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Optimal use of echocardiography in cardiac resynchronisation therapy
  1. Gabe B Bleeker1,
  2. Cheuk-Man Yu2,
  3. Petros Nihoyannopoulos3,
  4. Johan de Sutter4,
  5. Nico Van de Veire4,
  6. Eduard R Holman1,
  7. Martin J Schalij1,
  8. Ernst E van der Wall1,
  9. Jeroen J Bax1
  1. 1
    Department of Cardiology, Leiden University Medical Centre, Leiden, The Netherlands
  2. 2
    Division of Cardiology, Prince of Wales Hospital, Shatin, NT, Hong Kong
  3. 3
    Imperial College London, Hammersmith Hospital, London, UK
  4. 4
    Department of Cardiology, University Hospital, Ghent, Belgium
  1. Dr Gabe B Bleeker, Leiden University Medical Centre, Albinusdreef 2, Leiden, 2333 ZA The Netherlands; g.b.bleeker{at}lumc.nl

Abstract

Echocardiography has several roles in patients with cardiac resynchronisation therapy (CRT). First, it can optimise selection of CRT candidates by demonstration of left ventricular (LV) dyssynchrony. Second, it can be used to assess immediate response to CRT, including detection of acute LV resynchronisation. Echocardiography is also useful to evaluate long-term benefit from CRT. Finally, echocardiography is important in optimisation of pacemaker settings, including AV and VV optimisation.

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At present, cardiac resynchronisation therapy (CRT) is considered an important step forward in the treatment of patients with severe heart failure. To date, several large randomised trials have shown the sustained beneficial effects of CRT on heart failure symptoms and left ventricular (LV) function.13 However, in parallel with the impressive results for CRT in these large trials, a consistent percentage of patients did not respond to CRT (non-responders) when the traditional patient selection criteria (New York Heart Association (NYHA) class III–IV, LV ejection fraction <35% and QRS duration >120 ms) were applied.1 4 5

When response to CRT is defined using clinical measures (eg, improvement in NYHA class or quality of life) the prevalence of non-responders is about 30% and when echocardiographic measures (LV reverse remodelling, improvement in LV ejection fraction) are applied, the number of non-responders is usually around 40%.4 5

Reduction of the number of non-responders is one of the main challenges in the field of CRT today. Recent studies have indicated that selection of patients with a high likelihood of response is possible with several (new) echocardiographic techniques6 (box 1). In addition to patient selection, echocardiography is also useful to assess acute and long-term beneficial effects of CRT. Moreover, echocardiography is needed for the optimisation of pacemaker settings.711 These topics are discussed in this review.

Box 1: The techniques most widely used to assess LV dyssynchrony

  • M-mode echocardiography

  • Pulsed-wave tissue Doppler imaging

  • Colour-coded tissue Doppler imaging

  • Tissue synchronisation imaging

  • Strain imaging

  • Real time three-dimensional echocardiography

ECHOCARDIOGRAPHY TO PREDICT RESPONSE TO CRT

Recent studies examining non-response to CRT have indicated that none of the traditional selection criteria (NYHA class III–IV, LV ejection fraction ⩽35% and QRS duration >120 ms) were able to predict a positive response to CRT, thereby highlighting the need for improvement of the selection criteria.5 12 In search for better selection criteria, it has become clear that the key mechanism of benefit from CRT is the presence and subsequent reduction of LV dyssynchrony.4 5 Traditionally, QRS duration has been used as an (indirect) marker of LV dyssynchrony. Duration of the QRS complex, however, proved to be a poor marker of LV dyssynchrony, thereby explaining its low predictive value for response to CRT;13 14 indeed, QRS duration merely reflects inter- (right versus left) ventricular dyssynchrony.15

Various studies have recently demonstrated that patients with extensive baseline LV dyssynchrony have a high likelihood of response to CRT, whereas patients without baseline LV dyssynchrony do not respond to CRT. Of note, although interventricular dyssynchrony (between the right and the left ventricle) tends to decrease after CRT, this measure has limited value for the prediction of response to CRT.5 8

Many different techniques have been tested for their ability to detect and quantify LV dyssynchrony in CRT patients. Since this observation, several cardiac imaging techniques have been tested for their ability to detect and quantify LV dyssynchrony. Among the different techniques, echocardiography proved to be particularly well suited for detection of LV dyssynchrony in the clinical setting.

The most important echocardiographic techniques for detecting LV dyssynchrony in CRT patients will be discussed hereafter and are summarised in box 1, ranging from simple M-mode echocardiography to more sophisticated echocardiographic techniques, such as tissue Doppler imaging (TDI), strain (rate) imaging and three-dimensional-echocardiography.

