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Heart rate variability in familial Mediterranean fever

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Abstract

Familial Mediterranean fever (FMF) is a hereditary disease, characterized by recurrent episodes of fever and polyserositis. Heart rate variability (HRV) is a powerful, simple and reliable technique to evaluate autonomic nervous system function. Previous studies of physiologic parameters during tilt-test have suggested that patients with FMF have abnormal cardiovascular reactivity and occult dysautonomia. Prompted by these findings, the present study sought to evaluate HRV in patients with FMF, at rest and in the standing position. The study sample included 34 patients with FMF and 34 sex- and age-matched control subjects. All underwent electrocardiography according to strict criteria. HRV parameters were computed with custom-made software. There was no significant difference in HRV parameters, in either the supine or standing position, between the FMF and control groups. In both groups, the upright position was associated with a significant decrease, when compared with the supine position, in maximal RR interval, minimal RR, average RR, root square of successive differences in RR interval, number of intervals differing by >50 ms from preceding interval (NN50), NN50 divided by total number of intervals (pNN50) and high-frequency components as well as a significant increase in average heart rate, very low frequency or low-frequency components, low-frequency/high-frequency components ratio and total power. In conclusion, patients with FMF who are continuously treated with low-dose colchicine have not developed amyloidosis and have normal HRV parameters in the supine and upright position. Further investigation of occult dysautonomia in FMF is needed.

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Abbreviations

FMF:

Familial Mediterranean fever

HRV:

Heart rate variability

ANS:

Autonomic nervous system

ECG:

Electrocardiogram

SDNN:

Standard deviation of the RR interval

RMSSD:

Square root of the mean squared differences of successive RR intervals

NN50:

Number of NN intervals differing by >50 ms from the preceding interval

pNN50:

NN50 divided by the total number of RR intervals

VLF:

Very low frequency

LF:

Low frequency

HF:

High frequency

References

  1. Touitou I, Sarkisian T, Medlej-Hashim M, Tunca M, Livneh A, Cattan D, Yalcinkaya F, Ozen S, Majeed H, Ozdogan H, Kastner D, Booth D, Ben-Chetrit E, Pugnere D, Michelon C, Seguret F, Gershoni-Baruch R (2007) Country as the primary risk factor for renal amyloidosis in familial Mediterranean fever. Arthritis Rheum 56:1706–1712

    Article  PubMed  Google Scholar 

  2. Gershoni-Baruch R, Brik R, Zacks N, Shinawi M, Lidar M, Livneh A (2003) The contribution of genotypes at the MEFV and SAA1 loci to amyloidosis and disease severity in patients with familial Mediterranean fever. Arthritis Rheum 48:1149–1155

    Article  PubMed  Google Scholar 

  3. 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 

  4. Lachmann HJ, Goodman HJ, Gilbertson JA, Gallimore JR, Sabin CA, Gillmore JD, Hawkins PN (2007) Natural history and outcome in systemic AA amyloidosis. N Engl J Med 356:2361–2371

    Article  CAS  PubMed  Google Scholar 

  5. Gasparyan AY, Ugurlucan M (2008) The emerging issue of cardiovascular involvement in familial Mediterranean fever. Arch Med Sci 4:460–464

    Google Scholar 

  6. Tavil Y, Ureten K, Ozturk MA, Sen N, Kaya MG, Cemri M, Cengel A (2008) The detailed assessment of left and right ventricular functions by tissue Doppler imaging in patients with familial Mediterranean fever. Clin Rheumatol 27:189–194

    Article  PubMed  Google Scholar 

  7. Baysal T, Peru H, Oran B, Sahin TK, Koksal Y, Karaaslan S (2009) Left ventricular diastolic function evaluated with tissue Doppler imaging in children with familial Mediterranean fever. Clin Rheumatol 28:23–28

    Article  PubMed  Google Scholar 

  8. Nussinovitch U, Shoenfeld Y (2009) Autoimmunity and heart diseases: pathogenesis and diagnostic criteria. Arch Immunol Ther Exp 57:95–104

    Article  Google Scholar 

  9. Sari I, Karaoglu O, Can G, Akar S, Gulcu A, Birlik M, Akkoc N, Tunca M, Goktay Y, Onen F (2007) Early ultrasonographic markers of atherosclerosis in patients with familial Mediterranean fever. Clin Rheumatol 26:1467–1473

    Article  PubMed  Google Scholar 

  10. Akdogan A, Calguneri M, Yavuz B, Arslan EB, Kalyoncu U, Sahiner L, Karadag O, Ertenli I, Kiraz S, Aytemir K, Akata D, Tokgozoglu L, Oto A (2006) Are familial Mediterranean fever (FMF) patients at increased risk for atherosclerosis? Impaired endothelial function and increased intima media thickness are found in FMF. J Am Coll Cardiol 48:2351–2353

