Combined Use of High-Sensitivity Cardiac Troponin T and N-Terminal Pro-B Type Natriuretic Peptide Improves Measurements of Performance Over Established Mortality Risk Factors in Chronic Heart Failure

Marta de Antonio, MD; Josep Lupon, MD, PhD; Amparo Galan, MD, PhD; Joan Vila, MSc; Agustin Urrutia, MD, PhD; Antoni Bayes-Genis, MD, PhD

Disclosures

Am Heart J. 2012;163(5):821-828. 

In This Article

Abstract and Introduction

Abstract

Background Heart failure still maintains a high mortality. Biomarkers reflecting different pathophysiological pathways are under evaluation to better stratify the mortality risk. The objective was to assess high-sensitivity cardiac troponin T (hs-cTnT) in combination with N-terminal pro-B type natriuretic peptide (NT-proBNP) for risk stratification in a real-life cohort of ambulatory heart failure patients.
Methods We analyzed 876 consecutive patients (median age 70.3 years, median left ventricular ejection fraction 34%) treated at a heart failure unit. A combination of biomarkers reflecting myocyte injury (hs-cTnT) and myocardial stretch (NT-proBNP) was used in addition to an assessment based on established mortality risk factors (age, sex, left ventricular ejection fraction, New York Heart Association functional class, diabetes, estimated glomerular filtration rate, ischemic etiology, sodium, hemoglobin, β-blocker treatment, and angiotensin converting enzyme inhibitor or angiotensin II receptor blocker treatment).
Results During a median follow-up of 41.4 months, 311 patients died. In the multivariable Cox proportional hazards model, hs-cTnT and NT-proBNP were independent prognosticators (P = .003 each). The combined elevation of both biomarkers above cut-off values significantly increased the risk of death (HR 7.42 [95% CI, 5.23–10.54], P < .001). When hs-cTnT and NT-proBNP were individually included in a model with established mortality risk factors, measurements of performance significantly improved. Results obtained for hs-cTnT compared with NT-proBNP were superior according to comprehensive discrimination, calibration, and reclassification analysis (net reclassification indices of 7.7% and 1.5%, respectively).
Conclusions hs-cTnT provides significant prognostic information in a real-life cohort of patients with chronic heart failure. Simultaneous addition of hs-cTnT and NT-proBNP into a model that includes established risk factors improves mortality risk stratification.

Introduction

Chronic heart failure (HF) is a major and growing public health problem, with increasing incidence and prevalence.[1] Although significant advances have been made in the treatment of HF in recent decades, mortality remains high.[2] Outcomes in HF are highly variable and established risk markers such as New York Heart Association (NYHA) functional class, treatment, laboratory variables, and left ventricular ejection fraction (LVEF) do not fully explain the mortality risk of HF patients and fail to estimate an individual's prognosis.[3–5] Biomarkers of different pathophysiological processes of HF, such as myocardial stretch and injury, both associated with worse prognosis,[6–8] may help in mortality prediction. Accurate identification of high-risk patients is a prerequisite to indicate intensive monitoring or aggressive treatment.

Cardiac troponin, a marker of myocyte injury, predicts adverse clinical outcomes in acute[9–11] and chronic HF.[12] A high-sensitivity assay for cardiac troponin T (hs-cTnT) has recently become available; this assay detects low troponin concentrations and improves precision at the lower limit of detection.[13] Some reports suggest that hs-cTnT also provides relevant prognostic information in HF, yet these are small studies with short follow-up[14,15] or derive from randomized clinical trials.[16] N-terminal pro-B type natriuretic peptide (NT-proBNP), which indicates myocardial stretch, is currently recognized as a robust prognostic marker at all stages of HF, and for all related clinical outcomes.[17]

In the present study we evaluated the value of hs-cTnT and NT-proBNP levels in a large real-life cohort of ambulatory patients with HF and whether the incorporation of hs-cTnT on top of established mortality risk factors and NT-proBNP improved long-term mortality prediction.

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