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\begin{document}

\title{Global longitudinal strain and long-term outcome in patients presenting
to the emergency department with suspected acute coronary syndrome}



\author[1]{Alexander Fuks}%
\author[1]{Noah Liel-Cohen}%
\author[1]{David Blondheim}%
\author[2]{Sara Shimoni}%
\author[1]{Mohamed Jabaren}%
\author[1]{Marina Leitman}%
\author[3]{Salim Adawi}%
\author[3]{Ronen Jaffe}%
\author[1]{Basheer Karkabi}%
\author[3]{Ihab Asmer}%
\author[1]{Majdi Ganaeem}%
\author[4]{Sergio Kobal}%
\author[1]{Idit Lavi}%
\author[1]{Walid Saliba}%
\author[3]{Avinoam Shiran}%
\affil[1]{Affiliation not available}%
\affil[2]{Kaplan medical center}%
\affil[3]{Carmel Hospital}%
\affil[4]{Soroka Hospital}%


\vspace{-1em}



  
  \date{June 15, 2024}


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\selectlanguage{english}
\begin{abstract}
Aims: We have previously shown that 2-dimentional strain is not a useful
tool for ruling out acute coronary syndrome (ACS) in the emergency
department (ED). The aim of the present study was to determine whether
in patients with suspected ACS, global longitudinal strain (GLS),
measured in the ED using 2-dimensional strain imaging, can predict
long-term outcome. Methods: Long-term (median 7.7 years {[}IQR
6.7-8.2{]}) major adverse cardiac events (MACE; cardiac death, ACS,
revascularization, hospitalization for heart failure or atrial
fibrillation) and all-cause mortality data was available in 525/605
patients (87\%) enrolled in the Two-Dimensional Strain for Diagnosing
Chest Pain in the Emergency Room (2DSPER) study. The study prospectively
enrolled patients presenting to the ED with chest pain and suspected ACS
but without a diagnostic ECG or elevated troponin. GLS was computed
using echocardiograms performed within 24 hours of chest pain. MACE of
patients with worse GLS (\textgreater{} median GLS) was compared to
patients with better GLS (? median GLS). Results: Median GLS was
-18.7\%. MACE occurred in 47/261 (18\%) of patients with worse GLS as
compared with 45/264 (17\%) with better GLS, adjusted HR 0.87 (95\% CI
0.57-1.33, P=0.57). There was no significant difference in all-cause
mortality or individual end-points between groups. GLS did not predict
MACE even in patients with optimal 2-dimensional image quality (n=164,
adjusted HR=1.51, 95\% CI 0.76-3.0). Conclusions: GLS did not predict
long-term outcome in patients presenting to the ED with chest pain and
suspected ACS, supporting our findings in the 2DSPER study.%
\end{abstract}%



\sloppy


\textbf{Global longitudinal strain and long-term outcome in patients
presenting to the emergency department with suspected acute coronary
syndrome}

Alexander Fuks, MD,\textsuperscript{a} Noah Liel-Cohen,
MD,\textsuperscript{b} David S. Blondheim, MD,\textsuperscript{c,d} Sara
Shimoni, MD,\textsuperscript{e} Mohamed Jabaren,
MD,\textsuperscript{f}Marina Leitman, MD,\textsuperscript{g} Salim
Adawi, MD,\textsuperscript{a,d} Ronen Jaffe, MD,\textsuperscript{a,d}
Basheer Karkabi, MD,\textsuperscript{a,d} Ihab Asmer,
RDCS,\textsuperscript{a}Majdi Ganaeem, RDCS,\textsuperscript{a}

Sergio L. Kobal, MD,\textsuperscript{b} Idit Lavi,
MSc,\textsuperscript{h} Walid Saliba, MD,\textsuperscript{d,h} and
Avinoam Shiran, MD \textsuperscript{a,d}

\textsuperscript{a}Department of Cardiovascular Medicine, Lady Davis
Carmel Medical Center, Haifa, Israel, \textsuperscript{b}Division of
Cardiology, Soroka University Medical Center and Ben Gurion University
of the Negev, Beer Sheva, Israel, \textsuperscript{c}Department of
Cardiology, Hillel Yaffe Medical Center, Hadera, Israel,
and\textsuperscript{d}the Ruth and Bruce Rappaport Faculty of Medicine,
Technion, Israel Institute of Technology, Haifa,
Israel,\textsuperscript{e}Kaplan Medical Center, Rehovot, Hebrew
University, Jerusalem, Israel, \textsuperscript{f}Department of
Cardiology, Haemek Medical Center, Afula, Israel,
\textsuperscript{g}Department of Cardiology, Shamir Medical Center,
Zerifin and Sackler School of Medicine, Tel Aviv University, Israel,
\textsuperscript{h}Department of Community Medicine and Epidemiology,
Lady Davis Carmel Medical Center, Haifa, Israel

\textbf{Running head:} Outcome of suspected ACS by GLS

\textbf{Funding} : Supported by grants from Clalit Health Services,
Israel, and from the Israel Heart Society.

\textbf{Address for Correspondence:}

Prof. Avinoam Shiran, MD

Director, Department of Cardiology

Lady Davis Carmel Medical Center

7 Michal Street,

Haifa 34362, Israel

Tel: 972-4-825-0812

Fax: 972-4-825-0916

Email: av.shiran@gmail.com

ORCID 0000-0001-8500-602X

\textbf{Abstract}

\textbf{Aims:} We have previously shown that 2-dimentional strain is not
a useful tool for ruling out acute coronary syndrome (ACS) in the
emergency department (ED). The aim of the present study was to determine
whether in patients with suspected ACS, global longitudinal strain
(GLS), measured in the ED using 2-dimensional strain imaging, can
predict long-term outcome.

\textbf{Methods:} Long-term (median 7.7 years {[}IQR 6.7-8.2{]}) major
adverse cardiac events (MACE; cardiac death, ACS, revascularization,
hospitalization for heart failure or atrial fibrillation) and all-cause
mortality data was available in 525/605 patients (87\%) enrolled in the
Two-Dimensional Strain for Diagnosing Chest Pain in the Emergency Room
(2DSPER) study. The study prospectively enrolled patients presenting to
the ED with chest pain and suspected ACS but without a diagnostic ECG or
elevated troponin. GLS was computed using echocardiograms performed
within 24 hours of chest pain. MACE of patients with worse GLS
(\textgreater{} median GLS) was compared to patients with better GLS ([?]
median GLS).

