Heart Fail Rev (2006) 11:289–303DOI 10.1007/s10741-006-0230-1

Imaging of myocardial dyssynchrony in congestive heart failureBoaz D. Rosen · Albert C. Lardo · Ronald D. Berger

C© Springer Science + Business Media, LLC 2006

Abstract Heart failure constitutes a major health problem inUSA and Europe. Angiotensin converting enzyme inhibitorsand blockers were shown to reduce morbidity and mortal-ity in patients with CHF. Yet, their effectiveness is limited.A significant number of patients with heart failure mani-fest myocardial conduction abnormalities. Conduction ab-normalities, especially in the form of left bundle branch block(LBBB) may be associated with abnormal mechanical func-tion. Several studies demonstrated that these patients maygain benefit from biventricular (BiV) pacing in terms of im-provement in exercise tolerance, heart failure morbidity andeven decreased mortality. BiV pacing was also associatedwith improvement in ejection fraction, reduction in the ex-tent of mitral regurgitation and a decrease in cardiac size (re-verse remodeling). However, a significant number of patientsdo not gain benefit from biventricular pacing despite havingconduction abnormalities. The underlying reason is that theelectrical activity may not closely reflect mechanical activity.Several imaging modalities and techniques have been pro-posed to improve the selection of patients who may benefitfrom biventricular pacemakers. Of those, echo-Doppler, andespecially, Tissue Doppler Imaging has been demonstrated asimportant tools for evaluating patients for cardiac resynchro-nization therapy (CRT) and following their response. The ad-vantages of echo include accessibility, portability, its cost anda high temporal resolution. Yet, it is limited by its acousticwindows and scanning angles. MRI is a useful tool for evalu-ating patients for CRT by providing 3-D image of myocardial

B. D. Rosen (�) . A. C. Lardo . R. D. BergerDivision of Cardiology, Johns Hopkins University, Baltimore, MDe-mail: rosenbo 99@yahoo.com

B. D. RosenHeart Institute, Wolfson Medical Center, Holon, Israel

function. However, it is limited for follow-up after implan-tation due to its cost and a potential damage to the patientsor pacemakers. Dyssnchrony imaging is a rapidly evolvingfield. New imaging techniques such as speckle tracking arepromising and close update is needed to keep track of thedevelopments and the changes in this exciting field.

Keywords Congestive heart failure . Conductionabnormalities . Myocardial dyssnchrony . Biventricular(BiV) pacing . Cardiac resynchronization therapy (CRT) .

Tissue doppler imaging (TDI) . Strain . Strain rate

Introduction

Heart failure constitutes a major health problem in the UnitedStates and Europe. Approximately 5 million patients in theUSA suffer from congestive heart failure (CHF), and 500,000new patients are diagnosed annually as having CHF. Duringthe last 10 years, the number of annual hospitalizations dueto CHF increased from 500,000 to approximately 900,000.Moreover, CHF causes or contributes to 300,000 deaths peryear despite advances in therapy [1–7]. The prevalence ofheart failure increases with age and approximately 6–10% ofindividuals older than 65 years are diagnosed as having heartfailure [3]. With the aging of the population, the prevalenceof CHF is expected to increase.

Angiotensin converting enzyme (ACE) inhibitors and β-blockers have been shown to be effective in reducing morbid-ity and mortality in patients with CHF. Indeed, these drugs areconsidered as class I indication for the treatment of CHF [7].Yet, their efficacy is limited, mandating an additional therapyfor the treatment of heart failure, especially for patients withadvanced CHF (NYHA classes III and IV).

