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,

Elevation Myocardial Infarction−Ventricular Dilatation After ST-Segment Association Between Left Ventricular Global Longitudinal Strain and Adverse Left

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

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

doi: 10.1161/CIRCIMAGING.113.0009822014;7:74-81; originally published online November 1, 2013;Circ Cardiovasc Imaging. 

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74

Myocardial infarct size is a major determinant of subse-quent left ventricular (LV) remodeling and dysfunction,

both strong predictors of poor outcomes after ST-segment–elevation myocardial infarction (STEMI).1–3 Assessment of infarct size can be achieved by several methods, including quantification of cardiac biomarkers, 2-dimensional (2D) echocardiographic estimation of LV ejection fraction (EF) and wall motion score index (WMSI), and contrast-enhanced magnetic resonance imaging. Although measurement of cre-atinine kinase or troponin T levels is widely available, their accuracy to predict LV remodeling is modest.4,5 Alternatively, contrast-enhanced magnetic resonance imaging can accu-rately quantify the extent of myocardial scarring after myo-cardial 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 bed-side 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 remodel-ing and clinical outcome.2,6 However, several limitations exist in the quantification of these parameters by 2D echocardiog-raphy, including the assumption of symmetrical LV geometry, intraobserver and interobserver variability, and, in the case of WMSI, the requirement for expert observers.

Clinical Perspective on p 81

Novel echocardiographic imaging techniques such as speckle-tracking strain imaging provide information on myo-cardial tissue function, which is incremental to LVEF and WMSI to predict LV functional recovery and clinical out-come after STEMI.7,8 LV global longitudinal strain (GLS)

Background—Myocardial infarct size is a major determinant of left ventricular (LV) remodeling after ST-segment–elevation myocardial infarction. 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 ST-segment–elevation myocardial infarction.

Methods and Results—In the first ST-segment–elevation myocardial infarction 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 relationship between GLS groups and LV end-diastolic volume at 3 and 6 months (adjusted for clinical and echocardiographic variables) was assessed. The final study population comprised 1041 patients (60±12 years; 76% men). Median LVGLS was −15.0%. Patients with baseline LVGLS >−15.0% exhibited greater LV dilatation at 3 and 6 months compared with patients with GLS ≤−15.0% (LV end-diastolic volume 123±44 versus 106±36 mL and 121±43 versus 102±34 mL, 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. Further, net reclassification improvement index demonstrated significant incremental value of LVGLS for prediction of LV end-diastolic volume increase (0.14 [95% confidence interval, 0.00034–0.29]; P=0.04).

Conclusions—LVGLS before discharge after ST-segment–elevation myocardial infarction is independently associated with LV dilatation at follow-up. (Circ Cardiovasc Imaging. 2014;7:74-81.)

Key Words: echocardiography ◼ myocardial infarction ◼ ventricular remodeling

© 2013 American Heart Association, Inc.

Circ Cardiovasc Imaging is available at http://circimaging.ahajournals.org DOI: 10.1161/CIRCIMAGING.113.000982

Received April 11, 2013; accepted October 23, 2013.From the Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands (E.J., G.E.H., D.P.L., P.D., S.K., H.B., M.J.S., N.A.M.,

J.J.B., V.D.); and Discipline of Medicine, University of Adelaide and Flinders University, Adelaide, Australia (D.P.L.).The Data Supplement is available at http://circimaging.ahajournals.org/lookup/suppl/doi:10.1161/CIRCIMAGING.113.000982/-/DC1.Correspondence to Victoria Delgado, MD, PhD, Department of Cardiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The

Netherlands. E-mail v.delgado@lumc.nl

Association Between Left Ventricular Global Longitudinal Strain and Adverse Left Ventricular Dilatation After

ST-Segment–Elevation Myocardial InfarctionEmer Joyce, MB, BCh, BAO, MRCPI; Georgette E. Hoogslag, MSc;

Darryl P. Leong, MBBS, PhD; Philippe Debonnaire, MD; Spyridon Katsanos, MD; Helèn Boden, MD; Martin J. Schalij, MD, PhD; Nina Ajmone Marsan, MD, PhD;

Jeroen J. Bax, MD, PhD; Victoria Delgado, MD, PhD

Myocardial Infarction

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Joyce et al GLS and LV Dilatation After STEMI 75

measurement after STEMI has also demonstrated specific benefit compared with LVEF in 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 population. The aim of the current evaluation was to investi-gate whether LVGLS measurement before discharge predicts LV dilatation at 3 and 6 months after infarction in a large con-temporary STEMI population.

