Association Between Left Ventricular Global Longitudinal...

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Association Between Left Ventricular Global Longitudinal Strain and

Adverse Left Ventricular Dilatation After ST-segment Elevation

Myocardial Infarction

Joyce et al: GLS and LV Dilatation after STEMI

Emer Joyce1, MB BCh BAO, MRCPI; Georgette E. Hoogslag1, MSc;

Darryl P. Leong1,2, MBBS, PhD; Philippe Debonnaire1, MD;

Spyridon Katsanos1, MD; Helèn Boden1, MD; Martin J. Schalij1, MD, PhD;

Nina Ajmone Marsan1, MD, PhD; Jeroen J. Bax1, MD, PhD;

Victoria Delgado1, MD, PhD

1Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands;

2Discipline of Medicine, University of Adelaide and Flinders University, Adelaide, Australia.

Correspondence: Victoria Delgado, MD, PhD Dept. of Cardiology, Leiden University Medical Center Albinusdreef 2, 2333 ZA Leiden, the Netherlands Phone: +31 71 526 2020, Fax: +31 71 526 6809 Email address: [email protected]

DOI: 10.1161/CIRCIMAGING.113.000982

Journal Subject Codes: [31] Echocardiography; [4] Acute myocardial infarction; [115]

Remodeling

Cardiology, Leiden University Medical Center, Leiden, the Neth

edicine, University of Adelaide and Flinders University, Adelaid

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Abstract

Background—Myocardial infarct size is a major determinant of left ventricular (LV)

remodeling after ST-segment elevation myocardial infarction (STEMI). We evaluated

whether LV global longitudinal strain (GLS), proposed as a novel marker of infarct size, is

associated with 3- and 6-month LV dilatation after STEMI.

Methods and Results—In first STEMI patients treated with primary percutaneous coronary

intervention, baseline LVGLS was measured with 2-dimensional speckle-tracking

echocardiography. Patients were dichotomized according to median value. The independent

relation between GLS groups and LV end-diastolic volume (EDV) at 3- and 6-month

(adjusted for clinical and echocardiographic variables) was assessed. The final study

population comprised 1041 patients (60±12 years, 76% male). Median LVGLS was -15.0%.

Patients with baseline LVGLS >-15.0% exhibited greater LV dilatation at 3- and 6-months

compared to patients with GLS -15.0% (LVEDV 123 44 vs. 106 36ml and 121 43 vs.

102 34ml respectively; global group-time interaction p<0.001). This association retained the

same statistical significance after adjustment for various relevant demographic, clinical and

echocardiographic characteristics. Furthermore, net reclassification improvement index

demonstrated significant incremental value of LVGLS for prediction of LVEDV increase

(0.14 (95% CI 0.00034 - 0.29), p=0.04).

Conclusions—LVGLS prior to discharge after STEMI is independently associated with LV

dilatation at follow-up.

Key Words: echocardiography; global longitudinal strain; acute myocardial infarction; left

ventricular remodeling; infarct size

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Myocardial infarct size is a major determinant of subsequent left ventricular (LV) remodeling

and dysfunction, both strong predictors of poor outcomes after ST-segment myocardial

infarction (STEMI).1-3 Assessment of infarct size can be achieved by several methods

including quantification of cardiac biomarkers, 2-dimensional (2D) echocardiography

estimation of LV ejection fraction (EF) and wall motion score index (WMSI) and contrast-

enhanced magnetic resonance imaging (CE-MRI). Although measurement of creatinine

kinase (CK) or troponin T (TnT) levels is widely available, their accuracy to predict LV

remodeling is modest.4, 5 Alternatively, CE-MRI can accurately quantify the extent of

myocardial scarring after myocardial infarction and has become the new gold standard for

infarct size assessment in many randomized clinical trials. However, this imaging technique

is not available at the bedside and may not be feasible in some patients. In contrast,

echocardiography is widely available in the acute setting and thus has become the imaging

technique of first choice for risk stratification after myocardial infarction. LVEF and WMSI

measured early after STEMI are valid surrogates of infarct size and have become established

predictors of LV remodeling and clinical outcome.2, 6 However, several limitations exist in

the quantification of these parameters by 2D echocardiography, including the assumption of

symmetric LV geometry, intra- and inter-observer variability and, in the case of WMSI, the

requirement for expert observers.

