Friday, November 8, 2019

A 41 year old with chest pain and a Nondiagnostic Triage ECG. Thrombolytics prior to transfer for PCI.

This was sent by Tom Fiero, from Merced CA, and an avid reader of the blog.

"A 41 yo man presented with sudden severe chest pain, onset 1 hour prior to arrival."

"Here is the first ED ECG at 2242:"
What do you think?

"My partner was shown the ECG and he was not impressed."

"30 minutes later, I picked up the patient and saw this ECG, and I was concerned."

"I was worried about the slight ST depression in lead aVL, and the morphology of aVL."

"I sought a previous ECG and found one from 9 months prior:"
Smith analysis:

Much different
However, much of the difference may be due entirely to the QRS axis. 
1. QRS axis = approximately 45 deg in the old ECG, but 90 degrees (vertical) in presentation ECG.
2. T-wave axis is 30 degrees in the old ECG and 90 degrees in the presentation ECG.

Old ECG: QRST axis = ~15 degrees

Presentation ECG: QRST axis = ~ 0 degrees 

So there really is no significant change in the QRST axis, which measures T-wave inversion, but there is a change in both the QRS axis and the T-wave axis, and I don't really know the significance of this.  Nevertheless, I agree with the reader that aVL looks suspicous, but not diagnostic.

Dr. Fiero continues:
"At this point, the patient was also diaphoretic.  I ordered aspirin and heparin bolus.  BP was 220/110.  I ordered sublingual NTG.  I would order a NTG drip, but it holds up stat ground transfer because it requires a critical care nurse. So I ordered labetolol."

Then I ordered another ECG at 2316
"This is now obvious."
Smith: Agree.  Clearly an Inferior OMI

"I ordered TNK-tPA (Tenectaplase), since the transport time is too long to rely on PCI alone."

Smith comment:
1. If first medical contact to balloon time is greater than 120 minutes, which happens in more than 50% of transfers, then give thrombolytics and transfer for immediate PCI upon arrival.

Stated otherwise:

2. If door (at referring hospital) to balloon (at receiving center) time is greater than 90 minutes, then give thrombolytics.  When transport time is greater than 30 minutes, door to balloon time is greater than 90 minutes in more than 50% of cases.

"The patient was still having chest pain."
"Door to needle is greater than 90 minutes, hence TNK."
"And I recorded the 3rd ECG:"

More obvious still

"At this point, the patient was looking and feeling better.  We loaded him up and sent him."

"Before leaving, he admitted to amphetamine abuse about 10 hours prior to presentation."
"I thought I was maybe over-reacting with first ECG."
"Then I got the old EKG, and he looked ill, and I realized I was not overreacting."

The patient reperfused his RCA and had a good outcome.

Smith comments

A couple further points on thrombolytics prior to transfer:

1. Clopidogrel is a good idea and proven beneficial when giving thrombolytics for STEMI.  The dose in this situation is 300 mg.
-----Neither Prasugrel nor Ticagrelor have been studied, nor clopidogrel at a dose of 600 mg.
2. ASSENT-3 showed that the best antithrombotic for STEMI who are receiving thrombolytics is enoxaparin.

This is the dosing regimen 
(all regimens must be agreed upon between the referral and receiving institutions):
STEMI with thrombolytics, even if followed by transfer with immediate PCI:
Enoxaparin is the optimal choice:
  If less than 75 years old: 30 mg IV bolus,  followed in 15 min by 1 mg/kg subQ (max 100 mg)
  If over 75 years: No bolus, 0.75 mg/kg subQ (max 75 mg)

