Abstract
ObjectiveClinical studies using serum cardiac biomarkers to investigate a circadian variation in acute myocardial infarct (MI) size in ST-segment elevation myocardial infarction (STEMI) patients reperfused by primary percutaneous coronary intervention (PPCI) have produced mixed results. We aimed to investigate this phenomenon using acute MI size measured by cardiovascular magnetic resonance (CMR). MethodsPatient-level data was obtained from 4 randomized controlled trials investigating the MI-limiting effects of cardioprotective therapies in this pooled analysis. The primary analysis was performed in those patients with no pre-infarct angina; duration of ischemia >60min and <360min; Thrombolysis In Myocardial Infarction (TIMI) flow pre-PPCI ≤1; TIMI flow post-PPCI 3; and no collateral flow. Results169 out of 376 patients with CMR data met the inclusion criteria for the primary analysis. A 24-hour circadian variation in acute MI size as a % of the area-at-risk (%AAR), after adjusting for confounders, was observed with a peak and nadir MI size in patients with symptom onset between 00:00 and 01:00 and between 12:00 and 13:00 respectively (difference from the average MI size 5.2%, 95%CI 1.1–9.4%; p=0.013). This was associated with a non-significant circadian variation in left ventricular ejection fraction (LVEF) (difference from the average LVEF 5.9%, 95%CI −0.6–2.2%, p=0.073). There was no circadian variation in MI size or LVEF in the whole cohort. ConclusionsWe report a circadian variation in acute MI size assessed by CMR in a subset of STEMI patients treated by PPCI, with the largest and smallest MI size occurring in patients with symptom onset between 00:00 and 01:00 and between 12:00 and 13:00 respectively.
Highlights
The circadian rhythm has been shown to modulate cardiovascular physiology, impacting on parameters such as heart rate and blood pressure [8,9,10,11,12] via the expression of a circadian clock gene in the heart [13,14]
If a circadian dependence in acute myocardial infarction (MI) size is observed by Cardiovascular magnetic resonance (CMR), this would be an important factor to be taken into account in the design of future randomized controlled trials (RCTs) aiming to reduce MI size
This was a pooled analysis of patient-level data obtained from 4 published randomized controlled trials investigating the benefit of cardioprotective therapies in segment elevation myocardial infarction (STEMI) patients treated by primary percutaneous coronary intervention (PPCI), and using acute MI size by CMR as an end-point (Table 1)
Summary
The circadian rhythm has been shown to modulate cardiovascular physiology, impacting on parameters such as heart rate and blood pressure [8,9,10,11,12] via the expression of a circadian clock gene in the heart [13,14]. A circadian oscillation has been shown to impact on the expression of some proteins in the pro-survival pathways [15], and the susceptibility of the myocardium to acute ischemia/ reperfusion injury (IRI), following myocardial infarction (MI) in mammalian hearts [16,17]. Durgan et al [18] reported the existence of circadian dependence in MI size according to the time of day in a murine model of acute myocardial IRI. Several groups have investigated whether a circadian variation exists in ST-segment elevation myocardial infarction (STEMI) patients but the results have been conflicting, both in terms of the timings for the peak and the nadir of acute MI size [1,2,3] and whether the phenomenon exists at all in humans [19]. If a circadian dependence in acute MI size is observed by CMR, this would be an important factor to be taken into account in the design of future randomized controlled trials (RCTs) aiming to reduce MI size
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
