Download The Prognostic Value of Left Atrial Peak Reservoir Strain in Acute

The Prognostic Value of Left Atrial Peak Reservoir Strain
in Acute Myocardial Infarction Is Dependent on Left
Ventricular Longitudinal Function and Left Atrial Size
Mads Ersbøll, MD; Mads J. Andersen, MD; Nana Valeur, MD, PhD; Ulrik Madvig Mogensen, MD;
Homa Waziri, MD; Jacob Eifer Møller, MD, PhD, DSci; Christian Hassager, MD, DSci;
Peter Søgaard, MD, DSci; Lars Køber, MD, DSci
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Background—Peak atrial longitudinal strain (PALS) during the reservoir phase has been proposed as a measure of left atrium
function in a range of cardiac conditions, with the potential for added pathophysiological insight and prognostic value.
However, no studies have assessed the interrelation of PALS and left ventricular longitudinal strain (global longitudinal
strain) in large-scale populations in regard to prognosis.
Methods and Results—We prospectively included 843 patients (mean age 62.1±11.8; 74% male) with acute myocardial
infarction and measured global longitudinal strain, left atrium volumes, and PALS within 48 hours of admission. PALS
was related to a composite outcome of death and heart failure hospitalization. Reduced PALS was associated with
hypertension, diabetes mellitus, and Killip class >1 (P<0.05 for all). Reduced PALS was associated with impairment of
all measures of left ventricular systolic and diastolic function, and the correlation between global longitudinal strain and
PALS was highly significant (P<0.001; r=–0.71). During follow-up (median 23.0 months Q1–Q3, 16.8–26.0), a total of 76
patients (9.0%) reached the composite end point of which 47 patients died (5.6%), and 29 patients were hospitalized for
heart failure (3.4%). PALS was significantly associated with outcome (hazard ratio [HR], 0.88; 95% confidence interval
[CI], 0.85–0.90; P<0.001); however, no independent effect of PALS (HR, 1.00; 95% CI, 0.94–1.05; P=0.87) was found
when adjusting for global longitudinal strain (HR, 1.20; 95% CI, 1.09–1.33; P<0.001), maximum left atrium volume
before mitral valve opening (HR, 1.02; 95% CI, 1.01–1.04; P=0.006), and age (HR, 1.06; 95% CI, 1.03–1.08; P<0.001).
Conclusions—PALS provides a composite measure of left ventricular longitudinal systolic function and maximum left
atrium volume before mitral valve opening, and as such contains no added information when these readily obtained
measures are known. (Circ Cardiovasc Imaging. 2013;6:26-33.)
Key Words: acute myocardial infarction ◼ atrial strain ◼ echocardiography ◼ longitudinal strain ◼ prognosis
L
eft atrial dilatation is well recognized as a strong predictor
of adverse outcome, after acute myocardial infarction
(MI) and in a range of other cardiac pathologies. The left
atrium (LA) is directly exposed to left ventricular (LV) cavity
pressure during diastole, thus an enlarged LA is a robust marker
of increased LV filling pressure in absence of LA volume
overload, which provides a causal link between LA dilatation
and poor outcome.1 Left atrial function is traditionally
described by 3 phases: (1) a reservoir phase during LV systole,
(2) conduit phase from the pulmonary vasculature to the LV
during early diastole, and (3) active booster pump function
in late diastole.2 The phasic LA volumes and the derived
volume changes throughout the cardiac cycle have been related
to adverse prognosis.3,4 Recently, 2-dimensional speckletracking echocardiography-based analysis of LA deformation
during the reservoir phase (peak atrial longitudinal strain
[PALS]) has been reported in several studies with encouraging
results in hypertension, diabetes mellitus, atrial fibrillation,
heart failure (HF), and ST-elevation myocardial infarction
(STEMI).5–10 Finally, a recent consensus statement from the
European Association of Echocardiography/American Society
of Echocardiography (EAE/ASE) has endorsed the promising
value of LA-deformation imaging for potentially adding
information about preclinical heart disease.11
Clinical Perspective on p 33
Barbier et al12 demonstrated that LA reservoir function is
determined by the longitudinal descent of the cardiac base
and LA chamber stiffness. The reciprocating changes in LV
and LA volumes within the nearly constant total cardiac volume suggest that any measure of LA function will be strongly
Received June 26, 2011; accepted November 9, 2012.
