“Door-In to Door-Out” Delay in Patients with Acute ST-Segment Elevation Myocardial Infarction Transferred for Primary Percutaneous Coronary Intervention in a Metropolitan STEMI Network of a Developing Country

Abstract

Background

Routine performance measures of primary percutaneous coronary intervention (PCI) within an ST-segment elevation myocardial infarction (STEMI) network are needed to improve care.

Objective

We evaluated the door-in to door-out (DI–DO) delays at the initial hospitals in STEMI patients as a routine performance measure of the metropolitan STEMI network.

Patients and Methods

We retrospectively analyzed the DI–DO time from 1,076 patients with acute STEMI who were transferred by ground ambulance to a primary PCI center for primary PCI between 4 October 2014 and 1 April 2019. Correlation analysis between DI–DO times and total ischemia time was performed using Spearman's test. Logistic regression analyses were used to find variables associated with a longer DI–DO time.

Results

Median DI–DO time was 180 minutes (25th percentile to 75th percentile: 120–252 minutes). DI–DO time showed a positive correlation with total ischemia time ( r  = 0.4, p  < 0.001). The median door-to-device time at the PCI center was 70 minutes (25th percentile to 75th percentile: 58–88 minutes). Multivariate analysis showed that women patients were independently associated with DI–DO time > 120 minutes (odds ratio 1.55, 95% confidence interval 1.03 to 2.33, p  = 0.03).

Conclusion

The DI–DO time reported in this study has not reached the guideline recommendation. To improve the overall performance of primary PCI in the region, interventions aimed at improving the DI–DO time at the initial hospitals and specific threat for women patients with STEMI are possibly the best efforts in improving the total ischemia time.

A rapid diagnosis and direct transfer for primary percutaneous coronary intervention (PCI) have been associated with a reduction in total ischemia time ^{1 2} and are effective in reducing the mortality of patients with acute ST-segment elevation myocardial infarction (STEMI). ³ However, in the real-world setting, it is often difficult to achieve a timely reperfusion therapy due to local barriers. ^{4 5 6 7} Moreover, STEMI patients who initially presented to a non-PCI center and planned for primary PCI, the interhospital transfer process often creates a longer reperfusion time. ⁸ To improve the overall care of STEMI patients both in the pre-PCI center and PCI capable hospitals setting, several time metrics are developed and are used routinely for measuring the performance of a regional STEMI network including door-in to door-out (DI–DO) time, door-to-device (DTD) time, and total ischemia time. ⁹ Of those, the DI–DO time is used to measure the care performance of treating patients with acute STEMI at the initial health center before transferring the patient to the designated PCI center for primary PCI. Importantly, the delay in DI–DO time is associated with higher in-hospital mortality. ¹⁰

In this study, we evaluated the DI–DO time of STEMI patients who were transferred from non-PCI capable health centers or PCI centers without 24/7 service to a PCI center for primary PCI as part of the routine performance measures of the metropolitan STEMI network. The results are expected to give insights and ideas to improve the care of the STEMI patients in the metropolitan area, particularly at the first hospital where the patient initially seeks help.

Methods

Study Design

This study was a retrospective analysis of the Jakarta Acute Coronary Syndrome (JAC) registry database as part of the regional STEMI network program. All patients who admitted to a single PCI center through a transfer process were recorded. The hospital provides primary PCI (24 hours per day, 7 days per week service) and hosts the STEMI network in the metropolitan area. The PCI center located in the west region of the metropolitan and is the largest tertiary academic cardiovascular hospital in the country. The metropolitan area covers around 11 million populations with a density of 15,000 population/m ² . The JAC registry has been used widely as the main source of data for measuring the performance of the STEMI network in Jakarta, Indonesia. ^{11 12 13}

Patient Identification and Data Collection

Patients were identified from the JAC registry database during the period of 4 October 2014 to 1 April 2019, which consists of 3,464 patients with STEMI. Patients with STEMI who were admitted to the PCI center for primary PCI through a transfer process or interhospital transfer ( n  = 1,742) were recorded. A complete dataset was available in 1,076 patients and included in the final analysis.

