Download Prognostic Value of Global Myocardial Performance Indices in Acute

Prognostic Value of Global Myocardial
Performance Indices in Acute
Myocardial Infarction*
Comparison to Measures of Systolic and Diastolic
Left Ventricular Function
Ehud Schwammenthal, MD; Yehuda Adler, MD; Keren Amichai, MD;
Alik Sagie, MD; Solomon Behar, MD; Hanoch Hod, MD; and
Micha S. Feinberg, MD
Study objectives: Assessment of global myocardial performance by a single index (ie, the
myocardial performance index [MPI]) has been suggested as an appealing alternative to
the individual assessment of systolic and diastolic left ventricular (LV) function We sought to
test the prognostic value of MPI in comparison to clinical characteristics and echocardiographic
parameters of LV filling and ejection in acute myocardial infarction (AMI).
Patients: Four hundred seventeen consecutive patients with AMI were examined within 24 h of
hospital admission.
Interventions: Doppler echocardiographic measures of systolic, diastolic, and global myocardial
performance were assessed within 24 h of hospital admission. In addition to MPI (ie, the sum of
the isovolumic time intervals divided by ejection time), we determined the isovolumic/heterovolumic time ratio, which expresses the time “wasted” by the myocardium to generate and
decrease LV pressure without moving blood.
Results: The end points of the study at 30 days were death (4.7%), congestive heart failure (23%),
and recurrent infarction (4.8%), and occurred in 109 patients, who were compared as group B to
314 patients without an event (group A). Multivariate analysis identified only age (odds ratio [OR],
1.04; 95% confidence interval [CI], 1.02 to 1.07), LV ejection fraction (LVEF) < 40% (OR, 3.82;
95% CI, 2.15 to 6.87), and E-wave deceleration time (EDT) of < 130 ms (OR, 2.29; 95% CI, 1.0
to 5.21) as independent predictors of adverse events.
Conclusion: LVEF and EDT are powerful and independent echocardiographic predictors of poor
outcome following AMI, and are superior to indexes of global LV performance. Both parameters
should be taken into consideration when deciding about the management of these patients.
(CHEST 2003; 124:1645–1651)
Key words: acute myocardial infarction; diastolic left ventricular function; Doppler echocardiography; myocardial
performance index
Abbreviations: AMI ⫽ acute myocardial infarction; CI ⫽ confidence interval; E/A ⫽ peak E-wave velocity/peak
A-wave velocity ratio; EDT ⫽ E-wave deceleration time; I/H ⫽ isovolumic time/heterovolumic time ratio; LV ⫽ left
ventricle, ventricular; LVEF ⫽ left ventricular ejection fraction; MPI ⫽ myocardial performance index; OR ⫽ odds
ratio
of global myocardial performance by a
A ssessment
single index has been suggested as an appealing
alternative to the individual assessment of systolic
and diastolic left ventricular (LV) function.1– 6 In
*From the Heart Institute (Drs. Schwammenthal, Amichai, Behar, Hod, and Feinberg) and Cardiac Rehabilitation Institute
(Dr. Adler), Chaim Sheba Medical Center, Tel Hashomer, Israel;
and the Department of Cardiology (Dr. Sagie), Rabin Medical
Center, Petach-Tiqvah, Israel.
Manuscript received May 23, 2002; revision accepted March 20,
2003.
www.chestjournal.org
1995, Tei and colleagues1,2 proposed a Dopplerderived time interval index, which was defined as the
sum of isovolumic contraction time and relaxation
time divided by ejection time. This myocardial performance index (MPI) can be obtained easily from
Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail:
[email protected]).
