(Circulation. 2001;103:1232.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
Deceleration Time in Ischemic Cardiomyopathy
Relation to Echocardiographic and Scintigraphic Indices of Myocardial Viability and Functional Recovery After Revascularization
From the Section of Cardiology, Department of Medicine (Y.Y., S.F.N., S.S., K.S., Z.-X.H., M.S.V., M.A.Q., W.A.Z.), and the Department of Surgery (M.J.R., G.V.L., J.F.H.), Baylor College of Medicine, Houston, Tex.
Correspondence and reprint requests to Sherif F. Nagueh, MD, 6550 Fannin St, SM-1246, Houston, Texas 77030-2717. E-mail sherifn{at}bcm.tmc.edu
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Abstract |
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 Top Abstract IntroductionMethodsResultsDiscussionReferences |
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Background—In patients with heart failure secondary to left ventricular (LV) systolic dysfunction, a short deceleration time (DT) successfully predicts clinical outcome. The impact of myocardial viability and revascularization on the mitral inflow velocities, however, is unknown.
Methods and
Results—Forty patients with ischemic
cardiomyopathy underwent 201Tl scintigraphy
(SPECT) and 2D, Doppler, and dobutamine echocardiography (DE, to 40
µg · kg-1 · min-1)
2 days before CABG. Echocardiography was repeated 3 months after
revascularization to determine recovery of function. Significant
correlations were present between DT and LV contractile reserve by DE
(r=0.72), scar perfusion defect
by SPECT (r=-0.69), and the
change in ejection fraction (
EF) after surgery
(r=0.77) (all
P<0.01). DT >150 ms
effectively identified (sensitivity 79%, specificity 81%) patients
with EF 
5%. The population was divided into 2 groups according to
DT: group 1 (DT >150 ms, n=21) and group 2 (DT 
150 ms, n=19). At
baseline, NYHA class, LV EF, age, and use of cardiovascular drugs were
similar between the 2 groups. The number of viable segments by both DE
and SPECT, however, was higher in group 1 (both
P<0.01), and only patients in
group 1 had an increase in EF (29±4.8% to 40±8%,
P<0.01) after surgery. Death
and heart transplantation occurred in 7 patients from group 2 and 1
patient from group 1
(P=0.017).
Conclusions—In patients with ischemic cardiomyopathy, the reduced amount of viable myocardium results in a restrictive mitral inflow pattern, which in turn predicts poor survival.
Key Words: echocardiography • scintigraphy • cardiomyopathy • hibernation • diastole
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Introduction |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Doppler echocardiography provides unique information that is helpful in the management of patients with congestive heart failure (CHF). In particular, the mitral inflow pattern accurately predicts left ventricular (LV) filling pressures and survival in patients with CHF secondary to LV systolic dysfunction.1 2 3 4 5 6 Although a persistently restrictive mitral inflow pattern with a short early diastolic (E) velocity deceleration time (DT) despite optimal medical therapy is associated with an advanced NYHA class and poor survival, the impact of myocardial viability and revascularization on the mitral inflow velocities is unknown. We postulated that in patients with ischemic cardiomyopathy (IC), the mitral inflow pattern is critically dependent on the amount of viable myocardium. Therefore, we sought to evaluate the relation between the DT of the E velocity and the echocardiographic and scintigraphic indices of myocardial viability and functional recovery in patients with IC. We also examined the changes in the Doppler pattern after revascularization.
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Methods |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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The Baylor College of Medicine Institutional Review Board approved the investigation, and all patients provided written, informed consent before their participation. The study population was composed of 40 patients with LV systolic dysfunction secondary to IC who were scheduled to undergo CABG. None of the patients had evidence of an acute coronary syndrome, valvular heart disease, or primary cardiomyopathy, and all had moderate to severe LV systolic dysfunction at rest.
Echocardiographic Studies
Echocardiographic studies were performed with either
a Hewlett-Packard (5500) or an Acuson (Sequoia) ultrasound system an
average of 2 days before revascularization. All patients were able to
lie supine without dyspnea and were imaged in a left lateral position.