\textbf{Results:} Median GLS was -18.7\%. MACE occurred in 47/261 (18\%)
of patients with worse GLS as compared with 45/264 (17\%) with better
GLS, adjusted HR 0.87 (95\% CI 0.57-1.33, \emph{P} =0.57). There was no
significant difference in all-cause mortality or individual end-points
between groups. GLS did not predict MACE even in patients with optimal
2-dimensional image quality (n=164, adjusted HR=1.51, 95\% CI 0.76-3.0).

\textbf{Conclusions:} GLS did not predict long-term outcome in patients
presenting to the ED with chest pain and suspected ACS, supporting our
findings in the 2DSPER study.

\emph{Clinical Trial Registration}\textbf{---}
URL:http://.clinicaltrials.gov. Unique identifier: NCT01163019.

\textbf{Key Words:} Global longitudinal strain, speckle tracking
echocardiography, major adverse cardiac events, long-term outcome, acute
coronary syndrome

Left ventricular (LV) systolic function, routinely assessed by
echocardiography, is an important predictor of patient
outcome.\textsuperscript{1} Left ventricular ejection fraction (LVEF),
commonly used to assess LV systolic function, is operator dependent, has
significant interobserver variability, and does not necessarily
represent myocardial contractility.\textsuperscript{2,3} Two-dimensional
longitudinal strain (2DLS) using speckle tracking imaging
echocardiography can be analyzed using an automated, reproducible tool
for the assessment of global and segmental LV
function.\textsuperscript{4--6} Global longitudinal strain (GLS),
calculated from 18 LV segments, has been shown to correlate well with
pressure-volume loop-derived contractility
indices.\textsuperscript{2}GLS has been shown to be an independent
predictor of outcome, better than LVEF, in patients with heart failure,
myocardial infarction and valvular heart disease.\textsuperscript{7--11}

Despite the fact that the use of GLS is recommended by current
guidelines, the recently published SUCCOUR (Strain Surveillance of
Chemotherapy for Improving Cardiovascular Outcomes) study, a prospective
multicenter randomized trial, failed to meet its primary endpoint,
preventing a significant reduction in LVEF at 1 year using a GLS-guided
strategy.\textsuperscript{12--14} These results emphasize the need for
large prospective studies to evaluate the utility of GLS in routine
clinical practice.

The 2-Dimensional Strain Echocardiography for Diagnosing Chest Pain in
the Emergency Room (2DSPER) study was a multicenter, prospective,
blinded study designed to assess the utility of 2DLS in the assessment
of low to moderate risk patients presenting to the emergency department
(ED) with suspected acute coronary syndrome (ACS).\textsuperscript{15}In
that study 2DLS was not found to be a useful tool for ruling out ACS in
the ED, despite the fact that several small studies had reported that
2DLS can accurately detect coronary artery disease (CAD) and identify
patients with ACS.\textsuperscript{16--21} This discrepancy could be
partly explained by the fact that unlike the other studies, in which
most patients without ACS had normal 2DLS, in 2DSPER many patients
without ACS had abnormal 2DLS. The prognostic significance of abnormal
2DLS in these patients is unclear, and to the best of our knowledge,
there are no studies that assessed the utility of 2DLS for the
prediction of outcome in patients presenting to the ED with chest pain.

The aim of the present study was to determine whether GLS can predict
long-term outcome in patients presenting to the ED with suspected ACS.

\section*{Methods}

{\label{methods}}

\textbf{Study population}

The 2DSPER was a prospective multicenter blinded study conducted by the
Israeli Echo Research Group.\textsuperscript{15} Patients over the age
of 45 who presented to the ED with chest pain and suspected ACS were
enrolled from 11 Israeli medical centers participating in the study
between September 2010 and February 2014. Patients were excluded if they
had [?]1mm ST segment deviation, elevated initial troponin, previous
myocardial infarction or coronary bypass surgery, other than normal
sinus rhythm, complete left bundle brunch block, moderate or severe
valvular heart disease or cardiomyopathy.

Patients were diagnosed as having ACS based on the clinical presentation
and evidence of myocardial ischemia on stress ECG, stress
echocardiography or scintigraphy and/or in the presence of a culprit
lesion ([?]70 stenosis in a major coronary artery) on coronary computed
tomography angiography (CCTA) or invasive coronary angiography.

The study was approved by the local institutional review board of each
participating center and all patients signed an informed consent form.

\textbf{Echocardiography}

Transthoracic echocardiography was performed using commercially
available General Electric systems (VIVID Q, S6 or Vivid 7, GE Vingmed
Ultrasound AS, Horten, Norway). Apical long axis, 4-chamber and
2-chamber views were digitally recorded at a frame rate of
\textgreater{}40 fps for offline 2DLS analysis. Standard
echocardiographic findings, but not 2DLS findings, were available to the
attending physician.

An echo study was performed within 24h of the patients' last chest pain
episode. Patients with suboptimal 2D echo image quality, defined as [?]2
technically suboptimal segments from apical views, were excluded from
the study. All echocardiograms were analyzed in a core lab (Lady Davis
Carmel Medical Center) by a single experienced sonographer (IA) blinded
to all clinical data. Of the 700 patients initially enrolled in the
2DSPER study 48 (6.9\%) did not meet the 2D echo image quality criteria
and were withdrawn from the study after the initial core lab analysis.
The final cohort included 605 patients who had complete clinical and
echocardiographic data, including adequate 2DLS analysis. In all 605
patients included, tracking in all LV segments was feasible according to
the 2DLS analysis software.

