Characterization of prehospital time delay in primary percutaneous coronary intervention for acute myocardial infarction: analysis of geographical infrastructure-dependent and -independent components

A total of 1341 STEMI patients in the 8-month registry were enrolled in this study. Although the number of cases in the registry is relatively small, the crude incidence of STEMI was calculated to be 37.4 (/100,000 persons/year), similar to previous Japanese registry data [20, 21]. In addition, a high percentage (86%) of PCI facilities in Hokkaido participated in the survey, indicating that there was probably minimal selection bias among the study subjects and facilities.

The median TIT in the present study cohort was 185 min, which is comparable to TIT data in high-income countries (2.0–4.0 h) [22,23,24]. Factors that were shown to be associated with prolonged TIT in previous studies include age, sex, type of symptoms, misinterpretation of the disease by patients or medical practitioners, absence of a witness, time of onset, use of EMS, social class, and distance from a hospital at the time of onset [15, 18, 24,25,26,27,28]. Older patients are more likely to have atypical or asymptomatic symptoms [27]. Sex differences were attributed to age, comorbidities, symptoms, social support, and insurance characteristics [25, 27]. Social and emotional factors can also contribute to delays in seeking care. For example, concern for social propriety can delay care-seeking because people do not want to trouble others. Additionally, patients may feel embarrassed when symptoms occur during off-hours and when they consider the possibility that their symptoms are not severe [28]. Consistent with earlier findings, advanced age, absence of a witness, nighttime onset, no EMS call, and symptom onset in a rural region (without direct transfer) were associated with prolonged TIT in the present study (Table 2).

As expected, ODT and TIT in the Direct ambulance-transport group were the shortest among the four groups with different transport pathways (Fig. 3). DBT in the inter-facility transport group tended to be shorter than that in the direct transport group. The reason why DBT in the inter-facility transfer group tended to be shorter than that in the direct transfer group is that the diagnosis of AMI had already been made at the previous medical facility, and the time for treatment and explanation was therefore reduced at the medical facility to which the patient was transferred. However, the shortening was not sufficient to compensate for the time delay caused by going through a non-PCI facility. These results are consistent with those of earlier studies [29, 30]. The proportion of ODT in TIT was much larger than that of DBT, confirming that prehospital delay is a significant cause of TIT prolongation.

The proportion of STEMI patients with ODT ≤ 120 min was 56% in the present registry (Fig. 4A). One of the major components of ODT is the patient’s decision time [25], and thus public education programs for improving the recognition of AMI and promoting the use of EMS have been conducted in some countries since the 1980s. However, such public interventions have not markedly changed the situation, and a recent study in Germany showed that TIT instead increased from 1994 to 2002 [26]. In the present study, we used pretransport time as an index of the patient’s decision time and it was found that pretransport time significantly differed between the Direct ambulance-transport group and the Inter-facility ambulance-transport group (median 40 vs. 63 min) (Fig. 3). Older age and nocturnal onset were associated with pretransport time prolongation (Table 2), which may be due to differences in symptoms and/or patient responsiveness to those symptoms [31]. These findings suggest that public and patient education should focus on the elderly and appropriate treatment-seeking behavior for STEMI symptoms at night. Interestingly, winter onset was associated with shorter pretransport time, despite the fact that AMI patients admitted in the cold season tend to have worse severity and prognosis [32]. This may be related to shorter pretransport time in winter, particularly in the interval from onset to EMS call (as shown in Additional file 1: Table S1).

