Background: NTproBNP is a proven marker for heart failure and congestive heart failure. Secretoneurin is a novel cardiac marker, associated with worsening heart failure and adverse arrhythmic events. A benefit from combing both markers has not been shown yet, especially in patients with ICD.
Aim: The current study aims to evaluate a potential additional diagnostic benefit form combing NTproBNP and Secretoneurin in regard of mortality and course of EF in patients with ICD, compared to each biomarker separately.
Methods: 406 patients who received regular follow-ups in our out-patient clinic for ICDs were recruited into this prospective study. Each patient received echocardiographic examination upon study recruitment and at least once per year during follow up (median 8 follow up echocardiographies). Blood samples were gathered upon study inclusion. According to initial EF and changes in EF, patients were either classified as preserved (pEF; EF>40% in every echocardiography; n=132), reduced (HFrEF; each EF≤40%; n=74), recovered (HFrecEF; EF initially ≤40%, but improved over time and stayed >40% thereafter; n=22), undulating (EF repeatedly changing between > and ≤40%; n=56) or worsened (initial EF>40% but worsened and stayed ≤40%; n=13). Patients who died during follow-up were analysed separately (n=109).
Results: Patients were mostly male (84%) and median age was 68 years (IQR 58-77 years). Median EF was 40% upon study inclusion (IQR 31%-53%) and 207 patients received their ICD due to secondary prevention (51%). 109 Patients died during follow up (median 2 years, IQR 1-4 years).
To evaluate a potential additional diagnostic benefit form combing NTproBNP and Secretoneurin both biomarkers were multiplied. Patients with preserved EF showed significantly lower levels of the combined biomarker than patients with reduced, recovered or undulating EF (each p <0.05), mirroring the results of Secretoneurin and NTproBNP separately. Patients who died during follow-up showed significantly higher levels of this combined biomarker upon study inclusion compared to surviving patients, as well as to each EF group separately (each p<0.05). In ROC-analyses, combined Biomarker showed good AUC to predict mortality (AUC 0.79). In patients with an initial EF>40%, it showed a satisfying AUC to predict future temporary or permanent deterioration of EF below 40% (AUC 0.75). In Kaplan-Mayer analysis, patients with both Secretoneurin and NTproBNP above median showed a significantly higher mortality than patients with none or only one biomarker above median (p < 0.001). In COX regression analyses, Secretoneurin*NTproBNP was significantly associated with mortality, independent from NTproBNP and Secretoneurin, as well as from age, sex, ICD indication, EF and Serum creatinine. In binary logistic regression analysis, patients with initial EF>40%, Secretoneurin and NTproBNP above median proved itself a significant and independent predictor for a future temporary or permanent worsening of EF>40% (p < 0.05), independent form age, sex, serum creatinine, Diabetes and hypertension, as well as independent from NTproBNP or Secretoneurin (p < 0.05, both biomarkers also dichotomised).
Conclusion: In the current study, combining NTproBNP and Secretoneurin showed additional benefit in predicting mortality, as well as a future worsening of EF.