All 605 echocardiograms included in the final 2DSPER study cohort were
reviewed by a second experienced sonographer (MG) blinded to all
clinical and 2DLS data. Studies with the best image quality, defined as
optimal visualization of all left ventricular segments throughout the
cardiac cycle in all 3 apical views, were classified by the blinded
sonographer as high quality, and the rest as low
quality.\textsuperscript{22}

All echocardiograms were analyzed using a dedicated 2DLS software
(EchoPAC SW version 113.0.3; GE Vingmed Ultrasound AS). For each patient
GLS was computed by averaging all 18 segments. Reproducibility of GLS
measurements in the 2DSPER study has been previously
reported.\textsuperscript{15}

\textbf{Long-term follow-up}

Long-term follow-up was available in 6 of the 11 centers participated in
the 2DSPER study. Data on major adverse cardiac events (MACE, defined as
cardiac death, ACS, revascularization, hospitalization for heart failure
or atrial fibrillation) and all-cause mortality was collected using
electronic patient records between October 2018 and May 2020. We defined
cardiac death as death resulting from an acute myocardial infarction,
sudden cardiac death or heart failure, or death due to a cardiac
procedure.\textsuperscript{23}

\textbf{Statistical analysis}

Continuous variables are presented as mean\selectlanguage{ngerman}±SD or medians and
interquartile range, and categorical variables as numbers and
percentages. Patients were divided into worse GLS group
(GLS\textgreater{}median) and better GLS group (GLS\selectlanguage{english}[?]median).
Characteristics of worse and better GLS groups were compared using the
Student's \emph{t} -test or the Mann Whitney test as appropriate for
continuous variables and \selectlanguage{greek}χ\selectlanguage{english}\textsuperscript{2} or Fisher's exact test for
categorical data. Survival curves for MACE were constructed using the
Kaplan--Meier method and compared between GLS groups using the log-rank
test. Patients were followed from the date of discharge till the first
occurrence of MACE, non-cardiac death or end of follow-up, whichever
came first. Cox proportional hazard regression models were used to
calculate hazards ratios (HR) and corresponding 95\% confidence
intervals (CI) for MACE, it's individual components and all-cause
mortality, and to assess the univariate and the multivariate predictors
of MACE. Models were adjusted for relevant demographic, clinical and
echocardiographic variables. Differences were considered statistically
significant at the 2-sided \emph{P} \textless{}0.05. Statistical
analyses were performed using IBM SPSS Statistics 24.0 (IBM, New York,
NY).

\section*{Results}

{\label{results}}

\textbf{Study population}

Long-term follow up was available in 525 patients (87\% of the 605
patients included in the final analysis of 2DSPER, 99\% of the 529
patients from the 6 centers with available long-term follow-up). A
histogram of GLS values derived from the baseline echocardiogram in the
525 patients with available long-term follow-up is presented in Figure
1. Median GLS was -18.7\%. Patients were divided into ``better GLS''
group (GLS [?] -18.7\%, n=264) and ``worse GLS'' group (GLS \textgreater{}
-18.7\%, n=261). GLS was abnormal (\textgreater{} -17\% according to
current guidelines) in 120/525 patients
(23\%).\textsuperscript{24}Patient characteristics are summarized in
Table 1. Patients with worse GLS were more likely to be men. There was
no difference in coronary risk factors, except for smoking which was
more prevalent in patients with worse GLS. Patients with worse GLS had a
higher body mass index, and higher creatinine and hemoglobin levels.
There was no difference in medical treatment between groups

Echocardiographic findings are summarized in Table 2. Patients with
worse GLS were: less likely to have high 2D image quality, more likely
to have lower LVEF and wall motion abnormality and more likely to have
thicker LV walls. Although they had more impaired early LV relaxation,
there was no difference in their E/e' ratio.

Data from initial ED visit and hospitalization is presented in Table 3.
Patients with worse GLS were more likely to be admitted to the hospital
and undergo invasive coronary angiography, and less likely to undergo
coronary computed tomography angiography. They were more likely to be
diagnosed with ACS, mostly unstable angina pectoris, and undergo
revascularization.

\textbf{Long term outcome}

Median follow-up was 7.7 years (IQR 6.7-8.2 years). There was no
difference in long-term all-cause mortality between groups (Table 4).
Long-term MACE occurred in 92 patients (17.5\%). Cardiac death was very
low in both groups, and there was no significant difference in long-term
MACE or in the individual end-points between groups (Table 4, Figure 2).
ACS or revascularization accounted for 68/92 (74\%) of MACE.
Hospitalization for heart failure was rare even in the group of patients
with worse GLS. We repeated the analysis with a GLS cutoff value of
-17\%, the cutoff value for abnormal GLS.\textsuperscript{24} There was
no significant difference in long-term MACE between patients with normal
vs. abnormal GLS (log-rank \emph{P} =0.64).

To determine whether suboptimal 2D image quality was the cause of our
findings, we repeated the same analysis in the 164 patients with optimal
2D image quality (better GLS: n= 97, worse GLS: n=67). Long-term MACE
tended to be higher in the worse GLS group (HR=1.85, 95\%CI
0.94-3.63,\emph{P} =0.07(, but there was no statistically significant
difference in MACE after adjustment for history of CAD, hypertension and
ACS at presentation (HR=1.51, 95\% CI 0.76-3.0, \emph{P} =0.24).

Independent predictors of long-term MACE were male gender, hypertension,
history of CAD and ACS at presentation (Table 5). Thus, a worse GLS did
not predict long-term outcome.

\section*{Discussion}

{\label{discussion}}

Our data clearly show that in patients presenting to the ED with chest
pain and suspected ACS, GLS does not predict long term outcome, namely
cardiac death, ACS, revascularization, hospitalization for heart failure
or atrial fibrillation. The results were the same whether we defined
worse GLS as GLS \textgreater{} -18.7\% (median GLS) or GLS
\textgreater{} -17\% (abnormal GLS according to guidelines), or when we
analyzed only patients with optimal 2D echo image quality. To the best
of our knowledge, this is the first study to report the effect of GLS on
long-term outcome in patients with suspected ACS. We have previously
reported a significantly higher 6-month MACE in patients with ACS as
compared to patients in which ACS was excluded (5.8\% vs. 0.6\%,\emph{P}
=0.0002).\textsuperscript{15} The fact that 6-month MACE was extremely
rare in 2DSPER in patients in whom ACS was excluded, suggests that the
likelihood of missing significant CAD in these patients was very low.

GLS has been shown to be a good predictor of outcome, better than LVEF,
in patients with heart failure, myocardial infarction and severe
valvular disease.\textsuperscript{7--11,25} In a meta-analysis of 16
published articles which included 5721 patients, Kalam et al concluded
that GLS predicts all-cause mortality and MACE (cardiac death,
hospitalization for heart failure and malignant
arrhythmia).\textsuperscript{10} Most of the patients included in the
meta-analysis had myocardial infarction, heart failure or severe
valvular or myocardial disease. In contrast to our study population,
these patients were sicker, had a wider range of GLS values and included
more patients with abnormal GLS values, thus explaining the discrepancy
between the other studies and ours. Even in patients with heart failure
and preserved LVEF, mean GLS was worse and standard deviation wider, as
compared to our group of patients with worse GLS (-15.2 \selectlanguage{ngerman}± 4.6\% in the
study of Park et al, compared to -16.7±1.5\% in our
study).\textsuperscript{9} Most of our patients had good LV function. In
2DSPER, patients without ACS had worse GLS as compared to control groups
in previous studies reporting high diagnostic accuracy of
2DLS.\textsuperscript{17,19} Worse GLS, however, was not associated with
poor outcome in our study.