The length of ODT for STEMI patients can be influenced not only by patient and hospital factors but also by factors related to patient transportation, such as geographical distance, number of routes from the onset location to a PCI facility, and availability of EMS. A study by Jena et al. showed that infrastructural factors could have a significant impact on outcomes of patients with myocardial infarction [33]. They showed that ambulance travel time was prolonged by 4.4 min and that adjusted 30-day mortality increased by 3.4% during big city marathons that involved widespread road closure and diversion of the EMS. In the present study, ODT was analyzed separately as a factor dependent on geographic infrastructure, min-PST, and as a factor dependent on other factors, eDAD, in order to identify appropriate and effective interventions. The percentages of patients in the short eDAD group who had onset in urban medical regions and did not across medical regions were higher than those in the long eDAD group (Additional file 1: Table S2). Emergency medical teams in Japan are organized by medical region, and Hokkaido has 21 medical regions (Additional file 1: Fig. S1A and B). Therefore, patients tend to be initially transported to a medical institution in the medical region to which they belong, even if there is a hospital nearby in a neighboring medical region and if the hospital is far away or is a non-PCI facility. The shorter eDAD in urban medical regions may be due to more PCI facilities and fewer inter-facility transfers, making it less likely for a second eDAD to occur. The factors related to eDAD prolongation included not only factors associated with pretransport time prolongation (i.e., older age and nighttime onset) but also no EMS call and inter-facility transfer, regardless of regional differences (Table 3). These findings suggest that it may be possible to shorten eDAD, even under the condition of the current geographic infrastructure, by increasing the proportion of direct EMS transport. On the other hand, there are certain areas in Hokkaido where min-PST is unacceptably long (Additional file 1: Fig. S2). In these areas, it was found that patient guidance and the efforts and cooperation of the EMS team could not effectively shorten ODT. This suggests that other treatment strategies or improving the geographic infrastructure may be necessary to reduce ODT in these areas.

The cumulative frequency distribution of ODT showed that ODT was more than 120 min in nearly half of the STEMI patients enrolled in the survey (Fig. 4A). This indicates that further interventions are necessary to shorten ODT in Hokkaido. However, if eDAD is eliminated, only "true" geographic infrastructure-dependent time remains, and ODT is projected to be less than 120 min in more than 90% of cases in Hokkaido (Fig. 4B). This projection suggests that eDAD, as well as the infrastructure for STEMI patient transport, is an important target to increase the number of STEMI patients who can receive timely PCI. In addition, the projection indicates that at least a few percent of patients cannot receive timely PCI. In such cases, fibrinolytic therapy [1,2,3, 34] (which is not common in Japan [23]) or air medical services to transport patients to PCI facilities [35] may be options.

Poor clinical outcome in the present study was predicted by age ≥ 75 years, Killip class 3/4 on arrival, and EMS call as in earlier studies [16, 17] (Table 4, Model 1). Onset in a rural region with inter-facility transfer was also associated with poor outcomes. Differences in medical resources and the extension of TIT may explain the association. Efforts to increase the percentage of direct transport and the previously mentioned fibrinolytic therapy or utilization of air medical services may provide solutions. On the other hand, the association between prolonged TIT and worsening clinical outcomes in STEMI patients has been inconsistent in observational studies [9, 36], and such an association was not found in the present study subjects (Table 4, Model 2). Possible explanations for this inconsistency include confounding and selection bias in study subjects [9], misalignment of onset of coronary occlusion and symptom onset, lack of consideration of parameters that influence the severity of myocardial ischemia such as presence or absence of pre-infarct angina [37], and differences in length of the follow-up period between the studies. Although the impact of short TIT on the outcome of STEMI remains controversial, an attempt to shorten TIT would be justified since it potentially increases the benefit of primary PCI without specific adverse effects.

Study limitations

There are several limitations of the present study. First, this study was a non-randomized observational study; thus, causal relationships between the parameters and/or outcomes cannot be concluded. Second, there may have been some selection bias for enrolment because the present study included only patients with information for the onset of symptoms, reaching a PCI facility, and undergoing primary PCI. Third, we could not use cardiac function, heart failure, or cardiovascular death as clinical endpoints since they were not prespecified in data collection sheets in the Hokkaido Acute Coronary Care Survey. Fourth, data for medications prior to STEMI onset, comorbidities, and therapy afforded in non-PCI facilities were unavailable and could not be used to adjust the study subjects' clinical outcomes. Finally, consumer-available GIS software does not take into account the difference between standard ground transportation time and ambulance transportation time, and eDAD may therefore have been underestimated in this study.

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