Contemporary ED Management of Patients with Chest Pain :

A Concise Guide for the High-sensitivity Troponin Era

James Andruchow, MD, MSc, FRCPC, ABEM

September 28, 2018

Faculty Presenter Disclosure:Dr. James Andruchow

Relationships with Financial Sponsors:

- No personal financial relationships of any kind with industry

- Unrestricted investigator-initiated research grant: - “External validation of three emergency department rapid rule-out

protocols for myocardial infarction using a high sensitivity troponin assay” (Roche Diagnostics)

- No other disclosures/conflicts to report

Disclosure of Financial Support

Cardiology for the Non-Cardiologist has received financial support from the following Pharmaceutical companies:

Bayer, Bristol-Meyers Squibb/Pfizer, Servier, Novartis, Amgen, AstraZeneca and Merck in the form of unrestricted educational grants.

Potential Conflicts of Interest: None

Mitigating Potential Bias• While we have received unrestricted educational grants from several pharmaceutical companies, most presentations have no mention of specific products and are unrelated to the supporting companies or their products. No specific presentations will be supported or sponsored by a specific company.

• Information on specific products will be presented in the context of an unbiased overview of all products related to treating patients.

• All scientific research related to, reported or used in this CME activity in support or justification of patient care recommendations conforms to the generally accepted standards.

• Clinical medicine is based in evidence that is accepted within the profession.

Objective

To provide a current evidence-based review of management of ED patients with chest pain using high-sensitivity troponin

Caveat

All high-sensitivity troponin assays demonstrate similar clinical performance.

This talk will present data for Roche Diagnostics hs-cTnTbecause we have experience with this assay in the Calgary zone.

Background

• Chest pain is one of the most common reasons for visiting an emergency department• ~600,000 ED visits in Canada annually

• Most patients don’t have a myocardial infarction (AMI prevalence 8-15%)

• Missed diagnoses can lead to serious morbidity and mortality

• High-sensitivity cardiac troponin (hs-cTn) assays have the potential to fundamentally change how we evaluate chest pain patients

History is everything

Perform a focused physical exam and/or POCUSto exclude other diagnoses

So you’ve decided to rule out MI…

• Evaluation is contingent on two tests:

• Electrocardiogram

• Compare with old ECGs

• Perform serial ECGs, especially for patients with active chest pain or high risk presentations

• Troponin

• Conventional assay:• Serial troponins over 3-6 hours

• High-sensitivity assay:• New strategies are possible

Do you work at an institution primarily using a high-sensitivity troponin assay?

A. Yes

B. No

C. I’m not sure

What is High-Sensitivity Troponin?

• 2 major criteria define high-sensitivity cardiac troponin assays (hs-cTn)

• Sensitivity:• Able to detect very low troponin levels

• At least 50% (ideally, 95%) of healthy individuals should have a measurable troponin level

• Precision:• Results must be precise and reproducible

• Total imprecision (coefficient of variation = SD/mean) at 99th percentile must be less than 10%

Chenevier-Gobeaux C et al. Arch Cardiovasc Disease 2015

• “High-sensitivity assays are recommended over less sensitive ones.”

• “… 0 h/1 h assessments are recommended when high-sensitivity cardiac troponin assays with a validated algorithm are available.

The 0 h/1 h algorithms rely on two concepts:

• first, high-sensitivity cardiac troponin is a continuous variable and the probability of MI increases with increasing high-sensitivity cardiac troponin values;

• second, early absolute changes of the levels within 1 h can be used as surrogates for absolute changes over 3 h or 6 h and provide incremental diagnostic value to the cardiac troponin assessment at presentation.”

2015 ESC ACS Guidelines

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hs-cTn 2

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Normal Variation Small Ischemic Event Large Ischemic Event

A. Conventional troponin assay interpretation

B. High-sensitivity troponin assay interpretation

Conventional vs

High-SensitivityAssay

Interpretation

*Nonischemic ECG and hs-cTnT < 5ng/L

Outcome Pooled Sensitivity (95% CI)

AMI 98.7 (96.6-99.5)

30d MACE 98.0 (94.7-99.3)

High-sensitivity Troponin:

Very low levels

on presentation

Outcome Sensitivity (%)

AMI 96.0

30d Mortality 99.5

High-sensitivity Troponin:

2-hourAlgorithm

Can these data be combined into a unified algorithm?

