Apaches Cor

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JJCC-870; No. of Pages 9
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Journal of Cardiology xxx (2014) xxxxxx
Contents lists available at ScienceDirect
Journal of Cardiology
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Original article
New scoring system (APACHE-HF) for predicting adverse outcomes in

patients with acute heart failure: Evaluation of the APACHE II and
Modied APACHE II scoring systems
Hirotake Okazaki (MD) a , Akihiro Shirakabe (MD, PhD) a, , Noritake Hata (MD, PhD) a ,
Masanori Yamamoto (MD, PhD) a , Nobuaki Kobayashi (MD, PhD) a ,
Takuro Shinada (MD, PhD) a , Kazunori Tomita (MD) a , Masafumi Tsurumi (MD) a ,
Masato Matsushita (MD) a , Yoshiya Yamamoto (MD) a , Shinya Yokoyama (MD, PhD) a ,
Kuniya Asai (MD, PhD) b , Wataru Shimizu (MD, PhD, FJCC) b
a
b
Division of Intensive Care Unit, Chiba Hokusoh Hospital, Nippon Medical School, Chiba, Japan
Department of Cardiovascular Medicine, Nippon Medical School, Tokyo, Japan
a r t i c l e
i n f o
Article history:
Received 2 December 2013
Received in revised form 4 February 2014
Accepted 19 February 2014
Available online xxx
Keywords:
Acute heart failure syndrome
Mortality
Prognosis
Scoring
a b s t r a c t
Background: No scoring system for assessing acute heart failure (AHF) has been reported.
Methods and results: Data for 824 AHF patients were analyzed. The subjects were divided into an alive
(n = 750) and a dead group (n = 74). We constructed a predictive scoring system based on eight signicant
APACHE II factors in the alive group [mean arterial pressure (MAP), pulse, sodium, potassium, hematocrit,
creatinine, age, and Glasgow Coma Scale (GCS); giving each one point], dened as the APACHE-HF score.
The patients were assigned to ve groups by the APACHE-HF score [Group 1: point 0 (n = 70), Group 2:
points 1 and 2 (n = 343), Group 3: points 3 and 4 (n = 294), Group 4: points 5 and 6 (n = 106), and Group
5: points 7 and 8 (n = 11)]. A higher optimal balance was observed in the APACHE-HF between sensitivity
and specicity [87.8%, 63.9%; area under the curve (AUC) = 0.779] at 2.5 points than in the APACHE II
(47.3%, 67.3%; AUC = 0.558) at 17.5 points. The multivariate Cox regression model identied belonging
to Group 5 [hazard ratio (HR): 7.764, 95% condence interval (CI) 1.58638.009], Group 4 (HR: 6.903,
95%CI 1.94024.568) or Group 3 (HR: 5.335, 95%CI 1.58217.994) to be an independent predictor of
3-year mortality. The KaplanMeier curves revealed a poorer prognosis, including all-cause death and
HF events (death, readmission-HF), in Group 5 and Group 4 than in the other groups, in Group 3 than in
Group 2 or Group 1, and in Group 2 than in Group 1.
Conclusions: The new scoring system including MAP, pulse, sodium, potassium, hematocrit, creatinine,
age, and GCS (APACHE-HF) can be used to predict adverse outcomes of AHF.
2014 Published by Elsevier Ltd on behalf of Japanese College of Cardiology.
Introduction
The Acute Physiology and Chronic Health Evaluation (APACHE)
scoring system was rst established in 1981 to predict the prognosis in patients receiving intensive care (Fig. 1A) [1]. Subsequently,
the APACHE II, III, and IV systems were published over the past
20 years [24].
Corresponding author at: Division of Intensive Care Unit, Chiba Hokusoh Hospital, Nippon Medical School, 1715 Kamagari, Inzai, Chiba 270-1694, Japan.
Tel.: +81 476 99 1111; fax: +81 476 99 1911.
E-mail address: s6042@nms.ac.jp (A. Shirakabe).
The APACHE II system consists of three parts, including the

