Comparison of real-time contrast echocardiography and low-dose dobutamine stress echocardiography in predicting the left ventricular functional recovery in patients after acute myocardial

www.elsevier.com/locate/ijcard

International Journal of Cardi

Comparison of real-time contrast echocardiography and low-dose

dobutamine stress echocardiography in predicting the left ventricular

functional recovery in patients after acute myocardial infarction

under different therapeutic interventionB

Wei-Chun Huanga, Kuan-Rau Chioua,b, Chun-Peng Liua,b, Shoa-Lin Lina,b,T, Doyal Leea,Guang-Yuan Mara, Shih-Hung Hsiaoa, Ming-Ho Kunga, Chuen-Wang Chioua,b, Tzu-Wen Linc

aDivision of Cardiology, Kaohsiung Veterans General Hospital, No.386, Dar-Chung First Road, Kaohsiung City, Taiwan, ROCbNational Yang-Ming University, School of Medicine, Taipei City, Taiwan, ROC

cChengshiu Institute of Technology, Kaohsiung City, Taiwan, ROC

Received 22 March 2004; received in revised form 13 August 2004; accepted 12 December 2004

Available online 19 March 2005

Abstract

Background: Early prediction of left ventricular (LV) functional recovery after acute myocardial infarction (AMI) remains challenging. This

prospective study aims to compare real-time myocardial contrast echocardiography (MCE) with low-dose dobutamine stress

echocardiography (LDDSE) in predicting the LV functional recovery in patients after AMI who underwent different therapeutic

interventions.

Methods: Ninety-two patients with AMI were divided into 3 groups: primary coronary intervention group (n=34), thrombolysis group (n=30)

and conservative therapy group (n=28). MCE was performed 2.3F0.7 days after chest pain onset. LDDSE was done within 2 days of MCE

study. Follow-up echocardiography was performed 4 months later.

Results: Patients treated by primary coronary intervention or thrombolysis had significantly lower regional perfusion score (0.65F0.53 vs.

1.01F0.49, p=0.008; 0.78F0.55 vs. 1.01F0.49, p=0.03), better contractile reserve (regional dobutamine Dwall motion score -1.12F0.39 vs.

�0.80F0.43, p=0.01; �0.99F0.50 vs. �0.80F0.43, p=0.08) and LV function recovery (regional Dwall motion score �1.67F0.53 vs.

�1.02F0.46, p=0.003; �1.42F0.58 vs. �1.02F0.46, p=0.03) than those of conservative therapy group. MCE and LDDSE showed good

concordance for predicting LV functional recovery (kappa=0.63, pb0.001). Perfusion score index had a good correlation with LV functional

recovery (r=�0.75, pb0.001).

Conclusions: This study demonstrates that perfusion score index obtained from real-time MCE is comparable to LDDSE in predicting the LV

functional recovery even under different therapeutic interventions. Revascularization results in better preservation of myocardial

microvascular integrity, regional contractile reserve and LV functional recovery.

D 2005 Elsevier Ireland Ltd. All rights reserved.

Keywords: Acute myocardial infarction; Low-dose dobutamine stress echocardiography; Myocardial contrast echocardiography; Primary coronary

intervention; Thrombolysis

0167-5273/$ - see front matter D 2005 Elsevier Ireland Ltd. All rights reserved.

doi:10.1016/j.ijcard.2004.12.022

B Supported in part by the Kaohsiung Veterans General Hospital, Grant

No. VGHKS 91-41, and by Veterans General Hospital, Tsin-Hua, Yang-

Ming Research Program, Grant No. VTY 92-G3-03.

T Corresponding author. Division of Cardiology, Kaohsiung Veterans

General Hospital, No.386, Dar-Chung First Road, Kaohsiung City, Taiwan,

ROC. Tel.: +886 7346 8278; fax: +886 7350 5220.

E-mail address: [email protected] (S.-L. Lin).

1. Introduction

In the process of left ventricular (LV) functional recovery

after acute myocardial infarction (AMI), infarct size,

location, transmurality, patency of infarct related artery,

microvascular integrity and different therapeutic interven-

ology 104 (2005) 81–91

Fig. 1. Real-time myocardial contrast echocardiographic images of a patient with first acute anterior myocardial infarction at end-diastole (left panel) and end-

systole (right panel). This patient received conservative therapy due to late arrival to our hospital and follow-up coronary angiography showed 95% stenosis of

left anterior descending coronary artery. Arrows showed mid-septal, apical–septal and apex segments without contrast opacification i.e. non-viable

myocardium, which correlated well with non-viable area at follow up two-dimensional echocardiograms 4-month later.

W.-C. Huang et al. / International Journal of Cardiology 104 (2005) 81–9182

tions are involved [1]. Early prediction of LV functional

recovery after AMI remains challenging [2]. Low-dose

dobutamine stress echocardiography (LDDSE) is a good

choice of imaging modality to assess LV functional recovery

and myocardial viability [3].

Myocardial contrast echocardiography (MCE) is a new

technique to evaluate coronary artery disease in a simple,

noninvasive, easily accessible, and cost-effective manner

[4,5] (Fig. 1). It has been demonstrated that intracoronary

[6,7] and intravenous [8,9] MCE allows prediction of LV

functional recovery after primary percutaneous coronary

intervention in patients with AMI. Application of MCE may

have incremental value to the LDDSE for the prediction of

functional recovery in patients after AMI [10]. The non-

invasive evaluation of the impact of different therapy

strategies including primary coronary intervention, throm-

bolysis or conservative therapy may have clinical signifi-

cance. However, there exists no published data on the

comparison of real-time MCE and LDDSE in early

predicting LV functional recovery in patients after AMI

with special emphasis on different therapeutic approaches.

The prospective study was undertaken to compare MCE

with LDDSE in early prediction of LV functional recovery

under different therapeutic interventions.

2. Materials and methods

2.1. Patients

Between May 2002 and February 2004, one-hundred

and fifteen consecutive patients with first Q-wave AMI

were admitted in our hospital. Diagnosis of AMI was

made on the basis of typical anginal pain lasting more than

30 min, ST-segment elevation z0.2 mV in z2 contiguous

electrocardiogram leads, biochemical evidence of peak

creatine kinase more than 2 times of upper limit of normal,

and wall motion abnormalities by echocardiography.