MethodsPatient PopulationPatients admitted with a first STEMI treated with primary percutane-ous coronary intervention 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 percutaneous coronary intervention, and standardized outpatient follow-up. Baseline 2D echocardiog-raphy 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. Two-dimensional 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 hospitalization or who were in cardiogenic shock requiring ino-tropic or mechanical circulatory support or in atrial fibrillation at time of baseline echocardiography were excluded. Finally, patients with reinfarction before 6-month echocardiography were also excluded.

Clinical data were prospectively collected in the departmental Cardiology Information System (EPD-Vision, Leiden University Medical Center) and retrospectively analyzed. For this retrospective analysis of clinically acquired data, the institutional review board waived the need for patients’ written informed consent.

Two-Dimensional Transthoracic EchocardiographyPatients were imaged in the left lateral decubitus position using a com-mercially 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 soft-ware (GE Healthcare). LV end-systolic volume, LVEDV, and LVEF were quantified at baseline and at 3- and 6-month follow-up using the Simpson biplane technique.14 The intraobserver and interobserver agreement for assessment of LVEDV at our laboratory has been previ-ously 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=hy-pokinesis, 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 was graded according to cur-rent recommendations.16 Diastolic function was assessed according to standard recommendations.17 Left atrial volume was evaluated with the biplane Simpson technique and indexed to body surface area.14

GLS AnalysisLVGLS 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 of >40 frames per second to ensure reliable analysis by the software. The end-systolic frame was defined in the apical long-axis view by marking the closure of the aortic valve. After 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 discard-ed. LVGLS was provided by the software as the average value of the peak systolic longitudinal strain of the 3 apical views, using a 17-seg-ment model, in a bull’s-eye plot (Figure 1). As previously reported, the intraobserver and interobserver variability for the measurement of LVGLS in our institution was 0.1±2.2% and 0.2±0.8%, respectively.18

Statistical AnalysisContinuous, normally distributed variables are presented as mean and standard deviation or standard error, as appropriate. Non-normally distributed data are presented as median and interquartile range. Categorical variables are presented as frequencies and per-centages. The total population was divided into 2 groups based on the median value of LVGLS. Continuous variables were compared between the 2 groups using the Student t test, Mann–Whitney U test, or χ2 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 months) 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 model-ing analysis structure. To determine whether baseline LVGLS was associated with subsequent change in LVEDV, it was modeled in an interaction term with time. If this group–time interaction term was significant, it indicated a time-dependent relationship between base-line GLS and LVEDV. Post hoc testing was then performed to deter-mine the time points at which LVEDV differed between the LVGLS groups. Other important and potentially confounding baseline clini-cal and echocardiographic predictors known to influence outcome and 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.

In addition, to evaluate the incremental value of LVGLS com-pared with clinical and conventional echocardiographic variables in predicting LV dilatation after STEMI, likelihood ratio test and net reclassification improvement index were performed.19 Net reclassi-fication improvement was used to evaluate the incremental value of baseline LVGLS in reclassifying the risk of individuals developing ≥20% increase in LVEDV 6-months after STEMI.20 To assess robust-ness of our initial model, sensitivity analysis was performed, exclud-ing those patients who had died and those who did not have either 3- or 6-month or both echocardiographic data sets available for the initial analysis.

All statistical tests were 2-sided, and a value of P <0.05 was con-sidered statistically significant. Statistical analysis was performed using STATA version 11 (STATA Corp; College Station, TX). The authors had full access to the data and take responsibility for its integ-rity. All authors have read and agreed to the article as written.

ResultsBaseline CharacteristicsOf the 1245 patients initially evaluated, 102 (8%) were excluded because of previous myocardial infarction. Twenty-two (2%) patients died during index hospitalization. An additional 30 patients were excluded because of cardiogenic shock (n=10; 1%) or atrial fibrillation at the time of base-line echocardiography (n=20; 2%). Of the remaining 1091 patients, baseline LVGLS measurement was not possible because of inadequate image quality and too low frame rate in 23 patients (2%). Reinfarction before 6 months had sub-sequently occurred in 2.5% (n=27) of these patients, and after their exclusion, the final study population comprised 1041 patients (Figure I in the Data Supplement). Table 1

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76 Circ Cardiovasc Imaging January 2014

summarizes the baseline characteristics of the patient popula-tion (mean age, 60±12 years; 76% men).

