INTRODUCTION

Early reperfusion therapies such as thrombolysis and percutaneous coronary intervention (PCI) can reduce mortality rates among patient with ST Elevation Myocardial Infarction (STEMI). In developing countries like Malaysia, thrombolytic therapy is a major treatment for patients who present with STEMI (Loch et al. 2013). Thrombolytic therapy has been estimated to save 65 lives per 1000 patient treated and maximum efficacy is achieved when treatment is initiated within one hour from the onset of symptoms (Yaylali et al. 2010). Door to needle time (DTN) is the interval between the patient’s arrival at the emergency department and initiation of thrombolytic therapy (Jehangir et al. 2009). The Malaysian Clinical Practice Guideline on STEMI 2014 (MOH website) advised the implementation of a 30 minutes DTN (Azarisman et al. 2008). The Malaysian Ministry of Health National Patient Safety Indicator 2009 states that percentage of acute STEMI patient receiving thrombolytic therapy within 30 minutes of Emergency Department (ED) presentation should be more than 70%. Early reperfusion is crucial as time lost is equivalent to myocardium lost (Kumolosasi et al. 2013).

There are three components which determine the time between the onset of myocardial infarction (MI) and administration of thrombolytic therapy. The three components are time in seeking medical attention, transport delay and door to needle time. Efforts to reduce these components will lead to improving survival of patients with acute MI. The first two components are mostly dependent on patient awareness and efforts to seek medical attention. Data concerning DTN in a multidisciplinary teaching hospital such as Universiti Kebangsaan Malaysia Medical Centre (UKMMC) is lacking. This study was done to determine the average DTN time in a tertiary teaching Hospital. It also determines whether national target of DTN time in tertiary hospitals has been achieved and if not what are the factors leading to this delay

MATERIALs AND METHODS

The general objective of this study was to determine the mean DTN time for thrombolytic therapy in ED, UKMMC. Specific objectives were to determine door to ECG time, mean door to drug delivery time, mean time of drug preparation, percentage of achieved DTN time and factors causing delay on DTN time. Factors that were studied, included multiple referrals, incorrect ECG interpretation, delay drug preparation, need for resuscitation and unusual presentation. 

This was a prospective cross-sectional study from May 2016 until May 2017 and conducted in UKMMC. This study included all patients who presented to ED, UKMMC and were diagnosed with acute STEMI and received fibrinolytic therapy in ED from May 2016 until May 2017. For each patient the demographic data and clinical data were recorded. The clinical data included the time onset of symptom, time arrival to ED UKMMC, time ECG done, and time drug preparation (Tenecteplase) and time thrombolysis start.

All patients diagnosed with Acute STEMI based on the current universal definition of AMI 2013 American College of Cardiology Foundation/American Heart Association for the management of ST elevation Myocardial Infarction and thrombolysed at ED, UKMMC from May 2015-May 2016 were included.

Diagnosis of STEMI was established based on the presence of any two of the following:

i. Ischemic symptoms :

Typical: Chest, upper extremity, jaw or epigastric discomfort with exertion or at rest. The discomfort associated with acute MI usually lasts at least 20 minutes. Often the discomfort is diffuse, not localized, not positional, not affected by movement of the region and it may be accompanied by diaphoresis, nausea or syncope. 

Atypical:  palpitations or cardiac arrest or even without symptoms especially in women, the elderly, diabetics, or post-operative and critically ill patients.

ii. Electrocardiogram:

Diagnostic ST elevation as defined by American Heart Association (AHA) for the Universal Definition of Myocardial Infarction as new ST elevation at the J point in at least 2 contiguous leads of ≥2 mm (0.2 mV) in men or ≥1.5 mm (0.15 mV) in women in leads V2–V3 and/or of ≥1 mm (0.1 mV) in other contiguous chest leads or the limb leads. Presumed new left bundle brunch block on ECG was also included as a candidate for thrombolysis.

iii. Cardiac Biomarker:

Raised level of cardiac enzymes (Troponin T / CK MB)

Patient who received fibrinolytic therapy at others centers and patient who underwent primary PCI were excluded.  