Criteria for exclusion included the following: postinfarct

angina, in hospital reinfarction, persistent LV failure,

significant ventricular arrhythmias, significant valvular

disease or primary myocardial disease, left bundle branch

block, paced rhythm, patients who died within the first 72

h, allergy to blood products and previous myocardial

infarction and total occlusion of infarct-related artery by

follow-up angiography. Twenty-three of 115 patients were

excluded, including: three underwent rescue coronary

intervention due to post-infarct angina, four died during

follow-up periods, three lost follow-up and others (13

cases) due to total occlusion of infarct-related artery by

follow-up angiography. Therefore, a total of 92 patients

were included in the study. All but 9 patients were men

(mean age 63.5F14.5 years). We divided all patients into 3

groups: primary coronary intervention group (34 patients),

thrombolysis group (30 patients) and conservative therapy

group (28 patients).

2.2. Study protocol

During hospitalization, peak creatine kinase level was

acquired from serial measurements every 6 h. All patients

received baseline two-dimensional echocardiography at the

same time as MCE, underwent both MCE and LDDSE

during hospitalization and two-dimensional echocardiogra-

phy 4 months after AMI attack. Physical examinations were

performed on hospital admission. Drug history and the

W.-C. Huang et al. / International Journal of Cardiology 104 (2005) 81–91 83

clinical history of risk factors, such as diabetes mellitus,

hypertension, smoking and hyperlipidemia, were recorded

from detailed chart review by a staff physician. The study

protocol was approved by the Human Research Committee

of our hospital. All patients gave oral informed consent for

participation in the study.

2.3. Myocardial contrast echocardiography

MCE associated with electrocardiographic, blood pres-

sure and two-dimensional echocardiographic monitoring

were performed in all patients within 2.3F0.7 days since

chest pain onset (Fig. 2). The commercial echocardiographic

machine (SONOS 5500 imaging system, Philips Medical

Systems, Andover, Massachusetts, USA) equipped with S3

transducer of 1–3 MHz was used. Specific instrumentation

setting used for MCE included a low mechanical index of

0.1, harmonic power modulation mode, compress of 65~70,

and maximal line densities. Gain was set at the level below

70% in order to avoid a myocardial dbloomingT artifact,

adjusted at the beginning of rest study, and then kept

constant during subsequent image acquisitions. Homoge-

nous back-scatter grey level was kept throughout entire wall

of LV. These setting allowed a frame rate N20 Hz during

MCE study. Focus was set at mitral valve. If possible apical

defect occurs, the focus moves up toward apex because

moving the focus to the level of potential perfusion defects

can eliminate false-positive perfusion defects.

We used perfluorocarbon exposed sonicated dextrose

albumin (PESDA) solution for the MCE study. The PESDA

solution was made as previously described method [11]. In

brief, a 10 ml perfluoropropane gas was mixed with a 20 ml

Fig. 2. Real-time myocardial contrast echocardiographic images of another patient

end-systole (right panel). This patient had undergone a primary coronary interven

contrast opacification of infarcted myocardium at apical–septal and apex segmen

functional recovery in all infracted area 4 months later.

of 3:1 mixture of 5% dextrose and 5% human albumin,

which was sonicated for 80 s using a 20-kHz probe

incorporating with a XL2020 sonicator (Misonix, New

York). Slow boluses of 0.3–0.5 ml PESDA solution were

injected intravenously and followed by a 5 ml saline push,

which lasted over 15~20 s. A physician performed all

contrast injections; with slight adjustments in contrast

quantity and bolus rate, depending on the adequacy of an

initial test injection in the apical four-chamber view.

Minimal amount of contrast was used to achieve myocardial

opacification in order to avoid blooming and attenuation

artifacts. bFlashQ imaging, manually triggered transient high

mechanical index imaging for 5 flames, was used at peak

contrast intensity to destroy microbubbles within myocar-

dium in order to exclude artifact and observe myocardial

replenishment. Real time MCE image was stored into high

quality VHS videotape and acquired 10–20 beats following

flash imaging with apical four-, two- and three-chamber

views on an optical disk. Nonstandard apical views were

occasionally used in an attempt to overcome localized area

of attenuation. When ventricular premature beats or deep

breath were noted, these relative frames were ignored due to

possible wall motion artifact.

The 17-segment model of the LV was used [12].

Perfusion defect was assessed by replenishment in the

initial 1–2 s post flash. Perfusion image of each segment

was graded on a 3-point scale (0=homogeneous contrast

opacification, 1=reduced, patchy or heterogeneous contrast

opacification, 2=no contrast opacification). Regional perfu-

sion score index was calculated by dividing the sum of the

perfusion scores for individual segments within dysfunc-

tional segments by the number of dysfunctional (akinesia or

with first acute anterior myocardial infarction at end-diastole (left panel) and

tion, myocardial contrast echocardiographic images revealed homogenous

ts (arrows). Follow up two-dimensional echocardiograms showed the LV


dyskinesia) segments [8]. Only akinesia or dyskinesia

segments at baseline were analyzed for assessment of viable

myocardium. A perfusion defect was excluded in a normal

contracting segment. Artifacts were differentiated from

perfusion defect prior to final analysis, including attenu-

ation, poor window, contrast destruction and other artifacts.

The presence of viable myocardium was defined as

homogenous or heterogeneous contrast opacification in at

least one view, i.e. perfusion score=b0Q or b1Q [9].

2.4. Low-dose dobutamine stress echocardiography

LDDSE associated with continuous electrocardio-

graphic, blood pressure and two-dimensional echocardio-

graphic monitoring were performed in all patients with the

same S3 transducer within 4.2F0.6 days after chest pain.

Beta-blocker was held for 24 h before the LDDSE. Two-

dimensional echocardiography was performed before,

during, and after dobutamine infusion at left decubitus

position with the same scanner. We also used tissue

harmonic imaging in order to optimize endocardial border

visualization. The echocardiographic tomographic views

were obtained with standard parasternal long- and short-

axis views at the level of the papillary muscle, apical four-,

two- and three-chamber views. Dobutamine was infused

with a volumetric pump similar to previous reported

method [13]. Except baseline two-dimensional echocardio-

graphic images, echocardiographic recordings were also

acquired at the end of the first 3 min (at 5 Ag/kg/min of

dobutamine infusion), the following 3 min (at 10 Ag/kg/min), and the 6-min recovery phase after stopping the

dobutamine infusion. All echocardiographic images were

recorded by high-quality videotape and acquired in an

optical disk in quad-screen cineloop format to facilitate

review and interpretation.