Transfer of patients with STEMI and use of thrombolytics
Dr Meyers and I wrote the ACS chapter in the EmRap “CorePendium” (Compendium of Emergency Medicine, an online Textbook).  Here is the section on Transfer of STEMI patients which I wrote. 
Transfer for PCI-only vs. thrombolytics prior to transfer for STEMI
  • If delay from first medical contact to PCI will be greater than 120 minutes (and it almost always is)
    • Then Thrombolytics first
  • If delay is less than 120 minutes, then transfer for PCI without thrombolytics
Facilitated PCI (thrombolytics) with full adjunctive antithrombotic therapy and P2Y12 inhibition, when patient cannot get PCI within one hour for STEMI
  • STREAM study (Armstrong et al. 2013). Patients presenting to non-PCI hospital.  All transferred.
  • Randomized to:
    • 1) TNK-tPA before transfer
      • Standard dose bolus tenecteplase (½ dose in patients over 75 years of age) with clopidogrel 300 mg and enoxaparin (30 mg IV + 1 mg/kg subcutaneous) before transport to a PCI-capable hospital.
    • 2) No TNK-tPA before transfer
  • PCI-only group:
    • Patients in the PCI-only group were treated very fast, with 100 minutes from symptom onset to sheath insertion (Armstrong et al. 2013)
  • Thrombolytic before PCI group:
    • Emergency coronary angiography was performed if fibrinolysis failed (this was measured by resolution of pain and ST-segment elevation on the ECG). 
      • Thus, it is analogous to planned rescue PCI (see Rescue PCI below)
    • Otherwise, angiography was performed 6 to 24 hours after randomization. 
  • The primary endpoint was a composite of death, shock, congestive heart failure, or reinfarction up to 30 days. 
  • Results:
    • 36% of lytic patients required urgent PCI.  Mean time from randomization to angiography for these patients was 2.2 hours, vs. 17 hours for the other 64%. 
    • The primary end point occurred in 116 of 939 patients (12.4%) in the fibrinolysis group with rescue, and in 135 of 943 patients (14.3%) in the primary PCI group (p=0.21
    • Intracranial hemorrhage was 1.0% for TNK-tPA vs. 0.2%.
  • Conclusion: Transfer for PCI without thrombolytics is best if PCI at receiving facility can be done in less than 120 minutes from first medical contact, or less than 90 minutes from STEMI diagnosis in first ED.
Thrombolytics prior to Transfer to a PCI capable facility, then rescue PCI if no reperfusion for STEMI
  • TRANSFER AMI (Cantor et al. 2009).
  • High risk STEMI: BP less than 100, HR greater than 100 Killip class II, III, ST depression of at least 2 mm in precordial leads, ST elevation in right precordial leads (right ventricular MI
  • All patients get TNK-tPA.
  • 80-90% received clopidogrel 300 mg (75 mg for age over 75).
  • Enoxaparin (not for age over 75) or UFH (50-50).  Doses not specified, presumably standard doses.
  • Patients randomized to: 
    • 1) Standard Rx:
      • Transfer only if there is persistent ST elevation (less than 50% ST resolution)
      • No transfer if there is reperfusion (ST resolution)
    • 2) Transfer with immediate PCI regardless of reperfusion.
  • Results: Intervention group had PCI a median of 2.8 hours after randomization
    • 30-day severe adverse outcomes 17.2% vs. 11.0% (NNT = 16)
  • Conclusion: All high risk STEMI should be immediately transferred after thrombolytics
Thrombolytics prior to transfer to a PCI capable facility, then routine PCI regardless of reperfusion for STEMI
  • CARESS-in-AMI (Di Mario et al. 2008)
    • Patients: High risk STEMI, had at least one high risk feature treated initially at non-PCI hospital
      • Extensive ST elevation, new LBBB, previous MI, Killip class greater than or equal to 2, LVEF less than 35%
