Reevaluating cirrhotic cardiomyopathy diagnostics

N/A. We read with interest the recent review article by Liu et al.[1]Liu H. Naser J.A. Lin G. Lee S.S. Cardiomyopathy in cirrhosis: from pathophysiology to clinical care.JHEP Rep. 2024; 6100911Google Scholar in which they explored the relative effectiveness of the two published guidelines for diagnosis of cirrhotic cardiomyopathy (CCM) and proposed the addition of a prolonged QT interval to these diagnostic criteria. While they should be commended for their summary of the extant literature in the field; we believe that there is additional literature that merits attention and which could further highlight the complexities of the CCM diagnosis. Firstly, the authors highlight that patients with cirrhosis have hypercontractile left ventricular function at rest leading to a reduced contractile reserve, and concluded that there was currently a lack of standardized criteria to define this phenomenon, leading to its omission from the 2019 CCM diagnostic criteria.[1]Liu H. Naser J.A. Lin G. Lee S.S. Cardiomyopathy in cirrhosis: from pathophysiology to clinical care.JHEP Rep. 2024; 6100911Google Scholar,[2]Izzy M. VanWagner L.B. Lin G. Altieri M. Findlay J.Y. Oh J.K. et al.Redefining cirrhotic cardiomyopathy for the Modern Era.Hepatology. 2020; 71: 334-345Crossref PubMed Scopus (181) Google Scholar The fact that an increased cardiac output could be a surrogate for cirrhotic cardiomyopathy and in turn its adverse sequelae at first seems counter intuitive, however work from our group published subsequent to these criteria has provided further support for this hypothesis and proposed a new diagnostic criteria to better define this concept.[3]Koshy A.N. Farouque O. Cailes B. Testro A. Ramchand J. Sajeev J.K. et al.Impaired cardiac reserve on dobutamine stress Echocardiography predicts the Development of hepatorenal syndrome.Am J Gastroenterol. 2020; 115: 388-397Crossref PubMed Scopus (26) Google Scholar We propose that an impaired increase in cardiac output of less than 25% upon low-dose dobutamine challenge, which correlates with a four-fold higher risk of hepatorenal syndrome, should be integrated into the diagnostic criteria.[2]Izzy M. VanWagner L.B. Lin G. Altieri M. Findlay J.Y. Oh J.K. et al.Redefining cirrhotic cardiomyopathy for the Modern Era.Hepatology. 2020; 71: 334-345Crossref PubMed Scopus (181) Google Scholar,[3]Koshy A.N. Farouque O. Cailes B. Testro A. Ramchand J. Sajeev J.K. et al.Impaired cardiac reserve on dobutamine stress Echocardiography predicts the Development of hepatorenal syndrome.Am J Gastroenterol. 2020; 115: 388-397Crossref PubMed Scopus (26) Google Scholar These findings support the hypothesis that it is a lack of contractile reserve on stress testing, rather than a reduced baseline left ventricular ejection fraction, which is a feature of CCM and work is ongoing to further investigate the use of this new diagnostic criterion as a potential diagnostic tool for the diagnosis of CCM that could contribute to future guidelines. Furthermore, while the addition of global longitudinal strain (GLS) has been proposed in the diagnosis of CCM, the accuracy in GLS to ascertain subclinical changes in cardiac function in patients with a hyperdynamic resting function is unclear. Regarding the addition of a prolonged QT interval as a criterion for CCM, our findings suggest that, while it correlates with ventricular arrhythmia risk, it does not necessarily predict post-transplant complications or mortality.4Cailes B. Koshy A.N. Gow P. Weinberg L. Srivastava P. Testro A. et al.Inducible left ventricular Outflow Tract Obstruction in patients Undergoing liver transplantation: Prevalence, Predictors, and association with Cardiovascular Events.Transplantation. 2021; 105: 354-362Crossref PubMed Scopus (2) Google Scholar, 5Ko J. Koshy A.N. Han H.C. Weinberg L. Gow P. Testro A. et al.Effect of liver transplantation on QT-interval prolongation and impact on mortality.Int J Cardiol. 2021; 326: 158-163Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 6Koshy A.N. Ko J. Farouque O. Cooray S.D. Han H.C. Cailes B. et al.Effect of QT interval prolongation on cardiac arrest following liver transplantation and derivation of a risk index.Am J Transpl. 2021; 21: 593-603Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar There is also a lack of correlation between electrocardiographic and structural cardiac changes in cirrhosis, indicating distinct pathophysiological mechanisms for CCM and QT interval prolongation.[7]Koshy A.N. Gow P.J. Testro A. Teh A.W. Ko J. Lim H.S. et al.Relationship between QT interval prolongation and structural abnormalities in cirrhotic cardiomyopathy: a change in the current paradigm.Am J Transpl. 2021; 21: 2240-2245Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar This necessitates further exploration before its inclusion in diagnostic criteria. Whilst we agree with the authors contention that the 2019 Cirrhotic Cardiomyopathy Consortium (CCC)[2]Izzy M. VanWagner L.B. Lin G. Altieri M. Findlay J.Y. Oh J.K. et al.Redefining cirrhotic cardiomyopathy for the Modern Era.Hepatology. 2020; 71: 334-345Crossref PubMed Scopus (181) Google Scholar guidelines appear to have better predictive and discriminatory ability than the previously proposed 2005 World Congress of Gastroenterology (WCG), we put forward that there is certainly still scope to improve these criteria further. These criteria focus entirely on resting echocardiographic indices and the decision to omit any reference to an impaired contractile reserve appears to potentially be a significant one, as the hyperdynamic resting left ventricular function which is often associated with more severe liver disease likely represent patients encroaching on their cardiac reserve at rest. Further studies in this area are required to refine the diagnostic criteria for CCM and establish what cardiac testing is appropriate for establishing this diagnosis in the future. BC, OF, AM and ANK all contributed to writing of the article. The authors have not received any financial support for the production of this manuscript. The authors have no conflicts of interest to report, excluding the fact that they have previously published in the area as referenced in the text. The following is/are the supplementary data to this article. Download .docx (.04 MB) Help with docx files Download .pdf (.3 MB) Help with pdf files Cardiomyopathy in cirrhosis: From pathophysiology to clinical careJHEP ReportsVol. 6Issue 1PreviewCirrhotic cardiomyopathy (CCM) is defined as systolic or diastolic dysfunction in the absence of prior heart disease or another identifiable cause in patients with cirrhosis, in whom it is an important determinant of outcome. Its underlying pathogenic/pathophysiological mechanisms are rooted in two distinct pathways: 1) factors associated with portal hypertension, hyperdynamic circulation, gut bacterial/endotoxin translocation and the resultant inflammatory phenotype; 2) hepatocellular insufficiency with altered synthesis or metabolism of substances such as proteins, lipids, carbohydrates, bile acids and hormones. Full-Text PDF Open Access