Autonomic dysfunction is common in liver cirrhosis and is associated with cardiac dysfunction and mortality
prospective observational study
Palavras-chave:
Liver cirrhosis, Heart rate, Mortality, Heart diseasesResumo
BACKGROUND: Although autonomic dysfunction has been shown to be associated with liver cirrhosis, the prevalence and prognostic implications are unclear. Abnormal heart rate variability (HRV), a measure of autonomic function, has not been well investigated in cirrhosis. OBJECTIVE: To evaluate the prevalence of high-risk HRV parameters in a cohort of cirrhotic patients and their association with cardiac dysfunction and mortality. DESIGN AND SETTING: Prospective observational study conducted in the Federal University of São Paulo. METHOD: A cohort of 120 patients, comprising 17 healthy controls and 103 cirrhotic outpatients, was evaluated and followed for 10 months. HRV analysis was based on 24-hour Holter monitoring and defined using time-domain and frequency-domain parameters. RESULTS: The HRV parameters were statistically lower in cirrhotic patients than in healthy subjects. Highrisk HRV parameters were prevalent, such that 64% had at least one high-risk parameter. Time-domain parameters correlated with Child scores (P < 0.0001). In regression models, HRV parameters were independent predictors of diastolic dysfunction and mortality. During 10 months of follow-up, there were 11 deaths, all of patients with at least one high-risk HRV parameter. Kaplan-Meier analysis estimated low survival rates among patients with standard deviation of normal-to-normal RR intervals (SDNN) < 100. CONCLUSION: Reduced HRV is prevalent in liver cirrhosis and is related to cardiac dysfunction, severity of liver disease and mortality. Abnormal high-risk HRV parameters are prevalent among cirrhotic patients and are also predictors of mortality. Our findings highlight the need for a more careful cardiac evaluation of cirrhotic patients.
Downloads
Referências
Møller, Henriksen JH. Cirrhotic cardiomyopathy. J Hepatol. 2010;53(1):179-
PMID: 20462649; https://doi.org/10.1016/j.jhep.2010.02.023.
Møller S, Hobolth L, Winkler C, Bendtsen F, Christensen E. Determinants of the hyperdynamic circulation and central hypovolaemia in cirrhosis. Gut. 2011;60(9):1254-9. PMID: 21504996; https://doi.org/10.1136/gut.2010.23547.
Trevisani F, Sica G, Mainquà P, et al. Autonomic dysfunction and hyperdynamic circulation in cirrhosis with ascites. Hepatology. 1999;30(6):1387-92. PMID: 10573516; https://doi.org/10.1002/hep.510300613.
Møller S, Iversen JS, Henriksen JH, Bendtsen F. Reduced baroreflex sensitivity in alcoholic cirrhosis: relations to hemodynamics and humoral systems. Am J Physiol Heart Circ Physiol. 2007;292(6):H2966-72. PMID: 17293491; https://doi.org/10.1152/ajpheart.01227.2006.
Genovesi S, Prata Pizzala DM, Pozzi M, et al. QT interval prolongation and decreased heart rate variability in cirrhotic patients: relevance of hepatic venous pressure gradient and serum calcium. Clin Sci (Lond). 2009;116(12):851-9. PMID: 19076059; https://doi.org/10.1042/CS20080325.
Day CP, James OF, Butler TJ, Campbell RW. QT prolongation and sudden cardiac death in patients with alcoholic liver disease. Lancet. 1993;341(8858):1423-8. PMID: 8099138; https://doi.org/10.1016/0140-6736(93)90879-L.
Bal JS, Thuluvath PJ. Prolongation of QTc interval: relationship with etiology and severity of liver disease, mortality and liver transplantation. Liver Int. 2003;23(4):243-8. PMID: 12895263; https://doi.org/10.1034/j.1600-0676.2003.00833.x.
Rajendra Acharya U, Paul Joseph K, Kannathal N, Lim CM, Suri JS. Heart rate variability: a review. Med Biol Eng Comput. 2006;44(12):1031-51. PMID: 17111118; https://doi.org/10.1007/s11517-006-0119-0.
Lunzer MR, Newman SP, Bernard AG, et al. Impaired cardiovascular responsiveness in liver disease. Lancet. 1975;2(7931):382-5. PMID: 51190; https://doi.org/10.1016/S0140-6736(75)92896-2.
Hendrickse MT, Thuluvath PJ, Triger DR. Natural history of autonomic neuropathy in chronic liver disease. Lancet. 1992;339(8807):1462-4. PMID: 1351136; https://doi.org/10.1016/0140-6736(92)92042-E.
Chaudhry V, Corse AM, O’Brian R, et al. Autonomic and peripheral (sensorimotor) neuropathy in chronic liver disease: A clinical and electrophysiologic study. Hepatology. 1999;29(6):1698-703. PMID: 10347110; https://doi.org/10.1002/hep.510290630.
Fleisher LA, Fleckenstein JF, Frank SM, Thuluvath PJ. Heart rate variability as a predictor of autonomic dysfunction in patients awaiting liver transplantation. Dig Dis Sci. 2000;45(2):340-4. PMID: 10711448; https://doi.org/10.1023/A:1005468711494.
Kleiger RE, Miller JP, Bigger JT, Moss AJ. Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am J Cardiol. 1987;59(4):256-62. PMID: 3812275; https://doi.org/10.1016/0002-9149(87)90795-8.