Novel echocardiographic imaging techniques such as speckle-tracking strain imaging provide

information on myocardial tissue function which is incremental to LVEF and WMSI to

predict LV functional recovery and clinical outcome after STEMI.7, 8 LV global longitudinal

strain (GLS) measurement after STEMI has also demonstrated specific benefit over LVEF in

the evaluation of the extent of post-STEMI LV myocardial injury.9, 10 However, despite being

proposed as a novel marker of infarct size, few studies have specifically investigated the

relationship between baseline LVGLS and LV remodeling in the contemporary post-STEMI

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population. The aim of the current evaluation was to investigate whether LVGLS

measurement prior to discharge predicts LV dilatation at 3- and 6-month post-infarction in a

large contemporary STEMI population.

Methods

Patient population

Patients admitted with a first STEMI treated with primary percutaneous coronary intervention

(PCI) from February 2004 to December 2008 and included in an ongoing registry were

evaluated.11 All patients were treated according to the institutional MISSION! protocol based

on the recent guidelines.12, 13 This clinical framework includes optimal guidelines-based

medical therapy, 2D echocardiography performed within 48 hours after primary PCI and

standardized outpatient follow-up. Baseline 2D echocardiography was used to assess LV

function after STEMI with traditional parameters (LV volume based indices and WMSI).

Speckle-tracking analysis was used to calculate LVGLS at baseline and patients were divided

into 2 groups based on the median value. 2D echocardiography was repeated at 3- and 6-

month follow-up and the independent association between LVGLS groups and increase in

LV end-diastolic volume (EDV) was assessed. Patients who died during index hospitalisation

or who were in cardiogenic shock requiring inotropic or mechanical circulatory support or in

atrial fibrillation at time of baseline echocardiography were excluded. Finally, patients with

reinfarction prior to 6-month echocardiography were also excluded.

Clinical data was prospectively collected in the departmental Cardiology Information System

(EPD-Vision®, Leiden University Medical Center) and retrospectively analysed. For this

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2D echocardiography performed within 48 hours after primary

patient follow-up. Baseline 2D echocardiography was used to s

TEMI with traditional parameters (LV volume based indices and

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retrospective analysis of clinically acquired data, the Institutional Review Board waived the

need of patient written informed consent.

2D transthoracic echocardiography

Patients were imaged in the left lateral decubitus position using a commercially available

system (Vivid 7, GE Healthcare, Horten, Norway) equipped with a 3.5-MHz transducer.

Analysis of echocardiographic images was performed offline using EchoPAC version 11.0.0

software (GE Healthcare). LV end-systolic volume (LVESV), LVEDV and LVEF were

quantified at baseline and at 3 and 6-months follow-up using the Simpson’s biplane

technique.14 The intra- and interobserver agreement for assessment of LVEDV at our

laboratory has been previously reported as 93% and 92% respectively.15 Qualitative

assessment of regional wall motion was performed for each patient by dividing the LV into

16 segments. Each segment was then scored individually based on its motion and systolic

thickening (1=normokinesis, 2=hypokinesis, 3=akinesis, 4=dyskinesis) and WMSI was

calculated as the sum of the segment scores divided by the number of segments scored.14

Severity of mitral regurgitation (MR) was graded according to current recommendations.16

Diastolic function was assessed according to standard recommendations.17 Left atrial volume

was evaluated with the biplane Simpson’s technique and indexed to body surface area

(LAVI).14

Global longitudinal strain analysis

LVGLS was quantified from the apical 4-, 2- and 3-chamber views stored as digital cine-

loops and processed offline using commercially available speckle-tracking analysis software

(EchoPac 112.0.1, GE Medical Systems, Horten, Norway). Images were recorded with frame

rates >40 frames per second to ensure reliable analysis by the software. The end-systolic

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frame was defined in the apical long-axis view by marking the closure of the aortic valve.

Following this, the LV endocardial border was traced at end systole in all 3 apical views and

the automatically created region of interest was manually adjusted to the thickness of the

myocardium. Tracking quality was assessed in all segments and if tracking was of poor

quality segments were discarded. LVGLS was provided by the software as the average value

of the peak systolic longitudinal strain of the 3 apical views, using a 17-segment model, in a

bull’s-eye plot (Figure 1). As previously reported, the intra- and interobserver variability for

the measurement of LVGLS in our institution is 0.1±2.2% and 0.2±0.8% respectively.18

Statistical analysis

Continuous, normally distributed variables are presented as mean and standard deviation

(SD) or standard error (SE) as appropriate. Non-normally distributed data are presented as

median and interquartile range. Categorical variables are presented as frequencies and

percentages. The total population was divided into 2 groups based on the median value of

LVGLS. Continuous variables were compared between the 2 groups using Student-t test,

Mann Whitney U test or X2 test as appropriate.

