Patients who have open-heart surgery in the afternoon may fare better than those who have surgery in the morning because the body's circadian rhythm may be better able to help the heart heal later in the day, according to a study in The Lancet.
According to STAT News, the study is the latest in a growing body of work indicating that time of day can affect the efficacy of medical treatments, including multiple studies showing that vaccines and cancer treatments could be affected by what time of the day the treatment is administered.
For the study, researchers assessed 596 patients who had a heart valve replacement, with half undergoing morning surgeries and half undergoing afternoon surgeries. The researchers found that by the 500th day post-surgery:
- 54 out of the 298 patients who had morning surgeries had adverse effects during recovery; and
- 28 out of the 298 patients who had afternoon surgeries had adverse effects during recovery.
The researchers determined that patients undergoing surgery in the afternoon had roughly half the risk of complications compared with patients who had surgery in the morning. Overall, the researchers estimated that for every 11 patients who received afternoon surgeries, one major event—such as a myocardial infarction or acute heart failure—could be avoided.
The researchers also conducted a randomized controlled trial assessing 88 patients who all received the same surgical procedure, with half of them having it in the morning and the other half in the afternoon. In that assessment, the researchers found that the people who had afternoon surgeries had lower levels of tissue damage called myocardial ischaemia-reperfusion injuries—which experts say could lead to a higher chance of short- or long-term mortality—than those who had surgery in the morning.
The researchers then examined tissue samples from a subgroup of 30 patients in randomized trial. When the researchers imitated the process of the heart refilling with blood, as would happen at the end of the heart surgery, they found that tissue from patients who had afternoon surgeries regained its ability to contract more quickly than did tissue from those who had morning surgeries. They also found that almost 300 genes varied in how they expressed themselves in heart tissue over the course of a day, which the researchers said may explain why heart tissue varies in its ability to heal based on time of day.
In turn, the researchers conducted a final test to see if they could make heart tissue heal as it does in the afternoon at different points of the day. For the test, the researchers selected the Rev-Erbα gene, which expresses itself substantially more in the morning than in the afternoon, and studied how mouse hearts reacted when the gene was removed or blocked. The researchers found when the gene was removed or blocked, mice who had morning surgeries recovered with fewer side effects than usual.
David Montaigne, the lead author on the study and a professor at the University of Lille-France, said the findings show that scheduling afternoon surgeries could lower the patient's risk of injury or death during recovery. "There are few other surgical options to reduce the risk of post-surgery heart damage, meaning new techniques to protect patients are needed," he said. "Our findings suggest this is because part of the biological mechanism behind the damage is affected by a person's circadian clock and the underlying genes that control it."
Bart Staels, a study author and professor at the University of Lille-France, suggested the findings might propel the development of gene-modulating drugs to aid heart recovery. "One could imagine, quite rapidly, a pharmacological approach that could basically wipe out the effects between morning and afternoon," he said.
That said, Staels said, as of now, it is "totally impossible to abandon surgery in the morning." And while patients should not be deterred from having the "life-saving" surgery, Staels recommended that if providers "can identify patients at highest risk, they will definitely benefit from being pushed into the afternoon and that would be reasonable."
In an editorial accompanying the study, cardiologists Thomas Bochaton and Michel Ovize, both of the Hôpital Louis Pradel, issued a similar recommendation, stating, "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" (Blau, STAT News, 10/26; Gallagher, BBC, 10/27).
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