www.elsevier.com/locate/ijcard

International Journal of Cardio

Correlation between the tissue Doppler, strain rate, strain imaging during

the dobutamine infusion and coronary fractional flow reserve

during catheterization: a comparative study

Sinan Dagdelena,*, Murat Yucea, Yunus Emiroglub, Mehmet Ergelenb, Selcuk Palab,

Ali Cevat Tanalpb, Akin Izgib, Cevat Kirmab

aAcibadem Hastanesi, Tekin sk. No. 18, Acibadem, Kadikoy, Istanbul, TurkeybKosuyolu Heart and Research Hospital, Istanbul, Turkey

Received 1 December 2003; received in revised form 11 May 2004; accepted 18 May 2004

Available online 28 August 2004

Abstract

Coronary fractional flow reserve (FFR) as an invasive, and dobutamine stress echocardiography (DSE) as a noninvasive technique were

used to detect critical coronary stenosis. This study was undertaken to assess correlation between these two techniques by using tissue

Doppler, strain rate (SR), and strain imaging (S).

Methods: In 17 patients (aged 54.9F12.6, 4 F), a total of 22 vessels were studied. On dobutamine stress echocardiography, baseline and peak

systolic (Sm), early (Em) and late (Am) diastolic myocardial velocities, SR and S were recorded from parasternal view (mid-posterior

segment) for radial and apical view (mid-septum) for longitudinal deformation. Then coronary FFR was performed by using intracoronary

adenosine infusion, and the value of V0.75 was accepted as critical coronary stenosis.

Results: FFR was found to be significant in 10 vessels (FFR critical). Baseline Sm, Em/Am, SR, S values, and peak Em/Am, SR, S values

were similar between critical or noncritical FFR groups. Baseline Sm and Em, and change between baseline and peak Sm and S were

significantly higher in noncritical FFR group ( pb0.01, b0.05, b0.001, b0.001, respectively). In all vessels, FFR after adenosine infusion

showed a poor correlation with WMSI, Em, Am, Em/Am values, and the change in SR values (r=�0.22, 0.16, �0.14, 0.21, 18, respectively)

showed a good correlation with the change in S (r=0.51; p=0.014), and a very good correlation with the change in Sm values (r=0.77;

pb0.001) during DSE. When FFR values at left coronary system were analyzed for longitudinal SR and S values, it had a mild correlation

with SR (r=0.47, p=0.044) and a good correlation with S (r=0.66, p=0.002).

Conclusion: The quantification of regional myocardial deformation by using DSE rather than the motion would be more appropriate in

detecting the ischemic dysfunctional segment supplied by the critical coronary stenosis. Strain measurement during the dobutamine infusion

may provide an information on the FFR results of the culprit vessel.

D 2004 Elsevier Ireland Ltd. All rights reserved.

Keywords: Stress echocardiography; Strain rate; Coronary flow reserve

1. Introduction

Dobutamine stress echocardiography (DSE) is a well-

established method for detecting inducible ischemia. Ische-

mia is defined by a regional reduction or deterioration of

0167-5273/$ - see front matter D 2004 Elsevier Ireland Ltd. All rights reserved.

doi:10.1016/j.ijcard.2004.05.012

* Corresponding author. Tel.: +90 216 544 41 23; fax: +90 216 325 87

59.

E-mail address: sinandagdelen@hotmail.com (S. Dagdelen).

myocardial thickening or inward motion of the endocardial

border [1,2]. However, visual assessment of regional

myocardial function during dobutamine stress echocardiog-

raphy has been shown to be highly subjective and dependent

on image quality [3,4]. These difficulties required a new

fully quantitative method to evaluate stress echocardio-

grams. Regional strain rate measuring the rate of myocardial

deformation and regional strain defining the total amount of

deformation can now be derived by post-processing a high

logy 102 (2005) 127–136

S. Dagdelen et al. / International Journal of Cardiology 102 (2005) 127–136128

frame rate myocardial Doppler velocity data set [5]. Left

ventricular wall motion is depicted accurately at rest and

during ischemia, including dobutamine-induced ischemia

[6,7]. Recent reports on the use of strain rate (SR) imaging

during DSE for viability and ischemia are promising [8,9].

Also, it has been showed that Doppler SR imaging is

feasible and able to objectively differentiate between the

ischemic and the nonischemic myocardium compared to

conventional DSE [10].

The shortcomings of angiography to assess the physio-

logic significance of coronary atherosclerosis are well

known [11,12]. Particularly in patients with diffuse disease

or unstable coronary syndromes, the angiogram is of little

help to ascertain the potential of an individual stenosis to

cause reversible myocardial ischemia.