Standard parasternal and apical views were acquired first, and mitral
inflow was recorded by pulse Doppler in the apical 4-chamber view, with
the sample volume positioned at the valve
tips.7 Dobutamine infusion
(DE) was initiated at a dose of 2.5
µg · kg-1 · min-1
and advanced at 3-minute intervals to 5, 7.5, 10, 20, 30, and 40
µg · kg-1
· min-1.8
Continuous monitoring of ECG and blood pressure was performed
throughout the infusion. Images were recorded on both videotape and
digital format for later analysis. Three months after surgery, the
patients’ LV systolic function and mitral inflow velocities were
reevaluated with a resting echocardiographic
study.
Echocardiographic Analysis
Analysis was performed by 2 observers blinded to the
clinical, scintigraphic, and each other’s data. Observer A (Y.Y.)
measured only the following parameters: mitral inflow peak E velocity,
peak filling velocity at atrial contraction (A velocity), E/A
ratio, acceleration time and DT of peak E velocity, isovolumic
relaxation time (IVRT), A duration, and the atrial filling fraction
(AFF). Measurements were made in 3 cardiac cycles and averaged by
previously reported
techniques.7 Observer B
(S.F.N.), who was unaware of the Doppler data and sequence of studies,
interpreted the 2D echocardiogram. LV ejection fraction (EF) was
calculated with the multiple-disk
method9 at baseline, during
DE (at 10
µg · kg-1 · min-1),
and 3 months after surgery. The numbers of viable and nonviable
segments were derived from the response to dobutamine. Segments with
any response were considered viable, including segments with a
biphasic, sustained, and ischemic
response.8 We recently
observed10 that segments
defined as viable by the above criteria have significantly less
interstitial fibrosis (2% to 3%) than segments without any
contractile response to dobutamine (28%). LV contractile reserve was
computed as the difference between the highest EF measured during
low-dose DE and that at baseline.
SPECT Myocardial Scintigraphy
Rest-redistribution 201Tl
scintigraphy (single photon emission CT, SPECT) was performed as
previously reported from our
laboratory.10 A
large-field-of-view rotating gamma camera with a high-resolution
parallel-hole collimator was used. Thirty-two frames were acquired over
a 180° arc. The images were reconstructed with a filtered
back-projection algorithm and a Butterworth filter with a cutoff
frequency of 0.5 Nyquist and an order of 5. Reconstructed tomograms
were reoriented in the standard short, horizontal long, and vertical
long axes for interpretation and quantification. Experienced
nuclear cardiologists who had no knowledge of any other patient data
quantified SPECT images. Defect size was derived by the polar map
method. The raw polar maps for each patient were statistically compared
with a corresponding normal data bank to determine the perfusion defect
size. Segments with a maximal uptake (rest or redistribution) of 60%
were considered
viable.10
Statistical Analysis
Unpaired Student’s
t or
2 tests were used to compare the
clinical, echocardiographic, and scintigraphic data between the 2
groups of patients as divided by DT. Paired
t testing was applied to
compare the changes in EF and mitral velocities after revascularization
in each group. The 3 groups of patients divided by baseline DT and
change in EF (EF) after surgery were compared by ANOVA and
Bonferroni-corrected t tests
for pairwise comparisons. Regression analysis was used to relate DT to
both DE and SPECT indices of viability, EF, and duration of stay in
the intensive care unit (ICU). Significance was set at a value of
P<0.05.
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Results |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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All 40 patients had symptoms of heart failure before surgery, and the majority complained of angina (62%). Before the baseline echocardiographic study and after clinical evaluation, attempts were made to maximize cardiac medications, and doses were advanced as tolerated. Typical medication regimens included ACE inhibitors (captopril, average daily dose 90 mg; lisinopril, 20 mg), nitrates (isosorbide dinitrate 90 mg), diuretics (furosemide 80 mg, metolazone 2.5 mg), ß-blockers (metoprolol 75 mg), and digoxin (0.25 mg).
