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Liver, Pancreas and Biliary Tract| Volume 51, ISSUE 5, P695-702, May 2019

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Which heart rate variability index is an independent predictor of mortality in cirrhosis?

Published:September 24, 2018DOI:https://doi.org/10.1016/j.dld.2018.09.011

      Abstract

      Background

      Liver cirrhosis is associated with reduced heart rate variability (HRV), which indicates impaired integrity of cardiovascular control in this patient population. There are several different indices for HRV quantification. The present study was designed to: 1) determine which of the HRV indices is best at predicting mortality in patients with cirrhosis; 2) verify if such ability to predict mortality is independent of the severity of hepatic failure.

      Methods

      Ten minutes electrocardiogram was recorded in 74 patients with cirrhosis. Heart rate fluctuations were quantified using statistical, geometrical and non-linear analysis. The patients were followed-up for 18 months and information was collected on the occurrence of death/liver transplantation.

      Results

      During the follow-up period, 24 patients (32%) died or were transplanted for hepatic decompensation. Cox’s regression analysis showed that SDNN (total HRV), cSDNN (corrected SDNN), SD1 (short-term HRV), SD2 (long-terms HRV) and spectral indices could predict survival in these patients. However, only SD2 and cSDNN were shown to be independent of MELD in predicting survival. The prognostic value of HRV indices was independent of age, gender, use of beta blockers, and the aetiology of liver disease.

      Conclusion

      Two HRV indices were identified that could predict mortality in patients with cirrhosis, independently of MELD. These indices are potentially useful tools for survival prediction.

      Keywords

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      References

        • Mokdad A.A.
        • Lopez A.D.
        • Shahraz S.
        • Lozano R.
        • Mokdad A.H.
        • Stanaway J.
        • et al.
        Liver cirrhosis mortality in 187 countries between 1980 and 2010: a systematic analysis.
        BMC Med. 2014; 12: 145
        • Arvaniti V.
        • D’Amico G.
        • Fede G.
        • Manousou P.
        • Tsochatzis E.
        • Pleguezuelo M.
        • et al.
        Infections in patients with cirrhosis increase mortality four-fold and should be used in determining prognosis.
        Gastroenterology. 2010; 139 (1246–1256.e5)
        • Zipprich A.
        • Garcia-Tsao G.
        • Rogowski S.
        • Fleig W.E.
        • Seufferlein T.
        • Dollinger M.M.
        Prognostic indicators of survival in patients with compensated and decompensated cirrhosis.
        Liver Int. 2012; 32: 1407-1414
        • Montagnese S.
        • De Rui M.
        • Schiff S.
        • Ceranto E.
        • Valenti P.
        • Angeli P.
        • et al.
        Prognostic benefit of the addition of a quantitative index of hepatic encephalopathy to the MELD score: the MELD-EEG.
        Liver Int. 2015; 35: 58-64
        • Tsuji H.
        • Venditti F.J.
        • Manders E.S.
        • Evans J.C.
        • Larson M.G.
        • Feldman C.L.
        • et al.
        Reduced heart rate variability and mortalit risk in an elderly cohort the framingham heart study.
        Circulation. 1994; : 878-883
        • Mani A.R.
        • Montagnese S.
        • Jackson C.D.
        • Jenkins C.W.
        • Head I.M.
        • Stephens R.C.
        • et al.
        Decreased heart rate variability in patients with cirrhosis relates to the presence and degree of hepatic encephalopathy.
        Am J Physiol Gastrointest Liver Physiol. 2009; 296: G330-G338
        • Hoshi R.A.
        • Pastre C.M.
        • Vanderlei L.C.M.
        • Godoy M.F.
        Poincaré plot indexes of heart rate variability: Relationships with other nonlinear variables.
        Auton Neurosci. 2013; 177: 271-274
      1. Peng C. ‐K., Havlin S, Stanley HE, Goldberger AL. Quantification of scaling exponents and crossover phenomena in nonstationary heartbeat time series. Chaos An Interdiscip J Nonlinear Sci [Internet] 1995 March 5(1):82–7. [Cited 4 July 2018]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11538314.

