Table 8.1. Recommendations for the use of biomarkers in HFrEF patients.

Recommendations	Class	LE	Comment	Table 2018	Ref.
Measurement of BNP or NT-proBNP when HF diagnosis is in question and as a screening test in primary care.	I	A	2018 recommendation remains current.	Item 4.3 (page 451)	See 2018
Measurement of BNP or NT-proBNP for prognostic stratification in patients with HF.	I	A	2018 recommendation remains current.	Item 4.3 (page 451)	See 2018
Measurement of BNP or NT-proBNP as a complement to physical examination to assess response to treatment in HF patients in case of questions about their clinical status.	IIa	B	MODIFIED: Two recent studies, one randomized, the other observational, support that indication.	Item 4.3 (page 451)	84, 110
Serial measurements of BNP or NT-proBNP to guide treatment, with biomarker targets.	IIb	B	MODIFIED: A recent meta-analysis, including data from the Guide-IT trial, support that indication.	Item 4.3 (page 451)	111, 112
Natriuretic peptides may be used to assess patient response to a given treatment. In terms of strategy, the treatment is clinically directed and the biomarker is measured before and after with no specific target. New studies have come up to confirm what had already been shown by a subanalysis of the PARADIGM-HF trial, where patients who had lowered their NT-proBNP to below 1000 pg/mL after the initiation of enalapril or sacubitril-valsartan had lower mortality and fewer hospitalizations for HF.113 In the PIONEER-HF trial following up on patients hospitalized for HF after discharge, sacubitril-valsartan produced a greater decrease in NT-proBNP than enalapril after 4 weeks (46.7 vs 25.3 percent), leading to a smaller number of events from sacubitril-valsartan use.84 In the Prove-HF trial, where chronic HF patients used sacubitril-valsartan, there was a significant decrease in NT-proBNP after the medication had been used for 14 days. The NT-proBNP decrease was associated with reverse remodeling during the 12 months of follow-up and had a smaller event rate.110 Conversely, the use of peptides to guide treatment (with natriuretic peptide targets) is controversial. Though the strategy was not superior to conventional management in the Guide-IT trial, previous surveys have found different results.112 Another trial, Protect,114, NT-proBNP-guided therapy was superior to standard of care, with reduced event rates, improved quality of life, and favorable effects on cardiac remodeling. The Time-CHF115 and Battlescarred116 trials found the strategy led to decreases in mortality in patients under the age of 75. In addition, a recent meta-analysis including 4,554 patients and incorporating patients from the Guide-IT trial found lower hospitalization rates and all-cause mortality from natriuretic peptide-guided treatment.111

HF: heart failure; NT-proBNP: N-terminal portion of B-type natriuretic peptide.