What happens when you give morphine for chest pain in ACS? And what is pseudo-normalization of T-waves?

Written by Magnus Nossen, with edits by Smith

The patient in today's case is a 70-year-old farmer. He has a history of coronary artery disease and a STEMI two years prior that was treated with primary PCI. He contacted EMS due to acute onset chest pain and feeling unwell and fatigued. He was given ASA and sublingual NTG and taken to the ED. 

At the time of this initial ED ECG, his symptoms were improving

ECG #1 on admission to the ED

The patient was not seen quickly in the ED as it was a busy shift and the ECG did not meet STEMI criteria. 

He subsequently developed worsening chest pain. 

The below ECG was recorded. Does this repeat ECG shed any light on what is going on? 

ECG #2 repeat in the ED.

These two ECGs look similar at first glance. 

However, there are very important dynamic changes between the two recordings. 

The first ECG, taken after NTG administration and during pain relief, shows signs consistent with re-perfused lateral and posterior OMI. There are T-wave inversions in leads I and aVL. Also of note are tall T-waves in the right precordial leads. These anterior T waves are not hyperacute, but rather a result of posterior wall reperfusion. (Posterior reperfusion T-waves). The inferior T-waves are also large because they are reciprocal to the lateral reperfusion. 

If you look closely at the two ECGs side by side, you can see the dynamic change.  Below, I have placed the ECGs side by side for comparison  

On the repeat ECG, the T-waves in aVL are not nearly as negative as they were on the admission ECG. The T-wave amplitude in the inferior and anterior leads is decreasing. This, in the context of worsening chest pain, is evidence of reocclusion of the infarct-related artery and active OMI in development. 

Chest pain was increasing at the time of ECG #2 which prompted evaluation by the physician caring for the patient. 

The patient was placed on an NTG drip and given morphine. 

The subtle ECG changes were not recognized. 

After NTG and morphine, the patient's symptoms improved. The ECG below was recorded. What do you think?

ECG #3 while on NG drip and after morphine

At this point, the patient reported less severe symptoms, although he still had chest pain. The improvement in symptoms was attributed to the NTG drip. The following was noted in the patient's chart. "Pain is improving and ischemic T-wave inversions are no longer present". 

This assessment is incorrect. The ECG clearly shows worsening ischemic changes. ECG #3 shows evolution of reocclusion, now with upright T-waves in I and aVL (this is called pseudonormalization), inferior reciprocal ST depression in inferior leads (with down-up T-waves), and increasing STD in precordial leads with decreasing T-wave amplitude (also due to reocclusion to blood supply to the posterior wall).  This is all diagnostic of active (not reperfused) acute posterior  OMI.  

These are obvious OMI findings that do not meet STEMI criteria. 

Pain improvement cannot be due to NTG with the above ECG. 

It must be a result of the morphine that was administered. 

These findings were not recognized, and because the patient (after morphine) reported improved symptoms, urgent coronary angiography was not performed. 

The troponin I on admission was 54ng/L. The repeat troponin I the following morning returned at 27.890ng/l.  This has become a very large infarction.

Below is the Queen of Hearts (QoH) interpretation for each of the ECGs in today's case. For ECG #1 she sees reperfused OMI, for ECG #2 she sees reperfused OMI but with low confidence (as the artery is re-occluding). ECG #3 is easily recognized as OMI and the AI model recommends immediate revascularization

The patient in today's case received suboptimal care and suffered a substantial myocardial infarction. He eventually underwent CAG, where a circumflex occlusion was stented. Despite the delayed therapy, the patient did well clinically.

This case highlights how T-waves are very important in the assessment of ischemia and dynamic changes in acute coronary syndrome. 

T-wave inversions in the acute phase of ACS are usually a welcome finding, indicating reperfusion. 

If TWI disappears or reverses, always consider re- occlusion (pseudonormalization)! 

I have often seen colleagues worry about T-wave inversions as a sign of ongoing ischemia.  But T-wave inversion in leads overlying the infarcted territory is a good sign: a sign of reperfusion. 

