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Cirrhotic Cardiomyopathy: Pathogenic Mechanisms and Management Strategies

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Complications of Cirrhosis

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Abstract

Cirrhotic cardiomyopathy is defined as attenuated systolic and diastolic contractile responses to stress stimuli, electrophysiological repolarization changes, including prolonged QT interval, and enlargement or hypertrophy of cardiac chambers. The abnormal ventricular function is manifested under conditions of physiological or pharmacological stress, such as liver transplantation and transjugular intrahepatic portosystemic shunt insertion. Attenuated myocardial beta-adrenergic receptor function, increased activity of cardiac contractility inhibitors such as tumor necrosis factor-alpha, nitric oxide and carbon monoxide, and apoptosis have been shown to play an important role in the pathogenesis of this condition. The diagnostic criteria include abnormal systolic contractile responses to stress, diastolic dysfunction at rest, and the absence of clinically significant primary cardiopulmonary disease. Current pharmacological treatment is nonspecific and directed towards alleviation of left ventricular failure. Liver transplantation is currently the only proven treatment with a specific effect on cirrhotic cardiomyopathy.

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Notes

  1. 1.

    These are the preliminary Cirrhotic Cardiomyopathy Working Group criteria presented at the Montreal World Congress of Gastroenterology 2005 consensus meeting organized by SS Lee.

References

  1. Yang YY, Liu H, Nam SW, Kunos G, Lee SS. Mechanisms of TNFalpha-induced cardiac dysfunction in cholestatic bile duct-ligated mice: interaction between TNFalpha and endocannabinoids. J Hepatol. 2010;53(2):298–306.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Liu H, Ma Z, Lee SS. Contribution of nitric oxide to the pathogenesis of cirrhotic cardiomyopathy in bile duct-ligated rats. Gastroenterology. 2000;118(5):937–44.

    Article  CAS  PubMed  Google Scholar 

  3. Liu H, Song D, Lee SS. Role of heme oxygenase-carbon monoxide pathway in pathogenesis of cirrhotic cardiomyopathy in the rat. Am J Physiol Gastrointest Liver Physiol. 2001;280(1):G68–74.

    CAS  PubMed  Google Scholar 

  4. Nam SW, Liu H, Wong JZ, Feng AY, Chu G, Merchant N, Lee SS. Cardiomyocyte apoptosis contributes to pathogenesis of cirrhotic cardiomyopathy in bile duct-ligated mice. Clin Sci. 2014;127:519–26.

    Article  CAS  PubMed  Google Scholar 

  5. Kowalski HJ, Abelmann WH. The cardiac output at rest in Laennec's cirrhosis. J Clin Invest. 1953;32(10):1025–33.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Lee SS. Cardiac abnormalities in liver cirrhosis. West J Med. 1989;151(5):530–5.

    PubMed Central  CAS  PubMed  Google Scholar 

  7. Ma Z, Lee SS. Cirrhotic cardiomyopathy: getting to the heart of the matter. Hepatology. 1996;24(2):451–9.

    Article  CAS  PubMed  Google Scholar 

  8. Moller S, Henriksen JH. Cirrhotic cardiomyopathy: a pathophysiological review of circulatory dysfunction in liver disease. Heart. 2002;87(1):9–15.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Baik SK, Fouad TR, Lee SS. Cirrhotic cardiomyopathy. Orphanet J Rare Dis. 2007;2:15.

    Article  PubMed Central  PubMed  Google Scholar 

  10. Gaskari SA, Honar H, Lee SS. Therapy insight: cirrhotic cardiomyopathy. Nat Clin Prac Gastroenterol Hepatol. 2006;3(6):329–37.

    Article  CAS  Google Scholar 

  11. Gould L, Shariff M, Zahir M, Di Lieto M. Cardiac hemodynamics in alcoholic patients with chronic liver disease and a presystolic gallop. J Clin Invest. 1969;48(5):860–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Sucharov CC. Beta-adrenergic pathways in human heart failure. Expert Rev Cardiovasc Ther. 2007;5(1):119–24.

    Article  CAS  PubMed  Google Scholar 

  13. Marian AJ. Beta-adrenergic receptors signaling heart failure in mice, rabbits and humans. J Mol Cell Cardiol. 2006;41(1):11–3.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Lee SS, Marty J, Mantz J, Samain E, Braillon A, Lebrec D. Desensitization of myocardial beta-adrenergic receptors in cirrhotic rats. Hepatology. 1990; 12(3 Pt 1):481–5.

