In the present examination of patients undergoing primary PCI for ST-elevation myocardial infarction, we observed a greater than a two-fold higher risk for subsequent combined in-hospital mortality, myocardial infarction and target vessel revascularization among patients treated during off-hours compared to routine-hours. In examining whether circadian-related biologic differences were factors, we found that the majority of lesion characteristics in both groups were quite similar, including the rates of TIMI Grade 0 Flow prior to PCI, presence of thrombus, location of infarct-related artery, and ACC classification scores of the lesions. Patients presenting off-hours had similar clinical characteristics as well, with the notable exception of higher rates of cardiogenic shock and multi-vessel coronary artery disease.
Despite similar lesion characteristics, we found that lesions treated at night were more often accompanied by procedural complications including dissection. Procedural success was a significant factor in subsequent adverse outcomes, but even patients with successful procedures had higher risk of adverse events during off hours.
Our findings are consistent with the prior observation that higher angioplasty failure rates occur at night, though hitherto there has not been sufficient angiographic or procedural information to understand potential causes. (15
) In this respect, those complications which may be related to operator performance such as vessel dissection, were more frequent at night, whereas complications potentially related to lesion characteristics, such as distal embolization, were not. The use of time-consuming devices was also less frequent at night than during daytime hours, despite similar lesion characteristics. It is possible that diurnal differences in lesion characteristics, such as less TIMI Grade 3 flow in the infarct related artery at the time of intervention during off-hours, and diurnal differences in clinical characteristics, such as higher rates of cardiogenic shock, additionally affected operator performance. Lower rates of pre-procedural thienopyridine use during off-hours also may have contributed to higher procedural complications and reduced success.
When procedural success was not achieved, operators were more likely to state that the ‘lesion did not respond appropriately’ during off-hours. We found no significant differences in characteristics indicative of lesion complexity associated with adverse events after PCI (25
). However, flow characteristics prior to PCI were less favorable in off-hours patients, and rates of TIMI Grade 3 Flow were less often achieved after off-hours PCI. It is possible that circadian variations may be associated with differential outcomes following primary PCI. Notably, platelet aggregation is heightened during the morning hours (27
). A pro-thrombotic state has been associated with treatment outcome after both fibrinolytic therapy and elective PCI, with resistance to fibrinolytic therapy observed in the early morning hours (29
). Thus while it is possible that lack of procedural success was purely operator or procedurally related, it is likely that in some cases biologic factors also contributed to the lower success rates of PCI during off-hours, as poorer flow was present prior to PCI.
Although delays in treatment time have been shown to be a factor in poorer outcomes during off-hours (6
), in the present study, off-hour angioplasty was not associated with significant delay when using symptom onset to PCI time. Further, we found that the incidence of adverse events was only slightly higher on weekends, a time when delays would be expected to be greater than weekdays, with the majority of difference consistently occurring between nighttime versus daytime PCI, regardless of weekday or weekend. In addition, daytime outcomes were only slightly, and not statistically significantly, better during weekdays than weekends, suggesting that time delay was only one factor for subsequent adverse events.
Sicker patients may present during off-hours because of inability to wait for routine-hours. However, the converse has been postulated; namely, that waiting for routine hours will increase the risk for those who wait, independent of their initial severity. It has also been postulated that off-hours patients are sicker because MI onset while sleeping may lead to longer ischemic times upon arrival. We found higher rates of cardiogenic shock and higher rates of multi-vessel coronary artery disease in those patients presenting during off hours. In addition, TIMI Grade 3 Flow upon arrival to the catheterization laboratory was less likely upon arrival, although the infarct related artery was equally likely to be completely occluded in both groups. However, after accounting for these factors, off-hours presentation remained associated with poorer outcomes.
Unlike prior analyses, which mostly have been comprised of very large registries, we were able to examine detailed clinical and angiographic features in MI patients.(5
) In this regard, although difficult to study all potential factors, we found few differences in a wide variety of characteristics, leaving the possibilities of circadian-related differences and operator performance. As mentioned previously, a role for circadian biologic differences may be suggested by less favorable flow upon angiography and after PCI, and possibly by higher rates of multi-vessel coronary artery disease and cardiogenic shock. The possibility of operator fatigue also warrants careful consideration, as this is a potentially modifiable risk factor, and changes in public policy could mitigate its impact. For instance, there has been a recent strong emphasis on the need for public health measures aimed at improving quality of care in MI patients. Regionalization of MI care has been advocated by some, to allow shorter DTB times, and higher volume operators, both of which have been demonstrated to improve outcome. (32
) In a similar fashion, regional or high volume centers may be able to provide resources including more operators or less daytime duties in nighttime operators, which could reduce the impact of possible operator fatigue. If presently proposed measures are implemented in parallel to those which additionally address operator and staff fatigue, they may further enhance the benefits of primary PCI. (33
Finally, our findings suggesting that the potential hazard of off hours PCI is not solely related to differences in door to balloon time are supported by a recent analysis of the Get With the Guidelines (GWTG)-CAD database, where over 62,000 patients were examined, and found to have similar mortality rates, despite longer door to balloon times in the off hours group.(36
) Importantly, that analysis differed from the present study in that ours is exclusively a primary PCI cohort, whereas the GWTG database included 12% who received fibrinolysis, 34% who received no reperfusion therapy, and only 42% who had any revascularization. In addition, only 32% of patients in that study had ST elevation MI. Nonetheless, the STEMI cohort in that analysis also had no significant difference in mortality by time of presentation, but even in this cohort, only 60% underwent cardiac catheterization, and only 70% underwent any revascularization, whereas in our study, all patients underwent primary PCI for STEMI. Finally, our study by definition includes centers which have the capacity to provide primary PCI, whereas the GWTG database looks at many different types of care centers, including some without primary PCI capability. The wide variety of care and severity of illness in the patients examined in that study may have contributed to lack of appreciable differences in overall mortality by time of presentation, even in STEMI patients. Interestingly, despite these differences, Jneid et al., similarly conclude that ‘although ...campaigns to reduce time to reperfusion are laudable, improvements in DTB times should be complemented by multifaceted approaches to optimize multiple levels of medical care in parallel...”
This analysis uses symptom onset to PCI time. The prognostic significance of symptom onset is not clear, as some prior analyses have suggested lack of reliability, while others have found symptom onset to be more predictive of adverse events than DTB time. (34
) However, our evaluation of weekend PCI by time allows some understanding of the impact of a ‘closed’ cardiac catheterization laboratory and the effects of its delays in door to balloon time. Weekend PCI analysis is a means of stratifying outcome, though separate multivariable adjustments were not made for this particular exploratory analysis. The number of control variables required in multivariate models is high given this event rate, leading to over fitted models. Finally, in this cohort study, it is possible that differences that are not fully controlled by the statistical methods exist.
The current study observed over 2.7-fold higher risk for in-hospital mortality, myocardial infarction, and repeat target vessel revascularization in patients treated with primary PCI during off-hours. Off-hours primary PCI was associated with lower angiographic success, and higher complication rates, and may suggest both biologic factors including poorer anterograde flow, as well as nighttime performance issues such as operator fatigue, reduced utilization of adjunctive devices, and lower pre-procedural thienopyridine use as contributors to poorer outcome. As such, factors that extend beyond differences in DTB time may contribute to poorer outcomes in patients presenting with myocardial infarction during off hours.