Cardiac dysfunction in spontaneous bacterial peritonitis: A manifestation of cirrhotic cardiomyopathy?

“Nothing in this world is so powerful as an idea whose time has come. ” —Victor Hugo Cirrhosis is associated with cardiovascular disturbances. Half a century ago, Kowalski and Abelmann described the hyperdynamic circulation in cirrhotic patients: increased cardiac output and low arterial pressure as the result of a decreased peripheral vascular resistance.1 Since then, many studies have delineated the underlying mechanisms and complications of the hyperdynamic circulation (reviewed in Groszmann2); its existence and clinical significance are undisputed. The same cannot be said of a condition termed “cirrhotic cardiomyopathy. ” It seems paradoxical to speak of a cardiomyopathy when baseline ventricular contractility is increased. However, Gould et al. in 1969 demonstrated that cardiac contractile response to stimuli was depressed in patients with alcoholic cirrhosis, a phenomenon presumed by the investigators to reflect the presence of a mild or latent alcoholic cardiomyopathy.3 Several studies over the next decade, all done in alcoholic patients, confirmed these findings. Only in the mid-1980s did some studies suggest that the depressed cardiac function is the result of cirrhosis rather than alcohol. Gerbes et al. found downregulated -adrenergic receptor density in lymphocytes (thought to reflect cardiac -adrenoceptors) from patients with decompensated cirrhosis,4 while in the CCl4rat model of cirrhosis, Caramelo et al. found that volume infusions decreased cardiac output, thus indicating ventricular failure.5 In 1990, we documented down-regulation of ventricular -adrenoceptors in rats with biliary cirrhosis.6 Since then, a large number of studies have incontrovertibly demonstrated that both patients and animal models with nonalcoholic cirrhosis show blunted cardiac inotropic and chronotropic responses to diverse stimuli such as exercise, drugs, hemorrhage, surgery, or other stresses (reviewed7-9). Thus was born the general definition of cirrhotic cardiomyopathy: depressed responsiveness to stimuli in the face of increased baseline contractility. Abnormal cardiac function is not limited to contractility. Several studies have shown electrophysiologic changes in cirrhotic patients. Repolarization abnormalities including QT interval prolongation10 (reviewed7,9,11) and increased dispersion of the systolic electromechanical interval12 have been documented. The mechanisms underlying these electrophysiologic abnormalities remain unclear, but a study in cirrhotic rats suggests that depressed function of 2 types of ventricular K channels may play a role.13 In the absence of accepted parameters to define cirrhotic cardiomyopathy, the exact extent of this syndrome remains unclear. Not all patients with cirrhosis show a clear depression of systolic contractility with stimuli. However, it seems that virtually all patients with cirrhosis show some depression of diastolic function, i.e., evidence of a stiff, noncompliant ventricle.14,15 This is not surprising given that most myocardial diseases that result in heart failure first show evidence of a noncompliant ventricle (diastolic dysfunction) before overt systolic contractile failure occurs. The lack of universally accepted definitions has also led some skeptics to conclude that the syndrome does not exist, or at most, is a “normal” reactive response to the hyperdynamic circulation, i.e., a volume-overloaded but compensated ventricle. Not all studies support the existence of this syndrome; for example, a recent study in rats with biliary cirrhosis found only eccentric left ventricular hypertrophy16 with no obvious cardiodepression in isolated perfused hearts from these rats. However, further examination of the data indicates that contractility corrected for ventricular mass is reduced by approximately 17%. 16 Another issue is that overt heart failure is extremely rare in cirrhotic patients in the absence of alcoholism. All other cardiomyopathies eventually progress to overt heart Abbreviations: TIPS, transjugular intrahepatic stents; SBP, spontaneous bacterial peritonitis; TNF, tumor necrosis factor . From the Liver Unit, University of Calgary, Calgary, Alberta, Canada. Supported by operating research grants from the Canadian Institutes for Health Research and a Senior Scholarship Award from the Alberta Heritage Foundation for Medical Research. Address reprint requests to: Samuel S. Lee, M.D., 3330 Hospital Dr. NW, Liver Unit, University of Calgary, Calgary, AB, T2N 4N1, Canada. E-mail: samlee@ucalgary.ca; fax: 403-270-0995. Copyright © 2003 by the American Association for the Study of Liver Diseases. 0270-9139/03/3805-0004$30.00/0 doi:10.1053/jhep.2003. 50489