The EMERGE Trial: Emergency vs Delayed Catheterization in Survivors of Out-of-Hospital Cardiac Arrest

Background: Previous observational studies published in 2015 (Geri 2015)(Vyas 2015) indicated that early cardiac catheterization in patients with out-of-hospital cardiac arrest (OHCA) might improve mortality and result in more favorable neurological outcomes. The TOMAHAWK (Desch 2021), COACT (Abella 2019), and PEARL (Lemkes 2019) trials examined patients with OHCA without ST elevation with a shockable rhythm, and investigators found no difference in delayed versus emergency angiogram. However, there are no clear guidelines for management in post-cardiac arrest patients without ST-segment elevations on ECG.

Clinical Question: In patients who suffer an OHCA without ST-segment elevation on the post-resuscitation ECG, will early coronary angiogram (CAG) vs. delayed CAG improve outcomes?

Article: How-Berlemont C, Lamhaut L, Diehl J, et al. Emergency vs Delayed Coronary Angiogram in Survivors of Out-of-Hospital Cardiac Arrest: Results of the Randomized, Multicentric EMERGE Trial. JAMA Cardiol. Published online June 08, 2022. PMID: 35675081

What They Did:

• National, multicenter, randomized control, open-label parallel trial performed at 22 centers in FrancePatients enrolled from January 19, 2017 –  November 23, 2020.
• Assigned survivors of an OHCA without ST-segment elevation on ECG 1:1 ratio to either emergency (direct transfer) or delayed (48 to 96 hours) for CAG
• Meta-analysis was done with three RCT trials TOMAHAWK (Desch 2021), COACT (Abella 2019), and PEARL (Lemkes 2019) trials.

Inclusion criteria: 

• > 18 years old who had an OHCA with the return of spontaneous circulation (ROSC)
• No obvious non-cardiac related etiology
• Admitted to hospital with an intensive care unit and 24/7 interventional cardiology

Exclusion criteria:

• <18 years of age
• In-hospital cardiac arrest
• Patients without ROSC
• ST-segment elevation on the post-resuscitation ECG
• Suspected non-cardiac etiology
• Presence of comorbidities with life expectancy of < 1 year
• Pregnancy
• Adults subject to legal protection (guardianship or curatorship)

Intervention: 

• Emergent CAG: Patients were transferred directly to the catheterization lab where a CAG was performed at the hospital.

Comparator:

• Delayed CAG: Patients were admitted to the ICU, and CAG was performed after 48-96 hours.

Primary Outcomes: 

• The 180-day survival rate with Cerebral Performance Category (CPC) < 2

Cerebral Performance Category:

• CPC 1: Good cerebral performance. Conscious, alert, able to work, might have a mild neurological or psychological deficit
• CPC 2: Moderate cerebral disability. Conscious, sufficient cerebral function for independent activities of daily life. Able to work in a sheltered environment
• CPC 3: Severe cerebral disability. Conscious, dependent on others for daily support because of impaired brain function. Ranges from ambulatory state to severe dementia or paralysis.
• CPC 4: Coma or vegetative state. Any degree of coma without the presence of all brain death criteria. Unawareness, even if one appears awake (vegetative) without interacting with the environment, may have spontaneous eye-opening and sleep/ awake cycles. Cerebral unresponsiveness
• CPC 5: Brain death. Apnea, areflexia, EEG silence, etc.

Secondary Outcomes:

• Shock, ventricular tachycardia, and/or fibrillation within 48 hours after hospital admission.
• Changes in left ventricular ejection fraction from baseline (at admission) and 180 days.
• Major Neurologic Sequelae
  • CPC scale 3 and 4  assessed in the intensive care unit at discharge, 90 days, 180 days.
• All-cause mortality
• Hospital LOS

Results: 

• 338 Randomized → 59 excluded for various reasons
• 279 randomized to delayed or early CAG
• 141 patients allocated to emergency CAG → 138 included in ITT analysis
  • 126 received intervention
    • 15 died before catheterization
  • 89 died by 3 months follow up
  • 1 died at 6 months follow up
• 138 patients allocated to delayed CAG → 137 included in ITT analysis
  • 51 patients received allocated intervention
  • 87 did not receive intervention
    • 61 patients died before the intervention
    • 23 had catheterization before 48 h
    • 92 died by 3 months follow up

Critical Results:

• Primary Outcome:
  • No statistically significant difference in 180-day survival rates with CPC 1 or 2
  • 34.1% (47 of 141) in the emergency CAG group
  • 30.7% (42 of 138) in the delayed CAG group
  • HR, 0.87; 95% CI, 0.65–1.15; P= 0.32
• Secondary Outcomes:
  • No statistically significant difference in overall 180-day survival rates
  • 36.2% (51 of 141) in the emergency CAG group
  • 33.3% (46 of 138) in the delayed CAG group
  • HR, 0.86; 95% CI, 0.64–1.15; P= 0.31
  • No statistically significant difference in any secondary outcomes

Strengths:

• Investigators asked heavily debated, and patients centered questions
• Primary and secondary outcomes were patient-oriented
• Inclusion of multiple centers increases the external validity
• Centralized electronic randomization process
• Wider non-shockable rhythm was analyzed as the previous study focused only on shockable rhythm
• Investigator performed an intention-to-treat analysis

Limitations:

• Study performed in a single country. Results may not be generalizable.
• The study was stopped early due to a lack of enrollment.
• Investigators did not achieve their target sample size making the study underpowered.
• The enrolled cohort appears to be a convenience sample. It’s unclear how many patients sustained a cardiac arrest but were not enrolled, indicating the presence of selection bias.
• There are differences within the demographic:
  • More women in the delayed group
  • Delayed group had higher witnessed arrest and bystander CPR
  • Delayed group had more non-shockable rhythms
• Protocol violations were common. Only 51 of 138 patients randomized to the delayed CAG received the allocated intervention.
• Open-label study introducing the potential for co-intervention bias: Providers were aware of study allocation by nature of the treatment (CAG). 
  • Providers could have provided more aggressive medical management to one group.
• There is very little information on the methodology of the meta-analysis.

