Disclaimer: The manuscript and its contents are confidential,

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intended for journal review purposes only, and not to be further

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URL: http://jaha-submit.aha-journals.org
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Title: A Risk Score for Asian Patients with ST-segment Elevation
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Myocardial Infarction Treated by Primary Percutaneous Coronary

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Intervention
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Manuscript number: JAHA/2017/008217

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Author(s): Derek Hausenloy, Duke-NUS Graduate Medical School Singapore

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Heerajnarain Bulluck, Papworth Hospital NHS trust

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Huili Zheng, National Registry of Diseases Office, Health Promotion

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Board, Singapore

Mark Chan, National University Heart Centre Singapore

Nicolas Foin, Imperial College London

David Foo, Tan Tock Seng Hospital

Chee Lee, Khoo Teck Puat Hospital

Soo Teik Lim, National Heart Centre Singapore

 Anders Sahlen, National Heart Centre Singapore

Huay-Cheem Tan, National University Heart Centre Singapore

Jack Tan, National Heart Centre Singapore

Khim Leng Tong, Changi General Hospital

Aaron Sung Lung Wong, National Heart Centre Singapore

Philip Wong, National Heart Centre Singapore

Khung Keong Yeo, National Heart Centre Singapore

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Ling Foo, Health Promotion Board

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Terrance Siang Jin Chua, Department of Cardiology, National Heart

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Centre, Singapore

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Tian Hai Koh, National Heart Centre Singapore

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 A Risk Score for Asian Patients with ST-segment Elevation
Myocardial Infarction Treated by Primary Percutaneous
Coronary Intervention

Heerajnarain Bulluck MBBS, PhD1,2,3, Huili Zheng MSc4, Mark Y. Chan MBBS, MHS5,
Nicolas Foin PhD2, 3, David C Foo MBBS7, Chee W. Lee MBBS, DPhil8, Soo T. Lim
MBBS6, Anders Sahlen PhD6,9, Huay C. Tan MBBS5, Jack W. Tan MBBS6, Khim L. Tong10,
Aaron S. Wong MBBS6, Philip E. Wong MBBS6, Khung K. Yeo MBBS6, Ling L. Foo PhD4,
Terrance S. Chua MBBS6, Tian H. Koh MBBS6, Derek J. Hausenloy MBChB, PhD1,2,3,11

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1
The Hatter Cardiovascular Institute, Institute of Cardiovascular Science, University College

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London, United Kingdom
2
Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore,

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Singapore

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3
National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore

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4
National Registry of Disease Office, Health Promotion Board, Singapore
5

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National University Heart Centre, Singapore
6
Department of Cardiology, National Heart Centre Singapore
7

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Tan Tock Seng Hospital, Singapore, Singapore
8
Khoo Teck Puat Hospital, Singapore, Singapore
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9
Karolinska Institutet, Department of Cardiology, Stockholm, Sweden
10
Changi General Hospital, Singapore
11
Yong Loo Lin School of Medicine, National University Singapore, Singapore
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Running title: A STEMI risk score for Asians

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Competing interests: Dr. Yeo received honoraria from Boston Scientific, Abbott Vascular,
and St. Jude Medical; is a consultant for Boston Scientific; is a proctor for Abbott Vascular;
received research grant support from Medtronic; and received speaker fees from St. Jude
, a in e
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Medical. Dr. Wong is a Senior Consultant at the National Heart Center Singapore and is the
CEO/CTO of Innoheart Pre-clinical CRO Singapore.
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Funding: Prof Mark Y. Chan receives salary support from a National Medical Research
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Council Clinician Scientist Award (NMRC/CSA-INV/0001/2016). Prof D J Hausenloy is

supported by the Singapore Ministry of Health’s National Medical Research Council under its
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Clinician Scientist-Senior Investigator scheme (NMRC/CSA-SI/0011/2017) and

Collaborative Centre Grant scheme (NMRC/CGAug16C006), the Singapore Ministry of
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Education Academic Research Fund Tier 2 (MOE2016-T2-2-021) and the EU-

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CARDIOPROTECTION CA16225 Cooperation in Science and Technology (COST) Action

Corresponding author:

Professor Derek J Hausenloy

Cardiovascular & Metabolic Diseases Program
Duke-NUS Graduate Medical School Singapore
8 College Road,
Singapore 169857
Tel +65 65166719
Email derek.hausenloy@duke-nus.edu.sg

1
 ABSTRACT

Background: Asians have different risk profiles. We aimed to devise a new risk

score using a real-world patient registry to predict in-hospital, 30-days and 1-year

mortality in Asian patients with ST-segment elevation myocardial infarction (STEMI)

treated by primary percutaneous coronary intervention (PPCI).

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Methods: All STEMI patients treated by PPCI between 2007 and 2014 were

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identified from the Singapore Myocardial Infarction Registry (SMIR), and were

cl w en
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divided into the derivation cohort (70% of the cohort) and the validation cohort (30%

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of the cohort). The outcomes of interest were in-hospital, 30-days and 1-year

he l ts
mortality.
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Results: A total of 10,784 eligible STEMI patients (comprising Chinese, Malays and
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Indians) were included. In-hospital, 30-days and 1-year mortality rates were 6.9%,
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7.4% and 10.2%, respectively. From the derivation cohort (n=7,549), age, Killip
nd te ma

class, cardiac arrest, creatinine, hemoglobin, troponin, anterior STEMI location and a
, a in e
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history of diabetes, assessed on admission, were multivariate predictors of in-hospital,

on ti r:

30-days and 1-year mortality. A history of ischemic heart disease, hypertension,

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dyslipidemia and ethnicity were multivariate predictors of 1-year mortality only. The
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c-statistic was 0.878 (95%CI 0.862-0.892) for in-hospital mortality, 0.861 (95%CI
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0.844-0.878) for 30-day mortality and 0.862 (0.848-0.876) for 1-year mortality.