In addition, most patients with ACS included in 2DSPER had unstable
angina pectoris and one vessel disease, and good outcome is expected in
such patients. In sicker patients with myocardial enzyme leak and severe
CAD, 2DLS is unnecessary for the diagnosis of ACS.\textsuperscript{26}

Although 2DLS and GLS are accurate, reproducible and automated measures
of LV contraction, they are dependent on 2D echo image quality and
loading conditions which limit their accuracy, similar to
LVEF.\textsuperscript{4,27,28} Another measure of LV strain, global
circumferential strain, has been shown to be a better predictor of
outcome when compared to GLS.\textsuperscript{25} In 2DSPER we used a
new 2DLS parameter, the peak systolic strain value identifying the worst
20\% LV segments (PSS20\%), since this parameter was reported to
outperform GLS in diagnosing ACS, because of its ability to identify
minor wall motion abnormalities.\textsuperscript{17} Unfortunately, in
the 2DSPER study PSS20\% was not superior to GLS in diagnosing
ACS.\textsuperscript{15} Similar to most other studies assessing the
utility of LV strain in predicting outcome, we used GLS, since GLS is a
simple and robust diagnostic tool, readily available in most commercial
echo machines.

In our study, independent predictors of long-term MACE were history of
CAD, ACS diagnosis, male gender and hypertension, but not GLS. Only 14\%
of our study population had ACS, and recurrent ACS or revascularization
accounted for the majority of long-term events included in MACE, not
heart failure or cardiac death. In a study from Poland of 2731 patients
with unstable angina pectoris, the predictors of death or coronary
events during 3 years follow-up were age, kidney disease, hypertension,
diabetes, previous stroke and previous percutaneous coronary
interventions.\textsuperscript{29} In another study of 230 patients
discharged from the ED with a diagnosis of chest pain of undetermined
origin, 4.4\% had MACE during 12 months of follow-up, and the predictors
of MACE were abnormal ECG, diabetes, or preexisting
CAD.\textsuperscript{30} As expected, in our study similar to the other
studies, markers of CAD at baseline predicted late coronary events. GLS,
contrary to previous reports, not only failed to accurately identify ACS
in the ED, but failed to predict future cardiac events as well, thus
extending our findings from the 2DSPER multicenter study, of a limited
value for GLS in low-risk patients presenting to the ED with suspected
ACS.

\textbf{Limitations}

Long-term follow-up in our study was incomplete (87\% of the patients
included in 2DSPER had long-term follow-up). Long-term follow-up,
however, was available in 99\% of the patients included in the 6 centers
participating in the currents study, thus minimizing selection bias.
Given the unequivocal nature of our results (Figure 2), it is highly
unlikely that complete follow-up would significantly alter our findings.
GLS is dependent on 2D image quality.\textsuperscript{22,27} In 2DPSER
mid-range systems, frequently utilized in the ED, were used. We do not
know whether using high-end machines would have significantly improved
GLS accuracy and its predictive power. However, only patients with
adequate 2D image quality were included in 2DSPER, hence making our
findings relevant to everyday practice. Furthermore, GLS did not predict
outcome even in the subgroup of patients with optimal 2D echo image
quality.

\textbf{Conclusions}

GLS did not predict long-term outcome in patients presenting to the ED
with chest pain and suspected ACS with neither a diagnostic ECG or
elevated cardiac enzymes. These data support our findings in the
original 2DSPER multicenter study, and together with the SUCCOUR study,
emphasize the need for large prospective trials to evaluate the clinical
utility of GLS. We conclude that 2DLS is not a useful tool for the
diagnosis of ACS and for predicting outcome in low to intermediate risk
patients presenting to the ED with chest pain and suspected ACS.

\textbf{Conflict of interest:} NLC, DSB, SS, MJ, ML and AS report
non-financial support from GE Healthcare, Haifa, Israel, during the
conduct of the study.



\textbf{References}

1. Quiñones MA, Greenberg BH, Kopelen HA, Koilpillai C, Limacher MC,
Shindler DM, Shelton BJ, Weiner DH. Echocardiographic predictors of
clinical outcome in patients with left ventricular dysfunction enrolled
in the SOLVD registry and trials: Significance of left ventricular
hypertrophy. \emph{J Am Coll Cardiol} 2000;35:1237--1244.

2. Kovács A, Oláh A, Lux Á, Mátyás C, Németh BT, Kellermayer D, Ruppert
M, Török M, Szabó L, Meltzer A, Assabiny A, Birtalan E, Merkely B,
Radovits T. Strain and strain rate by speckle-tracking echocardiography
correlate with pressure-volume loop-derived contractility indices in a
rat model of athlete's heart. \emph{Am J Physiol - Hear Circ
Physiol}2015;308:743--748.

3. Oh JK, Pellikka PA, Panza JA, Biernat J, Attisano T, Manahan BG,
Wiste HJ, Lin G, Lee K, Miller FA, Stevens S, Sopko G, She L, Velazquez
EJ. Core lab analysis of baseline echocardiographic studies in the STICH
trial and recommendation for use of echocardiography in future clinical
trials. \emph{J Am Soc Echocardiogr} 2012;25:327--336.

4. Liel-Cohen N, Tsadok Y, Beeri R, Lysyansky P, Agmon Y, Feinberg MS,
Fehske W, Gilon D, Hay I, Kuperstein R, Leitman M, Deutsch L, Rosenmann
D, Sagie A, Shimoni S, Vaturi M, Friedman Z, Blondheim DS. A new tool
for automatic assessment of segmental wall motion based on longitudinal
2D strain a multicenter study by the israeli echocardiography research
group. \emph{Circ Cardiovasc Imaging} 2010;3:47--53.

5. Reisner SA, Lysyansky P, Agmon Y, Mutlak D, Lessick J, Friedman Z.
Global longitudinal strain: A novel index of left ventricular systolic
function. \emph{J Am Soc Echocardiogr} 2004;17:630--633.

