The main finding of the present study is that BNP and NT-proBNP are equally strong and independent predictors of outcome at hospital discharge. Direct comparison of the predictive accuracy of BNP and NT-proBNP did not reveal significant differences.
Rational use of these peptides is currently recommended in patients with HF in several clinical settings: on admission for decompensated heart failure, after a major treatment effect, at hospital discharge when euvolaemia is reached, and during ambulatory follow-up [2
]. A single measurement of a B-type natriuretic peptide provides strong and independent prognostic information in patients with heart failure.
Previously, we observed in the COACH study that BNP levels are lower in patients with HF with preserved ejection fraction (HFpEF) than in patients with HF with reduced ejection fraction (HFrEF), but for a given BNP level, the prognosis in patients with HFpEF is as poor as in those with HFrEF [3
]. Patients with HFpEF were older, more often female, and had a higher systolic blood pressure and body mass index, and haemoglobin levels were lower than in those with HFrEF.
Inclusion of BNP or NT-proBNP concentrations in the diagnostic algorithm of HF is important both in clinical decision making and for proper design of trials. In concordance with proposed pathophysiological concepts, our recent analyses of multiple biomarkers from COACH showed that in HFpEF patients, inflammation and angiogenesis-mediated interactions were predominant, while stretch-mediated interactions were found in HFrEF [2
Interestingly, in HFpEF patients with low BNP (<100 pg/ml) or low NT-proBNP (<300 pg/ml), quality of life, heart failure-related symptoms and clinical outcomes were similar to those with elevated BNP levels [17
Furthermore, we reported on the added value of a diverse group of 29 biomarkers on top of a clinical risk model in COACH with and without NT-proBNP. Low risk was defined as a biomarker cut-off at the 10th percentile associated with high positive predictive value for 30-day and 180-day mortality and HF rehospitalisation [18
HF symptom relief and euvolaemia reached at hospital discharge is an important point of time for measurement of BNP or NT-proBNP. Their concentrations may serve as targets for optimal fluid status or markers of disease evolution during follow-up in addition to clinical parameters, and in biomarker-guided management in HFrEF [19
BNP versus NT-proBNP in heart failure
Plasma levels of the biological active BNP and inactive N‑terminal fragment of BNP are closely correlated with each other in HF patients, as confirmed by the results of our study. The Valsartan Heart Failure Trial (Val-HeFT) study group provided a direct comparison of the prognostic value of BNP and NT-proBNP in 3,916 patients with chronic and stable HF [5
]. They found that both peptides were powerful independent markers of outcome in HF, but NT-proBNP was superior to BNP in predicting mortality and morbidity or hospitalisation for HF. In 164 patients (99% men) hospitalised for decompensated HF, Waldo and coworkers found that admission and discharge NT-proBNP (AUC 0.788 and AUC 0.834) had superior prognostic power for all-cause mortality within 90 days post-discharge, when compared with BNP (AUC 0.644, p
< 0.01 and AUC 0.709, p
< 0.01) [6
]. Also in a small study, 171 patients with acute HF, Noveanu and coworkers reported that predischarge levels of BNP and NT-proBNP reliably predicted one-year mortality (AUC 0.78 and 0.77 respectively); however, prediction of one-year HF readmission was poor for both markers [7
]. In a subgroup analysis of 306 patients with acute HF (FINN-AKVA cohort), both BNP and NT-proBNP failed to improve prediction of 5‑year survival [8
]. In 563 patients, we found that the prognostic performance (all-cause mortality or HF hospitalisation during 18 months) of BNP and NT-proBNP at the time of hospital discharge were comparable.
From other studies, it became apparent that patient- and assay-related factors influence both BNP and NT-proBNP concentrations [2
]. In head-to-head comparisons, distinct discrepancies in individual patients demonstrated that both markers are clinically not completely equivalent [7
]. Furthermore, BNP was found to be more sensitive to rapid haemodynamic changes in acute heart failure than NT-proBNP [8
]. Importantly, monitoring by means of BNP testing of chronic heart failure patients on exogenous administered BNP or guideline-recommended sacubitril-valsartan treatment, may be impaired, in contrast to NT-proBNP, which is not a substrate for neprilysin inhibition [24
]. So, these issues should be taken into account while applying serial testing for risk stratification and (long-term) monitoring of HF patients. Analyses of NT-proBNP and BNP in HFrEF patients who participated in the PARADIGM-HF study revealed that NT-proBNP decreases on treatment with sacubutril-valsartan, reflecting reduced cardiac wall stress, while BNP increases, reflecting drug action [25
]. However, the relative increases in BNP concentrations in that randomised study were small (median baseline BNP value approximately 200 pg/ml to a median of about 225 pg/ml in the sacubitril-valsartan arm at 8‑month follow-up).
Furthermore, it is unlikely that small increments of BNP on that drug will interfere with the diagnostic applications of BNP in patients with acute or decompensated heart failure, usually associated with large increments of BNP.
The present analysis was observational in design and is therefore only hypothesis-generating. In the current retrospective analysis of a randomised controlled trial, we only included medical therapy at hospital discharge. In that way, modifications in the drug treatment and non-pharmacological therapy during follow-up were not accounted for in our analysis. The COACH study was powered for the primary composite endpoint, time to hospitalisation for HF or all-cause mortality, but not for the separate, secondary endpoint all-cause mortality.
Also, the COACH study was conducted at a time when not all currently recommended drugs for chronic HF were used and use of device therapy has also markedly increased since then, which may have affected our findings [12