Cirrhotic cardiomyopathy: Toward an optimized definition

Since the early 1950s, the presence of a hyperdynamic circulation in patients with cirrhosis has been recognized. Invasive and echocardiographic studies revealed increases in both cardiac output and volumes, and the term cirrhotic cardiomyopathy (CCM) was applied in the late 1970s denoting a hyperdynamic unloaded failing heart.[1] Subsequently, a considerable number of original experimental and human studies and review articles emerged attempting to clarify, elucidate, and define the entity of CCM. It was generally agreed that a combination of systolic dysfunction, impaired diastolic relaxation, and electrophysiological disturbances such as prolonged QTc interval characterized CCM.[2] This led to a first attempt of a working definition of CCM, which was launched at a working party held at the World Congress of Gastroenterology in Montreal in 2005.[2] This definition comprised, in addition to systolic and diastolic dysfunction, several supportive criteria reflecting different aspects of cardiac pathology (Table 1). During the next 15 years, the echocardiographic techniques developed in particular with respect to tissue Doppler and strain imaging and new echovariables emerged such as global longitudinal strain (GLS), a measure of systolic function, and septal e'. The advent of new tissue Doppler imaging measures to assess tissue velocities have improved the accuracy of assessing systolic and diastolic dysfunction, where septal e', lateral e', and E/e' all reflect left ventricular filling pressure.[3] Taking this into account, Izzy et al. and The Cirrhotic Cardiomyopathy Consortium recently proposed new criteria for CCM published in 2020, including septal e' velocity, E/e' ratio, and left atrial volume index.[4] The revised 2020 criteria were largely adapted from the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging and permit the assessment of CCM both at rest and during stress (Table 1). Applying new diagnostic criteria of CCM may result in different figures with respect to prevalence and selection of patients with different associations to morbidity, cardiac dysfunction, and outcome after stressful procedures, surgical complications, major adverse cardiac events (MACE), and mortality. Briefly, new definitions recruit other patients, but the key issue is if we catch patients with “true” CCM. For example, the prevalence according to the 2005 criteria may be as high as 50%, whereas it averages 28%–35% when applying the 2020 criteria.[5,6] TABLE 1 - Old and new criteria for CCM World Congress of Gastroenterology criteria 2005 Systolic dysfunction (any of the following) Blunted contractile response on stress testing LVEF <55% Diastolic dysfunction (any of the following) Deceleration time >200 ms Isovolumetric relaxation time >80 ms E/A < 1 Supportive criteria Electromechanical abnormalities Abnormal chronotropic response to stress Electromechanical uncoupling Prolonged QTc interval Enlarged left atrium Increased left ventricular mass Increased pro‐BNP and BNP Increased troponin I Criteria proposed by the Cirrhotic Cardiomyopathy Consortium 2020 Systolic dysfunction (any of the following) LVEF ≤50% Absolute GLS <18% or >22% Advanced diastolic dysfunction (one or more of the following) Septal e' velocity <7 cm/s E/e' ratio ≥ 15 LAVI >34 ml/m2 TR velocity > 2.8 m/s Areas for further validation Abnormal chronotropic or inotropic response Electrocardiographic changes Electromechanical uncoupling Myocardial mass change Serum biomarkers Chamber enlargement ECV by CMRI Abbreviations: BNP, brain natriuretic peptide; CCM, cirrhotic cardiomyopathy; CMRI, cardiac magnetic resonance imaging; ECV, extracellular volume; GLS, global longitudinal strain; LAVI, left atrial volume index: LVEF, left ventricular ejection fraction; TR, tricuspid regurgitation. In this issue of Liver Transplantation, Spann et al. have approached this question by comparing the definitions of CCM with clinical output in terms of MACE and cardiac function.[7] In a single‐center retrospective study, the authors included 210 of 1165 patients with pre–liver transplantation echocardiography and eligibility criteria. The authors applied MACE comprising arrythmia, heart failure, cardiac arrest, or cardiac death as primary composite endpoints. According to the 2005 criteria, 162 patients (77%) had CCM. According to the 2020 criteria, the figure was 64 (30%), respectively. In the follow‐up period, 44 MACE and 31 deaths were associated with the 2020 but not the 2005 criteria. With respect to diastolic dysfunction, the Doppler tissue variable septal e' predicted MACE after liver transplantation. Based on these findings, the authors concluded that CCM according to the 2020 criteria associates with risk of MACE. Moreover, septal e' as a marker of diastolic dysfunction appears to be the best echocardiographic predictor for MACE after liver transplantation. The results of Spann et al. are interesting for several reasons. First, applying the 2020 criteria results in a differential and lower prevalence of CCM, which seems to include a different patient population suffering a higher risk of MACE. Second, implementation of newer tissue Doppler imaging measures allows the authors to include other pathophysiological aspects of CCM than the older criteria allowed. Thus, for example, inclusion of the left atrial volume index (LAVI) takes into account the morphological and functional changes of the left atrium, which previously have been shown to be of predictive value.[8] Increased extracellular volume may reflect augmented fibrogenesis in the myocardium and represent a pathophysiological substrate of CCM as also mentioned by the authors.[9] Low septal e´ as the most predictive variable for MACE also points to diastolic dysfunction as an essential element for the development of CCM, in particular after liver transplantation. There are, however, some caveats to the study. The authors conducted the study retrospectively with the inclusion of only 210 of 1165 patients. Moreover, the authors did not consider GLS, which was not measured in all patients. In addition, patients with low left ventricular ejection fraction (LVEF) were not considered for liver transplantation although they might have had CCM, which may introduce a bias. This implies that there is still room for improvement and modification of the diagnostic criteria for the purpose of a better prognostic relevance.[6] Nevertheless, the article by Spann et al. represents an important step forward in our attempts to define those patients with cirrhosis with a cardiac dysfunction who may suffer an increased risk of MACE. Although the 2020 criteria may not be perfect, they include less load‐dependent measures of diastolic dysfunction. On the other hand, the 2020 criteria may not sufficiently take cardiovascular stress tests and biomarkers into consideration. Hopefully the future will see new prospective studies that will use complete echocardiographic measures to further delineate and optimize the relevant criteria for selecting patients at risk. CONFLICT OF INTEREST Nothing to report.