The Relationship between Time from Myocardial

Infarction, Left Ventricular Dyssynchrony, and the Risk

for Ventricular Arrhythmia: Speckle-Tracking
Echocardiographic Analysis
Darryl P. Leong, MBBS, MPH, PhD, Georgette E. Hoogslag, MD, Sebastiaan R. D. Piers, MD, Ulas H€ oke, MD,
Joep Thijssen, MD, Nina Ajmone Marsan, MD, PhD, Martin J. Schalij, MD, PhD, Katja Zeppenfeld, MD, PhD,
Jeroen J. Bax, MD, PhD, and Victoria Delgado, MD, PhD, Adelaide, Australia; Hamilton, Ontario, Canada; and
Leiden, The Netherlands

Background: Differences in arrhythmogenic substrate may explain the variable efficacy of implantable
cardioverter-defibrillators (ICDs) in primary sudden cardiac death prevention over time after myocardial infarc-
tion (MI). Speckle-tracking echocardiography allows the assessment left ventricular (LV) dyssynchrony, which
may reflect the electromechanical heterogeneity of myocardial tissue. The aim of the present study was to
evaluate the relationship among LV dyssynchrony, age of MI, and their association with the risk for ventricular
tachycardia (VT) after MI.

Methods: A total of 206 patients (median age, 67 years; 87% men) with prior MIs (median MI age, 6.2 years;
interquartile range, 0.66–15 years) who underwent programmed electrical stimulation, speckle-tracking echo-
cardiography, and ICD implantation were retrospectively evaluated. LV dyssynchrony was defined as the stan-
dard deviation of time to peak longitudinal systolic strain values using speckle-tracking strain
echocardiography. LV scar burden was evaluated by the percentage of segments exhibiting scar (defined
as an absolute longitudinal strain of magnitude < 4.5%). Patients were followed up for the occurrence of first
monomorphic VT requiring ICD therapy (antitachycardia pacing or shock) for a median of 24 months.

Results: In total, 75 individuals experienced the primary end point of monomorphic VT. LV dyssynchrony was
independently associated with the occurrence of VT at follow-up (hazard ratio per 10-msec increase, 1.12;
95% confidence interval, 1.07–1.18; P < .001), together with nonrevascularization of the infarct-related artery
and VT inducibility. Patients with older (>180 months) MIs had a higher likelihood of VT inducibility (88% vs
63%, P = .003) and greater scar burden (14.7 6 15.8% vs 10.7 6 11.4%, P = .03) compared with patients
with recent (<8 months) MIs.

Conclusions: LV dyssynchrony is independently associated with the occurrence of VT after MI. (J Am Soc
Echocardiogr 2015;-:---.)

Keywords: Myocardial infarction, Ventricular tachycardia, Scar, Strain, Echocardiography

Sudden cardiac death (SCD), which is attributed mostly to ventricular (ICD) in patients with left ventricular (LV) ejection fractions (LVEFs)
tachycardia (VT), accounts for approximately 50% of all deaths in pa- # 35% within 40 days after myocardial infarction (MI) has not
tients with coronary heart disease.1 The interaction between the ar- demonstrated a survival advantage,2 despite the known survival
rhythmogenic substrate and several factors that influence electrical benefit of ICD use in other patients with LVEFs # 35%.3
stability (e.g., autonomic tone, myocardial ischemia) is crucial in the Moreover, a progressive increase in mortality risk late after MI has
genesis of VT. The use of an implantable cardioverter-defibrillator been described among ICD recipients.4 Differences in

From the Disciplines of Medicine, Flinders University and the University of Medical, Lantheus Medical Imaging, and GE Healthcare. Dr Delgado has received
Adelaide, Adelaide, Australia (D.P.L.); the Population Health Research Institute, consulting fees from St. Jude Medical and Medtronic and speaking fees from Ab-
McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada bott Vascular. The remaining authors have no conflicts of interest to disclose.
(D.P.L.); and the Department of Cardiology, Leiden University Medical Center, Reprint requests: Victoria Delgado, MD, PhD, Leiden University Medical Center,
Leiden, The Netherlands (G.E.H., S.R.D.P., U.H., J.T., N.A.M., M.J.S., K.Z., Department of Cardiology, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
J.J.B., V.D.). (E-mail: [email protected]).
Dr Leong is supported by the National Health and Medical Research Council of 0894-7317/$36.00
Australia, the National Heart Foundation of Australia, and the E. J. Moran Campbell
Copyright 2015 by the American Society of Echocardiography.
Career Award (McMaster University). The Department of Cardiology has received
http://dx.doi.org/10.1016/j.echo.2014.12.012
research grants from Biotronik, Medtronic, Boston Scientific Corporation, St. Jude
1
2 Leong et al Journal of the American Society of Echocardiography
- 2015

