Impact of Using Cardiac Biomarkers for Defining Pre-Heart Failure

Quick Takes

  • The addition of elevated cardiac biomarkers to the definition of Stage B (“pre-HF”) leads to more individuals being reclassified from Stage A (“at-risk for HF”) to Stage B.
  • The presence of elevated cardiac biomarkers, especially in the presence of structural heart disease, in Stage B HF is associated with an increased risk of incident HF and all-cause death.
  • This may help alert clinicians to increase their focus on HF prevention strategies for these patients.

Study Questions:

What is the impact and prognostic implication of including cardiac biomarkers as a part of the definition for Stage B heart failure (HF) in the new multisociety HF guideline?


Previous HF guidelines defined Stage A HF as high risk for HF without structural heart disease or prior/current symptoms and Stage B HF (“pre-HF”) as existing structural heart disease without prior/current symptoms. The new 2022 American Heart Association/American College of Cardiology/Heart Failure Society of America (AHA/ACC/HFSA) HF guideline modified the definition of Stage B HF to include an option for elevated cardiac biomarkers without prior/current symptoms. The authors sought to assess the prognostic impact of reclassifying patients to Stage B HF based on this new definition.

Participants from the prospective, population-based ARIC (Atherosclerosis Risk in Communities) study examining cardiovascular disease incidence were used for this analysis. Participants at a predetermined follow-up visit (2011-2013) without prevalent HF and with cardiac biomarker/echocardiography data were included. Biomarkers measured included N-terminal pro–B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hs-TnT). Participants were then classified based on the 2022 HF guidelines as having Stage A or Stage B HF. Stage B participants were subcategorized as Stage B (biomarker only), Stage B (echo only), or Stage B (echo + biomarker) based on what criteria were used to meet the definition. Incident HF and all-cause death were assessed for each group.


A total of 5,324 participants were included in this study (mean age 75.8 ± 5.2 years, 58.6% women, median follow-up 7.2 years). Of these participants, there were 998 (18.7%) in the Stage A, 4,326 (81.3%) in the Stage B, 1,123 (21.1%) in the Stage B (biomarker only), 852 (16.0%) in the Stage B (echo only), and 2,351 (44.2%) in the Stage B (echo + biomarker) groups. When compared with the Stage A HF group, participants with a Stage B classification had an associated increased risk for incident HF (hazard ratio [HR], 3.70; 95% confidence interval [CI], 2.58-5.30) and all-cause death (HR, 1.94; 95% CI, 1.53-2.46). When looking at the Stage B subgroups, Stage B (biomarker only) and Stage B (echo only) were both associated with an increased risk of incident HF, though only Stage B (biomarker only) was associated with increased risk of all-cause death. The Stage B (echo + biomarker) group had the highest risk for incident HF (HR, 6.34; 95% CI, 4.37-9.19) and all-cause death (HR, 2.53; 95% CI, 1.98-3.23).


Use of the new biomarker-based definition for Stage B HF accounted for 21.1% of older adults without prevalent HF in the study being reclassified from Stage A to Stage B HF. Use of biomarkers helped in determining risk for incident HF and all-cause death.


The new definition of Stage B HF now includes the use of elevated cardiac biomarkers or structural heart disease as criteria for the definition. Additionally, there is a criterion for presence of elevated intracardiac filling pressures as well (not studied in this publication). This new definition will significantly increase the number of patients we recognize as having Stage B HF (21.2% of all Stage A and B patients based on this study). Results of this study also are reassuring that this reclassification helps to better prognostic and risk stratify patients at higher risk of developing HF or dying. This may lead to an increased focus on HF prevention strategies in this population, and possibly better clinical outcomes.

Clinical Topics: Geriatric Cardiology, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Prevention, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Echocardiography/Ultrasound

Keywords: Biomarkers, Diagnostic Imaging, Echocardiography, Geriatrics, Heart Failure, Natriuretic Peptide, Brain, Prognosis, Risk, Secondary Prevention, Troponin T

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