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Archives of cardiovascular diseases
Volume 110, n° 1
pages 60-68 (janvier 2017)
Doi : 10.1016/j.acvd.2016.12.002
Received : 22 September 2016 ;  accepted : 1 December 2016
Mechanical dyssynchrony in heart failure: Still a valid concept for optimizing treatment?
Asynchronisme mécanique et insuffisance cardiaque : un concept valide pour optimiser la thérapie ?

Elena Galli a, b, c, Christophe Leclercq a, b, c, Erwan Donal a, b, c,
a Service de cardiologie, CHU de Rennes, 35000 Rennes, France 
b LTSI, université de Rennes 1, 35000 Rennes, France 
c Inserm, UMR 1099, 35000 Rennes, France 

Corresponding author. CIC-IT 804, LISI Inserm U642, service de cardiologie, CHU Pontchaillu, rue H.-Leguillou, 35033 Rennes, France.

Cardiac resynchronization therapy (CRT) has had a major favourable impact on the care of patients with symptomatic heart failure, left ventricular ejection fraction<35% and enlarged QRS. Despite this, about 35% of patients who undergo CRT in accordance with current guidelines are “non-responders”. Therefore, more accurate selection of CRT candidates would significantly improve patient benefit and decrease costs. In the past decade, some small non-randomized studies have shown that estimation of left ventricular dyssynchrony by echocardiography might be useful to ameliorate the selection of patients for CRT. These preliminary findings have been challenged by the results of large randomized surveys, such as the Prospect and EchoCRT trials, which demonstrated that no left ventricular mechanical dyssynchrony variable could accurately predict CRT response. In recent years, improvements in myocardial imaging techniques, and the potential of fusion imaging to facilitate our understanding of the physiological basis of dyssynchrony and plan lead delivery, have let us suppose that imaging might play a role in the future of CRT. The aim of the present paper is to provide an overview of recent advances in the field of imaging-guided CRT. The role of imaging in the assessment of CRT candidates, in guiding lead implantation, and in the optimization of CRT delivery will be addressed, together with the limitations of these new techniques.

The full text of this article is available in PDF format.

La resynchronization cardiaque par stimulation biventriculaire a fait l’objet d’études démontrant de manière indéniable son intérêt pour mieux traiter les patients insuffisants cardiaques ayant une fraction d’éjection35 % et des QRS130ms. Trente-cinq pour cent des patients implantés ne tirent, cependant, pas bénéfice de la thérapie. Il y aurait donc un intérêt à définir des critères plus fins qui permettrait de mieux sélectionner, de mieux implanter les patients susceptibles de tirer bénéfice de la resynchronisation. Les techniques d’imagerie, échographique surtout, ont été testé depuis de nombreuses années avec des résultats globalement insuffisants. Prospect ou Echo-CRT ont semé le trouble sur la valeur de la sélection des patients par l’échocardiographie. Pourtant, il y a eu des progrès dans les techniques et dans la compréhension des asynchronismes. Il y a donc des raisons de penser qu’il pourrait y avoir une place à l’imagerie dans l’optimisation de l’utilisation de la resynchronisation cardiaque dans le traitement des sujets insuffisants cardiaques systoliques. Nous proposons ici une revue des techniques et des utilisations les plus récentes de l’imagerie cardiaque dans la sélection et dans l’aide à l’optimisation du mode de resynchronisation utilisé chez un patient donné. Nous abordons les espoirs et les limites encore existantes dans ces approches.

The full text of this article is available in PDF format.

Keywords : Cardiac resynchronization, Selection, Imaging, Echocardiography

Mots clés : Resynchronisation cardiaque, Sélection, Imagerie, Échocardiographie

Abbreviations : 2DE, 3DE, CMRI, CRT, LBBB, LV, STE


Cardiac resynchronization therapy (CRT) has had a major favourable impact on the care of patients with symptomatic heart failure, left ventricular (LV) systolic dysfunction and enlarged QRS [1]. Despite this, cumulative evidence shows that 25–35% of patients exhibit an unfavourable clinical or echocardiographic response to CRT [2].

This evidence has encouraged research into novel indices and strategies that can reliably predict CRT response. In the past decade, multiple single-centre trials and the Cardiac resynchronization in heart failure (CARE-HF) trial have demonstrated that LV mechanical dyssynchrony indices assessed by echocardiography can predict response to CRT and long-term outcome [3, 4, 5]. However, these results were challenged by the multicentre PROSPECT (predictors of response to CRT) trial, in which no single LV mechanical dyssynchrony variable could accurately predict CRT response [2]. Moreover, the EchoCRT trial has shown that in patients with symptomatic heart failure, a narrow QRS complex and echocardiographic evidence of time delays between left ventricle (LV) wall motions, CRT does not reduce morbidity, and even increases mortality [6, 7]. Therefore, the role of imaging in the selection of patients for CRT remains a hot topic of debate.

