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n e w e ng l a n d j o u r na l
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original article
A bs t r ac t
Background
We analyzed hospitalizations for acute decompensated heart failure between October 2001 and January 2004 that were recorded in the Acute Decompensated Heart
Failure National Registry (ADHERE). Entry criteria included a troponin level that
was obtained at the time of hospitalization in patients with a serum creatinine
level of less than 2.0 mg per deciliter (177 mol per liter). A positive troponin test was
defined as a cardiac troponin I level of 1.0 g per liter or higher or a cardiac troponin T level of 0.1 g per liter or higher.
Results
From the Department of Emergency Medicine, Cleveland Clinic Foundation, Cleveland (W.F.P.); the Division of Cardiology
(T.D.M.) and the Department of Laboratory Medicine (A.H.B.W.), University of
California at San Francisco, San Francisco;
AhmansonUCLA Cardiomyopathy Center, UCLA, Los Angeles (G.C.F.); the Department of Emergency Medicine, University of California, Davis, Sacramento
(D.D.); the Department of Statistics, Scios,
Mountain View, CA (J.W.); and the Department of Laboratory Medicine and Pathology, Hennepin County Medical Center and University of Minnesota School
of Medicine, Minneapolis (F.S.A.). Address reprint requests to Dr. Peacock at
the Department of Emergency Medicine
E19, Cleveland Clinic Foundation, 9500
Euclid Ave., Cleveland OH 44195, or at
peacocw@ccf.org.
N Engl J Med 2008;358:2117-26.
Copyright 2008 Massachusetts Medical Society.
Conclusions
In patients with acute decompensated heart failure, a positive cardiac troponin test is
associated with higher in-hospital mortality, independently of other predictive variables. (ClinicalTrials.gov number, NCT00366639.)
Downloaded from www.nejm.org on May 5, 2010 . Copyright 2008 Massachusetts Medical Society. All rights reserved.
2117
The
n e w e ng l a n d j o u r na l
Me thods
Registry Data
With the use of data from the Acute Decompensated Heart Failure National Registry (ADHERE),
we analyzed outcomes associated with elevated
troponin levels in patients with acute decompen2118
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Statistical Analysis
R e sult s
Troponin Levels and Characteristics
of the Patients
Troponin levels were measured at the time of admission in 84,872 of 105,388 hospitalized patients
(80.5%), with 67,924 patients meeting all inclusion
and exclusion criteria. Overall, 4240 patients (6.2%)
were positive for troponin on admission. Characteristics of the patients according to whether
they were positive or negative for troponin are
summarized in Table 1. There were small but significant differences between the two troponin
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2119
The
n e w e ng l a n d j o u r na l
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Characteristic
Age (yr)
P Value
73.314.0
72.914.0
0.05
48
45
<0.001
73
70
0.27
Black
19
20
Other
53
52
<0.001
31
36
<0.001
<0.001
23
31
58
56
0.002
37
30
<0.001
61
58
<0.001
29
32
<0.001
0.03
Diabetes
42
41
0.19
Hypertension
72
73
0.54
Hyperlipidemia
36
34
0.02
Current smoker
16
14
0.001
18
16
<0.001
12
16
<0.001
14132
14732
<0.001
3516
3917
<0.001
61
51
<0.001
111.437.4
113.841.0
<0.001
29
33
<0.001
2120
Dyspnea
87
91
<0.001
Edema
60
66
<0.001
Fatigue
30
30
0.76
Pulmonary edema
88
88
0.30
Rales
72
70
0.03
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Table 1. (Continued.)
Positive for Troponin Negative for Troponin
(N=4240)
(N=63,684)
Characteristic
P Value
In-hospital treatment
Interval to first diuretic (hr)
Median
2.4
2.2
1.06.8
1.05.1
91
93
<0.001
Furosemide
88
89
<0.001
Bumetanide
0.004
Other
0.12
0.746
Interquartile range
<0.001
Diuretics (% of patients)
Any
4.1
4.3
1.121.3
1.019.8
Any
18
<0.001
Dobutamine
<0.001
Interquartile range
Inotropes (% of patients)
Dopamine
11
<0.001
Milrinone
<0.001
Vasodilators (% of patients)
Any
28
18
<0.001
Nesiritide
11
<0.001
Nitroglycerin
20
10
<0.001
Nitroprusside
<0.001
agents, and vasodilators than were troponin-negative patients. There were also differences in resource
utilization and mortality according to treatment
(Tables 2 and 3 and Fig. 3). However, among troponin-positive patients, mortality, as indicated by
the adjusted odds ratio, was independent of treatment. The adjusted odds ratio for the troponinpositive group as compared with the troponin-negative group was 1.84 (95% CI, 1.43 to 2.36) in the
subgroup of patients who were treated with inotropic agents and 1.96 (95% CI, 1.37 to 2.81) in the
subgroup treated with vasodilators (P<0.001 for
both comparisons by the Wald test). Finally, there
was no interaction between treatment and troponin status with respect to mortality. The adjusted
odds ratio for death among patients receiving inotropic agents as compared with those receiving
vasodilators was 4.44 (95% CI, 2.90 to 6.81) for
the troponin-positive group and 4.54 (95% CI, 3.75
to 5.49) for the troponin-negative group (P<0.001
for both comparisons by the Wald test).
