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Therapy Insight: cirrhotic cardiomyopathy

Nature Clinical Practice Gastroenterology & Hepatology volume 3, pages 329–337 (2006)Cite this article

Abstract

Liver cirrhosis is associated with several cardiovascular disturbances. These disturbances include hyperdynamic systemic circulation, manifested by an increased cardiac output and decreased peripheral vascular resistance and arterial pressure. Despite the baseline increase in cardiac output, cardiac function in patients with cirrhosis is abnormal in several respects. Patients show attenuated systolic and diastolic contractile responses to stress stimuli, electrophysiological repolarization changes, including prolonged QT interval, and enlargement or hypertrophy of cardiac chambers. This constellation of cardiac abnormalities is termed cirrhotic cardiomyopathy. It has been suggested that cirrhotic cardiomyopathy has a role in the pathogenesis of cardiac dysfunction and even overt heart failure after transjugular intrahepatic portosystemic shunt placement, major surgery and liver transplantation. Cardiac dysfunction contributes to morbidity and mortality after liver transplantation, even in many patients who have no prior history of cardiac disease. Depressed cardiac contractility contributes to the pathogenesis of hepatorenal syndrome, especially in patients with spontaneous bacterial peritonitis. Pathogenic mechanisms underlying cirrhotic cardiomyopathy include cardiomyocyte-membrane biophysical changes, attenuation of the stimulatory β-adrenergic system and overactivity of negative inotropic systems mediated via cyclic GMP. The clinical features, general diagnostic criteria, pathogenesis and treatment of cirrhotic cardiomyopathy are discussed in this review.

Key Points

  • Cirrhotic cardiomyopathy can be found in patients with any form of cirrhosis

  • Cardinal features of cirrhotic cardiomyopathy include blunted contractile responses to stress and repolarization abnormalities

  • Multiple pathogenic mechanisms in the cardiomyocyte plasma membrane are responsible for cirrhotic cardiomyopathy

  • Treatment measures for cirrhotic cardiomyopathy are mainly supportive and empirical

  • Cardiac function generally normalizes after liver transplantation

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Figure 1: Schematic representation of the mechanisms involved in altered contractile function in cirrhotic cardiomyocytes.

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References

  1. Lee SS (1989) Cardiac abnormalities in liver cirrhosis. West J Med 151: 530–535

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Ma Z and SS Lee (1996) Cirrhotic cardiomyopathy: getting to the heart of the matter. Hepatology 24: 451–459

    CAS  PubMed  Google Scholar 

  3. Kowalski HJ and WH Abelmann (1953) The cardiac output at rest in Laennec's cirrhosis. J Clin Invest 32: 1025–1033

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Regan TJ et al. (1969) Ventricular function in noncardiacs with alcoholic fatty liver: role of ethanol in the production of cardiomyopathy. J Clin Invest 48: 397–407

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Gould L et al. (1969) Cardiac hemodynamics in alcoholic patients with chronic liver disease and a presystolic gallop. J Clin Invest 48: 860–868

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Limas CJ et al. (1974) Impaired left ventricular function in alcoholic cirrhosis with ascites. Ineffectiveness of ouabain. Circulation 49: 754–760

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Liu H and Lee SS (1999) Cardiopulmonary dysfunction in cirrhosis. J Gastroenterol Hepatol 14: 600–608

    CAS  PubMed  Google Scholar 

  9. Liu H et al. (2002) Cirrhotic cardiomyopathy. Gastroenterol Clin Biol 26: 842–847

    PubMed  Google Scholar 

  10. Baik SK and Lee SS (2004) Cirrhotic cardiomyopathy: causes and consequences. J Gastroenterol Hepatol 19 (Suppl): S185–S190

    Google Scholar 

  11. Ma Z et al. (1994) Membrane physical properties determine cardiac beta-adrenergic receptor function in cirrhotic rats. Am J Physiol 267 (Pt 1): G87–G93

    CAS  PubMed  Google Scholar 

  12. Ma Z et al. (1997) Effects of altered cardiac membrane fluidity on beta-adrenergic receptor signalling in rats with cirrhotic cardiomyopathy. J Hepatol 26: 904–912