In this review, we seek to provide an update on the advances in cardiac imaging in the field of CRT, and to discuss the main pathophysiological factors that may determine CRT response. Additionally, we would like to underline the potential role of imaging in guiding lead implantation, and to emphasize the potential benefits of a multimodality approach in the selection of CRT candidates. Finally, we will address the role of cardiac imaging in the optimization of CRT and in the follow-up of CRT recipients.

Role of echocardiography in the selection of CRT candidates

In the normal heart, all LV segments contract in a relative synchronized fashion, and contribute to blood ejection into the aorta. In some patients with heart failure, LV mechanical dyssynchrony may occur, and can be attributed to electromechanical activation delay, regional differences in contractility or regional scars. Many echocardiographic predictors of CRT response have been proposed. Most of these variables are based on measurements of time intervals between velocities of the segments of the LV wall, but their predictive value is not sufficiently robust to replace routine selection criteria for CRT [3, 4, 5, 6, 7, 8]. Also, these time-delay indices are not sufficiently reproducible.

Although QRS duration is currently the main selection criterion for CRT implantation, QRS duration is not perfectly correlated with CRT success rate. Recent European society of cardiology guidelines on heart failure state that CRT is contraindicated in patients with QRS duration<130ms [9]. Patients with broad QRS and left bundle branch block (LBBB) but with no mechanical dyssynchrony have been described, indicating that the electromechanical correlation is variable and complex even in the presence of broad LBBB. Nevertheless, until now, it has been believed that only dyssynchrony of electrical origin is likely to respond to CRT [8, 10]. Distinguishing different aetiologies of LV dyssynchrony might explain the substantial fraction of patients with a wide QRS who were non-responders to CRT in large trials; this supports the development of variables and imaging modalities that can facilitate that distinction.

Septal flash and apical rocking: two specific myocardial signatures of mechanical dyssynchrony

The direct mechanical consequences of dyssynchronous contraction induced by LBBB can be described by septal flash and apical rocking. Septal flash is defined as an early fast inward motion of the interventricular septum during the isovolumic contraction period. This motion leads to an outward motion of the anterolateral wall, which pulls the apex laterally during the ejection time, and induces a typical apex motion pattern, described as apical rocking (Figure 1) [11, 12]. In normal subjects, all LV walls move in a homogeneous fashion towards or away from the apex, depending on the phase of the cardiac cycle (systole versus diastole). In contrast, in patients with dyssynchrony, early activation of one wall, without the corresponding contraction of the contralateral wall, results in the early contracting wall moving away from the original position of the apex, while the non/late-contracting wall is pulled towards this position. When this happens, the displacement of the initially contracting wall will be negative (away from the apex), while the non-contracting wall will be positive (towards the apex), creating the first phase of the rocking motion. Once the late contracting wall is finally activated, it will pull the wall that contracted initially in the opposite direction, creating the second phase of this rocking motion.

Figure 1

Figure 1. 

Example of septal flash identified on two-dimensional grey-scale images. A. The presence of an abnormal contraction and relaxation of the septum within the isovolumic contraction period results in a short inward motion of the septum (arrows). B. The delayed activation of the lateral wall then pulls the apex laterally during the ejection time, while stretching the septum; this typical apex motion pattern is described as “apical rocking”.


Septal flash and apical rocking are qualitative variables that can be easily identified without the use of specific software. These “tools” have been reported as qualitative or quantitative [11, 13, 14, 15]; both are reported to be highly reproducible and applicable even without any specific expertise. Also, Parsai et al. have shown that the presence of septal flash or its appearance/increase at low-dose dobutamine infusion in CRT candidates is associated with significant reverse LV remodelling after CRT [11, 16]. The value of apical rocking at rest and, especially, during low-dose dobutamine infusion, has been demonstrated, as for septal flash. The presence of apical rocking is associated with both echocardiographic (odds ratio 10.77, 95% confidence interval 4.12–28.13) and clinical (hazard ratio 2.73, 95% confidence interval 1.26–5.91) response to CRT, and the presence of both septal flash and apical rocking in CRT candidates is associated with increased long-term survival [17]. A large retrospective demonstration of the clinical value of apical rocking as a qualitative index has been reported, and a recent paper confirmed its value, and quantified it using a longitudinal strain-derived approach [13]. So, these two approaches are extremely valuable, but are slightly different: septal flash focuses on the isovolumic contraction phase, whereas apical rocking focuses on the systolic phase. They can we both observed in a same patient or distinctively [14].

