Cirrhotic Cardiomyopathy

Saleh A. Alqahtani; Tamer R. Fouad; Samuel S. Lee

doi:10.1055/s-2008-1040321

Seminars in Liver Disease, Inhaltsverzeichnis

Semin Liver Dis 2008; 28(1): 059-069
DOI: 10.1055/s-2008-1040321

Cirrhotic Cardiomyopathy

Saleh A. Alqahtani¹ , Tamer R. Fouad² , Samuel S. Lee²

¹Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota
²Liver Unit, University of Calgary, Calgary, Alberta, Canada

Abstract

ABSTRACT

Liver cirrhosis is associated with several cardiovascular abnormalities. Despite an increased baseline cardiac output, cirrhotic patients have a suboptimal ventricular response to stress. This phenomenon is called cirrhotic cardiomyopathy. The pathogenesis of this syndrome is multifactorial and includes diminished β-adrenergic receptor signal transduction, cardiomyocyte cellular plasma membrane dysfunction, and increased activity or levels of cardiodepressant substances such as cytokines, endogenous cannabinoids, and nitric oxide. Although cirrhotic cardiomyopathy is usually clinically mild or silent, overt heart failure can be precipitated by stresses such as liver transplantation or transjugular intrahepatic portosystemic shunt insertion. Moreover, cirrhotic cardiomyopathy may play a role in the pathogenesis of hepatorenal syndrome. Treatment of this condition is mainly supportive. Orthotopic liver transplantation appears to improve or normalize the condition, generally after a period of several months.

KEYWORDS

Cirrhotic cardiomyopathy - cirrhosis - heart failure - QT interval - hyperdynamic circulation

