Circadian Dependence of Infarct Size and Left Ventricular Function After ST Elevation Myocardial Infarction

Abstract

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.