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290 Heart Fail Rev (2006) 11:289–303

Dyssynchrony in heart failure, cardiacresynchronization therapy (CRT)

Approximately third of the patients with heart failure demon-strate intraventricular conduction abnormalities [8–10].These conduction abnormalities are usually in the formof complete left bundle branch block (LBBB) or intra-ventricular conduction delay (IVCD) and are related to in-creased morbidity and mortality [9, 11]. Electrical conduc-tion abnormalities have been shown to be associated withimpaired global left ventricular function [12]. It has beenshown by tagged MRI that abnormal electrical activation byright ventricular pacing caused a redistribution in regionalmyocardial work and LV function expressed as myocardialstrains. During ventricular pacing, systolic fiber strain and ex-ternal work were markedly reduced in regions adjacent to thepacing site, and gradually increased to more than twice (com-pared to normal) in remote regions that include the free LVwall [13]. This redistribution of regional work was associatedwith changes in myocardial perfusion [14]. With increasingtime of dyssnchrony, these changes in regional workload havebeen translated to structural changes. Indeed, wall width ofearly activated regions (e.g septal thickness) became thin-ner than the later-activated posterior wall [15]. With furtherinvestigation, it has been shown that pre-excitation of thoseregions that demonstrate delayed activation by LV free wallpacing or biventricular (BiV) pacing, can improve contrac-tile LV function in patients with heart failure and completeLBBB [16, 17]. This improvement in the contractile func-tion was associated with reduction of energy cost resultingin enhanced mechanical efficiency [18, 19].

These studies set the stage to investigate the effect of car-diac resynchronization therapy (CRT) in patients with CHFand intraventricular conduction delays in large multi-centertrials. The design and the results of those studies are shownin Table 1. Both the Multisite Stimulation in Cardiomyopa-thy (MUSTIC) and Multicenter InSync Randomized Clini-cal Evaluation (MIRACLE) trials demonstrated benefit frombiventricular pacing in terms of improvement in exercise tol-erance, CHF symptoms and a decrease in hospitalizationsrelated to worsening of CHF [20, 21]. In the Comparison ofMedical Therapy, Pacing, and Defibrillation in Heart Fail-ure (COMPANION) study there was a 36% mortality re-duction in patients with advanced CHF who were treatedby implantable cardioverter defibrillators (ICD’s) and BiVpacing, and a trend toward mortality reduction (24%) inthose who were treated with BiV pacing only, when com-pared to maximal pharmacologic therapy. Finally, in the Car-diac Resynchronization- Heart Failure study (CARE-HF),there was a 35% reduction of mortality in patients who weretreated by CRT only and were followed for 29 months [22].These beneficial effects of CRT were accompanied by reduc-tion in left ventricular size and improvement in global my-

ocardial function , i.e reverse remodeling. Follow-up studiesdemonstrated a significant reduction in end-systolic and end-diastolic volumes, decrease in the severity of mitral regurgi-tation and an increase in ejection fraction of approximately5% or more [22–32]. These favorable effects were noted aftershort periods as well as after long term follow-up (6 monthsup to 18 months).

Limitations of electrical dyssynchrony as a parameterfor selecting of patients for CRT

Intra-ventricular conduction delay determined by QRS dura-tion and measured by surface ECG has been a major crite-rion for including patients in the large multicenter trials thatstudied the efficacy of CRT. Indeed, the ECG inclusion cri-teria for the MUSTIC, MIRACLE and COMPANION trialswere QRS duration of >150 ms, ≥130 ms and ≥120 ms,respectively [20, 21, 33]. However, the results of studies thatinvestigated the relationship between baseline QRS widthand the effects of CRT were conflicting. A better response toCRT in patients with longer QRS duration was seen in somestudies [34, 35]. However, in other studies, initial QRS dura-tion was found to be a poor predictor of long-term response[20, 27, 36]. Moreover, Leclercq et al. demonstrated an acuteimprovement in the LV hemodynamics and regional func-tion by LV epicardial pacing. This pacing mode was associ-ated with a significantly increased electrical dispersion [17].These findings should be viewed in the appropriate perspec-tive since approximately one third of the patients who fulfillthe ECG criteria for CRT do not obtain a clinical benefit fromCRT [20, 37]. In the opposite side of the spectrum, Achilliet al. documented a favorable response from CRT in patientswith advanced CHF who were refractory to pharmacologictreatment and had a narrow QRS (QRS duration ≤120 ms).Their response was not significantly different from the re-sponse of patients with longer QRS durations [23]. There-fore, for a better selection of the appropriate candidates whomay benefit from CRT, the criterion of electrical dyssyn-chrony is not sufficient, and additional proof of a mechan-ical contractile dyssnchrony or discoordination is essential.Different imaging modalities, of whom echocardiographyplays a major role, are utilized to address the issue of mechan-ical synchrony (or dyssynchrony). These imaging modalitiesmay facilitate the appropriate selection of patients for BiVpacing, optimizing and up-tuning their pacing parametersand following of the response to CRT.

