The prognostic role of regular NT-proBNP measurement after a rapid-up titration programme of guideline-directed medical therapy in heart failure: essential or superfluous?
B Muk, Z S Forrai, K Czurko, A P Raduly, M B Kovacs, A Borbely, J Papp, O Ratosi, N Nyolczas, O Kiss-Jakab, A Szilagyi, K Hati, P Andreka, Z S Piroth, F Banfi-BacsardiAbstract
Introduction
The assessment of N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels is of importance in identifying a worse prognosis in heart failure (HF). The 2023 ESC HF Guidelines (GLs) recommend the rapid up-titration (RT) of GL-directed medical therapy (GDMT) for all patients (pts) after an index HF hospitalisation (HFH). However, the prognostic effect of changes of NT-proBNP after an RT Programme (RTP) in HF remains unclear.
Aims
To assess the changes of NT-proBNP levels during a 6-month follow-up period (FUP) among pts previously participating in the RTP of GDMT and to evaluate the prognostic effect of >10% increment of NT-proBNP on the composite endpoint of all-cause mortality (ACM) and HFH.
Patients and methods: In accordance with the 2023 ESC HF GLs, a 6-week RTP was developed and launched as part of the daily practice of HF Outpatient Clinics of five national secondary/tertiary cardiology centres. NT-proBNP was measured routinely before-, at the end of the 6-week RTP and at 6 months of FUP. The data of a consecutive group of the first 101 pts (male: 82%, age: 56[49-65] years, de novo HF: 71%, LVEF: 23[19-30]%, NT-proBNP before the RTP: 1698[875-3019] pg/mL, GDMT at discharge: RASi/target doses [TD] of RASi: 99%/15%, βB/TD βB: 96%/7%, MRA/TD MRA: 99%/78%, SGLT2i: 96%, triple therapy [TT: RASi + βB + MRA]/TD TT: 96%/2%, quadruple therapy [QT: TT + SGLT2i]/TD QT: 94%/0%) completing the RTP and having NT-proBNP measured at all 3 time points were assessed. Changes in NT-proBNP values were compared using the Friedman test. ACM, and the composite of ACM/HFH were compared between the subgroups with and without an increase in NT-proBNP by >10% using Kaplan-Meier method and log-rank test. The prognostic effect of an NT-proBNP increment >10% on ACM/HFH was investigated with Cox-regression analysis.
Results
Median NT-proBNP values significantly decreased during the FUP (1698[875-3019] vs 950[539-2449] vs 654[296-2657] pg/mL, p<0.001; before RTP vs after RTP vs 6-month FUP). After completing the RTP, 20% of the cohort had a >10% increment in NT-proBNP during the FUP. In terms of NT-proBNP categories, no differences were observed regarding the proportion of pts on TDs of GDMT (≥50% of TDs of QT: 85% vs 80%, TD QT: 45% vs 51%; pts with vs without a >10% increment of NT-proBNP during FUP).
During a median FUP of 421 [262-551] days, ACM/HFH occurred significantly more often among those with >10% increment of NT-proBNP (25% vs 1%, p<0.001). According to the multivariate Cox regression analysis, >10% increment of NT-proBNP after the RTP proved to be a positive predictor of ACM/HFH (HR: 14.336, 95% CI: 1.624-137.346, p=0.017).
Conclusions
The results of our multicentre analysis underscore the strategic role of the RTP in optimising GDMT in everyday practice. According to our study, routine measurement of NT-proBNP should be part of regular FUP even after RTP, as even its > 10% increment is shown to be a positive predictor of ACM/HFH.