    CAS  PubMed  Google Scholar 

  13. Ma Z et al. (1996) Role of altered beta-adrenoceptor signal transduction in the pathogenesis of cirrhotic cardiomyopathy in rats. Gastroenterology 110: 1191–1198

    CAS  PubMed  Google Scholar 

  14. van Obbergh L et al. (1996) Cardiac modifications occurring in the ascitic rat with biliary cirrhosis are nitric oxide related. J Hepatol 24: 747–752

    CAS  PubMed  Google Scholar 

  15. Liu H et al. (2000) Contribution of nitric oxide to the pathogenesis of cirrhotic cardiomyopathy in bile duct-ligated rats. Gastroenterology 118: 937–944

    CAS  PubMed  Google Scholar 

  16. Ewing JF et al. (1994) Induction of heart heme oxygenase-1 (HSP32) by hyperthermia: possible role in stress-mediated elevation of cyclic 3′:5′-guanosine monophosphate. J Pharmacol Exp Ther 271: 408–414

    CAS  PubMed  Google Scholar 

  17. Tohse N et al. (1995) Cyclic GMP-mediated inhibition of L-type Ca2+ channel activity by human natriuretic peptide in rabbit heart cells. Br J Pharmacol 114: 1076–1082

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Liu H et al. (2001) Role of heme oxygenase–carbon monoxide pathway in pathogenesis of cirrhotic cardiomyopathy in the rat. Am J Physiol Gastrointest Liver Physiol 280: G68–G74

    CAS  PubMed  Google Scholar 

  19. Bonz A et al. (2003) Cannabinoids acting on CB1 receptors decrease contractile performance in human atrial muscle. J Cardiovasc Pharmacol 41: 657–664

    CAS  PubMed  Google Scholar 

  20. Ford WR et al. (2002) Evidence of a novel site mediating anandamide-induced negative inotropic and coronary vasodilatator responses in rat isolated hearts. Br J Pharmacol 135: 1191–1198

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Batkai S et al. (2001) Endocannabinoids acting at vascular CB1 receptors mediate the vasodilated state in advanced liver cirrhosis. Nat Med 7: 827–832

    CAS  PubMed  Google Scholar 

  22. Gaskari SA et al. (2005) Role of endocannabinoids in the pathogenesis of cirrhotic cardiomyopathy in bile duct-ligated rats. Br J Pharmacol 146: 315–323

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Ward CA et al. (1997) Potassium currents in atrial and ventricular myocytes from a rat model of cirrhosis. Am J Physiol 273: G537–G544

    CAS  PubMed  Google Scholar 

  24. Ward CA et al. (2001) Altered cellular calcium regulatory systems in a rat model of cirrhotic cardiomyopathy. Gastroenterology 121: 1209–1218

    CAS  PubMed  Google Scholar 

  25. Grose RD et al. (1995) Exercise-induced left ventricular dysfunction in alcoholic and non-alcoholic cirrhosis. J Hepatol 22: 326–332

    CAS  PubMed  Google Scholar 

  26. Finucci G et al. (1996) Left ventricular diastolic function in liver cirrhosis. Scand J Gastroenterol 31: 279–284

    CAS  PubMed  Google Scholar 

  27. Pozzi M et al. (1997) Evidence of functional and structural cardiac abnormalities in cirrhotic patients with and without ascites. Hepatology 26: 1131–1137

    CAS  PubMed  Google Scholar 

  28. Wong F et al. (1999) Role of cardiac structural and functional abnormalities in the pathogenesis of hyperdynamic circulation and renal sodium retention in cirrhosis. Clin Sci (Lond) 97: 259–267

    CAS  Google Scholar 

  29. Wong F et al. (2001) The cardiac response to exercise in cirrhosis. Gut 49: 268–275

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Inserte J et al. (2003) Left ventricular hypertrophy in rats with biliary cirrhosis. Hepatology 38: 589–598

    CAS  PubMed  Google Scholar 

  31. Finucci G et al. (1998) Q-T interval prolongation in liver cirrhosis. Reversibility after orthotopic liver transplantation. Jpn Heart J 39: 321–329

    CAS  PubMed  Google Scholar 

  32. Bernardi M et al. (1998) Q-T interval prolongation in cirrhosis: prevalence, relationship with severity, and etiology of the disease and possible pathogenetic factors. Hepatology 27: 28–34