Imaging mechanical dyssynchrony by echocardiography

Although determination of inter-ventricular and intraventric-ular dyssnchrony gained much importance along with the

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Heart Fail Rev (2006) 11:289–303 291

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Springer

292 Heart Fail Rev (2006) 11:289–303

Tabl

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Heart Fail Rev (2006) 11:289–303 293

Fig. 1 Measurement of septalto posterior wall motion delay(SPWMD) by M-Modeechocardiograpy. The image wasacquired in short axis view at thelevel of the papillary muscles.Point ‘a’ marks peak systolicthickening of the septum whilepoint ‘b’ indicates the peakthickening of the posterior wall.The time difference betweenthose points is 330 ms. (From:Pitzalis MV, Iacoviello M,Romito R et al. Cardiacresynchronization therapytailored by echocardiographicevaluation of ventricularasynchrony. J Am Coll Cardiol.2002;40:1615–1622.)

development of CRT, it should be remembered that myocar-dial synchrony is also important in the level of the atrioven-tricular (A-V) conduction. Too long A-V delay is associ-ated with a decrease in early diastolic filling time and mitralvalve incompetence causing diastolic mitral regurgitation.Too short delay interferes with the late contribution of theatrial contraction to the diastolic filling (atrial kick). Bothimpair diastolic ventricular filling and reduce stroke volume[16, 38–42]. Thus, an optimization of the A-V delay is re-quired, and can be guided by echo-Doppler imaging. Optimalventricular filling can be achieved by choosing the longestdiastolic filling time which will not cause a truncation ofthe A wave [41]. This improved filling is associated withan increase in the aortic velocity -time integral (VTI), sys-tolic blood pressure, pulse pressure and the rate of rise in theLV pressure (dP/dT) [39–42]. Optimal A-V delay for mostof the patients is approximately 120–130 ms, but shouldbe tailored individually, according to echocardiographicguidance.

Selection of the appropriate patients for CRT is vital giventhe limitations of the electrical criteria (e.g QRS duration).Ventricular mechanical dyssnchrony can be demonstrated bynumerous echocardiographic parameters.

Interventricular mechanical dyssnychrony can be assessedby measuring the time from end diastole (or the beginningof the QRS complex on ECG) to the onset of aortic and pul-monary ejection (aortic and pulmonary pre-ejection times)

[38, 43, 44]. Bordachar et al. demonstrated in RV pacedpatients that an inter-ventricular difference of more than50 ms (aortic preejection interval longer than pulmonarypre-ejection interval) should be considered as a significantinterventricular dyssynchrony [44]. Other researchers con-sider a difference of more than 40 ms between the pul-monary and the aortic pre-ejection times as a significant de-lay [38]. Indeed, it has been shown that after BiV pacing,the interventricular mechanical delay decreased substantially[23, 32, 36, 38].

Several echocardiographic parameters have been used todemonstrate the severity of the intraventricular mechanicalasynchrony. Pitzalis et al. demonstrated by M-mode echocar-diography that a long septal to posterior wall motion delay(SPWMD) was a strong predictor for reverse remodeling andbenefit from CRT [36]. SPWMD ≥130 ms was found to havea high positive predictive value for having benefit after BiVpacing. This method (Fig. 1) takes advantage of the high tem-poral resolution that can be achieved by M-Mode imaging.However, it is not useful in many patients, especially thosewith ischemic cardiomyopathy in whom the inter-ventricularseptum is akinetic.

