End-stage liver disease is linked to cardiovascular complications that can manifest as hyperdynamic circulation and may progress to overt heart failure in the context of cirrhotic cardiomyopathy (CCM). The incidence of CCM is significantly elevated among individuals with cirrhosis. However, due to the absence of overt symptoms at rest and the preservation of left ventricular systolic function, the diagnosis is frequently overlooked. The severity of CCM correlates directly with the degree of liver disease and is associated with poorer prognostic outcomes in both pre- and post-transplantation. Diagnosis is important because CCM is a major contributor to perioperative cardiovascular complications (including pulmonary edema and death) after liver transplant. These complications arise from the rapid escalation of systemic vascular resistance, which unmasks the subclinical left ventricular systolic dysfunction. Another clinical context in which CCM becomes evident is following transjugular intrahepatic portosystemic shunt placement. The abrupt increase in preload from blood redistribution can precipitate cardiac decompensation. The purpose of this review is to increase clinical recognition of this specific phenotype of heart failure with preserved ejection fraction. It aims to synthetize the pathophysiological mechanisms, definition, and diagnostic of CCM, also to highlight its clinical significance in the cirrhotic population and explore the possible therapeutic options. A literature review was performed using Pubmed and focused on the relevant and recent articles and trials concerning CCM. Based on literature data and on institutional experience, we propose an algorithm for cardiac assessment in cirrhosis to improve CCM diagnosis and ensure better outcomes.

Background: In end-stage liver disease (ESLD), cardiovascular changes are frequent and relate to the presence of hyperdynamic circulation. In 2019, diagnostic criteria for cirrhotic cardiomyopathy (CCM) were updated to include tissue Doppler and speckle tracking imaging in defining left ventricle (LV) systolic and diastolic dysfunction. Evaluation of diastolic function remains challenging, with frequent indeterminate cases and emerging evidence of worse prognosis. The aim of the present study was to evaluate the prevalence of LV systolic and diastolic dysfunction in cirrhosis, in correlation with liver disease severity and potential prognostic implications. Methods: We performed an observational, retrospective, non-randomized, single-center study that included 99 cirrhotic patients evaluated for liver transplant (LT) in a tertiary center. Liver disease severity and complications were analyzed with survival and echocardiography data to determine potential correlations with prognosis. For statistical analysis, IBM^® SPSS^® Statistics version 20 (Chicago, IL, USA) was utilized. A two-sided p-value < 0.05 was considered statistically significant. Results: Left atrial (LA) volume index (r = 0.230, p = 0.022), LA reservoir strain (r = 0.291, p = 0.003), and LA contraction strain absolute value (r = 0.223, p = 0.027) positively correlated with the severity of liver disease expressed by MELD Na score. LA dilation (≥34 mL/m²) was the most common echocardiographic finding. It was present in 69.7% of patients, with one third having severe LA dilation (>45 mL/m²), which was associated with worse survival (log rank p = 0.019). LA contraction strain with an absolute value higher than 16% was also associated with worse survival (log rank p = 0.024). In multivariable Cox analysis, only MELD-Na and LA volume index remained independently associated with mortality. Diastolic dysfunction appeared more prevalent among the non-surviving patients irrespective of the diagnostic criteria used (p = 0.023 for American Society of Echocardiography 2016 criteria; p = 0.032 for CCM 2019 criteria). On binomial logistic regression, the presence of significant diastolic dysfunction (>grade 1) was associated with an increased probability of composite end-point of death or LT in the presence of liver disease severity confounders. The use of the LA stiffness index in discerning diastolic function in patients with standard inconclusive evaluation may warrant further investigation. Conclusions: Echocardiographic alterations, particularly LA enlargement, are associated with liver disease severity and clinical outcomes in ESLD. These findings are hypothesis-generating and suggest a potential role for echocardiography in risk stratification, warranting validation in larger prospective studies.

Background: Chemokine CCL5 may drive inflammation and vascular risk in advanced liver disease, but its cardiovascular implications are unclear. Secreted by hepatic, endothelial, macrophage, and lymphocytic cells, CCL5 is involved in cytokine regulation. Its serum levels rise in acute liver injury and hepatocellular carcinoma (HCC), but decline with fibrosis progression in end-stage liver disease (ESLD). CCL5 has also been linked to atherosclerosis. This study aimed to evaluate serum CCL5 levels in ESLD patients listed for liver transplantation (LT) and to assess their potential role as markers of cardiovascular (CV) risk and portal hypertension. Methods: We conducted an observational cohort study. Between 2019 and 2022, patients with ESLD evaluated for LT were enrolled. Data on liver pathology, CV risk, and laboratory parameters were collected. Serum CCL5 concentrations were measured using Sigma Aldrich^® CCL5 ELISA kits (MilliporeSigma, St. Louis, MO, USA). The database was analyzed with IBM^® SPSS^® Statistics version 20 (Chicago, IL, USA). Results: Overall, 46 patients were included, 50% with viral hepatitis and 28.3% with alcohol-related liver disease. HCC was present in 37% of cases. The median CV risk scores (CAD_LT = 7, mCAD_LT = 7, CAR_OLT = 18) placed the population at moderate CV risk. Serum CCL5 levels did not vary significantly between viral vs. non-viral cirrhosis (5511.8 vs. 6272.5 pg/mL, p = 0.15) and were not influenced by the presence of HCC (6098.4 vs. 5771.3 pg/mL, p = 0.55). We did not detect a correlation with MELD score (p = 0.21) or CV risk scores (CAD_LT: p = 0.58; mCAD_LT: p = 0.70; CAR_OLT: p = 0.22). Patients with thrombocytopenia (<100,000/µL, 54.3%) or a history of esophageal variceal ligation had lower CCL5 levels (5170.9 vs. 6750.8 pg/mL, p = 0.002 and 4252.0 vs. 6237.5 pg/mL, p = 0.003, respectively). Similarly, patients with a history of previous variceal bleeding and spontaneous bacterial peritonitis (SBP) had lower levels of CCL5 (4373.8 vs. 6119.9 pg/mL, p = 0.02 and 3404.3 vs. 6606.7 pg/mL, p = 0.01, respectively). We found a negative correlation between CCL5 and QTc interval duration (τ = −0.216, p = 0.037), left ventricle size (LV: τ = −0.235, p = 0.027), and pulmonary artery pressure (RV/RA gradient: τ = −0.225, p = 0.03). CCL5 correlated positively with the inflammatory markers C-reactive protein (CRP) (τ = 0.246, p = 0.018) and fibrinogen (r = 0.216, p = 0.04). Conclusions: In liver transplant candidates, serum CCL5 is not associated with cardiovascular risk scores or coronary atherosclerotic burden, but is inversely associated with clinical markers of portal hypertension severity. These findings suggest that CCL5 may serve as a potential non-invasive surrogate marker of portal hypertension rather than a cardiovascular risk biomarker in ESLD.