Improvement of myocardial performance (Tei) index closely reflects intrinsic improvement of cardiac function: assessment in revascularized hibernating myocardium.

Abstract

Myocardial performance index (MPI), or Tei index, is an indicator of systolic and diastolic myocardial function. MPI increases in case of cardiac dysfunction; however, whether reversal of left ventricular dysfunction is also reflected by concomitant improvement (i.e., decrease) of MPI is unknown.
Fifty-two patients with chronic ischemic cardiomyopathy and viable myocardium by dobutamine stress echocardiography were studied by echocardiography before and more than 4 months after cardiac revascularization. Patients were in optimal medical therapy, which remained unchanged following revascularization.
At baseline, ejection fraction (EF: 32 ± 6%) and wall motion score index (WMSI: 2.37 ± 0.32) were impaired, and MPI averaged 0.71 ± 0.19. Revascularization markedly improved EF (44 ± 10%, P < 0.0001) and WMSI (1.77 ± 0.44, P < 0.0001). MPI also improved (0.59 ± 0.26, P < 0.0001), and its decrease was significantly correlated with the improvement in EF (r =-0.68, P < 0.0001) and to the extent of viable myocardium (r =-0.45, P = 0.0007). Responders to revascularization (≥5% increase in EF at follow-up, n = 40% and 77%) achieved a significant improvement in MPI at follow-up in contrast with nonresponders (-23 ± 25% vs. 0.02 ± 0.18%, P = 0.001). Improvement in MPI was largely driven by a significant reduction in isovolumic contraction time (P < 0.001) with consequent prolongation of the ejection phase.
In patients with chronic ischemic cardiomyopathy, MPI improves along with recovery of function, reflecting the intrinsic improvement of viable segments induced by revascularization.

Full text

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DOI: 10.1111/j.1540-8175.2011.01575.x
C ? 2011, Wiley Periodicals, Inc.
Improvement of Myocardial Performance (Tei) Index
Closely Reflects Intrinsic Improvement of Cardiac
Function: Assessment in Revascularized Hibernating
Myocardium
Erberto Carluccio, M.D.,∗Paolo Biagioli, M.D.,∗Gianfranco Alunni, M.D.,∗Adriano Murrone, M.D.,∗
Cinzia Zuchi, M.D.,∗Emilia Biscottini, M.D.,∗Rosanna Lauciello, M.D.,∗Paola Pantano, M.D.,∗
Federico Gentile, M.D., F.A.C.C.,†‡ Rick A Nishimura, M.D., F.A.C.C.,‡
and Giuseppe Ambrosio, M.D., Ph.D., F.A.C.C.∗
∗Divisions of Cardiology, University of Perugia School of Medicine, Perugia, Italy; †Centro
Medico-Diagnostico, Napoli, Italy; and ‡Mayo Clinic, Rochester, Minnesota
Background: Myocardial performance index (MPI), or Tei index, is an indicator of systolic and diastolic
myocardial function. MPI increases in case of cardiac dysfunction; however, whether reversal of left ven-
tricular dysfunction is also reflected by concomitant improvement (i.e., decrease) of MPI is unknown.