The primary modeling approach was linear mixed effects model analysis with LVEDV as the

dependent variable and time (0, 3- and 6-month) as the principal fixed effect. The main

predictor variable of interest was baseline LVGLS. Of note, missing data points did not

exclude subjects from the analysis, as inherent in the mixed modeling analysis structure. To

determine whether baseline LVGLS was associated with subsequent change in LVEDV, it

was modelled in an interaction term with time. If this group-time interaction term was

significant, it indicated a time-dependent relationship between baseline GLS and LVEDV.

Post hoc testing was then performed to determine the time points at which LVEDV differed

between the LVGLS groups. Other important and potentially confounding baseline clinical

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and echocardiographic predictors known to influence outcome and/or LV systolic function

after STEMI were similarly tested for their ability to predict change in LVEDV over time.

The effect of baseline LVGLS on change in LVEDV was also adjusted for these parameters.

Additionally, in order to evaluate the incremental value of LVGLS over clinical and

conventional echocardiographic variables in predicting LV dilatation following STEMI,

likelihood ratio test and net reclassification improvement (NRI) index were performed.19 NRI

was used to evaluate the incremental value of baseline LVGLS in reclassifying the risk of

individuals developing 20% increase in LVEDV 6-month post-STEMI.20 To assess

robustness of our initial model, sensitivity analysis was performed excluding those patients

who had died and/or those did not have either 3- or 6-month or both echocardiographic

datasets available for the initial analysis.

All statistical tests were two-sided, and a p value of <0.05 was considered statistically

significant. Statistical analysis was performed using STATA version 11 (STATA Corp.,

College Station, Texas). The authors had full access to the data and take responsibility for its

integrity. All authors have read and agreed to the manuscript as written.

Results

Baseline characteristics

Of 1245 patients initially evaluated, 102 (8%) were excluded due to previous myocardial

infarction. Twenty-two (2%) patients died during index hospitalisation. A further 30 patients

were excluded due to cardiogenic shock (n=10, 1%) or atrial fibrillation at time of baseline

echocardiography (n=20, 2%). Of the remaining 1091 patients, baseline LVGLS

measurement was not possible due to inadequate image quality and/or too low frame rate in

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23 patients (2%). Reinfarction prior to 6-months had subsequently occurred in 2.5% (n=27)

of these patients, and following their exclusion, the final study population comprised 1041

patients (Supplemental Figure 1). Table 1 summarizes the baseline characteristics of the

patient population (mean age was 60±12 years, 76% male).

Baseline LVGLS

Median LVGLS was -15.0% (interquartile range: -12.1%, -18.0%) for the total population.

Baseline characteristics according to LVGLS >-15.0% (n=520) and -15.0% (n=521) are

shown in Table 1. Patients with LVGLS >-15.0% more frequently had diabetes, the LAD as

the culprit vessel, multivessel disease and higher cardiac biomarker concentrations compared

to patients with LVGLS -15.0%. On echocardiography, patients with LVGLS >-15.0% had

significantly larger LV volumes and WMSI and lower LVEF compared to their counterparts.

Regarding diastolic parameters, E/E’ ratio was significantly higher and E/A ratio,

deceleration time and E’ were significantly lower in patients with LVGLS >-15.0%.Presence

of grade 2 MR or LAVI did not differ significantly between the 2 groups.

Follow-up

Across the total patient population, LVEDV increased significantly between baseline and 3-

and 6-month follow-up (from 103±34 to 115±41 and to 112±40ml, respectively, p<0.001)

while LVESV did not change significantly overall (from 55±22 to 57±29 and to 54±29ml,

respectively, p=0.21). Additionally, the number of patients showing grade 2 MR over length

of follow-up also increased significantly (from 6.0% to 7.9% and to 7.7%, respectively,

p=0.006).

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Predictors of change in LVEDV from baseline to follow-up

Table 2 details the results of linear mixed model analyses. Higher WMSI was significantly

associated with LV remodeling as were male gender, LAD infarct compared to non-LAD,

higher discharge heart rate and peak troponin concentration and lower LAVI at baseline.

Regarding LVGLS, although baseline LVEDV was higher in patients with baseline LVGLS

>-15.0% compared to -15.0%, this difference was no significant after adjustment for other

relevant baseline clinical characteristics (p=0.1). In addition, patients with baseline LVGLS

>-15.0% exhibited greater LV dilatation at 3- and 6-month (LVEDV 124 44 vs. 106 36ml,

p<0.001 and 121 43 vs. 102 34ml, p<0.001 respectively; group-time interaction term

p<0.001) compared to their counterparts. This association between LVGLS and increased LV

dilatation retained the same statistical significance after adjustment for all parameters

significantly different between GLS groups, in addition to other parameters considered

clinically significant (Figure 2).