Fractional flow reserve (FFR) is such an index, and is

defined as the ratio of maximum blood flow in a stenotic

artery to normal maximum flow in the same vessel [13]. In

contrast to most other invasive indices, FFR has a direct

clinical relevance for determining critical coronary stenosis

which causes myocardial ischemia [14]. The characteristics

of FFR have been extensively described and validated over

recent years. Fractional flow reserve can be calculated by

taking the ratio of mean distal coronary pressure to aortic

pressure during maximum coronary hyperemia, which

generally is induced by intracoronary adenosine adminis-

tration. In contrast to other invasive indices, FFR is not

dependent on changes in heart rate, blood pressure, or

contractility [15]; it also accounts for the presence of

collaterals [16], and has a high threshold value to indicate

inducible ischemia [17]. The bgray zoneQ is very limited,

which is important for clinical decision making in an

individual patient. In recent years, both SR imaging during

the DSE as noninvasive and the FFR as an invasive

technique have been extensively used to differentiate

between clinically and angiographically significant coronary

stenosis. However, the relationship between SR imaging

parameters during DSE and FFR is not clear. Thus, this

study investigates regional myocardial strain rate and strain

response during the DSE and its correlation with FFR in

patients with coronary artery disease.

2. Methods

2.1. Study population

The study population comprised 17 selected patients

referred for DSE to detect the presence or absence of

inducible ischemia. After DSE study, all patients underwent

coronary angiography. Patients not in sinus rhythm, with

bundle-branch block, with a prior history of myocardial

infarction within the last 2 months, more than mild

myocardial hypertrophy, dilated cardiomyopathy, persistent

atrial or ventricular arrhythmia, hypertension (systolic and

diastolic blood pressure N200/120 mm Hg, respectively),

more than mild valvular heart disease, or left ventricular

ejection fraction less than 35% were not included to the

study. After coronary angiography, exclusion criteria were as

follow: (1) incessant chest pain not responding to medical

therapy; (2) left main or severe three coronary artery disease;

(3) prior coronary artery bypass grafting; and (4) vessels that

were totally occluded or supplying an akinetic territory by

visual assessment of the left ventricular angiogram.

3. Study protocol

The ethical committee approved the study and informed

consent was obtained from all patients. Patients who were

scheduled for DSE and who did not have exclusion criteria

were included in the study consecutively. All subjects

consented to participate in the study after receiving detailed

protocol information. The day before DSE, all antianginal

medications were discontinued, which include beta block-

ers, Ca antagonists, and nitrates. Following DSE, within 6 to

12 h, all patients underwent coronary angiography without

taking any long acting medications. In the case of an anginal

attack during or after DSE, only sublingual short acting

nitrates were given to the patients. After the coronary

angiograms were reviewed, eligible coronary arteries that

were found to have stenosis of intermediate severity were

undertaken for FFR study. In the patients who have more

than one critical coronary stenosis, FFR study was made on

the coronary stenosis which is more important to make

decision whether the patient is a candidate for bypass

surgery or percutaneous coronary intervention alone. Frac-

tional flow reserve was measured just after coronary

angiography at the same setting. After the FFR study, the

myocardial segments supplying the coronary arteries studied

with the FFR were compared with the SR imaging

parameters of the same segments on DSE. In 17 patients,

the presence of 40% coronary stenosis was noted in one in

six, two in eight, three in four, and four in four cases. A total

of 22 vessels were evaluated by the FFR, and 22 left

ventricular segments supplying these coronary vessels were

studied by DSE and tissue Doppler examination. Among the

vessels studied by the FFR, 16 were for left anterior

descending, three for circumflex and three for right coronary

artery. In the patients studied for the right coronary arteries,

the right system vessels were dominant.

3.1. Transthoracic echocardiography

Studies were performed with a Vivid Five instrument

(GE Vingmed Ultrasound, manufactured in Horten, Nor-

way) using a phased-array duplex multifrequency trans-

ducer. In all subjects, the transducer was set at 2.5 MHz for

Doppler examination and 2.5 to 3.5 MHz for tissue imaging,

and second harmonic imaging was used. Two-dimensional,

M-Mode and Doppler echocardiography were obtained by

imaging of the parasternal long and short axes, by apical

Fig. 1. Tissue Doppler imaging from the mid-apikoseptal segment at rest

(upper) and during dobutamine stress (bottom) shows significant decrease

in early and increase in late diastolic myocardial velocity with dobutamine.

S. Dagdelen et al. / International Journal of Cardiology 102 (2005) 127–136 129

four-chamber view, and by apical two-chamber view. The

left ventricle was divided according to the 16-segment

model of the American Society of Echocardiography [18].

Each left ventricular segment was scored at rest and during

dobutamine stimulation as normokinetic, hypokinetic, aki-

netic, dyskinetic or aneurysmatic.

3.2. Dobutamine stress echocardiography

A graded dobutamine infusion was administered through

a peripheral arm vein. Three-minute stages were used at

infusion rates of 5, 10, 20, 30 and 40 g/kg/min, respectively.

