Towards a better characterization of cirrhosis-associated cardiomyopathy?
Authors: Ahmed Zaky, John D. Lang, Miriam Treggiari
Journal: Journal of Hepatology (2013)

‘Cirrhotic cardiomyopathy’ arose as a separate clinical entity when characterized by Lee and colleagues in 1989 [[1]Lee S.S. Cardiac abnormalities in liver cirrhosis.West J Med. 1989; 151: 530-535PubMed Google Scholar]. According to the World Congress of Gastroenterology [[2]Moller S. Henriksen J.H. Cirrhotic cardiomyopathy.J Hepatol. 2010; 53: 179-190Abstract Full Text Full Text PDF PubMed Scopus (242) Google Scholar], cirrhotic cardiomyopathy describes ‘cardiac dysfunction in patients with cirrhosis characterized by impaired contractile responsiveness to stress, diastolic dysfunction and electrophysiological abnormalities in the absence of known cardiac disease’ (Table 1). It is known that patients with cirrhotic cardiomyopathy have high mortality and morbidity [[3]Fouad T.R. Abdel-Razek W.M. Burak K.W. Bain V.G. Lee S.S. Prediction of cardiac complications after liver transplantation.Transplantation. 2009; 87: 763-770Crossref PubMed Scopus (114) Google Scholar]. Thus, there is a need that this entity be more accurately described.Table 1Working definition of cirrhotic cardiomyopathy [2]Moller S. Henriksen J.H. Cirrhotic cardiomyopathy.J Hepatol. 2010; 53: 179-190Abstract Full Text Full Text PDF PubMed Scopus (242) Google Scholar. Cardiac dysfunction in patients suffering from cirrhosis characterized by impaired contractile responsiveness to stress and/or altered diastolic relaxation with associated electrophysiological abnormalities in the absence of other known cardiac disease. Open table in a new tab Impaired contractile responsiveness to stress originated from reports of failure to increase one or more measures of cardiac performance including: cardiac output, ejection fraction, and stroke volume in response to stress, with elevation of left ventricular filling pressures. The changes in cardiac afterload have been reported inconsistently among studies; with afterload being elevated in some [4Regan 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: 397-407Crossref PubMed Scopus (161) Google Scholar, 5Caramelo C. Fernandez-Munoz D. Santos J.C. Blanchart A. Rodriguez-Puyol D. Lopez-Novoa J.M. et al.Effect of volume expansion on hemodynamics, capillary permeability and renal function in conscious, cirrhotic rats.Hepatology. 1986; 6: 129-134Crossref PubMed Scopus (84) Google Scholar] and reduced in others [[6]Wong F. Girgrah N. Graba J. Allidina Y. Liu P. Blendis L. The cardiac response to exercise in cirrhosis.Gut. 2001; 49: 268-275Crossref PubMed Scopus (203) Google Scholar]. Based on these observations, the consistent response of left ventricular output and filling pressures to varying stress-related changes in afterload was coined as stress-related contractile dysfunction. As a consequence, normal ventricular filling pressures coupled with an elevated output during resting conditions were perceived as appropriate function. In other words, left ventricular stroke volume, cardiac output, and ejection fraction have all been regarded as presumptive surrogates of intrinsic contractile function as a function of filling pressures. Several physiological considerations would argue against such interpretation of cardiac output and ejection fraction. First, cardiac output is the product of stroke volume and heart rate. Therefore, a hyperdynamic state characterized by an elevated heart rate may mask an intrinsic contractile dysfunction. Second, cardiac output and stroke volume are load-dependent indices that show mutually inverse proportionality with venous return and afterload. Therefore, reduction in afterload may mask both an intrinsic contractile dysfunction, as well as mild hypovolemia, during resting conditions. On the other hand, marked hypovolemia secondary to dehydration may mask an increase in cardiac output resulting from afterload reduction, as occurs in exercise. The same limitations apply to ejection fraction as a surrogate of ventricular contractility. An elevated resting left ventricular end diastolic volume, coupled with a decrease in end systolic volume due to a reduction in afterload, might explain the increase in resting ejection fraction that is unrelated to intrinsic contractile dysfunction [[7]Brutsaert