From The Heart Centre, Department of Cardiology, University Hospital Rigshospitalet, Denmark (M.E., M.J.A., U.M.M., H.W., J.E.M., C.H., L.K.); and
Department of Cardiology, University Hospital Gentofte, Denmark (N.V., P.S.).
The online-only Data Supplement is available at http://circimaging.ahajournals.org/lookup/suppl/doi:10.1161/CIRCIMAGING.112.978296/-/DC1.
Correspondence to Mads Ersbøll, The Heart Centre, Department of Cardiology, University Hospital Rigshospitalet, Denmark. E-mail mads.ersboell@
gmail.com
© 2012 American Heart Association, Inc.
Circ Cardiovasc Imaging is available at http://circimaging.ahajournals.org
26
DOI: 10.1161/CIRCIMAGING.112.978296
Ersbøll et al Left Atrial Function in Myocardial Infarction 27
influenced by LV longitudinal function. Furthermore, it has
been shown that the 4-chambered heart is a nearly constant
volume pump within 5±1%, which means that any change in
the long-axis dimension of the atrium must be reciprocated
by the ventricle and vice versa. Thus, any longitudinal elongation of the atrium must correspond to deformation of the
ventricle.13–15 However, none of the studies describing either
prognostic or pathophysiological importance of PALS have
adjusted for LV longitudinal function that is readily measured
by 2-dimensional speckle-tracking echocardiography.
Accordingly, the purpose of this study was to assess in
patients with MI: (1) the interdependence of LV and LA deformation and (2) the prognostic importance of PALS, when
adjusted for both LA size and global LV longitudinal function
assessed by global longitudinal strain (GLS).
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Methods
Study Design and Patient Population
Patients with definite MI referred for invasive coronary angiography, either acute because of STEMI or within 1 week of non-STEMI, were prospectively enrolled at 2 tertiary cardiac centers in the
Copenhagen region. All patients provided written informed consent
prior to transthoracic echocardiographic examination. Exclusion
criteria were as follows: aged <18 years, noncardiac disease with a
life expectancy of <1 year, or inability to provide written informed
consent. Furthermore, patients with atrial fibrillation or paced rhythm
during the examination and patients with severe aortic stenosis were
excluded from the analyses.
Based on hospital records obtained on admission information on diabetes mellitus and hypertension, a history of ischemic heart disease and
prior MI was registered. Findings in relation to coronary angiography, including culprit lesion, number of diseased vessels, left main involvement,
and type of revascularization (percutanous coronary intervention [PCI],
coronary artery bypass grafting [CABG], or no intervention), were registered. Objective signs of HF at presentation or during hospitalization
were scored according to the Killip classification scheme. Additional
biochemical sampling included creatinin, hemoglobin, and peak troponin during the hospital stay. The study was approved by the Regional
Scientific Ethics Committee (reference number H-D-2009–063).
Echocardiography
Echocardiography was performed within 48 hours of admission to
the tertiary center. Echocardiographic cine loops were obtained by recording 3 consecutive heart cycles. All examinations were performed
on a Vivid e9 (General Electric, Horten, Norway). Images were obtained at a frame rate of 60 to 90 frames per second and digitally
transferred to a remote workstation for offline analysis (Echopac BT
11.1.0, General Electric, Horten, Norway). Three experienced operators performed all patient examinations using a prespecified echocardiographic examination protocol detailing the acquisition of the LA
in all 3 apical projections, with specific attention to subsequent strain
analysis. All analyses were performed by a single experienced operator (M.E.) blinded to follow-up information.
Two-dimensional parasternal images were used to determine LV
cavity dimensions and wall thickness. LV mass was calculated from
the LV linear dimensions in the parasternal view. Left ventricular
ejection fraction (LVEF) was determined using the biplane Simpson
method. Wall motion scoring was performed by dividing the LV
into 16 segments, and each segment was assigned a score based on
myocardial thickening (1, normal or hyperkinesis; 2, hypokinesis; 3,
akinesis; and 4, dyskinesis). Wall motion score index was calculated
from the average score of all segments. All volumetric and dimensional measurements of the LV were indexed to body surface area
when appropriate, in accordance with EAE/ASE recommendations.2
Color Doppler examination of the mitral valve (MV) was performed in the apical window, and if more than trivial mitral regurgitation (MR) was present, it was quantified by calculating the effective
regurgitant orifice using the proximal isovelocity surface area method. Effective regurgitant orifice <0.20 cm2 was considered mild,
0.20 to 0.40 cm2 moderate, and >0.40 cm2 severe MR. Pulsed wave
Doppler recordings of mitral inflow were performed by placing a 2.5
mm sample volume at the tip of the MV leaflets during diastole. Peak
velocity of early (E) and atrial (A) diastolic filling, and MV deceleration time were measured and E/A-ratio calculated. Pulsed wave tissue
Doppler Imaging recordings were performed at the lateral and medial
mitral annulus using a 2.5 mm sample volume, with measurements of
myocardial peak early velocity (e’). The mean E/e’ ratio was calculated from an average of lateral and medial values of e’.16
LV Strain Analysis
LV longitudinal function was assessed by GLS using a semiautomatic algorithm (Automated Function Imaging, GE, Horten, Norway).