acute physiology score, chronic health points, and age points.
The total number of points for the three parts is calculated as the
APACHE II score. This score has been reported to be predictive
of adverse outcomes in patients requiring intensive care, such
as those with respiratory disease, severe pancreatitis, or severe
sepsis [59]. However, this scoring system involves many factors,
as described above; therefore, it cannot be applied easily, and
clinicians hesitate to use it in every patient.
In previous observational studies, various predictive factors for
detecting adverse outcomes in acute heart failure (AHF) patients
have been identied, including age [10], anemia [11], renal insufciency [12,13], poor liver function [14], high uric acid [15], high
lactate [16], low cholesterol [12,16], elevated blood glucose [17],
http://dx.doi.org/10.1016/j.jjcc.2014.03.002
0914-5087/ 2014 Published by Elsevier Ltd on behalf of Japanese College of Cardiology.
Please cite this article in press as: Okazaki H, et al. New scoring system (APACHE-HF) for predicting adverse outcomes in
patients with acute heart failure: Evaluation of the APACHE II and Modied APACHE II scoring systems. J Cardiol (2014),
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H. Okazaki et al. / Journal of Cardiology xxx (2014) xxxxxx
Fig. 1. Denition of each scoring system. (A) The APACHE II scoring system was dened in this study. (B) The Modied APACHE II scoring system was constructed based on the
signicant APACHE II factors in the alive group [mean blood pressure (BP), sodium, potassium, creatinine, age, and Glasgow Coma Scale (GCS)] and was given points based on
the APACHE II system. (C) The APACHE-HF scoring system was constructed based on the signicant APACHE II factors in the alive group (mean BP, pulse, sodium, potassium,
creatinine, hematocrit, age, and GCS) and was given one point for each cut-off value. The cut-off value for each factor was dened by the receiver-operating characteristic
(ROC) curve as follows: mean BP [91.5 mmHg, area under the ROC curve (AUC) = 0.678, p < 0.001), pulse (110.5 beats/min, AUC = 0.594, p = 0.008), sodium (137.5 mmol/L,
AUC = 0.613, p = 0.001), potassium (4.85 mmol/L, AUC = 0.601, p = 0.004), hematocrit (36.95 mg/dL, AUC = 0.617, p = 0.001), creatinine (1.475 mg/dL, AUC = 0.676, p < 0.001), age
(71.5 years, AUC = 0.572, p = 0.042) and GCS (13.5, AUC = 0.567, p = 0.058)].
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hyperkalemia [12], hyponatremia [18], brain-type natriuretic peptide (BNP), and left ventricular ejection fraction. With respect to
patients with AHF, no predictive scoring system has been established, and evaluations of the APACHE II system have rarely been
reported. We therefore evaluated the efcacy of the APACHE II and
our newly established scoring system for AHF patients.
Methods
Subjects
Clinical data were collected from 824 patients with AHF who
were admitted to the intensive care unit at Chiba Hokusoh Hospital,
Nippon Medical School between January 2000 and July 2012. AHF
was dened as either new-onset HF or decompensation of chronic
HF with symptoms sufcient to warrant hospitalization [19]. HF
was diagnosed according to the Framingham criteria for a clinical
diagnosis of HF based on the satisfaction of two major criteria or
one major and two minor criteria [20]. All patients had a New York
Heart Association (NYHA) functional class of either Class III or IV.
AHF patients with one of the following criteria were admitted to
the intensive care unit (ICU) by physicians decision in the present
study: (1) patients who need high projectile oxygen inhalation
(including mechanical support) to treat orthopnea, (2) patients who
need intrope or mechanical support with low blood pressure, (3)
patients who need many types of diuretics to improve the general
or lung edema. Patients with HF caused by acute coronary syndrome were excluded from the study. All data were retrospectively
retrieved from hospital medical records.
in the group with lowest point as the referent was assessed using
a Cox regression hazard model.
Statistical analysis
All data were statistically analyzed using the SPSS 20.0J software
program (SPSS Japan Institute, Tokyo, Japan). All numerical data
were expressed as the mean standard deviation or median (range
or 2575% interquartile range) depending on normality. Unpaired
Students t-test or the MannWhitney U-test was used to compare
the two groups. Normality was assessed using the ShapiroWilk Wtest. Comparisons of all proportions were made using a chi-square
analysis. A p-value of less than 0.05 was considered to be statistically signicant. ROC curves were calculated to predict the cut-off
values, and the sensitivity, specicity and area, under the ROC curve
(AUC) were determined. The survival rates were analyzed between
the groups assigned based on the cut-off values of the ROC curves
for each scoring system using KaplanMeier curves, and signicant
differences were calculated using the log-rank test. A Cox regression analysis was performed to obtain the hazard ratios (HRs) for
90-day mortality and 90-day HF events. Subsequently, a multivariate analysis was performed using the variables with a p-value of
<0.05 in the univariate analysis to examine their independent associations with 90-day mortality and 90-day HF events. A p-value of
less than 0.05 was considered to be statistically signicant.
Ethical concerns
The institutional review board at Chiba Hokusoh Hospital, Nippon Medical School approved the study protocol.
Procedure
Results
AHF patients were divided into two groups according to inhospital mortality: the alive group (n = 750) and the dead group
(n = 74).
We established two new scoring systems for AHF comparing
the two groups. First, we compared the APACHE II score between
the two groups using a univariate analysis. Factors associated with
signicantly more points in the alive group were selected to construct the new scoring system. The total score of the signicant
factors in the alive group was dened as the Modied APACHE II
score. Second, we compared the data for APACHE II factors between
the two groups using a univariate analysis. We then scored the
total number of factors specic to survival discharge (giving one
point for each factor), dened as the APACHE-HF score. The cut-off
value for each factor to give one point was dened by the receiveroperating characteristic (ROC) curves for the in-hospital mortality
of each factor.