External validation (n=3,235) showed good discrimination of the model (c-statistic

0.855, 0.823, 0.837, respectively).

Conclusions: We have developed a new risk score for predicting mortality in Asian

STEMI patients treated by PPCI. This new risk score takes their specific risk profiles

2
 and ethnicity into account and could be used to guide management and improve

outcomes in Asian STEMI patients.

KEYWORDS: ST-segment elevation myocardial infarction, primary percutaneous

coronary intervention, risk score, Asians, mortality

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3
 INTRODUCTION

Despite prompt reperfusion of ST-segment elevation myocardial infarction (STEMI)

by primary percutaneous coronary intervention (PPCI), morbidity and mortality

remain significant.1, 2
However, not all STEMI patients have the same prognosis.

Those in the low-risk category have excellent prognosis3, whereas those with high-

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risk features have significantly worse outcomes with the risk of all-cause mortality

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reaching up to 35% at 30-days in those in the highest risk category.4 Therefore early

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risk-stratification of STEMI patients is important to guide in-patient management and

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follow-up in order to improve clinical outcomes.

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There are several risk scores available which can be used to risk-stratify
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STEMI patients at the time of hospitalization, and guide management.5 The most
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extensively investigated, and validated risk scores are the Global Registry of Acute
o
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6, 7
Coronary Events (GRACE) , and the Thrombolysis in Myocardial Infarction
no de nu

4
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(TIMI) risk scores, with the GRACE score performing better than the TIMI risk

score in a recent meta-analysis.8 The GRACE score can be used for all types of acute
, a in e
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coronary syndromes (ACS), and can predict in-hospital and 6-month mortality. On the
on ti r:
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4
other hand, there is a specific TIMI risk score for STEMI to predict 30-day
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mortality. However, the derivation and validation cohorts for these risk scores
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consisted predominantly of non-Asian patients treated by thrombolysis.

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1
About 60% of the world population resides in the Asia-Pacific region and

Asians are known to have a different and higher cardiovascular risk profile than the

western population.9 However, there has been limited research conducted in the ACS

population in this region so far due to factors such as language and cultural barriers,

potential ethical issues, and differences in regulatory processes in individual Asian

4
 countries10, but efforts are under way with the establishment of the Asia-Pacific Real

world evIdenCe on Outcome and Treatment of ACS (APRICOT) project.1

Singapore is a multi-ethnic country with Chinese (≈74%), Malays (≈13%) and

Indians (≈9%) accounting for the majority of the population. It has a state-funded,

mandatory, acute myocardial infarction (AMI) registry, called the Singapore

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Myocardial Infarction Registry (SMIR),11 with a dedicated team to collect data from

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all hospitals. We used this unbiased, real-world registry to determine which factors on

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admission would predict mortality in patients presenting with a STEMI and

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reperfused by PPCI, during hospitalization, at 30-days and 1-year. Secondly, we

he l ts
aimed to devise a new risk score that would be applicable to this population and that
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could be used to risk-stratify the reperfused STEMI patients, early during their
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hospitalization, in the current era.

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METHODS
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Population
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This was a retrospective study on data collected prospectively between 2007 and 2014
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by the National Registry of Diseases Office in SMIR. Data collection on all AMI
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cases from all public and private hospitals is mandated and funded by the state and
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yearly reports are generated for the Ministry of Health.11-13 Ethics approval was

obtained from the SingHealth Centralized Institutional Review Board and the

requirement for patient consent was waived. The study was conducted according to

the Declaration of Helsinki.

Inclusion and Exclusion criteria

5
 The main inclusion criteria were patients presenting to hospital with a STEMI within

12 hours of symptoms onset and were reperfused by PPCI. Patients with a STEMI but

not reperfused by PPCI or those with a LBBB were excluded as shown in the flow

chart in Figure 1.

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Clinical outcome of interest

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The main outcomes of interest were in-hospital mortality, 30-day mortality and 1-year

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mortality.

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Data collection
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Registry coordinators confirmed all diagnosis of STEMI from physical and electronic
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medical records and data on patients’ demographics, comorbidities, location of

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STEMI on ECG, initial blood results such as hemoglobin, creatinine and troponin T
, a in e
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or I were extracted. Details on Killip class and cardiac arrest in the ambulance or on
on ti r:

admission (prior to transfer to the cardiac catheterization laboratory) and symptom-to-

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balloon (S2B)/ door-to-balloon (D2B) times were also recorded. The International
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Classification of Diseases 9th Revision (ICD-9 Clinical Modification) code 410 was
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used to identify STEMI cases diagnosed from 2007 to 2011, whereas ICD-10 codes

I21 were used for STEMI cases diagnosed from 2012 to 2014. Data on admission

heart rate and blood pressure were not available in this registry.

STEMI was defined by a typical chest pain of 20 minutes and significant ST-segment

elevation (0.1 or 0.2 mV on two adjacent limb or precordial leads), and with a

corresponding rise in cardiac biomarkers.