    CAS  PubMed  Google Scholar 

  33. Bal JS and Thuluvath PJ (2003) Prolongation of QTc interval: relationship with etiology and severity of liver disease, mortality and liver transplantation. Liver Int 23: 243–248

    PubMed  Google Scholar 

  34. Trevisani F et al. (2003) QT interval in patients with non-cirrhotic portal hypertension and in cirrhotic patients treated with transjugular intrahepatic porto-systemic shunt. J Hepatol 38: 461–467

    PubMed  Google Scholar 

  35. Henriksen JH et al. (2002) Dyssynchronous electrical and mechanical systole in patients with cirrhosis. J Hepatol 36: 513–520

    PubMed  Google Scholar 

  36. Stein LB et al. (1992) Fatal torsade de pointes occurring in a patient receiving intravenous vasopressin and nitroglycerin. J Clin Gastroenterol 15: 171–174

    CAS  PubMed  Google Scholar 

  37. Faigel DO et al. (1995) Torsade de pointes complicating the treatment of bleeding esophageal varices: association with neuroleptics, vasopressin, and electrolyte imbalance. Am J Gastroenterol 90: 822–824

    CAS  PubMed  Google Scholar 

  38. Ruiz-del-Arbol L et al. (2005) Circulatory function and hepatorenal syndrome in cirrhosis. Hepatology 42: 439–447

    CAS  PubMed  Google Scholar 

  39. Ruiz-del-Arbol L et al. (2003) Systemic, renal, and hepatic hemodynamic derangement in cirrhotic patients with spontaneous bacterial peritonitis. Hepatology 38: 1210–1218

    PubMed  Google Scholar 

  40. Lee SS (2003) Cardiac dysfunction in spontaneous bacterial peritonitis: a manifestation of cirrhotic cardiomyopathy? Hepatology 38: 1089–1091

    PubMed  Google Scholar 

  41. Lenz K (2005) Hepatorenal syndrome—is it central hypovolemia, a cardiac disease, or part of gradually developing multiorgan dysfunction? Hepatology 42: 263–265

    PubMed  Google Scholar 

  42. Sola-Vera J and Such J (2004) Understanding the mechanisms of paracentesis-induced circulatory dysfunction. Eur J Gastroenterol Hepatol 16: 295–298

    PubMed  Google Scholar 

  43. Huonker M et al. (1999) Cardiac function and haemodynamics in alcoholic cirrhosis and effects of the transjugular intrahepatic portosystemic stent shunt. Gut 44: 743–748

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Lotterer E et al. (1999) Transjugular intrahepatic portosystemic shunt: short-term and long-term effects on hepatic and systemic hemodynamics in patients with cirrhosis. Hepatology 29: 632–639

    CAS  PubMed  Google Scholar 

  45. Wong F et al. (1995) Transjugular intrahepatic portosystemic stent shunt: effects on hemodynamics and sodium homeostasis in cirrhosis and refractory ascites. Ann Intern Med 122: 816–822

    CAS  PubMed  Google Scholar 

  46. Merli M et al. (2002) Modifications of cardiac function in cirrhotic patients treated with transjugular intrahepatic portosystemic shunt (TIPS). Am J Gastroenterol 97: 142–148

    PubMed  Google Scholar 

  47. Braverman AC et al. (1995) High-output congestive heart failure following transjugular intrahepatic portal-systemic shunting. Chest 107: 1467–1469

    CAS  PubMed  Google Scholar 

  48. Azoulay D et al. (1994) Transjugular intrahepatic portosystemic shunt worsens the hyperdynamic circulatory state of the cirrhotic patient: preliminary report of a prospective study. Hepatology 19: 129–132

    CAS  PubMed  Google Scholar 

  49. Salerno F et al. (2003) Humoral and cardiac effects of TIPS in cirrhotic patients with different “effective” blood volume. Hepatology 38: 1370–1377

    PubMed  Google Scholar 

  50. Gines P et al. (2002) Transjugular intrahepatic portosystemic shunting versus paracentesis plus albumin for refractory ascites in cirrhosis. Gastroenterology 123: 1839–1847

