Critical Appraisal of Medical System Performance for STEMI Management – a Comprehensive Analysis of Time Efficiency

The “Prof. Dr. C.C. Iliescu” Emergency Institute for Cardiovascular Diseases, Bucharest, Romania is part of a group of six hospitals that provide 24/7 services for emergency interventional cardiology procedures by a rotating schedule. Our institute provides these services two times per week, and referrals include the southeastern area of the country, covering approximately 71,000 km², with the longest distance of roughly 260 km.

The present analysis takes into consideration only patients admitted to the “Prof. Dr. C.C. Iliescu” Emergency Institute for Cardiovascular Diseases, which will be referred to as the “PCI center” throughout this manuscript. We prospectively included 500 consecutive patients admitted with a working diagnosis of STEMI, during a period of time of 14 months, from April 2022 to May 2023. STEMI was defined as persistent chest pain and/or other symptoms of myocardial ischemia associated with ST-segment elevation on at least two contiguous ECG leads, or newly diagnosed bundle branch block, accompanied by an increase in highly-sensitive cardiac troponin.8 Patients with non-ST elevation myocardial infarction were excluded from this analysis, regardless of the risk group. Patient outcomes were evaluated during index hospitalization, until discharge.

Interventional procedures were performed in accordance with conventional and local practices. All patients underwent emergency coronary angiography. PCI with stent implantation was performed in all cases where technical feasibility allowed it. All stents used in this population were second-generation drug-eluting stents (DESs). Angioplasty with drug-eluting balloons (DEBs) or plain-balloon-angioplasty (POBA) were used at the operator's discretion. Adjuvant equipment (such as aspiration thrombectomy) and the intraprocedural usage of GP IIb/IIIa antagonists are noted accordingly. If PCI was performed, the antiplatelet regimen included association of aspirin with a thienopyridine at the physician's preference (75 mg of clopidogrel or 180 mg of ticagrelor).

The methods of arrival at the PCI center assumed four possible scenarios: Arrival by ambulance from home (defined also as Primary route) was defined as transport from the scene of symptoms onset directly to the PCI center with an ambulance, without a provisional stop at another hospital. Transport from another hospital (defined also as Secondary route) implied a provisional stop at a different hospital before arrival at the PCI center (because of imperfect data, for this category of patients the First medical contact (FMC) timepoint was omitted, and only the First ECG timepoint was used, as it will be described). Self-presenter was defined as presentation to the emergency department of the PCI center using personal means of transportation. Already in-hospital was reserved for patients with a STEMI diagnosis established while already admitted to the PCI center.

The complete ischemic timelines were created using several key timepoints. Symptoms onset was used as the start point for the total ischemic time (if the patient presented with intermittent symptoms, the time recorded was the one of the symptoms that required ambulance notification or self-presentation to the hospital). First contact with ambulance (or FMC) was defined as the time when the ambulance arrived to the patient. First ECG was the time when the first recorded ECG was interpreted as ST-segment elevation or equivalent. Hospital arrival was defined as the time when the patient arrived in the emergency department of the PCI center. Arrival to cath lab was used interchangeably with Arterial access time, defined as the moment when the arterial sheath was in place. Wire passage was used as the timepoint when the coronary wire was placed distal to the culprit lesion regardless of the coronary flow. Revascularization time was defined as the moment when coronary flow was secured (mainly when the stent was placed, but the same timepoint was used if POBA or DEB were used as final angioplasty method). Total ischemic time (TIT) was defined as the period from symptoms onset to revascularization. Emergency system delay (EMS) was defined as the period from First contact with ambulance or First ECG (for transfers) until arrival at the PCI center. Hospital delay (delay within the PCI center) was defined as the period from arrival to the PCI center to revascularization.

PCI attempted was considered when an attempt was made to place a coronary wire in the culprit vessel, regardless of the outcome of angioplasty. Successful PCI was defined as <20% residual stenosis by visual inspection associated with TIMI 3 flow. For In-hospital myocardial reinfarction the fourth universal definition was used.¹³ Current recommendations were used to define In-hospital bleeding events.¹⁴

Categorical data is shown as absolute and relative values. Continuous variables are shown as mean ± standard deviation for values with normal distribution, or as median and interquartile range (IQR) for non-normally distributed values. Histograms and the Shapiro–Wilk test were used to assess for normality. Intergroup comparison for categorical variables was performed using the chi-squared test or Fisher's exact test, if appropriate. For continuous data, Student's t test or the Kolmogorov–Smirnov test were used. All reported p values are two-sided, and significance was established for values of <0.05. Data analysis was performed using IBM SPSS Statistics for Windows, version 20 (IBM Corp).

The final analysis includes a total number of 500 patients. Baseline characteristics and admission data for the study population are presented in Table 1. The large majority of the patients were male (74.6%), and the overall median age was 61.7 ± 12.08 years. There is also a clear preponderance of active or former smokers (63.4%). Arterial hyper-tension was the most frequently encountered comorbidity (75.2%), followed by type 2 diabetes (23.4%).