We determined the scores (APACHE II, Modied APACHE II, and
APACHE-HF) in each patient based on data obtained at admission,
according to a previous report [2], and evaluated the sensitivity,
specicity, and positive and negative predictive value for differentiating the alive and dead groups. ROC curves were calculated to
predict the optimal cut-off values.
Furthermore, the mid-term prognosis was evaluated in terms of
all-cause death and HF events dened as all-cause death or readmission due to HF. The patients were clinically followed up in a
routine outpatient clinic. For the patients followed up at other institutes, the nal prognosis was determined via telephone contact.
The patients were assigned to another two groups according to
the cut-off values of the ROC curves for the APACHE II, Modied
APACHE II, and APACHE-HF scores. The survival rates were then
analyzed using KaplanMeier curves according to the APACHE II,
Modied APACHE II, and APACHE-HF scores. The prognostic value of
the APACHE-HF score in these groups compared with that observed
Patient characteristics
The relationship between the treatment, including respiratory
support and medications prescribed during the rst 5 days, and
in-hospital mortality are shown in Table 1. The patient cohort
included 67.2% male subjects, with a median age of 74 years.
The systolic blood pressure (BP) values were signicantly lower,
the number of NYHA class IV patients was signicantly higher,
the serum hemoglobin levels were signicantly lower, the serum
urinary acid levels were signicantly higher, the serum BUN levels were signicantly higher, the serum C-reactive protein (CRP)
levels were signicantly higher, and the serum BNP levels were
signicantly higher in the dead group than in the alive group.
Denition of the Modied APACHE II and APACHE-HF scoring
systems
Regarding the APACHE II score, the following six factors were
signicantly different between the alive group and the dead group:
mean BP, sodium, potassium, creatinine, age, and Glasgow Coma
Scale (GCS) (Table 2). We constructed a predictive scoring system
based on the signicant APACHE II factors in the alive group (mean
BP, sodium, potassium, creatinine, age, and GCS; giving points
based on the APACHE II system), dened as the Modied APACHE
II score (Fig. 1B).
On the other hand, the following eight factors were signicantly different between the alive group and dead group:
mean BP, pulse, sodium, potassium, hematocrit, creatinine, age,
and GCS (Table 3). We constructed a predictive scoring system based on the signicant APACHE II factors in the alive
group (mean BP, pulse, sodium, potassium, creatinine, hematocrit, age, and GCS; giving one point based on each cut-off value),
dened as the APACHE-HF score (Fig. 1C). The cut-off values for
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Table 1
Relationships between the patient characteristics and in-hospital survival.
Characteristic
Total (n = 824)
Age (years)
Gender (male, %)
Type (new onset, %)
Etiology
Ischemic heart disease (yes, %)
Cardiomyopathy (yes, %)
Hypertensive heart disease (yes, %)
Valvular (yes, %)
Others (yes, %)
Past medical history
Hypertension (yes, %)
Diabetes mellitus (yes, %)
Dyslipidemia (yes, %)
Vital signs and status
SBP (mmHg)
SBP > 140 mmHg (yes, %)
SBP 100140 mmHg (yes, %)
SBP < 100 mmHg (yes, %)
Diastolic blood pressure (mmHg)
LVEF (%)
LVEF > 40% (%)
NYHA (IV, %)
Laboratory data
Total bilirubin (mg/dL)
Urinary acid (mg/dL)
BUN (mg/dL)
Hemoglobin (g/dL)
CRP (mg/dL)
BNP (pg/mL)
Respiratory support
Endotracheal intubation (yes, %)
NPPV (yes, %)
Medication (cases) during the rst 5 days
Furosemide (yes, %)
Nitroglycerin (yes, %)
Nicorandil (yes, %)
Carperitide (yes, %)
Dopamine (yes, %)
Dobutamine (yes, %)
ACE-I/ARB (yes, %)
-Blocker (yes, %)
Spironolactone (yes, %)
Outcome
ICU hospitalization (days)
Total hospitalization (days)
74 (6580)
554 (67.2%)
544 (66.0%)
74 (6480)
44 (59.5%)
43 (58.1%)
76 (7081)
510 (68.0%)
501 (66.8%)
0.041
0.153
0.157
554 (67.2%)
141 (17.1%)
143 (17.4%)
117 (21.5%)
22 (2.7%)
44 (59.5%)
14 (18.9%)
7 (9.5%)
20 (27.0%)
2 (2.7%)
510 (68.0%)
127 (16.9%)
136 (18.1%)
157 (20.9%)
20 (2.7%)
1.000
0.630
0.076
0.236
1.000
612 (74.3%)
341 (41.4%)
374 (45.4%)
47 (63.5%)
32 (43.2%)
25 (33.8%)
565 (75.3%)
309 (41.2%)
349 (46.5%)
0.036
0.805
0.038
160 (132186)
559 (67.8%)
232 (28.2%)
66 (8.0%)
90 (70100)
35.0 (2546)
295 (36.0%)
667 (80.9%)
0.6 (0.40.8)
6.8 (5.58.1)
23.2 (17.933.1)
12.5 (10.714.5)
0.56 (0.191.78)
805 (4151403)
Dead group (n = 74)
131 (107168)
31 (41.9%)
29 (39.2%)
13 (17.6%)
80 (6290)
32 (2245)
23 (31.9%)
66 (89.2%)
0.7 (0.41.0)
7.7 (5.99.6)
36.4 (21.548.7)
11.3 (10.314.2)
1.44 (0.564.58)
1363 (9271787)
Alive group (n = 750)
p-Value
162 (138188)
528 (70.4%)
203 (27.1%)
53 (7.1%)
90 (72100)
35 (2446)
272 (36.4%)
601 (80.1%)
<0.001
<0.001
0.031
0.005
<0.001
0.150
<0.001
0.003
0.6 (0.40.8)
6.7 (5.38.0)
22.7 (17.531.8)
12.5 (10.814.5)
0.52 (0.171.63)
753 (3991312)
0.166
0.001
<0.001
0.001
<0.001
<0.001
209 (25.4%)
310 (37.6%)
36 (48.6%)
24 (32.4%)
173 (23.1%)
286 (38.1%)
<0.001
0.380
781 (94.8%)
594 (69.1%)
95 (11.5%)
449 (54.5%)
238 (28.9.0%)
117 (21.5%)
333 (40.4%)
196 (23.8%)
296 (35.9%)
66 (89.2%)
37 (50.0%)
11 (14.9%)
45 (60.8%)
41 (55.4%)
36 (48.6%)
17 (22.9%)
16 (21.6%)
18 (24.3%)
715 (95.3%)
557 (74.3%)
84 (11.2%)
404 (53.9%)
197 (26.3%)
141 (18.8%)
316 (42.1%)
180 (24.0%)
278 (37.1%)
0.047
<0.001
0.341
0.272
<0.001
<0.001
0.001
0.775
0.031
5 (37)
29 (1849)
7 (417)
30 (1382)
5 (37)
29 (1847)
<0.001
0.489
SBP, systolic blood pressure; LVEF, left ventricular ejection fraction measured on echocardiography; NYHA, New York Heart Association; BUN, blood urea nitrogen; CRP,
C-reactive protein; BNP, brain natriuretic peptide; NPPV, non-invasive positive pressure ventilation; ACE-I, angiotensin-converting enzyme inhibitor ARB, angiotensin II
receptor blocker; ICU, intensive care unit.
p-Value between the alive group and dead group determined according to unpaired Students t-test and MannWhitney U-test.
Table 2
Relationships between the APACHE II score and in-hospital mortality.
All (n = 825)
Total APS
Body temperature ( C)
Mean blood pressure (mmHg)
Pulse (beats/min)
Respiratory rate (per min)
A-aDO2 (FiO2 > 0.5) or PaO2 (FiO2 < 0.5)
pH
Sodium (mmol/L)
Potassium (mmol/L)
Hematocrit (%)
Creatinine (mg/dL)
White blood cell (/m3 )
Age points
Chronic health points
Glasgow Coma Scale
0.39
1.51
1.53
1.36
0.91
1.59
0.05
0.22
0.55
0.96
0.16
5.05
0.53
0.94
0.57
1.36
1.23
1.20
1.46
1.60
0.35
0.66
0.90
1.35
0.44
1.26
1.54
2.49

