Therapies for Cirrhotic Cardiomyopathy: Current Perspectives and Future Possibilities

Abstract

Cirrhotic cardiomyopathy (CCM) is defined as cardiac dysfunction associated with cirrhosis in the absence of pre-existing heart disease. CCM manifests as the enlargement of cardiac chambers, attenuated systolic and diastolic contractile responses to stress stimuli, and repolarization changes. CCM significantly contributes to mortality and morbidity in patients who undergo liver transplantation and contributes to the pathogenesis of hepatorenal syndrome/acute kidney injury. There is currently no specific treatment. The traditional management for non-cirrhotic cardiomyopathies, such as vasodilators or diuretics, is not applicable because an important feature of cirrhosis is decreased systemic vascular resistance; therefore, vasodilators further worsen the peripheral vasodilatation and hypotension. Long-term diuretic use may cause electrolyte imbalances and potentially renal injury. The heart of the cirrhotic patient is insensitive to cardiac glycosides. Therefore, these types of medications are not useful in patients with CCM. Exploring the therapeutic strategies of CCM is of the utmost importance. The present review summarizes the possible treatment of CCM. We detail the current status of non-selective beta-blockers (NSBBs) in the management of cirrhotic patients and discuss the controversies surrounding NSBBs in clinical practice. Other possible therapeutic agents include drugs with antioxidant, anti-inflammatory, and anti-apoptotic functions; such effects may have potential clinical application. These drugs currently are mainly based on animal studies and include statins, taurine, spermidine, galectin inhibitors, albumin, and direct antioxidants. We conclude with speculations on the future research directions in CCM treatment.

Keywords: anti-apoptosis; anti-inflammation; antioxidants; beta blockers; cirrhotic cardiomyopathy; treatments.

Figure 1

Schematic diagram of pathogenic mechanisms of CCM and therapeutic targets. + denotes positive or stimulatory effect. —denotes negative or inhibitory effect. NSBB: non-specific beta-blocker. TNFα: tumor necrosis factor alpha. IL-1β: interleukin 1beta. HO: hemo oxygenase. CO: carbon monoxide. NO: nitric oxide. ROS: reactive oxygen species. PKA: protein kinase A. PKG: protein kinase G. N-Lac: N-acetyllactosamine.