High Sensitivity TroponinsMarch 27th 2014Rosalind Oakes

Troponin How troponins have changed What this means – advantages and

disadvantages of Hs Tn Hs Tn in the ED ADAPTED Cullen (2013)

Introduction

Calcium binds to troponin and exposes myosin binding sites on actin

A ‘regulatory muscle protein released into the circulation following acute cardiac injury’ Shah 2013

Part of the criteria for the universal definition of MI – ESC, AHA, ACC, WHF

What is troponin?

Hs Tn have been available since 2010

Newer assays are able to detect troponins at extremely low concentrations - to a level that we can detect troponin in healthy people

We can work out (with more reliability) the reference range of the normal population and determine the 99th centile.

We now think that the 99th centile is higher in men than women so the test should be sex specific

Normal values are difficult to derive – a population of blood donors would create a difference normal value than a sicker population presenting to ED

What has changed

Detecting as low as 3ng/L , ULN 14ng/L, ultra high sensitivity

Sensitivity for diagnosis of MI 73 -91% (Shah 2013)

Compare Sensitivity for ECG 28%

We now can detect troponin at much earlier from the onset of symptoms (no needs to wait for higher circulating troponin to become detectable) clinical implications for length of stay

Diagnosis of MI is likely to increase, how will we manage low troponin rises?

Does not exclude unstable angina

Sensitivity

Ability to rule in MI not as good as previous troponins

Specificity has been reported at 80-85%

May lead to over admission and over investigation

Not as specific

Serial testing of troponin improves specificity – to around 92%

Looking for a change in the troponin value (rise or fall) is part of MI definition

Delta values – 20% (older troponins) or 7-9 ng/L

Managing reduction in specificity

Troponin is specific for myocardial injury of some kind..

Type 2 MI Hypotension, tachyarrythmia, respiratory failure, sepsis

PE, Acute and chronic heart failure, renal failure, strenuous exercise, acute pericarditis/myocarditis, cardiac contusion, cardioversion, structural heart disease

Prognostic implications

Patient selection – risk stratification

Managing troponitis

International guidelines suggest measuring on arrival and then between 3-6hours after the first test, irrespective of onset of symptoms (Shah 2013)

Sensitivity of the test is similar at 3 and 12 hours for HsTn after onset of pain

Point is to demonstrate rise or fall in level (by greater than 20%) to show ACS (as opposed to other forms of myocardial injury)

When should we measure

Hospital

Trop Hours from presentation

SCGH 0,4

RPH Hs Tn 0,2

JHC Hs Tn 0,3,6 National Heart Foundation

Swans Hs Tn 1 0,3,6 Low risk discharged at 6 hours

RDH 0,9 Intermediate and high admit Cardiology

NSW State wide 0,9 if older trops0,3 if Hs Tn

Cairns Old Troponin

Low – 2, med -6, high Cardiology

Universal

Hs Tn 0,3,6

Application of Hs Tn

Risk Stratification with Hs-Tn in ED

Aim: will an accelerated pathway reduce LOS and is it safe?

For low and intermediate risk patients

Primary outcome: LOS and MACE

Compared Older pathway: 8 or 12 hour troponin (n=429) Accelerated pathway: Triple markers inc Hs Tn

(n=615)

ADAPTED - SCGH

Pre intervention pathway

Accelerated Pathway

MACE 19.9% 17.6%

LOS < 4hrs 27.7% 40.%

HOME 27.7% 39.7%

Admissions 70% 61%

Misses ? ?2%

ADAPTED

TIMI Score Calculation (1 point for each): - Age >= 65 - Aspirin use in the last 7 days (patient experiences chest

pain despite ASA use in past 7days) - At least 2 angina episodes within the last 24hrs - ST changes of at least 0.5mm on admission EKG - Elevated serum cardiac biomarkers - Known Coronary Artery Disease (CAD) (coronary stenosis

>= 50%) - At least 3 risk factors for CAD, such as: Hypertension ->

140/90 or on antihypertensives, current cigarette smoker, hypercholesterolemia, diabetes mellitus, Family history of premature CAD (CAD in male first-degree relative, or father less than 55, or female first-degree relative or mother less than 65).