Baseline LVGLSMedian LVGLS was −15.0% (interquartile range, −12.1% to −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 mellitus, the left anterior descending artery as the culprit vessel, multivessel disease, and higher cardiac biomarker concentrations compared with patients with LVGLS ≤−15.0%. On echocardiography, patients with LVGLS >−15.0% had significantly larger LV volumes and WMSI and lower LVEF compared with their counterparts. Regarding diastolic parameters, E/E′ ratio was significantly higher, and E/A ratio, deceleration time, and E′ were signifi-cantly lower in patients with LVGLS >−15.0%. Presence of grade ≥2 mitral regurgitation or left atrial volume index did not differ significantly between the 2 groups.

Follow-UpAcross the total patient population, LVEDV increased sig-nificantly between baseline and 3- and 6-month follow-up (from 103±34 to 115±41 and to 112±40 mL, respectively; P<0.001), whereas LV end-systolic volume did not change significantly overall (from 55±22 to 57±29 and to 54±29 mL, respectively; P=0.21). In addition, the number of patients showing grade ≥2 mitral regurgitation over length of follow-up also increased significantly (from 6.0% to 7.9% and to 7.7%, respectively; P=0.006).

Predictors of Change in LVEDV From Baseline to Follow-UpTable 2 details the results of linear mixed model analyses. Higher WMSI was significantly associated with LV remodeling, as were male sex, left anterior descending artery infarct com-pared with non–left anterior descending artery, higher discharge heart rate and peak troponin concentration, and lower LAVI at baseline. Regarding LVGLS, although baseline LVEDV was

Figure 1. Assessment of left ventricular (LV) global longitudinal strain (GLS) with speckle-tracking echocardiography. A, A patient with acute inferior myocardial infarction. LVGLS was abnormal at −17.2% but remained below (more negative) the cutoff threshold of −15.0%. During the course of 3- and 6-month follow-up, LV end-diastolic volume (EDV) did not increase significantly (134, 139, and 152 mL, respec-tively). B, A patient with acute anterior myocardial infarction. LVGLS was signifi-cantly impaired (less negative) at −11.4%. During the course of follow-up, LVEDV increased from 93 mL at baseline to 118 mL at 3 months and 129 mL at 6 months, representing a 39% increase overall. 2C indicates 2-chamber; 4C, 4-chamber; ANT, anterior; ANT_SEPT, anteroseptal; APLAX, apical long-axis view; and AVC, aortic valve closure INF, inferior; LAT, lateral; POST, posterior; and SEPT, septal.

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Joyce et al GLS and LV Dilatation After STEMI 77

higher in patients with baseline LVGLS >−15.0% compared with ≤−15.0%, this difference was nonsignificant after adjust-ment for other relevant baseline clinical characteristics (P=0.1). In addition, patients with baseline LVGLS >−15.0% exhib-ited greater LV dilatation at 3 and 6 months (LVEDV 124±44 versus 106±36 mL; P<0.001 and 121±43 versus 102±34 mL; P<0.001, respectively; group–time interaction term P<0.001)

compared with their counterparts. This association between LVGLS and increased LV dilatation retained the same statisti-cal 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

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, y 60±12 61±12 60±11 0.18

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

Current or previous smoking, n (%) 625 (60) 312 (60) 313 (60) 0.90

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

Family history of coronary artery disease, 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

Estimated glomerular filtration rate, mL/min per 1.73 m2

98±32 97±33 99±32 0.60

Left anterior descending coronary artery as culprit vessel

480 (46%) 338 (65%) 142 (27%) <0.001

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

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

Peak troponin T level, μg/L 4.3 (1.8–8.2) 6.4 (3.1–11) 2.9 (1.1–5.7) <0.001

Symptom-to-balloon onset, min 173 (126–259) 181 (132–277) 165 (120–244) 0.06

Time from reperfusion to echocardiography, h 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, mm Hg 114±17 114±16 115±17 0.39

Discharge diastolic blood pressure, mm Hg 69±11 70±11 69±11 0.50

Antiplatelets (≥1) 1041 (100%) 520 (100%) 521 (100%) …

Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker

1016 (98%) 504 (97%) 512 (98%) 0.21

β-Blockers 984 (95%) 491 (95%) 493 (95%) 0.99

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

Echocardiography

LV end-systolic volume, 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

Mitral regurgitation 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

Left atrial volume index, 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

Deceleration time, 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

Continuous data are presented as mean±SD or median and interquartile range. GLS indicates global longitudinal strain; LV, left ventricular; LVEF, left ventricular ejection fraction; LVEDV, left ventricular end-diastolic volume; and WMSI, wall motion score index.

*P values are given for the difference in baseline characteristics between LVGLS >−15.0% and LVGLS ≤−15.0% groups.