The infusion was stopped at the dose when N85% of age-

predicted heart rate was reached. Also, if the heart rate was

required to be increased, the infusion of dobutamine was

continued and supplemented with 0.25-mg doses of atropine

(to a maximal dose of 1 mg). Stress testing was terminated

either on patient request or when a new wall motion

abnormality, chest discomfort indicative of progressive

angina, dyspnea, decrease in systolic blood pressure (N40

mm Hg), arterial hypertension (RRN240/120 mm Hg),

severe arrhythmias or other serious adverse effects occurred.

During the DSE, the ischemic response has been defined

as a new wall motion abnormality, a decreased left

ventricular ejection fraction, and/or a worsening in the

abnormal myocardial segment at rest.

3.3. Tissue and strain Doppler imaging

Color tissue Doppler recordings were obtained at rest and

during dobutamine stress using the same apical transducer

positions. Longitudinally mid-apikoseptal segment from

apical four chamber view and mid-anterolateral segment

from apical two chamber view were used to evaluate left

anterior descending and diagonal coronary system; longi-

tudinally mid-posterolateral segment from apical four

chamber view was used for circumflex and optus marginal

coronary arteries; and radially mid-inferoposterior segment

from parasternal short axis view was used for dominant

right coronary artery. The ultrasonic beam was placed on the

two segments with less than 308 angles, between ultrasonic

beam direction and longitudinal axis of the myocardial

segment. Thus, instantaneous differences between the two

adjacent regions implied either compression or lengthening

of the tissue in between. Baseline and peak systolic (Sm),

early (Em) and late (Am) diastolic myocardial velocities

(Fig. 1), strain rate (SR) and strain (S) were measured from

the related segments (Fig. 2). The peak systolic tissue

velocity was determined as the maximal positive velocity

within 350 ms after the QRS complex. The tissue and strain

rate Doppler values were calculated as the difference

between the two velocity points along the ultrasonic beam

divided by the distance between the points (10 mm in our

analysis). Recordings were stored digitally as two-dimen-

sional cineloops and analyzed with customized dedicated

research software (EchoPAC, GE Vingmed Ultrasound,

Horten, Norway), and monitored with a Sony Multiscan

G200 (Vivid Five monitor assembly, Mexico). Digital loops

of single cardiac cycles were collected with a frame rate

varying from 60 to 65 frames/s, and to minimize the noise

level, the pulse repetition frequency was set to 250 to 300

Hz. The Nyquist limit for velocity was set between 8.9 and

14 mm/s. The differences between the two points per unit

length express instantaneous regional myocardial deforma-

tion or strain rate and have units of 1/s. By integrating the

velocity gradients over time, we obtained strain through the

cardiac cycle.

3.4. Pressure measurements and calculation of FFR

At the conclusion of coronary angiography, the coronary

artery was selectively engaged with a 7F guiding catheter. A

0.014-in. pressure guide wire (WaveWire, RADI Medical

Sytems, Upsala, Sweden) was set at zero, advanced into the

Fig. 3. Fractional flow reserve (FFR) from left anterior descending coronary

artery of the same patient depicted in Fig. 1. Before the adenosine infusion,

S. Dagdelen et al. / International Journal of Cardiology 102 (2005) 127–136130

coronary artery, normalized, and then positioned distal to

the stenosis to be measured. The aortic pressure and the

distal coronary pressure were measured continuously by the

guiding catheter and the pressure guide wire, respectively.

Fractional flow reserve was calculated as: FFR=Pd/Pa,

where Pd (distal coronary pressure) and Pa (aortic pressure)

were recorded simultaneously during maximal coronary

hyperemia induced by intracoronary bolus infusion of

adenosine (36 to 42 Ag in the left coronary artery system

and 18 to 24 Ag in the right coronary artery), as described

previously [19]. Coronary lesion in which FFR was 0.75

was accepted as noncritical stenosis; if the FFR was b0.75,

it was accepted as critical stenosis. The selection of 0.75 as

the cutoff value for the FFR in determining whether it is

critical or not was based on the results of previous studies

[14,20]; Fig. 3.

3.5. Statistics

Statistical analysis was performed using SPSS 11.0

statistical software (SPSS, Chicago, IL). In this study,

DSE, SR and S Doppler imaging parameters were obtained

from the left ventricular segment which is supplied by the

coronary artery investigated with the FFR. These were

analyzed and compared with the FFR values of the same

instrument calibration was 1.00 at rest (upper) and after adenosine infusion

(bottom), FFR value decreased from normal to 0.58.