On likelihood ratio test, LVGLS (according to median) provided significant incremental

value for the prediction of follow-up LV dilatation to a model containing all other significant

clinical and echocardiographic predictors of LV remodeling (male gender, LAD infarct, peak

troponin concentration, discharge heart rate, LAVI and WMSI) - log-likelihood difference of

17.8, p<0.001 for measuring LVGLS in addition to clinical predictors, LAVI and WMSI

compared with clinical predictors, LAVI and WMSI alone. In addition, NRI index

demonstrated significant incremental value of LVGLS to predict 20% increase in LVEDV

over and above multiple covariates – including age, gender, diabetes, infarct territory, multi-

vessel disease, Killip class, peak CK and troponin concentrations, glucose concentration,

symptom-to-balloon time, MR severity, discharge heart rate and neurohormonal therapy

prescription at discharge (NRI 0.14 (95% CI 0.00034 - 0.29), p=0.04).

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Finally, the analysis was performed after excluding patients who did not have both

echocardiographic datasets available for the initial analysis (n=144). In the remaining large

subgroup (n=897), the adjusted group-time interaction term p-value for this sensitivity

analysis remained <0.001.

Discussion

The present observational study shows that in the acute phase after STEMI, stratifying

patients according to median LVGLS (-15.0%) delineates a group of patients more likely to

show increased LV dilatation at follow-up. LVGLS >-15.0% was independently associated

with significantly larger LV volumes over both 3- and 6-month follow-up. Additionally

baseline LVGLS provided incremental value to a model containing peak troponin

concentration and WMSI to predict LVEDV increase after STEMI.

LVGLS as a marker of infarct size

Speckle-tracking derived LVGLS is a novel parameter of LV function which more closely

reflects intrinsic myocardial function than traditional parameters by evaluating the active

component of deformation.21 Moreover, speckle-tracking derived LVGLS is independent of

geometric assumptions and insonation angle and has relatively low intra- and inter-observer

variability.22 Due to these inherent advantages over other echocardiographic modalities,

several recent studies have investigated the role of LVGLS measurement as a marker of

infarct size, whether measured in the acute phase after revascularization 9, 10, 23 or at follow-

up.24, 25 A cut-off for LVGLS of -15% measured after reperfusion served as a more precise

predictor of large infarction than LVEF in 39 thrombolysis-treated STEMI patients.9 In a

larger group of primary PCI-treated patients, LVGLS measured at day 1 was also superior to

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LVEF in predicting 30-day infarct size.23 In our large population of contemporary STEMI

patients treated with primary PCI, a post-revascularization LVGLS value >-15.0% was

significantly associated with clinical characteristics traditionally indicative of larger infarct

size (diabetes, multivessel disease, higher biomarker levels). Additionally, these patients had

significantly more impaired global and regional systolic and diastolic function parameters

(including LVEF, WMSI and E’) as compared to the group of patients with more preserved

myocardial shortening (LVGLS -15.0%).

LVGLS and LV remodeling

Despite the demonstrated role of LVGLS in accurately identifying the extent of global

myocardial injury and dysfunction after infarction, few studies in the contemporary era have

specifically related LVGLS measurement in the acute phase after STEMI to the risk of LV

remodeling at follow-up. A substudy of the VALIANT (valsartan in acute myocardial

infarction trial) study including 603 post-STEMI patients with LV dysfunction, demonstrated

no significant association between myocardial longitudinal strain rate and LV remodeling.26

However, those patients were enrolled prior to the systematic use of primary PCI and other

current guideline-based anti-remodeling therapies. Studies involving modern era STEMI

patients, which have demonstrated an association between LVGLS and LV remodeling, are

limited by small numbers, variable LV remodeling definitions and shorter follow-up

periods.27, 28 The current evaluation considerably expands on previous studies by relating

baseline LVGLS measurement in a large cohort of contemporary STEMI patients to accepted

echocardiographic outcomes on systematic 3- and 6-month follow-up. Patients with LVGLS

>-15% were significantly more likely to display pathological LV dilatation at both 3- and 6-

months after STEMI. This relationship remained significant even after adjusting for multiple

clinical parameters known to influence post-STEMI outcome. Importantly, repeating the

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ed LVGLS measurement in the acute phase after STEMI to the r

llow-up. A substudy of the VALIANT (valsartan in acute myo a

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analysis per quartile of GLS (supplemental file) showed a stepwise relationship between less

negative (more impaired) GLS and progressive LV dilatation, with the greatest and most

significant increase in LVEDV at both 3- and 6-month occurring in those patients in the

highest quartile of GLS (>-12.1%). The finding that LVGLS measurement prior to discharge

can identify patients at increased risk of LV dilatation is particularly relevant given it can be

quantified at rest and without need for pharmacological stressors, expensive contrast media or

exposure to ionizing radiation.