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78 Circ Cardiovasc Imaging January 2014

follow-up LV dilatation to a model containing all other signifi-cant clinical and echocardiographic predictors of LV remod-eling (male sex, left anterior descending artery infarct, peak troponin concentration, discharge heart rate, left atrial volume index, and WMSI; log-likelihood difference of 17.8, P<0.001 for measuring LVGLS in addition to clinical predictors, left atrial volume index and WMSI compared with clinical predic-tors, left atrial volume index and WMSI alone). In addition, net reclassification improvement index demonstrated signifi-cant incremental value of LVGLS to predict ≥20% increase in LVEDV over and above multiple covariates, including age, sex, diabetes mellitus, infarct territory, multivessel disease, Killip class, peak creatinine kinase and troponin concentra-tions, glucose concentration, symptom-to-balloon time, mitral regurgitation severity, discharge heart rate, and neurohormonal therapy prescription at discharge (net reclassification improve-ment, 0.14 [95% confidence interval, 0.00034–0.29]; P=0.04).

Finally, the analysis was performed after excluding patients who did not have both echocardiographic data sets available for the initial analysis (n=144). In the remaining large sub-group (n=897), the adjusted group–time interaction term P value for this sensitivity analysis remained <0.001.

DiscussionThe 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 during both 3- and 6-month follow-up. In addition, 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 SizeSpeckle-tracking–derived LVGLS is a novel parameter of LV function, which more closely reflects intrinsic myocar-dial function than traditional parameters by evaluating the active component of deformation.21 Further, speckle-tracking–derived LVGLS is independent of geometric assumptions and insonation angle and has relatively low intraobserver and interobserver variability.22 Because of these inherent

Table 2. Predictors of Change in LVEDV From Baseline to Follow-Up

CovariateCoefficient

(95% Confidence Interval) P Value*

Age, y 0.72

3-mo LVEDV 0.03 (−0.14 to 0.20)

6-mo LVEDV −0.05 (−0.22 to 0.13)

Diabetes mellitus 0.29

3-mo LVEDV 3.8 (−2.8 to 10)

6-mo LVEDV 5.1 (−1.6 to 12)

Male sex 0.05

3-mo LVEDV 1.3 (−3.3 to 5.8)

6-mo LVEDV 5.4 (0.86 to 10)

Left anterior descending coronary artery as culprit vessel

<0.001

3-mo LVEDV 4.0 (0.17 to 7.9)

6-mo LVEDV 9.0 (5.1 to 13)

Multivessel disease 0.63

3-mo LVEDV 1.9 (−2.0 to 5.8)

6-mo LVEDV 0.53 (−3.4 to 4.4)

Discharge heart rate, bpm

<0.001

3-mo LVEDV 0.02 (−0.14 to 0.18)

6-mo LVEDV 0.41 (0.25 to 0.57)

Peak troponin T concentration, μg/L

<0.001

3-mo LVEDV 1.6 (1.3 to 2.0)

6-mo LVEDV 1.6 (1.3 to 1.9)

Killip class ≥2 0.44

3-mo LVEDV −0.34 (−10 to 9.8)

6-mo LVEDV 5.9 (−4.6 to 16)

Time from reperfusion to echocardiography, h

0.4

3-mo LVEDV −0.00024 (−0.0035 to 0.0030)

6-mo LVEDV 0.0019 (−0.0014 to 0.0052)

β-Blocker at discharge 0.1

3-mo LVEDV −9.1 (−18 to −0.25)

6-mo LVEDV −7.1 (−16 to 2.1)

Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker at discharge

0.82

3-mo LVEDV −4.0 (−17 to 9.4)

6-mo LVEDV −3.2 (−17 to 10)

WMSI <0.001

3-mo LVEDV 16 (9.7 to 22)

6-mo LVEDV 18 (12 to 25)

Mitral regurgitation grade ≥2

0.11

3-mo LVEDV 5.7 (−2.8 to 14)

6-mo LVEDV −3.6 (−12 to 4.7)

(Continued )

Left atrial volume index <0.001

3-mo LVEDV −0.35 (−0.59 to −0.12)

6-mo LVEDV −0.43 (−0.66 to −0.19)

LVGLS >−15.0% vs ≤−15.0% <0.001

3-mo LVEDV 6.7 (2.8 to 11)

6-mo LVEDV 10 (6.3 to 14)

GLS indicates global longitudinal strain; LV, left ventricular; LVEDV, left ventricular end-diastolic volume; and WMSI, wall motion score index.

*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.

