Table 2.

Clinical trials regarding NPs measurement for diagnosis, cardiac dysfunction, and therapy monitoring.

Author	Clinical setting	Patients	Study design	Main findings
Maisel et al. [16]	Patients with acute decompensated heart failure (ADHF).	464	Entrance criteria included a BNP level >100 pg/mL. Admitted patients were divided into two groups based on B-type natriuretic peptide (BNP) levels above and below 200 pg/mL to study differences in outcome rates.	The BNP levels can predict future outcomes and thus may aid physicians in making triage decisions about whether to admit or discharge patients. Emerging clinical data will help further refine biomarker-guided outpatient therapeutic and monitoring strategies involving BNP.
Luchner et al. [17]	Patients with ADHF	1086	Primary endpoint was hospital admission; secondary endpoints were intermediate/intensive care unit (IMC/ICU) admission, length of stay, rehospitalization and death, or rehospitalization.	Knowledge of N-terminal pro-B-type natriuretic peptides (NT-proBNP) had no significant effect on the primary endpoint hospital admission and the secondary endpoints. Patients with high open NT-proBNP (>1800 pg/mL) were more likely to be admitted to the hospital and IMC/ICU, whereas patients with low open NT-proBNP (<150 pg/mL) were less likely to be admitted compared with patients with blinded NT-proBNP.
Bettencourt et al. [18]	Patients with ADHF	182	The goal of the study was to evaluate the value NT-proBNP in predicting death or hospital readmission after discharge of HF patients.	Variations in NT-proBNP levels are related to hospital readmission and death within 6 months. NT-proBNP levels are potentially useful in the evaluation of treatment efficacy and might help clinicians in planning discharge of HF patients.
Masson et al. [19]	Patients with chronic and stable HFs.	3916	This work aimed to provide a direct comparison of the prognostic value of BNP and NT-proBNP in patients with chronic and stable HFs.	BNP and NT-proBNP showed subtle differences in their relation to clinical characteristics and prognostic performance in a large population of patients with chronic and stable HF. They were the most powerful independent markers of outcome in HFs.
Troughton et al. [20, 21]	Patients with systolic heart failure (SHF).	106	This study was designed to characterize the importance of echocardiographic indexes as determinants of BNP levels in patients with SHF.	Plasma BNP levels are significantly related to diastolic indexes measured from tissue Doppler imaging (TDI) and color M-Mode in SHF. BNP levels reflect the severity of diastolic abnormality, right ventricle (RV) dysfunction, and mitral regurgitation. These findings may explain the powerful relationship of BNP to symptoms and prognosis in SHF.
Bistola et al. [22]	Patients with advanced chronic HF (CHF).	102	Patients with CHF were studied by 2-dimensional conventional and TDI echocardiographies of the left and right ventricles. Patients were followed for 6 months for major cardiovascular events.	RV TDI systolic velocity, dilated cardiomyopathy, digoxin treatment, and female gender were associated with increased cardiovascular death. RV TDI indexes combined with increased plasma BNP additively predict adverse cardiac outcomes in advanced CHF.
Jourdain et al. [23]	New York Heart Association functional class II to III patients with CHF	220	Patients with CHF considered optimally treated were randomized to medical treatment according to either current guidelines or a goal of decreasing BNP plasma levels <100 pg/mL. The primary combined endpoint was CHF-related death or hospital stay for CHF.	In optimally treated CHF patients, a BNP-guided strategy reduced the risk of CHF-related death or hospital stay for CHF. The result was mainly obtained through an increase in ACEI and beta-blocker dosages.
Cohen-Solal et al. [24]	Patients with ADHF	1327	The purpose of this analysis was to examine whether decreases in BNP levels during the first few days of hospitalization were associated with greater survival in patients with ADHF.	Patients with lowered BNP on treatment for ADHF had reduced mortality risks (31- and 180-day) compared to those with little or no BNP decrease. These results suggest that early lowering of BNP predicts both short- and long-term mortality risks. BNP reduction may therefore serve as a suitable prognostic marker of all cause mortality.
Richards et al. [25]	Patients with ischemic LV dysfunction	297	They sought to assess plasma concentrations of NT-proBNP and adrenomedullin for the prediction of adverse outcomes and responses to treatment.	In patients with established ischemic LV dysfunction, plasma concentrations of NT-proBNP and adrenomedullin are independent predictors of mortality and HF. Carvedilol reduced mortality and HF in patients with higher pretreatment plasma NT-proBNP and adrenomedullin.