Correspondence to: Ehud Schwammenthal, MD, Heart Institute,
Sheba Medical Center, Tel Hashomer, Israel; e-mail: sehud@
post.tau.ac.il
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1645
mitral inflow and LV outflow velocity time intervals
with good reproducibility, and is independent from
LV geometry and heart rate.2 It correlates well with
invasive measures of systolic and diastolic LV function,3 and has been reported to correlate better with
patient outcome than conventional echocardiographic parameters in various myocardial diseases.7,8
However, little information is available about the
clinical value of the MPI in patients with acute
myocardial infarction (AMI).9,10 Because morbidity
and mortality from AMI are affected by both systolic
and diastolic myocardial dysfunction, a parameter
that integrates both components might be of particular value in this setting. In a small group of patients,
Poulsen et al9 found the MPI to be the strongest
independent predictor of the development of inhospital congestive heart failure in patients with
AMI. At the 1-year follow-up, MPI remained a
significant, yet less powerful, predictor of poor outcome than restrictive LV filling.10
The purpose of the present study was to test the
prognostic value of MPI in comparison to clinical
characteristics and echocardiographic parameters of
LV filling and ejection in a large, consecutive group
of patients with AMI. In addition, we sought to
examine whether the assessment of global myocardial performance can be improved by relating the
sum of the isovolumic time intervals to the sum of
the heterovolumic time intervals (ejection time and
filling time). This isovolumic time/heterovolumic
time ratio (I/H) index should express the time “wasted” by the myocardium to generate and decrease LV
pressure without moving blood (ie, without performing external work).
Materials and Methods
ings, electrocardiograms during the hospital course and 30-day
follow-up were prospectively collected.
Two-Dimensional and Pulsed-Wave Doppler Echocardiography
All patients underwent a complete echocardiographic examination (SONOS 2500 ultrasound system with a 2.5-MHz transducer; Hewlett-Packard; Andover, MA). Data were stored on
high-quality videotape for subsequent analysis. The mitral inflow
velocity was recorded using pulsed-wave Doppler echocardiography with the sample volume positioned between the tips of the
mitral leaflets, and LV outflow velocity was measured just below
the aortic valve. LV volumes and LV ejection fraction (LVEF)
were determined using the modified biplane Simpson method,
when ⱖ 80% of the endocardial border could be delineated in
both the four-chamber and two-chamber views, and by the
single-plane method, when ⱖ 80% of the endocardial border
could be delineated only in the four-chamber view.12,13 Measurements of peak E-wave and A-wave velocity, peak E-wave velocity/
peak A-wave velocity ratio (E/A), and E-wave deceleration time
(EDT) were performed in a standard manner.14 –22 Stroke distance was measured as the time-velocity integral of the systolic
outflow tract velocity signal. Doppler time intervals were obtained, as demonstrated in Figure 1, from an average of five
cardiac cycles. The sum of isovolumic contraction and relaxation
time was obtained by subtracting ejection time (Fig 1, b) from the
interval between two mitral inflow periods (Fig 1, a). MPI then
was determined as (a ⫺ b)/b. I/H was determined as (a ⫺ b)/
(b ⫹ c), where c is the mitral filling period. All measurements
were performed by an experienced observer who was blinded to
the clinical data.
Statistical Analysis
The results were expressed as the mean ⫾ SD. The comparison of clinical characteristics was performed by ␹2 analysis for
categoric variables, and by analysis of variance for continuous
variables. A p value of ⬍ 0.05 was considered to be significant.
Multivariate analysis was performed to identify independent risk
predictors for the combined end point of death, heart failure, and
reinfarction at 30 days, using the Cox proportional hazards
model.23 The end point heart failure was defined as new-onset
heart failure during hospitalization (Killip classification, ⱖ 2), or
persistence or worsening of heart failure despite treatment.
Study Population
During the 1-year study period, 451 consecutive patients with
documented AMI were admitted to the coronary care units of
Sheba and Rabin Medical Centers. Myocardial infarction was
diagnosed when at least two of the following criteria were
present: chest pain lasting ⬎ 30 min; typical ECG changes; and
elevated creatine kinase-MB fraction. Myocardial infarction location was determined using ECG criteria.11 Twelve patients
died shortly after coronary care unit admission, before an echocardiographic study could be performed. Twenty-two patients
could not be examined by echocardiography within 48 h of
hospital admission due to logistic limitations. The remaining 417
patients constitute the study population. Patients were included
in a registry that was accumulated during the screening period of
the Argatroban in Acute Myocardial Infarction-2 study, a multicenter trial that was designed to assess the safety and relative
efficacy of direct antithrombin therapy (ie, argatroban) compared
with therapy with IV heparin in patients with AMI who are
receiving thrombolytic therapy. Argatroban exerted neither a
favorable nor an adverse detectable effect on outcome. Relevant
data on medical history, physical examination, laboratory find-
Results
At the end of the study period, 19 patients (4.7%)
had died, 96 patients (23%) were in heart failure
(Killip classification, ⱖ 2), and 20 patients (4.8%)
had experienced a recurrent myocardial infarction. A
total of 103 patients (25%) had reached at least one
end point and were compared as group B to the 314
patients (75%) without an end point (group A).
