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Circulation. 2022;145:e895–e1032. DOI: 10.1161/CIR.0000000000001063 May 3, 2022 e911 CLINICAL STATEMENTS AND GUIDELINES 4.2 Use of Biomarkers for Prevention, Initial Diagnosis, and Risk Stratification Recommendations for Use of Biomarkers for Prevention, Initial Diagnosis, and Risk Stratification Referenced studies that support the recommendations are summarized in the Online Data Supplements. COR LOE Recommendations 1 A 1. In patients presenting with dyspnea, measurement of B-type natriuretic peptide (BNP) or N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) is useful to support a diagnosis or exclusion of HF.1–12 1 A 2. In patients with chronic HF, measurements of BNP or NT-proBNP levels are recommended for risk stratification.11,13–29 1 A 3. In patients hospitalized for HF, measurement of BNP or NT-proBNP levels at admission is recommended to establish prognosis.11,13–19 2a B-R 4. In patients at risk of developing HF, BNP or NT-proBNP–based screening followed by team-based care, including a cardiovascular specialist, can be useful to prevent the development of LV dysfunction or new-onset HF.30,31 2a B-NR 5. In patients hospitalized for HF, a predischarge BNP or NT-proBNP level can be useful to inform the trajectory of the patient and establish a postdischarge prognosis.14,17,20–29 Synopsis Assays for BNP and NT-proBNP are frequently used to establish the presence and severity of HF. In general, BNP and NT-proBNP levels are similar, and either can be used in patient care settings as long as their respective absolute values and cut-points are not used interchangeably.32–34 Obesity is associated with lower levels of BNP and NT-proBNP thereby reducing their diagnostic sensitivity.35,36 A substantial evidence base supports the use of natriuretic peptide biomarkers for excluding HF as a cause of symptoms in ambulatory and emergency department settings. Although a reduction in BNP and NT-proBNP has been associated with better outcomes, the evidence for treatment guidance using serial BNP or NT-proBNP measurements remains insufficient.37–39 Lastly, a widening array of biomarkers including markers of myocardial injury, inflammation, oxidative stress, vascular dysfunction, and matrix remodeling have been shown to provide incremental prognostic information over natriuretic peptides but remain without evidence of an incremental management benefit.13,40–49 Recommendation-Specific Supportive Text 1. Measurement of BNP and NT-proBNP levels in the ambulatory setting for a suspected cardiac cause of dyspnea provides incremental diagnostic value to clinical judgment when the cause of dyspnea is unclear and the physical examination equivocal.1–9 In the emergency setting, BNP and NT-proBNP levels have higher sensitivity than specificity and may be more useful for ruling out HF than ruling in HF. Although lower levels of BNP and NT-proBNP may help exclude the presence of HF, and higher levels have high positive predictive value to diagnose HF, increases in both BNP and NT-proBNP levels have been reported in patients with various cardiac and noncardiac causes (Table 6).50–53 2. and 3. Higher levels of BNP and NT-proBNP are associated with a greater risk for adverse shortand long-term outcomes in patients with HF, including all-cause and cardiovascular death and major cardiovascular events.11,13–19 Studies have shown incremental prognostic value of these biomarkers to standard approaches of CVD risk assessment.11,16 Not all patients may need biomarker measurement for prognostication, especially if they already have advanced HF with established poor prognosis or persistently elevated levels of biomarkers in former settings. 4. The STOP-HF (St Vincent’s Screening to Prevent Heart Failure) study is a large single-center trial of patients at risk of HF, defined by the presence of hypertension, diabetes, or known vascular disease but without established LV systolic dysfunction or symptomatic HF, who were randomly assigned to screening with BNP testing or usual care.31 Participants in the intervention group with BNP levels ≥50 pg/mL underwent echocardiography and referral to a cardiovascular specialist.31 All patients received coaching by a specialist nurse who provided education on the importance of adherence to medication and healthy lifestyle behaviors.31 BNP-based screening reduced the composite endpoint of incident asymptomatic LV dysfunction with or without newly diagnosed HF. Similarly, accelerated uptitration of renin-angiotensin-aldosterone system (RAAS) antagonists and beta blockers reduced cardiac events in patients with diabetes and elevated NT-proBNP levels but without cardiac disease at baseline.30 Standardized screening for HF remains challenging as a result of the heterogeneity of risk factors across different patient populations. Studies are needed to assess the cost-effectiveness and risks of such screening, as well as its impact on QOL and mortality. 5. Predischarge BNP and NT-proBNP levels are strong predictors of the risk of death or hospital readmission for HF.14,17,20–29 Although patients in whom levels of BNP or NT-proBNP decreased with treatment had better outcomes than those without any changes or with a biomarker rise,14,23,28,29 targeting a certain threshold, value, or relative change in these biomarker levels during hospitalization has not been shown to be consistently effective in improving outcomes.37–39 Patients in which GDMT Downloaded from http://ahajournals.org by on October 7, 2026