Briefly, 3 points (2 annular and 1 apical) were positioned in each of
the 3 apical projections enabling the software to track the myocardium
semiautomatically throughout the heart cycle. The region of interest
was adjusted to cover the thickness of the myocardium. Aortic valve
closure was identified on continuous wave Doppler recording through
the aortic valve. Careful inspection of tracking and manual correction, if needed, was performed, and in case of unsatisfactory tracking,
the segment would be excluded from the analysis. The Automated
Function Imaging algorithm allowed GLS to be calculated for each
of the 3 apical projections, if at least 5 out of 6 segments were sufficiently tracked. The algorithm then calculated overall GLS as the
average value of all 3 projections. If GLS could only be assessed in 2
of 3 apical projections, we calculated overall GLS as the average of
these 2. If GLS could not be assessed in ≥2 of the apical projections,
the patient examination was classified as having image quality insufficient for LV strain measurements.
LA Volumes and Deformation
LA volumes were calculated using the biplane area–length method
at 3 distinct points during the cardiac cycle and indexed to body surface area: (1) maximum volume before MV opening (LAmax), (2)
minimum volume before MV closing (LAmin), and (3) volume before LA contraction at the onset of the P-wave (LApreA). From these
volumes, the following volumetric indices of the LA were calculated:
(1) LA reservoir volume change (LAmax–LAmin), (2) LA total emptying fraction 100×([LAmax–LAmin]/LAmax), and (3) Active LA
emptying fraction 100×([LApreA–LAmin]/LAmin).
LA strain was assessed in the same apical 4C, 2C, and apical long
axis view (APLAX) projections used for GLS quantification. The
LA endocardial border was traced manually and adjusted to cover
the thickness of the LA walls, resulting in strain curves from a total
of 18 atrial segments. From the average of all 18 resulting strain
curves, we assessed global PALS as the maximum positive strain
value during LV systole (Figure 1). Segments were discarded if the
tracking algorithm was unable to track the myocardium sufficiently.
If more than 2 segments were not tracked properly, the projection
was discarded, and if PALS could not be assessed in ≥2 of the apical
projections, the patient examination was classified as having image
quality insufficient for LA strain measurements.
Follow-up and End Point Definition
The primary outcome was a composite of death from any cause and
hospitalization for HF. Information on all cause mortality was obtained from the Danish Civil Registration System. Information on HF
hospitalization was obtained from a systematic review of all hospital
admissions after the index MI. Hospitalization from HF was defined
as admission because of dyspnea, with objective signs of pulmonary
congestion and treatment with intravenous diuretics. Verification of
HF hospitalization was performed by an independent reviewer, unknowing of clinical and echocardiographic information relating to the
index MI.
28 Circ Cardiovasc Imaging January 2013
Figure 1. Example of 2-dimensional
speckle-tracking of the left atrium (LA; top
left) and the LV (top right). The resulting
strain curves for the LA (lower left) and
LV (lower right) are shown with markings
corresponding to peak atrial longitudinal
strain (PALS) and peak global longitudinal
strain (GLS).
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Statistical Analysis
All data are reported as mean±SD or median (first and third quartile, Q1–Q3). Baseline clinical and echocardiographic data were
analyzed according to GLS quartiles, using Cochran-Armitage
trend test for categorical variables and ANOVA for continuous
variables. All tests were 2-sided, and statistical significance was
defined as P<0.05. Interobserver and intraobserver reproducibility of PALS and GLS was assessed in 20 randomly selected patients, with calculation of bias (mean difference) and limits of
agreement (±1.96 SD). The relationship between PALS and GLS
were examined by correlation analysis. To explore the bivariate
impact of LA volume and GLS on PALS, we performed multiple
linear regression analysis with PALS as the dependent variable.