A 17-segment model of the LV was also used to evaluate

LV wall motion [12]. Each segment was graded on a 4-point

scale (0=normal or hyperkinesia; 1=hypokinesia; 2=akine-

sia; 3=dyskinesia). Regional wall motion score index was

calculated by dividing the sum of the wall motion scores for

individual segments within this area by the number of

dysfunctional (akinesia or dyskinesia) segments [2]. Each

wall motion score index was calculated at baseline and at

the end of 10 Ag/kg/min dobutamine infusion. LV end-

diastolic volume, end-systolic volume and ejection fraction

were measured by a modified Simpson’s biplane method

from apical four-chamber views during baseline and at the

end of peak stress. Images from each echo study in each

view were displayed side-by-side for subsequent wall

motion analysis. Only akinesia or dyskinesia segments at

baseline were analyzed for assessment of viable myocar-

dium. The presence of viable myocardium was defined as

z1 dyssynergic segment, which had z1 decrease of wall

motion score during dobutamine infusion compared with

baseline resting echocardiography. At the same time,

contractile reserve was assessed according to a continuous

parameter defined as dobutamine regional Dwall motion

score index expressing the difference between regional wall

motion score index at rest and peak-stress dobutamine. This

parameter provides information on the presence as well as

extent of contractile reserve of the dysfunctional myocar-

dium [9].

2.5. Follow-up resting two-dimensional echocardiography

Clinical and echocardiographic evaluations were per-

formed in all patients 4 months after chest pain onset. In

order to evaluate LV functional recovery, the differences

in regional wall motion score index (regional Dwall

motion score index, DWMSI) between the initial study

(WMSIBaseline) and the 4-month follow-up (WMSIFollow-up)

were measured [9]. Regional Dwall motion score index

ratio at follow-up (%) was defined as regional Dwall motion

score index at follow-up (WMSIFollow-up�WMSIBaseline)

divided by baseline regional wall motion score index

(WMSIBaseline). The presence of viable myocardium was

defined as z1 dyssynergic segment at baseline resting two-

dimensional echocardiography, which had z1 decrease of

wall motion score during follow-up. Other analysis method

was the same as LDDSE.

2.6. Therapeutic intervention and Coronary angiography

Patients who meet our diagnosis criteria of AMI were

initially treated with oxygen, intravenous nitroglycerin (if

systolic blood pressure N90 mmHg), aspirin (325 mg,

chewed), and intravenous heparin (given as a 5000-U

bolus). An intravenous infusion of heparin therapy was

begun after bolus of 5000 U and was adjusted to maintain

the partial-thromboplastin time at 1.5–2.0 times the control

value for the next three days. These patients were then

assigned to three different groups. If the patients visited our

emergency department within 12 h of the onset of ischemic

symptoms, these patients were randomly assigned to either

primary coronary intervention group or thrombolysis group.

If the patients visited our emergency department more than

12 h of onset of ischemic symptoms, these patients was

assigned to conservative therapy group.

In the primary coronary intervention group, Tirobifan

was infused immediately with a volumetric pump at 0.4

Ag/kg/min for the first 20 min and at 0.1 Ag/kg/min for

the following 3 days. These patients then underwent

coronary intervention promptly after they appeared at our

emergency room (within 362.7F155.9 min since chest

pain onset). Successful angioplasty was defined as the

restoration of Thrombolysis in Myocardial Infarction grade

3 flow with less than 50% residual stenosis, whether or

not to perform stent implantation was left to the judgment

of the operator.

In the thrombolysis group, all patients received recombi-

nant tissue-type plasminogen activator within 320.5F185.2

min after chest pain onset, with an intravenous bolus of 15


mg, followed by an infusion of 0.75 mg/kg of body weight

(not to exceed 50 mg) over a 30-min period and then 0.50

mg/kg (not to exceed 35 mg) over the next 60 min, for a

maximal total dose of 100 mg.

In the conservative therapy group, these patients were

admitted to coronary intensive care units as soon as possible

after infusion of continuous heparin therapy.

Among the above three groups, concurrent therapy was

left to the decision of the investigator, including beta-

blocking agent, angiotensin converting enzyme inhibitor,

calcium channel blocker, etc.

All patients received follow-up angiography. The

decision to proceed with revascularization was made on

clinical grounds by investigators. Follow-up two-dimen-

sional echocardiography was performed within 2 weeks

after angiography, if the duration of follow-up angiography

did not exceed 4 months. Coronary angiograms were

analyzed by another physician blind to clinical and

echocardiographic data. Quantitative coronary angiography

is used to measure coronary artery lesion dimensions and

stenosis.

2.7. Inter- and intraobserver variability

These LDDSE images were analyzed by two independ-

ent experienced reviewers blinded to the patients’ scinti-

graphic data and again by the same reviewer 4 weeks later.

LV wall motion score indices were visualized by both

systolic wall thickening and inward wall motion. Inter-

observer variability for the magnitude of stress echocardio-

graphic agreement was 7.3%, and intra-observer variability

was 6.8%. Disagreement was never more than 1 grade for a

single segment. The MCE images were also analyzed by

two independent experienced reviewers and again by the

same reviewer 4 weeks later. Inter-observer variability was

8.3%, and intra-observer variability was 6.5%.

2.8. Statistics

Categorical data are presented as absolute values and

percentages, whereas continuous variable are summarized as

mean valuesFstandard deviation. Chi-squared test was used

for comparison of categorical data. Two-tailed Student t-test

was performed for comparison of continuous data. Compar-

isons between groups of perfusion score index and wall

motion score index values at baseline, peak-stress LDDSE

and follow up were mad by two-tailed Student t test. The

sensitivity, specificity and accuracy for prediction of LV

viable myocardium were determined for both MCE and

LDDSE variables. Sensitivity and specificities were com-

pared using conventional method. In order to compare the

concordance between perfusion score index and dobutamine

Dwall motion score index, the Kappa analysis was used.

