Prognostic performance of serial in‐hospital measurements of copeptin and multiple novel biomarkers among patients with worsening heart failure: results from the MOLITOR study

Abstract

AimsIn heart failure, various biomarkers are established for diagnosis and risk stratification; however, little is known about the relevance of serial measurements during an episode worsening heart failure (WHF). This study sought to investigate the trajectory of natriuretic peptides and multiple novel biomarkers during hospitalization for WHF and to determine the best time point to predict outcome.Methods and resultsMOLITOR (Impact of Therapy Optimisation on the Level of Biomarkers in Patients with Acute and Decompensated Chronic Heart Failure) was an eight‐centre prospective study of 164 patients hospitalized with a primary diagnosis of WHF. C‐terminal fragment of pre‐pro‐vasopressin (copeptin), N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP), mid‐regional pro‐atrial natriuretic peptide (MR‐proANP), mid‐regional pro‐adrenomedullin (MR‐proADM), and C‐terminal pro‐endothelin‐1 (CT‐proET1) were measured on admission, after 24, 48, and 72 h, and every 72 h thereafter, at discharge and follow‐up visits. Their performance to predict all‐cause mortality and rehospitalization at 90 days was compared. All biomarkers decreased during recompensation (P < 0.05) except MR‐proADM. Copeptin at admission was the best predictor of 90 day mortality or rehospitalization (χ 2 = 16.63, C‐index = 0.724, P < 0.001), followed by NT‐proBNP (χ 2 = 10.53, C‐index = 0.646, P = 0.001), MR‐proADM (χ 2 = 9.29, C‐index = 0.686, P = 0.002), MR‐proANP (χ 2 = 8.75, C‐index = 0.631, P = 0.003), and CT‐proET1 (χ 2 = 6.60, C‐index = 0.64, P = 0.010). Re‐measurement of copeptin at 72 h and of NT‐proBNP at 48 h increased prognostic value (χ 2 = 23.48, C‐index = 0.718, P = 0.00001; χ 2 = 14.23, C‐index = 0.650, P = 0.00081, respectively).ConclusionsThis largest sample of serial measurements of multiple biomarkers in WHF found copeptin at admission with re‐measurement at 72 h to be the best predictor of 90 day mortality and rehospitalization.

The clinical application value of the plasma copeptin level in the assessment of heart failure with reduced left ventricular ejection fraction

“…However, no sensitive or specific biochemical factors have been reported. Although copeptin has been proven to be effective for the diagnosis of CHF and acute myocardial infarction in some studies, [ 13 – 15 ] little is known about the effectiveness of copeptin to assess HFrEF. In this study, we aimed to evaluate the effect of copeptin in HFrEF diagnosis.…”

Copeptin reliably reflects longitudinal right ventricular function

“…39 The prognostic value of copeptin was proven by further studies in patients suffering from chronic heart failure. 24,27,[40][41][42] Copeptin already has been analysed in left-sided heart failure or PAH. However, the diagnostic value of copeptin for exclusive RVF has rarely been investigated and therefore was the primary aim of the present study.…”

Lipid Metabolite Biomarkers in Cardiovascular Disease: Discovery and Biomechanism Translation from Human Studies

“…Currently, the clinical standard for diagnosis and prognosis for CVD depend on protein-based biomarkers such as troponins and N-terminal pro-B-type natriuretic peptide (NT-proBNP) for diagnoses, and LDL or HDL for prognosis. Other protein and hormonal biomarkers have been investigated [108][109][110]; however, these biomarkers might not be as specific as metabolomic biomarkers. Unlike these conventional clinical analytes, metabolomic biomarkers are heavily influenced by demographic, nutritional, medication, and environmental factors which may provide a more precise phenotype and add diagnostic and/or prognostic value.…”