Antialdosterone therapy in liver cirrhosis: a role for prevention of cirrhitc cardiomiopathy ?

Background and aims: Cirrhotic cardiomiopathy (CC) comprises a constellation of cardiac abnormalities associated with liver cirrhosis (LC) progression and due to multiple pathogenetic mechanisms; even if not responsible of overt heart failure, CC plays a major role in cardiac dysfunction complicating OLT or TIPPS placement. Our work aims at assessing the prevalence of CC and the different role of possible CC-associated factors. Materials and methods: 50 patients (17 f) affected by LC and 17 (6f) by chronic hepatitis were studied. Hemochromatosis, cardiopulmonary or alcohol-related diseases were excluded. All subjects were assessed for cardiac parameters (EF, Ea, TAPSE, E/A ratio and Deceleration time (DT), QTc interval); Child-Pugh score; ANF ,BNF, Epinephrine (E), Norepinephrine (NE), PRA, Aldosterone (A), nitric oxide (NO), IL-6 and TNF-a, PIIINP plasma levels; APRI, Fibroscore, 4-parameter scores; drugs history (type and exposition time). Results: We observed a significant prevalence of diastolic dysfunction in LC group (50% of patients had abnormal E/A ratio and 62% abnormal DT) with a higher prevalence in advanced disease (100% and 92 % of Child C patients had abnormal E/A ratio and DT, respectively). Prolonged QT (pQT) was present in 19 LC patients (38%) vs. 1 (6.25%) in ECA subjects (p<.001). At univariate analysis, diastolic dysfunction indices (abnormal DT and E/A ratio) resulted significantly related to NO, TNF-alfa, NE, E , A , PRA, ANP and BNP plasma levels; they both were also significantly related to plasma PIIINP levels , Fibroscore and 4-parameters fibrosis scores. A significant correlation between pQT interval and Child score, duration of disease (years), plasma levels of TNF-a, A, ANP, BNP, PIIINP and Fibroscore and 4-parameters scores was also present. E/A ratio, DT and pQT resulted significantly inversely related to antialdosterone therapy exposition (measured as AUC of time x dose). The table resumes the multivariate analysis’ results (stepwise multiple logistic regression) using E/A ratio <1 as dependent variable. Similar result were obtained when using pQT as dependent variable.  SE OR 95% CI p Antialdosterone exposition -.539 .137 0.66 0.43-0.78 .011 Child Score .621 .292 1.35 1.26-2.13 .019 Aldosterone .728 .325 1.26 1.15-3.58 .026 PIIINP .345 .121 1.06 1.02-1.18 .042 Conclusions: Antialdosterone exposition results inversely and independentely related to CC abnormalities, this suggesting a role for optimized (in terms of dose and timing) antialdosterone therapy in prevention of CC development.