Clinical Characteristics
Table 1 details the clinical characteristics of both
groups. As expected, patients with a poor outcomes
(group B) were older (p ⬍ 0.001), and a substantially
higher percentage of individuals had diabetes
(p ⬍ 0.001) and hypertension (p ⬍ 0.02), and had a
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Clinical Investigations
Figure 1. Derivation of the MPI and the I/H from Doppler tracings of mitral inflow and LV outflow.
a ⫽ time between filling periods, which equals the duration of mitral regurgitation (MR), when present;
b ⫽ ejection time (ET); c ⫽ filling time (FT). The sum of isovolumic contraction time (ICT) and
isovolumic relaxation time (IRT) can be obtained by the subtraction of b from a.
history of myocardial infarction (p ⫽ 0.03) or a history of heart failure (p ⬍ 0.001), when compared to
the patients with a favorable outcome (group A).
Significantly more patients in group B were in heart
failure at the time of hospital admission (p ⬍ 0.001).
Anterior-wall MI occurred more frequently in group
B (p ⬍ 0.001), and peak creatine phosphokinase
values were significantly higher on average
(p ⬍ 0.05).
Echocardiographic Parameters
Except for measures of diastolic LV size, the two
groups differed in all echocardiographic parameters
of LV filling and ejection, and in both indexes of
global myocardial performance (Table 2). The pa-
rameters that discriminated best between groups A
and B were LVEF (p ⬍ 0.000001)), stroke distance
(p ⬍ 0.00001), EDT (p ⬍ 0.000008), and I/H
(p ⬍ 0.00007). The mean percent difference (⌬)
between the two groups was highest for I/H
(0.18 ⫾ 0.08 vs 0.22 ⫾ 0.11, respectively; ⌬, 20%)
and LVEF (46 ⫾ 9 vs 40 ⫾ 10, respectively; ⌬, 14%).
Independent Predictors
Multivariate regression analysis identified only the
following as independent predictors of poor outcome
at 30 days (Table 3): LVEF ⱕ 40% (odds ratio [OR],
3.82; 95% confidence interval [CI], 2.15 to 6.87),
EDT ⱕ 130 ms (OR, 2.29; 95% CI, 1.01 to 5.21),
and age (OR, 1.04 per year; 95% CI, 1.02 to 1.07).
Table 1—Clinical Characteristics of the Study Group*
Parameter
Group A (n ⫽ 314)
Group B (n ⫽ 304)
p Value
Age, yr
Female gender
Diabetes
Hypertension
Previous MI
History of CHF
Killip classification of ⱖ 2 on hospital admission
Anterior wall MI
Inferior wall MI
Peak CPK, U/L
60 ⫾ 13
20
19
37
19
1
7
36
52
998 ⫾ 1,061
66 ⫾ 13
28
36
50
29
9
35
54
41
1,258 ⫾ 1,192
⬍ 0.001
0.07
0.001
0.02
0.03
⬍ 0.001
⬍ 0.001
⬍ 0.001
⬍ 0.06
⬍ 0.05
*Values given as mean ⫾ SD or %, unless otherwise indicated. CHF ⫽ congestive heart failure; CPK ⫽ creatine phosphokinase; MI ⫽ myocardial
infarction.
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Table 2—Echocardiographic Parameters
Parameter
Group A
(n ⫽ 314)
Group B
(n ⫽ 304)
p Value
LVEDD, cm
LVESD, cm
LVEDVI, mL/m2
LVESVI, mL/m2
LVEF, %
Stroke distance, cm
E/A
EDT, ms
MPI
I/H
5.0 ⫾ 0.5
3.3 ⫾ 0.6
67 ⫾ 20
37 ⫾ 15
46 ⫾ 9
19 ⫾ 4
1.1 ⫾ 0.5
174 ⫾ 36
0.43 ⫾ 0.16
0.18 ⫾ 0.08
5.1 ⫾ 0.6
3.6 ⫾ 0.6
70 ⫾ 20
42 ⫾ 16
40 ⫾ 10
17 ⫾ 4
1.3 ⫾ 1.1
157 ⫾ 35
0.50 ⫾ 0.22
0.22 ⫾ 0.11
0.27
0.002
0.23
0.002
⬍ 0.000001
⬍ 0.00001
0.002
⬍ 0.000008
⬍ 0.0023
⬍ 0.00007
*Values given as mean ⫾ SD, unless otherwise indicated.