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2121
The
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25
20
Troponin-positive
15
10
5
Troponin-negative
10
11
12
13
14
15
Days in Hospital
Revised
4-C
H/T
SIZE
22p3
ARTIST: ts
Line
H/T
Combo
JOB: 35815
ISSUE: 04-10-08
5.3
6
4
2
0
2.0
0.04
3.4
2.7
>0.040.10
>0.100.20
>0.20
Troponin I Quartile
No. of Patients
11,090
10,367
9323
9534
B
8
6.3
6
4
2
0
3.3
2.8
1.7
0.01
>0.010.02
>0.020.06
>0.06
Troponin T Quartile
No. of Patients
1773
502
1138
1119
2nd
3rd
FIGURE: 2 of 3
CASE
EMail
Enon
2122
ARTIST: ts
Line
H/T
Combo
4-C
H/T
of
m e dic i n e
Revised
SIZE
16p6
P Value
1565 (37)
10,493 (16)
<0.001
2.9 (1.65.0)
2.3 (1.24.1)
<0.001
4.1
3.7
0.007
5.1 (3.28.3)
4.1 (2.86.7)
<0.001
6.6
5.5
<0.001
164 (4)
478 (1)
<0.001
5.46 (4.546.57)
Hospital days
113 (3)
192 (<1)
<0.001
8.03 (6.3010.2)
Cardiac catheterization
1002 (24)
6383 (10)
<0.001
3.04 (2.813.28)
Mechanical ventilation
479 (11)
641 (1)
<0.001
2.68 (2.412.99)
* Means were adjusted for age, blood urea nitrogen level, systolic and diastolic blood pressure, creatinine level, sodium
level, heart rate, and presence or absence of dyspnea at rest. Odds ratios are for the troponin-positive group as compared with the troponin-negative group and were adjusted for age, blood urea nitrogen level, systolic and diastolic
blood pressure, creatinine level, sodium level, heart rate, and presence or absence of dyspnea at rest. CABG denotes
coronary-artery bypass graft, IABP intraaortic balloon pump, and IQR interquartile range.
P Value
460/3676 (13)
<0.001
1.84 (1.432.36)
104/461 (23)
Dobutamine
39/209 (19)
180/1847 (10)
<0.001
1.96 (1.322.91)
Dopamine
85/293 (29)
366/1797 (20)
<0.001
1.49 (1.121.99)
Milrinone
24/85 (28)
58/738 (8)
<0.001
4.65 (2.588.38)
Vasodilators only
Any
42/882 (5)
203/9308 (2)
<0.001
1.96 (1.372.81)
Nesiritide
14/324 (4)
125/4335 (3)
0.14
1.44 (0.802.59)
Nitroglycerin
32/630 (5)
93/5397 (2)
<0.001
2.55 (1.653.95)
Nitroprusside
0/28
0.35
NA
7/227 (3)
* Odds ratios are for the troponin-positive group as compared with the troponin-negative group and were adjusted for
age, blood urea nitrogen level, systolic and diastolic blood pressure, creatinine level, sodium level, heart rate, and presence or absence of dyspnea at rest. NA denotes not applicable.
Downloaded from www.nejm.org on May 5, 2010 . Copyright 2008 Massachusetts Medical Society. All rights reserved.