The STEMI diagnosis was made at the referral center as confirmed by the presence of ST segment elevation, or new left or right bundle branch block on the electrocardiogram (ECG). All the ECGs were transmitted to the PCI center to confirm the STEMI diagnosis. The time metrics for primary PCI (DI–DO, DTD, and total ischemia time) were recorded from the dataset. Data were analyzed anonymously with no direct patient contact. Data quality of the registry was maintained by a monthly evaluation by the primary investigator of the JAC registry (SD). The institutional review board of the hospital approved the study.

Study Outcome

The primary outcome of the study was DI–DO time. Other outcomes were DTD time and total ischemia time among the studied population.

Definition of Variables

DI–DO time was defined as time spent by the patient at the first health center before being transferred to the PCI center. ¹⁰ DTD time was defined as time period between emergency department admission at the PCI center and first device introduction after the coronary guide wire has crossed the culprit lesion. Total ischemia time was defined as time period between the start of the symptom (symptom onset) and first device introduction during primary PCI after the coronary guide wire has crossed the culprit lesion. ¹⁴ Distance from the referral center to the primary PCI center was calculated using Google maps. Off-hours admission was defined as admission at the primary PCI center during weeknights (Monday through Thursday; 4 pm to 7.30 am and Friday; 4.30 pm to 7.30 am ), weekends, and holidays. ¹³

Statistical Analysis

The time metrics (DI–DO and total ischemia time) were analyzed based on the health administrative region of the metropolitan area. Categorical data were presented as numbers (percentage) and the differences between groups were compared by chi-square or Fisher's exact test. Numerical data were presented as median values (25th to 75th percentile) and compared by Mann–Whitney U test. Correlation analysis between DI–DO times and total ischemia time was performed using Spearman's test. Logistic regression analyses were used to find variables associated with a longer DI–DO time (>120 minutes). Variables included into the multivariate analysis were distance to primary PCI center >20 miles, administrative region of the initial health centers, age >65 years, gender, off-hours admission at the primary PCI center, diabetes mellitus, hypertension, anterior myocardial infarction (MI), and Killip classification II to IV.

A p -value of <0.05 was considered statistically significant. All statistic computations were performed using PASW SPSS 22.

Results

Clinical Characteristics

The median age of the patient was 55 years, most commonly male (86%), smoker (69%), admitted to the primary PCI center during off-hours (65%) and had anterior wall myocardial infarction (55%). Most patients (90%) were referred from health centers located < 15 miles away from the PCI center ( Fig. 1 ). Only 35% of patients were referred from health centers located outside of the metropolitan area. Patient's characteristics can be seen in Table 1 .

Fig. 1.

Patient distribution ( n  = 1,076) according to distance to the percutaneous coronary intervention (PCI) center.

Table 1. Characteristics of STEMI patients transferred for primary PCI ( n  = 1,076) .

Characteristics	n (%) or median values
Demographic
Age, years	55 (48–61)
Male	923 (86)
Off-hours admission	705 (65)
Clinical history
Anterior wall myocardial infarction	591 (55)
Symptom onset 7–12 hours	520 (48)
Killip classification II–IV	240 (22)
TIMI risk score >4	389 (36)
Coronary artery disease risk factor
Smoker	747 (69)
Hypertension	589 (55)
Diabetes mellitus	286 (27)
Dyslipidemia	267 (25)
Family history of coronary artery disease	162 (15)
Administrative region of initial centers
Central Jakarta	93 (9)
West Jakarta	138 (13)
North Jakarta	112 (10)
South Jakarta	155 (14)
East Jakarta	202 (19)
Outside Jakarta	376 (35)
Time metrics, minute
Door-in to door-out time	180 (120–252)
Door-to-device time	70 (58–88)
Total ischemia time	461 (359–572)

Abbreviations: PCI, percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction; TIMI, thrombolysis in myocardial infarction.

Median values are presented as median (25th percentile–75th percentile).

Time Metrics for Primary PCI

The median DI–DO and total ischemia times of the studied population were 180 and 461 minutes, respectively ( Table 1 ). Only 63 patients (6.4%) reached the DI–DO time of ≤ 60 minutes ( Fig. 2 ). The DI–DO time was found to be similar in all centers within the administrative region of the metropolitan ( Fig. 3 ).

Fig. 2.