Fig. 2. Strain rate imaging from the same patient depicted in Fig. 1 and left

ventricular segment at rest (upper) and during dobutamine stress (bottom)

shows significant decrease in strain with dobutamine.

vessels. Strain Rate and S imaging parameters obtained

longitudinally (19 vessels except the right coronary artery)

correlated with the FFR values. The changes in baseline and

peak SR, S and tissue Doppler parameters were correlated

with the FFR values in all vessels (N=22). Analyzing the

longitudinal deformation of the related left ventricular

segment, right coronary investigation (three cases) was not

included for the comparison and the correlation of the SR

and S values. Fractional flow reserve values of all the vessels

were correlated with the ratio of the change between the

baseline and peak Doppler parameters for both longitudinal

and radial strain imaging. All the data analyses and

comparisons between imaging modalities were performed

on a segmental level. Continuous parameters were expressed

as meanFS.D. Grouped data were tested for normal

distribution and equality of S.D. and compared by a two-

tailed t test. Categorical variables were tested with Fisher

exact test and Chi-square test. Probability values of pb0.05

were considered statistically significant.

4. Results

Patients with and without ischemic response did not

differ significantly with respect to age, gender, medication,

hypertension, diabetes and previous myocardial infarction

(Table 1). Baseline and peak heart rate and blood pressure

measurements were not significantly different in patients

Table 1

Characteristics of all patients and with and without ischemic response

during dobutamine stress

Total Nonischemic Ischemic p

No. of patients 17 7 10

No. of vessels 22 10 12 NS

Female/male 4/13 1/6 3/7 NS

Age 54.9F12.6 58F15 53F11 NS

h-Blocker 13 6 7 NS

Nitrate 16 7 9 NS

Ca antagonists 1 1 0 NS

Hypertension 8 3 5 NS

Diabetes 3 2 1 NS

Previous non-Q/Q-MI 9 4 5 NS

MI=myocardial Infarction, BP=blood pressure.

S. Dagdelen et al. / International Journal of Cardiology 102 (2005) 127–136 131

who had ischemic and nonischemic response to DSE. No

adverse events occurred during DSE. The demographic and

the clinical characteristics of the patients are shown in

Table 1.

Ischemic response during DSE was observed in 10 of the

patients (n=17), and among the 12 vessel segments of all the

Table 2

Two-D and tissue and strain rate Doppler parameters of the patients during DSE

Total

Ischemic response at peak DSE (+/n) 10/17

WM abnormality on related segment (+/N) 12/22

Baseline ejection fraction, % 59F10

Angina (n) during DSE 7/17

Arrhytmia (n) during DSE 2/17

Hypertensive reaction (n) during DSE 3/17

Atropin required (n) 9/17

Baseline WMSI (N) 1.14F0.44

Peak WMSI 1.31F0.43

Changes in WMSI with DSE (%) 25.2F30.2

In all FFR-related LV segments (N: 22)

Baseline Sm (m/s) 0.039F0.019

Peak Sm (m/s) 0.049F0.037

Change in Sm (%) �6.1F57.7

Baseline Em (m/s) �0.47F0.022

Peak Em (m/s) �0.050F0.031

Change in Em (%) �27.6F75.8

Baseline Am (m/s) �0.045F0.021

Peak Am (m/s) �0.090F0.127

Change in Am (%) 23.8F42.9

Ratio of baseline Em/Am 1.34F1.12

Ratio of peak Em/Am 0.97F0.94

Change in Em/Am with DSE (%) �157F309

Change in SR with DSE (%) �46.8F122.3

Change in S with DSE (%) �23.7F61.5

Only in LV segments studied with longitudinal strain rate (n=19)

Baseline SR (s�1) �1.62F1.46

Peak SR (s�1) �1.48F1.57

Baseline S (%) �22.0F10.8

Peak S (%) �20.3F12.3

n: number of patients, N: number of vessels and related segments, LV: left ventr

index, FFR: fractional flow reserve, Sm: systolic myocardial velocity, Em: early dia

rate, S: strain.

vessels studied by the FFR (N=22) ( pN0.05). The incidence

of arrhythmia, hypertensive reaction and atropin require-

ment during the DSE were similar in both the patients with

and without ischemic response ( pN0.05 for all), but angina

was seen more frequently in the ischemic group ( p=0.024).

Baseline ejection fraction and left ventricular wall motion

score index (WMSI) were similar in both the ischemic and

the nonischemic groups during the DSE. Peak WMSI and

the change in WMSI during the DSE significantly increased

in the ischemic group ( p=0.001 and b0.001, respectively).

