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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
On-pump cardiac surgery provokes a predictable perioperative myocardial ischaemia–reperfusion injury which is associated with poor clinical outcomes. We determined the occurrence of time-of-the-day variation in perioperative myocardial injury in patients undergoing aortic valve replacement and its m...
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| Published in: | The Lancet (British edition) 2018-01, Vol.391 (10115), p.59-69 |
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
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| Summary: | On-pump cardiac surgery provokes a predictable perioperative myocardial ischaemia–reperfusion injury which is associated with poor clinical outcomes. We determined the occurrence of time-of-the-day variation in perioperative myocardial injury in patients undergoing aortic valve replacement and its molecular mechanisms.
We studied the incidence of major adverse cardiac events in a prospective observational single-centre cohort study of patients with severe aortic stenosis and preserved left ventricular ejection fraction (>50%) who were referred to our cardiovascular surgery department at Lille University Hospital (Lille, France) for aortic valve replacement and underwent surgery in the morning or afternoon. Patients were matched into pairs by propensity score. We also did a randomised study, in which we evaluated perioperative myocardial injury and myocardial samples of patients randomly assigned (1:1) via permuted block randomisation (block size of eight) to undergo isolated aortic valve replacement surgery either in the morning or afternoon. We also evaluated human and rodent myocardium in ex-vivo hypoxia–reoxygenation models and did a transcriptomic analysis in myocardial samples from the randomised patients to identify the signalling pathway(s) involved. The primary objective of the study was to assess whether myocardial tolerance of ischaemia–reperfusion differed depending on the timing of aortic valve replacement surgery (morning vs afternoon), as measured by the occurrence of major adverse cardiovascular events (cardiovascular death, myocardial infarction, and admission to hospital for acute heart failure). The randomised study is registered with ClinicalTrials.gov, number NCT02812901.
In the cohort study (n=596 patients in matched pairs who underwent either morning surgery [n=298] or afternoon surgery [n=298]), during the 500 days following aortic valve replacement, the incidence of major adverse cardiac events was lower in the afternoon surgery group than in the morning group: hazard ratio 0·50 (95% CI 0·32–0·77; p=0·0021). In the randomised study, 88 patients were randomly assigned to undergo surgery in the morning (n=44) or afternoon (n=44); perioperative myocardial injury assessed with the geometric mean of perioperative cardiac troponin T release was significantly lower in the afternoon group than in the morning group (estimated ratio of geometric means for afternoon to morning of 0·79 [95% CI 0·68–0·93; p=0·0045]). Ex-vivo analysis of human my |
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| ISSN: | 0140-6736 1474-547X |
| DOI: | 10.1016/S0140-6736(17)32132-3 |