Relation of Mitral Inflow Pattern to DE
Indices of Viability
Significant correlations were observed between DT and
LV contractile reserve (r=0.72,
r2=0.52,
P<0.01;
Figure 1
, left) and the number of viable segments
(r=0.84,
r2=0.71,
P<0.01;
Figure 1, right). Other Doppler parameters with significant
correlation to LV contractile reserve included IVRT,
r=0.46; AFF,
r=0.5; and the E/A ratio,
r=-0.58 (all
P<0.01). The number of viable
segments by DE was also related to IVRT
(r=0.5,
P<0.01), AFF
(r=0.44,
P<0.01), and E/A ratio
(r=-0.58,
P<0.01). The mitral inflow
pattern (DT >150 ms) was similar in patients in whom 50% of the
segments showed a biphasic or ischemic or sustained response
(P>0.1).
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Relation of Mitral Inflow Pattern to SPECT
Indices of Viability
Significant correlations were observed between DT and
the perfusion defect size by SPECT (total defect,
r=-0.5; % scar,
r=-0.69; both
P<0.01)
(Figure 2, right). Furthermore, a direct relation was noted
between the number of viable segments by SPECT and DT
(r=0.76,
P<0.01;
Figure 2, left). Other Doppler parameters likewise had
significant relations with SPECT indices of viability (number of viable
segments by SPECT versus AFF,
r=0.45; IVRT,
r=0.4; and E/A ratio,
r=-0.5;
P<0.05). DT was >150 ms in
patients with 50% of segments having 50% or 60% thallium
uptake (P>0.1) but was 150
ms in patients in whom 50% of the segments had thallium uptake
<50%
(P=0.03).
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Relation of Functional Recovery to the Mitral
Inflow Pattern, DE, and SPECT Indices of Viability
Significant relations were also observed between EF
at 3 months and DT as well as the number of viable segments by both DE
and SPECT (r=0.77,
r=0.83,
r=0.82, respectively, all
P<0.01;
Figure 3). With a receiver operating characteristic curve, a
DT >150 ms provided the best separation of patients with a EF >5%
and <5% (sensitivity 79%, specificity 81%).
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Several models were constructed to predict EF after
revascularization by DT and echocardiographic and scintigraphic indices
of myocardial viability. These variables in different combinations
accounted for 71% to 77% of the variance in the EF (number of
viable segments by DE and DT accounted for 71%,
r=0.84; number of viable
segments by SPECT and DT accounted for 72%,
r=0.85; and number of viable
segments by DE plus number of viable segments by SPECT accounted for
77%,
r=0.88).
Patient Groups and Clinical Outcome
Subsequently, we divided the patient cohort into 2
groups based on DT: group 1, DT >150 ms and group 2, DT 150 ms. At
baseline, age, NYHA class, LVEF, heart rate, and cardiac medications
were similar in both groups
(Table 1).
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By design, the 2 groups differed significantly in all
parameters derived from the mitral inflow velocity. Group 2 patients
had a higher E/A ratio, a shorter DT, and a lower AFF than group 1
patients
(Table 2). Importantly, DE indices of viability were
different between the 2 groups; group 1 patients had a significantly
higher contractile reserve and a greater number of viable segments than
did group 2 patients (both
P<0.001). Likewise, the total
defect size by SPECT (P=0.015)
and the scar percentage
(P=0.002) were larger in group
2. At follow-up 3 months later, LVEF by echocardiography increased
significantly in group 1 (29±4.8 to 40±8,
P<0.001) yet remained
unchanged in group 2 (27±8.6 to 27±10,
P=0.42).
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The clinical course also differed remarkably in the 2 groups
(Table 3). Group 1 patients had a shorter ICU stay, fewer
admissions for exacerbation of heart failure, and lower use of
diuretics after surgery (all
P<0.05). At 1 year, of the 19
patients with a DT 150 ms, 3 had died of progressive heart failure, 1
had died of sudden death, and 3 had undergone heart transplantation.
