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Korean J Anesthesiol > Epub ahead of print
Kwak: Response to "Comment on Association between non-anemic iron deficiency and outcomes following off-pump coronary artery bypass surgery: a retrospective analysis"
Dear Editor,
We received a Letter to the Editor regarding our recent publication in the Korean Journal of Anesthesiology titled “Reassessing the role of preoperative non-anemic iron deficiency in off-pump cardiac surgery: insights beyond a negative association.” [1] We appreciate the readers’ thoughtful comments and the opportunity to clarify several important aspects of our study [2].
First, regarding the assertion that the surgical nature of off-pump coronary artery bypass grafting (OPCAB) may attenuate the detectable impact of iron deficiency (ID), we agree with their observation that OPCAB is an inherently “low-sensitivity” model for detecting iron-related vulnerabilities. However, this was precisely why we examined this specific cohort: the study was intentionally designed to evaluate ID within a patient- and surgery-specific context, in which cardiopulmonary bypass-related hemodilution and inflammation are minimized. Notably, similar findings have been reported even in on-pump and mixed types of cardiac surgeries [3], where physiological stressors are far more pronounced. Although these are findings from single-center retrospective studies, this consistency suggests that the neutral association may not be solely attributable to the OPCAB setting, but may instead reflect a broader characteristic of non-anemic ID in cardiac surgery patients.
Second, regarding the concern that the interval between iron assessment and surgery was too short (a median of two days) to allow any therapeutic intervention, we respectfully disagree that this represents a methodological limitation. Our aim was not to evaluate the efficacy of iron replacement, but rather to classify patients’ baseline iron status as an exposure variable. In this context, the temporal proximity strengthens the internal validity of the study: a narrow interval reduces the likelihood of misclassification bias by ensuring that the iron profile closely reflects the patient’s true preoperative physiological state. Thus, a short testing-to-surgery interval should be viewed as a design strength rather than a constraint.
Finally, regarding whether postoperative ID was considered in the interpretation of the results, we acknowledge that postoperative iron metabolism was not captured, which limits our ability to characterize postoperative functional ID. However, postoperative inflammation-driven iron sequestration is expected in most patients. Given that the type of surgery in our cohort was uniform, the magnitude and pattern of postoperative inflammation were likely more consistent than they would be in heterogeneous cardiac surgery cohorts. Moreover, although this phenomenon would likely have been more pronounced in those patients already iron deficient preoperatively, it did not translate into differences in prognosis. Even in cardiopulmonary bypass cases, in which nearly all patients develop postoperative ID [4], preoperative non-anemic ID was not associated with a worse 90-day DAOH (days alive and out of hospital) [5].
We hope that our response contributes to a more balanced understanding of the study results and underscores the need for future prospective investigations to better define the role of non-anemic ID in cardiac surgery.

Funding: None.

Conflicts of Interest: No potential conflict of interest relevant to this article was reported.

References

1. Hsu HA, Lin WT, Hung MH. Comment on “Association between non-anemic iron deficiency and outcomes following off-pump coronary artery bypass surgery: a retrospective analysis”. Korean J Anesthesiol 2026. Advance Access published on February 3, 2026. doi:10.4097/kja.25986.
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2. Shin H, Kim HB, Shim JK, Song JW, Ko SH, Kwak YL. Association between non-anemic iron deficiency and outcomes following off-pump coronary artery bypass surgery: a retrospective analysis. Korean J Anesthesiol 2025; 78: 560-8.
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3. Peri V, Devlin P, Perry L, Richards T, Miles LF. Associations between nonanemic iron deficiency and postoperative outcomes in cardiac surgery: a systematic review and meta-analysis. Anesth Analg 2024; 139: 47-57.
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4. Tramarin R, Pistuddi V, Maresca L, Pavesi M, Castelvecchio S, Menicanti L, et al. Patterns and determinants of functional and absolute iron deficiency in patients undergoing cardiac rehabilitation following heart surgery. Eur J Prev Cardiol 2017; 24: 799-807.
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5. Kim HB, Shim JK, Ko SH, Kim HR, Lee CH, Kwak YL. Effect of iron deficiency without anaemia on days alive and out of hospital in patients undergoing valvular heart surgery. Anaesthesia 2022; 77: 562-9.
crossref pmid pdf


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