Does cardiac dysfunction explain deleterious effects of beta-blockers in cirrhosis and refractory ascites?^†

We read with great interest the study by Sersté et al.1 This is an impressive study of 151 patients with refractory ascites in whom beta-blockers were shown to have deleterious effects on survival. Despite meticulous analyses of the data, the authors did not find any plausible explanation for the differences between patients treated with beta-blockers and patients not treated with beta-blockers, such as differences in the degree of portal hypertension, the presence of esophageal varices, or liver dysfunction. However, the arterial blood pressure was lower in the beta-blocker group, and four characteristics—the presence of hepatocellular carcinoma, Child-Pugh score class C, refractory ascites as the etiology, and beta-blocker therapy—predicted death. Apart from the arterial blood pressure and heart rate, characteristics of cardiac function such as the cardiac output were not measured in the study. We therefore propose a potential contributing explanation for the dramatic effect of beta-blockers on survival in patients with refractory ascites. Treatment with a nonselective beta-blocker decreases cardiac output by blockade of the beta-1-adrenergic receptors. We believe that the pronounced inhibitory effect of propranolol on cardiac function may explain the increased mortality. It is well known that in patients with refractory ascites and circulatory dysfunction, renal function often deteriorates further with the development of hepatorenal syndrome. There seems to be a complex and bidirectional interaction between the heart and the kidneys, and different observations have suggested that a type of cardiac dysfunction known as cirrhotic cardiomyopathy significantly contributes to the pathophysiology of hepatorenal syndrome. A cardiorenal interaction may be a key element in the homeostasis of the extracellular fluid volume, arterial blood pressure, and effective/central blood volume. We believe that different observations point to impaired cardiac function in cirrhosis as part of the pathogenesis of hepatorenal syndrome.2-4 It has been demonstrated that patients with cirrhosis, before they develop type 1 hepatorenal syndrome, have decreased or relatively low cardiac output.2-4 In these patients, treatment by beta-blockers further reduces cardiac output, systemic perfusion, and peripheral oxygen delivery with potentially deleterious effects.2-4 We therefore propose an additional explanation for the reduced survival after beta-blocker treatment. We hypothesize that the reduction of the effective arterial blood volume and renal failure in patients with cirrhosis and refractory ascites are consequences of not only progressive arterial vasodilatation but also cardiac systolic dysfunction. The result of systolic dysfunction is relatively reduced cardiac output insufficient to maintain adequate arterial blood pressure and renal perfusion. These mechanisms are further hampered by treatment with beta-blockers and explain the deleterious effects in patients with refractory ascites, as described by Sersté et al. It would be useful to know whether the authors have data on specific causes of death in both groups, especially with respect to the development of renal impairment and the presence of hepatorenal syndrome. We suggest that future studies be designed to prospectively seek the relationship between beta-blocker treatment and simultaneous changes in cardiac and renal function.