        • Costa M.
        • Costa M.
        • Goldberger A.L.
        • Goldberger A.L.
        • Peng C.-K.
        • Peng C.-K.
        • et al.
        Multiscale Entropy Analysis (MSE).
        Entropy. 2005; 89: 1-8
        • Richman J.S.
        • Moorman J.R.
        Physiological time-series analysis using approximate entropy and sample entropy.
        Am J Physiol Heart Circ Physiol. 2000; 278: H2039-H2049
        • Sassi R.
        • Cerutti S.
        • Lombardi F.
        • Malik M.
        • Huikuri H.V.
        • Peng C.-K.
        • et al.
        Advances in heart rate variability signal analysis: joint position statement by the e-Cardiology ESC Working Group and the European Heart Rhythm Association co-endorsed by the Asia Pacific Heart Rhythm Society.
        Europace. 2015; 17: 1341-1353
        • Nolan J.
        • Batin P.D.
        • Andrews R.
        • Lindsay S.J.
        • Brooksby P.
        • Mullen M.
        • et al.
        Prospective study of heart rate variability and mortality in chronic heart failure: results of the United Kingdom heart failure evaluation and assessment of risk trial (UK-heart).
        Circulation. 1998; 98: 1510-1516
        • Drawz P.E.
        • Babineau D.C.
        • Brecklin C.
        • He J.
        • Kallem R.R.
        • Soliman E.Z.
        • et al.
        Heart rate variability is a predictor of mortality in chronic kidney disease: a report from the CRIC study.
        Am J Nephrol. 2013; 38: 517-528
        • Mäkikallio T.H.
        • Høiber S.
        • Køber L.
        • Torp-Pedersen C.
        • Peng C.K.
        • Goldberger A.L.
        • et al.
        Fractal analysis of heart rate dynamics as a predictor of mortality in patients with depressed left ventricular function after acute myocardial infarction. TRACE Investigators. TRAndolapril Cardiac Evaluation.
        Am J Cardiol. 1999; 83: 836-839
        • Ates F.
        • Topal E.
        • Kosar F.
        • Karincaoglu M.
        • Yildirim B.
        • Aksoy Y.
        • et al.
        The relationship of heart rate variability with severity and prognosis of cirrhosis.
        Dig Dis Sci. 2006; 51: 1614-1618
        • Chan K.-C.
        • Yeh J.-R.
        • Sun W.-Z.
        The role of autonomic dysfunction in predicting 1-year mortality after liver transplantation.
        Liver Int. 2017; 37: 1239-1248
        • Fleisher L.A.
        • Fleckenstein J.F.
        • Frank S.M.
        • Thuluvath P.J.
        Heart rate variability as a predictor of autonomic dysfunction in patients awaiting liver transplantation.
        Dig Dis Sci. 2000; 45: 340-344
      2. Monfredi O, Lyashkov AE, Johnsen A-B, Inada S, Schneider H, Wang R, et al. Biophysical Characterization of the Underappreciated and Important Relationship Between Heart Rate Variability and Heart RateNovelty and Significance. Hypertension [Internet] 2014;64(6):1334–43. Available from: 10.1161/HYPERTENSIONAHA.114.03782.

        • Taghipour M.
        • Eftekhari G.
        • Haddadian Z.
        • Mazloom R.
        • Mani M.
        • Mani A.R.
        Increased sample asymmetry and memory of cardiac time-series following endotoxin administration in cirrhotic rats.
        Physiol Meas. 2016; 37: N96-N104
        • Tarvainen M.P.
        • Niskanen J.-P.
        • Lipponen J.A.
        • Ranta-aho P.O.
        • Karjalainen P.A.
        Kubios HRV — Heart rate variability analysis software.
        Comput Methods Programs Biomed. 2014; 113: 210-220
        • Bhogal A.S.
        • Mani A.R.
        Pattern analysis of oxygen saturation variability in healthy individuals: entropy of pulse oximetry signals carries information about mean oxygen saturation.
        Front Physiol. 2017; 8: 555
        • Haddadian Z.
        • Eftekhari G.
        • Mazloom R.
        • Jazaeri F.
        • Dehpour A.R.
        • Mani A.R.
        Effect of endotoxin on heart rate dynamics in rats with cirrhosis.
        Auton Neurosci Basic Clin. 2013; 177: 104-113
      3. Tateishi Y, Oda S, Nakamura M, Watanabe K, Kuwaki T, Moriguchi T, et al. Depressed heart rate variability is associated with high IL-6 blood level and decline in the blood pressure in septic patients. Shock [Internet] 2007;28(5):549–53. [Cited 24 Aug 2018]. Available from: https://insights.ovid.com/pubmed?pmid=18075483.

      4. González-Clemente J-M, Vilardell C, Broch M, Megia A, Caixàs A, Giménez-Palop O, et al. Lower heart rate variability is associated with higher plasma concentrations of IL-6 in type 1 diabetes. Eur J Endocrinol [Internet]; 2007 Jul 1. [Cited 24 Aug 2018];157(1):31–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17609399.

