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Published on: June 10, 2025
Novel biomarker-driven prognostic models to predict morbidity and mortality in chronic heart failure: the
Stuart J Pocock1, João Pedro Ferreira2,3, John Gregson1
1Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK.
Insights
This study developed a prognostic tool for heart failure with reduced ejection fraction (HFrEF) using biomarkers N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT). The tool accurately predicts adverse outcomes and mortality in HFrEF patients.
Area of Science:
- Cardiology
- Biomarkers
- Prognostic Modeling
Background:
- Heart failure with reduced ejection fraction (HFrEF) poses significant prognostic challenges.
- Existing prognostic tools may not fully capture risk in contemporary heart failure populations.
- Biomarkers like NT-proBNP and hs-cTnT show strong associations with adverse outcomes in HFrEF.
Purpose of the Study:
- To develop and validate a biomarker-driven prognostic tool for chronic HFrEF.
- To identify key clinical variables and biomarkers for predicting adverse events in HFrEF.
- To create a risk model applicable for routine clinical use.
Main Methods:
- Utilized data from the EMPEROR-Reduced trial, including 3730 patients.
- Developed multivariable Cox regression models using stepwise selection for composite outcomes and mortality.
- Included candidate variables such as NT-proBNP, hs-cTnT, NYHA class, heart rate, and edema.
Main Results:
- NT-proBNP and hs-cTnT were dominant predictors of HF hospitalization, cardiovascular death, and all-cause mortality.
- A risk score incorporating eight variables demonstrated good discrimination (c-statistic = 0.73) for the primary outcome.
- Mortality risk models also showed good discrimination (c-statistic = 0.69) and were validated externally.
Conclusions:
- A combination of NT-proBNP, hs-cTnT, and select clinical variables provides robust prognostic assessment for HFrEF patients.
- This predictive tool kit is simple and can be readily implemented in clinical practice.
- The findings support enhanced risk stratification for improved HFrEF management.
Aims:
The aim of this study was to generate a biomarker-driven prognostic tool for patients with chronic HFrEF. Circulating levels of N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) each have a marked positive relationship with adverse outcomes in heart failure with reduced ejection fraction (HFrEF). A risk model incorporating biomarkers and clinical variables has not been validated in contemporary heart failure (HF) trials.
Methods And Results:
In EMPEROR-Reduced, 33 candidate variables were pre-selected. Multivariable Cox regression models were developed using stepwise selection for: (i) the primary composite outcome of HF hospitalization or cardiovascular death, (ii) all-cause death, and (iii) cardiovascular mortality. A total of 3730 patients were followed up for a median of 16 months, 823 (22%) patients had a primary outcome and 515 (14%) patients died, of whom 389 (10%) died from a cardiovascular cause. NT-proBNP and hs-cTnT were the dominant predictors of the primary outcome, and in addition, a shorter time since last HF hospitalization, longer time since HF diagnosis, lower systolic blood pressure, New York Heart Association (NYHA) Class III or IV, higher heart rate and peripheral oedema were key predictors (eight variables in total, all P < 0.001). The primary outcome risk score discriminated well (c-statistic = 0.73), with patients in the top 10th of risk having an event rate >9 times higher than those in the bottom 10th. Empagliflozin benefitted patients across risk levels for the primary outcome. NT-proBNP and hs-cTnT were also the dominant predictors of all-cause and cardiovascular mortality, followed by NYHA Class III or IV and ischaemic aetiology (four variables in total, all P < 0.001). The mortality risk model presented good event discrimination for all-cause and cardiovascular mortality (c-statistic = 0.69 for both). These simple models were externally validated in the BIOSTAT-CHF study, achieving similar c-statistics.
Conclusions:
The combination of NT-proBNP and hs-cTnT with a small number of readily available clinical variables provides prognostic assessment for patients with HFrEF. This predictive tool kit can be easily implemented for routine clinical use.
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