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Heart Rate Variability as a Predictor of Autonomic Dysfunction in Patients Awaiting Liver Transplantation

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Abstract

Chronic liver disease, both alcoholic and nonalcoholic, has been shown to be associated with autonomic neuropathy, as well as other hemodynamic and circulatory disturbances. In a longitudinal study, the presence of autonomic neuropathy and the severity of liver disease were independent risk factors for mortality. The aim of this study was to determine whether the severity of liver disease correlated with measures of heart rate variability. We studied 21 patients being evaluated for liver transplantation to determine if severity of disease correlated with heart rate variability and compared them to seven healthy controls. Heart rate variability was determined for a series of 500 consecutive R-R intervals during quiet breathing. Standard deviation, pNN50, a marker of parasympathetic function, and approximate entropy (ApEn), a recently described measure of regularity, were calculated. Four standard tests of autonomic function were also performed. pNN50 was significantly reduced in all liver disease patients compared to controls (P < 0.05). Both standard deviation and ApEn were significantly reduced in Child’s class C patients suggesting a generalized dysfunction in cardiovascular homeostasis. ApEn was significantly lower in the nonsurvivors during follow-up than the survivors (P < 0.05). In conclusion, increasing severity of liver failure is associated with a reduction in total heart rate variability and regularity. Measurement of heart rate variability offers a simple, noninvasive means of assessing the cardiovascular and autonomic effects of liver disease, particularly in those awaiting liver transplantation.

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REFERENCES

  1. Appel ML, Berger RD, Saul JP, Smith JM, Cohen RJ: Beatto-beat variability in cardiovascular variables: Noise or music? J Am Coll Cardiol 14:1139-1148, 1989

    Google Scholar 

  2. Malliani A, Pagani M, Lombardi F, Cerutti S: Cardiovascular neural regulation explored in the frequency domain. Circulation 84:482-492, 1991

    Google Scholar 

  3. Kleiger RE, Miller JP, Bigger JTJ, Moss AJ: Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am J Cardiol 59(4):256-262, 1987

    Google Scholar 

  4. Pincus S: Approximate entropy as a measure of system complexity. Proc Natl Acad Sci USA 88:2297-2301, 1991

    Google Scholar 

  5. Kaplan DT, Furman MI, Pincus SM, Ryan SM, Lipsitz LA, Goldberger AL: Aging and the complexity of cardiovascular dynamics. Biophys J 59(4):945-949, 1991

    Google Scholar 

  6. Fleisher LA, Pincus SM, Rosenbaum SH: Approximate entropy of heart rate as a correlate of postoperative ventricular dysfunction. Anesthesiology 78(4):683-692, 1993

    Google Scholar 

  7. Thuluvath PJ, Triger DR: Autonomic neuropathy and chronic liver disease. Q J Med 72(268):737-747, 1989

    Google Scholar 

  8. Lunzer MR, Newman SP, Bernard AG, Manghani KK, Sherlock SP, Ginsburg J: Impaired cardiovascular responsiveness in liver disease. Lancet 2(7931):382-385, 1975

    Google Scholar 

  9. Hendrickse MT, Thuluvath PJ, Triger DR: Natural history of autonomic neuropathy in chronic liver disease. Lancet 339(8807):1462-1464, 1992

    Google Scholar 

  10. Kleiger RE, Stein PK, Bosner MS, Rottman JN: Time domain measurements of heart rate variability. Cardiol Clin 10(3):487-498, 1992

    Google Scholar 

  11. Pincus SM, Gladstone IM, Ehrenkranz RA: A regularity statistic for medical data analysis. J Clin Monit 7(4):335-345, 1991

    Google Scholar 

  12. Ewing DJ, Clarke BF: Diagnosis and management of diabetic autonomic neuropathy. Br Med J (Clin Res Ed) 285(6346):916-918, 1982

    Google Scholar 

  13. Smith SE, Smith SA: Heart rate variability in healthy subjects measured with a bedside computer-based technique. Clin Sci (Colch) 61(4):379-383, 1981

    Google Scholar 

  14. Vybiral T, Bryg RJ, Maddens ME, Boden WE: Effect of passive tilt on sympathetic and parasympathetic components of heart rate variability in normal subjects. Am J Cardiol 63(15):1117-1120, 1989

    Google Scholar 

  15. Ewing DJ, Neilson JM, Travis P: New method for assessing cardiac parasympathetic activity using 24 hour electrocardiograms. Br Heart J 52(4):396-402, 1984

    Google Scholar 

  16. Bigger JTJ, Kleiger RE, Fleiss JL, Rolnitzky LM, Steinman RC, Miller JP: Components of heart rate variability measured during healing of acute myocardial infarction. Am J Cardiol 61(4):208-215, 1988

    Google Scholar 

  17. Hartman ML, Pincus SM, Johnson ML, Mathews DH, Faunt LM, Vance ML, Thorner MO, Veldhuis JD: Enhanced basal and disorderly growth hormone secretion distinguish acromegalic from normal pulsatile growth hormone release. J Clin Invest 94(3):1277-1288, 1994

    Google Scholar 

  18. Pincus SM, Keefe DL: Quantification of hormone pulsatility via an approximate entropy algorithm. Am J Physiol 262(5 Pt 1):E741-E754, 1992

    Google Scholar 

  19. Pincus SM, Cummins TR, Haddad GG: Heart rate control in normal and aborted-SIDS infants. Am J Physiol 264(3 Pt 2):R638-R646, 1993

    Google Scholar 

  20. Pincus SM, Viscarello RR: Approximate entropy: A regularity measure for fetal heart rate analysis. Obstet Gynecol 79(2):249-255, 1992

    Google Scholar 

  21. Pincus SM: Greater signal regularity may indicate increased system isolation. Math Biosci 122(2):161-181, 1994

    Google Scholar 

  22. Pincus SM, Goldberger AL: Physiological time-series analysis: What does regularity quantify? Am J Physiol 266(4 Pt 2):H1643-H1656, 1994

    Google Scholar 

  23. Ryan SM, Goldberger AL, Pincus SM, Mietus J, Lipsitz LA: Gender-and age-related differences in heart rate dynamics: are women more complex than men? J Am Coll Cardiol 24:1700-1707, 1994

    Google Scholar 

  24. Fleisher LA, DiPietro J, Pincus S: Increase in heart rate complexity during fetal development. Circulation 90:I-330, 1994 (abstract)

    Google Scholar 

  25. Kleiger RE, Bigger JT, Bosner MS, Chung MK, Cook JR, Rolnitzky LM, Steinman R, Fleiss JL: Stability over time of variables measuring heart rate variability in normal subjects. Am J Cardiol 68(6):626-630, 1991

    Google Scholar 

  26. Bigger JT Jr, Fleiss JL, Steinman RC, Rolnitzky LM, Schneider WJ, Stein PK: RR variability in healthy, middle-aged persons compared with patients with chronic heart disease or recent myocardial infarction. Circulation 91:1936-1943, 1995

    Google Scholar 

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Fleisher, L.A., Fleckenstein, J.F., Frank, S.M. et al. Heart Rate Variability as a Predictor of Autonomic Dysfunction in Patients Awaiting Liver Transplantation. Dig Dis Sci 45, 340–344 (2000). https://doi.org/10.1023/A:1005468711494

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