    Article  CAS  PubMed  Google Scholar 

  15. Ma Z, Miyamoto A, Lee SS. Role of altered beta-adrenoceptor signal transduction in the pathogenesis of cirrhotic cardiomyopathy in rats. Gastroenterology. 1996;110(4):1191–8.

    Article  CAS  PubMed  Google Scholar 

  16. Ma Z, Zhang Y, Huet PM, Lee SS. Differential effects of jaundice and cirrhosis on beta-adrenoceptor signaling in three rat models of cirrhotic cardiomyopathy. J Hepatol. 1999;30(3):485–91.

    Article  CAS  PubMed  Google Scholar 

  17. Ma Z, Meddings JB, Lee SS. Membrane physical properties determine cardiac beta-adrenergic receptor function in cirrhotic rats. Am J Physiol. 1994; 267(1 Pt 1):G87–93.

    CAS  PubMed  Google Scholar 

  18. Hare JM, Colucci WS. Role of nitric oxide in the regulation of myocardial function. Prog Cardiovasc Dis. 1995;38(2):155–66.

    Article  CAS  PubMed  Google Scholar 

  19. Kojda G, Kottenberg K. Regulation of basal myocardial function by NO. Cardiovasc Res. 1999;41(3):514–23.

    Article  CAS  PubMed  Google Scholar 

  20. Mery PF, Pavoine C, Belhassen L, Pecker F, Fischmeister R. Nitric oxide regulates cardiac Ca2+current. Involvement of cGMP-inhibited and cGMP-stimulated phosphodiesterases through guanylyl cyclase activation. J Biol Chem. 1993;268(35):26286–95.

    CAS  PubMed  Google Scholar 

  21. Mani AR, Ippolito S, Ollosson R, Moore KP. Nitration of cardiac proteins is associated with abnormal cardiac chronotropic responses in rats with biliary cirrhosis. Hepatology. 2006;43(4):847–56.

    Article  CAS  PubMed  Google Scholar 

  22. Liu L, Liu H, Nam SW, Lee SS. Protective effects of erythropoietin on cirrhotic cardiomyopathy in rats. Dig Liver Dis. 2012;44(12):1012–7.

    Article  CAS  PubMed  Google Scholar 

  23. Whalen EJ, Foster MW, Matsumoto A, Ozawa K, Violin JD, Que LG, Nelson CD, Benhar M, Keys JR, Rockman HA, et al. Regulation of beta-adrenergic receptor signaling by S-nitrosylation of G-protein-coupled receptor kinase 2. Cell. 2007;129(3):511–22.

    Article  CAS  PubMed  Google Scholar 

  24. Burgoyne JR, Madhani M, Cuello F, Charles RL, Brennan JP, Schroder E, Browning DD, Eaton P. Cysteine redox sensor in PKGIa enables oxidant-induced activation. Science. 2007;317(5843):1393–7.

    Article  CAS  PubMed  Google Scholar 

  25. Lin RS, Lee FY, Lee SD, Tsai YT, Lin HC, Lu RH, Hsu WC, Huang CC, Wang SS, Lo KJ. Endotoxemia in patients with chronic liver diseases: relationship to severity of liver diseases, presence of esophageal varices, and hyperdynamic circulation. J Hepatol. 1995;22(2):165–72.

    Article  CAS  PubMed  Google Scholar 

  26. Napoli J, Bishop GA, McCaughan GW. Increased intrahepatic messenger RNA expression of interleukins 2, 6, and 8 in human cirrhosis. Gastroenterology. 1994;107(3):789–98.

    Article  CAS  PubMed  Google Scholar 

  27. Wiest R, Garcia-Tsao G. Bacterial translocation (BT) in cirrhosis. Hepatology. 2005;41(3):422–33.

    Article  CAS  PubMed  Google Scholar 

  28. Funakoshi H, Kubota T, Kawamura N, Machida Y, Feldman AM, Tsutsui H, Shimokawa H, Takeshita A. Disruption of inducible nitric oxide synthase improves beta-adrenergic inotropic responsiveness but not the survival of mice with cytokine-induced cardiomyopathy. Circ Res. 2002;90(9):959–65.