Linear regression analysis was used to analyze the relation

between myocardial perfusion score and the regional wall

motion recovery assessed by regional Dwall motion score

index ratio at follow-up (%). A p-value of b0.05 was

considered statistically significant.

3. Results

We divided 92 patients into 3 groups: primary coronary

intervention group (34 patients), thrombolysis group (30

patients) and conservative therapy group (28 patients).

Among the three groups, there were nearly identical

baseline demographic, clinical, electrocardiographic, and

hemodynamic characteristics (Table 1). EKG location of

AMI revealed that 68.5% of our cases located at the anterior

wall and 31.5% located at the inferior wall. Mean Killip

class value was 1.87F0.91. There was a total of 615

dysfunctional segments identified. But 5.69% (n=35) of

these segments were inadequately visualized by MCE.

Therefore, 580 dysfunctional segments were available for

complete analysis: 36.0% dysfunctional segments (n=209)

in coronary intervention group, 32.9 % (n=191) in the

thrombolysis group and 31.1% (n=180) in the conservative

therapy group. The time from chest pain onset to thrombo-

lytic agent infusion (320.5F185.2 min) in the thrombolysis

group was not different from the time from chest pain onset

to balloon inflation (362.7F155.9 min) in the primary

coronary intervention group ( p=0.281).

3.1. Real-time myocardial contrast echocardiography

Real-time MCE revealed that perfusion segments (homo-

genous or heterogeneous contrast opacification) presented in

56.0% (n=325) of dysfunctional segments, including:

64.6% (n=135) perfusion segments of dysfunctional seg-

ments in primary coronary intervention group, 57.6%

(n=110) in thrombolysis group and 44.4% (n=80) in

conservative therapy group. Regional perfusion score index

collocated in an order of primary coronary intervention

group (0.65F0.53), thrombolysis group (0.78F0.55) and

conservative therapy group (1.01F0.49). Regional perfu-

sion score index in the conservative therapy group was

significantly higher than that in the primary coronary

intervention group ( p=0.008) and the thrombolysis group

( p=0.03) (Fig. 3). However, there was no significant

difference between the primary coronary intervention group

and the thrombolysis group ( p=0.37).

3.2. Low dose dobutamine stress echocardiography

LDDSE revealed viable segments in 45.9% (n=266) of

dysfunctional segments, including: 54.1% (n=113) viable

myocardium of dysfunctional segments in primary coronary

intervention group, 45.0% (n=86) in thrombolysis group

and 37.2% (n=67) in conservative therapy group. Regional

dobutamine Dwall motion score index in the primary

coronary intervention group (Fig. 4) showed significantly

more decrease than that in the conservative therapy group

Table 1

Baseline characteristics of the three study groups

Primary coronary

intervention group

Thrombolysis group Conservative therapy group p value

N=34 N=30 (36) N=28 (45)

Demographic data

Male 31 (91.2%) 26 (86.7%) 26 (92.9%) 0.710

Age (years old) 64.5F11.5 63.7F11.9 62.7F14.9 0.378

Risk factor

Hypertension (%) 11 (32.4%) 12 (40%) 15 (53.6%) 0.237

Diabetes mellitus (%) 11 (32.4%) 10 (33.3%) 11 (39.3%) 0.833

Hyperlipidemia (%) 26 (76.5%) 22 (73.3%) 21 (75.0%) 0.959

Total cholesterol (mg/dl) 195F37 187F41 189F43 0.512

High-density lipid (mg/dl) 38.6F12.6 41.2F13.7 42.1F17.8 0.219

Low-density lipid (mg/dl) 121F30 116F36 113F39 0.437

Current smoker (%) 19 (55.9%) 16 (53.3%) 15 (53.6%) 0.975

Killip classification 1.79F0.89 1.91F1.04 1.93F0.79 0.182

Laboratory data

Peak creatine kinase (IU/l) 3901F3958 3643F2954 3425F2349 0.197

Peak MB fraction (IU/l) 291F223 309F259 267F195 0.242

EKG location of acute myocardial infarction

Anterior wall infarction (%) 23 (67.6%) 21 (70.0%) 19 (67.9%) 0.976

Inferior wall infarction (%) 11 (32.4%) 9 (30.0%) 9 (32.1%) 0.976

Medication during hospitalization

Beta-blocker (%) 23 (67.6%) 20 (66.7%) 16 (57.1%) 0.65

Calcium channel blocker (%) 2 (5.9%) 1 (3.3%) 1 (3.6%) 0.858

ACE inhibitor (%) 20 (58.8%) 23 (76.7%) 23 (82.1%) 0.098

Angiotensin receptor blocker (%) 2 (5.9%) 1 (3.3%) 1 (3.6%) 0.858

Aspirin (%) 33 (97.1%) 25 (83.3%) 22 (78.6%) 0.076

Statin (%) 14 (41.2%) 10 (33.3%) 9 (32.1%) 0.716

Medication during out-patient department

Beta-blocker (%) 23 (67.6%) 17 (56.7%) 15 (53.6%) 0.486

Calcium channel blocker (%) 3 (8.8%) 4 (13.3%) 1 (3.6%) 0.419

ACE inhibitor (%) 17 (50.0%) 18 (60.0%) 16 (57.1%) 0.707

Angiotensin receptor blocker (%) 6 (17.6%) 7 (23.3%) 6 (21.4%) 0.848

Aspirin (%) 26 (76.5%) 22 (73.3%) 15 (53.6%) 0.121

Statin (%) 19 (55.9%) 12 (40.0%) 11 (39.3%) 0.320

Isorsorbide (%) 14 (41.2%) 13 (43.3%) 9 (32.1%) 0.652

Nicorandil (%) 6 (17.6%) 4 (13.3%) 1 (3.6%) 0.226

Vital sign at baseline echocardiography

Systolic blood pressure (mmHg) 121.9F19.2 115.7F13.8 118.2F18.4 0.349

Mean blood pressure (mmHg) 86.3F11.2 82.1F10.7 84.8F12.4 0.651

Heart rate (beats/min) 71.9F12.1 78.7F19.9 72.9F11.9 0.718

Baseline echocardiography

Included dyskinesia and akinesia segment (%) 209 (36.1%) 191 (37.4%) 180 (37.8%) 0.839

Regional WMSI 2.16F0.47 2.14F0.42 2.11F0.46 0.591

LV ejection fraction (%) 45.1F9.8 41.5F8.3 42.7F8.5 0.326

Vital sign during follow up echocardiography

Systolic blood pressure (mmHg) 136.1F35.8 128.3F25.1 129.9F25.4 0.294

Mean blood pressure (mmHg) 89.1F11.9 90.5F12.1 85.3F20.6 0.304

Heart rate (beats/min) 68.3F14.7 70.7F14.3 66.9F12.8 0.547

ACE, Angiotensin converting enzyme; BSA, Body surface area; CK, Creatine kinase; LV, Left ventricular; WMSI, Wall motion score index.