Techniques based on tissue Doppler imaging have beenproved to be very useful for evaluating patients who mayhave a favorable response to CRT. Time from end-diastoleto peak systolic motion in different segments of the left ven-tricle is measured as an indicator of the electro-mechanical

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294 Heart Fail Rev (2006) 11:289–303

Fig. 2 Tissue Doppler Imaging (TDI) before and after CRT. The yel-low curve indicates tissue velocity in the septum while the green linereflect the lateral wall velocity. A and B are images from a patient withCLBBB before and after CRT, respectively. Note the non-homogeneityof myocardial motion displayed by patches of blue areas (left upperimage) in the septal and basolateral segments, while the rest of the LVis red. After CRT (B) the entire LV is in red. Sm indicates peak systolic

motion, note that septal Sm occurs before lateral wall Sm. This timedifference is diminished after CRT. C and D are from a patient withcomplete LBBB and paradoxical septal motion that results in a signif-icant delay of the peak septal Sm (now septal Sm comes after lateralwall Sm). After CRT this time difference diminishes. This effect is seenalso in the color coded image. (homogenization of the color in Fig. 2D).(From: Yu et al, Circ. 2002, 105L 438–445.)

delay (Fig. 2). Larger differences in the time of mechanicalactivation in different regions indicate worse dyssnychronyand are good predictors for future benefit from CRT. Baxet al. showed that a cutoff value of ≥60 ms in basal-septal tobaso-lateral peak systolic motion could separate patients whoresponded to CRT from non-responders. In another work[27], intra-and inter-ventricular dyssnchrony (LV and LV-RVdyssynchrony, respectively) were measured from apical fourchamber and apical long axis views using as the differencesbetween the time to peak systolic motion of the septal,lateral, posterior and right ventricular free wall. Again, LVasynchrony of ≥60 ms, LV-RV asynchrony of ≥56 ms, andsum asynchrony ≥102 ms (sum of LV and maximal LV-RVdelay) were good predictors of functional recovery andreverse remodeling after CRT. Of those parameters, sumasynchrony (cutoff value of 102 ms) had the best sensitivity,specificity and accuracy (96%, 77% and 88%, respectively)[27].

The advantage of these parameters stems in their simplic-ity. However, middle-wall segments also display an electro-mechanical delay. Indeed, Yu et al. used a 6 basal 6 mid seg-mental model to evaluate the severity of dyssynchrony [45].This method is more demanding since it requires acquiringtissue Doppler images from three views (apical 2, 3 and 4chamber views). Yet, this analysis yields a more comprehen-sive evaluation of the left ventricule. Indeed, the standarddeviation of the time to peak systolic motion in 12 segments(Ts-SD-12 ) performed better than from other parameters inpredicting reverse remodeling after CRT. With a cutoff ofTs-SD-12 = 34.4 ms the sensitivity and specificity in diag-nosing those patients who had reverse remodeling were 87%and 81%, respectively [46].

The limitation of TDI is that myocardial velocity can bepassive due to tethering, or translation of the entire heart.Thus, the basal regions may have normal longitudinal veloc-ity after infarction, if the mid-ventricular segments contract

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Heart Fail Rev (2006) 11:289–303 295

Fig. 3 Tracings of strain rate and strain from the basolateral wall andbasal septum before and after CRT in a patient with dilated cardiomy-opathy and RV pacing. The green lines indicate strain and strain ratefrom the lateral, while the corresponding curves from the septum are de-picted in yellow. Before CRT, peak systolic strain rate and peak systolic

strain in the lateral wall are delayed. Strain rate and strain curves fromboth areas become much closer after CRT. The positive deflection ofthe strain in the lateral wall, reflects initial myocardial stretching priorto contraction (red arrow). This deflection disappears with BiV pacing

