ST-elevation myocardial infarction (STEMI) is a medical emergency that has high morbidity and mortality if not promptly and appropriately treated. Since mortality is higher in the first few hours, and early reperfusion, ideally by primary percutaneous coronary intervention (PPCI), is associated with better prognosis, it is essential to transport patients as quickly and safely as possible to the catheterization laboratory.1,2

Based on the notion that “time is myocardium”, current guidelines recommend a target door-to-balloon time (DBT) of ≤90 min (ideally ≤60 min, especially in high-risk patients with anterior myocardial infarction [MI] who present early – within two hours of symptom onset – or who are seen in an institution with 24-hour PPCI capability), which is a measure of the quality of hospital care for STEMI patients.2,3 Various measures have been proposed and different programs implemented in order to improve the quality of care and to reduce delays in access to PPCI. A pre-hospital emergency medical system (EMS) is a crucial link in the chain of survival for STEMI patients, since it enables rapid diagnosis and referral for PPCI, with the patient being transported directly to a center capable of performing mechanical reperfusion, accompanied by a team trained in advanced life support.4–6 Pre-hospital diagnosis, triage and initial treatment by an EMS team have been shown to be associated with greater use of reperfusion therapy and reduced delays, leading to better clinical outcomes in STEMI.7,8 Nevertheless, studies report that the EMS continues to be underused and that many patients arrive at the hospital by their own means.4,9,10 The Portuguese Registry of Interventional Cardiology shows that despite greatly improved access in recent years to PPCI, only 38% of MI patients use the EMS.5

The objective of this study was to describe developments in pre-hospital transport of a series of STEMI patients undergoing PPCI over an eight-year period to 2015 and to characterize this population and assess the impact of recourse to the EMS on in-hospital and one-year clinical outcomes.

During the study period, 788 consecutive patients were admitted to our center for STEMI and underwent PPCI, of whom 24 were excluded due to incomplete data. Of the 764 analyzed, 256 (33.5%) were transported by the EMS and the remaining 508 by non-EMS means: 350 (45.8%) arrived at the emergency department by their own means, 105 (13.7%) were transferred from another hospital and 53 (6.9%) were transported by non-EMS ambulance. Figure 1 shows developments in type of hospital admission over the last eight years. There was a general trend for greater use of the EMS rather than patient's own means, although without statistical significance (p=0.241).

Figure 1.

Developments in type of hospital admission over the last eight years. EMS: pre-hospital emergency medical system.

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Table 1 summarizes the clinical, demographic and procedure-related characteristics of the EMS and non-EMS groups. There were no significant differences in cardiovascular risk factors, current therapy or procedure-related variables. Patients with previous infarction were more likely to use the EMS than those who presented with preinfarction angina. Although there were no significant differences in clinical risk scores (GRACE or TIMI) at admission, the EMS group more often presented in Killip class III/IV heart failure.

The study population presented a median TIT of 240 min (83.8% had TIT of >120 min) and median DBT was 85 min. The EMS group had significantly shorter TIT and DBT, by 91 and 29 min, respectively, compared to the non-EMS group (median TIT 195 [IQR 150] vs. 286 [IQR 360] min, p<0.001; and median DBT 61 [IQR 55] vs. 90 [IQR 90] min, p<0.001) (Table 2). A significantly larger proportion of patients in the EMS group achieved the target DBTs of ≤90 min (73.8% vs. 55.2%, p<0.001) and ≤60 min (49.6% vs. 33.9%, p<0.001) (Figure 2).

Figure 2.

Percentages of patients achieving door-to-balloon time of ≤60 and ≤90 min. DBT: door-to-balloon time; EMS: pre-hospital emergency medical system.

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With regard to in-hospital results (Table 3), there were no significant differences in peak enzyme levels, length of hospital stay or major adverse cardiac events. A lower percentage of patients in the EMS group presented moderate to severe left ventricular systolic dysfunction, albeit without statistical significance.

The no-reflow phenomenon was observed in 8.2% of patients after PCI, effective reperfusion being achieved in 91.8%. Patients who presented at the hospital earlier (DBT ≤60 min) showed significantly higher reperfusion rates (94.8% with DBT ≤60 min vs. 90.2% with DBT >60 min, p=0.020). Among the patient subgroup with DBT ≤60 min, those that used the EMS derived greater benefit, with effective reperfusion rates of 97.6% vs. 92.4% in the non-EMS group (p=0.042). Effective reperfusion was associated with significantly lower in-hospital mortality, 6.9% vs. 33.9% in those not effectively reperfused (p<0.001). After multivariate analysis (adjusted for Killip class at admission, age, diabetes, dyslipidemia, smoking, preinfarction angina and creatinine clearance), effective reperfusion was an independent predictor of in-hospital mortality (hazard ratio [HR]: 3.78 [95% confidence interval (CI) 1.69-8.47], p=0.001), as was presentation in Killip class III/IV and low creatinine clearance (HR: 10.72 [95% CI 5.46-21.06], p<0.001 and HR: 0.98 [95% CI 0.96-0.99], p=0.008), respectively.