Abbreviations
arrhythmogenic substrate early Ultrasound AS). Left atrial volume and LV end-systolic and end-
and late after MI may explain diastolic volumes were measured from the apical two- and four-
CI = Confidence interval those findings and underscore chamber views and indexed to body surface area. LVEF was
CRT-D = Biventricular the importance of substrate char- calculated using the biplane Simpson’s technique.9 Mitral regurgita-
implantable cardioverter- acterization to determine the tion severity was graded as none/mild or moderate/severe by incor-
defibrillator mechanisms of SCD. A key porating a number of echocardiographic indicators, including
feature of the myocardial regurgitant jet vena contracta width, proximal flow convergence,
GLS = Global longitudinal
substrate after MI is slow con- effective regurgitant orifice area measured with the proximal isoveloc-
strain
duction through inhomoge- ity surface area method, color jet area, continuous-wave Doppler
ICD = Implantable neous scar tissue.5,6 Collagen spectral profile intensity, E-wave velocity, and pulmonary venous
cardioverter-defibrillator deposition in particular within flow reversal.10
IQR = Interquartile range the infarct border zone may
occur over years after the index
LV = Left ventricular Strain Analysis
MI, resulting in progressive
separation of viable myocardial Evaluation of LV myocardial deformation was performed with
LVEF = Left ventricular
fibers and thus more dispersed speckle-tracking echocardiography.11 These measurements were per-
ejection fraction
electrical impulse propagation formed by two investigators blinded to patient outcomes using the Q-
MI = Myocardial infarction analysis application on an EchoPAC version 11.0.0 workstation. In
through the left ventricle.7
PES = Programmed electrical The emergence of speckle- each of the three apical views, the LV myocardium was manually con-
stimulation tracking echocardiography has toured, and the contours were adjusted to achieve optimal tracking of
permitted more refined evalua- all myocardial segments over the cardiac cycle. The software automat-
SCD = Sudden cardiac death ically generated curves of strain as a function of time (Figure 1). Using
tion of LV myocardial function
VT = Ventricular tachycardia and tissue characteristics after an 18-segment model derived from the three apical views, segmental
MI.8 This technique allows the peak systolic longitudinal myocardial strain and time to peak longitu-
assessment of the temporal heterogeneity of segmental myocardial dinal strain were recorded. Longitudinal strain in normally contracting
deformation, which may reflect the electromechanical heterogeneity myocardium is by convention negative, but for simplicity, we report
of myocardial tissue.9 With the use of speckle-tracking echocardiogra- absolute strain values, denoted as jstrainj. Thus, poorer myocardial
phy, in the present evaluation we investigated(1) the relationship be- contraction is reflected by a lower jstrainj value. Myocardial segments
tween MI age and LV mechanical and electrophysiologic were classified as having transmural scar if the longitudinal jstrainj
characteristics and(2) the association between LV dyssynchrony and value was <4.5%. This threshold has been previously validated
risk for VT in ICD recipients after MI. against late gadolinium enhancement cardiac magnetic resonance im-
aging.12
LV scar burden was evaluated by the percentage of LV segments
exhibiting transmural scar. LV dyssynchrony was defined as the stan-
METHODS dard deviation of values of time to peak longitudinal systolic strain in
this 18-segment model (Figure 1).11 Global longitudinal strain (GLS)
Patient Population
was measured as the mean of peak jstrainj values from each myocar-
The population comprised patients with prior MIs who underwent dial segment.11
programmed electrical stimulation (PES) followed by ICD implanta-
tion at the Leiden University Medical Center. All patients underwent
transthoracic echocardiography before or <6 months after ICD im- PES
plantation. For patients undergoing biventricular ICD (CRT-D) PES was performed according to current guidelines.13 In brief,
implantation, echocardiography was performed after CRT-D place- patients were studied in a fasting, nonsedated state and after the
ment, with the pacemaker on to ensure representation of current discontinuation of antiarrhythmic medications (except for amio-
physiology. Exclusion criteria were an uncertain date of MI, the pres- darone) for five half-lives.14 PES included up to three drive-cycle
ence of reversible ischemia, pacemaker dependence before ICD lengths (600, 500, and 400 msec) with up to three ventricular ex-
implantation, and the occurrence of VT between ICD insertion and trastimuli and burst pacing from the right ventricular apex and
echocardiography. right ventricular outflow tract. Positive response to PES was
All clinical, electrophysiologic, and echocardiographic data were defined as the reproducible induction of sustained monomorphic
collected in the departmental cardiology information system (EPD- VT lasting >30 sec or requiring termination because of hemody-
Vision; Leiden University Medical Center, Leiden, The namic compromise.
Netherlands) and retrospectively analyzed.
Outcomes
Echocardiography VT was identified from examination of ICD electrograms stored af-
Patients were imaged in the left lateral decubitus position using a ter device therapy administration. The appropriateness of this therapy
commercially available system equipped with 3.5-MHz and 5S trans- and the nature of the ventricular arrhythmia (to distinguish mono-
ducers (Vivid 7 and E9; GE Vingmed Ultrasound AS, Horten, morphic VT from polymorphic VT or ventricular fibrillation) were
Norway). Two-dimensional grayscale, color, pulsed-wave, and adjudicated by an electrophysiologist who was blinded to patients’
continuous-wave Doppler data were acquired in the parasternal clinical characteristics. The primary end point was the occurrence of
and apical views. Images were recorded digitally in cine-loop format first monomorphic VT requiring device therapy (antitachycardia pac-
and analyzed offline with EchoPAC version 11.0.0 (GE Vingmed ing or shock) after ICD implantation. Patients were censored at the
Journal of the American Society of Echocardiography Leong et al 3
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Figure 1 Speckle-tracking echocardiographic strain. Representative examples of speckle-tracking strain curves from two patients
with LVEFs of 55%. Patient A demonstrated greater heterogeneity in time to peak segmental strain compared with patient B. LVEF,
Left ventricular ejection fraction.
4 Leong et al Journal of the American Society of Echocardiography
- 2015