0.38
1.54
1.54
1.36
0.90
1.59
0.04
0.19
0.54
0.90
0.16
5.01
0.51
0.88
0.55
1.36
1.22
1.19
1.45
1.60
0.31
0.61
0.90
1.32
0.44
1.29
1.52
2.40
Dead group (n = 75)

0.51
1.22
1.39
1.38
1.00
1.58
0.18
0.46
0.61
1.61
0.14
5.39
0.68
1.59
0.67
1.33
1.24
1.27
1.52
1.51
0.60
0.91
0.88
1.51
0.40
0.90
1.63
2.90
p-Value
0.162
0.036
0.227
0.920
0.778
0.985
0.001
0.021
0.511
<0.001
0.873
0.027
0.386
0.006
APS, acute physiology score.

p-Value between the alive group and dead group determined according to MannWhitney U-test.
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Table 3
Relationships between the APACHE II data and in-hospital mortality.
Total APS
Body temperature ( C)
Mean blood pressure (mmHg)
Pulse (beats/min)
Respiratory rate (per min)
PaO2 (mmHg)
pH
Sodium (mmol/L)
Potassium (mmol/L)
Hematocrit (%)
Creatinine (mg/dL)
White blood cell (/m3 )
Age (years)
Chronic health points
Glasgow Coma Scale
All (n = 824)
Dead group (n = 74)
p-Value
36.3 (35.736.8)
112.0 (94130)
114 (95132)
30 (2335)
86.7 (65.5128.7)
7.32 (7.207.42)
140 (137142)
4.3 (3.94.7)
38.0 (33.243.7)
1.16 (0.911.73)
9775 (760012,653)
74 (6580)
0 (00)
15 (1515)
36.2 (35.736.8)
113 (95131)
116 (96132)
30 (2435)
85.8 (65.5123.8)
7.32 (7.197.42)
140 (138142)
4.2 (3.94.7)
38.5 (33.744.0)
1.13 (0.891.67)
9795 (764512,668)
74 (6480)
0 (00)
15 (1515)
36.4 (35.236.9)
97 (77114)
105 (82125)
30 (2335)
96.1 (67.2147.5)
7.21 (7.197.40)
137 (135141)
4.4 (3.95.2)
34.7 (30.739.7)
1.63 (1.152.55)
9625 (689012,353)
76 (7081)
0 (00)
15 (1315)
0.750
<0.001
0.008
0.411
0.136
0.873
0.001
0.004
0.001
<0.001
0.300
0.041
0.386
0.006
APS, acute physiology score.

p-Value between the alive group and dead group determined according to MannWhitney U-test.
Fig. 2. ROC curves for each scoring system. The APACHE II system demonstrated an
optimal balance between sensitivity and specicity (47.3% and 67.3%; AUC = 0.588,
p = 0.012) at 17.5 points (black line), while the Modied APACHE II system demonstrated an optimal balance between sensitivity and specicity (51.4% and 69.4%, AUC
0.590, p = 0.001) at 9.5 points (blue line) and the APACHE-HF system demonstrated
an optimal balance between sensitivity and specicity (87.8% and 63.9%, AUC 0.779,
p < 0.001) at 2.5 points (red line). ROC, receiver-operating characteristic; AUC, area
under the ROC curve; HF, heart failure.
each factor were dened by ROC curves as follows: mean BP

(91.5 mmHg, AUC = 0.678), pulse (110.5 beats/min, AUC = 0.594),
sodium (137.5 mmol/L, AUC = 0.613), potassium (4.85 mmol/L,
AUC = 0.601), hematocrit (36.95 mg/dL, AUC = 0.617), creatinine
(1.475 mg/dL, AUC = 0.676), age (71.5 years, AUC = 0.572), and GCS
(13.5, AUC = 0.567).
Predictive value of the Modied APACHE II and APACHE-HF
scoring systems
The APACHE II demonstrated an optimal balance between sensitivity and specicity (47.3% and 67.3%; AUC = 0.588) at 17.5 points,
selecting 9.5 points for the Modied APACHE II score as a cut-off
value (sensitivity 51.4%, specicity 69.4%, AUC 0.590). Meanwhile,
a cut-off value of 2.5 points for the APACHE-HF score produced
an optimal balance (sensitivity 87.8%, specicity 63.9%, AUC 0.779)
(Fig. 2). A higher optimal balance was observed in the APACHE-HF
score than in the APACHE II or Modied APACHE II scores.
Based on these cut-off values, the patients were divided into low
or high groups for each scoring system. The KaplanMeier survival
curves showed that the prognosis, including all-cause death, did
not differ between the patients with an APACHE II score of 17 and
those with an APACHE II score of 18. Meanwhile, the prognosis
was signicantly poorer in the patients with a Modied APACHE II
score of 10 than in those with a Modied APACHE II score of 9 and
in the patients with an APACHE-HF score of 3 than in those with
an APACHE II-HF score of 2 (Fig. 3A, C, and E). The KaplanMeier
survival curves showed that the prognosis, including HF events, was
signicantly poorer in the patients with an APACHE II score of 18,
a Modied APACHE II score of 10, and an APACHE-HF score of 3
than in those with an APACHE II score of 17, a Modied APACHE II
of 9, and an APACHE-HF score of 2, respectively (Fig. 3B, D, and
F).
The patients were assigned to ve groups based on the APACHEHF score [Group 1: point 0 (n = 70), Group 2: points 1 and 2 (n = 343),
Group 3: points 3 and 4 (n = 294), Group 4: points 5 and 6 (n = 106)
and Group 5: points 7 and 8 (n = 11)].
The multivariate Cox regression model identied belonging to Group 3 (HR: 7.700, 95%CI 0.93563.421), Group 4
(HR: 12.357, 95%CI 1.388110.010), or Group 5 (HR: 18.361, 95%CI
1.478228.145) as independent predictors of 90-day mortality
(Table 4). Furthermore, the multivariate Cox regression model identied belonging to Group 2 (HR: 3.253, 95%CI 1.1739.019), Group
3 (HR: 5.298, 95%CI 1.84215.238), Group 4 (HR: 6.201, 95%CI
2.04018.846), or Group 5 (HR: 9.413, 95%CI 2.43236.436) as independent predictors of HF events during the 90-day follow-up period
(Table 4). The KaplanMeier curves revealed a poorer prognosis,
including all-cause death and HF events, in Group 5 and Group 4
than in the other groups, in Group 3 than in Group 2 or Group 1,
and in Group 2 than in Group 1 (Fig. 4).
Discussion
In the present study, the APACHE II scoring system did not
exhibit an adequate AUC. Furthermore, the Modied APACHE II
scoring system was inadequate to predict the mid-term mortality.
The new scoring system named APACHE-HF, which comprised
a combination of parameters, including mean BP, pulse, sodium,
potassium, creatinine, hematocrit, age, and GCS, exhibited signicantly higher sensitivity and specicity with an adequate AUC and
could be used to predict adverse mid-term outcomes in patients
with AHF.
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(A)
Cumulave event
P=0.091
0.6
APACHE II 17 (n=544)
0.2
HF event
1.0
0.8
0.4
APACHEII
(B)
All cause death
1.0
Cumulave survival
APACHEII
0.8
P=0.151
0.6
0.4
0.2
days
days
0.0
0.0
0
No. at Risk
544
Low
High 280
(C)
30
60
90
507
255
487
249
466
234
No. at Risk
Low 544
High 280
(D)
Modied APACHE II
30
60
497
255
469
241
439
218
Modied APACHE II
All cause death
HF event
1.0
Cumulave event
1.0
Cumulave survival
90
0.8
P<0.001
0.6
0.4
Modied APACHE II 9 (n=558)