Among the 21 patients with a DT >150 ms, only 1 died of sepsis
(P=0.017). In the 40 patients
combined, significant relations were present between DT
(r=-0.73), both DE
(r=-0.67) and SPECT
(r=-0.65) indices of
viability, and duration of ICU stay (all
P<0.01).
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Doppler Velocities After Revascularization and
Their Relation to Viability and Clinical Outcome
Six group 2 patients (baseline DT 150 ms; 2a) had an
increase in DT after surgery of 40 ms (> mean±2 SD of interobserver
difference), whereas 13 patients had a shorter or unchanged DT (2b). In
the former 6 patients, DT increased from 113±27 to 184±31 ms
(P=0.004). Similarly,
consistent with an improvement in the diastolic filling pattern and
lower filling pressures, E/A ratio decreased (2.5±1.4 to 1.1±0.5,
P=0.06) and AFF (0.2±0.09 to
0.35±0.14, P=0.06) and IVRT
(70±16 to 97±34, P=0.03)
increased. Each patient in this subset had viable dysfunctional
segments and an improvement in LVEF
(Table 4). Furthermore, 5 of the 6 patients had a 2-grade
decrease in NYHA class, and 1 patient improved by 1 grade. In this
subset, there were no admissions for CHF, no deaths, and no heart
transplantations (P=0.04 versus
the remaining 13 group 2 patients).
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Conversely, the remaining 13 patients (2b) had further
shortening in DT (110±24 to 97±19 ms,
P<0.01) and IVRT (67±19 to
55±20 ms, P=0.002), along with
an increase in E/A ratio (2±0.8 to 3±1.4,
P=0.009) and a decrease in AFF
(0.21±0.14 to 0.17±0.1,
P=0.035). The number of viable
dysfunctional segments was small, and EF was minimal (range -6%
to 1%). Importantly, the 7 events of death or heart transplantation
occurred in this subgroup.
In group 1, overall DT was essentially unchanged (258±65 to 250±103 ms). Only 2 patients had shortening of DT (276 to 78 and 219 to 100 ms, respectively), 1 in the context of unstable angina and symptoms of pulmonary congestion and the other in the setting of acute myocardial infarction.
All 40 patients were then divided into 3 groups based on
baseline DT and change in EF after revascularization. Patients with few
viable dysfunctional segments (number of segments 1 to 3 by both DE and
SPECT) had a short DT at baseline and failed to recover systolic
function after surgery. As the number of viable segments increased (5
to 7 segments by DE and SPECT), EF increased after surgery, but DT was
still 150 ms at baseline. With further increase in the indices of
viability (9 to 10 viable segments by DE and SPECT), DT became >150 ms
(baseline value), and after revascularization the majority (19 of 21)
of these patients exhibited an improvement in EF (ANOVA,
P<0.001; all pairwise multiple
comparisons with P<0.03 for
number of viable segments by both DE and SPECT).
As expected, EF after surgery also was different between
the 3 groups: patients with 1 to 3 viable segments had no increase in
EF, those with 5 to 7 segments had an increment of 6.8±1.8%, and the
patients with 9 to 10 segments had the largest increase: 9.6±4%
(ANOVA, P<0.001; all pairwise
multiple comparisons,
P<0.05).
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Our study shows a strong association of the mitral inflow pattern with indices of myocardial viability in patients with IC undergoing CABG. These results help explain the association of DT with survival. As shown, when DT was
150 ms, DE and SPECT indices of
viability were reduced. Another important and novel finding of our
investigation is the ability of DT to predict functional recovery after
revascularization.
Relation Between DT, Myocardial Viability, and
Survival in Patients With IC
We observed a strong inverse correlation between DT and
the number of viable segments by both DE and SPECT. The presence of a
short DT was associated with a smaller number of viable segments, a
lack of recovery of LV systolic function, and a worse clinical outcome
after revascularization. These results were derived from a population
undergoing CABG and may not be applicable to patients who are deemed
unsuitable for mechanical revascularization. Nevertheless, we believe
that the associations between DT and viability indices help elucidate
the mechanism linking the mitral inflow pattern to survival in IC
patients. There is currently strong evidence that the presence and
extent of myocardial viability have a significant impact on the
clinical outcome of patients with IC. These observations have been
consistent irrespective of the imaging modality used or whether
viability is defined as preserved cellular metabolism by
PET,11 perfusion by either
SPECT12 or contrast
echocardiography,13 or
contractile
reserve.14 15
Therefore, the reduced amount of viable myocardium accounts for the
worse survival in those patients with IC who exhibit a restrictive
mitral inflow pattern.