Table 2. Continued

CovariateCoefficient

(95% Confidence Interval) P Value*

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Joyce et al GLS and LV Dilatation After STEMI 79

advantages compared with other echocardiographic modali-ties, several recent studies have investigated the role of LVGLS measurement as a marker of infarct size, whether measured in the acute phase after revascularization9,10,23 or at follow-up.24,25 A cutoff for LVGLS of −15% measured after reperfu-sion served as a more precise predictor of large infarction than LVEF in 39 thrombolysis-treated patients with STEMI.9 In a larger group of primary percutaneous coronary intervention-treated patients, LVGLS measured at day 1 was also superior to LVEF in predicting 30-day infarct size.23 In our large popu-lation of contemporary STEMI patients treated with primary percutaneous coronary intervention, a postrevascularization LVGLS value >−15.0% was significantly associated with clini-cal characteristics traditionally indicative of larger infarct size (diabetes mellitus, multivessel disease, and higher biomarker levels). In addition, these patients had significantly more impaired global and regional systolic and diastolic function parameters (including LVEF, WMSI, and E′) compared with the group of patients with more preserved myocardial shorten-ing (LVGLS ≤−15.0%).

LVGLS and LV RemodelingDespite the demonstrated role of LVGLS in accurately identi-fying the extent of global myocardial injury and dysfunction after infarction, few studies in the contemporary era have spe-cifically related LVGLS measurement in the acute phase after STEMI to the risk of LV remodeling at follow-up. A substudy of the Valsartan in Acute Myocardial Infarction Trial (VAL-IANT) study, including 603 post-STEMI patients with LV dysfunction, demonstrated no significant association between myocardial longitudinal strain rate and LV remodeling.26 How-ever, those patients were enrolled before the systematic use of primary percutaneous coronary intervention and other current guideline-based antiremodeling therapies. Studies involving modern era patients with STEMI, 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 consider-ably expands on previous studies by relating baseline LVGLS measurement in a large cohort of contemporary STEMI patients to accepted echocardiographic outcomes on system-atic 3- and 6-month follow-up. Patients with LVGLS >−15% were significantly more likely to display pathological LV dila-tation 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. Impor-tantly, repeating the analysis per quartile of GLS (Data Supple-ment) 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 months occurring in those patients in the highest quartile of GLS (>−12.1%). The finding that LVGLS measurement before discharge can identify patients at increased risk of LV dilata-tion is particularly relevant, given that 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 STEMIPrevious 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 before revascular-ization.30 However, segmental motion, and thus WMSI, unlike LVGLS, may be influenced by tethering of scar tissue by adja-cent viable myocardium. In the current study, we confirmed an advantage of LVGLS compared with WMSI for early risk stratification after STEMI. Although baseline WMSI was inde-pendently 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 seem 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 semiautomated, quantitative measure of LV systolic function, its future use for risk stratification in all patients with STEMI is highly foreseeable.

LimitationsThis was a retrospective evaluation. However, it reports prospec-tively collected real-world data on a large cohort of modern-era patients with STEMI treated optimally according to a dedi-cated, 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 rel-evant. In addition, echocardiography was performed within 48 hours after STEMI in all patients; the dynamic nature of LV function recovery after STEMI may lead to an underestima-tion of the systolic function during this time period. However, in the final adjusted model, time from reperfusion to base-line echocardiography did not have a significant effect on the

Figure 2. Left ventricular (LV) global longitudinal strain (GLS) stratified according to median value (−15.0%) and related to the change in LV end-diastolic volume (EDV) during 3- and 6-month follow-up, adjusted for multiple other relevant post-STEMI param-eters. Patients with LVGLS >−15.0% (represented by the green bars) showed a significantly higher increase in LVEDV at 3 and 6 months compared with those with LVGLS ≤−15.0% (represented by blue bars; P<0.001). ¶Adjusted P value). Data are presented as mean±standard error. CI indicates confidence interval; and STEMI, ST-segment–elevation myocardial infarction.

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80 Circ Cardiovasc Imaging January 2014

relationship between baseline LVGLS and follow-up LV dila-tation.2,6 Two-dimensional Simpson biplane method to assess LVEDV may be less accurate in the presence of foreshortening or irregular LV geometry and is associated with a high vari-ability.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 compared with other baseline characteristics (including discharge heart rate) known to influence later risk of remodeling. In addition, changes in medication at follow-up were not systematically recorded. However, it is known from a systematic overview of angiotensin-converting enzyme inhibi-tion in patients with STEMI that most of the survival benefit is observed in the first week.33,34 Intraobserver and interobserver variability measurements were not performed as part of the cur-rent study protocol. However, our laboratory performs LVGLS measurements in a standardized manner. The reproducibil-ity measurements for GLS from our laboratory were recently reported in a similar patient cohort to the current study popu-lation.18 Finally, contrast-enhanced magnetic resonance imag-ing would have been desirable to strengthen our observations on LVGLS and its relation to infarct size and subsequent LV remodeling. 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.