    • ½ dose reteplase, abciximab, heparin, aspirin, only 1 in 6 received upstream clopidogrel, but this is probably not so important because they did receive DAPT using abciximab.
    • Randomized to:
      • Immediate transfer for PCI or
      • Standard therapy: Transfer for rescue PCI only if needed
    • PCI in 85.6% of immediate group; rescue PCI in 30.3% of standard group
    • Median time from thrombolytics to transfer = 110 minutes in immediate group vs. 180 minutes in rescue group.
    • Composite of all-cause mortality, reinfarction, and refractory myocardial ischemia within 30 days (4.4% versus 10.7%, p = 0.004) in the immediate PCI group vs. standard care/rescue PCI group (NNT=17). 
      • No significant differences in major bleeding at 30 days (3.4% versus 2.3%, P0.47) or stroke (0.7% versus 1.3%, P0.50).
  • Meta-analysis including both high risk and non-high risk patients
    • Concluded that all patients should be transferred for early routine PCI after thrombolytics (Borgia et al. 2010).  
    • Early was defined as less than 24 hours. However, the figure below from an editorial (Granger 2011) representing the 7 trials in the meta-analysis shows that the time to PCI was usually very short.
  • Conclusions: 
    • All high risk patients who receive thrombolytics prior to transfer should have immediate angiography +/- PCI at the receiving facility, regardless of reperfusion status (in other words, not only the patients who need rescue PCI).  
    • Among non high risk patients who do not need rescue PCI, also consider immediate angio +/- PCI after a delay of 2-3 hours (O’Gara et al. 2013).
Half dose thrombolytics prior to transfer to a PCI capable facility for STEMI
  • Half dose thrombolytics prior to transfer appears to be a attractive option, without an increase in major bleeding. (Larson et al. 2012)           
    • Not a randomized trial
    • STEMI receiving center, with some referral hospitals are more than 60 miles distant
    • Compared to STEMI patients presenting directly to the receiving hospital
    • All received aspirin, clopidogrel, and unfractionated heparin (UFH) 
    • Those presenting to hospitals ≥60 miles away also received half-dose fibrinolytic with transfer for immediate PCI. 
    • Total 2634 consecutive STEMI patients from all sources 
      • 660 transferred from remote hospitals utilizing half-dose tenecteplase (TNK-tPA) 
      • 600 patients who presented directly to the PCI centre. 
      • Door to balloon time for direct vs. transfer: (mean +/- CI): 62 (44-83) vs. 122 (100-147)
      • No significant differences in 30-day mortality (5.5 vs. 5.6%; P= 0.94), stroke (1.1 vs. 1.3%; P= 0.66), major bleeding (1.5 vs. 1.8%; P= 0.65), or re-infarction/ischaemia (1.2 vs. 2.5%; P= 0.088) in patients receiving TNK vs. those presenting directly to the PCI centre, despite a significantly longer door-to-balloon time
Summary: Combination Reperfusion Strategies (Thrombolytics + PCI)
  • First, it is important to realize that only a percentage of STEMI patients who do not receive thrombolytics are actually transferred for PCI in a timely fashion, and thus thrombolytics prior to transfer should be strongly considered.
    • When drive time is over 30 minutes, only 42% of patients achieve first door to balloon time in less than 120 minutes.  Recommended time is first medical contact to balloon of time of less than 120 minutes (Vora et al. 2015).
  • Thus, according to the ACC/AHA, immediate transfer after thrombolytics is recommended:
    • For all failed reperfusion (for rescue PCI), ST resolution at least 70%
    • For all high risk patients
    • For all other patients, it is reasonable to transfer
Finally, Half dose thrombolytics prior to transfer appears to be a attractive option, without an increase in major bleeding. (Larson et al. 2012)