LVGLS versus WMSI in risk stratification after STEMI

Previous studies have consistently shown that WMSI evaluation is superior to LVEF for early

risk assessment after STEMI.6, 29 WMSI and LVGLS were recently shown to accurately

identify substantial infarction in non-STEMI patients prior to revascularization.30 However,

segmental motion and thus WMSI, unlike LVGLS, may be influenced by tethering of scar

tissue by adjacent viable myocardium. In the current study, we confirmed an advantage of

LVGLS over WMSI for early risk stratification after STEMI. While baseline WMSI was

independently associated with LV remodeling at 3- and 6-month follow-up, the addition of

LVGLS to a model containing WMSI provided incremental value for prediction of LVEDV

increase. Although the absolute differences in LVEDV at follow-up appear small, LVGLS

was both incremental to WMSI and significantly reclassified additional patients over and

above traditional post-STEMI risk parameters. Given these findings and the fact that LVGLS

provides a semi-automated, quantitative measure of LV systolic function its future use for

risk stratification in all STEMI patients is highly foreseeable.

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Limitations

This was a retrospective evaluation. However, it reports prospectively collected real-world

data on a large cohort of modern era STEMI patients treated optimally according to a

dedicated, guideline-based protocol.11 Patients in cardiogenic shock requiring supportive

therapy were not included in this study; therefore these findings may not apply to this

important patient group. However, these patients represent a high-risk group and additional

strategies for risk stratification are less clinically relevant. Additionally, echocardiography

was performed within 48 hours after STEMI in all patients; the dynamic nature of LV

function recovery following STEMI may lead to an underestimation of the systolic function

during this time period. However, in the final adjusted model, time from reperfusion to

baseline echocardiography did not have a significant effect on the relationship between

baseline LVGLS and follow-up LV dilatation.2, 6 2D Simpson’s biplane method to assess

LVEDV may be less accurate in the presence of foreshortening or irregular LV geometry and

is associated with a high variability.31 However, the prognostic value of LVEDV using this

method of assessment has been proven 32 and it remains the currently recommended method

to assess LV systolic function on 2D echocardiography.14 Changes in heart rate during

follow-up and their association with LV dilatation were not assessed. However, the aim of

the current study was to assess the effect of LVGLS measured in the acute phase after

STEMI on follow-up LV dilatation as compared to other baseline characteristics (including

discharge heart rate) known to influence later risk of remodeling. Additionally, changes in

medication at follow-up were not systematically recorded. However, it is known from a

systematic overview of angiotensin converter enzyme inhibition in STEMI patients that most

of the survival benefit is observed in the first week.33, 34 Intra- and interobserver variability

measurements were not performed as part of the current study protocol. However, our

laboratory performs LVGLS measurements in a standardized manner. The reproducibility

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14

measurements for GLS from our laboratory were recently reported in a similar patient cohort

to the current study population.18 Lastly, CE-MRI imaging would have been desirable to

strengthen our observations on LVGLS and its relation to infarct size and subsequent LV

remodelling. However, LVGLS provided significant incremental value to other established

parameters of infarct size – including peak troponin concentration and WMSI- for the

prediction of LV dilatation at follow-up.

Conclusion

Stratifying STEMI patients according to median value of LVGLS on baseline

echocardiography may serve as an additional marker of infarct size. Furthermore, LVGLS

prior to discharge after STEMI was an independent predictor of LV dilatation at both 3- and

6-month follow-up. This large contemporary registry study confirms the benefit of this quick,

inexpensive and widely available tool for risk stratification after STEMI.

Sources of Funding

E. Joyce is financially supported by a ESC training grant and by an Irish Cardiovascular

Educational Bursary from Merck Sharp & Dohme. G. Hoogslag received a PhD grant

provided by the Leiden University Medical Center. D. Leong is supported by the National

Health and Medical Research Council of Australia and the National Heart Foundation of

Australia. P. Debonnaire is supported by a Sadra Medical Research Grant (Boston Scientific).

Disclosures

The Department of Cardiology received grants from Biotronik, Medtronic, Boston Scientific

Corporation, St Jude Medical, Sadra Lotus and GE Healthcare. V. Delgado received

consulting fees from St. Jude Medical and Medtronic. The remaining authors have nothing to

disclose.