Furthermore, the proportion of variance in PALS explained by
GLS and LAmax, respectively, was calculated by partial correlation analysis.
The ability of measures of LA volumes, LA deformation indices, and GLS for prediction of the composite end point was examined in univariate Cox proportional hazard models. To examine the
independent and added prognostic value of PALS, we first created
a clinical Cox model consisting of age, history of diabetes mellitus, Killip class >1, and type of infarction (STEMI/non-STEMI).
Into this Cox model was then added (1) LVEF and LAmax, (2)
GLS, and (3) PALS, with calculation of –2 log likelihood, Akaike
Information Criterion, and concordance index at each step. The incremental improvement in model performance was assessed from
these parameters. Furthermore, we added PALS to a Cox model
consisting of only age, GLS, and LAmax to explore the independent value of PALS (1) without the constraints of a relatively limited number of events and (2) motivated by the findings in the
regression analyses of PALS, GLS, and LAmax. Finally, each
of the derived LA volumes was modeled in separate Cox models adjusted for GLS, age, and LAmax as forced entry covariates.
Assumptions of linearity and proportionality were assessed with
cumulated Martingale- and Schoenfeld residuals, respectively.
Both GLS and PALS violated the proportionality assumption, thus
a constant hazard ratio (HR) was calculated for the time interval
up until the first year, and a constant HR at another level after the
first year. The Cox model, including PALS, GLS, age, and LAmax,
was tested in 1000 bootstrap samples to assess the potential effect of PALS in randomly regenerated data. All statistical analyses were performed using R software (R Development Core Team
(2012). R: A language and environment for statistical computing.
R Foundation for Statistical Computing, Vienna, Austria. ISBN
3-900051-07-0, URL http://www.R-project.org/).
Results
Baseline Characteristics
A total of 1110 patients with MI were prospectively included,
53 patients were excluded because of atrial fibrillation (n=40),
ventricular paced rhythm (n=5), and severe aortic stenosis
(n=8). Out of the remaining 1057 patients, 51 patients had
images insufficient for GLS calculation (5%) and 163 (15%)
did not have sufficient tracking of the LA walls. Thus, 843
patients (mean age 62.1±11.8; 74% male) out of the total
study population of 1110 (76%) patients were eligible for
analyses in the present study. The baseline characteristics of
the patients according to quartiles of PALS are listed in Table 1.
Reduced PALS was associated with increasing age, higher
prevalence of hypertension, diabetes mellitus, previously
known HF, and in-hospital heart failure (Killip class >1).
Echocardiographic characteristics according to quartiles of
PALS are shown in Table 2. Reduced PALS was significantly
associated with all echocardiographic measures of reduced
systolic and diastolic function, as well as decreasing values of
LA functional parameters. The 163 patients without obtainable
PALS were not significantly different compared with the 843
patients in terms of LVEF, GLS, LAmax, LAmin, or E/e’ ratio.
Furthermore, no clinical differences were found in regard to age,
diabetes mellitus, known HF, prior MI, or proportion of STEMI;
however, hypertension was more prevalent among the excluded
patients (56% versus 45%; P<0.001) and BMI was higher (27.7
versus 26.5; P<0.001). Intraobserver and interobserver variability
for PALS was –0.71±2.20% and 0.31±3.8%, respectively.