MY Comment, by KEN GRAUER, MD (11/8/2019):
Interesting case by Drs. Tom Fiero and Stephen Smith, in which the title of this post tells all = “A 41yo with Chest Pain and Nondiagnostic Triage ECG”. My comments are focused on Lessons Learned” from the first 3 tracings shown.
  • For clarity — I’ve put these first 3 tracings shown together in Figure-1.
  • Please NOTE: My Comments below are subtle and clearly advanced. Are you up for the challenge?
Figure-1: The first 3 ECGs shown in this case (See text).

ECG #1: As is often the case — the History is KEY.
  • The patient is a 41yo man who presented with sudden severe chest pain that began 1 hour prior to arrival at the hospital. Given this worrisome clinical presentation — the onus of proof is on US to demonstrate that this is not OMI in progress, rather than the other way around ...

Although ECG #1 is not diagnostic of acute OMI by itself — this is not a “normal” ECG.
  • KEY Point: ECG #1 is not “negative” in the sense that it rules out anything. It is simply not diagnostic by itself of acute OMI.
  • There is sinus tachycardia at 115-120/minute. As always with sinus tachycardia — we need to find out WHY?
  • I suspect that lead V1 is placed too high on the chest because: i) there is a prominent negative component to the P wave in lead V1; ii) there is an r’ pattern in lead V1; and, iii) the overall appearance of lead V1 looks similar to that of lead aVR (CLICK HERE — for more on recognizing the likelihood of lead V1,V2 malposition).
  • Otherwise for ECG #1 — The PR interval is normal, and the QRS is narrow. The QTc may be borderline — though it is difficult to know what to make of the QTc given the rapid rate. The frontal plane axis is normal (ie, around +75 degrees). There is no chamber enlargement. If lead V1 is not misplaced — then there is an incomplete RBBB pattern (ie, an r’ in V1 with narrow terminal s waves in leads I and V6). Regarding Q-R-S-T Changes — there are no Q waves (other than perhaps in lead V1) — and R wave progression shows slightly delayed transition (the R does not become taller than the S wave is deep until between leads V4-to-V5). There is persistence of S waves through to lead V6.

The most remarkable findings in ECG #1 are regarding ST-T Wave Changes. These need to be interpreted in light of the fact that this patient presented with new-onset and severe chest pain, that began just 1 hour before this tracing was done:
  • There is non-specific ST-T wave flattening in a number of leads (ie, in leads I, V2, V5 and V6). The T wave is of relatively reduced amplitude in leads V3 and V4.
  • There is T wave inversion in lead aVL of ECG #1Although the T wave in lead aVL may normally be inverted when the QRS complex is predominantly negative in this lead — the size of this T wave (relative to the tiny size of the QRS in aVL) is disproportionately large and, this negative T wave in aVL looks fatter-than-it-should-be. This is a subtle change! That said, given the worrisome history — it should not be discounted!
  • NOTE: Although there is no ST elevation in the inferior leads — Did YOU notice that ST-T wave morphology changes almost from beat-to-beat in each of the inferior leads in ECG #1? A few complexes in the inferior leads do manifest ST segment straightening — which could be an early sign of acute OMI if the T wave inversion in lead aVL was to reflect a “reciprocal” change. BUT — because of this changing ST-T wave morphology from beat-to-beat in the inferior leads, it is hard to know which ST-T waves reflect what is really happening ... (This initial ED tracing should be repeated in short order).
BOTTOM Line Interpretation of ECG #1: Although ECG #1 is non-diagnostic of acute OMI — this is not a normal tracing. By itself it rules nothing out. BUT:
  • More information is needed before any conclusions can be reached. This includes repeating the ECG in short order (ideally within a few minutes) — looking for prior tracings on this patient — stat Echo at the bedside (looking for wall motion abnormality) — serial troponins — and, continued close observation of the patient until there can be greater certainty about the diagnosis.

QUESTION: baseline tracing (done 9 months earlier) was found ( = ECG #2). What differences do you see between ECG #1 and ECG #2? Does finding this previous ECG change your assessment of what you saw in ECG #1?
  • HINT: Be sure to do a lead-by-lead comparison of these 2 tracings in Figure-1.

