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. 2025 May 2:10.1007/s00246-025-03875-9.
doi: 10.1007/s00246-025-03875-9. Online ahead of print.

Reexploring the STRESS Trial: Subgroup Postoperative Outcomes Following Methylprednisolone for Infant Heart Surgery

Sudeep D Sunthankar  1 , Kevin D Hill  2 , Jeffrey P Jacobs  3 , H Scott Baldwin  4 , Marshall L Jacobs  5 , Jennifer S Li  2 , Eric M Graham  6 , Ashraf M Resheidat  7 , Venugopal Amula  8 , Mark S Bleiweis  3 , Eric L Wald  9 , Pirooz Eghtesady  10 , John P Scott  11 , Brett R Anderson  12 , Michael F Swartz  13 , Alexis Benscoter  14 , William Ravekes  15 , Prince J Kannankeril  4
Affiliations

Reexploring the STRESS Trial: Subgroup Postoperative Outcomes Following Methylprednisolone for Infant Heart Surgery

Sudeep D Sunthankar et al. Pediatr Cardiol. .

Abstract

Objective Assess the association between intraoperative methylprednisolone and specific postoperative outcomes among subgroups undergoing infant heart surgery.

Design: Subpopulation analyses of The Steroids to Reduce Systemic Inflammation after Infant Heart Surgery trial, a double-blind randomized placebo-controlled trial.

Setting: 24 congenital heart centers.

Patients: Infants (< 1 year old) undergoing heart surgery with cardiopulmonary bypass. Patients stratified by Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Congenital Heart Surgery (STAT) Mortality Category, age, gestational age, and presence of chromosomal or syndromic diagnosis (CSD).

Interventions: Methylprednisolone (30 mg/kg) versus placebo administered into cardiopulmonary bypass pump-priming fluid.

Measurements and main results: Outcomes included death, heart transplantation, mechanical circulatory support, reinterventions, and hospital length of stay. Ranked composite outcome (death, transplant, or one of 13 major complications) was compared between placebo and methylprednisolone for each subgroup using the win ratio. Methylprednisolone did not reduce odds of death, transplant, or mechanical circulatory support for any subgroup. Those receiving methylprednisolone had fewer catheterization or surgical reinterventions after STAT Category 1-3 operations [OR 0.50 (0.29-0.86)]; and fewer reoperations for bleeding among patients undergoing STAT Category 1-3 operations [OR 0.28 (0.09-0.87)], term infants [OR 0.30 (0.12-0.76)], and those without CSD [OR 0.22 (0.07-0.68)]. Length of stay was no different between methylprednisolone versus placebo. Those without chromosomal or syndromic diagnosis demonstrated a favorable association for methylprednisolone [win ratio 1.28 (1.01-1.61)] for the composite outcome.

Conclusion: Exploratory subpopulation analyses, although underpowered, suggest that methylprednisolone is not associated with significant harm and may benefit certain subpopulations.

Keywords: Cardiac surgery; Congenital heart disease; Critical care; Methylprednisolone.

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Conflict of interest statement

Declarations. Conflict of interest: Consultant for Autus Valve Technologies, Inc. (Anderson). Consultant for SpeialtyCare (J. Jacobs). For the remaining authors, no conflicts of interest are present.

Figures

Figure 1.
Figure 1.
Adjusted odds ratio (95% confidence interval) for binary outcomes of interest: (A) death, heart transplantation, and mechanical circulatory support, (B) Reintervention with heart catheterization and/or cardiac surgery, but excludes bleeding reoperations, and (C) Reoperaition due to bleeding. Odds ratio adjusted for STAT mortaltiy category, operative weight, and cardiopulmonary bypass time. Mechanical Circulatory Support (MCS).
Figure 2.
Figure 2.
Postoperative length of stay (PLOS) censored for death or transplant. No difference for PLOS between placebo and methylprednisolone by ordinal regression for any subgroup. PLOS bins were condensed for graphic visualization. Full data available in eTable 6 in Supplement 1
Figure 3.
Figure 3.
Distribution of ranked composite outcome for those with a score ≥ 91 categorized by treatment versus placebo for each subgroup.
Figure 4.
Figure 4.
Unmatched win ratio (WR) and 95% CI for the ranked composite outcome for each subgroup. WR > 1 predicts benefit of methylprednisolone. **P < 0.05. Full description of ranked outcomes are included in eTable 1 in Supplement 1. Ranked outcomes were based on priority assigned by parent manuscript.[2]
See this image and copyright information in PMC

References

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