0.2
0.8
P<0.001
0.6
0.4

0.2
days
days
0.0
0.0
0
No. at Risk
Low 558
High 266
(E)
30
60
90
518
239
503
231
487
213
No. at Risk
Low 558
High 266
(F)
APACHE-HF
30
60
90
515
237
488
222
463
194
APACHE-HF
All cause death
HF event
1.0
Cumulave event
Cumulave survival
1.0
0.8
P<0.001
0.6
0.4
APACHE-HF 2 (n=413)
APACHE-HF 3 (n=411)
0.2
No. at Risk
Low 413
High 411
P<0.001
0.6
0.4
APACHE-HF 2 (n=413)
APACHE-HF 3 (n=411)
0.2
days
0.0
0.8
30
60
90
390
367
382
352
387
322
days
0.0
0
No. at Risk
Low 413
High 411
30
60
90
390
362
371
339
359
298
Fig. 3. KaplanMeier curves for each scoring system. (A) The prognosis, including all-cause death, did not differ between the patients with an APACHE II score of 17 and
those with an APACHE II score of 18. (B) The prognosis, including HF events, was signicantly poorer in the patients with an APACHE II score of 18 than in those with an
APACHE II score of 17. (C) The prognosis, including all-cause death, was signicantly poorer in the patients with a Modied APACHE II score of 10 than in those with a
Modied APACHE II score of 9. (D) The prognosis, including HF events, was signicantly poorer in the patients with a Modied APACHE II score of 10 than in those with
a Modied APACHE II score of 9. (E) The prognosis, including all-cause death, was signicantly poorer in the patients with an APACHE-HF score of 3 than in those with
an APACHE II-HF score of 2. (F) The prognosis, including HF events, was signicantly poorer in the patients with an APACHE-HF score of 3 than in those with an APACHE
II-HF score of 2. HF, heart failure.
G Model
ARTICLE IN PRESS
Table 4
Cox regression analysis of the associations between 90-days cumulative mortality and events, and the clinical ndings.
Univariate analysis
HR
90-days mortality
Points of APACHE-HF score
Group 1 (point 0)
Group 2 (point 1, point 2)
Adjusting factors
APACHE II (per 1 point increase)
Modied APACHE II (per 1 point increase)
LVEF (per 1% increase)
NYHA (class IV)
Total bilirubin (per 0.1 mg/dL increase)
BUN (per 1.0 mg/dL increase)
Hemoglobin (per 1.0 g/dL increase)
BNP (per 10 pg/mL increase)
90-days HF Events
Points of APACHE-HF score
Group 1 (point 0)
Adjusting factors
APACHE-II (per 1 point increase)
Modied APACHE II (per 1 point increase)
LVEF (per 1% increase)
NYHA (class IV)
Total bilirubin (per 0.1 mg/dL increase)
BUN (per 1.0 mg/dL increase)
Hemoglobin (per 1.0 g/dL increase)
BNP (per 10 pg/mL increase)
1.000
1.221
7.603
17.522
20.637
1.054
1.120
0.987
2.352
1.011
1.026
0.861
1.002
1.000
4.315
7.047
10.723
14.126
1.032
1.082
0.991
1.723
1.086
1.019
0.925
1.001
Multivariate analysis
95%CI
p-Value
0.14710.139
1.03855.694
2.366129.756
2.147198.405
0.854
0.046
0.005
0.009
1.0131.097
1.0611.183
0.9701.003
1.0155.451
0.9971.026
1.0171.036
0.7860.945
1.0011.003
0.009
<0.001
0.987
0.046
0.120
<0.001
0.002
0.007
1.58211.769
2.59719.125
3.87029.717
4.13548.261
0.004
<0.001
<0.001
<0.001
1.0111.053
1.0501.115
0.9830.999
1.1892.497
0.9961.184
1.0131.025
0.8830.968
1.0011.002
0.002
<0.001
0.033
0.004
0.061
<0.001
0.001
0.001
HR
1.000
1.110
7.700
12.357
18.361
95%CI
p-Value
0.1279.694
0.93563.421
1.388110.010
1.478228.145
0.925
0.058
0.024
0.024
1.011
0.992
0.9361.092
0.8791.120
0.780
0.900
2.486
0.9186.729
0.073
1.015
1.107
1.001
1.0021.029
0.9741.258
0.9991.003
0.024
0.118
0.269
1.000
3.253
5.298
6.201
9.413
1.1739.019
1.84215.238
2.04018.846
2.43236.436
0.023
0.002
0.001
0.001
0.983
1.039
0.989
1.778
0.9461.021
0.9781.103
0.9800.998
1.1652.715
0.371
0.220
0.023
0.008
1.013
1.021
1.000
1.0051.020
0.9541.092
0.9991.001
0.001
0.553
0.461
HR, hazard ratio; CI, condence interval; HF, heart failure, LVEF, left ventricular ejection fraction measured on echocardiography; NYHA, New York Heart Association; BUN,
blood urea nitrogen; CRP, C-reactive protein; BNP, brain natriuretic peptide.
APACHE II scoring system and AHF

