Online Appendix for the following JACC article
TITLE: Growth Differentiation Factor 15: A Novel Risk Marker Adjunct to the EuroSCORE for Risk
Stratification in Cardiac Surgery Patients
AUTHORS: Matthias Heringlake, MD, Efstratios I. Charitos, MD, Nicola Gatz, Jan-Hendrik Käbler,
Anna Beilharz, Daniel Holz, Julika Schön, MD, Hauke Paarmann, MD, Michael Petersen, MD,
Thorsten Hanke, MD
APPENDIX
Table 1 – electronic supplement: Additive Euroscore: Risk factors, definitions and weights
(score)
Risk factor
Definition
Score
Age
Age per 5 years or part thereof
1
over 60 years
Sex
Female
1
Chronic pulmonary disease
Long-term use of
1
bronchodilators or steroids for
lung disease
Extracardiac arteriopathy
Any one or more of the
2
following: claudication,
carotid occlusion or .50%
stenosis, previous or planned
intervention on the abdominal
aorta, limb arteries or carotids
Neurological dysfunction
Disease severely affecting
2
ambulation or day-to-day
functioning
Previous cardiac surgery
Requiring opening of the
3
pericardium
Serum creatinine
> 200 mmol/l preoperatively
2
Active endocarditis
Patient still under antibiotic
3
treatment for endocarditis at
the time of surgery
Critical preoperative state
Any one or more of the
3
following: ventricular
tachycardia or fibrillation or
aborted sudden death,
preoperative cardiac massage,
preoperative ventilation
before arrival in the
anaesthetic room, preoperative
inotropic support, intraaortic
balloon counterpulsation or
preoperative acute renal
failure (anuria or oliguria,10
ml/h)
Cardiac-related factors:
Unstable angina
Rest angina requiring i.v.
2
nitrates until arrival in the
anaesthetic room
LV dysfunction
Moderate or LVEF 30 to 50%
1
Poor or LVEF < 30 3
3
Recent myocardial infarct (< 90
2
days)
Pulmonary hypertension
Systolic PA pressure > 60
2
mmHg
Operation-related factors:
Emergency
Carried out on referral before
2
the beginning of the next
working day
Other than isolated CABG
Major cardiac procedure other
2
than or in addition to CABG
Surgery on thoracic aorta
For disorder of ascending,
2
arch or descending aorta
Postinfarct septal rupture
4
Table 2 – electronic supplement
Relationship between preoperative Growth-differentiation-factor-15, demographics, and
variables representative of cardiovascular status and/or risk.
Variable
Spearman’s rank test /
significance
coefficient of contingence
age
0.46 (0.42 to 0.5)
p<0.0001
sex
0.04 *
P=0.150
body mass index
-0.03 (-0.08 to 0.02)
P = 0.175
surgical priority urgent/emergency
0.138 *
P<0.0001
CABG vs. NO-CABG
0.02 *
p=0.521
LVEF <30%
0.2 *
P=0.0872
eGFR
-0.48 (-0.52 to -0.44)
p<0.0001
NTproBNP
0.5 (0.46 to 0.54)
p<0.0001
hsTNT
0.52 (0.48 to 0.56)
p<0.0001
NTproBNP: N-terminal pro B-type natriuretic peptide; CABG: coronary artery bypass grafting; eGFR:
estimated glomerular filtration rate; IABP: intraaortic balloon pump; LVEF: left ventricular ejection
fraction; hsTNT: high-sensitive troponine-t. *: Coefficient of contingence: Chi-Square test.
Table 3 electronic supplement: Cox proportional hazards regression for 1-year mortality
Total cohort
Elective patients
N = 1438
N = 1196
Covariate
Hazard ratio
Additive
1.2327
significance
Hazard ratio
1.2842
P < 0.0001
P < 0.0001
Euroscore
(1.1709 to 1.2979)
(1.1980 to 1.3767)
NTproBNP
Not included
Not included
in the model
in the model
1.0001
Not included
hsTNT
significance
P = 0.0579
(1.000 to 1.0002)
GDF-15
in the model
1.0553
1.1571
P < 0.0001
(1.0288 to 1.0824)
P < 0.0001
(1.1002 to 1.2170)
Duration of
1.0018
Not included
P = 0.0247
surgery
(1.0002 to 1.0033)
Chi Square
122.811
in the model
P < 0.0001
72.542
P < 0.001
Cox proportional hazards regression employing the additive Euroscore, N-terminal pro B-type
natriuretic peptide (NTproBNP), high sensitive troponin T (hsTNT), Growth-differentiation factor 15
(GDF-15), and duration of surgery as continuous variables. Data are given as Hazard ratios with 95%
confidence intervals.
Table 4 electronic supplement: Net-reclassification improvement of additive Euroscore with GDF-15 for
1-year mortality.
a.
Updated model (risk categories)
% patients reclassified
Initial model
(risk categories)
OUTCOME ABSENT
0 - 2%
2–5%
5 – 10%
10 - 100%
0 – 2%
255
3
10
0
5
2- 5%
111
278
29
19
36
5 – 10%
0
259
82
77
80
10 – 100%
0
0
84
122
41
b.
Updated model (risk categories)
% patients reclassified
Initial model
(risk categories)
OUTCOME PRESENT
0 - 2%
2–5%
5 – 10%
10 - 100%
0 – 2%
4
0
2
0
33
2- 5%
6
3
2
3
79
5 – 10%
0
8
2
17
93
10 – 100%
0
0
11
51
18
Net-reclassification improvement (NRI) for 30 day mortality between the additive Euroscore predicted mortality
risk categories (initial model) and the additive Euroscore with Growth-differentiation factor 15 (GDF-15)
employing a cut- off level ≥ 1.8 ng/ml (updated model). The addition of GDF-15 resulted in a NRI of 0.2286
(95% C.I.: 0.0977 to 0.3595, p=0.00062.) and an integrated discrimination improvement of 0.0433 [95%
C.I.:0.027 to 0.0596, p<0.0001)