(�1.12F0.39 vs. -0.80F0.43, p=0.01). However, no statisti-

cally significant difference of dobutamine regional Dwall

motion score index in the thrombolysis group vs. the

conservative group (�0.99F0.50 vs. �0.80F0.43, p=0.08)

and in the primary coronary intervention group vs. the

thrombolysis group ( p=0.34).

Fig. 3. Comparison of regional perfusion score by myocardial contrast

echocardiography in the 3 study groups. Regional perfusion score index

collocated in an order of primary coronary intervention group, thrombolysis

group and conservative therapy group. Regional perfusion score index in

conservative therapy group was significantly higher than that in primary

coronary intervention group ( p=0.008) and that in thrombolysis group

( p=0.03). There was no significant difference of regional perfusion score

index between primary coronary intervention group and thrombolysis group

( p=0.37).

Fig. 5. Comparison of regional left ventricular wall motion score index

(WMSI) between baseline and follow-up two-dimensional echocardiog-

raphy 4 months later. Regional Dwall motion score index was defined as the

differences in regional wall motion score index between the initial study

and 4-month follow-up (WMSIFollow-up�WMSIBaseline). Regional Dwall

motion score index in the conservative therapy group showed a

significantly smaller difference than that in the primary coronary inter-

vention group (�1.02F0.46 vs. �1.67F0.53 ; p=0.003) and thrombolysis

group (�1.02F0.46 vs. �1.42F0.58 ; p=0.03). However, there was no

difference in the regional Dwall motion score index between the primary

coronary intervention group and the thrombolysis group (�1.67 F 0.53 vs.

�1.42 F 0.58, p=0.61).


3.3. Coronary Angiography

In the primary coronary intervention group, the initial

coronary angiography revealed that the infarcted related

artery was 67.6% (n=23) in left anterior descending

coronary artery, 5.9% (n=2) in left circumflex coronary

Fig. 4. Comparison of regional left ventricular wall motion score index

(WMSI) between baseline two-dimensional echocardiography and low

dose dobutamine stress echocardiography (LDDSE) at peak dose (10 Ag/kg/min). Dobutamine regional Dwall motion score index (WMSIPeak dose

LDDSE�WMSIBaseline) in the primary coronary intervention group was

significantly smaller than that of the conservative therapy group (�1.12F0.39 vs. �0.80F0.43; p=0.01). There was no difference of dobutamine

regional Dwall motion score index in the thrombolysis group vs. the

conservative group (�0.99F0.50 vs. �0.80F0.43; p=0.08) and in the

primary coronary intervention group vs. the thrombolysis group

( p=0.34).

artery and 26.5% (n=9) in right coronary artery. Degree of

stenosis of infarct related arteries showed that 29.4 %

(n=10) of them had 75–99% stenosis and 70.6% (n=24) of

Fig. 6. Relation between perfusion score index by myocardial contrast

echocardiography and regional Dwall motion score index ratio at follow-up

(%) by two-dimensional echocardiography. Regional Dwall motion score

index ratio at follow-up (%) was defined as regional Dwall motion score

index at follow-up (WMSIFollow-up�WMSIBaseline) divided by baseline

regional wall motion score index (WMSIBaseline). A linear relation existed

between perfusion score index and regional Dwall motion score index ratio

at follow-up (%) (r=�0.75, pb0.001). The lower the perfusion score index,

the better the microvascular integrity and left ventricular functional

recovery during follow up.

Table

2

Sensitivity,

specificityandaccuracy

ofMCEandLDDSEforpredictingtheviable

myocardium

in3groups

Follow-up

Primarycoronaryinterventiongroup

p-valueT

Thrombolysisgroup

p-valuea

Conservativetherapygroup

p-valueTT

2D

echo

MCE

LDDSE

MCE

LDDSE

MCE

LDDSE

Perfusion

segments

Non-perfusion

segments

Viable

segments

Non-viable

segments

Perfusion

segments

Non-perfusion

segments

Viable

segments

Non-viable

segments

Perfusion

segments

Non-viable

segments

Viable

segments

Non-viable

segments

Viable

segments

124

25

107

42

93

20

77

36

57

14

50

21

Non-viable

segments

11

49

654

17

61

969

23

86

17

92

Sensitivity(%

)83.2

71.8

0.02

82.3

68.1

0.01

80.3

70.4

0.18

Specificity(%

)81.7

90.0

0.19

78.2

88.5

0.09

78.9

84.4

0.30

Accuracy(%

)82.8

77.0

0.14

80.6

76.4

0.32

79.4

78.9

0.89

MCE=Myocardialcontrastechocardiography;LDDSE=Low

dose

dobutaminestress

echocardiography.

aComparethesensitivity,

specificityoraccuracy

betweenMCEandLDDSEin

thrombolysisgroup.

TComparethesensitivity,



primarycoronaryinterventiongroup.

TTComparethesensitivity,



conservativetherapygroup.


them had total occlusion. All patients in this group received

successful revascularization with the restoration of Throm-

bolysis in Myocardial Infarction grade 3 flows. Stent

implantation decided by the investigators were performed

in 73.5% (n=25) of patients. Results of follow-up coronary

angiography in the group showed that 14.7% (n=5) of

infarct-related coronary arteries had 75–89% stenosis and

11.8% (n=4) had 90~99% stenosis.