Volltext

Referenzen

REFERENCES

1 Kowalski H J, Abelmann W H. The cardiac output at rest in Laennec's cirrhosis. J Clin Invest. 1953; 32 1025-1033
2 Abelmann W H, Kowalski H J, McNeely W F. The hemodynamic response to exercise in patients with Laennec's cirrhosis. J Clin Invest. 1955; 34 690-695
3 Bayley T J, Segel N, Bishop J M. The circulatory changes in patients with cirrhosis of the liver at rest and during exercise. Clin Sci. 1964; 26 227-235
4 Murray J F, Dawson A M, Sherlock S. Circulatory changes in chronic liver disease. Am J Med. 1958; 24 358-367
5 Regan T J, Levinson G E, Oldewurtel H A, Frank M J, Weisse A B, Moschos C B. Ventricular function in noncardiacs with alcoholic fatty liver: role of ethanol in the production of cardiomyopathy. J Clin Invest. 1969; 48 397-407
6 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; 48 860-868
7 Limas C J, Guiha N H, Lekagul O, Cohn J N. Impaired left ventricular function in alcoholic cirrhosis with ascites: ineffectiveness of ouabain. Circulation. 1974; 49 754-760
8 Caramelo C, Fernandez-Munoz D, Santos J C et al.. Effect of volume expansion on hemodynamics, capillary permeability and renal function in conscious, cirrhotic rats. Hepatology. 1986; 6 129-134
9 Lee S S. Cardiac abnormalities in liver cirrhosis. West J Med. 1989; 151 530-535
10 Ma Z, Lee S S. Cirrhotic cardiomyopathy: getting to the heart of the matter. Hepatology. 1996; 24 451-459
11 Liu H, Lee S S. Cardiopulmonary dysfunction in cirrhosis. J Gastroenterol Hepatol. 1999; 14 600-608
12 Blendis L, Wong F. Is there a cirrhotic cardiomyopathy?. Am J Gastroenterol. 2000; 95 3026-3028
13 Moller S, Henriksen J H. Cirrhotic cardiomyopathy: a pathophysiological review of circulatory dysfunction in liver disease. Heart. 2002; 87 9-15
14 Baik S K, Lee S S. Cirrhotic cardiomyopathy: causes and consequences. J Gastroenterol Hepatol. 2004; 19(suppl 1) S185-S190
15 Kelbaek H, Eriksen J, Brynjolf I et al.. Cardiac performance in patients with asymptomatic alcoholic cirrhosis of the liver. Am J Cardiol. 1984; 54 852-855
16 Grose R D, Nolan J, Dillon J F et al.. Exercise-induced left ventricular dysfunction in alcoholic and non-alcoholic cirrhosis. J Hepatol. 1995; 22 326-332
17 Bernardi M, Trevisani F, Santini C et al.. Plasma norepinephrine, weak neurotransmitters, and renin activity during active tilting in liver cirrhosis: relationship with cardiovascular homeostasis and renal function. Hepatology. 1983; 3 56-64
18 Wong F, Girgrah N, Graba J, Allidina Y, Liu P, Blendis L. The cardiac response to exercise in cirrhosis. Gut. 2001; 49 268-275
19 Lunzer M R, Newman S P, Bernard A G, Manghani K K, Sherlock S P, Ginsburg J. Impaired cardiovascular responsiveness in liver disease. Lancet. 1975; 2 382-385
20 Decaux G, Cauchie P, Soupart A, Kruger M, Delwiche F. Role of vagal neuropathy in the hyponatraemia of alcoholic cirrhosis. Br Med J (Clin Res Ed). 1986; 293 1534-1536
21 Lee S S, Hadengue A, Moreau R, Sayegh R, Hillon P, Lebrec D. Postprandial hemodynamic responses in patients with cirrhosis. Hepatology. 1988; 8 647-651
22 Mashford M L, Mahon W A, Chalmers T C. Studies of the cardiovascular system in the hypotension of liver failure. N Engl J Med. 1962; 267 1071-1074
23 Mikulic E, Muñoz C, Puntoni L E, Lebrec D. Hemodynamic effects of dobutamine in patients with alcoholic cirrhosis. Clin Pharmacol Ther. 1983; 34 56-59
24 Ramond M J, Comoy E, Lebrec D. Alterations in isoprenaline sensitivity in patients with cirrhosis: evidence of abnormality of the sympathetic nervous activity. Br J Clin Pharmacol. 1986; 21 191-196
25 Finucci G, Desideri A, Sacerdoti D et al.. Left ventricular diastolic function in liver cirrhosis. Scand J Gastroenterol. 1996; 31 279-284