If there is persistent (not decreasing) chest pain and T-wave inversions, there is usually some type of secondary cause of inverted T waves such as LVH or wide QRS complexes. 

Here is an old (2015), but still very relevant, lecture on T-wave inversion by Dr. Smith: 

40 minute lecture on T-wave inversion

Learning points: 

• T-waves are often dynamic in ACS and may hint at reperfusion and re-occlusion before the ST-segment does. 
• In a patient with ACS symptoms disappearing TWI should be considered re-occlusion of the infarct related artery. 
• Be careful before administering morphine as it will improve pain. 
• T wave inversions are often caused by reperfusion.

Smith: Never give opiate pain relief unless you are committed to the cath lab!!  You will obscure the symptoms and think that your medical management is working to relieve ischemia, when it is only relieving pain!!

Here is evidence for this:

Opiates are associated with worse outcomes in Myocardial Infarction.

See this case: A man his 50s with chest pain. What happens when you treat with morphine rather than with reperfusion?

----See this study showing an association between morphine and mortality in ACS:
Use of Morphine in ACS is independently associated with mortality, at odds ratio of 1.4. Meine TJ, Roe M, Chen A, Patel M, Washam J, Ohman E, Peacock W, Pollack C, Gibler W, Peterson E. Association of intravenous morphine use and outcomes in acute coronary syndromes: Results from the CRUSADE Quality Improvement Initiative. Am Heart J. 2005;149:1043–1049.

And Another that we wrote:

----Bracey, A.  Meyers HP.  Smith SW.  Wei L. Singer DD.  Singer A.  Association between opioid analgesia and delays to cardiac catheterization of patients with occlusion Myocardial Infarctions. Academic Emergency Medicine 27(S1): S220; May 2020.  Abstract 556.

Main result: STEMI(-) OMI Patients

65 (23.9%) patients were found to have STEMI(-) occlusion myocardial infarction (OMI) at the time of cardiac catheterization. The 45 patients with STEMI(-) OMI without pre-cath opioids had a door-to-balloon time of 75 minutes, vs. 684 minutes for the 25 STEMI(-) OMI with pre-cath opioids.

High Risk ACS guidelines are only followed in 6% of patiients:

Lupu L, Taha L, Banai A, Shmueli H, Borohovitz A, Matetzky S, Gabarin M, Shuvy M, Beigel R, Orvin K, Minha S ’ar, Shacham Y, Banai S, Glikson M, Asher E. Immediate and early percutaneous coronary intervention in very high-risk and high-risk non-ST segment elevation myocardial infarction patients. Clin Cardiol [Internet]. 2022;Available from: https://onlinelibrary.wiley.com/doi/10.1002/clc.23781

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MY Comment, by KEN GRAUER, MD (3/14/2025):

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Today’s case is marked by an important and fundamental oversight that significantly delayed optimal treatment.

• This all-too-commonly occurring oversight stems from a failure to appreciate the sequential ECG changes that should be expected during the course of an acute evolving infarction.
• The Theory is Simple: Depending on the area of the heart involved — ST segments will elevate with inferior, lateral or anterior OMI when the "culprit" artery occludes — and return to baseline on the way toward T wave inversion when the culprit artery reopens (regardless of whether the artery is reperfused by PCI or thrombolysis — or opens spontaneously).
• The opposite occurs with posterior OMI (ie, there is ST depression with acute occlusion, that is maximal in leads V2,V3,V4 — with return of ST segments to baseline on the way toward developing tall, peaked chest lead T waves that are maximal in leads V2,V3,V4 when the occluded RCA or LCx reopens).
• KEY Point: Correlating each serial ECG to the presence and relative severity of CP at the time each each is done (ie, by a CP "scale" from 1-to-10 that is noted on the chart) — provides an important clue to the state (open or closed) of the "culprit" artery. For example, if posterior reperfusion T waves become less tall and less peaked with a sudden increase in CP severity — this could be a worrisome sign that the "culprit" RCA or LCx is once again occluding (and that ischemic ST depression will soon follow). This fundamental oversight occurred in today's case.

