SURAJ RAHEJA, MD

MICHIGAN HEART AND VASCULAR, ANN ARBOR, MI

MAKING SENSE OF TROPONIN LEVELS

DISCLOSURES

None

WHAT IS TROPONIN?

• Complex of 3 proteins (Troponin C, Troponin I, Troponin T) involved in calcium processing in skeletal + cardiac muscle

• When myocytes are damaged or undergo cell death, the TnI spills into the bloodstream and can be measured

• The assays are highly sensitive, and continue to detect smaller amounts of troponin, but as a result can have poor specificity

• A “positive troponin” alone does not equal MI!

• The presence of detectable troponin indicates the presence of myocardial strain or injury but not the cause

• Therefore, it should be used in combination with clinical history, provider suspicion, and EKG findings

ELEVATED TROPONIN LEVELS & OUTCOMES

Any level of Troponin whether due to myocardial injury or infarction is worse than no troponin.

Higher Troponin is worse than lower Troponin.

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• Kaplan-Meier survival curves in the 3 patient groups (unadjusted log-rank test P< .0001)

• Patients with myocardial infarction had a lower survival than patients with non-elevated troponin values (P < .0001)

• The survival in patients with myocardial injury was reduced compared with patients with myocardial infarction and non-elevated troponin (P < .0001 in both)

Elevated Troponin Levels & Outcomes

THE “HIGH SENSITIVITY” TROPONIN

New assays are able to detect much lower concentrations of the troponin protein

All things evolve with time. Old assay being phased out by manufacturers

Standard in Europe, becoming standard in US

Faster decision: Can provide earlier and more accurate information about myocardial injury

Evidence suggestive of improved ED efficiency, diagnosis, throughput and patient satisfaction

Because of the increased sensitivity, however, a significant percentage of patients without an acute coronary syndrome may have detectable hs-Trop

WHY USE HIGH SENSITIVITY TROPONINS?

Increasing the sensitivity of the troponin assay will allow providers to be more likely to detect troponin elevations/changes, miss fewer patients with plaque

rupture / ACS / USA, and enable patients to be discharged home more reliably

GENERAL POINTS ABOUT THE TEST

Classic assay measured in ng/mL -> New HS Trop assay in ng/L

Value is 1000x previous

Trop of 0.50 ng/mL = 500 ng/L

Trop of 8.5 ng/mL = 8500 ng/L

Trop of 100 ng/mL = 100,000 ng/L!

Assays not equivalent

Old assay ULN typically <0.04 ng/mL

HS assay upper limit of normal for

Men = 20 ng/L

Women = 15 ng/L

WHEN IS AN ABNORMAL HS-TNI AN ACUTE MYOCARDIAL INFARCTION?

Fourth Universal Definition of Type 1 Myocardial Infarction Detection of a rise and/or fall of cTn values with at least one value above the 99th percentile

URL and with at least one of the following:

Symptoms of acute myocardial ischemia

New ischemic ECG changes

Development of pathologic Q waves

Imaging evidence of new myocardial viability loss or new regional wall motion abnormality

Identify coronary thrombus by angiography

Positive predictive value: How accurately does an elevated troponin value reflect myocardial infarction?

If the PPV values are only in the range of 60%, what are the types of patients that have elevated troponins but no acute MI or coronary syndrome?

Type 1 MI is acute coronary

syndrome (ACS)

Type 2 MIs are supply-demand

mismatch

Type 1 MI vs Type 2 MI

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Whole number reporting (ng/L vs ng/mL decimal points) helps reduce confusion amongst multiple providers

Turnaround time from lab receipt of sample to result should be maintained at < 60 minutes (to make utility of lab as a rapid rule out / trend value)

Abnormal hs-cTn values reflect injury to myocardial cells, but do not indicate the underlying mechanism of injury

MI is clinical diagnosis not defined by troponin alone. Evidence of myocardial ischemia by clinical exam and/or EKG required, plus serial change in troponin (rise/fall) +/- myocardial imaging changes or thrombus by coronary angiography

Must use clinical judgment for differentiating non-ischemic injury vs myocardial infarction, then differentiate myocardial infarction etiology into severe illness / supply-demand mismatch vs plaque rupture / intracoronary thrombus

Rise in hs-cTn is faster than the prolonged duration of fall, related to size of MI and ultimate vessel patency

New ED algorithm could reduce ED time / observations / admissions

Will increased sensitivity of myocardial injury increase LOS and testing?

hs-TnI values which are rapidly or substantially increasing raise the likelihood of AMI

Higher values of detectable troponin are also associated with worse short and long-term cardiovascular morbidity

TIMING MATTERS AND SERIAL SAMPLING IS IMPORTANT

Delta values are generally not applicable if symptoms occurred greater than 12 hours prior to presentation

ACUTE OR CHRONIC INJURY?

Troponin does not differentiate acute from chronic injury

ACS should display a rise (and eventual peak) in hs-TnI over time

Chronic conditions that produce an elevation of hs-TnI rarely show an increase over time intervals of 1 to 2 hours.

A decrease in hs-TnI over time can indicate an acute injury that occurred days ago but is less specific for ACS

Chronic renal failure

10% of renal patients will have a chronically elevated hs-TnI

For chronically elevated patients, there is no absolute change clearly significant in the literature. Some have used 20% change as significant. Studies addressing this population have not been done

INTERPRETING HS-TNI

Use the lab to help differentiate myocardial injury vs infarction, and use serial samples when appropriate

Patients will fall into one of four categories:

Undetectable (very low hs-TnI), candidates for expedited discharge

Detectable but normal (below 99th percentile). Clinical suspicion and changes in levels between samples are important to determine significance

Mildly elevated / positive (above 99th percentile). Elevated risk but clinical suspicion and changes in levels determine significance. Some pts with chronic illness may have a baseline level in this range

Significantly elevated / positive. High risk patients, but may include some chronic illness patients

Time to discharge from ED reduced overall by 79 minutes | Mean total costs reduced by 20%

Conclusions: Use of hs-cTn does not lead to increased or inappropriate use of coronary angiography, but is associated with improved rule-out process, reduces need for stress testing

and time to discharge

Before hs-cTn assay After hs-cTn assay Statistical Significance

Use of stress testing 29% 10% p < 0.001

Rate of LHC / coronary angiography

23% 23% p = 0.092

Rate of LHC finding no disease

11% 7% p = 0.361

Discharge Diagnosis: Acute MI

10% 14% p < 0.01

Discharge Diagnosis: Unstable angina

14% 9% p < 0.01

SUMMARY AND KEY POINTS

Protocols for hs-trop rule-out are designed to have high negative predictive values for ED rule out patients,

but do not necessarily have good specificity for acute myocardial infarction.

Understanding the difference between myocardial injury and infarction is critical to interpreting hs-TnI

correctly.

Incorporation of clinical context and risk-stratification is key to guiding appropriate care of patients.

The lower the hs-TnI value and the less the delta between samples, the higher the negative predictive value.

The higher the hs-TnI value and the bigger the delta between samples, the more likely AMI is present.

Acute MI is defined by labs and clinical changes, not troponin value alone.

CLINICAL CONTEXT IS CRITICAL TO INTERPRETATION!

Use clinical context, and do not rely on the test alone!

- Does the patient have a suspicious history for ACS?

- Is there evidence of ischemia?

- Is there any acute rise and fall in the troponin results?

- What is the absolute value of the troponin abnormality?