ESC 2015 ACS

Guidelines

• Advocate for a 1-hour algorithm with a greater risk for misclassification based on assay variability

• Minimal differences between delta cutoffs

• Little clinical context provided

• No guidance for patients in the observational zone

Weaknesses of

ESC Guidelines

Calgary High-sensitivity

Troponin Pathway

Ruling out MI:

Very low hs-cTnTconcentrations on

arrival

AND

Non-ischemic ECG

Calgary Prospective

Study

Calgary Data: Very Low Concentrations on Arrival

*Data presented are irrespective of symptom duration

Ruling out MI:

2-hour Algorithm

AND

Non-ischemic ECG

Calgary 2-hour Algorithm:

Rule Out Rule In

Calgary 2-hour Algorithm:

Observational Zone

Navigating the Observational Zone

• Be cautious

• If troponin levels are not changing, and are near the patient’s previously recorded baseline level, ACS is unlikely

• If troponin levels are different from the patient’s prior baseline and/or rising strongly consider ACS:

• Send a 4-hour troponin, repeat the ECG, reassess the patient

• Consider non-ischemic causes of myocardial injury

• Disposition cautiously

Ruling out MI:

2-hour Algorithm

Observational Zone Guidance

You’ve ruled out MI… now what?

Unstable angina still exists

Disposition after R/O MI

• High risk features -> Cardiology Consult• Ischemic or dynamic ECG changes

• Serious arrhythmia noted or suspected

• Concerning clinical presentation

• No high risk features• Consider using the HEART score to aid disposition

• Consider urgent outpatient cardiology referral if:• Symptoms may have plausibly been caused by coronary ischemia

• There is an opportunity to improve the patient’s current management

• Give everyone (and document) good return to ED instructions

Summary I: Very Low hs-cTnT on Arrival

• The combination of a non-ischemic ECG and hs-cTnT < 5ng/L and >3 hours since symptom onset is:

• 100% Sensitive for AMI and 94.4% sensitive for 30-day MACE

• Can rapidly and safely rule out about one-third of patients

• “Less than 5, stay alive.”

Summary II: 2-hour Rule Out

• The combination of non-ischemic ECG and 0h/2h hs-cTnT < 14ng/L AND delta 0-2h < 4ng/L is:

• 100% sensitive for AMI

• 83.3% sensitive for 30-day MACE (history matters!)

• Can safely and rapidly rule out about two-thirds of patients

• Rule out delta mnemonic: “Less than 4, out the door.”

Summary III: 2-hour Rule-In

• The combination of 0h/2h hs-cTnT ≥ 53ng/L OR delta 0-2h ≥ 10ng/L

• PPV for acute MI is 82.8% (correct ~4 out of 5 times)

• 29.3% of rule-in patients go on to 30-day revascularization

• Rule In delta mnemonic : “10 or more, Cardiology floor.”

Summary IV: Disposition

• Be cautious with patients in the observational zone

• Send a 4-hour troponin if unsure

• Rising troponin levels are always concerning

• History matters

• Unstable angina still exists.

• High risk clinical presentations are always high risk

• Consider the HEART score to assess short-term risk and aid disposition for patients without high-risk features

• The Calgary Troponin Pathway is available to help

Post-Test

Can a single high-sensitivity troponin result safely rule-out MI for ED chest pain patients?

A. No

B. Yes, but the ECG must be non-ischemic

C. Yes, but it depends on symptom duration

D. B and C

E. Yes, regardless of ECG changes or symptom duration

What cutoff can you use to rule-out MI with a single high-sensitivity troponin (hs-cTnT) if symptoms are >3hours?

A. I don’t use single hs-cTnT testing to rule out MI

B. <3ng/L (Limit of blank)

C. <5ng/L (Limit of detection)

D. <14ng/L (Upper reference limit/99th percentile)

Based on local data, the 2-hour rapid diagnostic algorithm using hs-cTnT was ___% sensitive for ruling out AMI in ED chest pain patients with non-ischemic ECGs.