normally. Moreover, the measured myocardial velocities ofmid-segments are normally lower than basal segments. In or-der to address these limitations, strain and strain rate are used.Strain rate is a measure of the velocity gradient and it indi-cates the regional deformation rate, whereas strain is the mag-nitude of deformation or the time integral of strain rate [47].Acute myocardial ischemia and infarction cause changes inregional function demonstrated by acute reduction in sys-tolic strain and strain rate, and delayed activation manifestedas post systolic thickening. These changes are diagnostic[48–52].Moreover, changes in the distribution of myocardialfiber strains, and in their timing were also noted in patientswith CLBBB and heart failure. Those changes were reversedafter CRT [53]. Strain and strain rate in an RV paced patientbefore and after CRT are shown in Fig. 3. Yet, despite thefact that conceptually, it is more appropriate to study the re-gional active deformation (e.g strain) rather than velocity thatmay reflect passive as well active motion, post-processinganalysis of strain and strain rate is time consuming, and islimited by signal to noise ratio. Yu et al. showed that theperformance of TDI and especially S.D of the time to peak

systolic velocity in 12 regions (Ts-SD-12) is superior to strainand strain rate for the prediction of reverse remodeling [31].

The distance or the magnitude of the motion of each seg-ment during systole can be measured by tissue tracking, atechnique that is based on tissue velocity (TDI) and time data.In this technique, the location and the number of segmentsthat display delayed longitudinal contraction, (i.e contrac-tion after aortic valve closure) or post systolic shortening, socommon in patients with dilated cardiomyopathy and intra-ventricular conduction delays, are assessed. Sogaard et al.showed that the extent of those regions displaying delayedlongitudinal contraction by tissue tracking was a good predic-tor of long term efficacy from CRT [29]. Moreover, it has beenshown that global systolic contraction and ejection fractioncan be further optimized by setting up a time interval betweenthe activation of the LV and the RV or vice versa (V-V delay),thus providing a sequential activation of the LV and RV ratherthan a simultaneous activation of both chambers. By tissuetracking imaging it has shown that compared to a simultane-ous CRT, sequential activation was more effective in reduc-ing the number of segments displaying late contraction [28].

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Fig. 4 Tissue tracking images from a patient with idiopathic dilated car-diomyopathy before (upper panel) and after implantation of BiV pace-maker. Prior to the implantation, there are large gray zones in the lateralwall, free anterior and posterior walls. Gray areas indicate LV segmentsthat lack systolic motion toward the apex. There is also an abnormaldistribution of motion amplitude in the septum and the inferior wall.Mid-level and apical segments have higher motion amplitude (domi-

nant blue and green colors) than the basal segments (yellow colors).After CRT (lower panel), the gray zones diminish, and the distributionof motion amplitudes becomes normal, (e.g. the motion amplitude ofthe basal segments is higher than the mid- and apical segments, whichis the normal pattern of myocardial motion). (From Sogaard et al, JACC2002; 40: 723-730, Figure 4.)

A tissue tracking image of a patient with idiopathic dilatedcardiomyopathy before and after CRT is shown in Fig. 4.

Displacement curves are periodic, demonstrating a cycleof endocardial inward (systole) and outward (diastole) dis-placement. These curves can be analyzed by Fourier transfor-mation and can be expressed in the frequency domain. Thus,the extent of dyssnchrony between the septum and the lateralwall can be displayed as a phase delay. Indeed, despite thefact that the vast majority of the patients displayed a patternof complete LBBB on surface ECG, three patterns of periodicendocardial motion have been seen: 1. synchronous or near-synchronous motion (phase delay of <25◦) (4/34 patients).2. septal phase preceding the lateral wall phase (phase de-lay >25◦) (17/34 patients). 3. Tri-phasic pattern, or invertedseptal displacement (paradoxical septal motion) (13/34 pa-tients). The group of patients that benefited most from CRTwas group 2, i.e those with a delay of the lateral wall motion[54].

