October 26, 2017

expert reaction to research on timing of heart surgery

New research, published in The Lancet, combines observational study, randomised trial, tissue analysis and research in mice to investigate the link between time of day of surgery and health outcomes.

Dr Mike Knapton, Associate Medical Director at the British Heart Foundation, said:

“Thousands of people now have open heart surgery in the UK. These procedures can take many hours and come with a number of risks.  The time of day appears to be a significant factor in the outcome from surgery, with better outcomes if your surgery is in the afternoon.

“If this finding can be replicated in other hospitals this could be helpful to surgeons planning their operating list, for non-urgent heart surgery.

“The study also suggests that modifying the genes responsible for this phenomenon could lead to the development of new drugs to protect the heart from damage during open heart surgery.”

Dr John O’Neill, from the MRC Laboratory of Molecular Biology, said:

“This is an interesting correlative study which agrees with what we’d expect: that the human biological clock (circadian rhythm) affects how well people recover from heart surgery. Scientifically it is not hugely surprising, because just like every other cell in the body, heart cells have circadian rhythms that orchestrate their activity to anticipate the external rhythm of night and day – i.e. our heart ‘expects’ to work harder during the day than at night, with the opposite being true in mice. In healthy individuals, not engaged in shift work, our cardiovascular system has the greatest output around mid/late-afternoon, and explains why professional athletes usually record their best performances around this time.  In the morning, just after we’ve woken up, the cardiovascular system is not yet at peak performance, which partly explains why heart attacks and strokes are occur more frequently in the morning.  This new study may also explain why survival after aortic valve replacement is also poorer in the morning, both in terms of during the surgery and longer term survival.

“The study seems to have been very well-designed, and I have no doubts that the results of their analyses are robust.  The data in figure 2 of the paper are unsurprising: circadian clock-regulated gene activity is different between morning and afternoon, but it’s nice to see this measured in humans, given that so much of what we know about clock genes comes from mice and fruitflies (see the recent Nobel prize in Physiology or Medicine).

“The only caveat to this paper is that the observations could be explained equally well by morning-afternoon differences in the two surgical teams carrying out the operation rather than in the patients. I am not suggesting this is the case, but reading the methods section there were only two surgeons involved in the whole study, each performing two operations per day: one in the morning, the other in the afternoon. It is therefore plausible that the morning-afternoon difference could instead be attributable to the biological clock of the two surgeons, rather than the patients, if they both had late chronotypes for example (owls rather than larks). This alternative is quite possible, since we know that hand-eye co-ordination, concentration and cognitive abilities are also affected by time-of-day.

“This new research indicates that the circadian clock may affect outcomes from heart surgery, but understanding why and how to leverage this information requires more research.”

Dr Tim Chico, consultant cardiologist at the University of Sheffield, said:

“This is a very interesting study, but I agree with its authors that the findings are preliminary and need to be confirmed in a larger study in more than one hospital. If it is true that outcomes are worse if someone has their operation in the morning, this would have major implications for scheduling of operations. However, there are many factors that could explain this finding other than the circadian rhythms of the patient (or indeed the surgeon).

“The authors have identified a possible treatment in mice that could be given to reduce the damaging effect of surgery on the heart but it is possible that this would be beneficial to someone irrespective of their time of surgery, which would be very exciting. However, since this treatment has only been used in mice, it will take several years to know whether or not there is a realistic prospect of using it in human patients.”

* ‘Daytime variation of perioperative myocardial injury in cardiac surgery and its prevention by Rev-Erbα antagonism: a single-centre propensity-matched cohort study and a randomised study’ by David Montaigne et al. published in The Lancet on Thursday 26 October.

Declared interests

None declared