Speckle tracking-derived indices: from myocardial signature of mechanical dyssynchrony to cardiac work

Speckle tracking echocardiography (STE) is a relatively new technique that allows the evaluation of LV deformation. Among all strain variables, LV longitudinal strain shows good robustness and reproducibility, which makes it applicable in routine clinical practice [18]. Longitudinal strain assessment is much more reproducible than tissue Doppler, but is also more reproducible than measurements of diameters or pulse Doppler traces, as has been reported [19]. The evaluation of longitudinal strain in different LV segments allows the estimation of residual myocardial contractility, a variable that seems to be strictly linked to CRT response [20, 21, 22]. In dyssynchronous ventricles, delayed segments do not fully contribute to end-systolic function, because their contraction lasts after aortic valve closure (Figure 2). In the MUSIC study, the strain delay index, which corresponds to the difference between end-systolic strain (measured at aortic valve closure) and peak strain across LV segments, was used to estimate wasted myocardial work, and its entity was significantly correlated to the amount of positive LV remodelling after CRT [23].

Figure 2

Figure 2. 

Systolic strain traces from the septum and lateral wall in a patient with left bundle branch block. During left bundle branch block without cardiac resynchronization therapy, there is a marked septal shortening during pre-ejection, accompanied by pre-ejection lengthening in the lateral wall (green arrows). AV: aortic valve.


Using quite a similar approach, based on the estimation of strain integrals, Bernard et al. were able to estimate the entity of wasted myocardial work in CRT candidates, and to demonstrate a significant reduction in wasted work in the lateral myocardial wall in CRT responders [24]. Russell et al. recently introduced another non-invasive method to assess regional myocardial work: pressure-strain loops analysis. LV pressure is derived by a normalized reference curve, and the absolute pressure level is estimated from brachial artery cuff pressure (Figure 3) [25, 26]. The non-invasive LV pressure-strain loop area gives an accurate quantification of regional work, allows the distinction between electrical and mechanical dyssynchrony, and is correlated with regional myocardial glucose metabolism by positron emission tomography [26]. Analysis of regional work during electrical dyssynchrony may provide insights into mechanisms of remodelling and LV dysfunction. Nevertheless, validation data in large clinical trials are still lacking. The key value of these new approaches based on speckle tracking techniques is that they are much more robust than previous approaches and the indices are calculated automatically; this should lead to the best inter- and intracentre reproducibility. The results obtained by some researchers should be investigated and verified in other imaging laboratories and in the field of daily clinical practice.

Figure 3

Figure 3. 

Example of left ventricular pressure-strain loops in a patient with left bundle branch block in the lateral (LAT) wall and septal (SEPT) segments. In the lateral segment, the area of the loop reflects segmental work. In the septal segment, loop area is markedly reduced relative to the lateral segment, which implies that septal work is markedly reduced. Bullseyes represent cardiac work and wasted work ratio in a patient with left bundle branch block, which depicts the significant imbalance in cardiac work and work efficiency between the septum and the lateral wall. ANT: anterior; INF: inferior; POST: posterior.


The potential of three-dimensional echocardiography: semi-automatic assessment of time delays

Three-dimensional echocardiography (3DE) is an appealing novel imaging modality that allows rapid assessment of LV volumes and function. In the case of dyssynchrony, myocardial segments reach the minimal volume at very different times. The standard deviation of this time dispersion expressed as a percentage of the cardiac cycle is defined as the systolic dyssynchrony index [27], which has been associated with a positive CRT response and LV remodelling after CRT [27, 28]. 3DE-STE permits the contemporary assessment of all LV dyssynchrony components (longitudinal, radial and circumferential) using the same volume acquisition, avoiding the out-of-plane phenomenon inherent to two-dimensional (2D) imaging. Moreover, 3D area strain, a derived variable, seems to be very promising for the quantification of LV dyssynchrony. Thebault et al. have shown that 3D-STE might offer a new rapid means of quantifying global LV dyssynchrony [29]. Despite this, with respect to 2DE, 3DE is limited by a low temporal resolution, particularly in dilated hearts, and further validation is necessary to extend its applicability in everyday clinical practice.