In the thrombolysis group, results of follow-up coronary

angiography showed that 23.3% (n=7) of infarct-related

coronary arteries had 75–89% stenosis and 26.7% (n=8) had

90~99% stenosis.

In conservative therapy group, the follow-up angiogra-

phy disclosed that 46.4% (n=13) patients had 90~99%

stenosis of infarct-related coronary artery and 42.9%

patients (n=12) had 75-89% stenosis of infarct-related

coronary artery.

3.4. Follow-up two dimensional echocardiography

Follow-up two dimensional echocardiography revealed

viable segment in 57.4% (n=333) of dysfunctional seg-

ment, including: 71.3% viable myocardium of dysfunc-

tional segment (n=149) in primary coronary intervention

group, 59.2% (n=113) in thrombolysis group and 39.4%

(n=71) in conservative therapy group. Regional Dwall

motion score index in the conservative therapy group

(Fig. 5) showed a significantly smaller difference than

that in the primary coronary intervention group (�1.02F0.46 vs. �1.67F0.53, p=0.003) and thrombolysis group

(�1.02F0.45 vs. �1.43F0.58, p=0.03). However, there

was no statistically significant difference in regional

Dwall motion score index between the primary coronary

intervention group and the thrombolysis group (�1.67F0.53 vs. �1.43F0.58 , p=0.61). By linear regression

analysis, a linear relationship was found between myo-

cardial perfusion score and regional Dwall motion score

index ratio at follow-up (%) in all three group (r=�0.750,

pb0.001) (Fig. 6). It indicated that the preserved

myocardial perfusion predicted the later LV functional

recovery.

3.5. Sensitivity, specificity and accuracy for prediction of LV

functional recovery

Among three groups, there was a trend of higher

sensitivity in myocardial contrast echocardiography for

predicting viable myocardium and higher specificity in

LDDSE for predicting functional recovery. MCE and

LDDSE were shown to be nearly identical in overall

accuracy for predicting LV functional recovery (Table 2).

Real-time MCE and LDDSE showed good concordance for

predicting LV functional recovery (Kappa value=0.63,

pb0.001). There were no statistically significant differences

in sensitivities, specificities and accuracies of MCE in

predicting the LV functional recovery among these 3


groups. Similarly, no differences in sensitivities, specificities

and accuracies of LDDSE were also noted among these 3

groups.

4. Discussion

This study was aimed in assessing the functional

recovery by evaluating the myocardial perfusion using real

time MCE and contractile reserve using LDDSE with

special emphasis on patients who underwent different

therapeutic strategies. Different from previous studies, we

compare the performance of myocardial perfusion and

contractile reserve in patients after AMI who underwent

primary coronary intervention with glycoprotein IIb/IIIa

platelet receptor inhibitor, thrombolysis or conservative

therapy. This study showed that patients with AMI treated

by full reperfusion therapy, i.e. primary coronary interven-

tion with glycoprotein IIb/IIIa platelet receptor inhibitor

have significantly better microvascular integrity, contractile

reserve and LV function recovery than patients treated by

conservative therapy. The thrombolysis group is comparable

to primary coronary intervention group and better than

conservative therapy group in microvascular integrity,

contractile reserve and LV function recovery. This study

also revealed that both MCE and LDDSE can predict the LV

functional recovery in patients after acute myocardial

infarctions under different intervention.

4.1. Previous study

A primary determinant of long-term survival in patients

after AMI is residual LV function [14]. Major factors for LV

functional recovery include infarct size, infarct location,

transmurality and patency of infarct-related artery [15].

Several studies have demonstrated the benefits from

myocardial reperfusion, with subsequent reduction of infarct

size and associated improvement in later regional and global

ventricular function [16,17]. Gibbons et al. reported that

angioplasty provides short-term clinical advantage over

thrombolytic therapy with recombinant tissue-type plasmi-

nogen activator [18]. However, successful coronary recan-

alization does not always mean complete and sustained

restoration of myocardial perfusion due to the fact that

microcirculation may be functionally impaired and micro-

vascular network is structurally damaged [19]. Glycoprotein

IIb/IIIa platelet receptor inhibitor not only results in better

epicardial blood flow, but also leads to less no-reflow

phenomenon and better microvascular flow and LV func-

tional recovery in primary coronary intervention [20].

Identification of these pieces of potentially reversible

dysfunctional myocardium at the site of myocardial injury

has therapeutic and prognostic implication [6]. Intracoro-

nary or intravenous myocardial contrast echocardiography

can predict LV functional recovery in patients with AMI,

which correlated with nuclear perfusion, LDDSE or

coronary flow reserve measured by Doppler wire [6,8,21].

Most published data focus on the microvascular perfusion in

patients with AMI treated by primary coronary intervention

[8,9]. Swinburn et al. has reported that intravenous delayed-

triggered MCE can early predict viability and 69 (72%) of

their patients treated by thrombolysis were included [22].

However, they did not compare the impact of MCE in AMI

patients who underwent different therapeutic interventions.

4.2. This study

The myocardium of the MCE perfusion images was

interpreted as viable myocardium if the perfusion score is 0

or 1, i.e. homogeneous contrast opacification or reduced,

patchy or heterogeneous contrast opacification. Higher

scores indicated the presence of abnormal myocardial

perfusion, which implied the loss of myocardial micro-

vascular integrity. This study showed that regional perfusion

score index is the highest in conservative therapy group.

Regional perfusion score index in thrombolysis group and

primary coronary intervention group were not different. It

indicated that attempts at revascularization when possible (it

was not possible in the conservative groups) clearly resulted

in better microvascular perfusion to the risk area.

We excluded patients with total occlusion of infarct-

related artery after follow-up angiography in order to avoid

the bias, what the microvascular perfusion and LV func-

tional recovery may not occur in these patients with

persisting occluded arteries. Microvascular perfusion

depends on patency of infarct-related coronary artery and

adequacy of collateral flow to the risk area. The early

patency of infarct-related coronary artery in primary

coronary intervention and thrombolytic group is responsible

for the better microvascular perfusion when compared with

conservative therapy. Due to the fact that the glycoprotein

IIb/IIIa platelet receptor inhibitor was prescribed in all

patients of primary coronary intervention group, this

strategy may play one of the important roles in contributing

a better microvascular flow. The conservative group in this

study was treated well after the infarct is completed (N12 h).