26 Galderisi M, Dini F L, Temporelli P L, Colonna P, de Simone G. Doppler echocardiography for the assessment of left ventricular diastolic function: methodology, clinical and prognostic value. Ital Heart J Suppl. 2004; 5 86-97
27 Gaskari S A, Honar H, Lee S S. Therapy insight: cirrhotic cardiomyopathy. Nat Clin Pract Gastroenterol Hepatol. 2006; 3 329-337
28 Alexander J, Mishra P, Desai N, Ambadekar S, Gala B, Sawant P. Cirrhotic cardiomyopathy: Indian scenario. J Gastroenterol Hepatol. 2007; 22 395-399
29 Pozzi M, Carugo S, Boari G et al.. Evidence of functional and structural cardiac abnormalities in cirrhotic patients with and without ascites. Hepatology. 1997; 26 1131-1137
30 Torregrosa M, Aguade S, Dos L et al.. Cardiac alterations in cirrhosis: reversibility after liver transplantation. J Hepatol. 2005; 42 68-74
31 Bernardi M, Calandra 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 28-34
32 Kempler P, Szalay F, Váradi A et al.. Prolongation of the QTc-interval reflects the severity of autonomic neuropathy in primary biliary cirrhosis and in other non-alcoholic liver diseases. Z Gastroenterol. 1993; 31(suppl 2) 96-98
33 Finucci G, Lunardi F, Sacerdoti D. Q-T interval prolongation in liver cirrhosis: reversibility after orthotopic liver transplantation. Jpn Heart J. 1998; 39 321-329
34 Day C P, James O F, Butler T J, Campbell R W. QT prolongation and sudden cardiac death in patients with alcoholic liver disease. Lancet. 1993; 341 1423-1428
35 Mohamed R, Forsey P R, Davies M K, Neuberger J M. Effect of liver transplantation on QT interval prolongation and autonomic dysfunction in end-stage liver disease. Hepatology. 1996; 23 1128-1134
36 Bal J S, Thuluvath P J. Prolongation of QTc interval: relationship with etiology and severity of liver disease, mortality and liver transplantation. Liver Int. 2003; 23 243-248
37 Trevisani F, Merli M, Savelli F et al.. QT interval in patients with non-cirrhotic portal hypertension and in cirrhotic patients treated with transjugular intrahepatic porto-systemic shunt. J Hepatol. 2003; 38 461-467
38 Carey E J, Douglas D D. Effects of orthotopic liver transplantation on the corrected QT interval in patients with end-stage liver disease. Dig Dis Sci. 2005; 50 320-323
39 Hansen S, Møller S, Bendtsen F, Jensen G, Henriksen J H. Diurnal variation and dispersion in QT interval in cirrhosis: relation to haemodynamic changes. J Hepatol. 2007; , April 5 (Epub ahead of print)
40 Henriksen J H, Bendtsen F, Hansen E F, Møller S. Acute nonselective beta-adrenergic blockade reduces prolonged frequency-adjusted Q-T interval (QTc) in patients with cirrhosis. J Hepatol. 2004; 40 239-246
41 Zambruni A, Di Micoli A, Lubisco A, Domenicali M, Trevisani F, Bernardi M. QT interval correction in patients with cirrhosis. J Cardiovasc Electrophysiol. 2007; 18 77-82
42 Henriksen J H, Fuglsang S, Bendtsen F, Christensen E, Moller S. Dyssynchronous electrical and mechanical systole in patients with cirrhosis. J Hepatol. 2002; 36 513-520
43 Lee S S, Marty J, Mantz J, Samain E, Braillon A, Lebrec D. Desensitization of myocardial beta-adrenergic receptors in cirrhotic rats. Hepatology. 1990; 12 481-485
44 Inserte J, Perelló A, Agulló L et al.. Left ventricular hypertrophy in rats with biliary cirrhosis. Hepatology. 2003; 38 589-598
45 Wong F, Liu P, Lilly L, Bomzon A, Blendis L. Role of cardiac structural and functional abnormalities in the pathogenesis of hyperdynamic circulation and renal sodium retention in cirrhosis. Clin Sci. 1999; 97 259-267
46 Keller H, Bezjak V, Stegaru B, Buss J, Holm E, Heene D L. Ventricular function in cirrhosis and portasystemic shunt: a two-dimensional echocardiographic study. Hepatology. 1988; 8 658-662