Analysis of one-year follow-up (Table 4) showed that mortality was higher in the non-EMS group, but without statistical significance. There were also no significant differences in other adverse cardiac events. Figure 3 shows the one-year cumulative survival curve. In univariate analysis, age, diabetes, hypertension, current smoking, previous infarction or preinfarction angina, TIT, DBT, Killip class III/IV at admission and moderate/severe left ventricular dysfunction at discharge correlated with cumulative mortality. These variables and type of admission (EMS vs. non-EMS) were included in the multivariate analysis, which showed that only Killip class III/IV at admission (HR: 6.315 [95% CI: 3.314-12.042], p<0.001), moderate/severe left ventricular dysfunction (HR: 2.486 [95% CI: 1.352-4.57], p=0.003) and age (HR: 1.050 [95% CI: 1.020-1.082], p=0.001) remained as independent predictors, use of the EMS having no independent effect on this outcome. Similarly, there were no statistically significant differences in one-year mortality between patients with and without effective reperfusion (9.8% vs. 4.2%, p=0.105).

Figure 3.

Cumulative survival at one-year follow-up. EMS: pre-hospital emergency medical service.

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Following the implementation of various measures and programs in Portugal in recent years, our study shows a progressive increase in use of the EMS as opposed to patients’ own means, which has resulted in significant reductions in both DBT and TIT. Compared to the non-EMS group, patients using the pre-hospital EMS had significantly shorter reperfusion times, the target DBT of ≤90 min being achieved in 73.8%, and in 49.6% of these, DBT was ≤60 min. These results are in agreement with various studies that have shown the positive impact on reducing ischemic times of measures such as use of the EMS, pre-hospital ECG, and direct transport of STEMI patients to centers with catheterization laboratories.4,9–13 Nevertheless, only a third of patients in our study used the EMS, a disappointingly low proportion. As in a study by Fujii et al.,13 patients with previous MI were more likely to use the EMS, as were those in shock or with more severe heart failure at admission. This suggests that this group includes more severe patients, whose condition makes it easier to recognize the need to activate the EMS. In addition, with regard to those with previous infarction, the education and knowledge gained during the previous event means that they are more likely to recognize the symptoms and therefore to use the EMS.13 By contrast, patients with preinfarction angina are less likely to use the EMS, which may be explained by the fact that since angina can be intermittent these patients tend to perceive their condition as being less serious. Furthermore, in the above study by Fujii et al., patients who presented chest pain as the initial symptom, as opposed to syncope, dyspnea or disturbed consciousness, were less likely to use the EMS, which to some extent shows patients’ lack of knowledge, or failure to recognize the symptoms of MI, particularly atypical manifestations.13

Clinical and experimental studies have shown a direct and continuous relationship between ischemic time, transmural necrosis and microvascular obstruction. Thus, greater benefit will be derived if blood flow is restored sufficiently early to prevent irreversible necrosis.14–16 In a study by Francone et al., the percentage of myocardial salvage as assessed by cardiac magnetic resonance imaging was higher in the patient group with TIT ≤90 min, and the extent of microvascular obstruction was less.17 Eitel et al. also showed that the myocardial salvage index was higher in the first two hours following symptom onset and that the strongest predictors of this index were complete ST-segment resolution, time from symptom onset to reperfusion and anterior infarction.18