M-mode echocardiography

A relatively simple and elegant echocardiographic technique for the detection of LV dyssynchrony has been developed by Pitzalis et al, who used M-mode echocardiography to measure the delay between the systolic excursion of the (antero) septum and the posterior wall on the parasternal short-axis view, the so-called septal to posterior wall motion delay (SPWMD, fig 1A).16 17 In an initial study, including 20 patients, responders to CRT had a significantly larger SPWMD than non-responders. Using a cut-off value of 130 ms, SPWMD yielded an accuracy of 85% (sensitivity 100%, specificity 63%) to predict response after CRT.16 In a subsequent study the same authors evaluated another 60 patients and demonstrated that the cut-off value of 130 ms was a strong predictor of patient prognosis after CRT implantation.17

Figure 1 (A) Measurement of the septal to posterior wall motion delay using M-mode echocardiography. An M-mode recording through the (antero) septum and posterior left ventricular (LV) wall is obtained in the parasternal short-axis view. LV dyssynchrony is defined as the shortest interval between the maximal systolic displacement of the septum and the maximum systolic displacement of the LV posterior wall. Arrows indicate maximal systolic displacement. (B) Patient example in which assessment of LV dyssynchrony was not feasible with M-mode echocardiography owing to akinesia of the anteroseptal wall.

In contrast, however, Marcus et al recently obtained less favourable results with this technique. The SPWMD measurement was applied retrospectively in a large cohort (n = 79 patients, 72% ischaemic cardiomyopathy) of patients with heart failure who were included in the CONTAK-CD trial.18 The authors reported a sensitivity of 24% with a specificity of 66% to predict response to CRT, and the SPWMD could not be assessed in 50% of patients (fig 1B). Recent data in 98 patients with heart failure scheduled for CRT indicated that the poor interpretability of the SPWMD recordings was the result of the absence of a clear systolic motion on M-mode echocardiography due to akinesia of the interventricular septum (53%), the posterior wall (12%), or both (3%), or a poor acoustic window in the parasternal view (32%). Of note, in the patients without an interpretable SPWMD, LV dyssynchrony assessment was still feasible in 90% of patients when colour-coded TDI was applied.19

Tissue Doppler imaging

One of the most widely studied techniques for the assessment of LV dyssynchrony in the selection of CRT patients is TDI. This technique enables measurement of peak systolic velocities in different regions of the myocardium,4 5 20 and more importantly, the time intervals between electrical activity (QRS) and the mechanical activity (segmental peak systolic velocity) (fig 2).

Figure 2 Colour-coded tissue Doppler imaging in the apical four-chamber view in a normal person. The sample is placed offline in the basal part of the septum, demonstrating peak systolic velocity (PSV), and diastolic parameters (E′ and A′). AVO and AVC indicate aortic valve opening and closure, respectively.

The myocardial velocity curves can either be constructed online using pulsed-wave TDI (fig 3), or reconstructed offline from the two-dimensional colour-coded TDI images (fig 2). The advantages of colour-coded TDI over pulsed-wave TDI are the possibility for offline analysis and the possibility of analysing multiple segments in one heart beat, thereby avoiding potential errors from differences in cardiac frequency. In addition, the peak systolic velocity is displayed more accurate when colour-coded TDI is applied.

Figure 3 Pulsed-wave tissue Doppler imaging in the apical four-chamber view in a normal person. The pulsed-wave sample is placed online in the region of interest (basal part of the interventricular septum) and the myocardial velocity curve is derived. PSV, peak systolic velocity, E′ and A′ represent diastolic parameters.

To assess regional dyssynchrony, one commonly used method is to measure the time to peak systolic velocity of individual LV segments with reference to the QRS complex.4 5 Integration of this information allows accurate assessment of electromechanical coupling, estimation of severity of LV global delay and evaluation of LV dyssynchrony (fig 4).

Figure 4 (A) Two-segment colour-coded tissue Doppler imaging (TDI) in the apical four-chamber view in a normal person without left ventricular (LV) dyssynchrony. LV dyssynchrony is defined as the time delay in peak systolic volume between the basal septum and lateral wall. The arrow indicates peak systolic velocity of both the basal septum and lateral wall, illustrating perfect synchrony. (B) Two-segment colour-coded TDI in a patients with heart failure with LV dyssynchrony. The delay in peak systolic velocity between the basal septum and lateral wall is 130 ms, indicating severe LV dyssynchrony. Arrows indicate peak systolic velocities.

The number of segments used for evaluation of LV dyssynchrony varied among the different studies. Most frequently, two or four basal segments (septal, lateral, inferior, anterior) are evaluated. Bax et al evaluated 85 patients with heart failure with follow-up data obtained up to 1 year.5 Receiver operating characteristic curve analysis was performed and showed that LV dyssynchrony of ⩾65 ms was highly predictive of both clinical response (sensitivity/specificity 80%) and LV reverse remodelling (sensitivity/specificity 92%).