date of most recent outpatient appointment unless the primary end In 10 randomly selected individuals, echocardiographic strain
point occurred earlier. In addition, the occurrence and date of occur- measurements were repeated by a second investigator to determine
rence of the following significant competing risks were recorded if interobserver variability. The interrater agreement for classification
they took place after ICD implantation and before VT occurrence: of scar was evaluated by the k statistic and the interobserver vari-
polymorphic VT, ventricular fibrillation, upgrade to CRT-D, VT abla- ability for LV dyssynchrony and GLS by the intraclass correlation co-
tion, revascularization for acute coronary syndrome, or LV reconstruc- efficient for a two-way random-effects model for consistency of
tive surgery. agreement and by the absolute difference between observers
divided by the mean of the repeated observations expressed as a
percentage.
Statistical Analysis
For all tests, a two-sided a value of 0.05 was adopted to determine
Patients were divided into quartiles according to age of MI (i.e., time statistical significance. Analysis was performed using Stata version
from index MI to ICD insertion). Nominally, these groups were 13.1 (StataCorp LP, College Station, TX).
described as very old for the quartile with the oldest MI age and
recent for the quartile with the youngest MI age. Categorical data
are summarized as frequencies and percentages and were compared RESULTS
using c2 or Fisher exact tests as appropriate. Continuous variables are Patient Characteristics
presented as mean 6 SD or median (interquartile range [IQR]) and
A total of 206 patients (median age, 67 years; IQR, 57–73 years; 180
were compared between groups using analysis of variance or
[87%] men) meeting the inclusion criteria were studied. These
Kruskal-Wallis tests for normally and non-normally distributed data,
comprised 171 ICD recipients (83%) and 35 CRT-D recipients
respectively. Post hoc testing for pairwise comparisons was performed
(17%). The median MI age was 6.2 years (IQR, 0.66–15 years).
with Bonferroni adjustment. The relationship between scar percent-
Patient characteristics are displayed as a function of age of MI in
age and MI age was evaluated by generalized linear modeling.
Table 1. Individuals with very old MIs (MI age in the highest quartile,
Because of the highly skewed distribution and wide variance relative
>180 months prior) were of more advanced age (P < .001), had
to the mean of scar percentage, a negative binomial probability distri-
worse renal function (P = .007), and had longer QRS durations
bution was assumed.
(P < .001). They also had less frequent revascularization of the
For time-to-event (monomorphic VT) analysis, a competing-risks
infarct-related artery (P < .001), and the infarct-related artery more
strategy was adopted. A competing risk is an event whose occurrence
often subtended the inferoposterior LV segments (P = .03) compared
alters or precludes the occurrence of an event of interest (monomor-
with those with more recent MIs. These patients more often received
phic VT). When competing risks are present, competing-risks regres-
ICDs as secondary prevention (P = .002).
sion is regarded as an appropriate approach to time-to-event
analysis.15,16 In the present analysis, the following events occurring
before the occurrence of the primary end point of monomorphic Echocardiographic and Electrophysiologic
VT were treated as competing risks: ventricular fibrillation, Characteristics
polymorphic VT, ICD upgrade, coronary revascularization, and LV Table 2 summarizes the echocardiographic and electrophysiologic
reconstructive surgery.17-19 The covariates that were examined as characteristics of the patient population. Patients with very old
potential predictors of monomorphic VT were chosen on the basis MIs exhibited greater scar burden (14.7 6 15.8% vs 10.7 6
of clinical relevance or demonstrated prognostic value after MI. 11.4%, P = .03) and more left atrial dilatation (36 mL/m2 [IQR,
These covariates included. 27–50 mL/m2] vs 28 mL/m2 [IQR, 23–35 mL/m2], P = .005)
 Clinical factors (age, gender, hypertension, diabetes mellitus, infarct compared with patients with recent MIs (MI age in the lowest quar-
territory, New York Heart Association functional class III or IV, tile, <8 months). Patients with very old MIs showed a higher likeli-
creatinine clearance, ICD indication [secondary vs primary], revas- hood of VT inducibility compared with those with recent MIs (88%
cularization of the infarct-related artery, and age of MI), vs 63%, P = .003). To examine the possibility that the increase in
 QRS duration on electrocardiography, scar burden with infarct age was related to the confounding effects
 Conventional echocardiographic parameters (LV end-systolic vol- of changing practice over time with regard to revascularization of
ume index, left atrial volume index, and LVEF), the culprit artery, we also adjusted for revascularization status in
 Speckle-tracking echocardiographic parameters that formed the the generalized linear model of infarct age. This adjusted analysis
focus of the present study (GLS, LV scar burden, and LV dyssyn- did not significantly affect the positive relationship between scar
chrony), and burden and infarct age (coefficient, 0.15; 95% confidence interval
 VT inducibility on PES. [CI], 0.013–0.28; P = .03). We undertook two post hoc sensitivity
analyses in which a scarred segment was defined as one with jstrainj
Those covariates achieving P values < .20 at the univariate level < 4% and < 5%, respectively. The adjusted coefficients for the rela-
were evaluated in a multivariate competing-risks analysis that was tionship between scar burden and infarct age were 0.18 (95% CI,
performed with backward elimination. Differences in the cumulative 0.043 to 0.32; P = .01) and 0.11 (95% CI, 0.022 to 0.25;
incidence of monomorphic VT between groups were assessed.20 P = .10), respectively.
The incremental benefit of novel predictors of monomorphic VT
was evaluated first by the Wald test comparing the model with the
novel predictor and the model without the novel predictor. Second, Outcomes
the incremental value of novel risk predictors was evaluated using The median follow-up time after ICD implantation was 24 months
the integrated discrimination improvement index; a value significantly (IQR, 7.8–47 months). In total, 75 individuals experienced the pri-
greater than zero is indicative of additive discriminatory value of the mary end point of monomorphic VT, and 18 patients had competing
new risk predictor of interest.21 events. VT ablation was performed in six patients (3%) after ICD
Journal of the American Society of Echocardiography Leong et al 5
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Table 1 Patient characteristics