Methods: Fifty-two patients with chronic ischemic cardiomyopathy and viable myocardium by dobu-
tamine stress echocardiography were studied by echocardiography before and more than 4 months
after cardiac revascularization. Patients were in optimal medical therapy, which remained unchanged
following revascularization. Results: At baseline, ejection fraction (EF: 32 ± 6%) and wall motion score
index (WMSI: 2.37 ± 0.32) were impaired, and MPI averaged 0.71 ± 0.19. Revascularization markedly
improved EF (44 ± 10%, P < 0.0001) and WMSI (1.77 ± 0.44, P < 0.0001). MPI also improved (0.59 ±
0.26, P < 0.0001), and its decrease was significantly correlated with the improvement in EF (r = −0.68,
P < 0.0001) and to the extent of viable myocardium (r = −0.45, P = 0.0007). Responders to revascular-
ization (≥5% increase in EF at follow-up, n = 40% and 77%) achieved a significant improvement in MPI
at follow-up in contrast with nonresponders (−23 ± 25% vs. 0.02 ± 0.18%, P = 0.001). Improvement
in MPI was largely driven by a significant reduction in isovolumic contraction time (P < 0.001) with
consequent prolongation of the ejection phase. Conclusion: In patients with chronic ischemic cardiomy-
opathy, MPI improves along with recovery of function, reflecting the intrinsic improvement of viable
segments induced by revascularization. (Echocardiography, ****;**:1-9)
Key words: surgery coronary bypass, hibernation, diastolic dysfunction, ecocardiography dobutamine,
viability
In 1995, Chuwa Tei described the myocardial
performance index (MPI), defined as the sum of
isovolumic contraction and relaxation times di-
vided by the ejection time (ET) (Fig. 1).1MPI has
since gained acceptance as a reliable method for
the combined evaluation of left ventricular (LV)
systolic and diastolic performance, with potential
advantages over other indexes in many cardiac
diseases, such as amyloidosis, dilated cardiomy-
opathy, and myocardial infarction.2–7In patients
with dilated cardiomyopathy, this index, besides
reflecting the severity of LV dysfunction, was also
shown to be an independent prognostic factor
for mortality.5
Address
Giuseppe
gia, Ospedale S.M. della Misericordia, S. Andrea delle
Fratte, 06131 Perugia, Italy. Fax: +390755271244; E-mail:
giuseppe.ambrosio@ospedale.perugia.it
for
Ambrosio,
correspondence
M.D.,
and reprint
F.A.C.C.,
requests:
Cardiolo-Ph.D.,
MPI is simple and inexpensive to measure,
and it has been shown to be relatively indepen-
dent of heart rate, blood pressure, and LV ge-
ometry.8However, while the reliability of MPI
to detect cardiac dysfunction is well established,
little is known with respect to its capability to
pick up the improvement of function of dis-
eased hearts. This uncertainty mostly stems from
the inherent problem that drugs used to treat
heart failure have major effects on hemodynam-
ics and/or heart rate, which may cloud inter-
pretation of changes in MPI. Likewise, the im-
provement in cardiac function seen in many pa-
tients after cardiac resynchronization therapy in-
escapably occurs via marked changes in the du-
ration of LV conduction and contraction, which
also may affect the calculation of MPI. Being able
to show that MPI is also a reliable indicator of
improvement of function would undoubtedly in-
crease its attractiveness also as a simple means of
1

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Carluccio, et al.
Figure 1. Representation of measurements of Doppler time
intervals for the calculation of MPI (according to Tei et al.1).
MPI (ICT+IVRT/ET) is derived as (a−b/b), where a is the in-
terval between cessation and onset of the mitral inflow, and
therefore, it reflects the sum of ICT (the interval between ces-
sation of mitral inflow and onset of aortic valve flow) and iso-
volumic relaxation time (IVRT: the interval between the aortic
valve closure and the onset of mitral valve flow); whereas b is
the ET of LV outflow.
monitoring the effect of therapy in patients with
cardiac dysfunction.
It is now appreciated that ventricular dysfunc-
tion is not always an irreversible process, and in
a relatively large proportion of patients, it could
be due to a state of “dormant” myocardium,
i.e., “myocardial hibernation.”9,10Assessment of
myocardial viability has become a crucial step
in the decision-making process of patients with
chronic ischemic cardiomyopathy, since patients
with dysfunctional but viable myocardium are
likely to benefit from revascularization in terms
of improvement in LV systolic function,9,11,12re-
verse remodeling,13and reduced mortality.9,14
In the present study, we took advantage of the
peculiarclinicalconditionrepresentedbymyocar-
dial hibernation, in which LV systolic and diastolic
functionmayimproveasadirecteffectofrevascu-
larization, without concomitant confounding fac-
tors. Therefore, the aim of this study was to eval-
uate the effect of myocardial revascularization on
MPI, and its relation with the extent of myocar-
dialviability,inpatientswithchronicischemiccar-
diomyopathy and viable myocardium.
Methods:
Study Population:
From April 2002 to September 2007, patients
with chronic ischemic cardiomyopathy, in whom
surgical or percutaneous myocardial revascular-
ization was planned, were enrolled in the study
if they met the following inclusion criteria: (1) LV
ejection fraction (EF) <40%; (2) ≥70% stenosis in
atleastonemajorcoronaryarteryatangiography,
suitable for surgical or percutaneous revascular-
ization; (3) adequate echocardiographic window,
allowing evaluation offunctionin allLVsegments;
and (4) evidence of myocardial viability by low-
dose dobutamine echocardiography.
