Should Troponin be a Vital Sign? Perhaps, but only if Interpreted Using Pre-test Probability.

An 80-something non-english speaking patient complained of vertigo.  He was asked multiple times about chest pain or dyspnea, but repeatedly denied any such symptoms.

His vital signs were all normal.  His exam was normal.

He had a triage ECG at time 0 (ECG-1):

Computer read, with Physician overread: Sinus rhythm.  Possible right ventricular conduction delay. What do you think?

When I saw this without any other information, I said it was very suspicious for a high lateral MI.  In aVL, there is a tiny QRS with 0.5 mm of STE, and there is reciprocal ST depression in inferior leads.  If you see this, you must very closely question the patient about any chest symptoms, and even if no relevant symptoms, to be certain to look for old ECG, and to do serial ECGs and troponins.

There actually was an old ECG from about 4 years prior (ECG-2), which I’m not sure anyone saw:

Here the limb leads have much higher QRS voltage, without a correspondingly larger ST-T voltage. This means that the ST-T is out of proportion to the QRS on ECG-1

The clinicians did not see the finding on ECG-1.

The clinicians later stated they had had no suspicion of ACS, but that the faculty wanted a troponin anyway.  So troponin was ordered, and it returned some time within the next few hours (uncertain exactly when they saw it):

Troponin I = 27 ng/mL (900 x the upper limit of normal)

A 2nd ECG was recorded at 3 hours (ECG-3):

Computer, and physician overread:  Minimal ST depression What do you think?

The STE in aVL and STD in III and aVF is more pronounced, and now there is STD in V2 and V3.  This makes it diagnostic of a posterolateral OMI (especially with the troponin!).

A 3rd ECG was recorded at 3.5 hours (ECG-4):

Computer, and physician overread:  Minimal ST depression This is about the same.

This was in the chart:
“Troponin found to be elevated to 27. Patient denied chest pain on initial review of symptoms. Was now endorsing chest pain which began 30 minutes ago. Upon further questioning, he states that he has had intermittent chest pain since yesterday. Pain worsens when lying flat and improves with sitting up. Given 324 mg aspirin. Repeat ECG shows modest ST elevation in I and aVL and depression in inferior leads.”

The cath lab was activated.

Angiogram:
LM 30% ostial.
LAD 80% mid
LCx occluded mid (acute infarct lesion)
RCA 80% mid. distal stent patent.
PCI mid LCx

So this is an OMI (Occlusion Myocardial Infarction), but not a STEMI

Echo:
Decreased left ventricular systolic performance, mild/moderate.
The estimated left ventricular ejection fraction is in the range of
35-40%.
Regional wall motion abnormality (WMA):
Regional WMA: Inferobasal (this is another name for posterior), akinetic, small.
Regional WMA: Lateral, large, hypokinetic.

The patient went into cardiogenic shock and ultimately died of this MI.

Discussion

There are many, cardiologists especially, who think that Emergency Physicians order too many troponins.  Many come back “positive” and trigger many often unnecessary downstream tests.  In our UTROPIA study (NCT02060760), from which there are many publications, 85% of “positive” troponins (at least one value above the 99th %-ile upper reference limit (URL), were either type II MI or non-MI myocardial injury (acute or chronic myocardial injury).

Sandoval Y et al. Type 1 and 2 Myocardial Infarction and Myocardial Injury: Clinical Transition to High-Sensitivity Cardiac Troponin I.  American Journal of Medicine 130(12): 1431-1439, Dec. 2017.

Important: this was not due to high sensitivity troponin; the number of troponins greater than the 99% URL was lower with high sensitivity troponin I than with contemporary troponin I.

We published another study (see below) showing that, as expected, patient selection greatly influences the positive predictive value of troponin.

My opinion on this:

It is not that we necessarily order too many troponins.  However, we use the 99th percentile cutoff as a cutoff for diagnosis of type I MI, and too often assign a diagnosis of type I MI simply because there is a troponin above that URL.  It is this interpretation of the test which is often inappropriate, not necessarily the ordering of the test.  Only in the right clinical context is a slightly elevated troponin highly suspicious for type 1 MI.

However, no matter the clinical context, a troponin that is 30x, 100x, or 500x the URL is indeed most likely to be type I MI.

This figure comes from the Diamond T study (all type 1 MI were NSTEMI, not STEMI):

Notice that the 6 hour value (far right) is very low for type 2 MI.