    Article  CAS  PubMed  Google Scholar 

  29. Jobin C, Sartor RB. The I kappa B/NF-kappa B system: a key determinant of mucosalinflammation and protection. Am J Physiol Cell Physiol. 2000;278(3):C451–62.

    CAS  PubMed  Google Scholar 

  30. Hall G, Hasday JD, Rogers TB. Regulating the regulator: NF-kappa B signaling in heart. J Mol Cell Cardiol. 2006;41(4):580–91.

    Article  CAS  PubMed  Google Scholar 

  31. May MJ, D'Acquisto F, Madge LA, Glockner J, Pober JS, Ghosh S. Selective inhibition of NF-kappaB activation by a peptide that blocks the interaction of NEMO with the IkappaB kinase complex. Science. 2000;289(5484):1550–4.

    Article  CAS  PubMed  Google Scholar 

  32. Liu H, Lee SS. Nuclear factor-kappa B inhibition improves myocardial contractility in rats with cirrhotic cardiomyopathy. Liver Int: Off J Int Assoc Study Liver. 2008;28(5):640–8.

    Article  CAS  Google Scholar 

  33. Batkai S, Jarai Z, Wagner JA, Goparaju SK, Varga K, Liu J, Wang L, Mirshahi F, Khanolkar AD, Makriyannis A, et al. Endocannabinoids acting at vascular CB1 receptors mediate the vasodilated state in advanced liver cirrhosis. Nat Med. 2001;7(7):827–32.

    Article  CAS  PubMed  Google Scholar 

  34. Gaskari SA, Liu H, Moezi L, Li Y, Baik SK, Lee SS. Role of endocannabinoids in the pathogenesis of cirrhotic cardiomyopathy in bile duct-ligated rats. Br J Pharmacol. 2005;146(3):315–23.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Moezi L, Gaskari SA, Liu H, Baik SK, Dehpour AR, Lee SS. Anandamide mediates hyperdynamic circulation in cirrhotic rats via CB(1) and VR(1) receptors. Br J Pharmacol. 2006;149(7):898–908.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Abdelwahid E, Smith G. Apoptosis in chronic heart failure. Int J Cardiol. 2007;114(3):375.

    Article  PubMed  Google Scholar 

  37. Tostes S, Jr., Bertulucci Rocha-Rodrigues D, de Araujo Pereira G, Rodrigues V, Jr. Myocardiocyte apoptosis in heart failure in chronic Chagas’ disease. Int J Cardiol. 2005;99(2):233–7.

    Article  PubMed  Google Scholar 

  38. Wencker D, Chandra M, Nguyen K, Miao W, Garantziotis S, Factor SM, Shirani J, Armstrong RC, Kitsis RN. A mechanistic role for cardiac myocyte apoptosis in heart failure. J Clin Invest. 2003;111(10):1497–504.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Hayakawa Y, Chandra M, Miao W, Shirani J, Brown JH, Dorn GW, 2nd, Armstrong RC, Kitsis RN. Inhibition of cardiac myocyte apoptosis improves cardiac function and abolishes mortality in the peripartum cardiomyopathy of Galpha(q) transgenic mice. Circulation. 2003;108(24):3036–41.

    Article  CAS  PubMed  Google Scholar 

  40. Ghavami S, Hashemi M, Kadkhoda K, Alavian SM, Bay GH, Los M. Apoptosis in liver diseases—detection and therapeutic applications. Med Sci Monit. 2005;11(11):RA337–45.

    CAS  PubMed  Google Scholar 

  41. Feldstein AE, Canbay A, Angulo P, Taniai M, Burgart LJ, Lindor KD, Gores GJ. Hepatocyte apoptosis and fas expression are prominent features of human nonalcoholic steatohepatitis. Gastroenterology. 2003;125(2):437–43.

    Article  PubMed  Google Scholar 

  42. Lee JY, Chae DW, Kim SM, Nam ES, Jang MK, Lee JH, Kim HY, Yoo JY. Expression of FasL and perforin/granzyme B mRNA in chronic hepatitis B virus infection. J Viral Hepat. 2004;11(2):130–5.