Huikuri HV, Stein PK. Heart rate variability in risk stratification of cardiac patients. Prog Cardiovasc Dis. 2013;56(2):153-9. PMID: 24215747; https://doi.org/10.1016/j.pcad.2013.07.003.
Ates F, Topal E, Kosar F, et al. The relationship of heart rate variability with severity and prognosis of cirrhosis. Dig Dis Sci. 2006;51(9):1614-8. PMID: 16927142; https://doi.org/10.1016/j.pcad.2013.07.003.
Terziyski K, Andonov V, Marinov B, Kostianev S. Exercise performance and ventilatory efficiency in patients with mild and moderate liver cirrhosis. Clin Exp Pharmacol Physiol. 2008;35(2):135-40. PMID: 18197891; https://doi.org/10.1111/j.1440-1681.2007.04751.x.
de Lima DC, Ribeiro HS, Cristina R, et al. Functional status and heart rate variability in end-stage liver disease patients: Association with nutritional status. Nutrition. 2015;31(7-8):971-4. PMID: 26059370; https://doi.org/10.1016/j.nut.2015.01.014.
Mani AR, Montagnese S, Jackson CD, 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(2):G330-8. PMID: 19023029; https://doi.org/10.1152/ajpgi.90488.2008.
Mozos I. Arrhythmia risk in liver cirrhosis. World J Hepatol. 2015;7(4):662-
PMID: 25866603; https://doi.org/10.4254/wjh.v7.i4.662.
O’Shea RS, Dasarathy S, McCullough AJ; Practice Guideline Committee of the American Association for the Study of Liver Diseases; Practice Parameters Committee of the American College of Gastroenterology. Alcoholic liver disease. Hepatology. 2010;51(1):307-28. PMID: 20034030; https://doi.org/10.1002/hep.23258.
Bazzett HC. An analysis of the time-relations of electrocardiogram. Annals of Noninvasive Electrocardiology. 1997;2(2):177-94. https://doi.org/10.1111/j.1542-474X.1997.tb00325.x.
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. 1996;17:354-81. PMID: 8598068; https://doi.org/10.1093/oxfordjournals.eurheartj.a014868.
Nagueh SF, Appleton CP, Gillebert TC, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography. Eur J Echocardiogr. 2009;10(2):165-93. https://doi.org/10.1093/ejechocard/jep007
Dümcke CW, Møller S. Autonomic dysfunction in cirrhosis and portal hypertension. Scand J Clin Lab Invest. 2008;68(6):437-47. PMID: 18609092; https://doi.org/10.1080/00365510701813096.
Møller S, Henriksen JH. Cardiovascular complications of cirrhosis. Gut. 2008;57(2):268-78. PMID: 18192456; http://dx.doi.org/10.1136/gut.2006.112177.
Bajaj BK, Agarwal MP, Ram BK. Autonomic neuropathy in patients with hepatic cirrhosis. Postgrad Med J. 2003;79(933):408-11. PMID: 12897221; http://dx.doi.org/10.1136/pmj.79.933.408.
Baratta L, Tubani L, Merli M, et al. Long-term effect of liver transplantation on cirrhotic autonomic cardiac dysfunction. Dig Liver Dis. 2010;42(2):131-6. PMID: 19540819; https://doi.org/10.1016/j. dld.2009.05.009.
Milovanovic B, Milinic N, Trifunovic D, et al. Autonomic dysfunction in alcoholic cirrhosis and its relation to sudden cardiac death risk predictors. Gen Physiol Biophys. 2009;28 Spec No:251-61. PMID: 19893108.
Møller S, Wiinberg N, Hernriksen JH. Noninvasive 24-hour ambulatory arterial blood pressure monitoring in cirrhosis. Hepatology. 1995;22(1):88-95. PMID: 7601438; https://doi.org/10.1002/hep.1840220114.
Gerbes A, Remien J, Jüngst D, Sauerbruch T, Paumgartner G. Evidence for down-regulation of beta-2-adrenoceptors in cirrhotic patients with severe ascites. Lancet. 1986;1(8495):1409-11. PMID: 2872517; https://doi.org/10.1016/S0140-6736(86)91556-4.
Bernardi M, Galandra S, Colantoni A, et al. Q-T interval prolongation in cirrhosis: Prevalence, relationship with severity, and etiology of the disease and possible pathogenetic factors. Hepatology. 1998;27(1):28-34. PMID: 9425913; https://doi.org/10.1002/hep.510270106.
Henriksen JH, Bendtsen F, Hansen EF, Møller S. Acute non-selective β-adrenergic blockade reduces prolonged frequency-adjusted Q-T interval (QTc) in patients with cirrhosis. J Hepatol. 2004;40(2):239-46. PMID: 14739094; https://doi.org/10.1016/j.jhep.2003.10.026.
Hull SS, Vanoli E, Adamson PB, et al . Exercise training confers anticipatory protection from sudden death during acute myocardial ischemia. Circulation. 1994;89(2):548-52. PMID: 8313542; https://doi.org/10.1161/01.CIR.89.2.548.
La Rovere MT, Bigger JT Jr, Marcus FI, Mortara A, Schwartz PJ. Baroreflex sensitivity and heart-rate variabiltiy in prediction of total cardiac mortality after myocardial infarction. Lancet. 1998;351(9101):478-84. PMID: 9482439; https://doi.org/10.1016/S0140-6736(97)11144-8.
Downloads
Publicado
Como Citar
Edição
Seção
Licença
Este trabalho está licenciado sob uma licença Creative Commons Attribution 4.0 International License.