  • ECG #2 — again shows sinus tachycardia at a similar rate! This again raises the question of WHY is there sinus tachycardia? NOTE: This is relevant to this case — since much of the value of a comparison tracing might be lost IF the patient presented with similar circumstances (ie, new-onset chest pain) 9 months earlier when the previous ECG ( = ECG #2) was done.
  • As noted by Dr. Smith — there is no T wave inversion in lead aVL of ECG #2 — BUT — the frontal plane axis is quite different! That is, the QRS complex in both leads I and aVL of ECG #2 is now clearly positive. Thus, although the relative size and shape of the T wave inversion in ECG #1 should still raise suspicion of an acute change — the shift in frontal plane axis between the 2 tracings negates making any definitive conclusion.
  • There is a wide and deep Q wave in lead III of the baseline tracing ( = ECG #2). This is not seen in ECG #1. The significance of this finding is uncertain.
  • There has been a change in ST-T wave morphology between the 2 tracings in multiple leads! That is, the ST-T wave was upright and of normal appearance in leads I, V2, V3, V4 and V5 in the baseline tracing ( = ECG #2). And, even though the T wave was smaller-than-it-should-be in leads aVL and V6 of ECG #2 — the ST-T wave in these leads clearly looks more abnormal in ECG #1.

BOTTOM Line Comparison Assessment: Both tracings show sinus tachycardia at a similar rate. BUT — at least 7 leads show an increase in nonspecific ST-wave changes on the new tracing ( = ECG #1).
  • Once again — More information is needed before any conclusions can be reached. Nevertheless, given the worrisome history and, this patient’s worsening appearance (ie, as noted by Dr. Fiero above, the patient was now diaphoretic) — even though ECG #1 remains non-diagnostic — a high index of suspicion needs to be maintained!

2nd ECG in the ED ( = ECG #3 in Figure-1) was done at 23:16 ( = 34 minutes after ECG #1). While now obvious that ECG #3 confirms the diagnosis of acute OMI — I think it helpful to describe: i) the lead-by-lead changes that have occurred in the 34 minutes between ECG #1 and ECG #3 (Figure-1); andii) to take another look at the baseline ECG ( = ECG #2) in the interest of now determining with more certainty which changes in ECG #1 were indicative of this acute evolving event.
  • ECG #3 — again shows sinus tachycardia at a similar rate. There is a PVC.
  • There is now hyperacute Selevation in leads III and aVF (and probably also in lead II of ECG #3.
  • NOTE: The frontal plane axis in ECG #3 is now similar to what it was in the baseline ECG ( = ECG #2) — BUT — despite a predominantly positive QRS complex in lead aVL of ECG #3 — the T wave is inverted, in association with slight-but-real J-point ST depression in this lead! This mirror-image opposite ST-T wave picture in leads III and aVL of ECG #3 confirms the diagnosis of acute inferior OMI in this patient with new severe chest pain. It also confirms (albeit in retrospect) — that the suspicious shape of the T wave inversion in lead aVL of ECG #1 was in fact, a sentinel ST-wave change warning of imminent acute inferior OMI, even though ECG #1 was not yet diagnostic at that point (since inferior lead hyperacute ST elevation had not yet begun).
  • Assessment of all 3 tracings in Figure-1 also allows us (again, albeit in retrospect) — to conclude that the increase in nonspecific ST-T wave changes in at least 7 leads in ECG #1 compared to baseline ECG #2 was also indication of this patient’s imminent infarction.

Our THANKS to Drs. Fiero and Smith for presenting this case. CREDIT to Dr. Fiero — for excellent management of this case!



  1. Nice case and a wonderful review on Antithrombotics!
    Thanks a lot Sir for your generosity, sharing knowledge!

  2. Hi Dr. Smith,

    How do you explain that he is in Sinus tachy of 115 in the settings of OMI. You talked several times that tachycardia is very rare in those cases without cardiogenic shock.

    Thanks in advance!