The vast majority of patients (93%) presented with chest pain as the main symptom. Cardiac arrest was found as the sole clinical manifestation in 4.2% of the cases, and as an accompanying manifestation prior to hospital arrival in 7.6% of the cases. Prehospital thrombolysis was performed in 32 patients (6.4%). On the ECG from admission, ST-segment elevation was localized most often in inferior leads in 45% of cases, followed closely by anterior location in 43% of the cases. At the moment of arrival, a clinical picture equivalent of Killip classes II–IV was observed in 81 cases (16.2%), and overt cardiogenic shock was noted in 27 cases (5.4%). Transthoracic echocardiography was performed in all cases at the emergency department, before emergency angiography. Left ventricular ejection fraction was normal in 24.2% of the patients and below 30% in 10.2% of the patients (Table 1).

Data related to the diagnostic coronary angiography and to the PCI procedures are detailed in Table 2. The most frequent finding was single coronary vessel involvement (52.2%), followed by two-vessel disease (26.6%). Significant left main disease was identified in 5.8% of cases, most frequently associated with three-vessel involvement. Right coronary artery was considered the culprit vessel in 41.7% of cases, followed by left anterior descending artery (38.8%). The detailed distribution of culprit lesions by coronary segment is shown in Table 2. The culprit artery showed total flow obstruction (TIMI 0) in the majority of cases (62.6%) and normal coronary flow (TIMI 3) regardless of the underlying stenosis in 9.8% of cases. In patients with prehospital thrombolysis, a TIMI 0 flow was less frequently encountered (43.3% vs. 63.7%, p = 0.107), with the difference being distributed towards TIMI flows 1 and 2 (Table 3).

During the index procedure, PCI was attempted in 477 patients (95.4%) (Table 2). Radial access was the preferred vascular approach in 61.2% of the cases. The main predictors for femoral access were cardiac arrest prior to hospital admission, Killip classes III and IV, and body mass index <21 kg/m². There were no significant differences in procedural time variables between the two vascular approaches (Supplementary Table 2). With respect to possible vascular complications capable of prolonging hospitalization time, there appeared to be a significant difference in favor of the radial approach compared to the femoral approach (mean number of days until discharge 5.6 vs. 8.39, p = 0.03). However, the difference became non-significant when correction for confounding factors was made (5 vs. 5.93, p = 0.18) (Supplementary Table 2).

Successful PCI was achieved in 96.6% of the PCI attempted cases. Angioplasty with at least one stent was performed in 428 patients (85.6% of the entire population), with a total number of 540 stents implanted (DESs exclusively) (Table 2). The median stent length was 23 mm, and the median diameter was 3 mm. DEB was used in three cases (0.5%) in secondary culprit vessels: a diagonal artery and two marginal branches of the left circumflex. The median diameter of the DEB was 2.5 mm. POBA was used in 33 lesions (5.7%). Complete revascularization during the index procedure was achieved in 53.8% of the patients. The rate of periprocedural events was 7.4%; details are shown in Table 2. Pharmacological and mechanical vascular support were required in 5.4% and 2.6% of the cases, respectively.

In-hospital events are described in Supplementary Table 3. The median duration of hospitalization was 5 days, and the rate of in-hospital death was 5.6%. Treatment at discharge included aspirin in 97.6% of the cases, and a P2Y12 inhibitor was included in 93.8% of cases, predominantly ticagrelor (59.6%). Discharge treatment details are available in Supplementary Table 4.

Overall, the patients arrived to the PCI center predominantly via the secondary route (transfer from another hospital) in 59% of the cases, followed, in approximately a third of the instances, by the primary route (ambulance transport directly from the scene of symptoms onset) (Supplementary Table 5). However, when patients arrived from outside of Bucharest, primary route decreased to 14.5%, and the large majority of cases (75.3%) involved a provisional stop at another hospital, as illustrated in Figure 1. Regarding patients arriving from Bucharest, 55.3% arrived via a primary route and 35.2% were transferred from other hospitals.

The TIT represents the interval from symptoms onset to culprit vessel revascularization. Given that it embodies all the other time intervals used in STEMI studies, it has lost some of its robustness and significance as a target indicator. Therefore, current guidelines focus more on the components of the TIT.^7,8 Nevertheless, each second of myocardial ischemia leads to increases in infarct size and area of microvascular obstruction area.^15,16,17 Thus, TIT appears to be able to independently predict short- and long term mortality,¹⁸ even with greater accuracy compared to door-to-balloon time.¹⁹ There is no clear prognostic cutoff for TIT, with several studies reporting statistically relevant prognostic values from 180 min to 240 min.^20,21 A recent analysis revealed a linear relationship between TIT and mortality, with a cutoff of 300 min that determines an exponential increase in mortality.²² In our analysis, the median TIT was 389 min, with only 43.4% of the patients having a TIT shorter than 360 min. The most favorable category, by time efficacy, was represented by patients arriving directly by ambulance, of which 62.6% had a TIT of less than 360 min. This is concerning particularly when considering that a reduction in other relevant intervals, such as door-to-balloon time, seems to offer mortality advantages only in case of lower TIT.^15,20 Some authors consider that patient negligence and lack of awareness are main contributors to increased TIT,²³ suggesting that Patient delay is a core reason for increased ischemic time.