Quartile 1 (<8 mo) Quartile 2 (8–75 mo) Quartile 3 (75–180 mo) Quartile 4 (>180 mo)
Variable (n = 52) (n = 52) (n = 51) (n = 51) P
,†,‡
Age (y) 63 (51–71) 62 (53–67) 68 (58–73) 74 (67–76)* <.001
Men 47 (90%) 42 (81%) 43 (84%) 48 (94%) .20
Hypertension 25 (48%) 16 (31%) 17 (33%) 19 (37%) .30
Diabetes mellitus 13 (25%) 6 (12%) 8 (16%) 8 (16%) .30
Smoking .20
Never 20 (38%) 24 (46%) 19 (37%) 27 (53%)
Previous 11 (21%) 18 (35%) 20 (39%) 15 (29%)
Current 21 (41%) 10 (19%) 12 (24%) 9 (18%)
Infarct territory .03
Inferior/posterior 17 (33%) 15 (29%) 16 (31%) 28 (55%)
Anterior 35 (67%) 37 (71%) 35 (69%) 23 (45%)
NYHA class .04
I or II 48 (92%) 37 (71%) 38 (75%) 40 (78%)
III or IV 4 (8%) 15 (29%) 13 (25%) 11 (22%)
Secondary prevention ICD 34 (65%) 21 (40%) 29 (57%) 39 (76%) .002
Revascularized infarct-related artery 21 (40%) 24 (46%) 14 (27%) 1 (2%) <.001
AF/atrial flutter 5 (10%) 13 (25%) 13 (25%) 11 (22%) .10
Creatinine clearance (mL/min) 78 (56–103) 74 (58–98) 75 (59–94) 62 (48–77)*,†,‡ .007
QRS duration (msec) 107 6 26 109 6 23 130 6 26 138 6 35*,† <.001
AF, Atrial fibrillation; ICD, implantable cardioverter-defibrillator; NYHA, New York Heart Association.
Data are expressed as median (IQR), number (percentage), or mean 6 SD. The threshold P value for pairwise comparisons between groups was
P < .004, by Bonferroni adjustment.
*P < .004 compared with quartile 1.
†
P < .004 compared with quartile 2.
‡
P < .004 compared with quartile 3.