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2ML, Mollema SA, Delgado V, Atary JZ, Borleffs CJ, Boersma E,E, Schalij MJ, Bax JJ. Prognostic importance of strain and s rlSA, De ado V, Bertini M, Antoni ML, Boersma E, Holm n

all EE, Schalij MJ, Bax JJ. Viabili assessment with lobal eain predicts recovery of left ventricular function after acutet

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Table 1. Baseline characteristics of the patient population

Total Patient Population

(n=1041)

LVGLS >-15.0%

(n=520)

LVGLS -15.0%

(n=521)

p value*

Clinical

Age (years) 60±12 61±12 60±11 0.18

Male gender, n (%) 792 (76%) 390 (75%) 402 (77%) 0.45

Current or previous smoking, n (%)

625 (60%) 312 (60%) 313 (60%) 0.90

Diabetes, n (%) 99 (10%) 61 (12%) 38 (7%) 0.01

Family history of CAD, n (%)

455 (44%) 222 (43%) 233 (45%) 0.55

Hyperlipidemia, n (%) 187 (18%) 84 (16%) 103 (20%) 0.13

Hypertension, n (%) 328 (32%) 172 (33%) 156 (30%) 0.27

Killip class 2, n (%) 40 (4%) 23 (4%) 17 (3%) 0.32

Glucose level (mmol/L) 8.4±2.8 8.7±3.1 8.1±2.5 0.001

eGFR (ml/min/1.73m²) 98±32 97±33 99±32 0.60

LAD as culprit vessel 480 (46%) 338 (65%) 142 (27%) <0.001

Multivessel disease, n (%) 487 (47%) 259 (50%) 228 (44%) 0.04

Peak CPK (U/L) 1612 (771, 3164) 2363 (1286, 4080) 1124 (536, 2075) <0.001

Peak TnT level (ug/L) 4.3 (1.8, 8.2) 6.4 (3.1, 11) 2.9 (1.1, 5.7) <0.001

Symptom-to-balloon onset (minutes)

173 (126, 259) 181 (132, 277) 165 (120, 244) 0.06

Time from reperfusion-to-echocardiography (hours)

24 (24, 48) 24 (24, 48) 24 (24, 48) -

Discharge heart rate (bpm) 70±12 72±12 67±11 <0.001

Discharge systolic blood pressure (mmHg)

114±17 114±16 115±17 0.39

Discharge diastolic blood pressure (mmHg)

69±11 70±11 69±11 0.50

Antiplatelets ( 1) 1041 (100%) 520 (100%) 521 (100%) -

ACE inhibitor/ARB 1016 (98%) 504 (97%) 512 (98%) 0.21

101010101010103333333 (2(2(2(2(2(2(20%0%0%0%0%0%0%))))) ) )

328 (32%) 172 (33%) 156 (30%)

480 (46%) 338 (65%) 142 (27%)

32323232328888 (3(3(3(3(32%) 172 (3(3(3(3(33%) 156 (30%)

40 (((((4%4%4%%%))) )) 2223 ((4%4%4%%%) ) ) )) 177777 (((((3%3%3%3%3%) ))))

8.8888 4±4±±4±±22.2.22 8 8888 88.888 7±7±7±7±7±3.3333 11111 8.888.8.1±1±1±1±1±2.222.2 55 555

98±3±3±3±3±322222 979797979 ±3±3±3±3±333333 99±32

448080 ((4646%)%) 333388 (6(65%5%)) 141422 (2(27%7%))



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Beta-blockers 984 (95%) 491 (95%) 493 (95%) 0.99

Statins 1033 (99%) 516 (99%) 517 (99%) 0.61

Echocardiography

LVESV (ml) 55±22 61±23 48±18 <0.001

LVEDV (ml) 103±34 108±36 98±31 <0.001

LVEF (%) 47±9 44±9 51±8 <0.001

WMSI 1.4 (1.3, 1.7) 1.6 (1.4, 1.8) 1.3 (1.2, 1.5) <0.001

MR grade 2 61 (6%) 31 (6%) 30 (6%) 0.89

Moderate-severe aortic valve disease

23 (2.2%) 14 (2.7%) 9 (1.7%) 0.29

LAVI (ml/m2) 20±8 20±8 20±8 0.26

E/A 0.90 (0.73, 1.1) 0.84 (0.66, 1.1) 0.97 (0.79, 1.2) <0.001

DT (ms) 212 (167, 263) 199 (159, 246) 221 (177, 274) 0.001

E’ (cm/s) 5.4 (4.2, 6.8) 4.8 (3.5, 6.2) 6.1 (4.9, 7.4) <0.001

E/E’ ratio 12 (10, 15) 13 (10, 17) 11 (9, 14) <0.001

LVGLS (%) -15.0±4.2 -11.6±2.4 -18.4±2.5 <0.001

*p values are given for the difference in baseline characteristics between LVGLS >-15.0% and LVGLS -

15.0% groups. Continuous data are presented as mean SD or median and interquartile range.

ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; CAD, coronary artery disease; CPK,

creatinine phosphokinase; DT, decleration time; E/A, ratio of mitral inflow peak early velocity (E) to mitral

inflow peak late velocity (A); E’, mitral annular peak early velocity; E/E’, ratio of mitral inflow peak early

velocity to mitral annular peak early velocity; eGFR, estimated glomerular filtration rate; GLS, global

longitudinal strain; LAD, left anterior descending artery; LAVI, left atrial volume index; LV, left ventricular;

LVEF, left ventricular ejection fraction; LVEDV, left ventricular end diastolic volume; LVESV, left ventricular

end systolic volume; MR, mitral regurgitation; TnT, cardiac troponin T; WMSI, wall motion score index.

0.97 (0.79, 1.2)2)2)2)2)2)2)

222222221111111 (1(1(1(1(1(1(177777777777777,, 272727272727274)4)4)4)4)4)4)

5.4 .2 6. 4.8 3. 6.2 6.1 .9 7.

12 (10, 15) 13 (10, 17) 11 (9, 14)

-15.0±4.2 -11.6±2.4 -18.4±2.5

for the difference in baseline characteristics between LVGLS >-15.0% and L

5.55 44444 (4(((( .2.2.2.2.2, 6.8) 4.8 (3.33.33.5,5555 6.2) 6.1 (4.9, 7.4)

12 (10, 15)5)))5) 11333 (11000, 111117)7)7)7)7) 11 (9(9(9(9(9, 141444)

11-15.0±0±00±4.4.4 222 -111111.11 6±6±±6±2.22 444 111-118.8888 4±±±22.2 5555

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Table 2. Predictors of change in LVEDV from baseline to follow-up

Covariate Coefficient (95% confidence interval)

p value*

Age (years)

3m LVEDV

6m LVEDV

0.03 (-0.14 to 0.20)

-0.05 (-0.22 to 0.13)

0.72

Diabetes

3m LVEDV

6m LVEDV

3.8 (-2.8 to 10)

5.1 (-1.6 to 12)

0.29

Male gender

3m LVEDV

6m LVEDV

1.3 (-3.3 to 5.8)

5.4 (0.86 to 10)

0.05

LAD as culprit vessel

3m LVEDV

6m LVEDV

4.0 (0.17 to 7.9)

9.0 (5.1 to 13)

<0.001

Multivessel disease

3m LVEDV

6m LVEDV

1.9 (-2.0 to 5.8)

0.53 (-3.4 to 4.4)

0.63

Discharge heart rate (bpm)

3m LVEDV

6m LVEDV

0.02 (-0.14 to 0.18)

0.41 (0.25 to 0.57)

<0.001

Peak TnT concentration (ug/L)

3m LVEDV

6m LVEDV

1.6 (1.3 to 2.0)

1.6 (1.3 to 1.9)

<0.001

Killip class 2

3m LVEDV

6m LVEDV

-0.34 (-10 to 9.8)

5.9 (-4.6 to 16)

0.44

Time from reperfusion to echocardiography (hours)

-0.00024 (-0.0035 to 0.0030) 0.4

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3m LVEDV

6m LVEDV

0.0019 (-0.0014 to 0.0052)

Beta-blocker at discharge

3m LVEDV

6m LVEDV

-9.1 (-18 to -0.25)

-7.1 (-16 to 2.1)

0.1

ACE-I/ARB at discharge

3m LVEDV

6m LVEDV

-4.0 (-17 to 9.4)

-3.2 (-17 to 10)

0.82

WMSI

3m LVEDV

6m LVEDV

16 (9.7 to 22)

18 (12 to 25)

<0.001

MR grade 2

3m LVEDV

6m LVEDV

5.7 (-2.8 to 14)

-3.6 (-12 to 4.7)

0.11

LAVI

3m LVEDV

6m LVEDV

-0.35 (-0.59 to -0.12)

-0.43 (-0.66 to -0.19)

<0.001

LVGLS >-15.0 vs. -15.0%

3m LVEDV

6m LVEDV

6.7 (2.8 to 11)

10 (6.3 to 14)

<0.001

*p values represent the covariate-time interaction term; if significant (p<0.05), it indicates a time dependent

relationship between LVEDV and the particular covariate.

For abbreviations, see Table 1.

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Figure Legends

Figure 1. Assessment of LVGLS with speckle tracking echocardiography. (A) A patient with

acute inferior myocardial infarction. LVGLS was abnormal at -17.2% but remained below

(more negative) the cut-off threshold of -15.0%. Over the course of 3- and 6-month follow-

up, LVEDV did not increase significantly (134, 139 and 152ml respectively). (B) A patient

with acute anterior myocardial infarction. LVGLS was significantly impaired (less negative)

at -11.4%. Over the course of follow-up, LVEDV increased from 93ml at baseline to 118ml

at 3-month and 129ml at 6-month, representing a 39% increase overall.