ConclusionsStratifying patients with STEMI according to median value of LVGLS on baseline echocardiography may serve as an addi-tional marker of infarct size. Further, LVGLS before 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 FundingE. Joyce is financially supported by an ESC training grant and an Irish Cardiovascular Educational Bursary from Merck Sharp & Dohme. G. Hoogslag received a PhD grant provided by the Leiden University Medical Center. Dr Leong is supported by the National Health and Medical Research Council of Australia and the National Heart Foundation of Australia. Dr Debonnaire is supported by a Sadra Medical Research grant (Boston Scientific).

DisclosuresThe Department of Cardiology received grants from Biotronik, Medtronic, Boston Scientific Corporation, St Jude Medical, Sadra Lotus, and GE Healthcare. Dr Delgado received consulting fees from St. Jude Medical and Medtronic. The other authors report no conflicts.

References 1. Pfeffer MA, Braunwald E. Ventricular remodeling after myocardial infarc-

tion. Experimental observations and clinical implications. Circulation. 1990;81:1161–1172.

2. St John Sutton M, Pfeffer MA, Plappert T, Rouleau JL, Moyé LA, Dagenais GR, Lamas GA, Klein M, Sussex B, Goldman S. Quantitative

two-dimensional echocardiographic measurements are major predictors of adverse cardiovascular events after acute myocardial infarction. The protective effects of captopril. Circulation. 1994;89:68–75.

3. White HD, Norris RM, Brown MA, Brandt PW, Whitlock RM, Wild CJ. Left ventricular end-systolic volume as the major determinant of survival after recovery from myocardial infarction. Circulation. 1987;76:44–51.

4. Byrne RA, Ndrepepa G, Braun S, Tiroch K, Mehilli J, Schulz S, Schömig A, Kastrati A. Peak cardiac troponin-T level, scintigraphic myocardial infarct size and one-year prognosis in patients undergoing primary per-cutaneous coronary intervention for acute myocardial infarction. Am J Cardiol. 2010;106:1212–1217.

5. Chia S, Senatore F, Raffel OC, Lee H, Wackers FJ, Jang IK. Utility of cardiac biomarkers in predicting infarct size, left ventricular function, and clinical outcome after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. JACC Cardiovasc Interv. 2008;1:415–423.

6. Møller JE, Hillis GS, Oh JK, Reeder GS, Gersh BJ, Pellikka PA. Wall motion score index and ejection fraction for risk stratification after acute myocardial infarction. Am Heart J. 2006;151:419–425.

7. Antoni ML, Mollema SA, Delgado V, Atary JZ, Borleffs CJ, Boersma E, Holman ER, van der Wall EE, Schalij MJ, Bax JJ. Prognostic importance of strain and strain rate after acute myocardial infarction. Eur Heart J. 2010;31:1640–1647.

8. Mollema SA, Delgado V, Bertini M, Antoni ML, Boersma E, Holman ER, Stokkel MP, van der Wall EE, Schalij MJ, Bax JJ. Viability assessment with global left ventricular longitudinal strain predicts recovery of left ventricular function after acute myocardial infarction. Circ Cardiovasc Imaging. 2010;3:15–23.

9. Sjøli B, Ørn S, Grenne B, Vartdal T, Smiseth OA, Edvardsen T, Brunvand H. Comparison of left ventricular ejection fraction and left ventricular global strain as determinants of infarct size in patients with acute myocar-dial infarction. J Am Soc Echocardiogr. 2009;22:1232–1238.

10. Vartdal T, Brunvand H, Pettersen E, Smith HJ, Lyseggen E, Helle-Valle T, Skulstad H, Ihlen H, Edvardsen T. Early prediction of infarct size by strain Doppler echocardiography after coronary reperfusion. J Am Coll Cardiol. 2007;49:1715–1721.

11. Antoni ML, Boden H, Delgado V, Boersma E, Fox K, Schalij MJ, Bax JJ. Relationship between discharge heart rate and mortality in patients after acute myocardial infarction treated with primary percutaneous coronary intervention. Eur Heart J. 2012;33:96–102.