The APACHE II scoring system was rst published in 1985, and it
has been demonstrated that an increased APACHE II score on admission can be used to predict a worse in-hospital mortality and poor
long-term prognosis in intensive care patients [2]. The availability
of this scoring system has also been reported in the setting of both
endogenous and various surgical diseases requiring intensive care,
such as respiratory disease, abdominal sepsis, including acute pancreatitis, trauma, and postoperative diseases [69]. However, this
scoring system has not been evaluated in AHF patients. Moreover,
the APACHE II scoring system involves many factors and is cumbersome to apply; therefore, clinicians tend to hesitate to calculate
the score in all patients. It is necessary to develop a scoring system
that can be more easily and immediately applied in the emergency
department.
In the present study, the APACHE II scoring system was found
to have an inadequate AUC, while the Modied APACHE II scoring system could not be used to predict the mid-term mortality.
This might be due to inadequacies in the APACHE II point system.
The APACHE II scoring scale was originally developed for patients
with various diseases requiring care in the intensive care unit. In
fact, the majority of patients evaluated in the original study of
the APACHE II scoring system had non-cardiac diseases. Cardiac
patients comprised only 14.7% of cases, with HF patients accounting
for less than 1.5%. We therefore created a new scoring system suitable for HF patients based on a simple point method. This system
is dened as the APACHE-HF system, which exhibits signicantly
higher sensitivity and specicity with an adequate AUC compared
to the APACHE II and Modied APACHE II systems. Based on the
results of the present study, a combination of parameters, including
mean BP, pulse, sodium, potassium, creatinine, hematocrit, age, and

GCS, may be used to predict adverse outcomes of AHF.
Predictive factors for AHF
In previous observational studies, various predictive factors for
detecting adverse outcomes in AHF patients have been identied.
Among these factors, we showed the mean BP, pulse, sodium, potassium, creatinine, hematocrit, age, and GCS at the time of admission
to be predictive factors in AHF patients.
An age over 70 or 75 years has been reported to be associated
with a poor prognosis [12,14]. In addition, hypotension is one of the
most important determinants of the prognosis. Gheorghiade et al.
reported that a systolic pressure under 120 mmHg at the time of
admission was associated with a poor prognosis compared with a
systolic pressure over 120 mmHg [10,21]. It has also been reported
that a diastolic pressure under 100 mmHg or 90 mmHg on admission is associated with poor mortality [14,22]. According to a study
of mean arterial BP, a diastolic pressure under 90 mmHg is a strong
predictor of AHF [23]. We used the pulse rate as a substitute for
heart rate, which is a strong predictor of cardiovascular mortality and morbidity in the general population [24]. With respect to
AHF, Aaronson et al. found, in a study of 268 ambulatory patients
with advanced HF, that the resting heart rate was the best predictor of an adverse outcome [25,26]. In another example, Ishii
et al. showed that a heart rate over 113 beats/min on admission
is associated with a better cardiac event-free survival rate than a
heart rate under 112 beats/min [27]; these ndings support our
results. Hyponatremia is the most common electrolyte abnormality
in patients with AHF. In several large clinical trials, hyponatremia
was demonstrated to predict a poor prognosis [14,20,28]. The
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ARTICLE IN PRESS
APACHE-HF
All cause death
Cumulave
survival
1.0
0.8
0.6
0.4
Group 1
Group 2
Group 3
Group 4
P < 0.001
Group 5
0.2
days
0.0
0
No. at Risk
Group 1 70
Group 2 343
Group 3 294
Group 4 106
Group 5 11
30
60
90
66
324
271
86
10
65
317
262
81
9
63
315
242
72
8
depends on the degree of renal dysfunction [30,31]. For example, in

the data from the AHEAD registry, patients with a creatinine level
of >120 mmol/L on admission had a poor prognosis [15]. In another
report, a serum creatinine level over 1.5 mg/dL or 2.0 mg/dL on
admission was found to be a predictor of mortality [22,23]. Because
patients with AHF and anemia present more frequently with signicant renal dysfunction, renal dysfunction as a predictor of AHF
may have relevance to anemia. No relationship between the serum
potassium level on admission and the prognosis of AHF has been
reported to date; however, this phenomenon may be explained by
an association with renal dysfunction. The relationship between
consciousness disturbance on admission and AHF has not been adequately reported. Sicker AHF patients with shock and acidosis tend
to exhibit consciousness disturbance on admission. The level of
consciousness on admission is therefore a possible factor indicating
the general condition of AHF patients.
No AHF scoring systems including these key factors for AHF have
been previously reported; however, the development of a scoring
system that can be applied more easily and immediately in the
emergency department would be useful in the clinical setting for
treating AHF patients.
Study limitations
HF event
Cumulave event
1.0
0.8
0.6
0.4
0.2
Group 1
Group 2
Group 3
Group 4
P < 0.001
Group 5
days
0.0
0
No. at Risk
Group 1 70
Group 2 343
Group 3 294
Group 4 106
Group 5 11
30
60
90
66
324
266
86
10
65
306
250
80
9
62
297
225
66
7
Fig. 4. KaplanMeier curves for the APACHE-HF scoring system. (A) The
KaplanMeier curves revealed a poorer prognosis, including all-cause death, in
Group 5 and Group 4 than in the other groups, in Group 3 than in Group 2 or Group
1, and in Group 2 than in Group 1. (B) The KaplanMeier curves revealed a poorer
prognosis, including HF events, in Group 5 and Group 4 than in the other groups,
in Group 3 than in Group 2 or Group 1, and in Group 2 than in Group 1. HF, heart
failure.
present study also demonstrated a correlation between hyponatremia and high mortality or HF events, and the cut-off value for the
serum sodium level (Na 137 mmol/L.) was similar to the conventional denition of hyponatremia (Na < 135 mmol/L). Although the
relationship between hematocrit and the prognosis of HF remains
to be elucidated, anemia is a famous comorbidity of heart failure and has been reported to be a predictor of poor outcomes
in patients with chronic and acute HF [29]. Although most previous studies used the hemoglobin level as a marker of anemia,
the present study employed hematocrit because it is a constitutive factor of the APACHE II score. Renal dysfunction is also well
known to be a strong predictor of AHF, and the prognosis of AHF
There are several limitations associated with the present study