6
 Mortality was defined as death occurring from any cause in-hospital or up to 1 year

post-PPCI and the time of death was extracted from death certificates obtained from

the Registry of Births and Deaths.

Troponin T or I performed on admission was defined as abnormal if they were greater

than the 99th percentile of the reference range from each hospital laboratory.

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Statistical Analysis

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Continuous variables were expressed as median (25th, 75th percentile) and

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categorical variables were expressed as percentages. All analysis was performed using
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StataCorp. 2013. Stata Statistical Software: Release 13 (College Station, TX:
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StataCorp LP). The statistical methodology was similar to that used for the GRACE
o
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score derivation.6 Random selection was performed to divide the cohort into two
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groups with 70% of the cohort included in the derivation cohort and 30% in the
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validation cohort. Continuous data were expressed as median and interquartile range
, a in e
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and categorical data were reported as frequencies and percentages. Factors that were
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prognostic from GRACE, TIMI STEMI and the Controlled Abciximab and Device
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Investigation to Lower Late Angioplasty Complications (CADILLAC)14 risk scores

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and that were available from the SMIR were first included in the univariate logistic
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regression model. Other potentially prognostic factors such as cardiovascular risk

factors, ethnicity, gender, S2B and D2B were also included in the univariate logistic

regression model. Odd ratios (ORs) with 95% confidence interval (95% CI) were used

to assess the relationship between the included factors and mortality during

hospitalization, at 30 days and 1 year. Multivariate stepwise logistic regression with

backward elimination was subsequently used to determine the significant predictors

7
 of mortality among all the factors included in the univariate logistic regression model.

Only those factors that were significant with a P value of <0.05 were included in the

final multivariate logistic model. Missing data were handled as case deletion. No

imputation was performed for missing data. Hosmer-Lemeshow test was used to

assess the goodness of fit of the final multivariate regression model. C-statistic (area

under the curve) was used to assess the discriminatory power of the final multivariate

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regression model. A model with a c-statistic of >0.800 was considered to have good

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discrimination for clinical application.15 To evaluate the accuracy of the calibration,

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the predicted mortality was plotted against the observed mortality according to the

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deciles of predicted risk. The final multivariate regression model was used to develop
he l ts
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nomograms for patient risk.6 Internal validity was assessed using bootstrapping

techniques. External validity was assessed by applying the model to the validation
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cohort. The predicted probability of death was compared with the observed mortality
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according to the deciles of predicted risk and c-statistic was calculated with 95
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confidence intervals (95%CI).

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RESULTS
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Study population and baseline characteristics

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A total of 10,784 STEMI patients reperfused by PPCI from 2007 to 2014 were

identified in the SMIR. The overall mortality rate during hospitalization was 6.9%

(744/10,784) and was 7.4% (793/10,784) at 30 days and 10.2% (1,096/10,784) at 1

year.

8
 There were 7,549 reperfused STEMI patients in the derivation cohort, with a total of

785 (10.4%) deaths in this cohort at 1-year. The median age was 57.7 (50.6-66.3)

years old and 85.1% were male. The majority were Chinese (61.6%), followed by

Malays (19.9%) and Indians (16.8%). Around a third of the cohort had a history of

diabetes (28.3%) and half had a history of hypertension (52.8%), dyslipidemia

(45.6%) and were current smokers (48.1%). 3.8% suffered a cardiac arrest in the

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ambulance or on admission to the emergency department and 8.4% were in

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cardiogenic shock at presentation. Half of the patients presented with an anterior

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STEMI (50.2%), and half had an abnormal initial troponin T or I (47.0%). The

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median S2B time was 198 (128-365) minutes and the D2B time was 68 (52-93)
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minutes.
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There were 3,235 reperfused STEMI patients in the validation cohort, with a total of
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311 (9.6%) deaths in this cohort at 1-year. There was no significant difference in
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baseline characteristics between the derivation cohort and the validation cohort as
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summarized in Table 1 except for smoking history, that was statistically higher in the
, a in e
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validation cohort but clinically similar between the two groups (48.1% versus 50.9%,
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P=0.007).
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Predictors of in-hospital, 30-days and 1-year mortality

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Factors included in the univariate logistic regression analysis are summarized in the

Table 2. Factors significant on univariate analysis (P≤0.05) were included in the

multivariate logistic regression analysis and are summarized in Table 3. Age, Killip

class on admission, cardiac arrest on admission, creatinine, hemoglobin and troponin

on admission, anterior STEMI location and a history of diabetes were predictive of

mortality at all 3 time points (in-hospital, 30-days and 1 year). However, a history of

9
 ischemic heart disease (IHD), hypertension and dyslipidemia and ethnicity were

predictive of 1-year mortality only. The model performed very well with a c-statistic

of 0.878 for in-hospital mortality, 0.861 for 30-days mortality and 0.862 for 1-year

mortality.

Calibration of the predictions from these models was assessed by comparing the

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average predictions to the actual mortality across deciles and was found to be

s
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excellent as shown in Figure 2. Internal validation showed good predictive

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cl w en
discrimination of the models and the c-statistic remained unchanged at 0.878 (95%CI

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0.862-0.894) for in-hospital mortality, 0.861 (95%CI 0.844-0.878) for 30-days

he l ts
mortality and 0.862 (95%CI 0.848-0.876) for 1-year mortality with bootstrapping
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techniques.
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External validation was performed in the validation cohort of 3,235 patients. The
o
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model performed very well as shown in Figure 3 with a c-statistic of 0.855 (95%CI
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0.782-0.848) for in-hospital mortality, 0.823 (95%CI 0.793-0.854) for 30-days

, a in e

mortality and 0.837 (95%CI 0.811-0.862) for 1-year mortality.

