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Since velocity imaging is confounded by influence from velocities in other segments, the TDI-based modalities strain- and strain rate imaging SRI have been introduced to measure regional

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artery disease

Purpose of review

Tissue Doppler imaging (TDI) is a diagnostic method that

provides quantitative data about myocardial function The

present review discusses the most recent developments in the

application of TDI in coronary artery disease

Recent findings

The most widely used TDI modality is velocity imaging, and

systolic function is measured as peak velocity during LV

ejection Several recent studies show that TDI measurements

during the LV isovolumic phases provide unique information

regarding myocardial dysfunction Since velocity imaging is

confounded by influence from velocities in other segments, the

TDI-based modalities strain- and strain rate imaging (SRI) have

been introduced to measure regional shortening fraction and

shortening rate, respectively

Velocity imaging during stress echocardiography has been

validated clinically and appears equivalent, but not superior to

conventional visual assessment of grey scale images

Potentially, more comprehensive evaluation that includes the

use of SRI may improve the diagnostic power of TDI further

Preliminary reports suggest that TDI may have an important

role in the assessment of viability in acute coronary occlusion,

but this needs to be demonstrated in appropriately designed

clinical trials

Summary

At the present time tissue Doppler velocity imaging can be

recommended for clinical use, especially the pulsed mode

Strain rate imaging may be useful as additional imaging, but

needs further refinement before it is ready for routine clinical

use

Keywords

echocardiography, tissue Doppler, coronary artery disease,

acute myocardial infarction

Curr Opin Cardiol 19:421–429 © 2004 Lippincott Williams & Wilkins.

Introduction

In clinical practice left ventricular (LV) function is com-monly evaluated by 2-D and M-mode echocardiography These modalities have significant limitations,and tissue Doppler imaging (TDI) has been introduced as a quan-titative and more objective method for assessing myocar-dial function The TDI modalities include myocarmyocar-dial velocity imaging,displacement imaging,strain rate im-aging,and strain imaging (Fig 1) This review discusses the most recent developments in TDI-based cardiac di-agnostics,and discusses how TDI may be applied in the evaluation of patients with acute myocardial infarction as well as chronic coronary artery disease

Velocity imaging

As with Doppler flow,tissue Doppler (TDI) measures velocities by the Doppler shift of reflected ultrasound The signals are of low velocity and high intensity,and are obtained with low pass filtering and low gain Veloc-ities are measured in the conventional imaging planes, from apical views as longitudinal velocities and from parasternal views as radial velocities Velocities can be obtained using pulsed Doppler or color Doppler mode [1]

Pulsed Doppler measures velocities in one sample volume

at a time by spectral analysis Due to short pulse length, the spectrum is broad relative to the velocity scale This implies that peak velocities may be substantially higher than mean velocities,typically about 25% higher [2] The method is on line,relatively robust,easy to use,and quick

Color Doppler samples the velocities of all pixels in the sector nearly simultaneously,and by post processing ve-locities in different parts of the ventricle can be mea-sured on the same image (Fig 1) Velocities are obtained

by autocorrelation,which gives mean values By per-forming temporal integration of velocities from a

particu-lar region one obtains displacement curves In long-axis

views velocity and displacement increase progressively from apex towards base Color coding of the displace-ment values in the image has been proposed as an easy approach to detect regional myocardial dysfunction at rest and during stress echocardiography [3,4], but the technique needs further clinical testing

When myocardial velocities are measured by TDI the transducer represents a fixed extracardiac reference

a Department of Cardiology, Rikshospitalet University Hospital, Oslo, Norway and

b NTNU, Trondheim, Norway

Correspondence to Otto A Smiseth, Department of Cardiology, Rikshospitalet,

N-0027 Oslo, Norway

Tel: 4723070000; e-mail: o.a.smiseth@klinmed.uio.no

Current Opinion in Cardiology2004, 19:421–429

© 2004 Lippincott Williams & Wilkins

0268-4705

421

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point,and the velocities within a myocardial segment is

the net result of motion caused by contractions in that

segment,motion due to tethering to other segments,and

overall motion of the heart The effect of tethering

ex-plains why left ventricular (LV) longitudinal velocities

measured from an apical window,increase progressively

from the apex towards the base During the cardiac cycle

the ventricular apex is relatively stationary,while the

mitral ring moves towards and away from the apex during

systole and diastole,respectively Therefore,mitral ring

motion is in essence the sum of all longitudinal

shorten-ing and lengthenshorten-ing between the apex and the base

Thus,ischemia in the apical region causes reduced

myo-cardial velocities not only in the apex,but also in the

nonischemic basal portion of the ventricle [2,5]

