The time of day a patient receives open-heart surgery could impact their postoperative outcomes, according to a new study in The Lancet.

Patients who underwent surgical aortic valve replacement in the morning had double the risk of adverse cardiac events within the next 500 days versus those who had surgery in the afternoon. The cohort study contained 596 patients at Lille University Hospital in France, half of which received surgery in the morning and half of which received it in the afternoon.

In addition, the researchers performed a 1:1 randomized study of 88 patients to assess perioperative myocardial injury via cardiac troponin T values. Patients with afternoon surgeries had 21 percent lower volumes of cardiac troponin T, a marker for heart tissue injury that is associated with mortality.

Together, the findings suggest circadian rhythm plays an important role in the perioperative healing of heart tissue.

“One major adverse cardiac event was prevented for every 11 patients operated on in the afternoon,” David Montaigne, MD, and colleagues reported of their 596-patient analysis. “Notably, this decreased relative risk for afternoon patients was the result of decreased incidence of both immediate perioperative myocardial infarction and acute heart failure. Medium-term postoperative cardiovascular morbidity remained lower in the afternoon than in the morning patients even after exclusion of perioperative myocardial infarction events and in the subgroup of patients who underwent isolated aortic valve replacement.”

Along with the two human analyses, the researchers used genetic editing in a mouse study to see whether they could make heart muscle heal the same way regardless of time of day. They identified the Rev-Erbα gene “as a master switch in cardiomyocyte ischemia–reperfusion tolerance”—meaning by blocking or turning off its signaling pathway, the mice were able to recover from surgery after short sleep-to-wake transitions with fewer side effects. Mice are nocturnal, so the scientists used sleep-to-wake transitions rather than “morning” and “afternoon” for humans.

“Rev-Erbα is a unique circadian gene belonging simultaneously to the molecular circadian clock and to nuclear receptor families,” Montaigne and colleages reported. “As such, by contrast with most other circadian genes, it is a relevant pharmacological target, and several small molecules acting through this receptor have been identified. We provide the proof-of-concept that Rev-Erbα antagonism is potentially a useful strategy to limit ischaemia–reperfusion injury. The design and synthesis of novel compounds with higher activity and refined pharmacokinetic profiles is thus warranted to develop clinically effective and safe drugs.”

Of course, animal studies require confirmation in human beings, the authors noted. In addition, larger, randomized, multicenter trials could help validate their findings on the impact of surgery time and outcomes.

Even with those caveats, the results of this study be heeded, according to two French cardiologists who authored an accompanying editorial.

“Even before we have drugs available to regulate the circadian clock, one might propose that high-risk patients should preferentially be operated on in the afternoon,” wrote Thomas Bochaton, MD, and Michel Ovize, MD.