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A nomogram based on these models is shown in Figure 4 and can be used to calculate
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the risk score (SMIR STEMI risk score) to predict in-hospital, 30-days and 1-year
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mortality on a patient level basis. We designed a calculator to facilitate the

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implementation of this score in the clinical setting and it is available in the Online

Appendix.

DISCUSSION

The strength of the SMIR is that it is a mandatory registry and as such, all STEMI

patients treated by PPCI between 2007 and 2014 were captured. We have developed a

10
 new risk score to predict mortality in a cohort of Asian STEMI patients, comprising

predominantly of Chinese, Malay and Indians, reperfused by PPCI in the current era.

Age, Killip class on admission, cardiac arrest in ambulance/ on admission, creatinine,

hemoglobin and troponin on admission, anterior STEMI location and a history of

diabetes were predictive of in-hospital, 30-days and 1-year mortality. However, a

history of IHD, hypertension and dyslipidemia and ethnicity were predictive of 1-year

. o re
s
ed urp s a
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mortality only. Among the 3 main ethic groups, when compared to Chinese, Malays

os p t
cl w en
had the worst 1-year mortality, followed by the Indians. All these factors are available

is vie nt
either at the time of admission or within the first few hours following admission and

r d re co
can be used to predict in-hospital, 30-days and 1-year mortality very early during the
he l ts
rt na i
fu ur and
hospital stay. The availability of a risk score calculator (online appendix) would

further facilitate the implementation of this score in the clinical setting.

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The potential immediate utility of this risk score is to identify those low risk
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patients who could be discharged early (e.g. after 48-72 hours). Secondly, it could
nd te ma

potentially be used to identify those at high risk and who would benefit from more
, a in e
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aggressive up-titration of their prognostic medications (beta-blockers, angiotensin

on ti r:
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converting enzyme inhibitors, aldosterone antagonists etc.) and more frequent follow-
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ups. Last but not least, this score could also be used when counseling patients prior to
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discharge regarding their prognosis.

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The initial derivation cohort of the GRACE registry consisted of 13,708

patients recruited between 1999 and 2001 and only a third presented with a STEMI

and only 15.2% received reperfusion therapy.6 Furthermore, they only reported in-

hospital and 6 months mortality. Although the recruitment was done in 14 countries,

none were from Asia. However, the GRACE2 was subsequently expanded to more

countries, including hospitals in Asia.16 The risk profiles and prognosis for STEMI

11
 17, 18
and NSTEMI are different and therefore developing risk scores specific for

STEMI and NSTEMI may provide a more accurate prediction of their prognosis. The

TIMI risk score has a dedicated score for STEMI.4 The derivation cohort in the TIMI

STEMI risk score was recruited from >800 hospitals.4 However it was not clear how

many patients were Asians. Although 15,078 patients were enrolled between 1997

and 1998, they only included patients presenting within 6 hours of symptoms onset

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and only reported 30-day mortality.4 The derivation cohort of the CADILLAC score14

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included 2,082 STEMI patients recruited from 1997 to 1999 into a randomized

is vie nt
controlled trial. Patients presenting within 12 hours of symptoms onset were included

r d re co
and those in cardiogenic shock at presentation were excluded and therefore patients in
he l ts
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fu ur and
this cohort were not representative of the real world population. The Primary

Angioplasty in Myocardial Infarction II (PAMI-II) criteria19 (for 6-month mortality)

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20
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and Zwolle PPCI index (30-day mortality) can also be used to identify low risk
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patients for early discharge 2 but they were both derived from non-Asian cohorts with
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patients recruited in the 1990s, with the former comprising of 3,252 patients from an
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RCT and the latter including 1,791 patients from a registry for their derivation

The Korean Acute Myocardial Infarction Registry (KAMIR)21 recently

on ti r:

cohorts.
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reported a risk score for Asians, derived from a cohort of 14,885 patients but it was
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not clear how the risk score was derived.21 There was only one Asian ethnic group
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represented and they combined both STEMI and NSTEMI patients who either

underwent invasive reperfusion strategy or were medically managed. They only

reported 1-year mortality and they showed that the KAMIR score performed better

than the GRACE score both in the NSTEMI and STEMI, highlighting the need for a

risk score that is specific to the local population.21 Most recently, the Acute Coronary

Treatment and Intervention Outcomes Network (ACTION) risk score to predict in-

12
 hospital mortality in ACS was reported.22 They included a total of 243,440 patients

and unlike the SMIR, entry in the former registry was voluntary. Moreover, they

consisted predominantly of Caucasians and African Americans and they combined

both STEMI and NSTEMI in the model. Although they showed that STEMI had

worse outcomes in their model, it is likely that the other components of their score

would have carried different weight for STEMI and NSTEMI if they were analyzed

. o re
s
ed urp s a
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separately. The SMIR STEMI risk score is novel as it included all consecutive