    Article  CAS  PubMed  Google Scholar 

  43. Wong F, Girgrah N, Graba J, Allidina Y, Liu P, Blendis L. The cardiac response to exercise in cirrhosis. Gut. 2001;49(2):268–75.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. Donovan CL, Marcovitz PA, Punch JD, Bach DS, Brown KA, Lucey MR, Armstrong WF. Two-dimensional and dobutamine stress echocardiography in the preoperative assessment of patients with end-stage liver disease prior to orthotopic liver transplantation. Transplantation. 1996;61(8):1180–8.

    Article  CAS  PubMed  Google Scholar 

  45. Darstein F, Konig C, Hoppe-Lotichius M, Grimm D, Knapstein J, Mittler J, Zimmermann A, Otto G, Lang H, Galle PR, et al. Preoperative left ventricular hypertrophy is associated with reduced patient survival after liver transplantation. Clin Transplant. 2014;28(2):236–42.

    Article  CAS  PubMed  Google Scholar 

  46. Merli M, Valeriano V, Funaro S, Attili AF, Masini A, Efrati C, De CS, Riggio O. Modifications of cardiac function in cirrhotic patients treated with transjugular intrahepatic portosystemic shunt (TIPS). Am J Gastroenterol. 2002;97(1):142–8.

    Article  PubMed  Google Scholar 

  47. Gines P, Uriz J, Calahorra B, Garcia-Tsao G, Kamath PS, Del Arbol LR, Planas R, Bosch J, Arroyo V, Rodes J. Transjugular intrahepatic portosystemic shunting versus paracentesis plus albumin for refractory ascites in cirrhosis. Gastroenterology. 2002;123(6):1839–47.

    Article  PubMed  Google Scholar 

  48. Cazzaniga M, Salerno F, Pagnozzi G, Dionigi E, Visentin S, Cirello I, Meregaglia D, Nicolini A. Diastolic dysfunction is associated with poor survival in patients with cirrhosis with transjugular intrahepatic portosystemic shunt. Gut. 2007;56(6):869–75.

    Article  PubMed Central  PubMed  Google Scholar 

  49. Lee SS, Liu H. Cardiovascular determinants of survival in cirrhosis. Gut. 2007;56(6):746–8.

    Article  PubMed Central  PubMed  Google Scholar 

  50. Ruiz-del-Arbol L, Urman J, Fernandez J, Gonzalez M, Navasa M, Monescillo A, Albillos A, Jimenez W, Arroyo V. Systemic, renal, and hepatic hemodynamic derangement in cirrhotic patients with spontaneous bacterial peritonitis. Hepatology. 2003;38(5):1210–8.

    Article  PubMed  Google Scholar 

  51. Ruiz-del-Arbol L, Monescillo A, Arocena C, Valer P, Gines P, Moreira V, Milicua JM, Jimenez W, Arroyo V. Circulatory function and hepatorenal syndrome in cirrhosis. Hepatology. 2005;42(2):439–47.

    Article  CAS  PubMed  Google Scholar 

  52. Yang YY, Lin HC. The heart: pathophysiology and clinical implications of cirrhotic cardiomyopathy. J Chin Med Assoc. 75(12):619–23.

    Google Scholar 

  53. Bernardi M, Calandra S, Colantoni A, Trevisani F, Raimondo ML, Sica G, Schepis F, Mandini M, Simoni P, Contin M, 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.

    Article  CAS  PubMed  Google Scholar 

  54. Reiberger T, Ulbrich G, Ferlitsch A, Payer BA, Schwabl P, Pinter M, Heinisch BB, Trauner M, Kramer L, Peck-Radosavljevic M. Carvedilol for primary prophylaxis of variceal bleeding in cirrhotic patients with haemodynamic non-response to propranolol. Gut. 2013;62:1634–41.

    Article  CAS  PubMed  Google Scholar 

  55. Chopra V, Plaisance B, Cavusoglu E, Flanders SA, Eagle KA. Perioperative beta-blockers for major noncardiac surgery: Primum Non Nocere. Am J Med. 2009;122(3):222–9.

    Article  CAS  PubMed  Google Scholar 

  56. Safadi A, Homsi M, Maskoun W, Lane KA, Singh I, Sawada SG, Mahenthiran J. Perioperative risk predictors of cardiac outcomes in patients undergoing liver transplantation surgery. Circulation. 2009;120(13):1189–94.