12. O’Gara PT, Kushner FG, Ascheim DD, Casey DE Jr, Chung MK, de Lemos JA, Ettinger SM, Fang JC, Fesmire FM, Franklin BA, Granger CB, Krumholz HM, Linderbaum JA, Morrow DA, Newby LK, Ornato JP, Ou N, Radford MJ, Tamis-Holland JE, Tommaso CL, Tracy CM, Woo YJ, Zhao DX, Anderson JL, Jacobs AK, Halperin JL, Albert NM, Brindis RG, Creager MA, DeMets D, Guyton RA, Hochman JS, Kovacs RJ, Kushner FG, Ohman EM, Stevenson WG, Yancy CW; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;127:e362–e425.

13. Steg PG, James SK, Atar D, Badano LP, Blomstrom-Lundqvist C, Borger MA, Di MC, Dickstein K, Ducrocq G, Fernandez-Aviles F, Gershlick AH, Giannuzzi P, Halvorsen S, Huber K, Juni P, Kastrati A, Knuuti J, Lenzen MJ, Mahaffey KW, Valgimigli M, van ‘t HA, Widimsky P, Zahger D. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J. 2012;33:2569–619.

14. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise JS, Solomon SD, Spencer KT, Sutton MS, Stewart WJ. Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr. 2005;18:1440–63.

15. Mollema SA, Liem SS, Suffoletto MS, Bleeker GB, van der Hoeven BL, van de Veire NR, Boersma E, Holman ER, van der Wall EE, Schalij MJ, Gorcsan J III, Bax JJ. Left ventricular dyssynchrony acutely after myo-cardial infarction predicts left ventricular remodeling. J Am Coll Cardiol. 2007;50:1532–1540.

16. Lancellotti P, Moura L, Pierard LA, Agricola E, Popescu BA, Tribouilloy C, Hagendorff A, Monin JL, Badano L, Zamorano JL; European Association of Echocardiography. European Association of Echocardiography recom-mendations for the assessment of valvular regurgitation. Part 2: mitral

at Rijksuniversiteit Leiden on June 4, 2014http://circimaging.ahajournals.org/Downloaded from

Joyce et al GLS and LV Dilatation After STEMI 81

and tricuspid regurgitation (native valve disease). Eur J Echocardiogr. 2010;11:307–332.

17. Nagueh SF, Appleton CP, Gillebert TC, Marino PN, Oh JK, Smiseth OA, Waggoner AD, Flachskampf FA, Pellikka PA, Evangelista A. Recommendations for the evaluation of left ventricular diastolic function by echocardiography. J Am Soc Echocardiogr. 2009;22:107–133.

18. Antoni ML, Mollema SA, Atary JZ, Borleffs CJ, Boersma E, van de Veire NR, Holman ER, van der Wall EE, Schalij MJ, Bax JJ. Time course of global left ventricular strain after acute myocardial infarction. Eur Heart J. 2010;31:2006–2013.

19. Pencina MJ, D’Agostino RB Sr, D’Agostino RB Jr, Vasan RS. Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med. 2008;27:157–172; discussion 207.

20. Bolognese L, Neskovic AN, Parodi G, Cerisano G, Buonamici P, Santoro GM, Antoniucci D. Left ventricular remodeling after primary coronary angioplasty: patterns of left ventricular dilation and long-term prognostic implications. Circulation. 2002;106:2351–2357.

21. Behar V, Adam D, Lysyansky P, Friedman Z. The combined effect of non-linear filtration and window size on the accuracy of tissue displacement estimation using detected echo signals. Ultrasonics. 2004;41:743–753.

22. Perk G, Tunick PA, Kronzon I. Non-Doppler two-dimensional strain im-aging by echocardiography–from technical considerations to clinical ap-plications. J Am Soc Echocardiogr. 2007;20:234–243.

23. Munk K, Andersen NH, Nielsen SS, Bibby BM, Bøtker HE, Nielsen TT, Poulsen SH. Global longitudinal strain by speckle tracking for infarct size estimation. Eur J Echocardiogr. 2011;12:156–165.

24. Gjesdal O, Hopp E, Vartdal T, Lunde K, Helle-Valle T, Aakhus S, Smith HJ, Ihlen H, Edvardsen T. Global longitudinal strain measured by two-dimensional speckle tracking echocardiography is closely related to myo-cardial infarct size in chronic ischaemic heart disease. Clin Sci (Lond). 2007;113:287–296.