Impor-tantly,the reduced TDI velocities in basal segments do

not mean there is a reduction in function in these

seg-ments Likewise,due to tethering,contractions in

non-ischemic regions may cause velocities in neighboring

ischemic regions,and accordingly nonviable myocardium

appears to contract [2,5,6] The recently introduced TDI

modalities strain and strain rate imaging (SRI) may help

to overcome these limitations

Strain- and strain rate imaging

Strain means deformation and strain rate means

deforma-tion rate [7] Myocardial strain rate reflects how fast re-gional myocardial shortening or lengthening occurs,and

is calculated from myocardial Doppler velocities (V1and

V2) measured at two locations separated by a distance (L) [8] Strain rate equals the instantaneous spatial velocity gradient and has units of sec-1: SR = (V2-V1)/L Some

authors present the measurements as velocity gradient

in-stead of strain rate [9] When V1 and V2 are different there is deformation of the tissue in between In the case that the two locations are getting closer there is myocar-dial shortening,and when they move apart there is lengthening

Strain is calculated as the time integral of strain rate, most often using end-diastole as reference,and is a di-mensionless quantity [5] In clinical terms strain

repre-Figure 1 Tissue Doppler recordings from septum of a normal subject in a long axis view

The left column shows velocity tracings, with positive velocities towards the apex in systole, away from the apex in diastole The second column shows displacement curves obtained by temporal integration of the velocity curves The third column shows strain rate, obtained by a spatial derivation of velocity data Strain rate is negative

in systole (shortening) and positive in diastole (lengthening) The right column shows strain, obtained by temporal integration of strain rate The time axis is the same for all modalities Velocity and displacement decrease from base to apex, whereas strain and strain rate are similar in magnitude at all levels.

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sents regional myocardial shortening fraction when

mea-surements are done in the LV long axis,and thickening

fraction,in the short axis Alternatively one may report

strain values as percentage shortening and percentage

thicken-ing Strain rate represents regional myocardial shortening

rate and thickening rate,respectively.

Although strain and strain rate are load dependent [5]

this is not a major limitation in the assessment of

coro-nary artery disease,since finding of regional differences

is more important than absolute values

Methodological limitations of strain rate imaging

Since strain rate represents a difference between two

velocities there is a significant problem with random

noise The signal-to-noise ratio can be improved by

creasing the offset distance (strain length),which

in-creases the velocity difference The problem with

ran-dom noise can also be reduced by temporal averaging

within a heart cycle,and by averaging of multiple heart cycles However,these methods for noise reduction rep-resent compromises between optimal signal-to-noise ra-tio and requirements for spatial and temporal resolura-tion Semiquantitative information can be obtained directly from the color tissue recordings,and reduces the impor-tance of noise The derived curved color M-mode and 3-D color strain images (Fig 2) give a visual presentation

of data and may separate between true pathology and artefacts [10]

Another problem with strain rate imaging is strong sen-sitivity to misalignment between the cardiac axis and the echo beam Strains in the long axis are opposite to strains

in the short axis,and when there is misalignment the two strain tensors detract from each other [5] A recent study indicates that this problem might be less important [11] Angle problems can be reduced by using the smallest possible sector and recording one wall at a time

Figure 2 Reconstructed three-dimensional color-coded strain rate images of the left ventricle from a subject with

acute apical myocardial infarction

Longitudinal shortening (contraction) is shown in yellow

and lengthening in blue Top: reconstructed bull’s eye

views showing the whole ventricle at once, but with

distorted area representation Bottom: Three-dimensional

surfaces seen from the antero-apical aspect The left

image is recorded in mid systole and the blue colored area

represents positive strain rates, which means systolic

lengthening, and is typical for infarcted myocardium The

right image is from early diastole and the yellow colored

area, which represents negative strain rates indicates

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An experimental study by Hashimoto et al [12] suggests

that assessment of strain rate in different myocardial

lay-ers may be feasible This application has obvious

limita-tions with regard to lateral resolution,which is related to

the high density of echo beams that is required It

re-mains to be determined if this approach can be used in a

clinical setting

Tissue Doppler imaging-based indices of

myocardial function

Ejection phase indices

Tissue Doppler imaging has excellent ability to quantify

myocardial function and has good temporal resolution

[1,13] Ischemic regions are characterized by a decrease

in peak systolic ejection velocity,and a decrease in peak

early-diastolic myocardial lengthening velocity [14,15]