Patients were excluded if they had acute coro-
nary syndrome ≤3 months before the study, sig-
nificant valvular heart disease, or previous surgical
revascularization. Patients with atrial fibrillation,
frequent ventricular ectopy, or pacing rhythm
were also excluded. Many of these patients also
constitute the dataset of previous reports address-
ing LV remodeling and diastolic function.12,13
Study Protocol:
After signing the informed consent, a com-
prehensive two-dimensional (2D) and Doppler
echocardiography examination was performed at
baseline, under resting conditions; viability of
dyssynergic segments was then assessed by
contractile response to dobutamine (see be-
low). Therapy was maintained, except for beta-
blockers, which were transiently discontinued
48 hours before dobutamine echocardiography.
Patients were then referred to undergo revascu-
larization within a month. Follow-up evaluation,
performed at an average of 7.5 ± 2.8 months
after coronary revascularization, included repeat
assessmentofLVsystolicglobalandregionalfunc-
tion, as well as diastolic function.
Echocardiography:
Standard 2D and Doppler echocardiographic ex-
aminations were performed using commercially
available equipments (Sonos 5500, Philips Tech-
nologies, Andover, MA, USA, or Vivid-7, GE
Vingmed Sound, Horten, Norway). Both LV end-
diastolic volume (EDV) and end-systolic volume
(ESV) were calculated using the apical four- and
two-chamber views (biplane Simpson’s method)
and indexed by body surface area15; EF was cal-
culated by the standard formula. Regional wall
motion was assessed using a 16-segment model
of LV on a four-point grade scale.15Wall motion
score index (WMSI) was calculated as the sum of
the score of each segment, divided by the num-
ber of segments scored. Patients with mitral re-
gurgitation greater than mild (regurgitant jet area
≤4 cm2) were excluded.
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Hibernating Myocardium and Tei Index
LV MPI was derived from the mitral inflow and
LV outflow tract velocity time intervals, as shown
in Figure 1. Interval a (measured from cessation of
mitral inflow to the onset of subsequent mitral in-
flow) corresponds to the sum of the isovolumic
contraction time (ICT), ET, and isovolumic re-
laxation time (IRT). Interval b (corresponding to
the time interval from the onset of LV outflow
tract flow to its cessation) corresponds to LV
outflow ET. LV MPI was then calculated as (a –
b)/b, representing (ICT + IVRT)/ET (Fig. 1). For
all measurements, three consecutive cardiac cy-
cles were measured and averaged. Echocardio-
grams were recorded with a Super-VHS videotape
recorder, or digitally stored on optical disk. Sub-
sequent offline analysis was performed by two in-
vestigators without knowledge of clinical and an-
giographic data. Disagreements in interpretation
were resolved by consensus. Interobserver and in-
traobserver variability of echo measurements in
our laboratory were reported elsewhere.13Two
blinded observers independently calculated the
MPI in 15 randomly chosen patients, and also
repeated these measurements 5 days thereafter.
Fromthesemeasurements,wecalculated intraob-
server (5 ± 3%) and interobserver (7 ± 4%) vari-
ability.
Dobutamine Stress Echocardiography:
To assess LV contractile reserve, dobutamine was
infused i.v. at 5 mcg/kg for 5 minutes and in-
creasedupto15mcg/kgperminute,withstepsof
5minutes.Parasternallongandshortaxisandapi-
cal four- and two-chamber views were monitored
duringthestudy.WMSIwascalculated atbaseline
and at the end of dobutamine infusion. Myocar-
dial viability was defined by the improvement of
contractility of ≥1 grade from baseline in ≥2 ad-
jacent segments. Segments showing an ischemic
response during dobutamine infusion were also
considered as viable.16Both absolute number of
viable segments and viability index (number of
viable segments/numbers of total dysfunctional
segments) were computed.