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STEMI patients treated by PPCI as part of a compulsory nationwide registry and it

is vie nt
can predict in-hospital, 30-days and 1-year mortality in a specific group of patients

r d re co
(STEMI patients reperfused by PPCI) in the 3 main Asian ethnic groups. Table 4
he l ts
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fu ur and
summarizes the prognostic factors included in the SMIR STEMI risk score in

comparison to factors in the GRACE, TIMI STEMI and CADILLAC PAMI-II,

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Zwolle, KAMIR and ACTION scores. All factors except ethnicity and a history of
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dislipidemia were present in at least one of the other risk scores in one form or
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another. Ethnicity is pertinent in our cohort but whether this risk score would perform
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well in Asians from other countries remains to be assessed in future studies. Having a
on ti r:

history of dislipidemia was predictive of 1-year mortality in the unadjusted model but
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was protective against 1-year mortality in the adjusted model. A “lipid paradox” has
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23 24
previously been reported for in-hospital and 30-days mortality. Whether this
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protective effect is due to the lipid levels themselves or the treatment effect is not

known and could not be elucidated in this study as data on the lipid levels and

treatment prior to the STEMI and at 1 year were not available in this registry and

warrants further investigation in future studies.

Limitations

13
 We did not perform a direct comparison of the performance of the SMIR STEMI risk

score against the GRACE score, which is currently the most popular, due to data on

heart rate and blood pressure not being collected on admission. Less than 5% of the

reperfused STEMI patients underwent thrombolysis from 2007 to 2014 and were not

included in this analysis. Therefore whether the SMIR STEMI risk score would

perform well in those Asian countries where thrombolysis is still widely used for

. o re
s
ed urp s a
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STEMI1 remains to be investigated. Angiographic data were not available and were

os p t
cl w en
not included in the score. However, a previous study25 have shown that the

is vie nt
angiographic factors provided only a minor improvement in the c-statistic of a risk

r d re co
score to predict in-hospital mortality in patients undergoing PCI procedures. We did
he l ts
rt na i
fu ur and
not include events occurring during hospitalization that could have improved the risk

prediction for 30-days and 1-year mortality, as we wanted to keep the model simple,
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for easy adoption in the clinical setting. The derivation and validation cohort were
t t d f sc
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temporally different and the difference between the 2 cohorts could be due to a
nd te ma

temporal improvement in the delivery of PPCI care. Despite this, the c-statistic of the
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model to predict 30-days and 1-year mortality was high (≥0.840) in validation cohort,
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on ti r:

indicating good discrimination, confirming previous statistical reports that despite a

en e
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shift in the covariates, this did not have modelling implications.26

nf cla
co is
D

CONCLUSION

We used a real-world, national AMI registry to develop a risk score to predict in-

hospital, 30-days and 1-year mortality in Asian STEMI patients reperfused by PPCI.

This new risk score uses factors from previously published risk scores, but also takes

their specific risk profiles and ethnicity into account. It can be easily calculated from

14
 parameters obtained within the first few hours of admission using the calculator, and

could be used to risk-stratify patients, guide duration of hospital stay, short and

medium term management and follow-up, to improve outcomes in these patients.

ACKNOWLEDGEMENTS

. o re
s
ed urp s a
se
The authors are grateful for the efforts of all the SMIR Coordinators, Data Manager

os p t
cl w en
and Quality Assurance staff from NRDO.

is vie nt
r d re co
he l ts
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fu ur and

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. o re
s
ed urp s a
se
os p t
cl w en
is vie nt
r d re co
he l ts
rt na i
fu ur and
be j t
o or rip
o
t t d f sc
no de nu
nd te ma
, a in e
n
ly al, Th
on ti r:
en e
id im
nf cla
co is
D

17
 TABLES
Table 1: Baseline characteristics in the derivation and validation cohort

Derivation cohort Validation cohort P

(n=7549) (n=3235)

Age (years) 57.7 (50.6-66.3) 57.2 (50.2-65.7) 0.054

. o re
Gender, n (%) 0.819

s
ed urp s a
se
Male 6423 (85.1) 2758 (85.3)

os p t
cl w en
Female 1126 (14.9) 477 (14.7)

is vie nt
Ethnicity, n (%) 0.795

r d re co
Chinese 4651 (61.6) 2019 (62.4)

he l ts
Malay rt na i 1502 (19.9) 642 (19.9)
fu ur and
Indian 1266 (16.8) 518 (16.0)
be j t

Others 130 (1.7) 56 (1.7)

o or rip
o

Diabetes, n (%) 2137 (28.3) 911 (28.2) 0.876

t t d f sc
no de nu

Hypertension, n (%) 3989 (52.8) 1654 (51.1) 0.103

nd te ma

Dyslipidemia, n (%) 3443 (45.6) 1421 (43.9) 0.108

, a in e

IHD, n (%) 1156 (15.3) 462 (14.3) 0.169

n
ly al, Th

Smoker, n (%) 3631 (48.1) 1648 (50.9) 0.007

on ti r:
en e

BMI (kg/m2) 24.6 (22.3-27.2) 24.5 (22.2-27.2) 0.262

id im

Killip class, n (%) 0.935

nf cla

I 6252 (82.9) 2690 (83.2)

co is
D

II 381 (5.1) 156 (4.8)

III 278 (3.7) 114 (3.5)

IV 635 (8.4) 274 (8.5)

Cardiac arrest in 285 (3.8) 121 (3.7) 0.930

ambulance/on
admission, n (%)

Creatinine (µmol/L) 91 (77-109) 90 (77-108) 0.165

Hemoglobin (g/L) 146 (134-157) 147 (135-157) 0.226

18
 Abnormal troponin 3546 (47.0) 1538 (47.5) 0.587
T/I, n (%)

Anterior STEMI, n 3792 (50.2) 1614 (49.9) 0.746

(%)