25. Gjesdal O, Helle-Valle T, Hopp E, Lunde K, Vartdal T, Aakhus S, Smith HJ, Ihlen H, Edvardsen T. Noninvasive separation of large, medium, and small myocardial infarcts in survivors of reperfused ST-elevation myocardial in-farction: a comprehensive tissue Doppler and speckle-tracking echocardiog-raphy study. Circ Cardiovasc Imaging. 2008;1:189–196, 2 p following 196.

26. Hung CL, Verma A, Uno H, Shin SH, Bourgoun M, Hassanein AH, McMurray JJ, Velazquez EJ, Kober L, Pfeffer MA, Solomon SD;

VALIANT investigators. Longitudinal and circumferential strain rate, left ventricular remodeling, and prognosis after myocardial infarction. J Am Coll Cardiol. 2010;56:1812–1822.

27. Bochenek T, Wita K, Tabor Z, Grabka M, Krzych Ł, Wróbel W, Berger-Kucza A, Elżbieciak M, Doruchowska A, Gluza MT. Value of speckle-tracking echocardiography for prediction of left ventricular remodeling in patients with ST-elevation myocardial infarction treated by primary percutaneous intervention. J Am Soc Echocardiogr. 2011;24:1342–1348.

28. Zaliaduonyte-Peksiene D, Vaskelyte JJ, Mizariene V, Jurkevicius R, Zaliunas R. Does longitudinal strain predict left ventricular remodeling after myocardial infarction? Echocardiography. 2012;29:419–427.

29. Thune JJ, Køber L, Pfeffer MA, Skali H, Anavekar NS, Bourgoun M, Ghali JK, Arnold JM, Velazquez EJ, Solomon SD. Comparison of regional versus global assessment of left ventricular function in patients with left ventricular dysfunction, heart failure, or both after myocardial infarction: the valsartan in acute myocardial infarction echocardiographic study. J Am Soc Echocardiogr. 2006;19:1462–1465.

30. Eek C, Grenne B, Brunvand H, Aakhus S, Endresen K, Hol PK, Smith HJ, Smiseth OA, Edvardsen T, Skulstad H. Strain echocardiography and wall mo-tion score index predicts final infarct size in patients with non-ST-segment-elevation myocardial infarction. Circ Cardiovasc Imaging. 2010;3:187–194.

31. Himelman RB, Cassidy MM, Landzberg JS, Schiller NB. Reproducibility of quantitative two-dimensional echocardiography. Am Heart J. 1988; 115:425–431.

32. Solomon SD, Skali H, Anavekar NS, Bourgoun M, Barvik S, Ghali JK, Warnica JW, Khrakovskaya M, Arnold JM, Schwartz Y, Velazquez EJ, Califf RM, McMurray JV, Pfeffer MA. Changes in ventricular size and function in patients treated with valsartan, captopril, or both after myocar-dial infarction. Circulation. 2005;111:3411–3419.

33. ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group. ISIS-4: a randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58,050 patients with suspected acute myocardial infarction. Lancet. 1995;345:669–85.

34. Pfeffer MA, Greaves SC, Arnold JM, Glynn RJ, LaMotte FS, Lee RT, Menapace FJ Jr, Rapaport E, Ridker PM, Rouleau JL, Solomon SD, Hennekens CH. Early versus delayed angiotensin-converting enzyme inhibition therapy in acute myocardial infarction. The healing and early afterload reducing therapy trial. Circulation. 1997;95:2643–2651.

CLINICAL PERSPECTIVEIn this study, left ventricular (LV) global longitudinal strain (GLS) derived from 2-dimensional speckle-tracking echo-cardiography was measured in 1041 contemporary treated ST-segment–elevation myocardial infarction (STEMI) patients before discharge and related to the occurrence of LV dilatation at systematic 3- and 6-month follow-up. In the acute phase after STEMI, stratification of patients according to median LVGLS (−15.0%) delineated 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 during both 3- and 6-month follow-up compared with patients with LVGLS ≤−15.0%. Importantly, LVGLS also provided incremental value to traditional parameters for assessment of infarct size, including wall motion score index and peak troponin level, for prediction of LV enlargement after STEMI. Although the absolute differences in LV end-diastolic volume at follow-up seem small, LVGLS was both incremental to WMSI and significantly reclassified additional patients over and above known clinical and echocardiographic post-STEMI risk parameters. The finding that LVGLS measure-ment before discharge can identify patients at increased risk of LV dilatation is particularly relevant, given that it provides a semiautomated, quantitative measure of LV systolic function quantifiable at rest and without need for expert observers, pharmacological stressors, expensive contrast media, or exposure to ionizing radiation. This quick, inexpensive, and widely available tool may thus become a valuable tool for risk stratification after STEMI.

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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

5