Atfollow-up, LVsystolic anddiastolic functions
were reevaluated; a patient was classified as “re-
sponder” to revascularization if EF increased at
follow-up by ≥5% compared with baseline.17
Statistical Analysis:
Data are expressed as mean ± standard devia-
tion for continuous variables, or percentage for
categorical variables. Differences between groups
were compared by Student’s t-test for paramet-
ric data, and Mann-Whitney U test for nonpara-
metric data. Categorical variables were compared
by chi-square test (with Yates correction when
appropriate). Comparisons of echocardiographic
parameters at baseline, and at follow-up after
revascularization, among responders and non-
responders were made using repeated-measures
analysis of variance (SAS PROC GLM) to evaluate
the differences across time and between differ-
ent groups. Only if a statistical significance was
found, a t-test with Bonferroni correction was ap-
plied to all pairwise comparisons. To characterize
the predictors of functional recovery at follow-up
(?EF), univariable and multivariable linear regres-
sion analyses were performed including baseline
clinical (age and number of coronary vessels dis-
eased), echocardiographic (WMSI, EF, LV volume
indices, and MPI), and LDDE (changes in WMSI
and EF upon dobutamine infusion, and number
of viable segments) characteristics of the patients.
Only variables with P < 0.10 in univariable anal-
ysis were entered as covariates in the multivari-
able model. Multivariable regression was then
performed by stepwise backward selection.
Statistical analyses were handled by STATA
software (College Station, TX, USA), and SAS ver-
sion 9.2 (SAS Institute Inc, Cary, NC, USA). A P
value less than 0.05 was considered statistically
significant.
Results:
Clinical Findings:
Sixty eligible patients underwent myocardial
revascularization. Angioplasty was performed in
15 (29%) patients, and coronary artery bypass
graft in 37 (71%) patients. The modality of revas-
cularization was chosen by the attending physi-
cians, based on coronary anatomy and clinical
status. There were no periprocedural myocardial
infarctions. Of 60 revascularized patients, two
died before follow-up and five were lost at follow-
up. One patient was excluded because of acute
coronary syndrome prior to follow-up visit. The
remaining 52 patients constitute the final study
group. Table I summarizes baseline clinical and
demographic characteristics of the study popu-
lation. At the time of revascularization, all pa-
tients were receiving optimal medical therapy,
including beta blockers, angiotensin-converting
enzyme inhibitors/angiotensin receptor blockers,
and loop diuretics, as appropriate.
Baseline Parameters:
1) LVfunction
Table II, at baseline, the LV was enlarged,
and global and regional systolic functions
were depressed (EF = 32 ± 6%; WMSI =
2.37 ± 0.32). Baseline MPI was also im-
paired, averaging 0.71 ± 0.19, and it was
correlated to WMSI (r = 0.39, P = 0.0034).
2) Response to dobutamine: In the whole co-
hort, low-dose dobutamine infusion elicited
a substantial improvement of both EF (from
at rest:Asshown in
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Carluccio, et al.
TABLE I
Clinical Characteristics of Study Population
All patients (n = 52)
65 ± 9
43 (81)
1.87 ± 0.17
71 ± 12
126 ± 16
77 ± 10
2.86 ± 0.5
Age (years)
Male (%)
BSA (kg/m2)
Heart rate (beats/min)
Systolic BP (mmHg)
Diastolic BP (mmHg)
NYHA class
Risk factors
Hypertension (%)
Diabetes (%)†
Hypercholesterolemia (%)‡
Smoking (%)
Previous MI (%)
Medication
Beta-blocker (%)
ARB or ACEI
Diuretics (%)
Aspirin (%)
Coronary angiography
1-vessel disease (%)
2-vessel disease (%)
3-vessel disease (%)
Average degree of stenosis (%)
PTCA (%)
CABG (%)
∗
32 (62)
21 (40)
34 (65)
11 (21)
27 (52)
33 (63)
49 (94)
35 (67)
49 (94)
6 (12)
14 (27)
32 (62)
86 ± 12
15 (29)
37 (71)
ACEI = angiotensin-converting enzyme inhibitor; ARB = an-
giotensin receptor blocker; BP = blood pressure; BSA = body
surface area; LV = left ventricular; NYHA = New York Heart
Association; RBBB = right bundle branch block.
∗On therapy, or resting blood pressure >140/90 mmHg;†on
therapy, or fasting blood sugar >127 mg/dL;‡on therapy, or
total cholesterol >220 mg/dL.
32 ± 6% to 44 ± 9%, P < 0.0001) and
WMSI (from 2.37 ± 0.32 to 1.86 ± 0.35,
P < 0.0001), with an average of 5.6 ±
1.9 segments/patient showing contractile
recovery upon dobutamine infusion. An in-
verse relationship was observed between
baseline MPI and both absolute number of
viable segments (r = −0.47, P = 0.0004)
and viability index (r = −0.55, P < 0.0001,
Fig. 2), consistent with more severe im-
pairment of LV function associated with
poor contractile response to dobutamine
infusion.
