Scott: Submassive PE; What to do?

Clinical Pearls (Thanks to Dr. Ali Tabatabai for assistance with the summary)

• Where is the evidence?
  • No good evidence for Surgical or Endovascular Embolectomy for submassive PE at this time.
  • No large robust randomized controlled trials for submassive PE in general.
    • Guidelines are thus non-existent, treatment not standardized.
• Definitions:
  • Massive PE-  hemodynamic instability.
  • Submassive PE-  hemodynamically stable, with some RV dysfunction/strain:
    • Elevated Troponin or BNP.
    • TTE or CT evidence for RV dilation.
    • TTE evidence for RV systolic dysfunction or pHTN.
  • Low risk PE- none of the above
• Why do we lyse with thrombolytics?
  • Avoid pulmonary HTN and RHF.
    • Little data on these actual risks.
  • Guidelines:
    • ACEP- no data to make a recommendation.
    • AHA- can consider is decompensating OR higher risk.
    • ESC, ACCP-  recommend NOT using thrombolytics unless decompensating to massive PE
      • High bleeding risk; based on 2015 meta-analyses.
        • Short term mortality benefit was 2.5% vs 3.5% in AC only (statistically significant).
        • However, markedly higher rate on major bleed (such as ICH) in PE patients vs trials for MI patients.
        • Not due to lack of efficacy; but did note the high number needed to treat.
• How do we risk stratify?
  • We want to know who is likely to decompensate!
  • Risk scores:
    • PESI/sPESI/msPESI
      • Low risk scoring that has high sensitivity, but not specific.
      • Best used to determine who can be sent home.
    • ESC
      • Imaging of RV strain +/- lab evidence of RV strain:
        • One: low risk.
        • Both: moderate/high risk of decompensation.
      • Not able to be validated.
    • BOVA
      • Defines a stepwise increase in short term risk:

Source

• • • • Sens 26%, Spec 97%, PPV 42%, NPV 93%, PLR 7.93, NLR 0.76
• Safer alternatives?
  • Surgical and endovascular not being discussed as more data needed in comparison to heparin AC alone.
    • Likely safer in terms of bleeding risks.
  • Catheter-directed thrombolysis
    • ULTIMA trial a 2014, the only RCT,  a total of 59 pts.
      • Submassive defined as RV:LV ratio ≥ 1 on TTE.
        • Primary endpoint of improvement of RV:LV ratio at 24 hours.
          • However, unclear correlation to risk of hemodynamic decompensation.
      • Results:
        • No difference at 90 days.
        • No episodes of hemodynamic decompensation or recurrent VTE in either arm.
      • However, appears to be safe.
  • Half-dose thrombolysis
    • MOPETT a 2013 trial (the only RCT)
      • Radiographic diagnosis of intermediate risk based on # of lobes involved
        • Many patients had lab or imaging evidence of RV strain but was not an inclusion criterion
      • Treatments:
        • 50kg:
          • 10mg bolus, then 40mg over 2 hours.
        • <50 kg:
          • 0.5mg/kg with a 10mg bolus first, then rest over 2 hours.
      • Primary endpoints: pHTN (PAP ≥40mmHg on TTE) OR pHTN + PE.
        • Statistically significant improvement for both in treatment arm
          • However, without a right heart cath, the calculated PAP is suspect to some variability and error!
        • No episodes of bleeding in either arm
          • Mortality numbers similar to other cohorts
        • Improvement in PAP persisted at 48 hours, 6 months, and 28 (+/-5) months
  • Existing data show both catheter-directed and half-dose are safe, but efficacy data are limited
• Take Home Points:
  • Guidelines recommend against routine use of thrombolytics for submassive PE.
    • Identifying a higher risk patient group may change risk-benefit balance in favor of thrombolysis.
  • Lower risk therapies (e.g., CDT or half-dose thrombolysis) may also change this balance.
  • Frank discussion and shared decision making with patients is important.