APLAX, apical long-axis view; AVC, aortic valve closure; LV, left ventricular; LVEDV, left

ventricular end diastolic volume; 2C, 2-chamber; 4C, 4-chamber.

Figure 2. LVGLS stratified according to median value (-15.0%) and related to the change in

LVEDV over 3- and 6-month follow-up, adjusted for multiple other relevant post-STEMI

parameters. Patients with LVGLS >-15.0% (represented by the green bars) showed a

significantly higher increase in LVEDV at 3-months and 6-months compared to those with

LVGLS -15.0% (represented by the blue bars) (p<0.001). ¶ adjusted p value – see text for

details. Data is presented as mean SE.

CI, confidence interval; GLS, global longitudinal strain; LV, left ventricular; LVEDV, left

ventricular end diastolic volume; STEMI, ST-segment elevation myocardial infarction.

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Helèn Boden, Martin J. Schalij, Nina Ajmone Marsan, Jeroen J. Bax and Victoria DelgadoEmer Joyce, Georgette E. Hoogslag, Darryl P. Leong, Philippe Debonnaire, Spyridon Katsanos,

Dilatation After ST-segment Elevation Myocardial InfarctionAssociation Between Left Ventricular Global Longitudinal Strain and Adverse Left Ventricular

Print ISSN: 1941-9651. Online ISSN: 1942-0080 Copyright © 2013 American Heart Association, Inc. All rights reserved.

TX 75231is published by the American Heart Association, 7272 Greenville Avenue, Dallas,Circulation: Cardiovascular Imaging

published online November 1, 2013;Circ Cardiovasc Imaging.

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1

SUPPLEMENTAL MATERIAL

2

Supplemental Methods

Per Quartile Analysis

A per quartile analysis was performed which demonstrates similar findings to our

previous analysis in which baseline GLS was dichotomized by its median. Patients

were divided into 4 groups according to LV GLS quartile: quartile 1: LV GLS <-18%,

quartile 2: LV GLS between -18% and -15%, quartile 3: LV GLS between -14.9% and

-12.1% and quartile 4: LV GLS >-12.1%. The unadjusted association between

baseline GLS by quartile and change in left ventricular end-diastolic volume (LVEDV)

is illustrated in the figure below. A stepwise relationship between less negative GLS

(more impaired) and greater LV dilatation is illustrated (ie for each quartile worsening

in baseline LV GLS, there is progressive LV dilatation). The per quartile analysis was

repeated with adjustment for all the covariates used in the dichotomized model - age,

gender, diabetes, infarct location, multi-vessel disease, Killip class, discharge heart

rate, beta-blocker or angiotensin converting enzyme-inhibitor/angiotensin receptor

blocker use, mitral regurgitation severity, peak creatine kinase and troponin

concentrations, symptom-to-balloon time, baseline blood glucose concentration,

baseline LV end-systolic volume, LV ejection fraction, wall motion score index, E/A

ratio and deceleration time, E/E’ ratio and baseline left atrial volume index. The

results remained the same as for the analysis performed using median GLS to

dichotomize patients. The specific adjusted coefficients and associated 95%

confidence intervals per GLS quartile and p-values shown in the table below.

Analysis of the quartile-time interaction demonstrates a particularly marked

difference in LV remodeling between the highest and lowest quartiles of GLS

(quartile 4 vs. 1: 8.5 ml increase in LVEDV, 95% CI 2.7 to 14mls; p=0.004 at 3

months and 15 ml increase in LVEDV, 95% CI 8.8 to 20mls, p<0.001 at 6 months).

3

Time Baseline GLS quartile* Coefficient (95% CI)** p-value

3 months 2 -3.2 (-8.9 to 2.5) 0.3

3 0.85 (-4.9 to 6.6) 0.8

4 8.5 (2.7 to 14) 0.004

6 months 2 0.93 (-4.8 to 6.6) 0.8

3 5.3 (-0.42 to 11) 0.07

4 15 (8.8 to 20) <0.001

* the reference group is first quarter of GLS. ** adjusted by age, gender, diabetes, infarct

location, multi-vessel disease, Killip class, discharge heart rate, beta-blocker or angiotensin

converting enzyme-inhibitor/angiotensin receptor blocker use, mitral regurgitation severity,

peak creatine kinase and troponin concentrations, symptom-to-balloon time, baseline blood

glucose concentration, baseline LV end-systolic volume, LV ejection fraction, wall motion

score index, E/A ratio and deceleration time, E/E’ ratio and baseline left atrial volume index.

Supplemental Figures

4

Figure 1. Patient population

Association Between Left Ventricular Global Longitudinal...

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