Door-in to door-out time interval of the studied population ( n  = 1,076).

Fig. 3.

Door-in to door-out and total ischemia time of 1,706 ST-segment elevation myocardial infarction patients transferred for primary percutaneous coronary intervention according to the health administrative region.

Furthermore, the DI–DO time showed a positive correlation with total ischemia time ( r  = 0.4, p  < 0.001) ( Fig. 4 ).

Fig. 4.

Correlation between door-in to door-out and total ischemia time of the 1,706 ST-segment elevation myocardial infarction patients.

Predictors of Prolonged DI–DO Time

From multivariate analysis, female patients were associated with an increased risk of having DI–DO time >120 minutes (odds ratio [OR]= 1.54, 95% confidence interval [CI] 1.03–2.32, p  = 0.04) ( Table 2 ).

Table 2. Multivariate predictors of DI–DO time > 120 minutes.

	Odds ratio	95% Confidence interval	p -Value
Distance to PCI center >20 miles	0.47	0.30–0.80	0.007
North Jakarta	0.89	0.55–1.45	0.65
East Jakarta	0.86	0.58–1.28	0.45
South Jakarta	1.00	0.64–1.54	0.99
West Jakarta	0.82	0.53–1.27	0.37
Central Jakarta	0.70	0.43–1.15	0.16
Age >65 years	1.17	0.79–1.74	0.43
Women	1.54	1.03–2.32	0.03
Off-hours admission	0.79	0.59–1.04	0.10
Diabetes mellitus	1.00	0.74–1.35	0.99
Hypertension	0.84	0.64–1.10	0.21
Anterior myocardial infarction	0.91	0.69–1.19	0.49
Killip classification II–IV	1.09	0.78–1.51	0.62

Abbreviations: DI–DO, door-in to door-out; PCI, percutaneous coronary intervention.

Discussion

The main findings from this study are (1) median DI–DO time of the studied population was 180 minutes; (2) DI–DO time was correlated positively with total ischemia time; (3) women patients were associated with an increased risk of having a longer DI–DO time (>120 minutes).

The results suggest several insights to improve the care of STEMI patients in the region.

The targeted DI–DO time as recommended by the AHA Guideline for STEMI is ≤ 30 minutes. ¹⁴ However, in the real-world setting, it is often difficult to achieve the targeted DI–DO time, event in a well-established STEMI network such as in the United States, where only 14% of STEMI patients can reach a DI–DO time of ≤ 30 minutes. ¹⁰ Currently, the data on DI–DO time from developing countries are very limited; thus, the results of the present analysis may add additional knowledge to improve the care of STEMI patients.

Door-In to Door-Out Delay and Efforts for Improvement

The results of the present study suggest that the delay for primary PCI in the community was probably located at the initial health center, as shown by the prolonged DI–DO time (median of 180 minutes). Furthermore, only 6.4% of STEMI patients transferred for primary PCI reached a DI–DO time of ≤ 60 minutes ( Fig. 2 ). The DI–DO delay was found in all centers in the metropolitan area including those centers located at the west region where the PCI center is located ( Fig. 3 ).

However, the DTD time reported from this study (median of 70 minutes) has reached the guideline recommendation (≤ 90 minutes). The possible reason for the delay in DI–DO time at the initial centers in the metropolitan area is lack of awareness of the health centers about the regional STEMI network program. Several efforts to increase the STEMI awareness at the initial health centers including wide use of web-based application of the STEMI network program that has been developed ( www.jacregistry.pjnhk.go.id ) as a reminder of care process and to facilitate data entry at remote centers. Use of this real-time data collection method along with training of the nurses and physician who work at the referring health centers are all areas of improvement that may facilitate the care of STEMI patients, particularly when the patients first seek help at the non-PCI centers. Other strategies to improve DI–DO time include timely ECG transmission for a rapid ECG interpretation and STEMI diagnosis, ambulance and PCI center coordination, and development of ambulance navigation system.

Understanding the components of care that drives the outcomes can help formulate better pathways of care specifically tailored to the needs of a developed country or region. For instance, one opportunity presented by the issue of prolonged total ischemia time due to prolonged DI–DO time is whether the use of fibrinolytic therapy in patients with STEMI admitted in non-PCI centers while en route the patient to the PCI center (pharmacoinvasive strategy) may improve overall care.