S2B (minutes) 198 (128-365) 198 (126-352) 0.788

D2B (minutes) 68 (52-93) 68 (51-91) 0.586

IHD: ischemic heart disease; BMI: body mass index; STEMI: ST-segment elevation
myocardial infarction; S2B: symptom-to-balloon; D2B: door-to-balloon

. o re
s
ed urp s a
se
os p t
cl w en
is vie nt
r d re co
he l ts
rt na i
fu ur and
be j t
o or rip
o
t t d f sc
no de nu
nd te ma
, a in e
n
ly al, Th
on ti r:
en e
id im
nf cla
co is
D

19
 . d
ed de
os en
cl nt
is l, i
r d tia
he n
Table 2: Univariate regression model for prediction of mortality based on the derivation cohort

rt de
In-hospital mortality 30-days mortality 1-year mortality

fu nfi
Odds Ratio Individual Collective Odds Ratio Individual Collective Odds Ratio Individual Collective

be co
P P P P P P
(95% CI) (95% CI) (95% CI)

o e
t t ar
Age (years) 1.06 (1.06-1.07) <0.001 <0.001 1.06 (1.05-1.07) <0.001 <0.001 1.07 (1.07-1.08) <0.001 <0.001

no nts
Gender

nd te
Male 1.00 (reference) <0.001 1.00 (reference) <0.001 1.00 (reference) <0.001

, a on
Female 2.45 (2.00-2.99) <0.001 2.33 (1.91-2.84) <0.001 2.58 (2.17-3.05) <0.001

ly c
on its
Ethnicity

es nd
Chinese 1.00 (reference) 0.353 1.00 (reference) 0.478 1.00 (reference) 0.039

Malay os t a
1.14 (0.91-1.42) 0.247 1.12 (0.90-1.39) 0.300 1.14 (0.95-1.36) 0.168
rp rip
Indian 0.87 (0.67-1.12) 0.278 0.89 (0.70-1.14) 0.367 0.79 (0.64-0.99) 0.038
pu sc

Others 0.98 (0.50-1.95) 0.962 0.93 (0.47-1.86) 0.846 0.75 (0.42-1.47) 0.452
ew nu
vi a

Killip class on
re m

admission
al he
rn : T

I 1.00 (reference) <0.001 1.00 (reference) <0.001 1.00 (reference) <0.001

ou er
r j im
fo cla

20
is
D
 . d
ed de
os en
cl nt
is l, i
II 2.39 (1.61-3.55) <0.001 2.67 (1.86-3.84) <0.001 2.47 (1.81-3.36) <0.001

r d tia
III 7.05 (5.10-9.74) <0.001 5.85 (4.22-8.10) <0.001 6.73 (5.11-8.86) <0.001

he n
rt de
IV 15.76 (12.76-19.47) <0.001 13.63 (11.08-16.77) <0.001 10.66 (8.83-12.88) <0.001

fu nfi
Cardiac arrest in

be co
ambulance/on
admission

o e
t t ar
No

no nts
Yes 1.00 (reference) <0.001 1.00 (reference) <0.001 1.00 (reference) <0.001

nd te
13.13 (10.18-16.93) <0.001 11.31 (8.77-14.58) <0.001 9.16 (7.16-11.71) <0.001

, a on
Creatinine on 1.00 (1.00-1.00) <0.001 <0.001 1.00 (1.00-1.00) <0.001 <0.001 1.00 (1.00-1.01) <0.001 <0.001

ly c
admission

on its
(µmol/L)

es nd
Hemoglobin on 0.75 (0.72-0.78) <0.001 <0.001 0.76 (0.73-0.79) <0.001 <0.001 0.72 (0.69-0.74) <0.001 <0.001
admission (g/dL) os t a
rp rip
Troponin T/I
pu sc

Normal 1.00 (reference) <0.001 1.00 (reference) <0.001 1.00 (reference) <0.001
ew nu

Abnormal 1.92 (1.60-2.30) <0.001 1.96 (1.64-2.34) <0.001 2.08 (1.78-2.42) <0.001
vi a
re m

Diabetes
al he

No 1.00 (reference) <0.001 1.00 (reference) <0.001 1.00 (reference) <0.001

rn : T

Yes 2.23 (1.86-2.66) <0.001 2.14 (1.79-2.54) <0.001 2.23 (1.92-2.59) <0.001
ou er
r j im
fo cla

21
is
D
 . d
ed de
os en
cl nt
is l, i
Smoker

r d tia
No 1.00 (reference) <0.001 1.00 (reference) <0.001 1.00 (reference) <0.001

he n
rt de
Yes 0.45 (0.37-0.54) <0.001 0.50 (0.42-0.61) <0.001 0.48 (0.41-0.56) <0.001

fu nfi
be co
Hypertension

o e
t t ar
No 1.00 (reference) <0.001 1.00 (reference) <0.001 1.00 (reference) <0.001

no nts
Yes 1.79 (1.49-2.15) <0.001 1.81 (1.51-2.17) <0.001 2.20 (1.88-2.58) <0.001

nd te
Dyslipidemia

, a on
No 1.00 (reference) 0.476 1.00 (reference) 0.534 1.00 (reference) 0.004

ly c
on its
Yes 1.07 (0.89-1.27) 0.476 1.06 (0.89-1.26) 0.534 1.24 (1.07-1.44) 0.004

es nd
IHD

No 1.00 (reference) os t a 0.005 1.00 (reference) 0.002 1.00 (reference) <0.001

rp rip
Yes 1.37 (1.10-1.72) 0.005 1.41(1.13-1.75) 0.002 1.78 (1.49-2.13) <0.001
pu sc