    PubMed  Google Scholar 

  51. Salerno F et al. (2004) Randomized controlled study of TIPS versus paracentesis plus albumin in cirrhosis with severe ascites. Hepatology 40: 629–635

    CAS  PubMed  Google Scholar 

  52. Sanyal AJ et al. (2003) The North American study for the treatment of refractory ascites. Gastroenterology 124: 634–641

    PubMed  Google Scholar 

  53. Myers RP and Lee SS (2000) Cirrhotic cardiomyopathy and liver transplantation. Liver Transpl 6 (Suppl): S44–S52

    CAS  PubMed  Google Scholar 

  54. Therapondos G et al. (2004) Cardiac morbidity and mortality related to orthotopic liver transplantation. Liver Transpl 10: 1441–1453

    PubMed  Google Scholar 

  55. Marquez J et al. (1986) Cardiovascular depression secondary to ionic hypocalcemia during hepatic transplantation in humans. Anesthesiology 65: 457–461

    CAS  PubMed  Google Scholar 

  56. Nasraway SA et al. (1995) Hemodynamic correlates of outcome in patients undergoing orthotopic liver transplantation. Evidence for early postoperative myocardial depression. Chest 107: 218–224

    CAS  PubMed  Google Scholar 

  57. Therapondos G et al. (2002) Cardiac function after orthotopic liver transplantation and the effects of immunosuppression: a prospective randomized trial comparing cyclosporin (Neoral) and tacrolimus. Liver Transpl 8: 690–700

    PubMed  Google Scholar 

  58. Donovan CL et al. (1996) Two-dimensional and dobutamine stress echocardiography in the preoperative assessment of patients with end-stage liver disease prior to orthotopic liver transplantation. Transplantation 61: 1180–1188

    CAS  PubMed  Google Scholar 

  59. Sampathkumar P et al. (1998) Post-liver transplantation myocardial dysfunction. Liver Transpl Surg 4: 399–403

    CAS  PubMed  Google Scholar 

  60. Abbasoglu O et al. (1997) Hepatic artery stenosis after liver transplantation—incidence, presentation, treatment, and long term outcome. Transplantation 63: 250–255

    CAS  PubMed  Google Scholar 

  61. Liu H and Lee SS (2005) What happens to cirrhotic cardiomyopathy after liver transplantation? Hepatology 42: 1203–1205

    PubMed  Google Scholar 

  62. Mohamed R et al. (1996) Effect of liver transplantation on QT interval prolongation and autonomic dysfunction in end-stage liver disease. Hepatology 23: 1128–1134

    CAS  PubMed  Google Scholar 

  63. Torregrosa M et al. (2005) Cardiac alterations in cirrhosis: reversibility after liver transplantation. J Hepatol 42: 68–74

    PubMed  Google Scholar 

  64. Henriksen JH et al. (2004) Acute non-selective beta-adrenergic blockade reduces prolonged frequency-adjusted Q-T interval (QTc) in patients with cirrhosis. J Hepatol 40: 239–246

    CAS  PubMed  Google Scholar 

  65. Pozzi M et al. (2005) Cardiac, neuroadrenergic, and portal hemodynamic effects of prolonged aldosterone blockade in postviral child A cirrhosis. Am J Gastroenterol 100: 1110–1116

    CAS  PubMed  Google Scholar 

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Acknowledgements

SA Gaskari and H Honar contributed equally to this article. SA Gaskari is supported by a Heart and Stroke Foundation of Canada Doctoral Research award, and SS Lee, by an Alberta Heritage Foundation for Medical Research Senior Scholarship award.

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Authors and Affiliations

  1. PhD candidate University of Calgary, Calgary, AB, Canada

    Seyed A Gaskari

  2. Research Fellow University of Calgary, Calgary, AB, Canada

    Hooman Honar

  3. Professor of Medicine in the Liver Unit, at the University of Calgary, Calgary, AB, Canada

    Samuel S Lee

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  1. Seyed A Gaskari
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  2. Hooman Honar
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  3. Samuel S Lee
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Correspondence to Samuel S Lee.

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Gaskari, S., Honar, H. & Lee, S. Therapy Insight: cirrhotic cardiomyopathy. Nat Rev Gastroenterol Hepatol 3, 329–337 (2006). https://doi.org/10.1038/ncpgasthep0498

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