Appropriate Metrics to Evaluate the Performance of STEMI System of Care in a Developing Country

The barriers for a rapid reperfusion therapy within a STEMI system of care might be different between well-developed and developing countries. For example, other possible causes of delay in establishing a rapid primary PCI in STEMI patients in a developing country may be unpredictable arrival time of the transferred patients due to large variance of distance, traffic congestion, and transportation times.

The DTD time has been used widely to measure the performance of treating patient with acute STEMI within a STEMI network. However, the goal of a STEMI network is not only optimizing the DTD time at the primary PCI center but also minimizing the time from occlusion/symptom onset to reperfusion therapy. ¹⁵ In this case, the DTD time cannot be solely used to evaluate the performance of STEMI care in the community, particularly DTD time is not evaluating the performance of treating STEMI at the non-PCI center, where the patient initially seeks help.

The recent 2017 ESC guideline on STEMI has emphasized the time metric for primary PCI by eliminating the door-to-balloon time and replace it to “STEMI diagnosis to wire crossing” as the key performance of primary PCI. ¹⁵ This concept represents the performance of STEMI care in the acute phase, particularly in the first hospital before the patient reached the primary PCI center. Total ischemia time represents the key issue in treating STEMI patients including recognizing sign and symptom of heart attack, triaging and treating patient as soon as possible, not only “counting” when the patient enters an emergency room of a PCI center.

In developing countries, perhaps the first step in optimizing the STEMI care in the community is improving the pre-hospital or pre-PCI center care. It depends on the time frame from symptom onset-to-seek medical help, first medical contact-to- STEMI diagnosis, DI–DO time at the first hospital, and transportation time to the primary PCI center. ¹⁵ Patients who admitted directly to a primary PCI center were associated with shorter total ischemic time and lower 12-month mortality, suggesting that it is important to educate the public to find a PCI center directly if a sign and symptom of heart attack are suspected; thus, it should be part of the STEMI network program. ¹⁶ It should be noted that even in a developed country, patients with possible ischemic symptoms are still hesitate to immediately call the emergency medical service that may delay the reperfusion therapy. ¹⁷ It is suggested that the main ischemic time metric to evaluate the performance of a STEMI network in a developing country should be total ischemia time, where DI–DO time and direct presentation to a PCI center may partly play a role. The improvement in DI–DO time contributes to a shorter total ischemia time. The positive correlation between DI–DO and total ischemia time found in this study ( r  = 0.4, p  < 0.001) supports the concept.

In this study, we also found that female patients who presented with STEMI at the initial hospitals were likely to stay longer at the initial hospital before the transfer process to the primary PCI center (OR = 1.55, p  = 0.03). While the reasons for the prolonged DI–DO time in women are unclear, female patients presenting with STEMI have often been found to receive suboptimal health care utilization compared with men. ¹⁸ In a region with an established STEMI network, such gender disparities should not exist. Therefore, specific efforts should be made in women who presented with STEMI including wide use of the pre-hospital triage protocols.

A regional STEMI system of care has a central role in treating STEMI patients in the community. ^{19 20 21} The STEMI program should be focused on reducing the total ischemic time (from plaque rupture/onset of symptom to reperfusion therapy) and include efforts to minimize the patient-and system-related delay that may reflect the equally importance of both care at the initial center without PCI facilities and in the primary PCI center.

Study Limitation

First, transportation time was not specifically evaluated and may contribute to the delay in reperfusion therapy. Second, the distance between referral center and the primary PCI center was measured using Google maps that may have different results with the straight-line distance between the two centers. Third, we reported the primary PCI performance from patients that were transferred only to our center; thus, the results are not representing other PCI centers performance in the region. Fourth, we could not explore the reasons for delay in DI–DO time in details because the time intervals of the processes of care were unavailable. Finally, this study is observational, and residual confounding may account for the relationships we describe.

Conclusion

The DI–DO time reported in this study has not reached the guideline recommendation. To improve the overall performance of primary PCI in the region, interventions aimed at improving the DI–DO time at the initial hospitals, and specific threat for female patients with STEMI are possibly the best efforts in improving the total ischemia time.