BMI (kg/m2) 0.98 (0.94-1.00) 0.030 0.086 0.97 (0.95-1.00) 0.050 0.050 0.95 (0.93-0.97) <0.001 <0.001
ew nu

STEMI location
vi a
re m

Non-anterior 1.00 (reference) <0.001 1.00 (reference) <0.001 1.00 (reference) <0.001
al he

Anterior 1.46 (1.22-1.74) <0.001 1.96 (1.64-2.34) <0.001 1.40 (1.21-1.63) <0.001
rn : T
ou er
r j im
fo cla

22
is
D
 . d
ed de
os en
cl nt
is l, i
S2B (minutes) 1.00 (1.00-1.00) <0.001 <0.001 1.00 (1.00-1.00) <0.001 <0.001 1.00 (1.00-1.00) <0.001 <0.001

r d tia
he n
CI: confidence interval; IHD: ischemic heart disease; BMI: body mass index; STEMI: ST-segment elevation myocardial infarction; S2B: symptom-to-balloon

rt de
fu nfi
be co
o e
t t ar
no nts
nd te
, a on
ly c
on its
es nd
os t a
rp rip
pu sc
ew nu
vi a
re m
al he
rn : T
ou er
r j im
fo cla

23
is
D
 . d
ed de
os en
cl nt
is l, i
Table 3: Multivariate logistic regression model for prediction of mortality based on the derivation cohort

r d tia
he n
In-hospital mortality 30-days mortality 1-year mortality

rt de
Odds Ratio Individual Collective Odds Ratio Individual Collective Odds Ratio Individual Collective

fu nfi
P P P P P P
(95% CI) (95% CI) (95% CI)

be co
Age (years) 1.06 (1.05-1.07) <0.001 <0.001 1.05 (1.04-1.07) <0.001 <0.001 1.06 (1.05-1.07) <0.001 <0.001

o e
t t ar
Gender Not significant Not significant Not significant

no nts
Male

nd te
Female

, a on
Ethnicity

ly c
on its
Chinese Not significant Not significant 1.00 (reference) 0.004

es nd
Malay 1.48 (1.19-1.85) <0.001

Indian os t a 1.01 (0.77-1.31) 0.952

rp rip
Others 1.02 (0.50-2.09) 0.953
pu sc

Killip class on
ew nu

admission
vi a
re m

I 1.00 (reference) <0.001 1.00 (reference) <0.001 1.00 (reference) <0.001

al he
rn : T
ou er
r j im
fo cla

24
is
D
 . d
ed de
os en
cl nt
is l, i
II 1.64 (1.08-2.48) 0.021 1.78 (1.21-2.62) 0.003 1.54 (1.10-2.15) 0.013

r d tia
III 3.19 (2.24-4.56) <0.001 2.67 (1.87 -3.82) <0.001 3.03 (2.21-4.16) <0.001

he n
rt de
IV 9.77 (7.70-12.38) <0.001 8.46 (6.71-10.66) <0.001 6.86 (5.51-8.53) <0.001

fu nfi
Cardiac arrest in

be co
ambulance/on
admission

o e
t t ar
No 1.00 (reference) <0.001 1.00 (reference) <0.001 1.00 (reference) <0.001

no nts
Yes 8.24 (5.99-11.34) <0.001 6.83 (4.99-9.34) <0.001 6.34 (5.51-8.53) <0.001

nd te
Creatinine on 1.00 (1.00-1.00) <0.001 <0.001 1.00 (1.00-1.00) <0.001 <0.001 1.00 (1.00-1.00) <0.001 <0.001

, a on
admission

ly c
(µmol/L)

on its
Hemoglobin on 0.94(0.89-0.99) 0.025 0.025 0.94 (0.89-0.99) 0.014 0.014 0.89 (0.85-0.93) <0.001 <0.001

es nd
admission (g/dL)

Troponin T/I on os t a
rp rip
admission
pu sc

Normal 1.00 (reference) <0.001 1.00 (reference) <0.001 1.00 (reference) <0.001
ew nu

Abnormal 1.69 (1.37-2.10) <0.001 1.71 (1.39-2.11) <0.001 1.72 (1.44-2.06) <0.001
vi a
re m
al he
rn : T
ou er
r j im
fo cla

25
is
D
 . d
ed de
os en
cl nt
is l, i
Diabetes

r d tia
No 1.00 (reference) <0.001 1.00 (reference) <0.001 1.00 (reference) <0.001

he n
rt de
Yes 1.70 (1.37-2.11) <0.001 1.60 (1.30-1.97) <0.001 1.55 (1.27-1.89) <0.001

fu nfi
Smoker Not significant Not significant Not significant

be co
No

o e
t t ar
Yes

no nts
Hypertension Not significant Not significant

nd te
No 1.00 (reference) 0.003

, a on
Yes 1.37 (1.11-1.68) 0.003

ly c
on its
Dyslipidemia Not significant Not significant

es nd
No 1.00 (reference) <0.001

Yes os t a 0.67 (0.55-0.83) <0.001

rp rip
IHD
pu sc

No Not significant Not significant 1.00 (reference) 0.008

ew nu

Yes 1.37 (1.09-1.73) 0.008

vi a
re m

BMI (kg/m2) Not significant Not significant Not significant

al he
rn : T
ou er
r j im
fo cla

26
is
D
 . d
ed de
os en
cl nt
is l, i
STEMI location

r d tia
Non-anterior 1.00 (reference) 0.002 1.00 (reference) <0.001 1.00 (reference) <0.001