implantation: in four individuals, this occurred after a primary end These indicate that the measurement of LV dyssynchrony in addition
point event, whereas in the remaining two, the date of ablation was to PES provided superior prediction of subsequent VT.
treated as the study exit date. In a further eight patients, subsequent The cohort was dichotomized on the basis of the median value of
ICD upgrade to CRT-D resulted in study exit at the time of the up- LV dyssynchrony into those exhibiting LV dyssynchrony # 90 and >
grade. LV reconstructive surgery was performed in four individuals 90 msec. Those with LV dyssynchrony > 90 msec had a significantly
(2%) after ICD implantation: in two cases, this occurred after a pri- greater incidence of monomorphic VT compared with those with less
mary end point event, whereas in the other two, the date of surgery LV dyssynchrony (P < .001) (Figure 2).
was used as the study exit date.
Interobserver Variability
For segmental scar classification, the k statistic for interrater agreement
Time–to–Monomorphic VT Analysis was 0.72, indicating substantial concordance between observers. For
Table 3 contains the competing-risks regression for predictors of time GLS measurement, the average intraclass correlation coefficient was
to monomorphic VT. Those factors achieving univariate P values < 0.94 (95% CI, 0.74–0.98), while for LV dyssynchrony, it was 0.96
.20 included age, creatinine clearance, QRS duration, revasculariza- (95% CI, 0.84–0.99). The difference between observers expressed
tion of the infarct-related artery, age of MI, LV end-systolic volume in- as a percentage of the mean of their measurements was 0.022%
dex, LVEF, GLS, LV scar burden, LV dyssynchrony, and VT for GLS and 4.5% for LV dyssynchrony.
inducibility on PES. On multivariate analysis, nonrevascularization
of the infarct-related artery (P = .02), longer QRS duration
(P = .001), greater LV dyssynchrony (P < .001), and lower GLS DISCUSSION
(P = .02) were independently associated with later development of
VT. Each 10-msec increment in LV dyssynchrony was associated The main findings of this study are that (1) greater LV dyssyn-
with a 12% increase in the risk for monomorphic VT. In addition, chrony is associated with an increased risk for monomorphic VT,
the evaluation of LV dyssynchrony conferred incremental predictive independent of MI age and revascularization of the infarct-
value to an infarct-related artery nonrevascularization, QRS duration, related vessel, and (2) older MI is associated with greater LV scar
and GLS, as demonstrated by the Wald test (c2 = 17, P < .001) and an burden than more recent infarction, independent of whether the
integrated discrimination improvement index of 0.027 (P < .001). culprit artery was revascularized.
6 Leong et al Journal of the American Society of Echocardiography
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Table 2 Echocardiographic and electrophysiologic characteristics

