Impact of ECPR initiation time and age on survival in out-of-hospital cardiac arrest patients: on the measurement and meaning of ECPR initiation time: author’s reply

To the Editor,

We thank Jouffroy and Vivien for their thoughtful commentary on our article about the impact of extracorporeal cardiopulmonary resuscitation (ECPR) initiation time and age on survival after out‑of‑hospital cardiac arrest [1, 2]. Their remarks raise important points that merit clarification.

We acknowledge the concern about excluding the no‑flow interval and certain in‑hospital variables from our multivariable analysis. Reliable measurement of no‑flow duration was not feasible in a substantial subset of cases because some arrests were unwitnessed or the collapse time was uncertain. In our cohort, 82% of arrests were witnessed. For the remaining 18% no‑flow could not be established with confidence. Incorporating an imprecise estimate would have introduced greater measurement error, whereas excluding all unwitnessed arrests would have created selection bias and reduced statistical power. We therefore adjusted for witnessed status and bystander cardiopulmonary resuscitation, both standard Utstein indicators that correlate with no‑flow.

In‑hospital factors during resuscitation, including the quality of chest compressions, were unavailable with sufficient fidelity. Post-resuscitation treatments such as percutaneous coronary intervention and targeted temperature management were not included as covariates, as our goal was to isolate the independent effects of age and timing on survival. Conditioning on interventions that may lie on the causal pathway can introduce collider or mediator bias. Notably, there were no significant differences in the use of post-resuscitation treatments between age groups (Supplementary Table 1).

The commentary rightly emphasizes prehospital time. Our analysis accounted for this using call‑to‑hospital time [1]. This variable spans the period from the emergency call to hospital arrival and reflects both response and transport times. By including this measure in the multivariable model, we were able to differentiate prehospital from in-hospital delays. In our cohort, the call-to-hospital interval was shorter in older patients (Supplementary Table 1), supporting an interaction between low-flow duration and age and aligning with our principal findings.

The point regarding physiological age is well taken. Although chronological age cannot fully capture frailty, it remains a practical and reproducible metric and has consistently been identified as an independent predictor of ECPR outcomes in prior studies and guidelines [3–5]. Retrospectively assigning physiological age from registry data would require subjective criteria and compromise reliability and generalizability.

Our main objective was to determine whether the association between ECPR timing and survival varies with age. We used ECPR initiation time as a clinician-controlled proxy for the low‑flow duration, which is difficult to measure directly. After confirming that this variable was independent of prehospital time, we found a significant interaction with age, indicating a narrower therapeutic window for older adults.

In conclusion, while prehospital delay should not be underestimated, our findings highlight that in‑hospital delay deserves equal attention, particularly for older patients.

Abbreviation

ECPR

Extracorporeal cardiopulmonary resuscitation

Author contributions

D.K. and W.Y.K. drafted the main manuscript text and prepared Supplementary Table 1. D.K. and W.Y.K. approved the final manuscript and agree to be accountable for all aspects of the work.

Funding

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: RS-2024–00335934). The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, and approval of the manuscript; or the decision to submit the manuscript for publication.

Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

The KDCA approved the use of the data, and the Institutional Review Board of Asan Medical Center granted ethical approval with a waiver for informed consent (IRB No. 2023–0438).

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.