LV Function after Revascularization:
At a median follow-up evaluation of 7 months
(IQ range: 5–10), all patients were in stable
clinical and hemodynamic conditions, and there
had been no major changes in medications since
enrollment. Table II compares the echocardio-
graphic parameters at baseline and follow-up
after revascularization in the whole population.
TABLE II
Echocardiographic Characteristics at Baseline and after
Revascularization
BaselineFollow-upP value
EDVI (mL)
ESVI (mL)
EF (%)
WMSI
ICT (ms)
IVRT (ms)
LV ET (ms)
MPI
119±28
80±26
32±6
2.37±0.32
83±55
102±27
264±34
0.71±0.19
102±31
59±26
44±10
1.77±0.44
61±64
104±24
289±38
0.59±0.26
<0.0001
<0.0001
<0.0001
<0.0001
0.0043
0.5889
<0.0001
<0.0001
ICT = isovolumic contraction time; IVRT = isovolumic relax-
ation time; LV = left ventricular; ET = ejection time.
As shown, EF (+11.6 ± 8.0%), WMSI (−0.60 ±
0.36,) and LV volume indices (EDVI = −16.2 ±
23 mL/m2, ESVI = −21.0 ± 20 mL/m2),
all significantly improved at follow-up compared
with baseline (P < 0.0001 for all; Table II),
with an average of 5.1 ± 2.9 segments/patient
showing
≥1
sistentwiththe response
observedatbaseline.
differences in EF improvement at follow-up
between patients who were treated with percu-
taneous and those who underwent surgical revas-
cularization (EF increase 10 ± 7% vs 11 ± 7%,
P = 0.710).
Improvement of LV function after revascular-
ization was accompanied by a significant im-
provement of MPI in the whole population
(−17%, P < 0.0001, Table II, Fig. 3A), and this
improvement was related to the number of seg-
ments with sustained improvement during dobu-
tamine infusion (r = −0.38, P = 0.0050), to the
gradeof improvement,
to
There
con-
dobutamine
wereno
Figure 2. Relation between viability index and baseline MPI
values: the lower the number of viable segments during dobu-
tamine infusion, the higher the MPI at baseline.
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Hibernating Myocardium and Tei Index
Figure 3. A. Individual changes in
MPI from baseline to follow-up. B. Re-
lationship between improvement in EF
after revascularization and changes in
MPI from baseline to follow-up: recov-
ery of systolic function was paralleled
by improvement in MPI.
viability index (r = −0.55, P < 0.0001), to the
number of segment that actually recovered func-
tion after revascularization (r = −0.37, P <
0.0055), and to the extent of EF recovery at
follow-up (r = −0.68, P < 0.0001, Fig. 3B).
At follow-up, there were no appreciable
changes in blood pressure (delta systolic BP =
−1 ± 0.7 mmHg, P = 0.735; delta diastolic
BP = 2 ± 0.9 mmHg, P = 0.403), and heart
rate (delta HR −3 ± 0.14 bpm, P = 0.169), com-
pared with baseline. Furthermore, in individual
patients, small changes in BP and HR from base-
line to follow-up were not directionally related to
changes in MPI (data not shown).
Responders versus Nonresponders:
Figure 3A depicts individual changes of MPI from
baseline to follow-up after revascularization. As
shown, MPI decreased in the majority of patients;
however, there were also patients in whom MPI
did not decrease, or tended to increase. There-
fore, to better understand the individual behav-
ior of MPI after revascularization and its relation
with LV function, we divided our patients into
two groups on the basis of whether or not they
recovered LV function at follow-up.
Based on >5% increase in LV EF at follow-
up, 40 patients were classified as responders.17At
baseline, clinical characteristics (Table III), as well
as LV volumes and function (Table IV), did not
significantly differ between responders and non-
responders. However, nonresponders showed
significantly fewer viable segments during dobu-
tamine challenge (P = 0.0001, Table IV), and
higher values of baseline MPI compared with re-
sponders (P = 0.0028, Table IV). In particular,
baseline MPI was significantly correlated to EF
improvement after revascularization (r = −0.50,
P = 0.0001; Fig. 4), and this association remained
significant (P = 0.035) even after controlling for
viability indices in multivariable linear regression
model (Table V).
