

  7. Bagci S, Toy B, Tuzun A et al (2004) Continuity of cytokine activation in patients with familial Mediterranean fever. Clin Rheumatol 23:333–337

    Article  PubMed  Google Scholar 

  8. Kiraz S, Ertenli I, Arici M, Calguneri M, Haznedaroglu I, Celik I, Pay S, Kirazli S (1988) Effects of colchicine on inflammatory cytokines and selectins in familial Mediterranean fever. Clin Exp Rheumatol 16:721–724

    Google Scholar 

  9. TASK FORCE OF THE EUROPEAN SOCIETY OF CARDIOLOGY AND THE NORTH AMERICAN SOCIETY OF PACING AND ELECTROPHYSIOLOGY (1996) Heart rate variability. Standards of measurement, physiological interpretation, and clinical use. Eur Heart J 17:354–381

    Article  Google Scholar 

  10. Rozenbaum M, Naschitz JE, Yudashkin M, Rosner I, Sabo E, Shaviv N, Gaitini L, Zuckerman E, Yeshurun D (2002) Cardiovascular autonomic dysfunction in familial Mediterranean fever. J Rheumatol 29:987–989

    PubMed  Google Scholar 

  11. Rozenbaum M, Naschitz JE, Yudashkin M, Sabo E, Shaviv N, Gaitini L, Zuckerman E, Yeshurun D, Rosner I (2004) Cardiovascular reactivity score for the assessment of dysautonomia in familial Mediterranean fever. Rheumatol Int 24:147–152

    Article  PubMed  Google Scholar 

  12. Nussinovitch N, Livneh A, Katz K, Langevitz P, Feld O, Nussinovitch M, Volovitz B, Lidar M, Nussinovitch U (2011) Heart rate variability in familial Mediterranean fever. Rheumatol Int 31:39–43

    Article  PubMed  Google Scholar 

  13. Livneh A, Langevitz P, Zemer D, Zaks N, Kees S, Lidar T, Migdal A, Padeh S, Pras M (1997) Criteria for the diagnosis of familial Mediterranean fever. Arthritis Rheum 40:1879–1885

    Article  CAS  PubMed  Google Scholar 

  14. Ben-Chetrit E, Ozdogan H (2008) Non-response to colchicine in FMF—definition, causes and suggested solutions. Clin Exp Rheumatol 26(4 Suppl 50):49–51

    Google Scholar 

  15. Pras E, Livneh A, Balow JE Jr, Pras E, Kastner DL, Pras M, Langevitz P (1998) Clinical differences between North African and Iraqi Jews with familial Mediterranean fever. Am J Med Genet 75:216–219

    Article  CAS  PubMed  Google Scholar 

  16. Bruce RA, Kusumi F, Hosmer D (1973) Maximal oxygen intake and nomographic assessment of functional aerobic impairment in cardiovascular disease. Am Heart J 85:546–562

    Article  CAS  PubMed  Google Scholar 

  17. Naschitz JE, Sabo E, Naschitz S et al (2001) Hemodynamic instability in chronic fatigue syndrome: indices and diagnostic significance. Semin Arthritis Rheum 31:199–208

    Article  CAS  PubMed  Google Scholar 

  18. Naschitz JE, Sabo E, Naschitz S et al (2002) Fractal analysis and recurrence quantification analysis of heart rate and pulse transit time for diagnosing chronic fatigue syndrome. Clin Auton Res 12:262–274

    Article  Google Scholar 

  19. Thomas DE, Exton SA, Yousef ZR (2010) Heart rate deceleration after exercise predicts patients most likely to respond to cardiac resynchronisation therapy. Heart 96:1385–1389

    Article  CAS  PubMed  Google Scholar 

  20. Ardic I, Kaya MG, Yarlioglues M, Dogdu O, Celikbilek M, Akpek M, Akyol L, Torun E (2011) Rheumatol Int 31:121–125, Assessment of heart rate recovery index in patients with familial Mediterranean fever

    Article  PubMed  Google Scholar 

  21. Canpolat U, Dural M, Aytemir K, Akdoğan A, Kaya EB, Sahiner L, Yalçin U, Canpolat AG, Calgüneri M, Kabakçi G, Tokgözoğlu L, Oto A (2012) Evaluation of various cardiac autonomic indices in patients with familial Mediterranean fever on colchicine treatment. Auton Neurosci 167:70–74

    Article  PubMed  Google Scholar 

  22. Koca B, Kasapçopur O, Bakari S, Sönmez E, Oztunç F, Eroğlu AG, Saltik L, Calay O (2012) QT dispersion and cardiac involvement in children with Familial Mediterranean fever. Cardiol Young 22(4):404–409

    Article  PubMed  Google Scholar 

  23. Topal F, Tanindi A, Kurtoglu HG, Akbulut S, Kucukazman M, Topal FE (2011) QT dispersion is not increased in familial Mediterranean fever. J Int Med Res 39(5):2006–2011

    Article  CAS  PubMed  Google Scholar 

  24. Nussinovitch U, Kaminer K, Nussinovitch M, Volovitz B, Lidar M, Nussinovitch N, Livneh A (2012) QT interval variability in familial Mediterranean fever: a study in colchicine-responsive and colchicine-resistant patients. Clin Rheumatol 31(5):795–799

    Article  PubMed  Google Scholar 

  25. Nussinovitch U, Livneh A, Volovitz B, Nussinovitch M, Ben-Zvi I, Lidar M, Nussinovitch N (2012) Normal QT dispersion in colchicine-resistant familial Mediterranean fever (FMF). Clin Rheumatol 31(7):1093–1096