The importance of a multivariable approach

The Prospect trial showed that no single variable can really be applied on its own for the selection of CRT candidates. Later surveys proved that an integrated approach combining multiple variables may offer additional value to the selection of CRT candidates [11, 30, 31]. In an elegant study conducted on 200 patients with end-stage heart failure, Lafitte et al. showed that the combination of at least three different echocardiographic variables of LV dyssynchrony, including atrioventricular dyssynchrony, interventricular dyssynchrony, intraventricular dyssynchrony and radial and longitudinal evaluations of spatial and temporal LV dyssynchrony, was a better indicator of CRT response compared with each single variable [30]. A combined seven-point score, which includes clinical, electrocardiographic and echocardiographic data, named L2ANDS2 (Left bundle branch block [2 points], age>70 years, non-ischaemic heart failure, LV end-diastolic diameter<40mm/m2 [1 point], and Septal flash [2 points]), has shown good predictive accuracy for CRT response (area under the curve 0.75 for the C statistic). A L2ANDS2 score>5 had high specificity and a positive likelihood ratio (91.8 and 5.64, respectively), whereas a L2ANDS2 score<2 had high sensitivity and a negative likelihood ratio (97.9 and 0.19, respectively) for the prediction of CRT response [31]. So far, the use of a multivariable approach and scores to identify CRT responders has been applied in small observational retrospective studies with no or a very small control group. A prospective validation survey, with a large sample size and regular follow-up will be needed to support their routine application.

Echocardiography for optimizing lead positioning during CRT

In recent years, an increasing amount of literature seems to recognize that the position of the LV lead is an important determinant of CRT response [32, 33, 34, 35, 36]. In this setting, echocardiography and cardiac magnetic resonance imaging (CMRI) have been shown to be very useful in identification and quantification of scar, definition of the latest site of mechanical activation and identification of the best sites for lead positioning.

Identification of LV scar

The presence of a large LV scar is a strong independent predictor of poor clinical outcome [37] and unresponsiveness to CRT [20, 21, 22]. The presence of scarring impairs the CRT response for two reasons: it leaves insufficient viable tissue that can be recruited by CRT; and it does not allow adequate resynchronization. Therefore, the evaluation of scar position and extension by several imaging methods, including CMRI [22, 38, 39], nuclear imaging [37] and echocardiography [20, 21, 22, 40], might help to predict CRT response (Figure 4).

Figure 4

Figure 4. 

Example of the strain curves obtained in a patient with very severely depressed left ventricular systolic function. Some dispersion of the strain peaks exists, but part of this is related to a passive expansion of the myocardium, and some strain peaks are weaker than |5|%, which corresponds to too weak a systolic deformation to be related to a viable myocardium. ANT: anterior; AVC: aortic valve closure; INF: inferior; LAT: lateral; POST: posterior; SEPT: septal.


In 40 patients with end-stage heart failure and coronary artery disease undergoing CRT, Bleeker et al. evaluated the localization and transmurality of scar tissue by contrast-enhanced CMRI [22]. In this small population, patients with posterolateral scar tissue (n =14) showed a low response rate to CRT (14% versus 81%; P <0.05), without improvement in clinical or echocardiographic variables. Echocardiography can be useful to estimate the presence of myocardial scar (regional strain<5%) and to guide lead placement away from scar tissue [20, 21, 22, 40].

In a wide study conducted on 397 ischaemic heart failure patients, Delgado et al. showed that larger LV radial dyssynchrony, the lead placed at the latest activated LV segment and the absence of myocardial scar in the region of the LV pacing (identified by a peak systolic radial strain<16.5%) were all independent determinants of clinical improvement and long-term prognosis in CRT candidates [20].

Identification of the latest activated LV region (in the catheterization laboratory)

In recent decades, studies have supported the hypothesis that empiric LV lead placement, which maximizes the distance between LV and right ventricular pacing, is associated with better CRT response and a significant prognostic improvement [35, 41]. Nevertheless, in 567 patients, Kronborg et al. were unable to demonstrate that this presumed optimal LV lead position was associated with lower mortality or a better clinical response [41].

In the TARGET trial [33, 34], 220 CRT candidates were randomly assigned to selective LV lead placement at the site of the latest LV mechanical activation detected by STE or to traditional LV lead implantation. In patients receiving selective lead implantation, there was a greater proportion of responders at 6 months (70% vs 55%; P =0.031), and a lower rate of death and heart failure-related hospitalization (log-rank test, P =0.031). The superiority of the targeted versus the standard LV lead implantation approach was confirmed in the STARTER trial [36]; in this study, 187 CRT candidates were assigned in a 2:3 fashion to standard LV lead placement (n =77) or echocardiography-guided LV lead placement (n =110). The 2-year event-free survival rate was 73% in concordant or adjacent versus 46% in remote LV lead positions, indicating a 37% reduction in event rates. In a substudy of the STARTER trial, conducted in 151 patients, Marek et al. assessed the prognostic significance of LV lead positioning with respect to the echocardiographic site of latest activation in patients with intermediate QRS width (120–150ms) and a non-LBBB morphology [42]. When compared with patients with a concordant lead position, the patient group with a remote LV lead position had a very high event rate in terms of heart failure, hospitalization or death (hazard ratio 5.1, 95% CI 2.22–11.7; P <0.001). Interestingly, patients with non-LBBB morphology, whose LV lead was concordant or adjacent to the site of latest mechanical activation, had survival rates that were similar to those observed in patients with LBBB receiving CRT.