Interrelation Between PALS, LA Volumes, and GLS
There was a significant linear relation between PALS and
GLS (P<0.001, r=–0.71). A curvilinear relation existed
between PALS and LAmax with greater variation of PALS
in the lower ranges of LAmax, whereas higher LAmax was
associated with a more definite reduction in PALS (Figure 2A
and 2B). Multiple regression analysis of PALS demonstrated
that both GLS and LAmax were independently associated
Ersbøll et al Left Atrial Function in Myocardial Infarction 29
Table 1. Baseline Clinical Characteristics According to Quartiles of PALS
PALS (%)
>32.3
n=211
27.3–32.3
n=211
22.5–27.3
n=211
<22.5
n=210
P value
Age, y
56.8±11.2
60.1±10.7
63.1±11.2
68.6±10.7
<0.001
Male sex
155 (74.2)
158 (75.9)
160 (77.3)
139 (66.5)
0.11
BMI, kg/m2
25.9±3.8
26.9±4.2
26.8±3.7
26.4±4.4
<0.05
<0.001
Characteristic
Medical history
Hypertension
60 (28.7)
88 (42.3)
104 (50.2)
118 (56.5)
Previous MI
24 (11.5)
25 (12.0)
20 (9.7)
33 (15.8)
0.25
Diabetes mellitus
15 (7.2)
27 (13.0)
24 (11.6)
41 (19.6)
<0.001
150 (71.8)
143 (68.8)
152 (73.4)
133 (63.6)
0.21
3 (1.4)
5 (2.4)
7 (3.4)
26 (12.4)
<0.001
Smoking
Heart failure
eGFR, mL/min per 1.73 m2
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82.9±12.0
78.3±15.0
73.6±18.9
<0.001
Killip class >1
83.2±9.5
7 (3.4)
7 (3.4)
32 (15.5)
74 (35.4)
<0.001
Heart rate, beats/min
69±11.6
69±10.6
73±12.7
79±14.0
<0.001
Systolic
130±17.2
134±19.7
128±21.7
126±23.1
<0.05
Diastolic
79±11.0
81±10.9
79±12.3
79±14.2
0.34
0.07
Blood pressure, mm Hg
Infarct classification
77 (36.5)
66 (31.3)
52 (24.6)
65 (31.0)
134 (63.5)
145 (68.7)
159 (75.4)
145 (69.0)
0.14
LAD involvement
68 (32.5)
73 (35.1)
93 (44.9)
104 (49.8)
<0.001
Multivessel disease
23 (11.0)
24 (11.5)
28 (13.5)
62 (29.7)
<0.001
Non-STEMI
STEMI
Intervention
Primary PCI
125 (59.2)
138 (65.4)
148 (70.1)
122 (58.1)
0.97
Subacute PCI
37 (17.5)
34 (16.1)
31 (14.7)
36 (17.1)
0.88
No PCI
49 (23.3)
39 (18.5)
32 (15.2)
52 (24.8)
0.86
Additional CABG
14 (6.7)
13 (6.3)
19 (9.2)
26 (12.4)
0.01
BMI indicates body mass index; CABG, coronary artery bypass grafting; eGFR, estimated glomerular filtration rate; LAD, left anterior descending artery; PALS, peak
atrial longitudinal strain; PCI, percutaneous coronary intervention; and STEMI, ST-elevation myocardial infarction.
with PALS. However, the partial correlation of PALS and
LAmax after removal of the effect of GLS was lower when
compared with that between PALS and GLS after the removal
of LAmax (–0.33 versus –0.71), confirmed by a bivariate distribution plot of PALS as a function of GLS and LAmax quartiles (Figure 3).
Relation Between PALS, LA Volumes, GLS, and
Outcome
During follow-up (median 23.0 months Q1–Q3, 16.8–26.0), a
total of 76 patients (9.0%) reached the combined end point, of
which 47 patients died (5.6%) and 29 patients were hospitalized
for HF (3.4%). Global PALS was significantly associated with
outcome (HR, 0.88; 95% confidence interval [CI], 0.85–0.90;
P<0.001) in univariate analysis. Both addition of LVEF and
LAmax to the clinical model and subsequent addition of GLS
improved overall model fit as assessed by the decrease in –2
log likelihood and Akaike Information Criterion. Addition of
PALS did not improve model performance further and, in fact,
worsened the Akaike Information Criterion because of the
built-in penalization of overfitting. Results of the multivariable
stepwise modeling are given in Table 3. Adjustment for age,
GLS, and LAmax removed the effect of PALS (HR, 0.97;
95% CI, 0.92–1.03; P=0.44) without the time-varying effect.
When modeling the effect of GLS and PALS with constant
HRs up until the first year, GLS continued to be independently
prognostic (first year HR, 1.20; 95% CI, 1.09–1.33; P<0.001
and after first year HR, 1.26; 95% CI, 1.13–1.40; P<0.001),
whereas PALS remained nonsignificant (HR first year, 1.00;
95% CI, 0.94–1.05; P=0.87). Age (HR, 1.06; 95% CI, 1.03–
1.08; P<0.001) and LAmax (HR, 1.02; 95% CI, 1.01–1.04;
P=0.006) remained independently associated with outcome.
Because of a high degree of correlation, we assessed LAmin
and LAmax in 2 different models, all other covariates being
unchanged, and overall model performance was similar (both
C-index=0.81). No significant interactions between GLS and
LAmax or LAmin could be detected in the Cox models.
