Introducing the Aspect-PLUS™ ST2 Test

James V. Snider, Ph.D.PresidentCritical Diagnostics

Heart Failure 2015

Why produce a FAST assay for ST2?

• Using the 1st generation ELISA many things were accomplished

• ST2 is CE marked for sale in the EU and is cleared by the US FDA, CFDA and KFDA as an aid in risk stratification of patients with heart failure.

• Included in the 2013 ACCF/AHA guidelines for heart failure patient management.

• In 2014 the AMA issued a unique CPT code for ST2, 83006, and in January 2015 CMS issued a favorable coverage/payment decision.

• April 2015 the AJC published the International ST2 Consensus Panel paper summarizing the clinical value of ST2. – Twelve chapters and over 80 pages summarizing the support for

clinical use of ST2 across all 4 stages of heart failure.

ST2 Clinical Value• In published research studies ST2 is

consistently the most robust prognostic marker reported

• With its low RCV it is ideally suited for patient monitoring

• ST2 is not adversely effected by typical confounders such as renal dysfunction and obesity

• Emerging evidence shows the utility of using ST2 to personalize patient therapy

Serial ST2 Measurements: Basel ADHF Cohort

Breidhardt, et al. 2013, J. Card. Failure

ST2 Predicts Therapy ResponseCu

mul

ativ

e su

rviv

al

Days

BB treated ST2 responder

untreated ST2 responderuntreated ST2 non-responder

BB treated ST2 non-responder

p=0.62p=0.1

• Risk is not absolute! • It can be attenuated!!

Breidhardt, et al. 2013, J. Card. Failure

RR=2.8

ST2 Therapeutic Response:PROTECT Study

Non- Rarely Mostly Full

CV events by ST2 time in response

% time in response

% w

ith C

V ev

ents

0.0

0.2

0.4

0.6

0.8

1.0

Non-responderRarely responderMostly responderFull responder

N=46 N=28 N=30 N=41

Summary: • Time in ST2 response (<35

ng/ml) is closely tied to outcomes in chronic HF due to LVSD.

• The prognostic value of sST2 is independent of relevant covariates, including NT-proBNP.

• “Only sST2 appeared to provide incremental prognostic information and reflect changes in myocardial remodeling over time.”

Gaggin et al. 2014, JACC HF

Cardiovascular events by baseline sST2 and final achieved β-blocker (BB) dose

Gaggin H et al. Circ Heart Fail 2013;6:1206-1213 Copyright © American Heart Association, Inc. All rights reserved.

p = 0.09

P < 0.001

for trend

Stage B NYHA Class I HF ProgressionBiomarker Levels and Therapy in Subsequent Visits

1 2 3 4 5 6 70

10

20

30

40

50

60

70

80

90

0

100

200

300

400

500

600

700

800

900S T

2 (n

g/m

L)

NT-

pro B

NP

(pg/

mL)

β blocker increased

β blocker increased

ACE-inhibitorincreased

Visits

Aspect-PLUS™ ST2 Test• Quantitative 

fluorescent lateral flow immunoassay format

• System is comprised of a disposable, single use cassette and a fluorescent reader

• Uses EDTA plasma as the test specimen

• Result in 20 minutes• Analytical performance 

comparable to the Presage® ST2 Assay

Aspect-PLUS™ ST2 Test: Performance

Parameter Presage® ST2 Assay Aspect-PLUS™ ST2 TestLimit of Quantitation (LoQ) 2.4 ng/ml 12.5 ng/ml

Linearity Limit 200 ng/ml 257 ng/ml

Intra-Assay Precision 4.0% 10.4%

Inter-Assay Precision 6.4% 13.6%

Hook Effect No hook effect up to 200 ng/ml No hook effect up to 2000 ng/ml

Interfering SubstancesNo effect observed from 5 endogenous and 49 therapeutic 

substances

Specimen EDTA or heparin plasma, serum EDTA plasma

Specimen volume 0.020 ml 0.035 ml

Method Concordance: Passing-Bablok regression

No significant deviation from linearity (y = 1.01x + 5.8, p=0.75, ). And a correlation coefficient (R) of 0.92.

Conclusions• ST2 is established as a powerful biomarker

tool for personalization and optimization of heart failure patient care

• The Aspect-PLUS™ ST2 Test is the first rapid test providing a cost effective solution for ST2 testing

• The Aspect-PLUS™ ST2 Test is comparable to the established Presage® ST2 Assay and meets the requirements for IVD analytical performance.