    Article  PubMed  Google Scholar 

  11. Stojanovich L, Milovanovich B, de Luka SR, Popovich-Kuzmanovich D, Bisenich V, Djukanovich B, Randjelovich T, Krotin M (2007) Cardiovascular autonomic dysfunction in systemic lupus, rheumatoid arthritis, primary Sjogren syndrome and other autoimmune diseases. Lupus 16:181–185

    CAS  PubMed  Google Scholar 

  12. Maule S, Quadri R, Mirante D, Pellerito RA, Marucco E, Marinone C, Vergani D, Chiandussi L, Zanone MM (1997) Autonomic nervous dysfunction in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA): possible pathogenic role of autoantibodies to autonomic nervous structures. Clin Exp Immunol 110:423–427

    Article  CAS  PubMed  Google Scholar 

  13. (1996) Heart rate variability. Standards of measurement, physiological interpretation, and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Eur Heart J 17:354–381

  14. (1996) Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Circulation 93:1043–1106

  15. 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 

  16. 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 

  17. Naschitz JE, Rosner I, Rozenbaum M, Fields M, Isseroff H, Babich JP, Zuckerman E, Elias N, Yeshurun D, Naschitz S, Sabo E (2004) Patterns of cardiovascular reactivity in disease diagnosis. Q J Med 97:141–151

    CAS  Google Scholar 

  18. Kleiger RE, Stein PK, Bigger JT Jr (2005) Heart rate variability: measurement and clinical utility. Ann Noninvasive Electrocardiol 10:88–101

    Article  PubMed  Google Scholar 

  19. Hilz MJ, Dutsch M (2006) Quantitative studies of autonomic function. Muscle Nerve 33:6–20

    Article  PubMed  Google Scholar 

  20. England JD, Gronseth GS, Franklin G, Carter GT, Kinsella LJ, Cohen JA, Asbury AK, Szigeti K, Lupski JR, Latov N, Lewis RA, Low PA, Fisher MA, Herrmann DN, Howard JF, Jr., Lauria G, Miller RG, Polydefkis M, Sumner AJ (2009) Practice parameter: evaluation of distal symmetric polyneuropathy: role of autonomic testing, nerve biopsy, and skin biopsy (an evidence-based review). Report of the American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and American Academy of Physical Medicine and Rehabilitation. Neurology 72:177–184

    Google Scholar 

  21. Freeman R (2006) Assessment of cardiovascular autonomic function. Clin Neurophysiol 117:716–730

    Article  PubMed  Google Scholar 

  22. Klein I (1983) Colchicine stimulates the rate of contraction of heart cells in culture. Cardiovasc Res 17:459–465

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We wish to thank Dr. Hillary Voet of the Hebrew University of Jerusalem, Faculty of Agricultural Food and Environmental Quality Sciences, for her assistance with the statistical analysis. We also thank Gloria Ginzach, Hanni Penn and Phyllis Curchack Kornspan for their editorial assistance. This study is dedicated to the memory of Haim Gueron.

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Authors and Affiliations

  1. Hypertension Unit, Department of Internal Medicine D, Chaim Sheba Medical Center, Tel Hashomer, Israel

    Naomi Nussinovitch

  2. Department of Medicine F, Sheba Medical Center, The Heller Institute of Medical Research, Tel Hashomer, Israel

    Avi Livneh, Pnina Langevitz, Olga Feld & Merav Lidar

  3. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Naomi Nussinovitch, Avi Livneh, Keren Katz, Pnina Langevitz, Olga Feld, Moshe Nussinovitch, Benjamin Volovitz, Merav Lidar & Udi Nussinovitch

  4. Department of Pediatrics C, Schneider Children’s Medical Center of Israel, Petach Tikva, Israel

    Moshe Nussinovitch & Benjamin Volovitz

  5. Department of Internal Medicine B, Sheba Medical Center, Tel Hashomer, Israel

    Udi Nussinovitch

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  1. Naomi Nussinovitch
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  2. Avi Livneh
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  3. Keren Katz
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  4. Pnina Langevitz
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  6. Moshe Nussinovitch
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  9. Udi Nussinovitch
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Correspondence to Naomi Nussinovitch.

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Nussinovitch, N., Livneh, A., Katz, K. et al. Heart rate variability in familial Mediterranean fever. Rheumatol Int 31, 39–43 (2011). https://doi.org/10.1007/s00296-009-1214-y

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  • DOI: https://doi.org/10.1007/s00296-009-1214-y

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