he n
rt de
Anterior 1.40 (1.14-1.73) 0.002 1.44 (1.18-1.76) <0.001 1.41 (1.18-1.68) <0.001

fu nfi
S2B (minutes) Not significant Not significant Not significant

be co
P=1.000; c-statistic=0.878 (0.862-0.894)* P=1.000; c-statistic=0.861 (0.844-0.878)* P=1.000; c-statistic=0.862 (0.848-0.876)*

o e
t t ar
* P based on Hosmer-Lemeshow goodness-of-fit test with a P>0.05 indicating good fit; c-statistic based on area-under the curve

no nts
CI: confidence interval; IHD: ischemic heart disease; BMI: body mass index; STEMI: ST-segment elevation myocardial infarction; S2B: symptom-to-balloon

nd te
, a on
ly c
on its
es nd
os t a
rp rip
pu sc
ew nu
vi a
re m
al he
rn : T
ou er
r j im
fo cla

27
is
D
 . d
ed de
os en
cl nt
is l, i
Table 4: Comparison of SMIR STEMI risk score with GRACE, TIMI STEMI, CADILLAC, PAMI and Zwolle risk scores

r d tia
GRACE16 CADILLAC14 PAMI-II19 Zwolle20 KAMIR21 ACTION22

he n
SMIR TIMI-

rt de
STEMI4
c-statistic 0.86 c-statistic 0.82 c-statistic 0.83 c-statistic 0.78 c-statistic 0.91 c-statistic 0.83 c-statistic 0.88

fu nfi
c-statistic 0.65

be co
Age Yes Yes Yes Yes Yes Yes Yes Yes

o e
t t ar
Killip class on Yes Yes Yes Yes Yes Yes Yes Yes
admission

no nts
Anterior Yes ST-segment Yes (Anterior Yes (Anterior or Yes

nd te
STEMI deviation or LBBB) LBBB)

, a on
ly c
Creatinine on Yes Yes Yes Yes Yes (CrCl)

on its
admission (eGFR<60ml/min)

es nd
Cardiac arrest Yes Yes Yes
on admission
os t a
rp rip
1st reading of Yes Yes Yes
Troponin T/I
pu sc
ew nu

Hemoglobin on Yes Yes (Anemia)

admission
vi a
re m

Diabetes Yes Yes Yes (admission

al he

glucose)
rn : T
ou er
r j im
fo cla

28
is
D
 . d
ed de
os en
cl nt
is l, i
History IHD Yes Yes (angina)

r d tia
he n
Hypertension Yes Yes Yes

rt de
Dyslipidemia Yes

fu nfi
be co
Ethnicity Yes

o e
BMI/ weight No Yes (weight)

t t ar
Ischemic time Not significant Yes Yes

no nts
(>4 hours) (>4 hours)

nd te
, a on
Heart Rate Not available Yes Yes Yes Yes

ly c
Blood pressure Not available Yes Yes Yes

on its
Baseline LVEF Not available Yes Yes

es nd
<40%

3-vessel disease Not available

os t a Yes Yes
rp rip

Post PPCI Not available Yes Yes

pu sc

TIMI flow
ew nu

STEMI: ST-segment elevation myocardial infarction; BMI: body mass index; IHD: ischemic heart disease; LVEF: baseline LVEF, PPCI: primary
vi a
re m

percutaneous coronary intervention; TIMI: thrombolysis in myocardial infarction

al he
rn : T
ou er
r j im
fo cla

29
is
D
 D
co is
nf cla
FIGURES

id im
en e
on ti r:
ly al, Th
, a in e
nd te ma
n
no de nu
t t d f sc

30
o or rip
be j t
o
fu ur and
rt na i
he l ts
r d re co
is vie nt
Figure 1: Flow chart of STEMI patients from SMIR included in this study

cl w en
os p t
ed urp s a
. o re
se
s
 Figure 2: Internal validation of the models in the derivation cohort

There was good calibration of the models for in-hospital, 30-day and 1-year mortality with c-
statistic of 0.883, 0.859 and 0.857 respectively.

. o re
s
ed urp s a
se
os p t
cl w en
is vie nt
r d re co
he l ts
rt na i
fu ur and
be j t
o or rip
o
t t d f sc
no de nu
nd te ma
, a in e
n
ly al, Th
on ti r:
en e
id im
nf cla
co is
D

31
 Figure 3: External validation of the models in the validation cohort

There was good discrimination of the models for in-hospital, 30-day and 1-year mortality
with c-statistic of 0.855, 0.844 and 0.849 respectively.

. o re
s
ed urp s a
se
os p t
cl w en
is vie nt
r d re co
he l ts
rt na i
fu ur and
be j t
o or rip
o
t t d f sc
no de nu
nd te ma
, a in e
n
ly al, Th
on ti r:
en e
id im
nf cla
co is
D

32
D
is
fo cla
r j im
ou er
rn : T
al he
re m
vi a
ew nu
pu sc
rp rip
os t a
es nd
on its
Figure 4: Nomogram for risk score to predict mortality for individual patients

33
ly c
, a on
nd te
no nts
t t ar
o e
be co
fu nfi
rt de
he n
r d tia
is l, i
cl nt
os en
ed de
. d