All the tissue Doppler parameters (Sm, Em, Am), WMSI

and the ratio of the changes in the SR and S were compared

to 22 left ventricular segments supplied by the FFR related

coronary artery including the longitudinal and the radial

deformation aspects. However, nominal SR and S values

were compared only in the longitudinal deformation,

because the opposite direction of the radial SR and S values

was not convenient for evaluation together with the

longitudinal values. Thus, the last two parameters were

evaluated apart, which included the 19 FFR related vessels

and their related left ventricular segments. Peak Sm and the

Nonischemic Ischemic p

7 10

0 12 NS

62F5 57F13 NS

1 6 =0.024

0 2 NS

1 2 NS

4 5 NS

1.0F0.0 1.26F0.58 NS

1.0F0.0 1.57F0.45 =0.001

0 29.5F15.5 b0.001

0.038F0.014 0.039F0.023 NS

0.074F0.035 0.027F0.014 =0.02

41F21 �46F47 b0.001

�0.049F0.027 �0.046F0.019 NS

�0.064F0.038 �0.042F 0.020 NS

�21F97 �33F56 NS

�0.048F0.018 �0.045F0.021 NS

�0.064F0.027 �0.067F0.027 NS

12F50 33F35 NS

1.26F0.95 1.16F0.61 NS

1.32F1.17 0.72F0.53 NS

�68F122 �114F134 NS

�42.9F17.4 �50.0F61.2 NS

26.6F17.0 �65.9F52.1 b0.001

�1.66F0.90 �1.58F1.80 NS

�1.83F1.10 �1.23F1.86 NS

�22.6F10.2 �21.5F11.7 =0.02

�29.7F11.8 �13.4F7.2 b0.001

icle, DSE: dobutamine stress echocardiography, WMSI: wall motion score

stolic myocardial velocity, Am: late diastolic myocardial velocity, SR: strain

Table 3

Angiographic and fractional flow reserve (FFR) parameters of all vessels

and comparison of these parameters of culprit vessels with respect to critical

coronary during FFR

Total Noncritical

stenosis

Critical

stenosis

p

No. of vessels 22 12 10

Coronary stenosis

in related vessel

(%)

57F16 48F11 66F17 0.006

Left anterior

descending

system (+/N)

16/22 9 7 NS

Circumflex system

(+/N)

3/22 1 2 NS

Right coronary

artery (+/N)

3/22 2 1 NS

Baseline proximal

pressure

(mm Hg)

89F18 86F16 92F21 NS

Baseline distal

pressure

(mm Hg)

77F17 79F16 74F19 NS

Baseline flow ratio 0.87F0.09 0.92F0.03 0.82F0.11 =0.005

Proximal pressure

after adenosine

infusion

(mm Hg)

90F17 84F15 98F17 =0.052

Distal pressure

after adenosine

infusion

(mm Hg)

66F16 71F14 60F16 NS

FFR after

adenosine

infusion

0.74F0.16 0.85F0.05 0.61F0.14 b0.0001

Table 4

Fractional flow reserve (FFR) parameters only in the vessels which supply

the left ventricular segment that evaluated with longitudinal tissue Doppler

and strain rate

Noncritical

stenosis

Critical

stenosis

p

No. of vessels 10 9

Coronary stenosis in

related vessel (%)

49F11 67F18 =0.017

FFR 0.85F0.06 0.60F0.15 b0.001

WMSI at peak DSE 1.18F0.47 1.54F0.37 =0.082

Change in Sm at

peak DSE

0.38F0.26 �0.63F0.39 b0.001

Change in Em/Am ratio

at peak DSE

�0.72F1.17 �1.42F1.45 NS

SR at peak DSE �2.16F1.88 �0.73F0.60 =0.044

S at peak DSE (%) �27.7F11.2 �12.0F7.2 =0.002

Change in SR at peak DSE �0.43F1.74 �0.71F0.52 NS

Change in S at peak DSE 0.14F0.34 �0.67F0.49 =0.001

These include left anterior descending and circumflex coronary arteries

(n=19). These parameters of culprit vessels were compared with respect to

critical coronary during FFR.

All abbreviations were defined in Table 2.

S. Dagdelen et al. / International Journal of Cardiology 102 (2005) 127–136132

changes in Sm and S during the DSE were significantly

decreased at the related segments in the ischemic group

( p=0.001 and b0.001, respectively). Although the baseline

and the peak SR at the peak DSE were not different among

the two groups, the baseline and the peak S at the peak DSE

were significantly decreased in the ischemic group ( p=0.02,

pb0.001), when analyzed for the longitudinal strain

deformation (n=19). All the above parameters are docu-

mented in Table 2.

The fractional flow reserve was studied in 22 vessels, and

10 of them were found to be critically decreased. Angio-

graphic coronary stenosis was significantly greater in the

critical vessels during the FFR measurements ( p=0.006).

Coronary artery distribution investigated by the FFR was

similar in the critical and noncritical coronary stenotic group.

Baseline proximal and distal coronary pressure and proximal

and distal pressure after adenosine infusion were not

different in the coronary artery with critical and noncritical

stenosis. Baseline flow ratio in the vessel and FFR after

adenosine infusion were significantly lower in the critical

stenotic group ( p=0.005, pb0.0001, respectively). The

distribution of the FFR parameters is documented in Table 3.

