Circadian variation in primary angioplasty for acute MI
Primary percutaneous coronary intervention (PCI) is the treatment of choice for acute myocardial infarction (MI). This lifesaving procedure, therefore, needs to be available 24 hours a day, 7 days a week. It is important to determine whether the outcome of primary PCI is as good during off-hours as during regular working hours in the hospital. Two important variables may play a role in determining this.
First, is the pathophysiology of acute MI or the presentation of the disease different during normal working hours compared with off-hours? There is a circadian variation in the time of symptom onset for patients with acute MI as well as with other cardiovascular events, such as unstable angina, sudden cardiac death, transient MI, and ischemic stroke.1-6 Objective assessment with plasma creatine kinase levels has shown a marked circadian variation in the onset of MI, with a peak incidence occurring between 6:00 am and noon and a lower incidence occurring at night.1
Second, is there a difference in the care delivered during routine working hours compared with off-hours? The Maximal Individual Therapy in Acute Myocardial Infarction (MITRA) study group examined patterns of performance of primary PCI between patients receiving treatment during daytime and nighttime hours.7 Of 491 patients, 77% were treated during the day, and only 23% were treated at night. Patients in the night group had a shorter time to presentation. There was no significant difference between the two groups in clinical outcome. Because of the huge difference between the number of nighttime-treated patients in the eight centers (from 8% to 44%) and the small number of patients treated at night (23%), selection bias may have played a role in the MITRA analysis. The effect on clinical outcome of circadian variations in either symptom onset or treatment has not been studied in hospitals, where all acute ST-segment elevation MI patients are treated with primary angioplasty. We therefore investigated the circadian variation in symptom onset, hospital admission, and first balloon inflation in patients with acute MI. Additionally, we studied the influence of these circadian patterns on clinical outcome in patients with acute ST-segment elevation MI treated with primary angioplasty during routine working hours and during off-hours.
Patients and methods
We studied 1,702 consecutive patients with acute ST-segment elevation MI, treated at our hospital, including those who presented within 6 hours after symptom onset. Patient characteristics were described previously.8 The ambulance crew or staff at one of the 11 referring hospitals located within 94 km from our hospital diagnosed acute MI in 860 patients. All patients from these hospitals who require PCI are referred to our hospital.
The 860 patients received aspirin (500 mg intravenously [IV]) and heparin (> 5,000 IU IV) before transportation to our hospital. For the remaining 842 patients, the diagnosis of acute MI was established in our hospital, and they received IV aspirin and heparin after admission before going to the catheterization laboratory. No patients received fi-brinolytic therapy or glycoprotein IIb/IIIa blockers before angiography. All primary PCI procedures, during both routine working hours and off-hours, were performed by senior staff members. Follow-up
for 30 days was completed for all patients.
The frequency of symptom onset, hospital admission, and first balloon inflation was associated with a circadian variation. The patterns of frequency of symptom onset, hospital admission, and first balloon inflation were similar, with some circadian variation (figure 1). There was also a circadian variation in the 30-day mortality rate. The mortality rate in the first 30 days after successful angioplasty was 2.2%, compared with 17% after failed angioplasty, confirming the strong relationship between mortality and angioplasty failure (figure 1).
The majority of patients (53%) were treated during the routine working hours of our hospital, between 8:00 am and 6:00 pm. There was no difference in clinical baseline characteristics and antegrade flow in the infarct-related artery between patients treated from 8:00 am to 6:00 pm and those treated from 6:00 pm to 8:00 am. Patients treated between 6:00 pm and 8:00 am had a significantly higher rate of failed angioplasty procedures compared with patients treated between 8:00 am and 6:00 pm (figure 2). The 30-day mortality rate was also higher for patients treated from 6:00 pm to 8:00 am compared with patients treated from 8:00 am to 6:00 pm (figure 3).
Our study confirms that there is a circadian variation in the time of symptom onset, hospital admission, and treatment of acute MI. Because of the distribution in time of onset of MI, most primary angioplasty procedures are performed during regular working hours, from 8:00 am to 6:00 pm. The observation that patients treated during off-hours had a worse outcome, with a higher rate
of angioplasty failure and, as a result, a higher 30-day mortality rate, is the more important finding. There may be three reasons for this. First, there may be different baseline clinical characteristics associated with better outcomes for patients who are treated during the day; among patients who have MIs at night, an increased risk of congestive heart failure has been reported.9 In our study, there were no differences in the baseline clinical characteristics, including Killip class, between patients treated during the day and those treated at night, suggesting that this mechanism was not involved in our study.
Second, the efficacy of reperfusion therapy may be at least partly related to circadian variations. These variations have been documented for platelet aggregation,10 coronary flow, viscosity, cortisol levels, epinephrine levels, and activated partial thromboplastin time and thrombin time. It has been suggested that fibrinolysis increases at night, as shown by levels of tissue-type plasminogen activator and other factors related to natural fibrinolytic activity. Additionally, a circadian pattern in the efficacy of streptokinase and tissue-type plasminogen activator has been reported.11,12 The efficacy of several thrombolytic agents may thus be related to the circadian variation in the balance between prothrombotic mechanisms and the natural fibrinolytic system. The success of primary angioplasty may also be affected by this balance.
Third, quality of care may be related to the time of day the patient receives treatment. The time of delay from admission to first balloon inflation13 and hospital and physician volume14 are reportedly related to outcome after primary angioplasty. It is therefore conceivable that the quality of care delivered during the day may differ from the care given
at night because of variations in the performance of the physicians, catheterization laboratory, and coronary care staff. Even high-volume centers may have significant intercenter variation in outcome for patients treated with primary angioplasty.15
Clinical outcome is influenced by time from hospital admission to first balloon inflation, which may serve as an indication of quality of care. Our study showed no circadian variation in the time from hospital admission to first balloon inflation, suggesting consistent quality of care; our hospital strives to provide optimal quality care for large numbers of patients with acute MI 24 hours a day, 7 days a week. This mechanism, however, appears to at least partly explain the results of our study.
Whether the higher incidence of failed angioplasty for patients treated during off-hours is related to circadian variations in the balance between natural prothrombotic and fibrinolytic factors or to the quality of care could not be analyzed by our data. It is necessary to develop techniques to evaluate quality of care for patients with acute ST-segment elevation MI who are treated with primary angioplasty, and if the balance between prothrombotic mechanisms and the natural fibrinolytic system
is shown to play a role, beneficial adjunctive medication should be developed.
There is a circadian variation in patients presenting with acute MI, which has an enormous effect on
the success of primary angioplasty. Most patients are treated during regular working hours, and they have a higher procedural success rate and a better clinical outcome than patients treated during off-hours.