Prognostic role of highly sensitive cardiac troponin I in patients with systolic heart failure

doi:10.1016/j.ahj.2009.10.022

American Heart Journal

Volume 159, Issue 1, January 2010, Pages 63-67

https://doi.org/10.1016/j.ahj.2009.10.022 Get rights and content

Background

Cardiac troponin T (cTnT) and cardiac troponin I (cTnI) are useful biomarkers in patients with chronic heart failure (CHF). However, the clinical use has limitations due to the low sensitivity of a conventional commercial assay system. Recently, a high sensitive-cTnI (hs-cTnI) commercial assay has become available.

Methods

To compare the prognostic value of cTnT and hs-cTnI, we measured hemodynamic parameters and serum levels of cTnT, hs-cTnI and N-terminal pro–brain natriuretic peptide (NT-proBNP)in 258 consecutive CHF patients and then followed these patients for a mean period of 2.6 years. In both assays of cTnT and hs-cTnI, the lowest concentration at which the coeffi cient of variation was ≤10% were 0.03 ng/mL, respectively. Therefore, in the present study, an elevated cTnT or cTnI test was defined as a level of ≥0.03 ng/mL.

Results

During long-term follow up, there were 20 cardiac deaths. In 258 CHF patients, serum cTnT were elevated (≥0.03 ng/mL) in 32 patients (12%) and serum hs-cTnI was elevated (≥0.03 ng/mL) in 112 patients (43%). On stepwise multivariate analyses, high plasma NT-proBNP (≥627 pg/mL, P = .0063) and hs-cTnI (≥0.03 ng/mL) (P = .016) were independent significant prognostic predictors but cTnT (≥0.03 ng/mL) was not. The hazard ratio for mortality of patients with high plasma NT-proBNP (≥627 pg/mL) and hs-cTnI (≥0.03 ng/mL) was 5.74 (95% CI, 2.33-14.28, P < .0001) compared to that of those with low NT-proBNP (<627 pg/mL) or hs-cTnI (<0.03 ng/mL).

Conclusions

These findings indicate that a high plasma concentration of hs-cTnI is an independent and useful prognostic predictor in patients with CHF.

Section snippets

Patients

The subjects were 258 consecutive symptomatic CHF patients (left ventricular ejection fraction [LVEF] <45%) as previously reported.13, 14 Patients with recent (within 2 months) ischemic heart disease, those on dialysis therapy, and patients with high creatinine (≥2.5 mg/dL) were excluded. Informed consent was obtained from all patients before participation in the study, and the protocol was approved by the Human Investigations Committee of our institution. New York Heart Association (NYHA)

Patient characteristics

Table I summarizes patient characteristics according to survival. During a median follow-up of 2.6 years, 20 patients died of cardiac-related causes. Of 258 CHF patients, serum cTnT concentrations were elevated (≥0.03 ng/mL) in 32 patients (12%) and serum hs-cTnI concentrations were elevated (≥0.03 ng/mL) in 112 patients (43%). Kaplan-Meier curves for cardiac death by cTnT and hs-cTnI are shown in Figure 1. There was a significant correlation between log cTnT and log hs-cTnI in 32 patients in

Discussion

In this study, we demonstrated for the first time the prognostic value of hs-cTnI in patients with CHF. We measured serum concentrations of cTnT (fourth-generation Elecsys Troponin T immunoassay; Roche Diagnostics) and measured serum hs-cTnI (Siemens Healthcare Diagnostics) in the same 258 CHF patients with a low LVEF (<45%). In these patients, serum cTnT concentrations were elevated (≥0.03 ng/mL) in 32 patients (12%) and serum hs-cTnI concentrations were elevated (≥0.03 ng/mL) in 112 patients

Acknowledgements

We wish to thank Ms. Yohko Watanabe for excellent technical assistance. We also express thanks to Mr. Daniel Mrozek for assistance in preparing the manuscript.

References (24)

MaedaK. et al.
High levels of plasma brain natriuretic peptide and interleukin-6 after optimized treatment for heart failure are independent risk factors for morbidity and mortality in patients with congestive heart failure
J Am Coll Cardiol
(2000)
RichardsA.M. et al.
Plasma N-terminal pro-brain natriuretic peptide and adrenomedullin: prognostic utility and prediction of benefit from carvedilol in chronic ischemic left ventricular dysfunction. Australia-New Zealand Heart Failure Group
J Am Coll Cardiol
(2001)
IshiiJ. et al.
Risk stratification using a combination of cardiac troponin T and brain natriuretic peptide in patients hospitalized for worsening chronic heart failure
Am J Cardiol
(2002)
SetsutaK. et al.
Use of cytosolic and myofibril markers in the detection of ongoing myocardial damage in patients with chronic heart failure
Am J Med
(2002)
TsutamotoT. et al.
Relationship between renal function and plasma brain natriuretic peptide in patients with heart failure
J Am Coll Cardiol
(2006)
RalliS. et al.
Relationship between anemia, cardiac troponin I, and B-type natriuretic peptide levels and mortality in patients with advanced heart failure
Am Heart J
(2005)
FonarowG.C. et al.
Usefulness of B-type natriuretic peptide and cardiac troponin levels to predict in-hospital mortality from ADHERE
Am J Cardiol
(2008)
TsutamotoT. et al.
Attenuation of compensation of endogenous cardiac natriuretic peptide system in chronic heart failure: prognostic role of plasma brain natriuretic peptide concentration in patients with chronic symptomatic left ventricular dysfunction
Circulation
(1997)
AnandI.S. et al.
Changes in brain natriuretic peptide and norepinephrine over time and mortality and morbidity in the Valsartan Heart Failure Trial (Val-HeFT)
Circulation
(2003)
SatoY. et al.
Persistently increased serum concentrations of cardiac troponin t in patients with idiopathic dilated cardiomyopathy are predictive of adverse outcomes
Circulation
(2001)

HorwichT.B. et al.

is associated with impaired hemodynamics, progressive left ventricular dysfunction, and increased mortality rates in advanced heart failure

Circulation

(2003)

IshiiJ. et al.

Prognostic value of combination of cardiac troponin T and B-type natriuretic peptide after initiation of treatment in patients with chronic heart failure

Clin Chem

(2003)

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Clinical InvestigationCongestive Heart FailurePrognostic role of highly sensitive cardiac troponin I in patients with systolic heart failure

Background

Methods

Results

Conclusions

Section snippets

Patients

Patient characteristics

Discussion

Acknowledgements

J Am Coll Cardiol

J Am Coll Cardiol

Am J Cardiol

Am J Med

J Am Coll Cardiol

Am Heart J

Am J Cardiol

Attenuation of compensation of endogenous cardiac natriuretic peptide system in chronic heart failure: prognostic role of plasma brain natriuretic peptide concentration in patients with chronic symptomatic left ventricular dysfunction

Circulation

Changes in brain natriuretic peptide and norepinephrine over time and mortality and morbidity in the Valsartan Heart Failure Trial (Val-HeFT)

Circulation

Persistently increased serum concentrations of cardiac troponin t in patients with idiopathic dilated cardiomyopathy are predictive of adverse outcomes

Circulation

is associated with impaired hemodynamics, progressive left ventricular dysfunction, and increased mortality rates in advanced heart failure

Circulation

Prognostic value of combination of cardiac troponin T and B-type natriuretic peptide after initiation of treatment in patients with chronic heart failure

Clin Chem

Clinical Investigation
Congestive Heart Failure
Prognostic role of highly sensitive cardiac troponin I in patients with systolic heart failure