Measurement of peak ejection velocity is the most

widely used TDI measure for quantifying regional

func-tion in suspected coronary artery disease Longitudinal

velocity measurements are more reproducible than radial

velocities,and are therefore usually preferred On the

other hand longitudinal velocities show more variability

between segments and this complicates clinical use

Re-cently,reference values were presented from a group of

normal individuals [16] There is,however,need for

larger age- and sex-stratified studies and these should

include measurement of strain and strain rate as well

Several groups are currently working with establishing

such reference values

A number of studies suggest that analysis of function

during the isovolumic LV phases provide additional

im-portant diagnostic information In the subsequent para-graphs we will review some of the studies

Preejection indices

Preejection velocity predicts recovery of function after reperfusion

Experimental studies indicate that velocities during iso-volumic contraction (IVC) may serve as a means to de-termine degree of myocardial dysfunction during ische-mia [17] In ventricles with preserved systolic function there is a dominantly positive longitudinal velocity dur-ing IVC,with only a minor negative velocity component With progressive ischemia the positive velocity compo-nent diminishes,and the negative compocompo-nent increases During severe ischemia the positive component is lost and replaced by a large negative IVC velocity (Fig 3) The negative IVC velocity is a reflection of the early systolic lengthening,which is a hallmark of severe

ische-mia Penicka et al [18] tested the ability of IVC velocities

to predict recovery of myocardial function after coronary revascularization in myocardial infarction They showed that a positive IVC velocity after revascularization pre-dicted recovery of function in the reperfused area This study suggests that measurement of IVC velocities may provide important diagnostic information with regard to myocardial viability after coronary reperfusion

Does myocardial IVC acceleration reflect inotropy?

Similar to LV ejection fraction,peak systolic ejection

velocity is preload and afterload dependent Vogel et al.

[19] proposed that myocardial IVC acceleration (IVA)

Figure 3 Data from an experimental study before (left panel) and during coronary artery occlusion (right panel)

Before coronary occlusion there is a dominantly positive Doppler velocity spike during IVC and a more protracted velocity during ejection During IVR there are only minor velocity spikes During coronary occlusion the velocity profile is dominated by a large negative velocity during IVC and a marked positive velocity during IVR, while ejection velocities are near zero The lower panels show regional function by sonomicrometry, and confirms that the negative IVC velocity during LAD occlusion represents systolic lengthening and the positive IVR velocity means

postsystolic shortening Modified from Edvardsen et al.

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would be a load-independent measure of contractility In

an animal model they measured longitudinal myocardial

velocities near the LV base,and demonstrated that IVA

reflected myocardial contractility,and appeared to be

load independent However,this study was done in the

nonischemic ventricle,and measurements were taken

near the mitral ring,which means they measured in

es-sence global LV function In a recent experimental study

Lyseggen et al [20] validated IVA as a measure of

re-gional function during myocardial ischemia This study

confirmed that IVA was related to global LV

contractil-ity,but IVA did not reflect function in the ischemic

myocardium Thus,IVA appears to have limited

poten-tial to serve as a measure of regional function during

ischemia

Postejection indices

It has been known for long that postsystolic shortening

(LV long axis) and postsystolic thickening (short axis) are

characteristic features of ischemic myocardium [21] As

alternative terminology one may use postejection

shorten-ing and thickenshorten-ing,since the myocardium shortens and

thickens after aortic valve closure Postsystolic

shorten-ing can be measured directly with strain Doppler

echo-cardiography and is measured as myocardial shortening

that occurs after cessation of aortic forward flow

Post-systolic shortening can also be imaged by velocity

imag-ing,and is in the long axis represented by a positive

velocity component during isovolumic relaxation (IVR)

Figure 4 demonstrates postsystolic shortening as

mea-sured by velocity imaging

As demonstrated by Voigt et al [22] minor degrees of

postsystolic shortening occurs in normal myocardium,

and is not pathologic unless it exceeds a certain magni-tude in absolute terms or represents a substantial fraction (> 20%) of total myocardial shortening (Fig 5) The mechanism of postsystolic shortening in normal myocar-dium is not defined,but may be related to the LV shape changes and untwisting motion that occur during IVR