D.L. Cardiac dysfunction in heart failure: the cardiologist’s love affair with time.Prog Cardiovasc Dis. 2006; 49: 157-181Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar]. Third, ejection fraction is a marker of the more circularly arranged myocardial fibers, which are less vulnerable than the longitudinally arranged subendocardial fibers to ischemia and fibrosis [[7]Brutsaert D.L. Cardiac dysfunction in heart failure: the cardiologist’s love affair with time.Prog Cardiovasc Dis. 2006; 49: 157-181Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar]. Therefore, a normal resting ejection fraction may not necessarily represent normal intrinsic ventricular contractile function. Fourth, there are multiple technical limitations in the measurement of ejection fraction by echocardiography such as: less accurate border detection in postoperative and mechanically ventilated patients, and underestimation of end diastolic volumes [[8]Thys D.M. Hillel Z. Goldman M.E. Mindich B.P. Kaplan J.A. A comparison of hemodynamic indices derived by invasive monitoring and two-dimensional echocardiography.Anesthesiology. 1987; 67: 630-634Crossref PubMed Scopus (136) Google Scholar]. Fifth, elevated ventricular pressures may not necessarily reflect a contractile dysfunction highlighting the widely adopted term ‘heart failure with preserved ejection fraction’. Consistent with these insights, a recent study using Doppler tissue imaging in patients with liver cirrhosis demonstrated a decline in the resting peak left ventricular systolic velocity and strain rate, suggesting a decline in the more vulnerable longitudinally arranged fibers [[9]Kazankov K. Holland-Fischer P. Andersen N.H. Torp P. Sloth E. Aagaard N.K. et al.Resting myocardial dysfunction in cirrhosis quantified by tissue Doppler imaging.Liver Int. 2011; 31: 534-540Crossref PubMed Scopus (87) Google Scholar]. Taken together, these observations suggest that more sensitive markers of left ventricular intrinsic contractile dysfunction could be useful to better define cirrhotic cardiomyopathy. Cardiac diastolic dysfunction has been sought in the current definition of cirrhotic cardiomyopathy (Table 1). Normally, the velocity of early rapid ventricular filling (denoted by E) is greater than the later filling phase that is dependent on atrial contraction (denoted by A) [[10]Nagueh S.F. Appleton C.P. Gillebert T.C. Marino P.N. Oh J.K. Smiseth O.A. et al.Recommendations for the evaluation of left ventricular diastolic function by echocardiography.Eur J Echocardiogr. 2009; 10: 165-193Crossref PubMed Scopus (1693) Google Scholar]. Therefore, E/A <1 may denote impaired ventricular relaxation. A low E/A, however, is highly preload-determined. Decompensated patients suffering from cirrhosis may retain fluids that may mask an underlying diastolic dysfunction. Also, E/A <1 may be a normal age-related finding. Moreover, The American Society of Echocardiography has included tissue Doppler imaging criteria in the diagnosis of diastolic dysfunction [[10]Nagueh S.F. Appleton C.P. Gillebert T.C. Marino P.N. Oh J.K. Smiseth O.A. et al.Recommendations for the evaluation of left ventricular diastolic function by echocardiography.Eur J Echocardiogr. 2009; 10: 165-193Crossref PubMed Scopus (1693) Google Scholar]. Doppler tissue imaging measures the slow velocity high amplitude annular tissue motion (denoted by E′) that is less affected by preload. An increase in the E/E′ ratio has been used as a more sensitive measure of diastolic dysfunction. It is therefore necessary to include more sensitive markers of left ventricular diastolic dysfunction into a description of cirrhotic cardiomyopathy. Given the emerging evidence of the presence of more sensitive markers of left ventricular dysfunction that are not pathognomonic to liver cirrhosis, the term ‘cirrhosis-associated’ may be a more adequate term than ‘cirrhotic’ cardiomyopathy. In summary, cardiac dysfunction in cirrhosis may not only be stress-related. There is a need to apply new technology in exploring more sensitive markers of left ventricular dysfunction in cirrhosis. Equally important, there is a need to explore the role of other chambers of the heart, such as the right ventricle, in the characterization and prognosis of cirrhosis-associated cardiomyopathy. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.