Various recent studies have focused on DBT and its impact on clinical outcomes, but the results have been conflicting. Efforts to reduce DBT have not consistently been associated with reduced mortality.6,19 Some studies failed to show improved prognosis despite progressively shorter ischemic times.19–21 Our study found that although patients in the EMS group presented significantly shorter DBT and TIT, this was not reflected in lower mortality or fewer in-hospital major cardiac events. Similarly, although there was a trend for lower mortality in the EMS group at one-year follow-up, the survival curve diverging during follow-up, the difference was not statistically significant. These results are in line with those of large-scale studies, particularly that of Menees et al., which included 96738 STEMI patients undergoing PPCI, and showed that despite annual reductions in DBT, in-hospital and short-term mortality rates remained unchanged, even after analysis of risk subgroups.19 A Portuguese study by Bettencourt et al. also showed that although use of the EMS had a significant impact on reducing ischemic times, this was not reflected in significant differences in clinical course or in-hospital or one-year mortality.22 On the other hand, several other studies have reported an association between reductions in DBT and improved clinical outcomes.23,24 Such conflicting results may be due to the presence of multiple confounding factors. While DBT is an essential component, it does not fully reflect TIT since it does not take into consideration the time between symptom onset and admission, and does not necessarily mean significantly shorter TIT. A study by Prasad et al., which assessed the effect of TIT and DBT on microvascular perfusion, showed that TIT is an independent predictor of impaired myocardial perfusion as determined by both reduced myocardial blush grade and incomplete resolution of ST-segment elevation, and that this is associated with three-year mortality. DBT of ≤90 min only had an impact in patients with TIT of less than two hours.25 Other studies, such as those of Solhpour et al.26 and Sardar et al.,27 which compared the impact of reductions in TIT and DBT, showed that TIT is a better predictor of infarct size and 30-day mortality. Shiomi et al. also showed that a reduction in DBT was independently associated with lower risk for the composite endpoint of death and heart failure in patients who presented early (≤120 min) but not in those who presented later, which highlights the importance of seeking rapid medical attention.28 Many patients present late, outside the critical window for myocardial salvage. This may partly explain our results, since although the EMS helped to reduce ischemic times, median TIT in both groups was over two hours, which may have lessened the potential benefit of shorter DBT. However, in recent years, new reperfusion techniques and drug therapies have led to a significant reduction in mortality due to STEMI.2,6 Great emphasis has been placed on DBT and various efforts have been made to reduce it, not only during the pre-hospital period but also during in-hospital triage and management. In our study, even though the EMS group had significantly shorter DBT, both groups presented DBT of ≤90 min, with a median difference of 29 min. This raises the question of what benefits in terms of clinical outcomes can be expected from a modest reduction in ischemic times, particularly in an era in which mortality is already relatively low. DBT may now have reached the point where further reductions will have little impact on in-hospital or short-term mortality but may affect long-term outcomes or future hospitalizations for heart failure.6,14 However, our study showed that patients who presented earlier (DBT ≤60 min) had a significantly higher rate of effective reperfusion (particularly those in the EMS group), and that this was independently associated with significantly lower in-hospital mortality. This reflects the beneficial effect of early presentation on angiographic results and its correlation with in-hospital clinical outcomes.

When analyzing the impact of ischemic times on clinical outcomes, other confounding variables should be taken into account. Patients with longer DBT may have had other reasons for delay in seeking medical attention, including comorbidities or a more severe clinical setting that required stabilization before PPCI, which in itself would confer a worse prognosis. Furthermore, patients who use the EMS may generally have less favorable characteristics. In our study, the percentage of patients in Killip class III/IV at admission was significantly higher in the EMS group, and this parameter, together with age and moderate/severe left ventricular dysfunction, was an independent predictor of cumulative mortality. The time from symptom onset may not in fact correspond to TIT; many patients present silent ischemia, atypical or fluctuating symptoms with prodomal angina, which can make it difficult to establish the actual time of symptom onset. In addition, as in other studies on this subject, our analysis did not include patients who died before reaching hospital, which introduces a survival bias.4,6,13,19,29

Reducing TIT in the context of STEMI should still be a priority. There are many benefits, especially in areas without ready access to PPCI and in patients who present late. Additional efforts to raise awareness among the general public of the symptoms of MI and of the importance of seeking early treatment, aimed at reducing delays in seeking medical attention and in transport (particularly by using the pre-hospital EMS), may lead to more patients presenting in the first hours of ischemia when the benefits are greatest, which will undoubtedly be reflected in clinical outcomes.

The study has the limitations inherent to its retrospective, observational nature and the fact that it is based on the experience of a single center and may not therefore be fully representative of the situation in the country as a whole. The study did not include patients who suffered sudden death before coronary angiography could be performed, nor did it analyze those who underwent resuscitation by EMS teams, which means that the true impact of the EMS on mortality may be underestimated. Presenting symptoms, socioeconomic data and educational levels of the study population were not analyzed, nor were the reasons that they did or did not activate the EMS.

Our study found that recourse to the EMS significantly reduced ischemic times. Although this improvement was not directly associated with significant differences in mortality or in-hospital or one-year clinical outcomes, it was associated with higher rates of effective reperfusion that were reflected in lower in-hospital mortality. Recent years have seen a trend for increased use of the EMS, albeit still less than desirable, and a significant percentage of patients continue to present late, with TIT of >120 min. New measures and increased efforts to raise awareness among the general population should continue in order to improve the prognosis of STEMI patients.

The authors have no conflicts of interest to declare.