Postsystolic shortening and viability in acute myocardial infarction

Postsystolic shortening by DTI has been proposed as a marker of myocardial viability during acute coronary oc-clusion,with the rationale that it may represent active myocardial contraction Postsystolic shortening,how-ever,may occur in entirely passive or necrotic dium as well as in actively contracting ischemic myocar-dium [23] Therefore,the isolated finding of postsystolic shortening is nonspecific with regard to tissue viability The mechanism of postsystolic shortening in passive myocardium is analogous to the behavior of a stretched elastic spring; it will recoil passively when the stretching force is removed Thus,dyskinetic myocardium,which

by definition is stretched in systole by nonischemic cardium,will recoil during IVR when nonischemic myo-cardium relaxes and the stretching force drops abruptly

However,measurement of postsystolic shortening may help to identify viable myocardium,provided that strains during IVC and ejection are assessed simultaneously First,if postsystolic shortening occurs in the absence of systolic lengthening passive recoil can be excluded,and therefore the postsystolic shortening represents delayed active contraction [23] Second,as suggested by recent experimental data,when a segment is dyskinetic,but the

Figure 4 Postsystolic shortening in ischemic myocardium

Myocardial velocity curves from a patient with significant

stenosis of the left anterior descending coronary artery.

The dashed curve shows longitudinal velocity in a normal

lateral segment The continuous curve shows velocity in an

ischemic segment in mid septum This ischemic segment

has reduced systolic velocity, and during early diastole

there is a marked positive velocity (arrow), which

represents postsystolic shortening S, systolic velocity; E’,

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postsystolic shortening far exceeds the systolic

lengthen-ing in magnitude,it is likely that active contraction

con-tributes to postsystolic shortening [24] Thus,Skulstad et

al [24] proposed that the ratio between systolic

length-ening and combined late systolic and postsystolic

short-ening may serve as a marker of active as opposed to

passive postsystolic shortening The rationale for this

as-sociation is that active wall tension will limit systolic

lengthening and enhance active postsystolic shortening

A postsystolic strain index expressed as ratio between

postsystolic shortening and systolic shortening has been

proposed by Kukulski et al [25•] They showed that this

index was a highly sensitive and specific marker of

myo-cardial dysfunction during acute myomyo-cardial ischemia

Although this index may be useful since it “normalizes”

the postsystolic shortening values,it has an evident

limi-tation when studying segments with akinesia,and

there-fore very small systolic strain In the latter case even a

postsystolic shortening of trivial magnitude may

repre-sent a large fraction of systolic strain [26] In these cases

the absolute rather than the relative postsystolic

short-ening will be of interest

Song et al [27] investigated patients several months after

myocardial infarction and found that postsystolic

thick-ening as demonstrated by TDI was associated with signs

of tissue viability The study,however,was limited by

absence of reference method or postintervention data

that confirmed viability

From a clinical perspective the differentiation between

active and passive postsystolic shortening is critical,since

active contraction implies viable myocardium

Potentially,assessment of postsystolic shortening may help in patient triage in acute myocardial infarction,in particular when thrombolysis has been primary treat-ment and transfer for rescue PCI is considered At the present time,however,we lack prospective trials that confirm the clinical value of assessing postsystolic short-ening in acute myocardial infarction

Postsystolic shortening in stress echocardiography

In the setting of stress echocardiography,when postsys-tolic shortening is absent during baseline,but appears during dobutamine it is a marker of myocardial ischemia [28•] (Fig 6)

Furthermore,as demonstrated in an experimental study

by Weidemann et al [26] dobutamine-induced

enhance-ment of postsystolic thickening along with a reduction of systolic thickening differentiates nontransmural from transmural chronic infarctions Therefore,measurement

of postsystolic shortening/thickening is a promising ap-proach in the analysis of stress-echocardiography record-ings

Stress echocardiography

Conventional stress echocardiography is based on visual assessment of systolic wall thickening and endocardial excursion,and suffers from being subjective and pro-vides only qualitative or semiquantitative data [29] Fur-thermore,visual assessment has poor temporal resolu-tion,and therefore has limited ability to detect more subtle changes in myocardial function [30,31] Tissue Doppler represents a means to quantify regional function objectively and with much better temporal resolution [32,33] Pulsed Doppler is too time consuming to allow measurements from all segments during the final stress

Figure 5 Postsystolic shortening in a normal individual

Recordings from the midseptal region in a young control subject, showing strain rate (a) and strain (b) ECG is included for referencing The timings of mitral valve closure (MVC), aortic valve opening (AVO), aortic valve closure (AVC), and mitral valve opening (MVO) are indicated In this person there is slight postsystolic shortening that starts at the time of mitral valve opening,

as indicated by negative strain rate and a decrease in

strain Reproduced from Voigt et al [22].