Finally, we assessed the added contribution of the derived
LA volumes previously defined for the prediction of the
composite end point. When GLS, age, and LAmax were in
the models, LA reservoir volume change (HR, 0.97; 95% CI,
0.91–1.02; P=0.25), LA total emptying fraction (HR, 0.99;
95% CI, 0.97–1.01; P=0.22), and active LA emptying fraction
(HR, 1.00; 95% CI 0.99–1.02, P=0.40) did not contain
independent prognostic information, whereas GLS, age, and
LAmax were independently prognostic.
30 Circ Cardiovasc Imaging January 2013
Table 2. Baseline Echocardiographic Characteristics According to Quartiles of PALS
PALS (%)
Characteristic
>32.3
n=211
27.3–32.3
n=211
22.5–27.3
n=211
<22.5
n=210
P value
LV systolic function
LV EDV, mL
84±23
87±25
89±26
100±37
<0.001
LV ESV, mL
37±14
42±17
45±19
60±31
<0.001
LVEF, %
56±7
53±8
50±9
42±12
<0.001
WMSI
1.2±0.2
1.3±0.2
1.5±0,3
1.7±0.3
<0.001
LVMI, g/m2
81±18
86±21
96±25
105±30
<0.001
–16.8±2.4
–15.0±2.6
–13.0±2.5
–10.3±3.1
<0.001
GLS, %
Left atrial volumes (mL/m2)
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LAmax
32±9
33±10
34±10
40±12
<0.001
LAmin
15±5
17±6
18±6
25±10
<0.001
LApreA
22±7
24±7
26±8
33±12
<0.001
LA reservoir volume change
17±6
16±6
16±5
15±6
0.02
LA total emptying fraction
52±8
48±14
46±8
38±10
<0.001
LA active emptying fraction
48±24
45±27
41±22
32±21
<0.001
LV diastolic function
E/e’ ratio
8.5±2.2
9.4±2.8
10.9±3.8
14.5±6.4
<0.001
E/A ratio
1.1±0.3
1.0±0.3
1.0±0.3
1.3±0.7
<0.001
MV Dec. time, ms
196±45
194±49
188±50
166±55
<0.001
0 (0)
4 (2)
5 (2)
19 (9)
<0.001
2.4 (0.4)
2.3 (0.4)
2.1 (0.4)
1.9 (0.4)
<0.001
MR moderate-to-severe
TAPSE
EDV indicates end-diastolic volume; EF, ejection fraction; ESV, end-systolic volume; GLS, global longitudinal strain; LA, left atrium; LV, left ventricle; LVMI, left
ventricular mass index; MV, mitral valve; PALS, peak atrial longitudinal strain; TAPSE, tricuspid annular plane systolic excursion; and WMSI, wall motion score index.
Discussion
The major findings of the present study were as follows: (1)
Reduced PALS is significantly related to the burden of comorbidities, progressively deteriorating indices of LV systolic and
diastolic function, and predicted adverse outcome; (2) PALS is
closely associated with GLS and to a lesser extent LA dilatation
per se; (3) PALS does not add further information in regard to
adverse outcome, when readily obtainable indices of LV longitudinal systolic function and diastolic indices are known; and (4)
GLS and LA dilatation seem to be the major drivers of apparent
Figure 2. A, (red) Inverse relationship between peak atrial longitudinal strain (PALS) and global longitudinal strain (GLS). B, (blue) inverse
relationship between PALS and left atrial maximum volume (LAmax).
Ersbøll et al Left Atrial Function in Myocardial Infarction 31
Figure 3. Bivariate distribution of peak atrial longitudinal strain (PALS) values as a function of global
longitudinal strain (GLS) and left atrial maximum
volume (LAmax) quartiles with axes showing the
direction of impaired GLS and dilated left atrium
(LA) and the resulting reductions in PALS. Worsening GLS confers larger reduction in PALS given
constant LAmax, whereas progressively dilated LA
given a constant GLS reduces PALS by a smaller
magnitude.
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LA functional deterioration, questioning the independent and
added value of assessing LA deformation in patients with MI.
LA Function in Relation to GLS
The LA reservoir phase has been shown to depend initially on
LA-relaxation properties after the preceding LA contraction,
and later the downward motion of the mitral plane driven by LV
longitudinal shortening but modulated by LA compliance.12
This study also demonstrated that right ventricular (RV)
function was not a determinant of LA reservoir function.
