Objectives: To assess the prognostic value of the estimation of plasma volume, or of their variation beyond clinical examination in a post-hoc analysis of the Eplerenone Post-Acute Myocardial Infarction (AMI) Heart Failure (HF) Efficacy and Survival Study (EPHESUS).Background: Assessing congestion post-discharge is challenging but of paramount importance to optimize patient management and to prevent hospital readmissions.Methods: The present analysis was performed in a subset of 4957 patients with available data (within a full dataset of 6632 patients). Study endpoint was cardiovascular death and/or hospitalization for HF between month 1 and month 3 after post-AMI HF. Estimated plasma volume variation (ΔePVS) between baseline and month 1 was estimated by the Strauss formula, which includes hemoglobin and hematocrit ratios. Other potential predictors including congestion surrogates, hemodynamic and renal variables, and medical history variables were tested. An instantaneous estimation of plasma volume at month 1, ePVS M1, was defined and also tested.Results: Multivariate analysis was performed using stepwise logistic regression. ΔePVS was selected in the model (OR=1.01, p=0.004). The corresponding prognostic gain measured by integrated discrimination improvement (IDI) was significant (7.57 %, p=0.01). Nevertheless, ePVS M1 was found to be a better predictor than ΔePVS.Conclusion: In HF complicating MI, congestion as assessed by the Strauss formula and an instantaneous derived measurement of plasma volume provided a predictive value of early cardiovascular events, beyond routine clinical assessment. Prospective trials assessing congestion management guided by this simple tool to monitor plasma volume are warranted.