A particularly interesting observation in this study is the
interaction of myocardial viability, mitral inflow velocities, and
functional recovery after revascularization in patients with a short
DT. As noted above, in the presence of 5 to 7 viable segments (by both
DE and SPECT), LV systolic function can improve despite the presence of
a DT 150 ms. In these patients, the mitral inflow pattern improves
after surgery corresponding to a reduction in filling pressures. It is
probable that the relief of ischemia and the improvement in systolic
function after revascularization lead to the observed changes in
diastolic function. It is also possible that myocyte (and myocardial)
elasticity normalizes with successful revascularization of the
hibernating myocardium, leading to a reduction in LV stiffness and
filling pressures and hence the changes in the mitral inflow
pattern.
Reasons for a Short DT in Patients With
IC
In patients with IC, replacement fibrosis occurs
secondary to myocardial necrosis that develops because of prolonged
repetitive ischemia and/or infarction. We have previously
shown10 that nonviable
segments by DE have a larger amount of fibrosis. Likewise,
we10 16 and
others17 18 have
noted a strong relationship between viability assessed by SPECT (both
201Tl and 99mTc)
and regional fibrosis. Therefore, IC patients with large amounts of
nonviable myocardium have more extensive fibrosis.
In patients with IC, DT has been shown to be highly predictive of filling pressures.19 20 In addition, Himura et al21 showed a good correlation between the mitral inflow pattern and late diastolic LV stiffness in patients with a reduced EF. Data from an animal model of pacing-induced heart failure indicate that DT has a strong relation with LV stiffness.22 23 Therefore, the short DT in IC patients is the result of increased chamber stiffness. We believe that the increased interstitial fibrosis is in all likelihood the cause of the abnormal stiffness of IC hearts. There is ample evidence relating LV stiffness and fibrosis in animal models and in patients. For example, animal data show that regression of interstitial collagen is accompanied by an improvement in LV compliance.24 Likewise, in the clinical arena, studies have shown a strong relation of fibrosis to LV stiffness in patients with aortic valve disease.25 Similar to the findings in animal studies, a long-term reduction in filling pressures was associated with a decrease in LV fibrous tissue content after valve replacement. Therefore, it is reasonable to conclude that advanced interstitial fibrosis plays an important pathophysiological role in increasing both stiffness and filling pressures in patients with IC and that this results in a restrictive mitral inflow pattern.
Conclusions
The reduced amount of viable myocardium may be the link
that explains why the restrictive mitral inflow pattern is a powerful
predictor of survival in patients with
IC.1 2 3 4 5 6
More importantly, our study identifies the mitral inflow pattern as a
potential predictor of viability and functional recovery in patients
with myocardial hibernation. In the presence of 5 to 7 viable
segments, however, EF may still improve after revascularization despite
a short
DT.
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Acknowledgments |
|---|
Dr Nagueh is supported by a Scientist Development Grant (0030235N) from the American Heart Association, National Center, Dallas, Tex. We thank Maria Frias for her assistance.
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Footnotes |
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Guest Editor for this article was A. Jamil Tajik, Mayo Clinic, Rochester, Minn.
Received August 10, 2000; revision received October 13, 2000; accepted November 11, 2000.
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G. A. Whalley, R. N. Doughty, G. D. Gamble, S. P. Wright, H. J. Walsh, S. A. Muncaster, and N. Sharpe Pseudonormal mitral filling pattern predicts hospital re-admission in patients with congestive heart failure J. Am. Coll. Cardiol., June 5, 2002; 39(11): 1787 - 1795. [Abstract] [Full Text] [PDF]
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