Quartile 1 (<8 mo) Quartile 2 (8–75 mo) Quartile 3 (75–180 mo) Quartile 4 (>180 mo)
Variable (n = 52) (n = 52) (n = 51) (n = 51) P
2
LVESVI (mL/m ) 41 (33 to 52) 49 (34 to 66) 49 (33 to 64) 47 (35 to 65) .20
LVEDVI (mL/m2) 69 (57 to 85) 80 (65 to 97) 79 (59 to 100) 77 (56 to 97) .30
LAVI (mL/m2) 28 (23 to 35) 27 (21 to 37) 32 (22 to 40) 36 (27 to 50)*,† .005
Moderate/severe MR 1 (2%) 5 (10%) 4 (9%) 6 (12%) .20
LVEF (%) 41 6 9.9 40 6 13 38 6 11 36 6 8.2 .10
GLS (%) 10.9 (9.81 to 14.3) 12.8 (10.4 to 14.9) 10.1 (8.25 to 13.6) 11.7 (8.58 to 13.4) .10
LV percentage scar (%) 10.7 6 11.4 12.1 6 15.1 13.1 6 12.9 14.7 6 15.8* .03
Patients with $1 dyskinetic myocardial segment 7 (13%) 12 (23%) 11 (25%) 10 (20%) .60
LV dyssynchrony (msec) 82 6 29 81 6 34 97 6 40 91 6 43 .09
VT inducible 33 (63%) 30 (58%) 36 (71%) 45 (88%) .003
VF/PVT inducible 8 (15%) 18 (35%) 8 (16%) 4 (8%) .006
GLS, Global longitudinal strain; LAVI, left atrial volume index; LV, left ventricular; LVEDVI, left ventricular end-diastolic volume index; LVEF, left ven-
tricular ejection fraction; LVESVI, left ventricular end-systolic volume index; MR, mitral regurgitation; PVT, polymorphic ventricular tachycardia; VF,
ventricular fibrillation; VT, ventricular tachycardia.
Data are expressed as median (IQR), number (percentage), or mean 6 SD.
*P < .004 compared with quartile 1.
†
P < .004 compared with quartile 2.

Table 3 Multiple competing-risks regression for the occurrence of VT

Univariate Multivariate

Variable SHR (95% CI) P SHR (95% CI) P

Age 1.02 (1.00–1.05) .03 0.995 (0.963–1.03) .90

Female gender 0.83 (0.43–1.6) .60
Hypertension 0.81 (0.50–1.3) .40
Diabetes mellitus 1.0 (0.58–1.9) .90
NYHA class III or IV 1.1 (0.63–1.9) .70
Creatinine clearance 0.988 (0.981–0.996) .002 0.998 (0.989–1.00) .70
QRS duration 1.012 (1.006–1.019) <.001 1.011 (1.004–1.019) .001
Anterior infarct-related territory 0.94 (0.59–1.5) .80
Secondary prevention ICD 1.4 (0.86–2.4) .20
Revascularized infarct-related artery 0.42 (0.23–0.79) .007 0.49 (0.26–0.91) .02
Time from index MI 1.002 (1.001–1.004) .005 0.9999 (0.9971–1.003) 1.00
LVESVI 1.007 (1.000–1.013) .05 0.9920 (0.9843–0.9998) .05
LAVI 1.00 (0.989–1.02) .70
LVEF 0.97 (0.95–0.99) .008 0.99 (0.96–1.0) .60
GLS, % reduction in magnitude 1.08 (1.02–1.15) .01 1.08 (1.02 –1.16) .02
LV percentage scar 1.03 (1.01–1.04) .001 0.997 (0.969–1.03) .80
LV dyssynchrony, 10-msec increase 1.14 (1.09–1.19) <.001 1.12 (1.06–1.18) <.001
VT inducible 2.9 (1.6–5.5) .001 1.8 (0.90–3.5) .10
GLS, Global longitudinal strain; ICD, implantable cardioverter-defibrillator; LAVI, left atrial volume index; LV, left ventricular; LVEF, left ventricular
ejection fraction; LVESVI, left ventricular end-systolic volume index; MI, myocardial infarction; NYHA, New York Heart Association; SHR, subdis-
tribution hazard ratio; VT, ventricular tachycardia.