Finally, a method called Contrast Variability Imaging(CVI) has been developed [6]. This imaging method is basedon the temporal variance of pixel intensity in the interface be-tween the myocardial wall and the contrast enhanced cavity(Fig. 5–I). This method improves wall detection and facili-

tates the quantitative analysis of regional wall motion. Usingregional fractional area change in 24 sectors (Fig. 5–II), theextent of spatial and temporal dyssynchrony defined as thecoefficient of variation (standard deviation/mean) of the ex-tent of regional fractional area change in different sectorsand their timing, respectively, were analyzed. Both temporaland spatial dyssnchrony diminished after LV or BiV pacing[6].

Echocardiographic follow-up after CRT

The echocardiographic findings that indicate improved my-ocardial synchrony include shorter differences in the time topeak systolic velocity of various segments (for example timeto peak systolic velocity in the basal-septum versus baso-lateral segment or smaller Ts-SD-12 values) seen in TVI (Fig.2). Other parameters that may indicate favorable response toCRT include smaller septal- to posterior wall motion delayand shorter time difference of the onset of pulmonary to aorticejection.

The expected favorable responses to CRT are an improve-ment in stroke volume (expressed as an increase in the aortic

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Fig. 5 I. Apical four chamber view before contrast (A), after contrastbut without image processing (B), and after Cardiac Variability Im-age (CVI) processing (C). This image processing enhances the borderbetween the blood pool and the myocardial wall, and this facilitatesendocardial contouring (D) and quantification of endocardial motion.II. Regional fractional area change (RFAC) in the septum and lateralwalls without (off) and with (on) left ventricular pacing. These curveswere obtained from CVI apical four chamber image, beginning at theend diastole and ending in end-systole. A indicates apical-septal seg-

ments while B indicates baso-septal segments. C and D indicate thebaso-lateral and apico-lateral segments, respectively. Without LV pac-ing (off- thin line) there is an initial contraction in the septum indicatedby a negative deflection and then expansion (positive deflection), whilein the lateral wall, there is initial expansion and then contraction. WithLV pacing (on- thick line), the initial and late expansion in the lateralwall and the septum disappears and the contraction is more homoge-nous. (From: Kawaguchi M et al., JACC 2002, 39(12): 2052–2058.)

velocity time integral), a greater ejection fraction and a de-crease in the severity of mitral regurgitation. These effectscan be seen shortly after the onset of BiV pacing as wellas after long term follow-up. In addition, reverse remod-eling manifested as reduction in the LV end systolic andend diastolic diameters and volumes is expected [23, 24, 27,30, 32, 45, 55]. Also there is an improvement in diastolicparameters including longer isovolumetric relaxation time,

reduced E/A ratio, and an increased deceleration time ofthe E wave. All these changes indicate transition toward aless advanced stage of diastolic dysfunction (stage I or II)[56]. Of importance is the clinical response that includesinitially an increase in pulse pressure, aortic systolic pres-sure, and eventually and most importantly symptomatic im-provement, better exercise tolerance and a reduced CHFmorbidity .

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Fig. 6 Myocardial MR tagging.A and B: Diastolic frames ashort axis slice in the plane ofthe papillary muscle withvertical and horizontal tags. C:Long axis slice (four chamberview). D,E and F: Systolicframes

Imaging mechanical dyssynchrony by radionuclideangiography and MRI

Echocardiography is the main imaging modality used toevaluate myocardial dyssnchrony. The main advantages ofechocardiography are high temporal resolution, widespreadavailability, accessibility and cost effectiveness. Its limita-tions include operator dependence, occasional difficulties ob-taining appropriate acoustic windows and angle restrictionwhich limit the number of segments available for evaluation.Therefore, the entire 3-D spectrum of myocardial deforma-tion and motion cannot be studied. With angle correctionsand analysis of myocardial deformation using speckle track-ing technique, these limitations can be obviated. Alternativemodalities for assessing myocardial dyssnchrony include ra-dionuclide angiography and MRI.