Analyzing the longitudinal strain rate segments (except

right coronary artery and radial strain rate) at 19 left

ventricular segments, the WMSI during the DSE was not

different in the vessels with critical and noncritical stenosis

during the FFR after adenosine infusion ( p=0.08). Although

the WMSI at the peak DSE was not different, changes in the

Sm values, SR, S and changes in the S values at the peak

DSE were significantly lower in the critical FFR vessels

than the noncritical ones ( pb0.001, p=0.044, p=0.002,

p=0.001, respectively) (Table 4).

When critical coronary stenosis during the FFR measure-

ment (n=10 critical vessels) was analyzed, the WMSI, Sm,

Em/Am, Am, SR and S values showed significant change at

the peak DSE. On these cases, although the WMSI, Em/Am

and Am values were significantly increased ( pb0.001,

p=0.041, p=0.037, respectively), the Sm, SR and S values

were significantly decreased ( p=0.04, p=0.01, p=0.019,

respectively) (Table 5).

In all the vessels, the FFR after adenosine infusion

showed a poor correlation with the WMSI, Em, Am, Em/

Am values, and the change in SR values (r=�0.22, 0.16,

�0.14, 0.21, 18, respectively), and a good correlation with

the change in S (r=0.51; p=0.014), and a very good

correlation with the change in Sm values (r=0.77;

pb0.001) at the peak DSE. So, even though the change in

the SR values at the peak DSE did not have a good

correlation in all the vessels analyzed by the FFR, it had a

good correlation in the critical stenotic vessels found in the

FFR measurement (r=0.59). When the FFR values at the left

coronary system (only in the vessels supplying the related

left ventricular segments that were evaluated with the

longitudinal strain rate) were analyzed for the longitudinal

SR and S values, it had a mild correlation with SR (r=0.47,

p=0.044) and a good correlation with S (r=0.66, p=0.002).

After the FFR study, six of the vessels were scheduled for

coronary bypass surgery, four of them for percutaneous

Table 5

Parameters of the vessels found critical during FFR measurement, and its

comparison with baseline and peak DSE parameters

No. of

vessels

(critical in

FFR)=10

Baseline DSE Peak DSE p

WMSI 1.16F0.47 1.51F0.36 b0.001

Sm (m/s) 0.041F0.024 0.027F0.015 =0.004

Em (m/s) �0.046F0.018 �0.040F0.017 NS

Am (m/s) �0.045F0.022 �0.068F0.028 =0.037

Em/Am 1.20F0.66 0.71F0.57 =0.041

SR (s�1) �0.098F1.06 �0.57F0.76 =0.010

S (%) �17.1F15.2 �10.2F8.8 =0.019

All abbreviations were defined in Table 2.

S. Dagdelen et al. / International Journal of Cardiology 102 (2005) 127–136 133

coronary revascularization and the remaining 12 vessels had

medical therapy.

5. Discussion

This study demonstrated that: (1) visual assessment of

the wall motion and the WMSI during the DSE are not

enough to detect critical coronary stenosis; (2) SR imaging

can be used for the assessment of the myocardial function in

a routine clinical setting; (3) SR imaging, in combination

with the dobutamine stimulation, is an accurate means to

determine critical coronary stenosis determined by the FFR

study; and (4) SR imaging is favorable in comparison with

the two-dimensional echocardiography and tissue Doppler

imaging in the determination of critical coronary stenosis

and has a good correlation with the FFR measurements of

the culprit vessel.

The shortcomings of angiography to assess the physio-

logic significance of coronary atherosclerosis are well

known. Particularly in patients with diffuse disease or

unstable coronary syndromes, the angiogram is of little help

to ascertain the potential of an individual stenosis to cause

reversible myocardial ischemia. Fractional flow reserve was

defined to dissolve this problem. So, it has been used to

differentiate whether angiographically moderate coronary

stenotic lesions are critical or not [21].

Many noninvasive techniques have been used to identify

myocardial ischemia induced by coronary stenosis. Two-

dimensional DSE has been used as a widely available and

cheap method for assessment of myocardial viability.

However, the method is limited by the subjective evaluation

process [3]. Assessment of myocardial contractility in

segments adjacent to infarct-related areas is difficult. There

have been many prior attempts to quantify regional

myocardial function during stress echocardiography. Our

findings demonstrate that ischemic left ventricular segments

generally show a hypokinetic response during the DSE as

previously declared. As we showed in our study, visual

assessment of left ventricular ischemia has many limitations,

and may cause misinterpretation.

In any case, the present study showed that although the

WMSI increased in the critical coronary stenotic group, it did

not significantly change compared to critical and noncritical

coronary stenosis during the FFR study ( p=0.08). Ultra-

sound-based methods have attempted to quantify either

short- or long-axis function of the left ventricle. It has been

based either on automated border detection [22], colour

kinesis [23], anatomic M-model [24], the measurement of

atrioventricular valve plane displacement [25], or regional

myocardial velocities [26]. However, the diagnostic accu-

racy of these methods is inherently limited, as all of them are

based only on quantifying regional myocardial motion which

can be influenced both by overall heart motion and by

motion induced by tethering to adjacent segments [27].