47 Spatt S D, Rosenblatt P. The incidence of hypertension in portal cirrhosis: a study of 80 necropsied cases of portal cirrhosis. Ann Intern Med. 1949; 31 479-483
48 Hall E M, Olsen A Y, Davis F E. Portal cirrhosis: clinical and pathologic review of 782 cases from 16,600 necropsies. Am J Pathol. 1953; 29 993-1027
49 Lunseth J H, Olmstead E G, Abboud F. A study of heart disease in one hundred eight hospitalized patients dying with portal cirrhosis. AMA Arch Intern Med. 1958; 102 405-413
50 Ocel J J, Edwards W D, Tazelaar H D, Petrovic L M, Edwards B S, Kamath P S. Heart and liver disease in 32 patients undergoing biopsy of both organs, with implications for heart or liver transplantation. Mayo Clin Proc. 2004; 79 492-501
51 Silver M A, Maisel A, Yancy C W et al.. BNP Consensus Panel 2004: a clinical approach for the diagnostic, prognostic, screening, treatment monitoring, and therapeutic roles of natriuretic peptides in cardiovascular diseases. Congest Heart Fail. 2004; 10(suppl 3) 1-30
52 Pateron D, Beyne P, Laperche T et al.. Elevated circulating cardiac troponin I in patients with cirrhosis. Hepatology. 1999; 29 640-643
53 Wong F, Siu S, Liu P, Blendis L M. Brain natriuretic peptide: is it a predictor of cardiomyopathy in cirrhosis?. Clin Sci (Lond). 2001; 101 621-628
54 Yildiz R, Yildirim B, Karincaoglu M, Harputluoglu M, Hilmioglu F. Brain natriuretic peptide and severity of disease in non-alcoholic cirrhotic patients. J Gastroenterol Hepatol. 2005; 20 1115-1120
55 Henriksen J H, Gotze J P, Fuglsang S, Christensen E, Bendtsen F, Moller S. Increased circulating pro-brain natriuretic peptide (proBNP) and brain natriuretic peptide (BNP) in patients with cirrhosis: relation to cardiovascular dysfunction and severity of disease. Gut. 2003; 52 1511-1517
56 Zambruni A, Trevisani F, Gülberg V et al.. Daily profile of circulating C-type natriuretic peptide in pre-ascitic cirrhosis and in normal subjects: relationship with renal function. Scand J Gastroenterol. 2007; 42 642-647
57 Milani A, Zaccaria R, Bombardieri G, Gasbarrini A, Pola P. Cirrhotic cardiomyopathy. Dig Liver Dis. 2007; 39 507-515
58 Liu H, Song D, Lee S S. Cirrhotic cardiomyopathy. Gastroenterol Clin Biol. 2002; 26 842-847
59 Myers R P, Lee S S. Cirrhotic cardiomyopathy and liver transplantation. Liver Transpl. 2000; 6 S44-S52
60 Donovan C L, Marcovitz P A, Punch J D et al.. 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 1180-1188
61 Sampathkumar P, Lerman A, Kim B Y et al.. Post-liver transplantation myocardial dysfunction. Liver Transpl Surg. 1998; 4 399-403
62 Therapondos G, Flapan A D, Plevris J N, Hayes P C. Cardiac morbidity and mortality related to orthotopic liver transplantation. Liver Transpl. 2004; 10 1441-1453
63 Starzl T E, Demetris A J, Van Thiel D. Liver transplantation (2). N Engl J Med. 1989; 321 1092-1099
64 Marquez J, Martin D, Virji M A et al.. Cardiovascular depression secondary to ionic hypocalcemia during hepatic transplantation in humans. Anesthesiology. 1986; 65 457-461
65 Johnston S D, Morris J K, Cramb R, Gunson B K, Neuberger J. Cardiovascular morbidity and mortality after orthotopic liver transplantation. Transplantation. 2002; 73 901-906
66 Park S C, Beerman L B, Gartner J C et al.. Echocardiographic findings before and after liver transplantation. Am J Cardiol. 1985; 55 1373-1378
67 Nasraway S A, Klein R D, Spanier T B et al.. Hemodynamic correlates of outcome in patients undergoing orthotopic liver transplantation: evidence for early postoperative myocardial depression. Chest. 1995; 107 218-224
68 Piscaglia F, Zironi G, Gaiani S et al.. Systemic and splanchnic hemodynamic changes after liver transplantation for cirrhosis: a long-term prospective study. Hepatology. 1999; 30 58-64