With multiple gated equilibrium blood pool scintigraphy(MUGA), inter-ventricular dyssynchrony was evaluated inpatients with dilated cardiomyopathy and different types ofconduction delays. Inter-ventricular temporal delay of my-ocardial motion was studied using phase image analysis, andmean phase angles were computed for the right and left ven-tricle. After BiV pacing, the mean inter-ventricular phaseangle delay was reduced from 27.5◦ to 14.1◦ (p = 0.01),and there was a very good correlation between the degreeof improvement of dyssnchrony after CRT and the improve-ment in the ejection fraction (r = 0.86, p < 0.001) [57].Recently, new parameters (entropy and synchrony) that uti-lize phase and amplitude analysis to quantify the timing andthe magnitude of the contraction have been described [58].The application of radio-nuclear studies to evaluate patientswith dilated cardiomyopathy with conduction delays is not

widespread, and is limited by the spatial and temporal reso-lution, cost and radioactive radiation.

MRI is a powerful imaging modality for quantitative as-sessment of 3-D myocardial structure and function. Measure-ments of end diastolic, end systolic volumes and LV mass aswell as stroke volume and ejection fraction are accurate andhighly reproducible [59]. This high reproducibility enablesperforming studies with smaller sample size to detect tempo-ral changes in myocardial size and function after myocardialinjury and to monitor therapeutic response [60]. A quanti-tative analysis of regional LV function can be performed byMR tagging [61, 62] (Fig. 6). Tags are temporary featuresthat are applied non-invasively during the imaging processby spatial modulation of magnetization (SPAMM) technique.These tags move along with the myocardial deformation andthe deformation of these taglines yields information about re-gional myocardial function during systole and early diastole.Regional myocardial deformation can be expressed as my-ocardial strains. Myocardial deformation during systole anddiastole is three dimensional, and analysis of the tag motionprovides information of the strains in 3-D [63–65]. Its mainadvantage over echocardiography is that it is not limited toacoustic windows, and scanning angles, and in contrast toechocardiography, the full scope of the myocardial defor-mation can be quantified. Finally, there is high correlationbetween strains determined by echocardiography and MRI[66]. With the use of MRI, a comprehensive 3-D strain mapsof the entire LV can be constructed and the magnitude ofstrains at different times can be displayed using a color en-coded map. An example of such a mechanical activation map[17] for three pacing modes (RV apical pacing, LV free walland BiV pacing) is shown in Fig. 7.

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Fig. 7 Mechanical LVactivation map for three pacingmodes -Right apical (RA)pacing, LV free wall (LV-P) andbiventricular pacing (BiV-P).The color map is based oncalculation of regionalcircumferential strain. Bluecolor indicates circumferentialshortening and yellow indicatesstretching. During RA pacing,contraction is asynchronouswith early septal shortening(blue) and LV free wallstretching (yellow). With LV-Pand BiV pacing, the mechanicalactivation maps are moresynchronous without initial freewall stretching. Duringmid-systole and late systole,shortening of the septum and theLV free wall can be seen. (FromLeclercq et al, Circ 2002; 106:1760–1763.)

FINDTAGS method [65] has been extensively utilized inanimal models and provided insight to the mechanical effectsof dyssynchrony [17]. However, the complicated and lengthof the post processing analysis pose important limitationsto its clinical application. Harmonic Phase (HARP) method(Diagnosoft, Palo Alto, Ca) is a technique that extracts tagmotion data from harmonic spectral peaks in the k-space[67]. HARP technique markedly shortens the post process-ing analysis time, and facilitates its use in clinical settings.It has been validated against a well established standard [68]and has a high inter- and intra-observer reproducibility [69].Recently, HARP method has been used to define optimal pac-ing sites for biventricular pacing in a dog model heart failure[70]. Strain Encoded (SENC) imaging, is novel method de-rived from tagging applied orthogonal to the imaging planeyielding a high resolution real time data of longitudinal strainin short axis images [71, 72].

