Decreased cholinesterase level combined with renal dysfunction and sympathetic denervation associated with increased cardiac mortality in systolic heart failure

Aims: Cardiac mortality in patients with heart failure (HF) is likely to be aggravated by malnutrition, assessed by serum cholinesterase (ChE) level, as well as by kidney dysfunction or impairment of cardiac sympathetic denervation. Their prognostic interactions, however, have not been determined.Methods: A total of 991 systolic HF patients were enrolled in our HF database following clinical evaluation including evaluation of the nutrition state and assessment of standardized heart-to-mediastinum ratio (sHMR) of iodine-123-labeled meta-iodobenzylguanidine activity. Patients were followed up for an average of 43 months with the primary endpoint of fatal cardiac events (CEs).Results: The CE patient group had a lower level of ChE, lower estimated glomerular filtration rate (eGFR) and lower late sHMR than those in the non-CE patient group. A five-parameter model with the addition of serum ChE selected in the multivariate logistic analysis (model 2) significantly increased the AUC predicting risk of cardiac events compared with a four-parameter model without serum ChE (model 1), and net reclassification analysis also suggested that the model with the addition of serum cholinesterase significantly improved cardiac event prediction. Moreover, in overall multivariate Cox hazard analysis, serum ChE, eGFR and late sHMR were identified to be significant prognostic determinants. HF patients with two or all of the prognostic variables of serum ChE < 230 U/L, eGFR < 48.8 ml/min/1.73 m(2) and late sHMR < 1.90 had significantly and incrementally increased CE rates compared to those in HF patients with none or only one of the prognostic variables.Conclusion: Decreases in cholinesterase level and kidney function further increase cardiac mortality risk in HF patients with impairment of cardiac sympathetic innervation.