    Article  PubMed  Google Scholar 

  26. Janse van Rensburg DC, Ker JA, Grant CC, Fletcher L (2012) Autonomic impairment in rheumatoid arthritis. Int J Rheum Dis 15:419–426

    Article  PubMed  Google Scholar 

  27. Aydemir M, Yazisiz V, Basarici I, Avci AB, Erbasan F, Belgi A, Terzioglu E (2010) Cardiac autonomic profile in rheumatoid arthritis and systemic lupus erythematosus. Lupus 19:255–261

    Article  CAS  PubMed  Google Scholar 

  28. Newton JL, Frith J, Powell D, Hackett K, Wilton K, Bowman S, Price E, Pease C, Andrews J, Emery P, Hunter J, Gupta M, Vadivelu S, Giles I, Isenberg D, Lanyon P, Jones A, Regan M, Cooper A, Moots R, Sutcliffe N, Bombardieri M, Pitzalis C, McLaren J, Young-Min S, Dasgupta B, Griffiths B, Lendrem D, Mitchell S, Ng WF, UK primary Sjögren’s syndrome registry (2012) Autonomic symptoms are common and are associated with overall symptom burden and disease activity in primary Sjogren’s syndrome. Ann Rheum Dis 71:1973–1979

    Article  PubMed  PubMed Central  Google Scholar 

  29. Straub RH, Zeuner M, Lock G, Rath H, Hein D, Scholmerich J, Lang B (1996) Autonomic and sensorimotor neuropathy in patients with systemic lupus erythematosus and systemic sclerosis. J Rheumatol 23:87–92

    CAS  PubMed  Google Scholar 

  30. Demir H, Keleştimur F, Tunç M, Kirnap M, Ozügül Y (1999) Hypothalamo-pituitary-adrenal axis and growth hormone axis in patients with rheumatoid arthritis. Scand J Rheumatol 28:41–46

    Article  CAS  PubMed  Google Scholar 

  31. Korkmaz C (2006) Is there a hypothalamic-pituitary-adrenal axis dysfunction in patients with familial Mediterranean fever? Clin Rheumatol 25:606–607

    Article  PubMed  Google Scholar 

  32. Korkmaz C, Colak O, Alatas O, Ozarslan A, Ergul B (2002) Early blunted cortisol response to insulin induced hypoglycaemia in familial Mediterranean fever. Clin Exp Rheumatol 20(4 Suppl 26):S8–S12

    CAS  PubMed  Google Scholar 

  33. Huppertz HI, Michels H (1988) The metaraminol provocation test in the diagnosis of familial Mediterranean fever. Monatsschr Kinderheilkd 136:243–245

    CAS  PubMed  Google Scholar 

  34. Peterson GM, McGinty JF (1988) Direct neurotoxic effects of colchicine on cholinergic neurons in medial septum and striatum. Neurosci Lett 94:46–51

    Article  CAS  PubMed  Google Scholar 

  35. Ginn SR, Peterson GM (1992) Studies related to the use of colchicine as a neurotoxin in the septohippocampal cholinergic system. Brain Res 590:144–152

    Article  CAS  PubMed  Google Scholar 

  36. Dinç A (2000) Non-period leg pain in patients with familial Mediterranean fever. Ann Rheum Dis 59:400

    Article  PubMed  PubMed Central  Google Scholar 

  37. Adams DH, Nash GB (1996) Disturbance of leucocyte circulation and adhesion to the endothelium as factors in circulatory pathology. Br J Anaesth 77:17–31

    Article  CAS  PubMed  Google Scholar 

  38. Vallejo M, Martínez-Martínez LA, Grijalva-Quijada S, Olguín-Ruvalcaba HM, Salas E, Hermosillo AG, Cárdenas M, Martínez-Lavín M (2013) Prevalence of fibromyalgia in vasovagal syncope. J Clin Rheumatol 19:111–114

    Article  PubMed  Google Scholar 

  39. da Cunha Ribeiro RP, Roschel H, Artioli GG, Dassouki T, Perandini LA, Calich AL, de Sá Pinto AL, Lima FR, Bonfá E, Gualano B (2011) Cardiac autonomic impairment and chronotropic incompetence in fibromyalgia. Arthritis Res Ther 13(6):R190

    Article  PubMed  PubMed Central  Google Scholar 

  40. Kulshreshtha P, Deepak KK (2013) Autonomic nervous system profile in fibromyalgia patients and its modulation by exercise: a mini review. Clin Physiol Funct Imaging 33:83–91

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatrics, Division of Cardiology, Dokuz Eylül University Faculty of Medicine, Izmir, Turkey

    Murat Şahin, Mustafa Kır & Nurettin Ünal

  2. Department of Public Health, Dokuz Eylül University Health Sciences Institute, Izmir, Turkey

    Pembe Keskinoğlu

  3. Department of Medical Genetics, Dokuz Eylül University Hospital, Izmir, Turkey

    Elçin Bora

  4. Department of Pediatrics, Division of Rheumatology, Dokuz Eylül University Hospital, 35340, Balçova, Izmir, Turkey

    Balahan Makay & Erbil Ünsal

Authors
  1. Murat Şahin
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  2. Mustafa Kır
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  3. Balahan Makay
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  4. Pembe Keskinoğlu
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  6. Erbil Ünsal
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Correspondence to Balahan Makay.

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Şahin, M., Kır, M., Makay, B. et al. Cardiac autonomic functions in children with familial Mediterranean fever. Clin Rheumatol 35, 1237–1244 (2016). https://doi.org/10.1007/s10067-014-2714-z

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  • DOI: https://doi.org/10.1007/s10067-014-2714-z

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