As previously observed, we showed in our analysis that

tissue velocity might be promising for detection of ischemic

myocardial segment, but it is not enough to differentiate real

ischemic segment from the nonischemic one during the

DSE. In theory, segmental strain/strain rate imaging can

largely overcome these limitations by measuring the

deformation derived from the local data. This should be

independent of the overall heart motion [28]. This benefit

has been confirmed in several studies which examined the

regional myocardial response to a dobutamine infusion, both

in the experimental and clinical settings [29,30]. However,

the routine use of the strain rate and strain measurements

during the dobutamine stress echo has been challenged as a

new quantitative method.

Evaluation of the real ischemic segment by using the

tissue Doppler velocity during the DSE, the Sm value and

the ratio of change in Sm were more reliable than the

diastolic tissue velocity parameters especially in patients

who had critical coronary stenosis during the FFR study

( pb0.001). However, still, in our study it is not easy to say

that the tissue Doppler velocity during the DSE is totally

reliable to detect the real ischemic segment. Since the tissue

Doppler imaging does not differentiate between the active

contraction and the passive following of tissue, the tethering

effect may cause misdiagnosis. Thus, the rotation and the

translation movements of the whole heart, as well as the

active contraction of the segments adjacent to the analyzed

segment, may affect the determined velocity. The point

velocity measured by the tissue Doppler imaging may

therefore incorrectly reflect the contractility of the analyzed

segment. Hoffmann et al. [8] investigated the use of the

tissue Doppler and the strain rate imaging, in combination

with the left ventricular stimulation, using dobutamine for

the identification of viable myocardium determined by the18FDG PET in patients with significant left ventricular

dysfunction. They showed that the increase in the peak

systolic strain rate during low-dose dobutamine stimulation

allows accurate differentiation between the different myo-

cardial viability states, and the strain rate imaging is superior

to the two-dimensional DSE and the tissue Doppler imaging

for the assessment of myocardial viability. This is con-

current with our findings, since we think that the tissue

S. Dagdelen et al. / International Journal of Cardiology 102 (2005) 127–136134

Doppler has more limitators compared with the strain rate

imaging during the DSE. In the study published by

Hoffmann, they investigated the patients with severe left

ventricular dysfunction; however, we investigated the left

ventricular segments which were not akinetic or dyskinetic.

Tissue Doppler parameters during the DSE may be

comparable with other invasive and the noninvasive

techniques. Voigt et al. [10] investigated the regional

myocardial strain rate and the strain response during the

DSE in patients and compared the results with the conven-

tional DSE readings, perfusion scintigraphy, and coronary

angiography. They showed that the strain rate imaging is

feasible in the clinical setting. It measured longitudinal

myocardial deformation directly independent of translation,

and offered parameters comparable and possibly superior to

the visually assessed regional wall thickening. This allowed

them to quantify strain rate, providing a cutoff value of these

parameters for the detection of stress-induced ischemia. We

also showed that the strain rate and the strain parameters

during the DSE were more reliable for detecting the real

ischemic myocardial segment referred by the FFR study.

These parameters analyze the critical coronary stenosis

during the FFR measurements and determine the ischemic

left ventricular segment during the DSE (for all pb0.05).

Voigt and colleagues showed that 43% of the patients had an

ischemic response in myocardial scintigraphy, and all

patients with inducible myocardial ischemia had significant

coronary stenosis (N50%) in the supplying coronary artery.

As we showed in our study, a N50% coronary stenosis in

quantitative assessment of coronary angiography is not

exactly enough to detect myocardial ischemia caused by that

stenosis, and 50% coronary stenosis may cause coronary

ischemia when compared to both myocardial ischemia and

to the FFR measurements.

Edvardsen et al. [31] evaluated whether the strain rate

imaging could detect acute myocardial ischemia or not, and

compared this new method with the tissue Doppler imaging

and the WMSI during acute coronary ischemia. They

investigated the patients undergoing angioplasty of the left

anterior descending coronary artery, and assessed left

ventricular longitudinal wall motion by the tissue and strain

Doppler imaging from the apical four-chamber view before,

during and after angioplasty from multiple myocardial

segments simultaneously. They concluded that the strain rate

imaging detected longitudinal dyskinesia during occlusion of

the left anterior descending coronary artery more frequently

than the tissue Doppler velocity. This conclusion is consistent

with our findings; we also found that in the event of the real

coronary ischemia, measurement of the strain rate imaging

during the DSEwas more reliable than the tissue Doppler and

visual assessment of the wall motion alone.