DATA COLLECTION

All patients with acute chest pain were triaged to critical or semi-critical area depending on the ACS diagnosis i.e. STEMI to critical area, NSTEMI (non-ST elevation MI) to semi critical area. Patients were tagged and followed-up. Those who fulfilled inclusion criteria were approached for the study and informed consent was obtained from patient or patient’s next of kin, once patient was stabilized or relatively stable. Consent included usage of patient’s information and the results of blood investigation for the purpose of the study.

Data collection was conducted using a specifically designed data collection sheet (refer appendix.

OPERATIONAL DEFINITION

STEMI

: STEMI is a clinical syndrome defined by characteristic symptoms of myocardial ischemia in association with persistent electrocardiographic (ECG) ST elevation and subsequent release of biomarkers of myocardial necrosis.Diagnostic ST elevation as defined by AHA as new ST elevation at the J point in at least 2 contiguous leads of ≥2 mm (0.2 mV) in men or ≥1.5 mm (0.15 mV) in women in leads V2-V3 and/or of ≥1 mm (0.1 mV) in other contiguous chest leads or the limb leads.

DTN

: Time from hospital arrival until administration of the fibrinolytic therapy

Door to ECG 

: Time from hospital arrival until ECG was performed

Order to drug delivery time (Tenecteplase preparation time)

: Time from decision for thrombolysis until delivery of drug.

Baseline Blood Pressure (BP)

: Blood Pressure before thrombolysis started

SAMPLE SIZE

Sample size was calculated using formula by Kish L

n= z x p(1-p)

           ∆Δ2

95% confidence level

z = Degree of confidence level (1.96 for 95% confidence level)

   = 1.96

Δ = Error of margin 0.05 (5%)

p = expected prevalence

Study by Loch et al. (2013) showed the prevalence of patient with DTN less than 30 minutes is 25%. The confidence level was 95%, therefore the sample size was

n= 1.96 x 0.25 (1-0.25)

            0.052

  = 147

STATISTICAL ANALYSIS

Data was analyzed using SPSS (Statistical Package for Social Science Version 19). Categorical data was presented in frequency and percentage. Continuous number was presented in mean + standard deviation. 

RESULTS

During the one-year period of study, a total of 98 patients who presented with diagnosis of STEMI were thrombolysed and agreed to participate in the study. Among 98 patients, 88.8% (n=87) of the patients were males while 11.2% (n=11) were females. The mean age was 56.3 years (SD, 13.8, range: 31- 116). Characteristic of patients were demonstrated in Table 1. 

The mean DTN time was 59.28 + 36.01 minutes with a median of 54.00 minutes. Among a total of 98 patients, only 22.4% (n=22) of patients were thrombolysed within 30 minutes from the arrival to the hospital. The mean Door to Electrocardiogram (ECG) time were 7.19 + 8.08 and the mean order to drug delivery time were 9.86 + 7.51. The door to needle time was shown in the Table 2.

The study observed that a total of 76 (77.6%) patients were thrombolysed beyond the 30 minutes target once arrived at hospital. Maximum delay of DTN time was 223 minutes.

Several factors were identified for causes of delay to deliver thrombolysis within 30 minutes of arrival to ED. The commonest cause of delay was multiple referral, 59.2% (n=45) of patients followed by delay to perform ECG within 10 minutes of arrival to hospital, 19.8% (n=15) of patients. Both, incorrect initial ECG interpretation and need for resuscitation before thrombolysis initiated contribute about 9.2% (n=7) each. The factors causing delay in thrombolysis were summarized in Table 3. 

Among 98 patients who presented with acute STEMI, 39.8% (n=39) of patients were diagnosed with anteroseptal STEMI  whereby 22.4 % (n=22) of patients were diagnosed with Inferior STEMI. The less common area of infarct was Posterolateral STEMI 1.0% (n=1). Table 4 summarized the area in MI involved during this study period.

