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Circadian dependence of infarct size and left ventricular function after ST elevation myocardial infarction
Ronald Reiter1, Cory Swingen, Luke Moore
1Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, MN 55407, USA.
Insights
Human heart attack (STEMI) infarct size and function depend on the time of day. Myocardial injury is greatest with early morning ischemia and reperfusion, impacting left ventricular function.
Area of Science:
- Cardiology
- Chronobiology
- Myocardial Infarction Research
Background:
- Rodent studies show infarct size after ischemia/reperfusion is circadian-dependent.
- It remains unknown if humans experience similar circadian variations in infarct size.
Purpose of the Study:
- To investigate the circadian dependence of infarct size in humans with ST-elevation myocardial infarction (STEMI).
Main Methods:
- Retrospective analysis of 1031 STEMI patients undergoing primary percutaneous coronary intervention.
- Identified 165 patients with known ischemic times (1-6 hours) and occluded arteries.
- Measured infarct size via creatine kinase (CK) release and assessed left ventricular ejection fraction (LVEF).
- Cardiac MRI used in a subgroup (n=45) for infarct and area-at-risk measurements.
Main Results:
- Infarct size, measured by CK release, significantly correlated with the time of day of STEMI onset (P<0.0001).
- Peak myocardial injury occurred with 1:00 am ischemia and 5:00 am reperfusion.
- LVEF, measured within 2 days, also showed circadian variation, with peak LVEF >7% higher than trough (43% vs 51%; P<0.03).
- Findings were corroborated by cardiac MRI data.
Conclusions:
- This study provides the first human evidence of a circadian dependence of myocardial infarct size and left ventricular function following STEMI.
- The time of ischemic onset significantly influences the extent of myocardial injury and subsequent cardiac function.
Rationale:
In rodents, infarct size after ischemia/reperfusion exhibits a circadian dependence on the time of coronary occlusion. It is not known if a similar circadian dependence of infarct size occurs in humans.
Objective:
To determine if humans exhibit a circadian dependence of infarct size in the setting of ST elevation myocardial infarction (STEMI).
Methods And Results:
A retrospective analysis of 1031 patients with STEMI referred for primary percutaneous coronary intervention with known ischemic times between 1 and 6 hours identified 165 patients with occluded arteries on presentation without evidence of preinfarction angina or collateral blood flow. Both ischemic duration and angiographic area at risk were not dependent on time of infarct onset. We observed that the extent of infarct size measured by creatine kinase release was significantly associated with time of day onset of infarction (P<0.0001). The greatest myocardial injury occurred at 1:00 am onset of ischemia and 5:00 am onset of reperfusion, with the peak creatine kinase measured at the peak of the curve being 82% higher than that recorded at the trough. Similarly, left ventricular ejection fraction measured within 2 days of infarction was also dependent on time of onset of STEMI with the absolute left ventricular ejection fraction at peak >7% higher than at trough (43% vs 51%; P<0.03). These findings were supported by a subgroup of patients (n = 45) who underwent cardiac MRI measurements of infarct size and area-at-risk measurements.
Conclusions:
The results of this study demonstrate for the first time in humans that myocardial infarct size and left ventricular function after STEMI have a circadian dependence on the time of day onset of ischemia.