However, the study published by Edvardsen has several

differences, and of course these bring some discussions to

the mind. All patients in their study had 75% coronary

stenosis angiographically; only the left anterior descending

coronary segment was investigated; all the strain rate

imaging were studied during total occlusion of the same

vessels; and their findings reflected acute myocardial

ischemia. However, in our study, the patients having 40%

coronary stenosis angiographically were admitted to the

study; vessels other than the left anterior descending

coronary artery were investigated. Also, we investigated

the possible chronic myocardial ischemia in these vessel

segments. In fact, we measured the fractional flow reserve

of the culprit vessels to determine the expressive action of

the strain rate imaging during the DSE in the event of any

mild-moderate to severe coronary stenosis.

Although the strain rate imaging during the DSE

measures longitudinal deformation, in our study, both the

SR and the change in SR were significantly reduced in the

ischemic segments, confirming earlier studies [6,32]. How-

ever, there are no studies to investigate the direct correlation

between the FFR measurement and the strain rate imaging

parameters of the left ventricular segment supplied by the

same vessel. We found that the strain rate imaging

parameters have a good correlation with the FFR measure-

ments of the culprit vessel. It is interesting that as

quantitative methods, the FFR study for coronary angiog-

raphy and strain rate imaging for the Doppler echocardiog-

raphy can be combined for evaluation and for planning

intervention. Both these techniques investigate maximal

reserve of the related parameters which interrogate criticism

of the coronary stenosis with adenosine infusion and the

ischemic expression of the myocardium during the DSE.

The correlation between SR imaging and FFR parameters

on stress in the vessels which have demonstrated critical

coronary stenosis is not surprising. The validity of a good

correlation between the same parameters in all 40% of

stenotic vessels is still interesting. We think that this finding

is very important, and is the most interesting result of this

study. The findings of the present study may be interpreted

such that angiographically chronic mild to moderate

coronary stenosis may insidiously cause myocardial injury.

5.1. Limitations

Strain measurements are angle-dependent, possibly more

so than any other Doppler modalities. Tissue deformation in

one direction is always associated with the deformations in

other directions to keep the mass of the structure constant.

Therefore, interpretations of the strains should be performed

with caution if the tissue direction deviates more than 308from the beam direction. The angle problem is a significant

limitation of this technique and repositioning of the trans-

ducer must be done to avoid the problem.

In this study, we assessed the longitudinal and radial

dimension to evaluate both left (longitudinal strain) and

right (radial strain from short axis view) coronary systems.

Important data about the radial and the circumferential strain

may therefore be misinterpretated. However, we analyzed

all the tissue Doppler parameters and the ratio of the change

in the strain rate parameters which are not mostly affected

S. Dagdelen et al. / International Journal of Cardiology 102 (2005) 127–136 135

from the longitudinal and the radial planes. So, the SR and

the S values that parameters exactly change from radial to

longitudinal planes were analyzed only for the cases studied

with longitudinal strain rate imaging.

As far as coronary selectivity goes, our study population

did not contain only one vessel system. We investigated

mostly the left anterior descending system, but also included

the circumflex and the right coronary systems.

In the present study, we did not investigate inter- and intra-

observer variability, so this is another limitation of this study.

5.2. Conclusion and future perspectives

Conventional DSE is a well-established method to detect

wall motion abnormality, but it seems that this subjective

evaluation is not enough to be a good standard. It is certain

that the WMSI significantly increases in the event of critical

coronary stenosis in the FFR measurements, but this

certainty is not valid in all degree of coronary stenosis.

During the DSE, the SR imaging may be used to improve

the relation between the DSE and the FFR measurements.

Critical or noncritical coronary stenosis shown by the FFR

measurements may not cause any visual wall motion

abnormalities all the time, and also mild hypokinesia

induced by moderate coronary stenosis may not make a

difference. In our study, we showed that the tissue and the

strain Doppler imaging parameters (especially Sm, Em/Am,

SR and S values) during the DSE significantly reflect the

myocardial ischemia convenient with the FFR values of the

culprit vessel. Although there is a poor correlation between

the WMSI and the FFR values in the same culprit vessels,

the quantitative tissue Doppler and SR imaging parameters

during the DSE have a good correlation with the FFR

values, especially on the Sm, SR and S.

The quantitation of regional myocardial deformation by

using the DSE rather than the wall motion abnormality

alone would be more appropriate in detecting ischemic

dysfunctional segment supplied by the critical or the

noncritical stenotic coronary artery. Strain rate measure-

ments during the dobutamine infusion may provide infor-

mation on the FFR results of the culprit vessel. Our study

population is not large enough to detect more data. These

are limited in terms of the formulation of the data between

the SR imaging and the FFR values, and to calculate the cut

of point values of them. Future studies including a larger

study population and more selective cases will be needed to

show the accuracy of SR imaging results during the DSE

when compared with the FFR values. These studies may

predict the functional improvement after revascularization.

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