that should be considered when interpreting the results. First, the
original APACHE II scoring system was based on the most deranged
(worst) physiologic value observed during the initial 24-h time
period assuming that all pertinent physiologic values were available. In the present study, we used vital signs and laboratory data
obtained on admission because AHF patients are in the most critical condition on admission. Therefore, this system may not reect
the worst condition of AHF patients. Second, the population evaluated in our study was limited to only patients admitted to the ICU,
and AHF patients admitted to general wards were excluded from
this study. However, the patients were seen by the closed ICU in
our institute, and all physicians in closed ICU are cardiologists.
Therefore, the majority of AHF patients were admitted to the ICU.
For example, the rate of CS1, CS2, and CS 3 (67.8%, 28.1%, and 8%)
patients were not different to the previous ATTEND registry with
hospitalized HF (49.5%, 42.4%, and 7.9%) [32]. The patients selection
bias might be minimal in the present study. Third, we persisted with
the evaluation of original APACHE II, therefore, the scoring system
did not include the widely accepted factors such as left ventricular
ejection fraction, NYHA class, blood urea nitrogen, hemoglobin, and
BNP. Further study will be needed to evaluate these factors for the
next new scoring system.
Conclusion
The APACHE II scoring system cannot be used to adequately predict the prognosis of patients with AHF. Our new scoring system
including mean BP, pulse, sodium, potassium, hematocrit, creatinine, age, and GCS was found to be effective in predicting adverse
outcomes in AHF patients.
Disclosures
None declared.
Conicts of interest
None declared.
G Model
ARTICLE IN PRESS
Acknowledgments
We are grateful to the staff of the ICU and the medical records
ofce at Chiba Hokusoh Hospital, Nippon Medical School for their
valuable assistance in collecting the medical data.
References
[1] Knaus WA, Zimmerman JE, Wagner DP, Draper EA, Lawrence DE. APACHE-Acute
Physiology and Chronic Health Evaluation: a physiologically based classication system. Crit Care Med 1981;9:5917.
[2] Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of
disease classication system. Crit Care Med 1985;13:81829.
[3] Knaus WA, Wagner DP, Draper EA, Zimmerman JE, Bergner M, Bastos PG, Sirio
CA, Murphy DJ, Lotring T, Damiano A, Harrell FE. The APACHE III prognostic
system. Risk prediction of hospital mortality for critically ill hospitalized adults.
Chest 1991;100:161936.
[4] Zimmerman JE, Kramer AA, McNair DS, Malila FM. Acute Physiology and
Chronic Health Evaluation (APACHE) IV: hospital mortality assessment for
todays critically ill patients. Crit Care Med 2006;34:1297310.
[5] Jacobs S, Chang RW, Lee B. One years experience with the APACHE II severity
of disease classication system in a general intensive care unit. Anaesthesia
1987;42:73844.
[6] Larvin M, McMahon MJ. APACHE-II score for assessment and monitoring of
acute pancreatitis. Lancet 1989;2:2015.
[7] Del Bufalo C, Morelli A, Bassein L, Fasano L, Quarta CC, Pacilli AM, Gunella G.
Severity scores in respiratory intensive care: APACHE II predicted mortality
better than SAPS II. Respir Care 1995;40:10427.
[8] Schein M. APACHE II score in abdominal sepsis. Arch Surg 1988;123:1288.
[9] Goldhill DR, Sumner A. APACHE II, data accuracy and outcome prediction.
Anaesthesia 1998;53:93743.
[10] Shiba N, Shimokawa H. Chronic heart failure in Japan: implications of the
CHART studies. Vasc Health Risk Manag 2008;4:10313.
[11] van der Meer P, Postmus D, Ponikowski P, Cleland JG, OConnor CM, Cotter
G, Metra M, Davison BA, Givertz MM, Mansoor GA, Teerlink JR, Massie BM,
Hillege HL, Voors AA. The predictive value of short-term changes in hemoglobin
concentration in patients presenting with acute decompensated heart failure.
J Am Coll Cardiol 2013;61:197381.
[12] Spinar J, Parenica J, Vitovec J, Widimsky P, Linhart A, Fedorco M, Malek F, Cihalik
C, Spinarova L, Miklik R, Felsoci M, Bambuch M, Dusek L, Jarkovsky J. Baseline characteristics and hospital mortality in the Acute Heart Failure Database
(AHEAD) Main registry. Crit Care 2011;15:R291.
[13] Hata N, Yokoyama S, Shinada T, Kobayashi N, Shirakabe A, Tomita K, Kitamura
M, Kurihara O, Takahashi Y. Acute kidney injury and outcomes in acute decompensated heart failure: evaluation of the RIFLE criteria in an acutely ill heart
failure population. Eur J Heart Fail 2010;12:327.
[14] Ambrosy AP, Vaduganathan M, Huffman MD, Khan S, Kwasny MJ, Fought AJ,
Maggioni AP, Swedberg K, Konstam MA, Zannad F, Gheorghiade M, EVEREST
Trial Investigators. Clinical course and predictive value of liver function tests
in patients hospitalized for worsening heart failure with reduced ejection fraction: an analysis of the EVEREST trial. Eur J Heart Fail 2012;14:30211.
[15] Malek F, Ostadal P, Parenica J, Jarkovsky J, Vitovec J, Widimsky P, Linhart A,
Fedorco M, Coufal Z, Miklik R, Kruger A, Vondrakova D, Spinar J. Uric acid,
allopurinol therapy, and mortality in patients with acute heart failureresults
of the Acute HEart FAilure Database registry. J Crit Care 2012;27(737):
e1124.
[16] Desmoulin F, Galinier M, Trouillet C, Berry M, Delmas C, Turkieh A, Massabuau
P, Taegtmeyer H, Smih F, Rouet P. Metabonomics analysis of plasma reveals the
lactate to cholesterol ratio as an independent prognostic factor of short-term
mortality in acute heart failure. PLoS ONE 2013;8:e60737.
[17] Mebazaa A, Gayat E, Lassus J, Meas T, Mueller C, Maggioni A, Peacock F, Spinar