Myocardial Infarction Age, Myocardial Scar, and VT Specifically, edema and inflammation early after MI are superseded
LV remodeling after MI is a complex time-related process involving ul- by collagen deposition and myocardial scar formation late after
trastructural and histologic myocardial changes that may be reflected MI.23 This process of scar formation in the infarct zone, as well as
in macroscopic alterations in LV geometry and function.22-24 myocardial collagen deposition in remote areas, continues months
Journal of the American Society of Echocardiography Leong et al 7
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dyssynchrony index. We found that greater LV dyssynchrony was

associated with an elevated risk for subsequent VT. There are several
possible explanations for this finding. First, LV dyssynchrony may pro-
mote ongoing ventricular remodeling, particularly in the infarct or
peri-infarct zones that form the LV substrate for VT. Second, LV dys-
synchrony may also be an indicator of scar and the functional conse-
quences of scar that promote VT.
There is growing recognition of the importance of myocardial
substrate characteristics in the pathogenesis of VT after MI.29 This
may be particularly true for monomorphic VT, which, in contrast
to polymorphic VT and ventricular fibrillation, is mediated by fixed
scar and heterogeneous scar conduction.6 In the present study,
although LV scar burden was associated with the occurrence of
VT during follow-up, LV dyssynchrony was independently associ-
ated with VT. Thus, LV dyssynchrony as a marker of the heterogene-
Figure 2 LV dyssynchrony and VT risk. Cumulative incidence of ity of LV activation seems able to characterize the substrate that
the primary end point of monomorphic VT that required ICD predisposes to VT.
therapy, as a function of LV dyssynchrony. The P value was ob- The results of the present evaluation are consistent with those of a
tained by the approach of Pepe and Mori.20 ICD, Implantable previous study showing that LV dyssynchrony was greater in post-MI
cardioverter-defibrillator; LV, left ventricular; VT, ventricular patients with recurrent VT.9 The present study also demonstrates that
tachycardia. LV dyssynchrony provides complementary information to QRS dura-
tion in the identification of patients who will experience recurrent VT.
to years after the index MI.23 This evolution is manifest by LV dilatation Both QRS duration and wider LV dyssynchrony, in addition to non-
and dysfunction.25-27 However, there isscant evidence on very late revascularization of the infarct-related artery and GLS, were shown
scar progression after MI. In the present study, a trend toward worse in the present study to be independently associated with the risk
LV systolic function was indeed observed in advancing quartiles of for subsequent VT.
MI age. In fact, a more marked and significant increase in LV scar
burden was demonstrated in advancing quartiles of MI age. This was Limitations
accompanied by increasing left atrial volume with increasing MI age, Echocardiography was performed at a single time point, so the tem-
a finding that provides some face validity to our observation of poral evolution of LV remodeling is inferred rather than proved by se-
increasing LV scar with MI age. These findings add to the existing rial measurements in each individual. This research was undertaken at
research by characterization of myocardial substrate very late after MI. a tertiary center among patients referred for electrophysiologic assess-
VT, an important cause of SCD after MI, has been associated with an ment and consideration for ICD placement. Referral bias is therefore
increased scar burden on electroanatomic mapping6 and using late gad- likely, which may have implications for the generalizability of the
olinium enhanced cardiac magnetic resonance imaging.28 Data from study findings. Our findings must be externally validated to confirm
the Multicenter Automatic Defibrillator Implantation Trial II study their clinical importance.
showed a direct association between mortality risk and increasing
time from MI; the presence of extensive scar after MI (as reflected by
an LVEF # 30%) was an independent determinant of lethal ventricular CONCLUSIONS
arrhythmias.4 The present study has delivered consistent findings by
demonstrating that at the univariate level, scar burden by speckle- LV dyssynchrony, which results from myocardial scar tissue inter-
tracking echocardiography is associated with the risk for monomorphic spersed with viable myocytes, is independently associated with the
VT. However, myocardial scar burden is only one of the characteristics subsequent occurrence of VT. Older MI exhibits greater scar burden,
of the arrhythmogenic substrate. Other factors, such as how scar influ- and more LV dyssynchrony independently of whether the culprit ar-
ences electrical impulse propagation and electromechanical coupling, tery was revascularized or not. These observations may help under-
may be important in the development of reentrant VT. standing of the survival benefit seen with ICD implantation later
after MI, compared with earlier.
LV Dyssynchrony and VT
Collagen deposition and remodeling occur after MI principally in the REFERENCES
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