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

Cardiovascular complications are the leading cause of mortality following liver transplantation (LT) 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 CLIF-C-organ failure (CLIF-C-OF), NACSELD-ACLF, and the novel Sundaram ACLF-LT-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, we assessed the severity of cardiac impairments with cardiac biomarkers and modified the SALT-M score, developing the SALT-M_ CARDIAC score to better predict post-LT mortality. In the ASAN-LT 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 (HF) and myocardial injury, using prospective measurements of B-type natriuretic peptide (BNP) and high-sensitivity troponin I (hsTnI), respectively. We assessed model performance using C-statistics, optimism-corrected C-statistics, and calibration metrics. Feature importance was assessed using Shapley additive explanations (SHAP) analysis, and a nomogram was constructed. Among patients with ACLF grade-3 and NACSELD-ACLF-positive, 32. 5% and 34. 8% had BNP >400pg/mL, suggestive of acute HF, while 12. 9% and 12. 3% had hsTnI levels >10-fold the upper limit, respectively. SHAP analysis identified BNP and hsTnI as important predictors of post-LT mortality. Incorporating cardiac biomarkers into NACSELD-ACLF and CLIF-C-OF 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-Mcardiac score improved the optimism-corrected C-index for 30-day mortality from 0. 73 to 0. 76 (P<0. 001). Nomogram using the SALT-M_ CARDIAC score was constructed to predict post-transplant survival. Cardiac impairment is prevalent in patients with ACLF and crucial for risk stratification. Integrating cardiac biomarkers into ACLF risk models improves post-LT survival predictions and emphasizes the importance of addressing cardiac impairments before LT for better outcomes.