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Advances in Heart Failure, Patient Management, ST2 Testing
Advances in Heart Failure, Patient Management, ST2 Testing
Patient Management,
ST2 Testing
Outline
Prognosis
Case Studies
2
Heart Failure
HF Revolving Door
4
Potential Clinical Uses of Biomarkers
ST2
CREATINE
TROPONIN
KINASE
CK-MB NP MARKERS
MYOGLOBIN
DIAGNOSIS PROGNOSIS/MANAGEMENT
5
What is ST2?
ST2 (growth STimulation expressed gene 2) is a member of the Interleukin-1
receptor family, and is formally known as interleukin 1 receptor like 1 (IL1RL-1).
IL-33 is its ligand.
Was first reported in 1989, but its function was not well elucidated.
IRAK
ERK NFkB
ST2
Anti remodeling
Anti hypertrophy
Anti fibrosis
CARDIOPROTECTION
Kakkar et al. Nat Rev Drug Discov 2008
2013 ACCF/AHA Guideline for the
Management of Heart Failure
ST2
(IIa, B)
ST2
(IIb, A)
Easy to Use:
Single Cutpoint
>
ng/mL
= RISK
ST2 is Associated with Symptom Severity
NYHA Class NYHA Class
200.0 200.0
180.0 180.0
160.0 160.0
140.0 140.0
P<0.0001 P<0.0001
120.0 120.0
100.0 100.0
80.0 80.0
60.0 60.0
40.0 40.0
20.0 20.0
- -
NYHA Class 1 NYHA Class 2 NYHA Class 3 NYHA Class 4 NYHA Class I NYHA Class II NYHA Class III NYHA Class IV
In a cohort of 879 heart failure patients ST2 did not show any correlation with
renal function whereas NT-proBNP concentrations increased significantly with
decreasing renal function.
BNP/NT-proBNP
+
ST2
When to Detect ST2
1. Inpatient setting
Destablised HF (Acutely Decompensated HF)
If one considers a 7 day average LOS (length of stay in hospital).
The diagnosis :
may include clinical judgement (or echo/x-ray/ NT-proBNP).
ST2 baseline value:
ST2 should be assessed within 24hrs of admission to establish severity and
risk
Hospital stay:
ST2 may be evaluated during hospital stay (day 3 or 4), to evaluate and guide
the therapy
Hospital discharge: certainly 24hrs before discharge
Post-MI
ST2 should be measured in the FIRST 24hrs following MI. A follow-up ST2
may be at day 5 or 10. When discharged, above should apply dependent on risk
profile.
Algorithm for using ST2 in acute myocardial infarction patients
STEMI or moderate-high risk NSTEMI
LEVF<40%
Measure ST2
No Serum creatinine
Defer additional
<2.5 mg/dL (menor
therapy
<2.0 mg/dL (women?
Yes
Provide close clinical Start spironoiactone
follow-up 25 mg daily
Laboratory
monitoring and dose
Daniels LB.2014) ST2: how to really do it right. In: Heart Failure: The Experts
Approach, Chapter 34, Alan S Maisel, Gerasimos S Filippatos. pp 283-288. titration as indicated
2. Ambulatory (outpatient) setting
Chronic HF
Dependent on risk of patient, it may be appropriate (for high risk HF) to re-
measure ST2 after 1 week. Dependent on concentration of ST2 (remember target
is below 35ng/ml) will determine the frequency of ST2 testing:
High risk (significantly above 35ng/ml) 2 weeks 1 month intervals
(Intermediated moderately above 35ng/ml) 1 month 3 month intervals)
Low risk (below 35ng/ml) 3 6 month intervals
Algorithm for using ST2 in chronic heart failure patients
Chronic heart failure with severe symptoms or
recent decompensation
Measure ST2
ST2 Decile
Rehman SU, Mueller T, Januzzi JL et al. J Am Coll Cardiol. 2008;52:1458-65.
In Chronic HF Risk is Much Higher
if ST2 >35 ng/mL
Reclassification
0.6
P < 0.001
0.4
0.2
0.0
1.2
1.0
0.8
0.6
0.4
0.2
0.0
ST2 ST2 + BNP ST2 + BNP + cTnT
N=35 N=69
N=115
N=68
ST2 Levels Predict Response to
Treatment: BB
2 p=0.62
p=0.1
3
Cumulative survival
Days
Breidthardt, et al. 2013 JCF
ST2 Provides Actionable Information
Adapted from Professor Antoni Genis-Bayes, Hospital Universitari Germans Trias i Pujol, Spain
Case: Stage B NYHA Class I HF
Biomarker Levels and Therapy in Subsequent Visits
ST2
NT-proBNP
Adapted from Professor Antoni Genis-Bayes, Hospital Universitari Germans Trias i Pujol, Spain
Patient K.E.
35
Started
25
20
19
ST2
15
10
Discharge No Re-admission
0 Clinic
8-Jan-15 24-Mar-15
Metoprolol 100
ST2 Concentration Levels (ng/mL)
BID
200 200
Hydralazine 10
TID
150
ST2
100 105
50
No Re-admission
Discharge Clinic
0
14-Dec-14 15-Mar-15
140 800
700
120
600
100 550
500 ST2
80 79 ST2 decreased at 78 BNP
both discharges 400
60 350
54 but still very high. 295 300
40 200
20 110 100
0 Admission Discharge Re-admission Discharge 0
28-Mar-15 30-Mar-15 10-Apr-15 13-Apr-15
41
Who is Using the Presage ST2 Assay?
More
Marketing in Asia-Pacific
Area Institution
Beijing Fuwai Hospital
Shanghai Zhongshan Hospital
China
Wuhan Asia Heart Hospital