In our analysis, overall patient delay was 200 min. Considering that TIT was 389 min, it becomes clear that more than half of the ischemic time is determined by the patient's lack of reaction. Even if we analyze only the patients who presented by ambulance (considering that EMS data for these patients is more accurate and there are no statistical interferences with emergency department delays), the patient delay remains at 48.4% of the TIT (Table 3). This can be attributed to various factors, most of which are related to patient education. However, correction of this behavior has proved harder than initially anticipated,^24,25,26 and more productive measures to increase patient awareness should be sought.

The recommended medical system delay is <120 min from the FMC to revascularization of the incriminated artery.8 In our analysis, this objective was accomplished in only 35.5% of the patients. The main source of system delay in accomplishing this target is identified as EMS delay for patients arriving by a secondary route, with a median time of 119 min from the STEMI diagnosis to arrival at the PCI center, whereas for the group of patients arriving by ambulance, the same interval had a median value of 40 min. This creates a delay of 1.8 h in STEMI diagnosis (Figure 3), which can be explained by several factors: delayed patient presentation to an emergency department (compared to those who call for an ambulance) or increased waiting time in the emergency department. Furthermore, the same group of patients showed an additional 1.3 h from the initial diagnosis to arrival at the PCI center, which can be explained by the time needed for transfer permission and ambulance arrival, by the delay created by other medical investigations (in case of atypical presentations), and transport time. Several other studies reveal similar issues when patients with STEMI arrive at the PCI center using secondary routes.^27,28,29 Accordingly, these delays may be considered inherent to a medical circuit in which multiple decision-making entities are involved, and their correction might be that much more problematic.

It is regarded as the most important indicator of quality of care and benefits from a wide array of research due to its association with mortality in pPCI and for its value as a hospital performance metric in patients with STEMI.¹⁹ The current recommended target for door-to-balloon interval is <90 min.⁸ Door-to-balloon time and mortality at 1 year seem to be independently associated, and for each 1-hour increase there is a 55% surge in 1-year mortality.⁵ In our analysis, the median time for door-to-balloon interval was 69 min, and the target of <90 min was met in 67.1% of the patients. The guidelines of the American College of Cardiology and of the American Heart Association recommend reaching this target for >85% of patients with STEMI.7 However, there is a substantial number of patients outside this recommended target globally, suggesting the difficulties in reaching this goal.³⁰ The time consumed at the emergency department of the tertiary center represents a significant contributor to this interval. In our analysis, all patients had transthoracic echocardiography evaluation before departure to the catheterization laboratory. While an echocardiographic evaluation provides an important amount of information and perhaps is able to reveal unexpected findings that could otherwise hinder a proper STEMI management, we should emphasize that currently there seems to be no amount of supplementary information that compensates for the overall time delay before revascularization. Current evidence suggests that bypassing the emergency department could shorten the door-to-balloon time by at least 20 min.^8,31

For pPCI to exert its clear advantage over fibrinolysis, it has to be performed inside a limited window of ischemia.^32,33 Although pPCI remains the preferred method of reperfusion, in this analysis the majority of patients did not meet the 120-min recommended threshold for revascularization. Nonetheless, the efficacy and safety of pharmacoinvasive reperfusion have been proven, and fibrinolytic therapy seems to compensate well for the additional ischemic time in patients who cannot reach pPCI as recommended.^34,35 Herein, prehospital thrombolysis was performed in 6.4% of the cases, while potential benefits from pharmacoinvasive reperfusion could have been expected in 64.5% of the patients. In favor of the regional reluctancy to administer fibrinolytics, an argument could be made that PCI center delay contributed to the underestimation of the FMC-to-revascularization interval. However, our data reveal that out of the 500 patients, 120 (24%) arrived at the PCI center more than 120 min after STEMI diagnosis, an interval which could have been more difficult to underestimate. This represents a category of patients who would have clearly benefited from fibrinolysis. The rate of prehospital thrombolysis seems unexpectedly low, but there are reports showing a steadily decreasing rate in Romania, from 45% in 2003 to 10.27% in 2011.¹²

The results of the present analysis should be interpreted in light of several limitations. First, they reveal the current situation regionally and cannot be extrapolated to a more generalized (national) level. Second, no data was collected to estimate door-in-door-out time, method of arrival at another hospital (self-presentation or ambulance transport), or reason for transport delay. Furthermore, for patients with prehospital thrombolysis, there are no data regarding the moment of fibrinolytics administration or clinical and ECG resolution.