Sandoval Y.  Nelson SE.  Smith SW.  Schulz KM.  Murakami M.  Pearce LA.  Apple FS.  Cardiac Troponin Changes to Distinguish Type 1 and Type 2 Myocardial Infarction and 180-Day Mortality Risk.  Acute Cardiovascular Care 2014;3(4):317-325.

Abstract

• For clarity — I have combined in Figure-1 the first 2 ECGs done in the ED, as well as the prior tracing done on this patient.

Figure-1: The first 2 ECGs done in this case, together with a prior tracing done 4 years earlier (See text).

• As per Dr. Smith — there is a tiny QRS complex in lead aVL, with what appears to be 0.5 mm of coved ST elevation. There is an equally tiny QRS complex in lead III, with subtle-but-real scooping depression that looks to be the “mirror-image” of the subtle ST elevation in lead aVL. Similar suggestion of reciprocal change is seen in lead aVF — but not in lead II. While I thought these changes were far from definitive — I agree with the excellent point emphasized by Dr. Smith = this clearly could represent OMI (high-lateral MI?), and the case needs immediate attention.
• Additional Thoughts about this 1st ECG: There is an RSr’ in lead V1 — with a QRS complex of normal duration. The question arises as to whether this represents incomplete RBBB? Technically, it does not — because there is no terminal s wave in lateral leads I and V6. I generally acknowledge this finding by simply writing, “RSr’ in lead V1”. Of note — transition is early (a prominent R wave is already forming by V2, and the R wave becomes predominant by lead V3). Of note — T waves are upright in all 6 chest leads. Often with complete or incomplete RBBB — there is ST-T depression in lead V1, and sometimes also in V2 and V3. Given our concern about possible subtle high-lateral OMI — this raises the question whether the upright T waves in leads V1 and V2 of this 1st ECG might be abnormal and reflect ischemia. I wasn’t certain of the answer to this from assessment of this single tracing.
• There are tiny initial q waves in multiple leads — including leads I, II, III, aVL, aVF, and V4,5,6. I suspected these small and narrow q waves seen in multiple leads were not significant.

• As per Dr. Smith — QRS amplitude in the limb leads was greater on the prior tracing. In addition — there is slight axis shift (ie, the QRS complex is almost entirely negative in lead III of the prior tracing — whereas it appears to be isoelectric in the 1st ECG). This is relevant — because the T wave inversion that we see isolated to lead III in the prior tracing is not necessarily abnormal (ie, T wave inversion may be normal when isolated to either lead III or aVF if the QRS complex in the same lead is predominantly negative).
• We do not see any hint of ST coving or elevation in lead aVL in the prior ECG. That said, given the axis shift that has occurred, with different QRS morphology now seen in aVL, I wasn’t sure about the significance (if any) of this change.
• A monophasic R wave, equal in amplitude to the thin S wave in lead V1 is seen in the prior tracing. There was no hint of the RSr’ seen in the 1st ECG. Transition was again early in the prior tracing (R=S by V2, with a predominant R wave by V3). Of note — the T wave was also positive in all 6 chest leads on this prior tracing — so this T wave positivity in all 6 chest leads is not a new finding.
• BOTTOM LINE — I didn’t think the prior tracing clarified the situation. We were still left with potential concern regarding the changes noted above for the initial ECG.

• In the 3 hours that passed since the 1st ECG was done — there is now clearly more coved ST elevation in lead aVL — and — more mirror-image ST depression (reciprocal change) in leads III and aVF. In addition, the 3rd inferior lead ( = lead II) now shows suggestion of reciprocal ST depression.
• In the anterior chest leads, since the 1st ECG was done — there is now J-point ST depression in leads V2 and V3 that was not previously present.
• In the lateral chest leads — there now appears to be slight-but-real ST elevation, with beginning T wave inversion in leads V5 and V6. Although admittedly difficult to assess because of baseline artifact in leads V5 and V6 in both tracings — I do think the new ST elevation in these leads is real.
• BOTTOM LINE — Even without the markedly increased Troponin in this case — the sequential ECG changes described above that developed between the time the 1st and 2nd ECGs were done (a time span of 3 hours) are diagnostic of acute postero-lateral OMI.

• Our THANKS to Dr. Smith for presenting this case.