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stage,while color Doppler recordings are obtained much

faster and measurements are done during post processing

[34]

Fraser et al [35•] in the MYDISE (MYocardial Doppler

In Stress Echocardiography) study have examined the

feasibility and reproducibility of segmental tissue

Dopp-ler in dobutamine stress echocardiography They

re-ported that analysis was feasible in 90% of examined

segments in 92 normal subjects,but their analysis was

limited to basal and mid wall segments Reproducibility

was examined in the same cine-loops from 10 subjects

Coefficients of variation for peak systolic velocity and

time to peak velocity were up to 18% in basal segments

and 28% in midwall segments at peak stress The clinical

utility of the method then depends on the magnitude of

the increase from baseline to peak stress

The same group addressed the diagnostic accuracy of

tissue Doppler in stress echo in a population of 289

sub-jects by Mädler et al [36•] Peak systolic velocity at peak

stress,rather than change in velocity from baseline was the best discriminator of disease,but sensitivity was only

63 to 69% and specificity 60 to 67% for the different vascular regions,which are somewhat lower values than previously reported by the Brisbane group [37]

How-ever,when Mädler et al [36] applied a regression model,

which included age,gender,and peak heart rate,sensi-tivity increased to 80 to 93% and specificity to 80 to 82% These results imply that not only heart rate,but also age and gender should be taken into account when interpret-ing stress echo by tissue Doppler Importantly,the Bris-bane group has shown that less-experienced observers obtain a significant improvement in sensitivity and ac-curacy using TDI relative to visual assessment in inter-preting dobutamine echocardiography [38]

A few studies using strain rate imaging in stress

echocar-diography have been recently published Davidavicius et

al [39] found that 95% of segments could be analyzed

Figure 6 Strain and strain rate responses during stress echo

This figure displays LV two-chamber perfusion scintigraphic images and color-coded strain rate images (a), and strain rate (b), strain (c), and ECG (d) traces prior to and at peak dobutamine stress The arrow in the upper right panel points to a perfusion defect Strain and strain rates are recorded from the ischemic region and a nonischemic region During peak stress the strain trace from the ischemic apical region demonstrates early-systolic lengthening and postsystolic shortening SRpeak sys indicate peak systolic strain Tbosand teosindicate beginning and end of shortening, respectively Emax, Eet, and Epsindicate max strain during the heart cycle, strain

during ejection and postsystolic strains, respectively Reproduced from Voigt et al [28].

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during dobutamine stress Due to noise problems strain

rate imaging was not feasible during treadmill or bicycle

stress The study,however,was small and was limited to

healthy individuals Kowalski et al [40] extended the

testing of SRI to patients with coronary artery disease

The normal response during dobutamine stress was an

increase in strain rate and strain at low dose dobutamine,

a further increase in strain rate at high dose,when strain

showed a plateau due to the increased heart rate Their

study confirms that SRI may have a clinical potential,but

was not designed to determine the ability of SRI to

di-agnose coronary artery disease

The clinical value of SRI was addressed by Voigt et al.

[28] The study included 44 patients and single photon

emission computed tomography (SPECT) was used as

reference method for ischemia The ratio of postsystolic

shortening to maximum segmental shortening was the

best parameter to identify stress-induced ischemia

Fur-thermore,compared with conventional gray scale readings

SRI curved M-mode improved sensitivity/specificity

from 81/82% to 86/89% The statistical significance of

this difference,however,is not given in the paper

Abra-ham et al [41] introduced the time to onset of regional

LV relaxation as a measure of ischemia during stress

echo This is an interesting approach that needs further

clinical testing

Conclusion

Tissue Doppler echocardiography has proved to be an

accurate method for quantitative evaluation of regional

myocardial function,and the most widely used measure

in coronary disease is peak velocity during LV ejection

So far TDI has not replaced conventional grey-scale

im-aging in the assessment of regional LV function Further

studies are needed to determine if inclusion of

pre-injection and post-ejection velocities and timing of

events may increase the diagnostic power Recent

devel-opments in 3-D cardiac imaging could allow more

com-prehensive visualization of myocardial function

Ulti-mately,for the clinician it is critical that the advantages

of the new quantitative methodologies outweigh their

disadvantages in terms of complexity and cost At the

present time tissue Doppler velocity imaging can be

rec-ommended for clinical use,especially the pulsed mode

Strain rate imaging may be useful as additional imaging,

but needs further refinement before it is ready for

rou-tine clinical use

References and recommended reading

Papers of particular interest, published within the annual period of review,

have been highlighted as:

• Of special interest

•• Of outstanding interest

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••

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