69 Glauser F L. Systemic hemodynamic and cardiac function changes in patients undergoing orthotopic liver transplantation. Chest. 1990; 98 1210-1215
70 Al-Hamoudi W, Alqahtani S, Ma M, Lee S S. Hemodynamics in the immediate postoperative period after liver transplantation in alcoholic and postviral cirrhosis [abstract]. Can J Gastroenterol. 2007; 21(suppl A) S029
71 Therapondos G, Flapan A D, Dollinger M M, Garden O J, Plevris J N, Hayes P C. Cardiac function after orthotopic liver transplantation and the effects of immunosuppression: a prospective randomized trial comparing cyclosporin (Neoral) and tacrolimus. Liver Transpl. 2002; 8 690-700
72 Acosta F, De La Morena G, Villegas M et al.. Evaluation of cardiac function before and after liver transplantation. Transplant Proc. 1999; 31 2369-2370
73 Liu H, Lee S S. What happens to cirrhotic cardiomyopathy after liver transplantation?. Hepatology. 2005; 42 1203-1205
74 Lee S S, Baik S K. Cardiovascular consequences of liver disease. In: Boyer TD, Wright T, Zakim MM Boyer's Hepatology: A Textbook of Liver Disease. 5th ed. Philadelphia, PA; WB Saunders Co Ltd 2006: 453-475
75 Azoulay D, Castaing D, Dennison A, Martino W, Eyraud D, Bismuth H. Transjugular intrahepatic portosystemic shunt worsens the hyperdynamic circulatory state of the cirrhotic patient: preliminary report of a prospective study. Hepatology. 1994; 19 129-132
76 Rodriguez-Laiz J M, Banares R, Echenagusia A et al.. Effects of transjugular intrahepatic portasystemic shunt (TIPS) on splanchnic and systemic hemodynamics, and hepatic function in patients with portal hypertension: preliminary results. Dig Dis Sci. 1995; 40 2121-2127
77 Quiroga J, Sangro B, Nunez M et al.. Transjugular intrahepatic portal-systemic shunt in the treatment of refractory ascites: effect on clinical, renal, humoral, and hemodynamic parameters. Hepatology. 1995; 21 986-994
78 Lotterer E, Wengert A, Fleig W E. Transjugular intrahepatic portosystemic shunt: short-term and long-term effects on hepatic and systemic hemodynamics in patients with cirrhosis. Hepatology. 1999; 29 632-639
79 Braverman A C, Steiner M A, Picus D, White H. High-output congestive heart failure following transjugular intrahepatic portal-systemic shunting. Chest. 1995; 107 1467-1469
80 Huonker M, Schumacher Y O, Ochs A, Sorichter S, Keul J, Rössle M. Cardiac function and haemodynamics in alcoholic cirrhosis and effects of the transjugular intrahepatic portosystemic stent shunt. Gut. 1999; 44 743-748
81 Ginès P, Uriz J, Calahorra B et al.. Transjugular intrahepatic portosystemic shunting versus paracentesis plus albumin for refractory ascites in cirrhosis. Gastroenterology. 2002; 123 1839-1847
82 Schwartz J M, Beymer C, Althaus S J et al.. Cardiopulmonary consequences of transjugular intrahepatic portosystemic shunts: role of increased pulmonary artery pressure. J Clin Gastroenterol. 2004; 38 590-594
83 Sanyal A J, Genning C, Reddy K R et al.. The North American Study for the Treatment of Refractory Ascites. Gastroenterology. 2003; 124 634-641
84 Salerno F, Merli M, Riggio O et al.. Randomized controlled study of TIPS versus paracentesis plus albumin in cirrhosis with severe ascites. Hepatology. 2004; 40 629-635
85 Cazzaniga M, Salerno F, Pagnozzi G et al.. Diastolic dysfunction is associated with poor survival in patients with cirrhosis with transjugular intrahepatic portosystemic shunt. Gut. 2007; 56 869-875
86 Lee S S, Liu H. Cardiovascular determinants of survival in cirrhosis. Gut. 2007; 56 746-748
87 Ruiz-del-Arbol L, Urman J, Fernández J et al.. Systemic, renal, and hepatic hemodynamic derangement in cirrhotic patients with spontaneous bacterial peritonitis. Hepatology. 2003; 38 1210-1218
