Sub-phenotypes in patients with out-of-hospital cardiac arrest who undergo extracorporeal cardiopulmonary resuscitation: a retrospective observational study from a multicenter registry

Abstract

Background: Out-of-hospital cardiac arrest (OHCA) has poor survival rates, but extracorporeal cardiopulmonary resuscitation (ECPR) shows promise for selected patients, as a second line of therapy after failure of conventional CPR to obtain return of spontaneous circulation, despite implementation challenges. This study aimed to identify distinct sub-phenotypes among patients with OHCA who undergo ECPR and to investigate their association with clinical outcomes.

Methods: This multi-center, retrospective, observational study used the Japanese Association for Acute Medicine OHCA registry from 83 hospitals that performed ECPR among 91 participating centers between June 2014 and December 2020. We included adult patients with OHCA who received ECPR during cardiac arrest. Three-class latent class analysis (LCA) was employed to identify sub-phenotypes based on 15 variables, including pre- and in-hospital factors. Logistic regression analysis was used to assess the association between sub-phenotypes and 30-day survival and neurological outcomes.

Results: A total of 1528 patients were included. The median low-flow time was 47 min (interquartile rage: 38-58 min). The 30-day survival rate for eligible patients was 20.9%. LCA identified three distinct sub-phenotypes: Standard ECPR Group (n = 702), Delayed ECPR Group (n = 457), and Non-shockable Rhythm Group (n = 369). The variables with high discriminative power in the LCA was low-flow time, followed by pre-hospital shock delivery and initial cardiac rhythm. Thirty-day survival rates varied significantly among the sub-phenotypes (p = 0.001): Standard ECPR Group (26.9%), Delayed ECPR Group (17.1%), and Non-shockable Rhythm Group (14.1%). Favorable neurological outcomes at 30 days also differed significantly (p = 0.004), with the Standard ECPR Group showing the highest rate (12.1%). After adjusting for covariates, both the Delayed ECPR Group (adjusted OR: 0.61, 95% CI 0.44-0.82) and Non-shockable Rhythm Group (adjusted OR: 0.47, 95% CI 0.32-0.68) had significantly lower odds of 30-day survival compared to the Standard ECPR Group.

Conclusions: Three clinically meaningful sub-phenotypes were identified using simple pre-hospital and in-hospital factors, with low-flow time emerging as the most critical discriminating factor. The sub-phenotypes showed significant associations with clinical outcomes and provide a practical framework for ECPR patient stratification. These findings suggest that timing optimization may be as important as rhythm characteristics for ECPR patient selection and support the development of sub-phenotype-specific treatment strategies.

Keywords: Cardiac arrest; Extracorporeal cardiopulmonary resuscitation; Latent class analysis; Sub-phenotype.

Fig. 1

Flowchart of study participants and the number of participants in each sub-phenotype. CMO: extracorporeal membrane oxygenation; ECPR: extracorporeal cardiopulmonary resuscitation; LCA: latent class analysis; OHCA: out-of-hospital cardiac arrest; ROSC: return of spontaneous circulation

Fig. 2

Discriminative power of each variable in descending order. CPR: cardiopulmonary resuscitation; ECMO: extracorporeal membrane oxygenation