As expected, LV volume indices, EF, and WMSI
significantly improved at follow-up in responders,
while they remained unchanged in nonrespon-
ders (Table IV).
MPI significantly decreased at follow-up in
responders (over time, P = 0.0018, repeated-
measures ANOVA), whereas no improvement was
observed in nonresponders. Therefore, at follow-
up, MPI remained significantly higher in nonre-
sponders compared with responders (P < 0.0001,
Table IV).
Components of MPI Improvement:
Changes in time interval components from base-
line to follow-up after revascularization are re-
ported in Table II, for the whole population. As
shown, at follow-up, ICT significantly decreased
(P = 0.0043), whereas IVRT did not substantially
change in the whole population. Consequently,
ET was significantly prolonged (P < 0.0001), re-
sulting in improvement (decrease) in MPI (P <
0.0001).
Changes in time interval components of MPI
in responders and nonresponders are reported in
Table IV. At baseline, responders had shorter ICT
compared with nonresponders (P = 0.0333), but
similar values of IVRT and duration of ejection
phase (ET). In responders, ICT decreased signif-
icantly at follow-up after revascularization (over
time P = 0.0365, repeated measures). In con-
trast, ICT did not significantly change in nonre-
sponders (P = 1.000). The IVRT did not signifi-
cantly change after revascularization (P = 1.000)
both in responders and nonresponders. The ET
significantly increased at follow-up in responders
(P = 0.0027) after revascularization, while there
was no significant change in ET in nonresponders
(Table IV).
Discussion:
The present study, which evaluates the effects
of myocardial revascularization on MPI in pa-
tients with ischemic cardiomyopathy and evi-
dence of myocardial viability, shows that: (1)
MPI decreased (i.e., improved) significantly af-
ter revascularization; (2) the improvement in MPI
was almost exclusively seen in patients who also
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Carluccio, et al.
TABLE III
Clinical Characteristics and Differences between Responders and Nonresponders
Responders
(n = 40)
65 ± 9
34 (85)
1.86 ± 0.18
70 ± 11
126 ± 16
78 ± 11
2.8 ± 0.6
Nonresponders
(n = 12)
67 ± 7
9 (75)
1.88 ± 0.13
73 ± 13
125 ± 14
75 ± 8
2.9 ± 0.8
P value
Age (years)
Male (%)
BSA (kg/m2)
Heart rate (beats/min)
Systolic BP (mmHg)
Diastolic BP (mmHg)
NYHA class
Risk factors
Hypertension (%)#
Diabetes (%)&
Hypercholesterolemia (%)§
Smoking (%)
Previous MI (%)
Medication
Beta-blocker (%)
ARB or ACEI
Diuretics (%)
Aspirin (%)
Coronary angiography
1-vessel disease (%)
2-vessel disease (%)
3-vessel disease (%)
Average degree of stenosis (%)
PTCA (%)
CABG (%)
0.5445
0.4219
0.7230
0.4130
0.8077
0.4600
26 (65)
18 (45)
28 (70)
10 (25)
19 (48)
6 (50)
3 (25)
6 (50)
1 (8)
8 (67)
0.349
0.216
0.202
0.215
0.244
25 (63)
38 (95)
27 (68)
38 (95)
8 (67)
11 (92)
8 (67)
11 (92)
0.928
0.664
0.957
0.664
4 (10)
10 (25)
26 (65)
88 ± 12
10 (25)
30 (75)
2 (17)
4 (33)
6 (50)
82 ± 13
5 (42)
7 (58)
0.880
0.859
0.549
0.1708
0.264
0.264
Abbreviations as in Table I.
showed significant recovery of EF; (3) MPI im-
provement was related to the extent of viable
myocardium undergoing revascularization; and
(4) improvement in MPI was largely driven by a
significant reduction in ICT with consequent pro-
longation of the ejection phase. To our knowl-
edge, these findings have not been previously
reported.
