Post on 13-Dec-2014
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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.