Cardiac Biomarkers and Risk Stratification in Liver Transplantation for Acute-on-chronic Liver Failure: Refining Current Risk Models for Improved Prediction of Posttransplant Mortality

BACKGROUND: Cardiovascular complications are the leading cause of mortality after liver transplant in patients with acute-on-chronic liver failure (ACLF). However, the extent of cardiac impairment in these patients remains unclear. Current risk models, including the Chronic Liver Failure Consortium-Organ Failure, the North American Consortium for the Study of End-stage Liver Disease (NACSELD)-ACLF, and the novel Sundaram ACLF-Liver Transplant-Mortality (SALT-M) scores primarily focus on blood pressure and the use of cardiovascular drugs, without directly assessing biomarkers of cardiac injury. To address the role of cardiac dysfunction, the authors assessed the severity of cardiac impairments with cardiac biomarkers and modified the SALT-M score, developing the SALT-M_ CARDIAC score to better predict mortality after liver transplant. METHODS: In the ASAN-Liver Transplant Registry from 2008 to 2019, 710 consecutive patients with ACLF (ACLF grade 3 [27.3%] and NACSELD-ACLF-positive [26.3%]) were evaluated for heart failure and myocardial injury, using prospective measurements of B-type natriuretic peptide (BNP) and high-sensitivity troponin I (hsTnI), respectively. The authors assessed model performance using C-statistics, optimism-corrected C-statistics, and calibration metrics. Feature importance was assessed using Shapley Additive exPlanations analysis, and a nomogram was constructed. RESULTS: Among patients with ACLF grade 3 and who were NACSELD-ACLF-positive, 32.5% and 34.8% had BNP greater than 400 pg/ml, suggestive of acute heart failure, while 12.9% and 12.3% had hsTnI levels greater than 10-fold the upper limit, respectively. Shapley Additive exPlanations analysis identified BNP and hsTnI as important predictors of mortality after liver transplant. Incorporating cardiac biomarkers into NACSELD-ACLF and Chronic Liver Failure Consortium-Organ Failure scores increased the C-index for 30-day mortality from 0.68 to 0.75 and 0.72 to 0.75, respectively. Compared to the original SALT-M score, the SALT-M_ CARDIAC score improved the optimism-corrected C-index for 30-day mortality from 0.73 to 0.76 ( P < 0.001). A nomogram using the SALT-M_ CARDIAC score was constructed to predict survival after transplant. CONCLUSIONS: Cardiac impairment is prevalent in patients with ACLF and crucial for risk stratification. Integrating cardiac biomarkers into ACLF risk models improves survival predictions after liver transplant and emphasizes the importance of addressing cardiac impairments before liver transplant for better outcomes.