LVEDD ⫽ LV end-diastolic diameter; LVEDVI ⫽ LV end-diastolic volume index; LVESD ⫽ LV end-systolic diameter;
LVESVI ⫽ LV end-systolic volume index.
MPI was not independently related to outcome in
this model (OR, 1.09; 95% CI, 0.59 to 2.14). Entering I/H instead of MPI into the model did not
achieve a significant improvement (OR, 1.24; 95%
CI, 0.66 to 2.30). The correlation between MPI and
the two independent echocardiographic predictors
of adverse outcome (ie, LVEF and EDT) was poor
(r ⫽ ⫺0.27 and r ⫽ ⫺0.12, respectively). The corresponding correlation coefficients for I/H were
r ⫽ ⫺0.35 and r ⫽ ⫺0.24, respectively.
Discussion
The present study failed to demonstrate any incremental prognostic value of global MPIs compared to
measures of systolic and diastolic LV function in a
large, consecutive, and prospectively examined
group of patients with AMI. Patients with poor and
favorable outcomes differed significantly in most
echocardiographic parameters of LV filling and ejection, and the discriminatory power of I/H was particularly high. However, only LVEF and EDT
Table 3—Multivariate Analysis of Predictors of Death,
Congestive Heart Failure, and Reinfarction at 30 Days
in 417 Patients with AMI
Parameter
OR
CI
Age*
Female gender
LVEF ⱕ 40%*
Stroke distance
E/A ⱖ 2.0
EDT ⱕ 130 ms*
MPI ⱖ 0.52
1.04
1.14
3.82
1.03
2.56
2.29
1.09
1.02–1.07
0.58–2.19
2.15–6.87
0.54–1.91
0.70–8.96
1.01–5.21
0.59–2.14
* ⫽ significant independent predictors of adverse events.
emerged as strong independent predictors of death,
heart failure, and reinfarction at 30 days following
AMI. These results are in accordance with the
concept that combinations of different degrees of
systolic and diastolic myocardial dysfunction are
prevalent among patients with AMI, and that both
components have a significant impact on patient
outcome. The study confirms the results of previous
smaller series,14,15,21,22 and reinforces the use of
these two parameters of filling and ejection for risk
stratification in patients with AMI.
Multiregression Analysis
If both components of myocardial function determine patient outcome, why did the global MPIs
fail? Multiregression analysis may reject a parameter due to lack of a sufficiently close association
to the respective end point, or despite a significant
association, if this parameter is closely correlated
to superior predictors of the end point. Since the
correlation of both MPIs to the two strong independent echocardiographic predictors of adverse
outcome was poor, it seems that the explanation is
simply a low predictive accuracy of these indexes.
In fact, 65 of the 103 patients (63%) with an
adverse event had a favorable MPI. Almost half of
the patients with a favorable MPI (48%), despite
poor outcome, had an LVEF of ⱕ 40%, and
approximately one quarter of these patients (26%)
had an EDT of ⱕ 140 ms.
Pseudonormalization
One possible factor that may have confounded the
diagnostic accuracy of the MPI is the phenomenon
of pseudonormalization. Dujardin et al8 argued that
the MPI was valuable in the risk assessment of
patients with dilated cardiomyopathy, irrespective of
the transmitral filling pattern, since they found that
patients with similar prognoses can have similar MPI
values despite having different filling patterns. With
the transition from a nonrestrictive to a restrictive
filling pattern, the shortening of the isovolumic
relaxation time occurs but would be counterbalanced
by a shortening in ejection time and the prolongation
of isovolumic contraction time (Fig 2). Therefore,
the index remained prognostically useful, whereas
mitral deceleration time could be misleading, according to the authors.8
In view of the pathophysiology of myocardial
dysfunction, and supported by the findings of this
study, a more appropriate interpretation is the
following one: with deteriorating myocardial function (indicated by a prolongation of isovolumic
contraction time, a shortening of ejection time,
and the appearance of a restrictive filling pattern)
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Clinical Investigations
Figure 2. Diagram illustrating the pseudonormalization of the MPI, but not the I/H, with
deterioration of LV function and the occurrence of a restrictive filling pattern. Left: impaired relaxation
filling pattern. Right: restrictive filling pattern. With deteriorating myocardial function, isovolumic
contraction time increases and ejection time shortens. Nevertheless, MPI remains unchanged due to
shortening of the isovolumic relaxation time, which reflects elevated filling pressure (ie, pseudonormalization). In contrast, I/H increases, because shortening of the IRT is counterbalanced by shortening
of the filling time that occurs with restrictive filling. See the legend of Figure 1 for abbreviations not
used in the text.
