Thrombolysis in Submassive PE – 1st JC 12.08.2015

 This is a retrospective entry. A huge congratulations to the EU team, for their first journal club meet on the 12 August 2015.

This week, we discuss about thrombolysis in submassive pulmonary embolism. As a kickstart, PEITHO trial is picked to be the opening ceremony article of this memorable event.

As per discussion the other day, several issues were pointed out from the conclusion of this study, it was indeed a well run trial with a good sample size of 1005. There is a positive result of which there is a significant reduction in the combination of all-cause mortality and hemodynamic decompensation (the study is powered to analysed this primary outcome). On the other hand, on the secondary outcome we noted that this difference is contributed mainly by the hemodynamic decompensation, whereas no reduction in terms of all cause mortality, but it is worth to point out that among the hemodynamic decompensation in the placebo group 5 of them require CPR. Major extracranial and stroke risk is significantly higher in the thrombolysis group.

This paper alone still not strong enough to change our practice, and the classification of submassive PE is still not a must from emergency unit point of view. It is however pointed that bedside ECHO skill will be beneficial. (not only in PE but in a lot of cases in resus especially undifferentiated shock)



  • Thrombolysis is a definitive treatment for massive PE
  • Non massive PE – anticoagulation alone
  • There is a new category introduced – Submassive PE (Variable definition) – To thrombolyse or just anticoagulant alone?

Definition (Adapted from AHA paper as attached – different papers use different definition)

  • Masssive PE : sustained hypotension, pulselessness or profound bradycardia
  • Submassive PE : non hypotensive, evidence of RV dysfunction or myocardial necrosis
    • RV dysfunction means the presence of at least 1 of the following:
      • RV dilation (apical 4-chamber RV diameter divided by LV diameter >0.9) or RV systolic dysfunction on echocardiography
      • RV dilation (4-chamber RV diameter divided by LV diameter >0.9) on CT
      • Elevation of BNP (>90 pg/mL)
      • Elevation of N-terminal pro-BNP (>500 pg/mL); or
      • Electrocardiographic changes (new complete or incomplete right bundle-branch block, anteroseptal ST elevation or depression, or anteroseptal T-wave inversion)
    • Myocardial necrosis:
      • Elevation of troponin I (>0.4 ng/mL) or
      • Elevation of troponin T (>0.1 ng/mL)

Clinical Question

  • Does thrombolysis in submassive PE make a better outcome (outcome differs in different papers – but generally looking at mortality and long term)?

What are the articles worth looking at that address this question?

  • ICOPER Registry 1999
  • MAPPET-3 Trial 2002
  • RIETE Trial 2006 (attached)
  • MOPPET Trial 2013 (attached)
  • PEITHO Trial 2014 (attached)
  • TOPCOAT Trial 2014 (attached)
  • Meta-analysis by Chaterjee et al 2014 (attached)
  • Meta-analysis by Nakamura et al 2014

FOAM Resources worth reading with regards to this issue

Retrospective Review of All CTPAs from IMPAX (From all EU location, apart from Llandough) – July 2014 till July 2015

  • A total of 150 scans requested
  • 27 of them positive for PE (ranging from minimal sub segmental to huge burden clot) – 18%
  • Out of the 27 cases, 11 of them have evidence of right heart strain as evidenced by CT (40.7%), 10 cases did not have any report with regard to right heart strain
  • With this short review, we have at least a 40% of PE cases are actually under category of submassive PE (based on right heart strain alone)
  • Compared to a review in a district hospital in New Zealand, with a detection rate of 14%, we are actually doing quite well 🙂

Suggestion to the department how are we going forward

  • To discuss in one of our next journal club regarding the meta-analysis as concluded in the previous meeting
  • To bring in ECHO as part of routine evaluation of those sick patient (RUSH Protocol for undifferentiated shock, FEEL Protocol for cardiac arrest)
  • A further retrospective review/audit on our current performance of our pulmonary embolism case
  • To try to categorise the patient whom we diagnosed PE in ED whether or not they are submassive PE with bedside ECHO and/or Trop 
  • A research project as outlined below

A Brief Research Proposal on Thrombolysis in Submassive PE

  • Thought process – thrombolysis will reduce all cause mortality and long term morbidity from pulmonary hypertension – but will cause increase bleeding
  • Hypothesis : Half dose thrombolysis in submassive for those 18-65 yr old, with a lower aPTT target in the initial phase, as per MOPPET protocol, will be able to reduce all cause mortality while maintaining the risk of bleeding tendency.
  • Multicenter, randomised controlled trial (all centre in wales with CTPA resources)
  • MOPPET trial half dose alteplase (50mg) vs placebo AND heparin as per MOPPET trial (aPTT target of 1.5-2.0X, rather than a higher target)
  • Primary outcome of all cause mortality
  • Secondary outcome of development into massive PE, long term pulmonary hypertension
  • Adverse reaction : bleeding (major & minor)
  • Inclusion criteria
    • 18-65 yr old
    • confirmed PE by CTPA or VQ scan
    • evidence of right heart strain – either a new right strain pattern on ECG, a right ventricular strain (including RV:LV ratio > 0.9) on ECHO (by emergency physician or cardiologist), CT evidence of reflux of contrast into IVC or right heart to left heart ratio > 0.9, or elevated troponin

All the discussed articles are available on the dropbox folder. Have a nice read 🙂

Nic Ngua

*Disclaimer : The opinions expressed by the finetuningem’s author/editor and those providing comments are theirs alone, and do not reflect the opinions of any professional organisation or group or any employee thereof.


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