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AIMS Obese patients have lower natriuretic peptide concentrations. We hypothesized that adjusting the concentration of N-terminal pro-B-type natriuretic peptide (NT-proBNP) for obesity could further increase its clinical utility in the early diagnosis of acute heart failure (AHF). METHODS AND RESULTS This hypothesis was tested in a prospective diagnostic study enrolling unselected patients presenting to the emergency department with acute dyspnoea. Two independent cardiologists/internists centrally adjudicated the final diagnosis using all individual patient information including cardiac imaging. NT-proBNP plasma concentrations were applied: first, using currently recommended cut-offs; second, using cut-offs lowered by 33% with body mass index (BMI) of 30-34.9 kg/m 2 and by 50% with BMI 35 kg/m 2 . Among 2038 patients, 509 (25%) were obese, of which 271 (53%) had AHF. The diagnostic accuracy of NT-proBNP as quantified by the area under the receiver-operating characteristic curve was lower in obese versus non-obese patients (0.890 vs. 0.938). For rapid AHF rule-out in obese patients, the currently recommended cut-off of 300 pg/ml achieved a sensitivity of 96.7% (95% confidence interval [CI] 93.8-98.2%), ruling out 29% of patients and missing 9 AHF patients. For rapid AHF rule-in, the age-dependent cut-off concentrations (age <50 years: 450 pg/ml; age 50-75 years: 900 pg/ml; age >75 years: 1800 pg/ml) achieved a specificity of 84.9% (95% CI 79.8-88.9%). Proportionally lowering the currently recommended cut-offs by BMI increased sensitivity to 98.2% (95% CI 95.8-99.2%), missing 5 AHF patients; reduced the proportion of AHF patients remaining in the 'gray zone' (48% vs. 26%; p = 0.002), achieving a specificity of 76.5% (95% CI 70.7-81.4%). CONCLUSIONS Adjusting NT-proBNP concentrations for obesity seems to further increase its clinical utility in the early diagnosis of AHF.

Background Quantifying the activity of the adrenomedullin system might help to monitor and guide treatment in acute heart failure (AHF) patients. The aims were to (1) identify AHF patients with marked benefit or harm from specific treatments at hospital discharge and (2) predict mortality by quantifying the adrenomedullin system activity. Methods This was a prospective multicentre study. AHF diagnosis and phenotype were centrally adjudicated by two independent cardiologists among patients presenting to the emergency department with acute dyspnoea. Adrenomedullin system activity was quantified using the biologically active component, bioactive adrenomedullin (bio-ADM), and a prohormone fragment, midregional proadrenomedullin (MR-proADM). Bio-ADM and MR-proADM concentrations were measured in a blinded fashion at presentation and at discharge. Interaction with specific treatments at discharge and the utility of these biomarkers on predicting outcomes during 365-day follow-up were assessed. Results Among 1886 patients with adjudicated AHF, 514 patients (27.3%) died during 365-day follow-up. After adjusting for age, creatinine, and treatment at discharge, patients with bio-ADM plasma concentrations above the median (> 44.6 pg/mL) derived disproportional benefit if treated with diuretics (interaction p values < 0.001). These findings were confirmed when quantifying adrenomedullin system activity using MR-proADM (n = 764) (interaction p values < 0.001). Patients with bio-ADM plasma concentrations above the median were at increased risk of death (hazard ratio 1.87, 95% CI 1.57–2.24; p < 0.001). For predicting 365-day all-cause mortality, both biomarkers performed well, with MR-proADM presenting an even higher predictive accuracy compared to bio-ADM (p < 0.001). Conclusions Quantifying the adrenomedullin’s system activity may help to personalise post-discharge diuretic treatment and enable accurate risk-prediction in AHF.