We find that tricuspid annular plane systolic excursion is
progressively diminished with reduced PALS; however, this
would also be confounded by impaired GLS, as more extensive
LV myocardial damage after the MI would inherently increase
the likelihood of simultaneous RV involvement. Whether RV
strain utilizing deformation analysis would impact on PALS,
independently of GLS and LAmax, should be explored in
future studies. Reduced PALS was associated with moderateto-severe MR that has been demonstrated previously7; however,
both LA dilatation through increased volume overloading and
impaired GLS18 are also associated with MR. Only 28 patients
(3.3%) had moderate-to-severe MR and were included in the
analyses as PALS, as well as GLS and LAmax, was expected
to be related to the MR.
Previous studies have shown that PALS, as a measure of LA
reservoir function, exhibits distinct abnormalities in a number of conditions, including hypertension, diabetes mellitus,
STEMI, cardiomyopathies, and HF with preserved LVEF.6,9,10,19
Based on this, PALS has been proposed as a measure of LA
intrinsic functional properties reflecting earlier stages of
Table 3. Stepwise Multivariable Cox Regression Modeling
Model 1
Clinical
Model 2
Clinical+LVEF+LA
β
P
Age
1.07
Diabetes
1.23
Killip class >1
Type of infarction (STEMI/nSTEMI)
Model 3
Clinical+LVEF+LA+GLS
Model 3
Clinical+LVEF+LA+GLS+PALS
β
P
β
P
β
<0.0001
1.06
<0.0001
1.06
<0.0001
1.06
<0.0001
0.47
1.14
0.64
1.09
0.77
1.09
0.76
3.44
<0.0001
1.79
0.03
1.47
0.17
1.47
0.16
1.00
0.99
1.01
0.96
0.96
0.86
0.95
0.83
LVEF
0.94
<0.0001
0.96
0.0005
0.95
0.0005
LAmax
1.02
0.048
1.02
0.041
1.02
0.04
GLS (first year)
1.18
0.03
1.18
0.03
GLS (later than first year)*
0.93
0.34
0.93
0.35
PALS (first year)
1.00
0.86
PALS (later than first year)*
0.96
0.32
Covariate
–2 log likelihood
927
882
876
876
AIC
934
894
890
893
Concordance index
0.79
0.83
0.83
0.83
AIC indicates Akaike Information Criterion; GLS, global longitudinal strain; LAmax, left atrial maximum volume; LVEF, left ventricular ejection fraction;
PALS, peak atrial longitudinal strain; and STEMI, ST elevation myocardial infarction.
*Conditioned on having survived the first year without event.
P
32 Circ Cardiovasc Imaging January 2013
diseases processes.20 However, in both hypertension and diabetes mellitus, early impairment of LV longitudinal function
can be detected by GLS before the onset of overt LV systolic
dysfunction,21,22 patients with STEMI exhibit marked impairment in GLS,23 and HF with preserved LVEF has been associated with impaired GLS.24 The present study demonstrates in
the largest population so far, with simultaneous measurements
of GLS and PALS, that these measures are collinear in nature
and that PALS is a reflection of GLS and LA dilatation.
PALS and GLS in Relation to Prognosis
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The prognostic value of PALS was significant for the prediction
of the combined end point death or HF hospitalization during
follow-up. Multivariable adjustment eliminated the effect of
PALS and overall model fit was not improved by the addition
of this parameter, when clinical information, LVEF, LAmax,
and GLS were in the model. Furthermore, when adjusted only
for GLS, LAmax, and age, there was still no significant effect
of PALS, which indicates that it contains no independent prognostic value, and the adjusted HR of PALS approaching 1.00
indicates that the results are not because of overfitting or low
power. Bootstrap validation found a significant independent
effect of PALS in only 10% of the 1000 samples, which further
argues against an independent effect of PALS. These findings
are consistent with the results of the linear regression analyses
and together substantiate the argument that PALS is merely a
composite measure of GLS and LA size. Furthermore, none
of the derived LA volumes emerged as independent predictors when GLS, LAmax, and age were in the model, despite
a relatively large sample size of 843 patients with 76 events.