Discussion:

• The study was stopped early due to insufficient enrollment. Investigators enrolled approximately 280 patients out of 970 planned. Studies stopped early can overestimate results. While the study provides interesting data, it’s underpowered, and we cannot draw firm conclusions. The study findings are similar to those reported in TOMAHAWK (Desch 2021), COACT (Abella 2019), and PEARL (Lemkes 2019) trials.
• Additionally, the trial had several biases. Firstly, the enrolled cohort appears to be a convenience sample. It’s unclear how many patients had an OHCA and were not enrolled. Next, the trial was open-label, and all care team members knew the allocation arm. Moreover, there is relatively little information regarding patient management outside the study intervention. Clinicians could potentially have managed one group more aggressively than the other. Next, 61 patients in the delayed CAG arm did not get catheterization due to hemodynamic instability, severe brain damage, or because they died before CAG, which introduces survivorship bias. Lastly, there are some differences in the demographics between the groups. The delayed group had a higher incidence of non-shockable rhythms. Could these demographic differences contribute to the outcomes?
• Meta-analyses have complex statistical rigor and methodology. The addition of the trial results to a meta-analysis seems haphazard. We know relatively little information about the search timeline, the number of reviewers, the agreement of reviewers, the use of bias assessment tools, or other common standards used in meta-analyses.

Authors’ Conclusion:  “In this randomized clinical trial, for patients who experience an OHCA without ST-segment elevation on ECG, a strategy of emergency CAG was not better than a strategy of delayed CAG with respect to 180-day survival rate and minimal neurologic sequelae.”

Clinical Bottom Line:

We agree with the author’s conclusion. There was no difference in outcomes in the data presented. The findings are similar to other recent studies. However, this study was markedly underpowered, making it difficult to draw firm conclusions. Based on the totality of the evidence, there is no indication for emergent cardiac catheterization in patients with OHCA without ST elevations.

For More on This Topic, Checkout:

MIRACLE2 Risk Score for Early Prediction of Neurologic Outcome in Out-of-Hospital Cardiac Arrest

TTM2: Hypothermia vs Normothermia for Out-of-Hospital Cardiac Arrest

References:

1. Geri, G., Dumas, F., Bougouin, W., Varenne, O., Daviaud, F., Pène, F., Lamhaut, L., Chiche, J.-D., Spaulding, C., Mira, J.-P., Empana, J.-P., & Cariou, A. (2015). Immediate percutaneous coronary intervention is associated with improved short- and long-term survival after out-of-hospital cardiac arrest. Circulation: Cardiovascular Interventions, 8(10). PMID: 26453685
2. Vyas, A., Chan, P. S., Cram, P., Nallamothu, B. K., McNally, B., & Girotra, S. (2015). Early coronary angiography and survival after out-of-hospital cardiac arrest. Circulation: Cardiovascular Interventions, 8(10). PMID: 26453686
3. Desch, S., Freund, A., Akin, I., Behnes, M., Preusch, M. R., Zelniker, T. A., Skurk, C., Landmesser, U., Graf, T., Eitel, I., Fuernau, G., Haake, H., Nordbeck, P., Hammer, F., Felix, S. B., Hassager, C., Engstrøm, T., Fichtlscherer, S., Ledwoch, J., … Thiele, H. (2021). Angiography after out-of-hospital cardiac arrest without st-segment elevation. New England Journal of Medicine, 385(27), 2544–2553. PMID: 34459570
4. Abella, B. S., & Gaieski, D. F. (2019). Coronary angiography after cardiac arrest — the right timing or the right patients? New England Journal of Medicine, 380(15), 1474–1475. PMID: 30883048
5. Lemkes, J. S., Janssens, G. N., van der Hoeven, N. W., Jewbali, L. S. D., Dubois, E. A., Meuwissen, M., Rijpstra, T. A., Bosker, H. A., Blans, M. J., Bleeker, G. B., Baak, R., Vlachojannis, G. J., Eikemans, B. J. W., van der Harst, P., van der Horst, I. C. C., Voskuil, M., van der Heijden, J. J., Beishuizen, A., Stoel, M., … van Royen, N. (2019). Coronary angiography after cardiac arrest without st-segment elevation. New England Journal of Medicine, 380(15), 1397–1407. PMID: 32876654

Guest Post By:

M. Ahmad Khan, MD
PGY-3, Emergency Medicine Resident
Nuvance Health, Poughkeepsie, New York
Email: khan.a@outlook.com

Marco Propersi, DO FAAEM
Vice-Chair/Associate Medical Director
Assistant Residency Program Director
Department of Emergency Medicine
Vassar Brothers Hospital, Poughkeepsie, New York
Twitter: @marco_propersi

Post-Peer Reviewed By: Salim R. Rezaie, MD (Twitter: @srrezaie), Anand Swaminathan, MD (Twitter: @EMSwami)

 

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