A. 90%

B. 95%

C. 99%

D. 100%

Based on local data, the 2-hour rapid diagnostic algorithm using correctly rules in AMI in more than ___% of ED chest pain patients.

A. 60%,

B. 70%

C. 80%

D. 90%

Would you be comfortable adopting a rapid diagnostic algorithm using high-sensitivity troponin for chest pain patients in your practice?

A. Yes

B. No

C. I’m not sure

References

• Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;130(25):e344-426.

• Andruchow JE, Kavsak PA, Mcrae AD. Contemporary Emergency Department Management of Patients with Chest Pain: A Concise Review and Guide for the High-Sensitivity Troponin Era. Can J Cardiol. 2018;34(2):98-108.

• Chenevier-Gobeaux C et al. High-sensitivity cardiac troponin assays: Answers to frequently asked questions. Arch Cardiovasc Disease 2015; 108:132-149

• Pickering JW, Than MP, Cullen L, et al. Rapid Rule-out of Acute Myocardial Infarction With a Single High-Sensitivity Cardiac Troponin T Measurement Below the Limit of Detection: A Collaborative Meta-analysis. Ann Intern Med. 2017;166(10):715-724.

• Reichlin T, Cullen L, Parsonage WA, et al. Two-hour algorithm for triage toward rule-out and rule-in of acute myocardial infarction using high-sensitivity cardiac troponin T. Am J Med. 2015;128(4):369-379.

• Roffi M, Patrono C, Collet JP, et al. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J. 2016;37(3):267-315.

andruchow.james@gmail.com

Extra Slides

Calgary Troponin Pathway

• Design:• Prospective cohort study at Foothills Medical

Centre

• Inclusion Criteria:• CEDIS chief complaint “chest pain – cardiac

features” or “cardiac-type pain”• Age 25-years or older• Required troponin testing to rule out AMI as per

the attending emergency physician

• Exclusion Criteria:• ECG with STEMI, clear acute ischemic ECG changes

or new arrhythmia• ACS past 30-days• Renal failure on dialysis• Hemodynamically unstable

Calgary Prospective

Study

• Patients enrolled by research assistants from 8am-8pm

• Emergency physicians completed case report forms

• Troponin samples (Roche hs-cTnT)• Clinical sample collected on presentation• Research sample collected by lab at 1 and 2

hours after the initial sample• Physicians blinded to the research sample

results

• Data Sources• 30-day structured telephone interview• SCM/DIMR• APPROACH• Vital statistics

Calgary Prospective

Study

• Primary Outcome:• Index AMI

• Secondary Outcomes:• 30-day AMI• 30-day Death• 30-day MACE

• Includes AMI, death, revascularization

• *All outcomes underwent 2 physician adjudication (board certified emergency physician and cardiologist)

Calgary Prospective

Study

Calgary Study:Time 0h Troponin

Calgary Study:Time 2h Troponin

Calgary Data: hs-cTnT < 5ng/L Missed AMI

• Missed AMI Case Presentation

• 52F presents with <1h chest pain• EKG LBBB, negative Sgarbossa• ED MD Impression:

“highly suspicious for ACS”• ED MD Plan if troponin negative:

• “Cardiology consult in ED”

• hs-cTnT:• 0h: 4ng/L• 2h: hemolysed• 4h: 93ng/L• Peak: 1172 ng/L

• Outcome:• Cath next day with 100% RCA occlusion and multivessel disease• RCA stent placed, did well

• Bottom line:• Hyperacute presentation• Patient would have likely been captured by the pathway

• No missed index AMI

• Missed 30d AMI/Death Case

• 53M hx longstanding crack cocaine abuse presents with 3-6 hours chest pain• EKG no ischemic changes• ED MD Impression:

“highly suspicious for ACS”• hs-cTnT:

• 0h: 9ng/L

• 2h: 8ng/L

• Pain free and normal ECG and discharged home

• Returned 2-hours later with new chest pain and transient STE Lead III• Repeat hs-cTnT 16, 44ng/L• Had cath same day showing 100% RCA occlusion, coronaries too ectatic for

intervention, recommended medical management and cocaine cessation• Declined addictions consult and discharged• Cardiac arrest 12-days later and died

• Bottom line:• High risk patient missed by the pathway

Calgary Data: 2h algorithm missed 30d AMI