Afternoon Heart Surgery May Reduce Muscle Injury But Evidence Remains Thin

The hypothesis that circadian biology influences surgical outcomes has gained traction over the past decade. The heart's tolerance for ischemia-reperfusion injury — the damage that occurs when blood flow is restored after a period of deprivation, as happens routinely during cardiopulmonary bypass — appears to vary across the 24-hour cycle. Several observational studies and one high-profile randomized trial suggested that afternoon cardiac surgery might reduce myocardial injury and improve outcomes compared to morning surgery. This Cochrane review was designed to rigorously evaluate that hypothesis using only randomized controlled trial evidence.

The review team searched CENTRAL, MEDLINE, Embase, and Web of Science Conference Proceedings through January 26, 2025, supplemented by ClinicalTrials.gov, the WHO International Clinical Trials Registry, reference checking, and direct author contact. Eligible studies were RCTs in adults undergoing on-pump cardiac surgery that explicitly compared late versus early surgical start times. Non-randomized studies and pediatric populations were excluded. Critical outcomes were short-term mortality (≤30 days), long-term mortality (>30 days), and perioperative myocardial infarction. Important secondary outcomes included perioperative myocardial injury, postoperative atrial fibrillation, left ventricular ejection fraction, ICU and hospital length of stay, and quality of life.

Despite the breadth of the search, only one RCT met inclusion criteria. This French trial enrolled 88 adults undergoing elective on-pump aortic valve replacement, randomizing them to either a morning or afternoon surgical start. The Cochrane Risk of Bias 2 tool was applied, and because only a single study was identified, no meta-analysis was possible — results were synthesized descriptively and certainty of evidence was assessed using GRADE methodology.

The single included study's most notable finding was a statistically significant reduction in perioperative myocardial injury in the afternoon surgery group, measured as cumulative troponin release over 72 hours (mean difference −46 ng/L × 72 h, 95% CI −79 to −13). This is a clinically meaningful biomarker signal suggesting less ischemia-reperfusion damage with later surgical timing. However, no deaths occurred in either group (risk ratio not estimable), and there was no statistically significant difference in perioperative myocardial infarction (RR 0.29, 95% CI 0.06 to 1.30), new-onset postoperative atrial fibrillation (RR 0.75, 95% CI 0.40 to 1.40), left ventricular ejection fraction below 45% at discharge (RR 0.40, 95% CI 0.08 to 1.95), need for inotropic support (RR 0.25, 95% CI 0.03 to 2.15), or length of hospital stay (MD 0.00, 95% CI −1.48 to 1.48). No data were available for ICU length of stay or quality of life.

The GRADE certainty ratings for all reported outcomes were very low, reflecting the single small study, imprecision of estimates, and inability to assess consistency across trials. The authors conclude that while the troponin signal is biologically plausible and directionally consistent with circadian physiology, it is insufficient to justify changes to surgical scheduling practice. The review underscores a striking gap: despite substantial mechanistic and observational literature on circadian effects in cardiac surgery, the RCT evidence base is essentially nonexistent. Larger, multicenter trials powered for hard clinical endpoints — mortality, major adverse cardiac events, quality of life — are urgently needed to determine whether time-of-day scheduling represents a genuinely modifiable factor in cardiac surgical outcomes.