These results support the hypothesis that different electromechanical substrates can be responsive to CRT, and highlight the value of an imaging-guided and personalized approach for CRT delivery.

The importance of multimodality imaging in lead placement: future direction

As emphasized in the previous paragraphs, the position of the LV lead in the area of latest mechanical activation, and far from scar tissue, is a potentially promising strategy for CRT success [20]. The posterolateral cardiac vein, which is the most common site for LV lead placement, does not always correspond to the best site of stimulation [33]. By using this imaging modality, a matching vein (by computed tomography) in the segment with the latest mechanical delay can be identified in about 50% of patients, and in 90–95% of patients if immediately adjacent segments are considered [43, 44]. In 39 CRT candidates, Bakos et al. used a bullseye plot to combine data from CMRI, computed tomography and 2D-STE, which allowed rapid identification of the most appropriate site for LV lead placement. An appropriate site for CRT delivery was obtained in 97% of patients, and was associated with a statistically significant reduction in LV end-systolic volume and improvement in left ventricular ejection fraction at 6-month follow-up [43]. Tobon-Gomez et al. used echocardiography and 3D-tagged CMRI datasets to create specific computational models that allowed the simulation of the electromechanical effect of different LV stimulation sites before CRT [45]; this made it possible to build a computer model that could accurately represent each patient's heart, and to increase current understanding of dyssynchrony mechanisms [45, 46, 47].

Cardiac imaging after device implantation

One of the main concerns regarding CRT is the lack of an unambiguous definition of CRT response. Many CRT trials have defined response to CRT as improvement in clinical variables (New York Heart Association functional class, quality of life, 6-minute walk distance) or improvement in LV systolic function and LV reverse remodelling at 3–6-month follow-up [2, 48, 49]. Although the correlation between LV remodelling, clinical improvement or survival after CRT is sometimes limited [2], we think that no good response to CRT can exist in the absence of either clinical or echocardiographic improvement, and we endorse the central role of echocardiography in the assessment of myocardial performance after CRT.

Another potential application of echocardiography after CRT is echocardiography-guided optimization of atrioventricular and interventricular delay. Some observational and underpowered randomized studies have indicated that atrioventricular and interventricular suboptimal delays are predictors of poor CRT, and highlight the significant clinical benefit after atrioventricular and interventricular optimization [50, 51, 52]. However, these findings have yet to be confirmed by larger randomized trials. The ongoing CARTEDO trial is the first prospective randomized double-blind trial to evaluate the additional advantage related to echocardiographic CRT optimization with respect to the benefit of CRT itself. Results are expected to improve current knowledge of pathophysiological changes after echocardiography-guided CRT optimization, and to help in the management of heart failure patients [52].


The role of imaging in the field of CRT is marginal in current guidelines. Nevertheless, recent advances in different imaging modalities, and increasing concerns regarding the delivery of personalized care to patients with heart failure, suggest that a multimodality approach, combining clinical, electrocardiographic and imaging data, would be of value in the identification of CRT responders.

Echocardiography is the imaging technique of first choice because of its widespread availability; it can provide information on LV dyssynchrony and the site of latest mechanical activation, and can identify the localization of myocardial scar tissue. With respect to echocardiography, late gadolinium enhancement CMRI shows greater spatial resolution, which is of value in the localization and quantification of myocardial scar. Computed tomography provides the electrophysiologist with significant information about the anatomy of the cardiac venous system, which facilitates lead localization at the best LV stimulation site. Finally, fusion imaging might provide a unique opportunity to accurately represent the patient heart, to study the effect of LV stimulation before CRT implantation and to increase current understanding of dyssynchrony mechanisms.

Sources of funding


Disclosure of interest

E.D.: grant from the company General Electric for a work in the field of this review.

The other authors declare that they have no competing interest.


E.G. and E.D. were responsible for the conception and design of the paper. All authors were responsible for drafting and revising the article.


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