Reviewing the History:

The history in today's case immediately places this 70-year old man in a higher-risk group for an acute event simply because: i) The patient has known coronary disease; and, ii) He experienced the onset of new CP severe enough to call EMS.

• While delays happen in a busy ED when there are more acute patients than clinicians to care for them — delay should not happen for a higher-risk patient because, “STEMI criteria are not met".
• Along the way — Morphine should not be used to determine if prompt cardiac cath is indicated (as it apparently was in this case). Morphine could have been given early on in today's case — because sudden onset of new CP in a patient with known coronary disease and an obviously abnormal initial ECG is already indication for prompt cath. 
• Once you know that prompt cath is needed (because history, ECG findings and troponin indicate acute coronary occlusion) — chest pain relief assumes high priority. But relieving CP before you establish the diagnosis of acute OMI masks symptoms, and only serves to delay the needed PCI (as occurred in today's case).

Reviewing the Serial ECGs:

For clarity and ease of comparison — I’ve put representative complexes from each of the 3 tracings in today’s case together in Figure-1.

• As noted by Dr. Nossen, although the initial ECG does not satisfy millimeter-based STEMI criteria — this tracing is markedly abnormal. It is diagnostic of acute postero-lateral OMI. Consistent with the clinical history of reduced CP at the time ECG #1 was recorded — this initial tracing already suggests spontaneous reperfusion because: i) There is deep T wave inversion in lead aVL; ii) The reciprocal of this lead aVL finding is seen in the form of terminal T wave positivity in each of the inferior leads; and, iii) Chest leads show overly tall, T wave peaking that is maximal in leads V2,V3,V4. 

KEY Point: As emphasized by Dr. Nossen — unless you place the serial ECGs you are assessing side-by-side — it is all-too-easy to overlook the "tell-tale" dynamic ST-T wave changes that become obvious when looking at Figure-1.

• Prove to yourself that there have been dynamic ST-T wave changes. Look lead-to-lead — and compare the relative size of ST-T waves in ECG #1 vs those in ECG #2. 
• If you look carefully — Isn't there a difference in ST-T wave appearance in no less than 10/12 leads? 
• Although the amount of change in ST-T waves between these 2 tracings may not be great in some leads — the consistency in the direction of these changes is unmistakeable (ie, T wave inversion and T wave peaking are clearly more accentuated in ECG #1 at the time the patient arrived in the ED and CP was decreasing after NTG).

Now look lead-by-lead and compare ST-T wave appearance in ECG #2 (at which time CP was increasing) — with ECG #3 (when CP was reduced by IV NTG and morphine).

• Isn't there a difference in ST-T wave appearance in virtually all leads?

BOTTOM Line: Lead-by-lead comparison between today's 3 serial tracings, when correlated to this patient's coming-and-going of CP — tells a convincing story of acute LCx occlusion.

• Relief of this patient's CP at the time ECG #1 was recorded — is consistent with the above described ECG signs of spontaneous reperfusion of this postero-lateral OMI.
• These reperfusion ST-T wave changes lessened in association with ECG #2 — because this repeat tracing was recorded at a time when CP had returned (ie, on the way toward developing high-lateral lead ST elevation and anterior lead ST depression from postero-lateral OMI).
• ECG #3 reflects further progression of "culprit" artery reocclusion — with ST elevation now clearly beginning in lead aVL — with more acute-looking reciprocal ST depression in inferior leads — and more acute-looking changes across the chest leads.
• Even allowing for failure to recognize acute OMI after ECG #1 — and failure to recognize acute OMI after ECG #2 — awareness of the fundament concept of sequential ECG changes discussed above is essential for the goal of optimizing salvage of viable myocardium (and at least recognizing acute OMI and the need for timely cath from ECG #3). 
• The lesson from today's oversights needs to be learned. 

Figure-1: Comparison between the 3 ECGs in today's case.