88 Liu H, Lee S S. TNF-alpha in cirrhotic cardiomyopathy [abstract]. J Hepatol. 2002; 36(suppl 1) 11
89 Lee S S. Cardiac dysfunction in spontaneous bacterial peritonitis: a manifestation of cirrhotic cardiomyopathy?. Hepatology. 2003; 38 1089-1091
90 Ruiz-del-Arbol L, Monescillo A, Arocena C et al.. Circulatory function and hepatorenal syndrome in cirrhosis. Hepatology. 2005; 42 439-447
91 Le Grimellec C, Friedlander G, el Yandouzi E H, Zlatkine P, Giocondi M C. Membrane fluidity and transport properties in epithelia. Kidney Int. 1992; 42 825-836
92 Lee R F, Glenn T K, Lee S S. Cardiac dysfunction in cirrhosis. Best Pract Res Clin Gastroenterol. 2007; 21 125-140
93 Ma Z, Miyamoto A, Lee S S. Role of altered beta-adrenoceptor signal transduction in the pathogenesis of cirrhotic cardiomyopathy in rats. Gastroenterology. 1996; 110 1191-1198
94 Ma Z, Meddings J B, Lee S S. Membrane physical properties determine cardiac beta-adrenergic receptor function in cirrhotic rats. Am J Physiol. 1994; 267 G87-G93
95 Fernández-Rodriguez C M, Romero J, Petros T J et al.. Circulating endogenous cannabinoid anandamide and portal, systemic and renal hemodynamics in cirrhosis. Liver Int. 2004; 24 477-483
96 Ford W R, Honan S A, White R, Hiley C R. Evidence of a novel site mediating anandamide-induced negative inotropic and coronary vasodilatator responses in rat isolated hearts. Br J Pharmacol. 2002; 135 1191-1198
97 Bonz A, Laser M, Kullmer S et al.. Cannabinoids acting on CB1 receptors decrease contractile performance in human atrial muscle. J Cardiovasc Pharmacol. 2003; 41 657-664
98 Gaskari S A, Liu H, Moezi L, Li Y, Baik S K, Lee S S. Role of endocannabinoids in the pathogenesis of cirrhotic cardiomyopathy in bile duct-ligated rats. Br J Pharmacol. 2005; 146 315-323
99 Liu H, Ma Z, Lee S S. Contribution of nitric oxide to the pathogenesis of cirrhotic cardiomyopathy in bile duct-ligated rats. Gastroenterology. 2000; 118 937-944
100 Van Obbergh L, Vallieres Y, Blaise G. Cardiac modifications occurring in the ascitic rat with biliary cirrhosis are nitric oxide related. J Hepatol. 1996; 24 747-752
101 Garcia-Estan J, Ortiz M C, Lee S S. Nitric oxide and renal and cardiac dysfunction in cirrhosis. Clin Sci (Lond). 2002; 102 213-222
102 Liu H, Song D, Lee S S. Role of heme oxygenase-carbon monoxide pathway in pathogenesis of cirrhotic cardiomyopathy in the rat. Am J Physiol Gastrointest Liver Physiol. 2001; 280 G68-G74
103 Cohen R A, Weisbrod R M, Gericke M, Yaghoubi M, Bierl C, Bolotina V M. Mechanism of nitric oxide-induced vasodilatation: refilling of intracellular stores by sarcoplasmic reticulum Ca2 + ATPase and inhibition of store-operated Ca2 + influx. Circ Res. 1999; 84 210-219
104 Meissner G, Henderson J S. Rapid calcium release from cardiac sarcoplasmic reticulum vesicles is dependent on Ca^{2 +} and is modulated by Mg^{2 +}, adenine nucleotide, and calmodulin. J Biol Chem. 1987; 262 3065-3073
105 Ward C A, Liu H, Lee S S. Altered cellular calcium regulatory systems in a rat model of cirrhotic cardiomyopathy. Gastroenterology. 2001; 121 1209-1218
106 O'Connor C M. The new heart failure guidelines: strategies for implementation. Am Heart J. 2007; 153(suppl) 2-5
107 Pozzi M, Grassi G, Ratti L et al.. Cardiac, neuroadrenergic, and portal hemodynamic effects of prolonged aldosterone blockade in postviral Child A cirrhosis. Am J Gastroenterol. 2005; 100 1110-1116
108 Ward C A, Ma Z, Lee S S, Giles W R. Potassium currents in atrial and ventricular myocytes from a rat model of cirrhosis. Am J Physiol. 1997; 273 G537-G544

Samuel S LeeM.D.

Liver Unit, University of Calgary

3330 Hospital Drive NW, Calgary, AB, Canada T2N 4N1

eMail: samlee@ucalgary.ca