J, Harjola VP, van Kimmenade R, Pathak A, Mueller T, Tavazzi L, Disomma S,
Metra M, et al. Association between elevated blood glucose and outcome in
acute heart failure: results from an international observational cohort. J Am
Coll Cardiol 2013;61:8209.
[18] Sato N, Gheorghiade M, Kajimoto K, Munakata R, Minami Y, Mizuno M,
Aokage T, Asai K, Sakata Y, Yumino D, Mizuno K, Takano T, ATTEND Investigators. Hyponatremia and in-hospital mortality in patients admitted for heart
failure (from the ATTEND registry). Am J Cardiol 2013;111:101925.
[19] Gheorghiade M, Zannad F, Sopko G, Klein L, Pina IL, Konstam MA, Massie
BM, Roland E, Targum S, Collins SP, Filippatos G, Tavazzi L. Acute heart failure syndromes: current state and framework for future research. Circulation
2005;112:395868.
[20] Nieminen MS, Harjola VP. Denition and epidemiology of acute heart failure
syndromes. Am J Cardiol 2005;96:5G10G.
[21] Gheorghiade M, Abraham WT, Albert NM, Greenberg BH, OConnor CM, She L,
Stough WG, Yancy CW, Young JB, Fonarow GC, OPTIMIZE-HF Investigators and
Coordinators. Systolic blood pressure at admission, clinical characteristics, and
outcomes in patients hospitalized with acute heart failure. J Am Med Assoc
2006;296:221726.
[22] Moleerergpoom W, Hengrussamee K, Piyayotai D, Jintapakorn W, Sukhum P,
Kunjara-Na-Ayudhya R, Suwanjutah T, Laothavorn P. Predictors of in-hospital
mortality in acute decompensated heart failure (Thai ADHERE). J Med Assoc
Thai 2013;96:15764.
[23] Adamopoulos C, Zannad F, Fay R, Mebazaa A, Cohen-Solal A, Guize L, Juilliere
Y, Alla F. Ejection fraction and blood pressure are important and interactive
predictors of 4-week mortality in severe acute heart failure. Eur J Heart Fail
2007;9:93541.
[24] Kannel WB, Kannel C, Paffenbarger Jr RS, Cupples LA. Heart rate and cardiovascular mortality: the Framingham Study. Am Heart J 1987;113:148994.
[25] Aaronson KD, Schwartz JS, Chen TM, Wong KL, Goin JE, Mancini DM. Development and prospective validation of a clinical index to predict survival in
ambulatory patients referred for cardiac transplant evaluation. Circulation
1997;95:26607.
[26] Lanza GA, Fox K, Crea F. Heart rate: a risk factor for cardiac diseases and outcomes? Pathophysiology of cardiac diseases and the potential role of heart rate
slowing. Adv Cardiol 2006;43:116.
[27] Ishii S, Inomata T, Ikeda Y, Nabeta T, Iwamoto M, Watanabe I, Naruke T, Shinagawa H, Koitabashi T, Nishii M, Takeuchi I, Izumi T. Clinical signicance of
heart rate during acute decompensated heart failure to predict left ventricular reverse remodeling and prognosis in response to therapies in nonischemic
dilated cardiomyopathy. Heart Vessels 2014;29:8896.
[28] Gheorghiade M, Abraham WT, Albert NM, Gattis Stough W, Greenberg BH,
OConnor CM, She L, Yancy CW, Young J, Fonarow GC, OPTIMIZE-HF Investigators and Coordinators. Relationship between admission serum sodium
concentration and clinical outcomes in patients hospitalized for heart failure:
an analysis from the OPTIMIZE-HF registry. Eur Heart J 2007;28:9808.
[29] von Haehling S, Schefold JC, Hodoscek LM, Doehner W, Mannaa M, Anker SD,
Lainscak M. Anaemia is an independent predictor of death in patients hospitalized for acute heart failure. Clin Res Cardiol 2010;99:10713.
[30] Shirakabe A, Hata N, Kobayashi N, Shinada T, Tomita K, Tsurumi M, Matsushita
M, Okazaki H, Yamamoto Y, Yokoyama S, Asai K, Mizuno K. Long-term prognostic impact after acute kidney injury in patients with acute heart failure. Int
Heart J 2012;53:3139.
[31] Shirakabe A, Hata N, Kobayashi N, Shinada T, Tomita K, Tsurumi M, Matsushita
M, Okazaki H, Yamamoto Y, Yokoyama S, Asai K, Mizuno K. Prognostic impact
of acute kidney injury in patients with acute decompensated heart failure. Circ
J 2013;77:68796.
[32] Sato N, Kajimoto K, Keida T, Mizuno M, Minami Y, Yumino D, Asai K, Murai
K, Muanakata R, Aokage T, Sakata Y, Mizuno K, Takano T, TEND Investigators.
Clinical features and outcome in hospitalized heart failure in Japan (from the
ATTEND Registry). Circ J 2013;77:94451.

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G Model

JJCC-870; No. of Pages 9

Contents lists available at ScienceDirect

New scoring system (APACHE-HF) for predicting adverse outcomes in

The APACHE II system consists of three parts, including the

Dead group (n = 74)

Alive group (n = 750)

Alive group (n = 750)

Dead group (n = 75)

APS, acute physiology score.

Alive group (n = 750)

Dead group (n = 74)

APS, acute physiology score.

each factor were dened by ROC curves as follows: mean BP

JJCC-870; No. of Pages 9

H. Okazaki et al. / Journal of Cardiology xxx (2014) xxxxxx

All cause death

All cause death

Modied APACHE II 9 (n=558)

Modied APACHE II 9 (n=558)

Modied APACHE II 10 (n=266)

Modied APACHE II 10 (n=266)

All cause death

APACHE II scoring system and AHF

mean BP, pulse, sodium, potassium, creatinine, hematocrit, age, and

JJCC-870; No. of Pages 9

H. Okazaki et al. / Journal of Cardiology xxx (2014) xxxxxx

All cause death

depends on the degree of renal dysfunction [30,31]. For example, in

There are several limitations associated with the present study

[17] Mebazaa A, Gayat E, Lassus J, Meas T, Mueller C, Maggioni A, Peacock F, Spinar

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