MPI has been shown to be a useful index of
LV function. Its main advantages are that it ap-
pears to be rather independent from geometric
assumption18and heart rate,10and to be simple,
TABLE IV
Echocardiographic Characteristics between Responders and Nonresponders
Baseline (n = 40)
Resp
Follow-up (n = 12)
RespNonrespP value Nonresp P value
EDVI (mL)
ESVI (mL)
EF (%)
WMSI
ICT (ms)
IVRT (ms)
LV ET (ms)
MPI
No. of viable segments
No. of recovered segments
119±27
80±26
33±6
2.33±0.33
72±54
102±27
267±32
0.66±0.17
6.1±1.7
–
117±32
82±26
30±5
2.49±0.26
121±44
99±27
252±39
0.88±0.16
3.8±1.3
–
1.000
1.000
1.000
0.7808
0.0333
0.7447
1.0000
0.0028
0.0001
96±28
51±22†
47±8†
1.61±0.37†
40±46‡
105±19§
296 ± 32¶
0.50±0.19#
–
6.2±2.2
∗
125±28
86±19
31±5
2.29±0.23
132±68
99±36
268±48
0.88±0.24
–
1.3±0.9
0.0152
0.0002
<0.0001
<0.0001
<0.0001
0.4245
0.0952
<0.0001
–
<0.0001
∗P = 0.0019 vs. baseline. Resp;†P < 0.0001 vs. baseline Resp;‡P = 0.0365 vs. baseline Resp;§P = 1.0000 vs. baseline Resp;
¶P = 0.0027 vs. baseline Resp;#P = 0.0018 vs. baseline Resp.
P values were calculated using repeated-measures ANOVA (differences over time).
6

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Hibernating Myocardium and Tei Index
Figure 4. Relationship between MPI at baseline and change
in LV EF after revascularization. The improvement in EF at
follow-up decreased with increasing values of MPI at baseline.
easy to obtain, and reproducible. Furthermore,
it has been shown to correlate with invasive19
measures of peak (+) dP/dt and (−) dP/dt,20,21
and it represents a unique index of both systolic
anddiastolicglobalventricularfunction.3,4Infact,
MPI may reflect systolic dysfunction through a
shortened ET and a lengthened ICT, and diastolic
dysfunction through a lengthened isovolumic re-
laxation time. Consequently, worsened LV per-
formance would increase MPI, whereas improved
performanceisexpectedtodecreaseMPI.Indeed,
in patients with dilated cardiomyopathy or my-
ocardial infarction, deterioration of LV function
over time is closely matched by progressive in-
crease in MPI.22By this same token, interventions
capable to reduce the isovolumic times and/or to
increase the ejection phase should reduce MPI,
consistent with the improvement in LV perfor-
mance. However, this crucial piece of information
had not been previously obtained.
In our study, revascularization of viable my-
ocardium was associated with a significant short-
ening in ICT and prolongation of LV ET at
follow-up, likely reflecting enhanced ventricular
function, so that MPI resulted significantly re-
duced at follow-up. Previous studies by many in-
vestigators, including our group, have shown that
revascularization of viable but dyssynergic my-
ocardiumresultsinsubstantialimprovementofLV
global and regional systolic function,11,16,17vol-
umes and geometry,13and diastolic function.12
However, the behavior of MPI in hibernating my-
ocardium, and its relation to LV functional im-
provement after revascularization, has not been
previouslyinvestigated.Importantly,thedecrease
of MPI seen in our study occurred in the absence
of appreciable changes in heart rate, blood pres-
sure, or loading conditions, while therapy also re-
mained unchanged. This indicates that MPI im-
provement was due to a primary improvement
TABLE V
Univariable and Multivariable Linear Regression Analysis:
Predictors of Recovery of Function after Revascularization
Univariable
Analysis
Multivariable
Analysis
BetaPCoefficientP
Age
No. of diseased
vessels
WMSI at
baseline
?WMSI during
LDDE
EDVI
ESVI
MPI at baseline
EF at baseline
?EF during
LDDE
No. of viable
segments
0.073
−0.06
0.604
0.641
−0.280.047
0.50
<0.0001
−0–07
−0.13
−0.50
0.23
0.34
0.578
0.346
<0.0001
0.103
0.015
−9.135 0.035
0.64
<0.00011.836
< 0.0001
EDVI = end-diastolic volume index; ESVI = end-systolic vol-
ume index; LDDE = low-dose dobutamine echo; MPI = my-
ocardial performance index; WMSI = wall motion score index.
of cardiac function (brought about by revascular-
ization), and not to other effects. The direct role
of effective myocardial revascularization is further
supported by the finding that MPI did not appre-
ciably change in the patients in whom EF did not
improve at follow-up, and by the finding that MPI
decrease was significantly related to the number
of dyssynergic segments that recovered function
after revascularization.