6. Leitman M, Lysyansky P, Sidenko S, Shir V, Peleg E, Binenbaum M,
Kaluski E, Krakover R, Vered Z. Two-dimensional strain-a novel software
for real-time quantitative echocardiographic assessment of myocardial
function. \emph{J Am Soc Echocardiogr} 2004;17:1021--1029.

7. Nagata Y, Takeuchi M, Wu VCC, Izumo M, Suzuki K, Sato K, Seo Y,
Akashi YJ, Aonuma K, Otsuji Y. Prognostic value of LV deformation
parameters using 2D and 3D speckle-tracking echocardiography in
asymptomatic patients with severe aortic stenosis and preserved LV
ejection fraction. \emph{JACC Cardiovasc Imaging} 2015;8:232--245.

8. Kim HM, Cho GY, Hwang IC, Choi HM, Park JB, Yoon YE, Kim HK.
Myocardial Strain in Prediction of Outcomes After Surgery for Severe
Mitral Regurgitation. \emph{JACC Cardiovasc Imaging} 2018;11:1235--1244.

9. Park JJ, Park JB, Park JH, Cho GY. Global Longitudinal Strain to
Predict Mortality in Patients With Acute Heart Failure. \emph{J Am Coll
Cardiol} 2018;71:1947--1957.

10. Kalam K, Otahal P, Marwick TH. Prognostic implications of global LV
dysfunction: A systematic review and meta-analysis of global
longitudinal strain and ejection fraction.
\emph{Heart}2014;100:1673--1680.

11. Haugaa KH, Grenne BL, Eek CH, Ersbøll M, Valeur N, Svendsen JH,
Florian A, Sjøli B, Brunvand H, Køber L, Voigt JU, Desmet W, Smiseth OA,
Edvardsen T. Strain echocardiography improves risk prediction of
ventricular arrhythmias after myocardial infarction. \emph{JACC
Cardiovasc Imaging} 2013;6:841--850.

12. Plana JC, Galderisi M, Barac A, Ewer MS, Ky B, Scherrer-Crosbie M,
Ganame J, Sebag IA, Agler DA, Badano LP, Banchs J, Cardinale D, Carver
J, Cerqueira M, Decara JM, Edvardsen T, Flamm SD, Force T, Griffin BP,
Jerusalem G, Liu JE, Magalhães A, Marwick T, Sanchez LY, Sicari R,
Villarraga HR, Lancellotti P. Expert consensus for multimodality imaging
evaluation of adult patients during and after cancer therapy: A report
from the American society of echocardiography and the European
association of cardiovascular imaging. \emph{J Am Soc
Echocardiogr}2014;27:911--939.

13. Moslehi JJ, Witteles RM. Global Longitudinal Strain in
Cardio-Oncology. \emph{J Am Coll Cardiol} 2021;77:402--404.

14. Thavendiranathan P, Negishi T, Somerset E, Negishi K, Penicka M,
Lemieux J, Aakhus S, Miyazaki S, Shirazi M, Galderisi M, Marwick TH.
Strain-Guided Management of Potentially Cardiotoxic Cancer
Therapy.\emph{J Am Coll Cardiol} 2021;77:392--401.

15. Shiran A, Blondheim DS, Shimoni S, Jabarren M, Rosenmann D, Sagie A,
Leibowitz D, Leitman M, Feinberg M, Beeri R, Adawi S, Shotan A, Goland
S, Bloch L, Kobal SL, Liel-Cohen N. Two-dimensional strain
echocardiography for diagnosing chest pain in the emergency room: a
multicentre prospective study by the Israeli echo research
group.\emph{Eur Hear J -- Cardiovasc Imaging} 2017;18:1016--1024.

16. Lee M, Chang S-A, Cho EJ, Park S-J, Choi J-O, Lee S-C, Oh JK, Park
SW. Role of strain values using automated function imaging on
transthoracic echocardiography for the assessment of acute chest pain in
emergency department. \emph{Int J Cardiovasc Imaging} 2015;31:547--556.

17. Shimoni S, Gendelman G, Ayzenberg O, Smirin N, Lysyansky P, Edri O,
Deutsch L, Caspi A, Friedman Z. Differential effects of coronary artery
stenosis on myocardial function: The value of myocardial strain analysis
for the detection of coronary artery disease. \emph{J Am Soc
Echocardiogr} 2011;24:748--757.

18. Nucifora G, Schuijf JD, Delgado V, Bertini M, Scholte AJHA, Ng ACT,
Werkhoven JM van, Jukema JW, Holman ER, Wall EE van der, Bax JJ.
Incremental value of subclinical left ventricular systolic dysfunction
for the identification of patients with obstructive coronary artery
disease. \emph{Am Heart J} 2010;159:148--157.

19. Dahlslett T, Karlsen S, Grenne B, Eek C, Sjøli B, Skulstad H,
Smiseth OA, Edvardsen T, Brunvand H. Early assessment of strain
echocardiography can accurately exclude significant coronary artery
stenosis in suspected non-ST-segment elevation acute coronary
syndrome.\emph{J Am Soc Echocardiogr} 2014;27:512--519.

20. Choi JO, Cho SW, Song Y Bin, Cho SJ, Song BG, Lee SC, Park SW.
Longitudinal 2D strain at rest predicts the presence of left main and
three vessel coronary artery disease in patients without regional wall
motion abnormality. \emph{Eur J Echocardiogr} 2009;10:695--701.

21. Caspar T, Samet H, Ohana M, Germain P, Ghannudi S El, Talha S, Morel
O, Ohlmann P. Longitudinal 2D strain can help diagnose coronary artery
disease in patients with suspected non-ST-elevation acute coronary
syndrome but apparent normal global and segmental systolic
function.\emph{Int J Cardiol} 2017;236:91--94.

22. Shiran A, Blondheim DS, Shimoni S, Jabarren M, Rosenmann D, Sagie A,
Leibowitz D, Leitman M, Feinberg MS, Beeri R, Adawi S, Asmer I, Ganaeem
M, Friedman Z, Liel-Cohen N. Effect of image quality on accuracy of
two-dimensional strain echocardiography for diagnosing ischemic chest
pain: a 2DSPER multicenter trial substudy. \emph{Int J Cardiovasc
Imaging} 2019;35:617--625.