    Article  PubMed  Google Scholar 

  57. Zambruni A, Trevisani F, Di Micoli A, Savelli F, Berzigotti A, Bracci E, Caraceni P, Domenicali M, Felline P, Zoli M, Bernardi M. Effect of chronic beta-blockade on QT interval in patients with liver cirrhosis. J Hepatol. 2008;48:415–21.

    Article  PubMed  Google Scholar 

  58. Krag A, Bendtsen F, Henriksen JH, Moller S. Low cardiac output predicts development of hepatorenal syndrome and survival in patients with cirrhosis and ascites. Gut. 59(1):105–10.

    Google Scholar 

  59. Cardenas A, Gines P. Therapy insight: management of hepatorenal syndrome. Nat Clin Pract Gastroenterol Hepatol. 2006;3(6):338–48.

    Article  CAS  PubMed  Google Scholar 

  60. von Lueder TG, Krum H. RAAS inhibitors and cardiovascular protection in large scale trials. Cardiovasc Drugs Ther. 27(2):171–9.

    Google Scholar 

  61. Kuiper JJ, Boomsma F, van Buren H, de Man R, Danser AH, van den Meiracker AH. Components of the renin-angiotensin-aldosterone system in plasma and ascites in hepatic cirrhosis. Eur J Clin Invest. 2008;38(12):939–44.

    Article  CAS  PubMed  Google Scholar 

  62. Pozzi M, Grassi G, Ratti L, Favini G, Dell'Oro R, Redaelli E, Calchera I, Boari G, Mancia G. Cardiac, neuroadrenergic, and portal hemodynamic effects of prolonged aldosterone blockade in postviral Child A cirrhosis. Am J Gastroenterol. 2005;100(5):1110–6.

    Article  CAS  PubMed  Google Scholar 

  63. Snyder N, Atterbury CE, Pinto Correia J, Conn HO. Increased concurrence of cirrhosis and bacterial endocarditis. A clinical and postmortem study. Gastroenterology. 1977;73(5):1107–13.

    CAS  PubMed  Google Scholar 

  64. Huonker M, Schumacher YO, Ochs A, Sorichter S, Keul J, Rossle M. Cardiac function and haemodynamics in alcoholic cirrhosis and effects of the transjugular intrahepatic portosystemic stent shunt. Gut. 1999;44(5):743–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  65. Sampathkumar P, Lerman A, Kim BY, Narr BJ, Poterucha JJ, Torsher LC, Plevak DJ. Post-liver transplantation myocardial dysfunction. Liver Transplant Surg. 1998;4(5):399–403.

    Article  CAS  Google Scholar 

  66. Nasraway SA, Klein RD, Spanier TB, Rohrer RJ, Freeman RB, R and WM, Benotti PN. Hemodynamic correlates of outcome in patients undergoing orthotopic liver transplantation. Evidence for early postoperative myocardial depression. Chest. 1995;107(1):218–24.

    Article  CAS  PubMed  Google Scholar 

  67. Rayes N, Bechstein WO, Keck H, Blumhardt G, Lohmann R, Neuhaus P. Changing patterns of causes of death after liver transplantation: an analysis of 41 cases in 382 patients. Transplant Proc. 1995;27(1):1237–8.

    CAS  PubMed  Google Scholar 

  68. Girgrah N, Reid G, MacKenzie S, Wong F. Cirrhotic cardiomyopathy: does it contribute to chronic fatigue and decreased health-related quality of life in cirrhosis? Can J Gastroenterol. 2003;17(9):545–51.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Liver Unit, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr. NW, T2N 4N1, Calgary, AB, Canada

    Hongqun Liu MD, PhD & Samuel S. Lee MD

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Correspondence to Samuel S. Lee MD .

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Editors and Affiliations

  1. Department of Transplant, Mayo Clinic, Jacksonville, Florida, USA

    Andrew P. Keaveny

  2. Institut de Malalties Digestives i Metaboliques, University of Barcelona, Barcelona, Spain

    Andrés Cárdenas

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Liu, H., Lee, S. (2015). Cirrhotic Cardiomyopathy: Pathogenic Mechanisms and Management Strategies. In: Keaveny, A., Cárdenas, A. (eds) Complications of Cirrhosis. Springer, Cham. https://doi.org/10.1007/978-3-319-13614-1_17

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