        • Wiese S.
        • Hove J.D.
        • Bendtsen F.
        • Møller S.
        Cirrhotic cardiomyopathy: pathogenesis and clinical relevance.
        Nat Rev Gastroenterol Hepatol. 2014; 11: 177-186
        • Møller S.
        • Lee S.S.
        Cirrhotic cardiomyopathy.
        J Hepatol. 2018; 0
        • Chessa M.
        • Butera G.
        • Lanza G.A.
        • Bossone E.
        • Delogu A.
        • De Rosa G.
        • et al.
        Role of heart rate variability in the early diagnosis of diabetic autonomic neuropathy in children.
        Herz. 2002; 27: 785-790
        • Akselrod S.
        • Gordon D.
        • Ubel F.A.
        • Shannon D.C.
        • Berger A.C.
        • Cohen R.J.
        Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control.
        Science. 1981; 213: 220-222
        • Fleisher L.A.
        • Frank S.M.
        • Sessler D.I.
        • Cheng C.
        • Matsukawa T.
        • Vannier C.A.
        Thermoregulation and heart rate variability.
        Clin Sci (Lond). 1996; 90: 97-103
        • Garrido M.
        • Saccardo D.
        • De Rui M.
        • Vettore E.
        • Verardo A.
        • Carraro P.
        • et al.
        Abnormalities in the 24-hour rhythm of skin temperature in cirrhosis: sleep-wake and general clinical implications.
        Liver Int. 2017; 37: 1833-1842
        • Mani A.R.
        • Mazloom R.
        • Haddadian Z.
        • Montagnese S.
        Body temperature fluctuation analysis in cirrhosis.
        Liver Int. 2018; 38: 378-379
      5. Task Force of The European Society of Cardiology and The North American, Society of Pacing and Electrophysiology (Membership. Guidelines Heart rate variability Standards of measurement, physiological interpretation, and clinical use. Eur Heart J [Internet] 1996;17:354–81 [Cited 25 August 2018]. Available from: https://www.escardio.org/static_file/Escardio/Guidelines/Scientific-Statements/guidelines-Heart-Rate-Variability-FT-1996.pdf.

        • Baratta L.
        • Tubani L.
        • Merli M.
        • Labbadia F.
        • Facchini D.
        • De Marco R.
        • et al.
        Long-term effect of liver transplantation on cirrhotic autonomic cardiac dysfunction.
        Dig Liver Dis. 2010; 42: 131-136
        • Bhogal A.S.
        • Montagnese S.
        • Mani A.R.
        The consideration of heart rate complexity as a co-morbidity factor for liver transplantation selection procedures.
        Liver Int. 2018; 38: 380
      6. De Castilho FM, Luiz A, Ribeiro P, Luiz J, Da Silva P, Nobre V, et al. Heart rate variability as predictor of mortality in sepsis: A prospective cohort study; 2017. [Cited 13 August 2018]; Available from: doi.org/10.1371/journal.pone.0180060.

        • Hajiasgharzadeh K.
        • Mirnajafi-Zadeh J.
        • Mani A.R.
        Interleukin-6 impairs chronotropic responsiveness to cholinergic stimulation and decreases heart rate variability in mice.
        Eur J Pharmacol. 2011; 673
      7. Olofsson PS, Rosas-Ballina M, Levine YA, Tracey KJ. Rethinking inflammation: Neural circuits in the regulation of immunity. Immunol Rev [Internet] 2012;248(1):188–204. [Cited 13 August 2018]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536565/pdf/nihms488462. pdf.

        • Mazloom R.
        • Eftekhari G.
        • Rahimi M.
        • Khori V.
        • Hajizadeh S.
        • Dehpour A.R.
        • et al.
        The role of α7 nicotinic acetylcholine receptor in modulation of heart rate dynamics in endotoxemic rats.
        PLoS One. 2013; 8
        • Eftekhari G.
        • Ahmadi Soleimani S.M.
        • Mani A.R.
        Heart rate variability, vagal activity and the pulse of inflammation.
        J Intern Med. 2013; 274
        • Eftekhari G.
        • Hajiasgharzadeh K.
        • Ahmadi-Soleimani S.M.
        • Dehpour A.R.
        • Semnanian S.
        • Mani A.R.
        Activation of central muscarinic receptor type 1 prevents development of endotoxin tolerance in rat liver.
        Eur J Pharmacol. 2014; : 740
        • Hajiasgharzadeh K.
        • Tavangar S.M.
        • Javan M.
        • Dehpour A.R.
        • Mani A.R.
        Does hepatic vagus nerve modulate the progression of biliary fibrosis in rats?.
        Auton Neurosci Basic Clin. 2014; : 185
      8. Hajiasgharzadeh K, Baradaran B. Cholinergic anti-inflammatory pathway and the liver [Internet]. Vol. 7, Advanced Pharmaceutical Bulletin; 2017;p. 507–13. [Cited 23 July 2018]. Available from: http://apb.tbzmed.ac.ir.

        • Liu H.
        • Jayakumar S.
        • Traboulsi M.
        • Lee S.S.
        Cirrhotic cardiomyopathy: implications for liver transplantation.
        Liver Transpl. 2017; 23: 826-835
        • Mani A.R.
        • Ippolito S.
        • Ollosson R.
        • Moore K.P.
        Nitration of cardiac proteins is associated with abnormal cardiac chronotropic responses in rats with biliary cirrhosis.
        Hepatology. 2006; 43: 847-856
        • Song D.
        • Sharkey K.A.
        • Breitman D.R.
        • Zhang Y.
        • Lee S.S.
        Disordered central cardiovascular regulation in portal hypertensive and cirrhotic rats.
        Am J Physiol Liver Physiol. 2001; 280: G420-G430