Cardiac biomarkers for risk stratification of arrhythmic death in patients with heart failure and reduced ejection fraction.

Objectives. Patients with heart failure and reduced left ventricular ejection fraction (HFrEF) are prone to ventricular tachyarrhythmias. We tested whether biomarkers C-terminal Endothelin 1 (CT-ET1), midregional pro atrial natriuretic peptide (MR-proANP) and midregional pro adrenomedullin (MR-proADM) might improve risk stratification for arrhythmic death.Methods: This prospective observational study included 160 heart failure patients with ischaemic cardiomyopathy (ICM) or non-ischaemic, dilated cardiomyopathy (DCM) and 30 control patients without heart disease. Primary endpoint was arrhythmic death (ArD) or resuscitated cardiac arrest (resCA).Results: A total of 61 patients died during the median follow-up of 7.0 [5.2-8.4] years. An ArD or resCA was observed in 48 patients. Plasma levels of CT-ET1 (p = 0.002), MR-proANP (p < 0.001) and MR-proADM (p = 0.013) were significantly higher in ICM or DCM patients compared to controls. MR-proANP levels in ICM patients were associated with a significantly increased risk for ArD or resCA (hazard ratio (HR) = 1.42, [95%CI: 1.08-1.85], p = 0.011) in a multivariable Cox regression model. Plasma levels of CT-ET1 (HR = 1.07 [0.98-1.17], p = 0.113) and MR-proADM (HR = 1.80 [0.92-3.55], p = 0.087) were not associated with ArD or resCA in ICM patients. No significant association with ArD or resCA was found in DCM patients. Multivariable Cox regression showed that CT-ET1 (HR = 1.14 [1.07-1.22], p < 0.001), MR-proANP (HR = 1.64 [1.29-2.08], p < 0.001) and MR-pro ADM (HR = 2.06 [1.12-3.77], p = 0.020) were associated with a higher risk for overall mortality.Conclusion: Patients with HFrEF had elevated levels of CT-ET1, MR-proANP and MR-proADM. Plasma levels of MR-proANP are useful as predictor for arrhythmic death in patients with ICM.