2123
The
24
n e w e ng l a n d j o u r na l
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23
20
16
13
12
8
No. of Patients
Troponin-Positive,
Inotrope
Troponin-Negative,
Inotrope
Troponin-Positive,
Vasodilator
Troponin-Negative,
Vasodilator
461
3676
882
9308
tion and length of stay in an intensive care unit ted for worsening heart failure, in-hospital death
are important determinants of cost, early identi- from cardiac causes occurred in 10 of 45 patients
fication of patients who will require greater (22%) who had cardiac troponin T levels higher
1st as compared with 4 of 53
AUTHOR: Peacock
resources could allow early implementation
of than 0.033 RETAKE
g per liter,
ICM
2nd
FIGURE:
3
of
3
aggressive therapy. The impactREG
of Fearly risk strati- (8%) who had lower
3rd cardiac troponin T levels
3
CASE
Revised
fication has been supported in other studies of (P=0.04). Cardiac
troponin T and brain natriLine
4-C
EMail
SIZE considered together, identiacute decompensated heart failure.
In
the B-Type
uretic
peptide,
when
ARTIST:
ts
H/T
H/T
16p6
Enon
Natriuretic Peptide for Acute Shortness
of Breath Combo
fied patients at low risk (3%), intermediate risk
AUTHOR,
NOTE:
Evaluation (BASEL) trial,13 simply establishing
an PLEASE
(11%),
and high risk (31%) for in-hospital death
Figure has been redrawn and type has been reset.
early, accurate diagnosis of heart failure decreased
(Pcarefully.
=0.006). A study of 159 patients with acute dePlease check
both length of stay and costs. Early risk stratifi- compensated heart failure showed that 24 patients
JOB: 35815
04-10-08
cation may help identify patients
who are likely (15%) hadISSUE:
high
levels of troponin.16 Of these
to receive the greatest benefit from early intensive patients, 20.8% died during hospitalization or had
therapy.
refractory heart failure, as compared with 3.7%
In an analysis of subjects in the Enhanced Feed of those with low troponin levels (odds ratio, 6.8;
back for Effective Cardiac Treatment (EFFECT) 95% CI, 1.5 to 31.2). Finally, in a subgroup analystudy, You et al. evaluated cardiac troponin I and sis of 133 patients in the Randomized Intravemortality in 2025 patients who were hospitalized nous TeZosentan 4 (RITZ-4) study, which involved
with heart failure.14 They reported that levels of patients with acute decompensated heart failure
cardiac troponin I higher than 0.5 g per liter, or an acute coronary syndrome, an elevated carwhich were present in 34.5% of the patients, were diac troponin I level before randomization was
an independent predictor of short-term death, associated with an increased rate of the composwith a doseresponse relationship. However, ap- ite end point of death, worsening heart failure,
plying these findings to those from centers that recurrent ischemia, or new myocardial infarction
used a different assay platform from that used within 72 hours (odds ratio, 1.15; 95% CI, 1.01
by EFFECT may be problematic. Furthermore, the to 1.32).17
rate of elevated troponin levels in the EFFECT
In hospitalized patients with acute decompenstudy is markedly higher than the rate in the cur- sated heart failure, but without classic signs of
rent study and in earlier analyses.15
acute myocardial infarction, troponin is correlat
Smaller studies of patients with heart failure ed with several physiological variables.4,18 In 26
have shown similar implications of elevated tro- hospitalized patients with heart failure, a signifiponin levels with respect to short-term morbidity cant correlation was found between cardiac troand mortality. In 98 consecutive patients admit- ponin T status and the left-ventricular-mass in2124
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2125
Dr. Peacock reports serving as a consultant to Abbott, Beckman Coulter, Biosite, Ortho Clinical Diagnostics, and Response
Biomedical; receiving honoraria from Abbott, Beckman Coulter,
Biosite, Ortho-Biotech, and Scios; and receiving grant support
from Abbott, Biosite, and Scios. Dr. Fonarow reports serving
as a consultant to Scios; receiving honoraria from Scios and
Biosite; and receiving grant support from the National Heart,
Lung, and Blood Institute. Dr. Diercks reports receiving honoraria from Scios and grant support from Dade Behring. Ms.
Wynne reports having been an employee of Johnson & Johnson.
Dr. Apple reports serving as a consultant to Abbott, Ortho
Clinical Diagnostics, and Biosite; receiving honoraria from Abbott and bioMrieux; and receiving grant support from Ortho
Clinical Diagnostics, bioMrieux, Abbott, Dade Behring, DPC,
Bayer, Response Biomedical, Mitsubishi Kagaku, and Roche.
No other potential conflict of interest relevant to this article
was reported.
References
1. Rosamond W, Flegal K, Friday G, et al.
2126
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