an increase in MPI is prevented by a shortening of
the isovolumic relaxation time. The shortened
isovolumic relaxation time reflects, of course, an
increase in left atrial pressure and not an improvement in relaxation. The lack of increase in MPI,
not the shortening of the EDT, is therefore misleading. The behavior of MPI can be accurately
termed pseudonormalization (Fig 2), since it has
the same pathophysiologic basis as pseudonormalization of the LV filling pattern.
The I/H was specifically designed to (partially)
solve the problem of pseudonormalization (Fig 2).
In patients with severe LV dysfunction, the shortening of the isovolumic relaxation time is accompanied by a shortening in filling time,24 –26 which is
taken into consideration by the I/H index. Therefore, in contrast to MPI, the I/H index increases,
more truthfully reflecting myocardial deterioration (Fig 2). Although pseudonormalization could
explain the high proportion of patients who had a
favorable MPI despite a poor prognosis, it cannot
be the only reason for the low predictive value of
the MPI, because the I/H index also was rejected
by the multivariate analysis.
Assessment of LV Function
The comprehensive assessment of LV function
requires information about cardiac pressure and
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volumes, and their change over time. It appears that
this cannot be achieved by a simple ratio of isovolumic time intervals and ejection time alone. The MPI
neglects whether the LV ejects a large or a small
portion of its filling volume during systole, yet LVEF
is a powerful measure of systolic ventricular function
(and outcome), for which the mere duration of
systole is a poor substitute. With the deterioration of
LV diastolic function, filling pressure will increase
(and EDT will decrease), yet the associated shortening of isovolumic relaxation time will prevent an
increase in MPI and will mask diastolic dysfunction
just when it becomes clinically relevant. An elevated
filling pressure, which is mirrored by a restrictive
filling pattern,16 –18 may reflect more extensive myocardial damage, or more extensive ischemia, and
therefore defines independently a high-risk subset of
patients, as was shown in this study. Consequently,
the assessment of LV function and risk stratification
is incomplete without an assessment of the transmitral filling pattern.
Limitations
The quality of a model depends on the cutoff
values chosen. For LVEF, EDT, and E/A, established and published cutoff values were used for
comparability.18 –20 For MPI, for which less data are
available in the setting of AMI, and I/H (a so-far
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1649
untested index), the border between the third and
fourth quartile of data distribution was used. The
cutoff value for MPI obtained by this method was
0.52, which turned out to be almost the exact
arithmetic mean of the cutoff values for MPI chosen
in the two studies by Poulsen et al9,10 (0.6 and 0.45,
respectively). Although all data collection was prospective and consecutive, the original purpose of the
data gathered was to assess the effect of argatroban
on patients with AMI. Twelve patients died shortly
after hospital admission, before an echocardiographic study could be performed (⬍ 2.7% of all
eligible patients, and 10% of all eligible patients who
had experienced an event), and 22 patients could not
be examined by echocardiography within 48 h of
hospital admission due to logistic limitations. It is
highly unlikely that these limitations have significantly affected the results of the study.
The present article deals with acute LV dysfunction in patients who were examined within 48 h of an
AMI. It is possible that indexes of global myocardial
performance are better suited to reflect chronic
myocardial disease, such as in dilated cardiomyopathy.8
In summary, LVEF and EDT are powerful and
independent echocardiographic predictors of poor
outcome following AMI, and are superior to indexes
of global LV performance. Both parameters should
be taken into consideration when deciding about the
management of these patients.
ACKNOWLEDGMENT: We would like to thank Valentina
Boyko, MSc, and Miriam Cohen, BSc, for their expert statistical
assistance.
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