23. Hicks KA, Tcheng JE, Bozkurt B, Chaitman BR, Cutlip DE, Farb A,
Fonarow GC, Jacobs JP, Jaff MR, Lichtman JH, Limacher MC, Mahaffey KW,
Mehran R, Nissen SE, Smith EE, Targum SL. 2014 ACC/AHA key data elements
and definitions for cardiovascular endpoint events in clinical trials: A
Report of the American College of Cardiology/American Heart Association
Task Force on Clinical Data Standards (Writing Committee to Develop
Cardiovascu. \emph{J Am Coll Cardiol} 2015;66:403--469.

24. Lang RM, Badano LP, Victor MA, Afilalo J, Armstrong A, Ernande L,
Flachskampf FA, Foster E, Goldstein SA, Kuznetsova T, Lancellotti P,
Muraru D, Picard MH, Retzschel ER, Rudski L, Spencer KT, Tsang W, Voigt
JU. Recommendations for cardiac chamber quantification by
echocardiography in adults: An update from the American Society of
Echocardiography and the European Association of Cardiovascular
Imaging.\emph{J Am Soc Echocardiogr} 2015;28:1-39.e14.

25. Cho GY, Marwick TH, Kim HS, Kim MK, Hong KS, Oh DJ. Global
2-Dimensional Strain as a New Prognosticator in Patients With Heart
Failure. \emph{J Am Coll Cardiol} 2009;54:618--624.

26. Collet J-P, Thiele H, Barbato E, Barthélémy O, Bauersachs J, Bhatt
DL, Dendale P, Dorobantu M, Edvardsen T, Folliguet T, Gale CP, Gilard M,
Jobs A, Jüni P, Lambrinou E, Lewis BS, Mehilli J, Meliga E, Merkely B,
Mueller C, Roffi M, Rutten FH, Sibbing D, Siontis GCM, Kastrati A, Mamas
MA, Aboyans V, Angiolillo DJ, Bueno H, Bugiardini R, Byrne RA,
Castelletti S, Chieffo A, Cornelissen V, Crea F, Delgado V, Drexel H,
Gierlotka M, Halvorsen S, Haugaa KH, Jankowska EA, Katus HA, Kinnaird T,
Kluin J, Kunadian V, Landmesser U, Leclercq C, Lettino M, Meinila L,
Mylotte D, et al. 2020 ESC Guidelines for the management of acute
coronary syndromes in patients presenting without persistent ST-segment
elevation. \emph{Eur Heart J} 2020:1--79.

27. Voigt JU, Pedrizzetti G, Lysyansky P, Marwick TH, Houle H, Baumann
R, Pedri S, Ito Y, Abe Y, Metz S, Song JH yu., Hamilton J, Sengupta PP,
Kolias TJ, D'Hooge J, Aurigemma GP, Thomas JD, Badano LP aol.
Definitions for a common standard for 2D speckle tracking
echocardiography: consensus document of the EACVI/ASE/Industry Task
Force to standardize deformation imaging. \emph{Eur Heart J Cardiovasc
Imaging} 2015;16:1--11.

28. Nesbitt GC, Mankad S, Oh JK. Strain imaging in echocardiography:
Methods and clinical applications. \emph{Int J Cardiovasc
Imaging}2009;25:9--22.

29. Piatek \selectlanguage{polish}Ł, \selectlanguage{english}Janion-Sadowska A, Piatek K, Zandecki \selectlanguage{polish}Ł, \selectlanguage{english}Zabojszcz M,
Siudak Z, Sadowski M. Long-term clinical outcomes in patients with
unstable angina undergoing percutaneous coronary interventions in a
contemporary registry data from Poland. \emph{Coron Artery
Dis}2020;31:215--221.

30. Prina LD, Decker WW, Weaver AL, High WA, Smars PA, Locke GR, Reeder
GS. Outcome of Patients with a Final Diagnosis of Chest Pain of
Undetermined Origin Admitted under the Suspicion of Acute Coronary
Syndrome: A Report from the Rochester Epidemiology Project. \emph{Ann
Emerg Med} 2004;43:59--67.

31. Antman EM, Cohen M, Bernink PJLM, McCabe CH, Horacek T, Papuchis G,
Mautner B, Corbalan R, Radley D, Braunwald E. The TIMI risk score for
unstable angina/non-ST elevation MI: A method for prognostication and
therapeutic decision making. \emph{JAMA} 2000;284:835--842.



\textbf{Figure Legends}

\textbf{Figure 1: Histogram of baseline GLS values in study population
(n=525)}

\textbf{Figure 2: Kaplan--Meier curves showing long-term MACE by GLS
groups}

Log-rank \emph{P} =0.57. Worse GLS: GLS\textgreater{} -18.7\% (median
GLS). Better GLS: GLS\textless{} -18.7\%.