    1. @ Nadav Shoua — THANKS for your Question Nadav. Your wrote it before I added My Comment (which I did just now …). It was interesting to me that all 3 tracings I show in Figure-1 manifest a fairly fast sinus tachycardia at a similar rate! I emphasize the point (which I believe is the point Dr. Smith always makes on this subject) — that we need to find out WHY there is sinus tachycardia? Did this patient also have heart failure? cardiogenic shock? or something else that might be responsible for his sinus tachycardia? (We are NOT told by the history given … ). Of dual interest, is the fact that the ECG done 9 months earlier ( = ECG #2 in my Figure-1) ALSO showed sinus tachycardia because: i) This makes it important (if at all possible) to look back in the patient’s chart to see WHAT was going on 9 months ago at the time this ECG was done?; and ii) The value of this baseline tracing as a “comparison tracing” would be LESS if the SAME circumstances (ie, new-onset chest pain) were occurring when this “baseline” tracing was done! Ideally, the “baseline” we should use would be obtained when the patient is NOT having symptoms … THANKS again for your question! — :)

    2. Yes, it is unusual, but Dr. Fiero did find out the reason why, mentioned at the end: the patient had taken methamphetamine.

    3. @ Nadav — I did not notice this either, as the 1 sentence, "He admitted to amphetamine abuse about 10 hours prior to presentation" was for me "hidden" (but PRESENT) within the long presentation. CREDIT to Dr. Fiero — as he persisted with the history BECAUSE OF the tachycardia UNTIL he was able to elicit from the patient a potential reason for this tachycardia. And THAT is a KEY point about this case — namely, that one should ALWAYS seek out a "reason" for sinus tachycardia. I'll add 2 additional points: i) Sinus Tach is not "just a little" over 100/minute — but rather 115-120/minute, which is DEFINITE sinus tach (and which is that much MORE reason to seek out some specific cause for the fast rate); and ii) The fact that sinus tach at a similar rate was ALSO present on the ECG done 9 months earlier on this patient TELLS HIS PROVIDERS that there is longterm misuse of stimulants (and that much more reason, if the patient follows through ... — for longterm follow-up and drug rehab). THANKS again for your question! — :)

  3. I was told that if the patient receives only thrombolytics you should use 300 mg of Clopidogrel and if the patient is candidate for PCI he/she should receive 600 mg of Clopidogrel. Is this correct?

    1. When giving thrombolytics (even if transferring for PCI), clopidogrel dose should not be greater than 300 mg. All the studies used that dose, and there is not study confirming the safety. Moreover, the benefit of the higher dose is achieving adequate platelet inhibition by the time of PCI (that is the time of highest risk of platelet activity). When transferring, the time to PCI is long and 300 mg will provide adequate inhibition by the time of PCI.

  4. thank you Steve and Ken for your elaborate discussion of this case.

    I suspect that the tachycardia might be secondary to the sympathetic overtone caused by the fact that the patient was in, initially, severe pain (he actually looked like an active "badness" (acute MI, dissection, other) when i first walked into the room : clutching his chest, and severely diaphoretic. i thought someone had poured water on him. perhaps there was residual sympathetic effect of the amphetamines as well.
    i acknowledge that studies show the benefit of early plavix in such cases. i nowadays (perhaps wrongly) leave the plavix order to the cardiologist at the receiving hospital because i have had many cases of patients having severe multi-vessel involvement on angio, and requiring emergent or urgent CABG. the chest surgeons loathe the bleeding complications of plavixed (i made it a verb) patients, and sometimes even delay the procedure. what do you think, steve?

    again, thank you gentlemen.

    1. Tom, it must be worked out ahead of time with your receiving center. All I can say is that all the studies of thrombolytics followed by transfer for immediate PCI used dual antiplatelet therapy, most with clopidogrel, some with GP IIb-IIIa inhibitors. Those studies' designs were based on studies in early 2000s that show benefit of clopidogrel when giving thrombolytics.


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