Once all the comprehensive strain data has been obtained,an index of myocardial dyssnchrony should be defined. Re-gional temporal variance of strain has been used to definedyssnchrony, similarly to its use in TDI [31, 46]. An alterna-tive approach is regional variance strain vector of the princi-pal strain. In this method, temporal as well as spatial elements(e.g. sites of late activation) of dyssnchrony are included[73, 74]. Finally, temporal uniformity of strain has been de-scribed. In this method, Fourier transformation of strain plotsis performed for different segments, and dyssnchrony is char-

acterized by analysis of the resultant waveforms. This ap-proach has been used by Leclercq et al. [17], and recentlyby Helm et al. [73]. For a comprehensive description of themethods of MR imaging and analysis, the interested readeris referred to a review of Lardo et al. in JACC [72].

Nelson et al. using tagged MRI, measured circumferen-tial strain and the variance of the timing of the peak systoliccircumfenential strain in ∼80 sites through the left ventriclein patients with dilated cardiomyopathy with conduction de-lay and controls. Coefficient of variance (CoV) of the timeto peak systolic shortening in patients with DCM was 201.4± 84.3% while in normal volunteers CoV was 28.0 ± 7.1%(p < 0.001). Moreover, baseline mechanical dyssnychronycorrelated with the improvement in dP/dT after BiV pac-ing [75]. Finally, the analysis of strain by echocardiographyis based on longitudinal strains (Ell). Using 3-D analysis ofstrains in dogs with heart failure and LBBB it has been shownthat the variance of circumferential strain (Ecc) reflect me-chanical dyssynchrony better than longitudinal strain (Ell),and it can better predict response to CRT [73]. Therefore,strain analysis based on determination of longitudinal strainis limited and measurement of circumferential strain mightbe advantageous.

Thus, MRI is a powerful tool for imaging and evaluat-ing mechanical dyssnchrony. MRI can evaluate 3-D defor-mations and their timing in the entire left ventricle and isnot limited to specific windows, planes or angles. However,

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there are important limitations to the routine use of MRIin the evaluation of patients undergoing CRT. Compared toechocardiography, it is more expensive and has a limitedaccessibility and portability. Moreover, the temporal reso-lution of echocardiography is better than MRI (7–10 ms vs30–40 ms, respectively). The most important limitation ofMRI for a routine evaluation of dyssnychrony is that its usein patients with ICD’s and pacemakers is not FDA approvedgiven the concern that the strong magnetic field imposedby the MR scanners might harm the patients as well as theelectronic devices.Traditionally, presence of an ICD or pace-maker has been considered a contraindication to the use ofMRI. This issue has been studied recently and it has beenshown by Rougin et al. that modern ICD’s and pacemakers(manufactured after 2000) are safe for MR studies [76].

Conclusions

Mechanical dyssynchrony is an important factor in patientswith advanced CHF due to ischemic and non-ischemicdilated cardiomyopathy. The importance of mechanicaldyssynchrony stems from the fact that it is amenable to treat-ment by BiV pacing. Biventricular pacing has been shownto reduce morbidity and mortality and to cause reverse re-modeling of the left ventricle. The traditional criterion usedto select patients for CRT has been prolonged QRS dura-tion seen in surface ECG, usually in the form of CLBBBor intra-ventricular conduction delays. However, this cri-terion has several limitations, since not all patients withintra-ventricular conduction delays demonstrate mechanicaldyssnchrony. Moreover, there are many patients (as muchas third) who have narrow QRS but evidence of mechanicaldyssnchrony. These limitations underscore the importance ofimaging of mechanical dyssnchrony. Of the various imagingmodalities, Doppler echocardiography and especially tissueDoppler imaging (TDI) has been proved to be the most impor-tant tool for imaging mechanical dyssnchrony. Other modal-ities, such as MRI (tagging) and radionuclide angiography(MUGA), provide a unique insight to the issue of mechanicaldyssnychrony by their ability to display the entire scope ofthree dimensional myocardial deformation.

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