Moreover, in follow-up angiographic data, conservative

therapy group has a greater rate of high degree (75~99%)

stenosis of infarct-related coronary artery, which indicated

the presence of more percentage of hibernating myocar-

dium. These findings could explain that patients in this

group had worse LV functional recovery.

In our LDDSE study, contractile reserve was collocated

in the order of primary coronary intervention group,

thrombolysis group and conservative therapy group. How-

ever, there was no statistically significance in the thrombol-

ysis group compared to the conservative group and the

primary coronary intervention group. There were several

explanations for these results. First, LDDSE might under-

estimate contractile reserve after AMI, because demand-

induced ischemia might be caused by limited myocardial

flow reserve due to distal vessel plugging, microemboli, and


poor collateral circulation in presence of an occluded artery

[23]. Second, inadequate blood supply to the risk area can

blunt functional response to dobutamine of dysfunction but

viable myocardium [24]. Third, the maximal dosage used in

our study (10 Ag/kg/min) may have been inadequate in some

of our patient in eliciting contractile reserve [23]. We

performed LDDSE 4.2F0.6 days after chest pain. It might

be too early to perform the study to elicit contractile reserve

in the thrombolysis and conservative therapy group. Fourth,

the small population size might play some roles in the cause.

For the follow-up study, patients in conservative therapy

group have significantly higher regional wall motion score

index than those in the other groups. It indicated that the

conservative therapy had a relatively poor recovery of LV

wall motion than those who underwent reperfusion thera-

pies. Besides, there was a trend of worse LV functional

recovery in the thrombolysis group compared to that in the

primary coronary intervention group, but this trend is not

statistically significant (Fig. 5). Infarct size in patients after

AMI is determined by myocardial perfusion, duration of

occlusion and size of risk area [25]. Our data demonstrated

that revascularization, whether primary coronary interven-

tion or thrombolysis, clearly resulted in better preservation

of myocardial microvascular integrity and LV functional

recovery during follow up. Furthermore, among these three

groups, myocardial perfusion score has a good correlation

with LV function recovery (r=�0.750, pb0.001) (Fig. 6).

Our results demonstrated that the lower the perfusion score

index, the better the microvascular integrity and LV func-

tional recovery during follow up.

Previous studies indicated that there was a high

sensitivity for MCE but a high specificity for LDDSE in

predicting the LV functional recovery in patients after AMI.

For the accuracy evaluation, MCE and LDDSE were shown

to be nearly identical in overall accuracy for predicting the

LV functional recovery [10]. We found that the real-time

MCE had a good concordance with LDDSE in predicting

the LV functional recovery (kappa value=0.63, pb0.001).

4.3. Limitation

Several limitations should be mentioned. First, small

number of patients is a limitation of this study. However, the

nearly identical baseline demographic, clinical, electro-

cardiographic, and hemodynamic characteristics (Table 1)

in these 3 groups make them eligible for comparative

analysis. Second, a semiquantitative scoring system was

used for MCE and LDDSE in this study. There is no

available commercialized quantitative software during the

study periods; we therefore used this scoring system in the

analysis [22]. Third, the attenuation artifacts in the inferior,

posterior, or lateral LV segments may have limited the

interpretation of MCE in these segments. We tried to use

nonstandard views to overcome the limitation. Besides, the

almost identical percentage (30.0~32.4%, p=0.976) of

patients with inferior infarction was included in these three

groups (Table 1). We believe that it may not affect the

statistic results in this study. Fourth, the constant contrast

concentrations were ensured by continuous infusion. We

used a slow bolus that was continued until all images had

been acquired in that view, which could maintain relatively

stable contrast concentrations during the image acquisition

period. The slow bolus method has the benefit of being

time-saving, rapid, and convenient for use. Moreover, the

smaller fluid loading may be important to avoid being

increase in the fluid loading for patients with AMI. Fifth,

MCE and LDDSE were not performed simultaneously; it

seems that microvascular perfusion could have changed for

this time interval. Sixth, one of the reasons why the

sensitivity of MCE is not significantly superior to that of

LDDE in the conservative therapy group (80.3% vs. 70.4%,

p=0.18, (Table 2)) could be because the refill time was not

prolonged enough [26].

5. Conclusions

This study has shown that perfusion score index obtained

from real-time MCE is comparable to LDDSE in predicting

the LV functional recovery in patients after AMI even under

different therapeutic interventions. We demonstrate that

revascularization, whether primary coronary intervention

or thrombolysis, clearly results in better preservation of

myocardial microvascular integrity, regional contractile

reserve and LV functional recovery during follow up than

conservative therapy.

Acknowledgements

The authors wish to thank Dr. Thomas Richard Porter

(University of Nebraska Medical Center) and Dr. Nam Sik

Chung (Yonsei University medical center) for their assis-

tance in the MCE study and Kuei-Fang Su, Shiaw-Mei An

and Tzu-Yin Kuo for their secretarial work.

References

[1] Pfeffer MA, Braunwald E. Ventricular remodeling after myocardial

infarction. Experimental observations and clinical implications.

Circulation 1990;81:1161–72.

[2] Garot P, Pascal O, Simon M, Monin JL, Teiger E, Garot J, et al.

Impact of microvascular integrity and local viability on LV

remodelling after reperfused acute myocardial infarction. Heart

2003;89:393–7.

[3] Smart SC, Sawada S, Ryan T, Segar D, Atherton L, Berkovitz K, et al.

Low-dose dobutamine echocardiography detects reversible dysfunc-

tion after thrombolytic therapy of acute myocardial infarction.

Circulation 1993;88:405–15.

[4] Teupe C, Takeuchi M, Yao J, Abadi C, Avelar E, Fritzsch T, et al.

Assessment of myocardial perfusion by myocardial contrast echocar-

diography using harmonic power and the transvenous contrast agent

SHU 563A in acute coronary occlusion and after reperfusion. Int J

Cardiol 2001;77:231–7.


[5] Olszowska M, Kostkiewicz M, Tracz W, Przewlocki T. Assessment of

myocardial perfusion in patients with coronary artery disease.

Comparison of myocardial contrast echocardiography and 99mTc

MIBI single photon emission computed tomography. Int J Cardiol

2003;90:49–55.