DISCUSSION

The result from this study showed significant delay in administrating thrombolytic therapy for patient presented with acute STEMI. Although most of the guidelines recommend a DTN time of less than 30 minutes, our hospital failed to achieve this target in most of the patients. The mean (+SD) DTN was 59.28 + 36.01 with median 54.00 +±36.01. Only 22.4% (n=22) of patients presented to the ED were thrombolysed within 30 minutes of arrival to our ED. Compared to the local study done by Loch et al. in 2013, it showed only 24% of patients with acute STEMI received thrombolytic therapy within 30 minutes after presentation to the ED. The mean and median of DTN recorded by Loch et al. were 69 minutes and 50 minutes, respectively.  Other study by Azarisman et al. (2008) showed that mean DTN at their Centre were 80.54 with only 20% of patient presented to their ED with acute STEMI thrombolysed within 30 minutes of presentation to their ED. The percentage was still low from our National Patient Safety Indicator that suggested more than 70% of patient presented with acute STEMI receiving thrombolytic therapy within 30 minutes of presentation at the ED. If we compared the DTN with developed countries like United Kingdom, the mean DTN ranges from 20 minutes to 70 minutes. Whereby in USA, the median door to needle times is 70 min (Heath et al. 2003) with the faster DTN stated by Gonzalez et al. (1992) was 46 minutes. In Australia, Hourigan et al.  (2000) stated the median DTN is 37 minutes after shifting to ED administration of thrombolytic therapy compared to median DTN 80 minutes before the intervention. Therefore, from this study, it can be stated that DTN in this ED was unacceptably delayed.

Our specific objective was to determine mean door to ECG time. It is because delay in obtaining the ECG is one of the modified factors that can contribute to delay DTN. The chest pain guideline (AHA) recommends that every patient with suspected Acute Coronary Syndrome (ACS) in ED should get an ECG immediately in the first 5-10 minutes after reaching the hospital. From this study, our mean (+SD) Door to ECG time was 7.19 +±8.08 which was less than 10 minutes as suggested by chest pain guideline. Unfortunately, 19.8% (n=15) patients in our study showed delay to perform ECG within 10 minutes upon arrival to our ED. The fastest ECG was done immediately after patient arrived to ED with the longest time to obtain the ECG was at 54 minutes from time of ED arrival. The study by Canadian, Vlahaki et al. 2008 stated that their median Door to ECG (DTE) time was 6 minutes. In India, the mean DTE was 6.98 minutes and study by Maharaj et al. (2012) showed their median DTE was 13 minutes. 

Several factors were identified for causes of delay for thrombolysis within 30 minutes of hospital arrival. Multiple referral account for 59.2% (n=45) patients, delay to perform ECG 19.8% (n=15) patients. Incorrect first ECG interpretation and need for resuscitation contribute to 9.2% (n=7) patients each. A study by Loch et al. (2013) stated that multiple referrals was the third causes of delay for early DTN in their Centre and showed multiple referral and hypertensive emergencies are the most causes of delay of DTN. Study in Cape Town also showed multiple referrals were the leading cause of delay in DTN (Maharaj et al. 2012). Whereby study by Jehangir et al. (2009) showed that incorrect initial ECG interpretation and need for resuscitation as the main cause of delay in DTN. It is assumed that once the patient is unstable such as hypotensive or underwent CPR, practitioners are reluctant to administer thrombolytic therapy. However, when contraindicated for thrombolytic therapy, i.e. acute ischemic stroke, pharmacological coronary reperfusion can be delayed for mechanical thrombectomy with better results. This would also avoid hemorrhagic complications from pharmacological thrombolysis (Hashim et al. 2018).

The anteroseptal STEMI 39.8% (n=39) was the most infarct area documented from our study. The second commonest infarct area was inferior wall, 22.4% (n=22) wall. This was followed by inferior with right ventricle (RV) 13.2% (n=13), inferior with RV and posterior wall involvement 9.2% (n=9), extensive 5.1% (n=5), anterior 3.1% (n=3) and posterolateral infarct 1.1% (n=1). This area of infarct was not much different from other studies worldwide. 

Some limitations of this study were identified. Comparing the sample size of the previous studies on the same subject, this study had a relatively small sample size. A larger prospective study may provide a better representation of our population.

CONCLUSION 

The finding of this study showed unaccepted delay in thrombolysis of acute STEMI. Multiple referrals significantly delayed DTN time. This can be shortened with swift decision from an ED Medical Officer/Registrar or Specialist on call or on floor. Pre-hospital ECG can be implemented to shorten door to ECG time. Resuscitation or CPR of an unstable patient should not be a reason for delay in thrombolytic therapy. In the future, pre-hospital thrombolysis could be implemented.