In the present study, a high value of MPI at
baseline was significantly associated to failure of
EF to improve after revascularization. This asso-
ciation remained significant even after control-
ling for viability indices in multivariable model
(Table V). Failure of LV function to improve af-
ter revascularization (despite the presence of vi-
able myocardium) represents a well-recognized
problem in clinical practice, and it accounts for
suboptimal specificity of diagnostic tests of my-
ocardial viability.23It has been suggested that
one important mechanism for the failure of viable
myocardium to recover function after revascular-
ization is the presence of extensive LV remodel-
ing at baseline. Bax et al.24evaluated 44 patients
with ischemic cardiomyopathy and evidence of
myocardial viability. They showed that the im-
provement in LV EF after revascularization was in-
versely related to baseline LV ESV, a higher LV ESV
being associated with a lower likelihood of im-
provement in LV EF after revascularization. Exten-
sive LV remodeling may further impair myocardial
performance and contraction efficiency,25with a
7

Page 8

Carluccio, et al.
consequent prolongation of isovolumic times and
reduction in the ejection phase.26In the present
study, we have evaluated the relation between
viability,MPI,andimprovementinLVEFatfollow-
up after revascularization. As expected, a signifi-
cant recovery of LV function after revasculariza-
tion was observed in most patients with viable
myocardium; however, there were also 12 (23%)
patients with viable myocardium who did not
improve after revascularization (nonresponders),
and whose baseline MPI values were significantly
higher than responders.
It is well known that the time course of re-
covery of function after revascularization may be
largely variable in viable segments, and the prob-
ability of recovery may be related to the severity
of myocardial damage.11In the present study,
echocardiographic evaluation at follow-up was
performed after a median time of 7 months (IQ
range: 5–10). In particular, none of our patients
had a follow-up evaluation after revascularization
less than 4 months so that the probability to have
patients who lack functional recovery was very
low. The duration of follow-up in our study did
not differ from that of other viability studies per-
formed in this kind of patients.9,11,13,14,16,17Such
a duration of follow-up seems to be sufficient
to appreciate a discrete recovery of LV function
secondary to revascularization of hibernating my-
ocardium. On the other hand, longer follow-up
evaluation may have the risk of altered findings. In
fact, histopathologic studies have suggested that
there may be a progressive increase of ultrastruc-
tural damage and of percentage of fibrosis as the
duration of follow-up evaluation increases.27,28
Limitations:
This study has some limitations. The sample size
of the study population is relatively small. This
was due to the design aimed at including pa-
tients with evidence of substantial myocardial vi-
ability by low-dose dobutamine echocardiogra-
phy and without extensive areas of scar tissue.
However, the results of the study are consistent,
and they may be interpreted as mostly prelimi-
nary findings, useful for large clinical study. The
MPI has also its disadvantages in that it is de-
rived from LV inflow and outflow Doppler veloc-
ities from two separate imaging planes that can-
not be recorded simultaneously. Importantly, it
cannot be measured in patients with atrial fibrilla-
tion, frequent ventricular ectopic beats, intraven-
tricular or atrioventricular conduction delay, and
paced rhythm. We excluded patients with these
characteristics, and therefore, our data may not
be applicable to all patients with chronic ischemic
cardiomyopathy.Inthisstudy,wepooledpatients
who received percutaneous or surgical revascu-
larization. It is known that these procedures may
differently affect LV function after revasculariza-
tion. However, no significant differences in LV
function improvement at follow-up were seen
in our population between patients undergoing
percutaneous and surgical revascularization (EF
increase at follow-up 10 ± 7% vs 11 ± 7%,
P = 0.710). Angiographic follow-up was not sys-
tematically performed after revascularization in
our patients. Graft occlusion or stent restenosis
may have occurred in some patients preventing
adequate recovery of function during follow-up.
However, none of the patients experienced new
symptoms of angina or had hospital readmission
because of acute coronary syndromes during the
follow-up period before echocardiographic eval-
uation.
Conclusions:
Ourobservations describethechangesin Doppler
MPI before and after revascularization in patients
with chronic ischemic cardiomyopathy and viable
myocardium, and indicate that intrinsic improve-
ment of cardiac function at follow-up is closely
paralleledbyimprovementofMPI.Therefore,MPI
may reliably reflect the changes of overall LV per-
formance over time.
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