\textbf{Table 1:} Patient Characteristics\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
Variable & \textbf{Better GLS} & \textbf{Worse GLS} & \emph{P}
Value\tabularnewline
\midrule
\endhead
& \emph{(n = 264)} & \emph{(n = 261)} &\tabularnewline
Age (y) & 58.7\selectlanguage{ngerman}±8.3 {[}57.3{]} & 57.4\selectlanguage{ngerman}±8.5 {[}56.0{]} &
0.07\tabularnewline
Male gender & 167 (63.3\%) & 210 (80.5\%) &
\textbf{\textless{}0.0001}\tabularnewline
Height (cm) & 169.8\selectlanguage{ngerman}±10.0 {[}170.0{]} & 171.5\selectlanguage{ngerman}±8.2 {[}172.0{]} &
\textbf{0.033}\tabularnewline
Weight (kg) & 80.0 \selectlanguage{ngerman}±15.0 {[}79.0{]} & 84.7\selectlanguage{ngerman}±15.5 {[}83.0{]} &
\textbf{0.001}\tabularnewline
BMI (kg/m\selectlanguage{ngerman}²) & 27.7\selectlanguage{ngerman}±4.5 {[}27.3{]} & 28.7\selectlanguage{ngerman}±4.7 {[}28.3{]} &
\textbf{0.01}\tabularnewline
Known CAD & 20 (7.6\%) & 28 (10.7\%) & 0.21\tabularnewline
Previous PCI & 17 (6.4\%) & 26 (10.0\%) & 0.14\tabularnewline
TIMI score\textsuperscript{*} & 1.64\selectlanguage{ngerman}±1.20 {[}1.0{]} & 1.82\selectlanguage{ngerman}±1.10
{[}2.0{]} & 0.06\tabularnewline
\emph{Risk factors} & & &\tabularnewline
Hypertension & 118 (44.7\%) & 127 (48.7\%) & 0.36\tabularnewline
Diabetes & 59 (22.3\%) & 72 (27.6\%) & 0.17\tabularnewline
Hyperlipidemia & 147 (55.7.0\%) & 149 (57.0\%) & 0.75\tabularnewline
FH of CAD & 94 (35.6\%) & 89 (34.0\%) & 0.72\tabularnewline
Current smoker & 80 (30.3\%) & 106 (40.6\%) &
\textbf{0.014}\tabularnewline
\emph{Medications at enrolment} & & &\tabularnewline
Aspirin & 110 (41.7\%) & 108 (41.4\%) & 0.97\tabularnewline
Beta blockers & 47 (17.8\%) & 49 (18.8\%) & 0.77\tabularnewline
Nitrates & 6 (2.3\%) & 3 (1.1\%) & 0.32\tabularnewline
ACE-I & 47 (17.8\%) & 59 (22.6\%) & 0.17\tabularnewline
ARB & 25 (9.3\%) & 18 (6.9\%) & 0.28\tabularnewline
CCB & 35 (13.3\%) & 28 (10.7\%) & 0.37\tabularnewline
\emph{Laboratory results} & & &\tabularnewline
Creatinine (mg\%) & 0.85\selectlanguage{ngerman}±0.18 {[}0.83{]} & 0.90\selectlanguage{ngerman}±0.20 {[}0.89{]} &
\textbf{0.004}\tabularnewline
Hb (g\%) & 13.9\selectlanguage{ngerman}±1.3 {[}14.0{]} & 14.3\selectlanguage{ngerman}±1.4 {[}14.3{]} &
\textbf{0.009}\tabularnewline
Troponin T (ng/L)+ & 15.32\selectlanguage{ngerman}±64.0 {[}7.0{]} & 34.8\selectlanguage{ngerman}±142.8 {[}4.0{]} &
0.73\tabularnewline
\bottomrule
\end{longtable}

\textsuperscript{*}Unstable angina/non-ST elevation myocardial
infarction TIMI score\textsuperscript{31}

+Highest troponin during initial emergency department admission

ACE-I= angiotensin converting enzyme inhibitor, ARB=angiotensin receptor
blocker, BMI=body mass index, CAD=coronary artery disease, CCB=calcium
channel blocker, FH=family history, Hb=hemoglobin, PCI=percutaneous
coronary intervention

\textbf{Table 2:} Echocardiographic findings\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
Variable & \textbf{Better GLS} & \textbf{Worse GLS} & \emph{P} Value &
\emph{P} Value\tabularnewline
\midrule
\endhead
& \emph{(n = 264)} & \emph{(n = 261)} & &\tabularnewline
High 2D image quality & 97 (36.7\%) & 67 (25.7\%) & \textbf{0.006} &
\textbf{0.006}\tabularnewline
Heart rate (beats/min)* & 66.7\selectlanguage{ngerman}±11.9 {[}66.0{]} & 68.5\selectlanguage{ngerman}±11.1 {[}67.0{]} &
0.07 & 0.07\tabularnewline
BP systolic (mmHg)*+ & 129.0\selectlanguage{ngerman}±18.2 {[}129.0{]} & 131.4\selectlanguage{ngerman}±18.7 {[}130.0{]} &
0.36 & 0.36\tabularnewline
BP diastolic (mmHg)*+ & 77.2\selectlanguage{ngerman}±9.3 {[}78.0{]} & 79.8\selectlanguage{ngerman}±12.9 {[}80.0{]} &
\textbf{0.01} & \textbf{0.01}\tabularnewline
LVEF (\%) & 62.0\selectlanguage{ngerman}±3.6 {[}60.0{]} & 59.5\selectlanguage{ngerman}±5.2 {[}60.0{]} &
\textbf{\textless{}0.0001} & \textbf{\textless{}0.0001}\tabularnewline
WMA & 9 (3.4\%) & 42 (16.1\%) & \textbf{\textless{}0.0001} &
\textbf{\textless{}0.0001}\tabularnewline
LVEDD (cm) & 4.5\selectlanguage{ngerman}±0.43 {[}4.5{]} & 4.6\selectlanguage{ngerman}±0.48 {[}4.5{]} & 0.05 &
0.05\tabularnewline
LVESD (cm) & 2.80\selectlanguage{ngerman}±0.43 {[}2.80{]} & 2.96\selectlanguage{ngerman}±0.55 {[}3.0{]} & \textbf{0.006}
& \textbf{0.006}\tabularnewline
IVS (cm) & 1.00\selectlanguage{ngerman}±0.15 {[}1.0{]} & 1.05\selectlanguage{ngerman}±0.17 {[}1.0{]} &
\textbf{\textless{}0.0001} &\tabularnewline
PW (cm) & 0.93\selectlanguage{ngerman}±0.13 {[}0.9{]} & 0.97\selectlanguage{ngerman}±0.15 {[}1.0{]} & \textbf{0.001}
&\tabularnewline
LA (cm) & 3.56\selectlanguage{ngerman}±0.47 {[}3.6{]} & 3.50\selectlanguage{ngerman}±0.46 {[}3.5{]} & 0.85
&\tabularnewline
PASP (mmHg) ++ & 25.65\selectlanguage{ngerman}±7.2 {[}25.0{]} & 24.4\selectlanguage{ngerman}±6.2 {[}23.5{]} & 0.1
&\tabularnewline
E (cm/sec) & 70.8\selectlanguage{ngerman}±15.0 {[}70.0{]} & 65.8\selectlanguage{ngerman}±15.1 {[}64.0{]} &
\textbf{\textless{}0.0001} &\tabularnewline
A (cm/sec) & 69.9\selectlanguage{ngerman}±17.6 {[}68.0{]} & 67.4\selectlanguage{ngerman}±17.5 {[}66.0{]} & 0.1
&\tabularnewline
E/A & 1.06\selectlanguage{ngerman}±0.30 {[}0.99{]} & 1.04\selectlanguage{ngerman}±0.50 {[}0.95{]} & 0.07 &
0.07\tabularnewline
DecT (msec) & 209.0\selectlanguage{ngerman}±48.7 {[}205.0{]} & 225.1\selectlanguage{ngerman}±53.4 {[}208.0{]} & 0.14 &
0.14\tabularnewline
e' septal (cm/sec) & 8.07\selectlanguage{ngerman}±2.08 {[}8.0{]} & 7.5\selectlanguage{ngerman}±2.0 {[}7.0{]} &
\textbf{0.001} & \textbf{0.001}\tabularnewline
e' lateral (cm/sec) & 10.3\selectlanguage{ngerman}±2.7 {[}10.0{]} & 9.3\selectlanguage{ngerman}±2.8 {[}9.0{]} &
\textbf{\textless{}0.0001} & \textbf{\textless{}0.0001}\tabularnewline
e' mean (cm/sec) & 9.1\selectlanguage{ngerman}±2.4 {[}9.0{]} & 8.2\selectlanguage{ngerman}±2.3 {[}8.5{]} &
\textbf{\textless{}0.0001} & \textbf{\textless{}0.0001}\tabularnewline
E/e' mean & 8.1\selectlanguage{ngerman}±2.6 {[}7.6{]} & 8.4\selectlanguage{ngerman}±3.2 {[}7.6{]} & 0.28
&\tabularnewline
GLS & -20.8\selectlanguage{ngerman}±1.6 {[}-20.5{]} & -16.7\selectlanguage{ngerman}±1.5 {[}-17.0{]} &
\textbf{\textless{}0.0001} &\tabularnewline
\bottomrule
\end{longtable}