Thus far, only 1 large-scale study (n=320) has examined the
effect of PALS in relation to prognosis, reporting a univariate
HR of 0.93 for a composite outcome of death, HF, and new MI,9
which is comparable with our results. However, no adjustment
for GLS was performed, although GLS is known to be reduced
in MI23 and associated with prognosis.25
Although experimental data have demonstrated that reservoir function also depends on LA compliance and LA
relaxation, this study suggests that the currently available
speckle-tracking techniques do not capture information
beyond that obtained with GLS and LAmax. The fundamental physiology of the near-constant volume of 4-chambered
heart predict that elongation of the LA during LV systole, as
assessed by PALS, must be reciprocated by the longitudinal
shortening of the LV (GLS).13–15 This implies that from a physiological viewpoint the value of PALS as a marker of early
disease or poor outcome is heavily confounded by GLS. In
this study, we provide the empirical evidence in a large population of patients with MI that PALS has no independent role
and is merely a reflection of LV longitudinal function. It is
conceivable that an isolated atrial myopathy without involvement of LV longitudinal function could be well characterized
with PALS; however, apart from true lone atrial fibrillation
and stiff LA syndrome,26 GLS will be an important confounder
in this regard. As LAmax is readily measured from standard
projections and with GLS becoming increasingly automated,
it seems counterintuitive given the present study findings to
elaborately quantify PALS.
Limitations
A significant proportion of patients did not have images suitable for LA strain assessment and the measurements are challenging. The algorithm for strain quantification was designed
for LV quantification, and as such not developed for LA strain
analysis. PALS was calculated from the average value of all
6 segments in each of the 3 apical projections, including the
LA roof region. Some studies have included only mid-LA
segments in all 3 apical projections,9 whereas others have
included all 3 projections, but omitted the LA region bordering the ascending aorta in the apical long-axis view and used
the p-wave as time reference for tracking.11 However, no definite consensus exists as to how many LA segments should be
included in the analysis. Finally, our results could be because
of low power preventing the detection of a true prognostic
effect of PALS; however, only 10% of the randomly regenerated bootstrap samples resulted in an independent effect of
PALS, which validates our findings internally.
Conclusions
The magnitude of PALS as assessed with 2-dimensional
speckle tracking in patients with acute MI is dependent on
GLS and LA size. Measurement of PALS confers no independent prognostic value, when these readily obtainable echocardiographic parameters are known. The added value of LA
reservoir function in patients with impaired LV longitudinal
function is questionable.
Sources of Funding
The authors would like to thank the following for providing financial
assistance with echocardiographic equipment and analytical software: Fondation Juchum, Switzerland; Beckett Fonden, Denmark;
Toyota Fonden, Denmark.
Disclosures
None.
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Clinical Perspective
Left atrium (LA) dilatation in the aftermath of acute myocardial infarction (MI) is a marker of long-standing elevated left
ventricular filling pressure and is associated with an adverse prognosis. Recently, attention has been directed toward a
functional evaluation of the LA using 2-dimensional speckle-tracking, with several studies reporting a better discriminative
and prognostic performance of these parameters than the more static LA maximum volume. A limitation to these studies,
however, is the lack of consideration of the fundamental physiology of the near-constant volume pump, which states that
any elongation of the atrium must be reciprocated by shortening of the ventricle (LV). Thus, the studies reporting peak atrial
longitudinal strain (PALS) had potential confounding by LV long-axis function. This study correlated PALS with global
LV longitudinal strain (GLS) in a large population of patients with MI and assessed the prognostic impact of LA function
in relation to GLS and LA maximum volume. We found that PALS and GLS were highly collinear, and that the prognostic
information of PALS is dependent on its interrelation with GLS and LA maximum volume. These findings are predictable
from the basic physiology of the near-constant volume pump heart. The results of this study provide empirical evidence to
support the concept that LA function cannot be considered an independent entity or independent prognostic marker, when
LV long-axis function and LA maximum volume are known.
The Prognostic Value of Left Atrial Peak Reservoir Strain in Acute Myocardial Infarction
Is Dependent on Left Ventricular Longitudinal Function and Left Atrial Size
Mads Ersbøll, Mads J. Andersen, Nana Valeur, Ulrik Madvig Mogensen, Homa Waziri, Jacob
Eifer Møller, Christian Hassager, Peter Søgaard and Lars Køber
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Circ Cardiovasc Imaging. 2013;6:26-33; originally published online November 27, 2012;
doi: 10.1161/CIRCIMAGING.112.978296
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Copyright © 2012 American Heart Association, Inc. All rights reserved.
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