TIMI Score Calculation

% risk at 14 days of: all-cause mortality, new or recurrent MI, or severe recurrent ischemia requiring urgent revascularization.

Score of 0-1 = 4.7% risk Score of 2 = 8.3% risk Score of 3 = 13.2% risk Score of 4 = 19.9% risk Score of 5 = 26.2% risk Score of 6-7 = at least 40.9% risk

TIMI Score Interpretation

Aim to validate hs-TnI within an accelerated diagnostic protocol for patients with possible ACS

Data collected from 2 separate studies ADAPT (AUS, NZ) and APACE (Swiss)

Prospective studies

All patients received normal standard care in each location

Blood drawn at presentation and at 2 hours for ADAPT and APACE and samples then frozen (ie time from presentation not time from symptoms)

Hs TNI > 26 ng/L

Cullen (2013)

Identified patients who were eligible for the acceleration diagnostic protocol being studied TIMI ≤1 , no ischaemic changes on ECG, and

normal 2 hour Hs-Tn1

Primary outcome was MACE within 30 days of presentation (including at presentation) MACE= Cardiac arrest, AMI, emergency

vascularisation, VT/VF, AV block

Cullen (2013)

Patients in ADP

Patients with MACE

% of patients in ADP without MACE

% of patients from ADP who had a stress test in 30 days

ADAPT 678(41.4%)

2 99.7% 65.8%

APACE 351(38.6%)

1 99.7% 18.2%

Results ADAPT (n=1635) MACE in entire cohort = 15.1% (n= 247)APACE (n=909) MACE in entire cohort = 17.2% (n=156)

Early discharge strategy utilizing a hsTn assay, TIMI ≤1, and non-ischemic ECG can safely decrease observation periods and admissions in approximately 40% of patients with suspected ACS

Cullen (2013) Conclusions

Ultra HS Troponins and problems with sensitivity

Attempts to risk stratify using ultra high sensitivity

Care of intermediate group in hospitals – safe discharge from ED or better managed in hospital

NICE release early rule out with HS Tn in October 2014

Summary & Future

Cullen et al, Validation of High-Sensitivity Troponin I in a 2-hour Diagnostic Strategy to Assess 30-Fay Outcomes in Emergency Department Patients With Possible Acute Coranary Syndrome. JACC 2013 Vol 62 No 14

Gamble, Carlton, Orr, Greaves. High sensitivity troponin, six lessons and a reading. Br J Cardiol 2013;20:109-12

Thygesen K, Alpert JS, Jaffe AS et al. Third Universal definition of MI. Eur Heart J 2012; 344

ADAPTED – SCGH, presentation slides by D Mountain Chest pain guidelines as being used March 2014 from

SCGH, RPH, JHC, Swans, RDH, NSW and Cairns

References

NSTEMI Guideline PathWest Laboratory Troponin I

Laboratory Troponin I on Admission

< 0.04 ug/L

≥ 0.04 ug/L

Repeat at 3 hrs (and at least 6 hours post onset of chest pain)

In the absence of ischaemic symptoms or ECG changes, consider alternatives and repeat in 3 hours

< 0.04 ug/L

≥ 0.04 ug/L

≥ 0.04 ug/L

< 0.04 ug/L

Low Risk of ACS

Possible Interference Check with Lab

≤ 50% Change

> 50% Change

Increased Risk of ACS. Treat if clinically indicated

Re-assess Risk of ACS Consider alternatives

http://www.heartfoundation.org.au/SiteCollectionDocuments/2011-ACS-addendum-article-in-press.pdf

NB : This is a PathWest Laboratory Medicine WA Troponin Method Guideline Only

Increased Risk of ACS. Treat if clinically indicated.