[6] Ito H, Tomooka T, Sakai N, Yu H, Higashino Y, Fujii K, et al. Lack of

myocardial perfusion immediately after successful thrombolysis. A

predictor of poor recovery of LV function in anterior myocardial

infarction. Circulation 1992;85:1699–705.

[7] Ragosta M, Camarano G, Kaul S, Powers ER, Sarembock IJ, Gimple

LW. Microvascular integrity indicates myocellular viability in patients

with recent myocardial infarction. New insights using myocardial

contrast echocardiography. Circulation 1994;89:2562–9.

[8] Lepper W, Hoffmann R, Kamp O, Franke A, de Cock CC, Kuhl HP, et

al. Assessment of myocardial reperfusion by intravenous myocardial

contrast echocardiography and coronary flow reserve after primary

percutaneous transluminal coronary angiography in patients with

acute myocardial infarction. Circulation 2000;101:2368–74.

[9] Mengozzi G, Rossini R, Palagi C, Musumeci G, Petronio A,

Limbruno U, et al. Usefulness of intravenous myocardial contrast

echocardiography in the early LV remodeling in acute myocardial

infarction. Am J Cardiol 2002;90:713–9.

[10] Senior R, Swinburn JM. Incremental value of myocardial contrast

echocardiography for the prediction of recovery of function in

dobutamine nonresponsive myocardium early after acute myocardial

infarction. Am J Cardiol 2003;91:397–402.

[11] Porter TR, Xie F, Kricsfeld D, Armbruster RW. Improved myocardial

contrast with second harmonic transient ultrasound response imaging

in humans using intravenous perfluorocarbon-exposed sonicated

dextrose albumin. J Am Coll Cardiol 1996;27:1497–501.

[12] Cerqueira MD, Weissman NJ, Dilsizian V, Jacobs AK, Kaul S, Laskey

WK, et al. Standardized myocardial segmentation and nomenclature

for tomographic imaging of the heart: a statement for healthcare

professionals from the Cardiac Imaging Committee of the Council on

Clinical Cardiology of the American Heart Association. Circulation

2002;105:539–42.

[13] Elhendy A, Trocino G, Salustri A, Cornel JH, Roelandt JR, Boersma

E, et al. Low-dose dobutamine echocardiography and rest-redistri-

bution thallium-201 tomography in the assessment of spontaneous

recovery of LV function after recent myocardial infarction. Am Heart

J 1996;131:1088–96.

[14] White HD, Norris RM, Brown MA, Brandt PW, Whitlock RM, Wild

CJ. LV end-systolic volume as the major determinant of survival after

recovery from myocardial infarction. Circulation 1987;76:44–51.

[15] Lamas GA, Flaker GC, Mitchell G, Smith Jr SC, Gersh BJ, Wun CC, et

al. Effect of infarct artery patency on prognosis after acute myocardial

infarction. The survival and ventricular enlargement investigators.

Circulation 1995;92:1101–9.

[16] Touchstone DA, Beller GA, Nygaard TW, Tedesco C, Kaul S.

Effects of successful intravenous reperfusion therapy on regional

myocardial function and geometry in humans: a tomographic

assessment using two-dimensional echocardiography. J Am Coll

Cardio 1989;13:1506–13.

[17] Touchstone DA, Beller GA, Nygaard TW, Tedesco C, Kaul S. Effect

of streptokinase on LV modeling and function after myocardial

infarction: the GISSI (Gruppo Italiano per lo Studio della Strepto-

chinasi nell’Infarto Miocardico) Trial. J Am Coll Cardiol 1989;

14:1149–58.

[18] Gibbons RJ, Holmes DR, Reeder GS, Bailey KR, Hopfenspirger MR,

Gersh BJ. Immediate angioplasty compared with the administration of

a thrombolytic agent followed by conservative treatment for myo-

cardial infarction. The Mayo Coronary Care Unit and Catheterization

Laboratory Groups. N Engl J Med 1993;328:685–91.

[19] Eeckhout E, Kern MJ. The coronary no-reflow phenomenon: a review

of mechanisms and therapies. Eur Heart J 2001;22:729–39.

[20] Petronio AS, Rovai D, Musumeci G, Baglini R, Nardi C, Limbruno U,

et al. Effects of abciximab on microvascular integrity and LV

functional recovery in patients with acute infarction treated by

primary coronary angioplasty. Eur Heart J 2003;24:67–76.

[21] Bolognese L, Antoniucci D, Rovai D, Buonamici P, Cerisano G,

Santoro GM, et al. Myocardial contrast echocardiography versus

dobutamine echocardiography for predicting functional recovery after

acute myocardial infarction treated with primary coronary angioplasty.

J Am Coll Cardiol 1996;28:1677–83.

[22] Swinburn JM, Lahiri A, Senior R. Intravenous myocardial contrast

echocardiography predicts recovery of dysynergic myocardium early

after acute myocardial infarction. J Am Coll Cardiol 2001;38:19–25.

[23] Sklenar J, Ismail S, Villanueva FS, Goodman NC, Glasheen WP, Kaul

S. Dobutamine echocardiography for determining the extent of

myocardial salvage after reperfusion. An experimental evaluation.

Circulation 1994;90:1502–12.

[24] Iliceto S, Galiuto L, Marchese A, Cavallari D, Colonna P, Biasco G, et

al. Analysis of microvascular integrity, contractile reserve, and

myocardial viability after acute myocardial infarction by dobutamine

echocardiography and myocardial contrast echocardiography. Am J

Cardiol 1996;77:441–5.

[25] Villanueva FS, Glasheen WP, Sklenar J, Kaul S. Assessment of risk

area during coronary occlusion and infarct size after reperfusion with

myocardial contrast echocardiography using left and right atrial

injections of contrast. Circulation 1993;88:596–604.

[26] Janardhanan R, Swinburn JM, Greaves K, Senior R. Usefulness of

myocardial contrast echocardiography using low-power continuous

imaging early after acute myocardial infarction to predict late

functional left ventricular recovery. Am J Cardiol 2003;92:493–7.

Comparison of real-time contrast echocardiography and low-dose dobutamine stress echocardiography in predicting the left ventricular functional recovery in patients after acute myocardial

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