Numbers in brackets represent medians

*At the time of echocardiography

+18 missing (3.4\%)

++230 unavailable (43.8\%)

BP=blood pressure, DecT=E-wave deceleration time, IVS=interventricular
septum, LA=left atrium, LVEDD=left ventricular end-diastolic diameter,
LVEF=left ventricular ejection fraction, LVESD=left ventricular
end-systolic diameter, PASP=pulmonary artery systolic pressure,
PW=posterior wall, WMA=wall motion abnormality

\textbf{Table 3:} Initial workup, coronary anatomy, revascularization
and final diagnosis\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
Variable & \textbf{Better GLS} & \textbf{Worse GLS} & \emph{P}
Value\tabularnewline
\midrule
\endhead
& \emph{(n = 264)} & \emph{(n = 261)} &\tabularnewline
Hospital admission & 163 (61.7\%) & 212 (81.2\%) &
\textbf{\textless{}0.0001}\tabularnewline
\emph{CCTA n (\%)} & 33 (12.5\%) & 17 (6.5\%) &
\textbf{0.02}\tabularnewline
Calcium score & 190.5\selectlanguage{ngerman}±288.3 {[}42.0{]} & 112.9\selectlanguage{ngerman}±225.4 {[}9.0{]} &
0.76\tabularnewline
\emph{Coronary angiography n (\%)} & 45 (17.0\%) & 74 (28.4\%) &
\textbf{0.002}\tabularnewline
1 vessel disease & 19/45 (42.2\%) & 27/74 (36.5\%) & 0.34\tabularnewline
Severe CAD* & 2/45 (4.4\%) & 6/74 (8.1\%) & 0.70\tabularnewline
Culprit lesion identified+ & 24/72 (33.3\%) & 43/87(49.4\%) &
\textbf{0.041}\tabularnewline
No culprit lesion identified & 48/72 (66.7\%) & 44/87 (50.6\%)
&\tabularnewline
\emph{Revascularization} & 22 (8.3\%) & 38 (14.6\%) &
\textbf{0.025}\tabularnewline
PCI & 22/22 (100\%) & 35/38 (92.0\%) & 0.29\tabularnewline
CABG & 0/22 (0\%) & 3/38 (7.9\%) & 0.18\tabularnewline
\emph{ACS} & 26 (9.8\%) & 47 (18.0\%) & \textbf{0.007}\tabularnewline
Unstable angina & 23/26 (88.5\%) & 40/47 (85.1\%) & 0.65\tabularnewline
NSTEMI & 3/26 (11.5\%) & 5/47 (10.6\%) &\tabularnewline
STEMI++ & 0/26 (0\%) & 2/47 (4.3\%) &\tabularnewline
\bottomrule
\end{longtable}

*Three vessel or left main or proximal left anterior descending CAD

+Diameter stenosis [?]70\% on CCTA or coronary angiography

++During observation

ACS=acute coronary syndrome, CABG=coronary artery bypass grafting,
CAD=coronary artery disease, CCTA=coronary computed tomography
angiography, NSTEMI=non-ST elevation myocardial infarction,
PCI=percutaneous coronary intervention, STEMI=ST-elevation myocardial
infarction

\textbf{Table 4:} Long-term outcome\selectlanguage{english}
\begin{longtable}[]{@{}lllllll@{}}
\toprule
\begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
Variable\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
\textbf{Better GLS} (n=264)\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
\textbf{Worse GLS} (n=261)\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
\textbf{Unadjusted HR} (95\% CI)\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
\emph{P} Value\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
\textbf{Adjusted HR} (95\% CI)\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
\emph{P} Value\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
All-cause mortality\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
16 (6.1\%)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
12 (4.6\%)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.77 (0.37-1.63)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.50\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.74 (0.34-1.61)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.45\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\textbf{MACE}\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
45 (17.0\%)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
47 (18.0\%)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
1.13 (0.75-1.70)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.57\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.87 (0.57-1.33)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.51\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Cardiac death\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
1 (0.4\%)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
2 (0.8\%)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
2.06 (0.18-22.68)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.56\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
-\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
ACS\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
20 (7.6\%)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
23 (8.8\%)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
1.24 (0.68-2.26)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.48\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.86 (0.47-1.47)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.64\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Revascularization\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
27 (10.2\%)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
28 (10.7\%)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
1.12 (0.66-1.90)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.68\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.83 (0.47-1.47)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.53\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Hospitalization for HF\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
5 (1.9\%)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
3 (1.1\%)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.63 (0.15-2.62)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.52\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.54 (0.13-2.40)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.41\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Atrial fibrillation\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
13 (4.9\%)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
8 (3.1\%)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.63 (0.26-1.51)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.29\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.69 (0.28-1.70)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.42\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

Adjusted HR for cardiac death could not be calculated due to small
numbers.

ACS=acute coronary syndrome, HF=heart failure, HR=hazard ratio,
MACE=major adverse cardiac events (cardiac death, ACS,
revascularization, hospitalization for heart failure or atrial
fibrillation)\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-1/Figure-1}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-2/Figure-2}

\end{center}
\end{figure}

\selectlanguage{english}
\FloatBarrier
\end{document}