Other studies have used a multiple segmental approach to create various models of LV dyssynchrony in order to predict a favourable response to CRT. Examples of these models include six basal LV segments, or a combination of six basal and six mid-LV segments. Notabartolo et al used the six basal LV segmental model from the three apical views. The authors measured the time to the highest peak velocity in either ejection phase or post-systolic shortening, and calculated the maximal time difference to generate the “peak velocity difference”.20 In 49 patients undergoing CRT, a peak velocity difference >110 ms at baseline predicted LV reverse remodelling at 3 months’ follow-up with a sensitivity of 97% and a specificity of 55%.20 Examination of ejection phase velocities seems to provide a better trade-off between sensitivity and specificity. Yu et al proposed to measure the standard deviation of the time to peak systolic velocity in ejection phase in the six basal/six mid-segmental model to compute the asynchrony index (or Ts-SD) (fig 5). With a population-derived cut-off value of 32.6 ms, the index was able to segregate responders from non-responders (defined as presence/absence of LV reverse remodelling).12 21

Figure 5 Twelve-segment colour-coded tissue Doppler imaging in a patient with LV dyssynchrony in multiple segments. Myocardial velocity curves were derived offline at basal and mid-levels of the left ventricle in the different walls. The time to peak systolic velocities during the ejection phase in each view are compared. The ejection phase is defined by the aortic valve opening (AVO) and aortic valve closure (AVC) markers. (A) Apical four-chamber view showing delay in the lateral wall. (B) Apical two-chamber view showing delay in the anterior wall. (C) Apical long-axis view showing delay in the posterior wall.

Another method to assess systolic dyssynchrony is to measure the time to onset of mechanical contraction in the ejection phase by pulsed-wave TDI (fig 3). The work by Penicka et al defined LV dyssynchrony as the maximal electromechanical delay among the three basal LV segments (septal, lateral and posterior wall).22 The authors reported a cut-off value of 102 ms, which yielded an accuracy of 88% to predict response to CRT (as defined by a relative increase in LV ejection fraction >25%).

Tissue synchronisation imaging

Another evolving technique to assess LV dyssynchrony is tissue synchronisation imaging (TSI) (Vivid 7, General Electric-Vingmed, Milwaukee, Wisconsin, USA).23 This technique automatically calculates the peak systolic velocities from TDI and displays the timing of peak systolic velocities as a colour map, allowing for a quick visualisation of the early activated segments (displayed in green) and identification of the latest activated segments (displayed in red), without the need for TDI curve analysis. In addition, quantitative assessment of regional delay is still possible (through construction of myocardial velocity curves, similar to TDI). Yu et al studied this qualitative approach in 56 patients with heart failure and reported a sensitivity of 82% with a specificity of 87% to predict response to CRT (fig 6).23

Figure 6 Tissue synchronisation imaging: the colours represent time to peak systolic velocity. Green corresponds to early mechanical activation; yellow/orange/red indicates a delayed peak systolic velocity in (A) a patient with a synchronous LV contraction (the entire left ventricle is coloured green); (B) a patient with delayed activation (indicated in orange/red) of the lateral wall.

Recently, a new three-dimensional probe (Vingmed Ultrasound, Horten, Norway) became commercially available allowing simultaneous acquisition of a triplane dataset and colour-coded TDI of the left ventricle. During post-processing (Echopac), the TSI option can be applied to the TDI triplane dataset. The timing of the peak systolic velocities is presented as a colour map in the apical four-, two- and three-chamber views during one single heartbeat. Additionally, by manually tracing the endocardial borders during post-processing (surface mapping) a three-dimensional volume is generated semiautomatically, portraying the area of latest activation allowing quick visual identification of the delayed LV segment (fig 7). If quantitative assessment of LV dyssynchrony is preferred than the regional myocardial velocity curves can be derived analogously to two-dimensional TSI analysis.

Figure 7 Example of tissue synchronisation imaging applied to a triplane dataset. The areas of latest mechanical activation are indicated in orange/red in the apical four-, two- and three-chamber views. The lower right panel shows a semiautomatically generated three-dimensional LV volume portraying the area of latest mechanical activation.

Strain (rate) imaging

Strain (rate) imaging (SRI) is a potentially interesting derivation from colour-coded TDI. In contrast to TDI, which only measures myocardial velocities, SRI examines the (rate of) myocardial deformation between two points in the region of interest. Accordingly, SRI has the potential advantage over TDI to differentiate between active and passive myocardial motion. Using SRI the extent of LV dyssynchrony can be quantified by measuring the time delays in time to peak systolic strain, comparable to TDI. Initial studies employing SRI to measure LV dyssynchrony from the apical views (measuring longitudinal strain) reported relatively low predictive values for response to CRT.21 The low predictive values were due to the relatively high angle dependency of SRI, which resulted in limited reproducibility of measurements.

Dohi et al produced more promising results when strain imaging was used to calculate LV dyssynchrony from the short-axis views (measuring radial strain) in 38 patients undergoing CRT. A difference of ⩾130 ms in septal versus posterior wall peak strain was strongly predictive of immediate improvement in stroke volume with CRT (sensitivity 95%, specificity 88%) (fig 8).24

Figure 8 Example of tissue Doppler-derived radial strain imaging in the parasternal short-axis view at the mid-left ventricular (LV) level in a patient with severe LV dyssynchrony (160 ms). LV dyssynchrony is defined as the difference in peak strain between the anteroseptum (yellow curve) and the posterior wall (green curve). Arrows indicate peak strain.

In addition, the same authors recently studied a new echocardiographic technique, speckle tracking, which can calculate myocardial strain from conventional two-dimensional echocardiography. The main advantage of this technique over TDI-derived strain is its lack of angle dependency (fig 9). In 48 patients undergoing CRT, a sensitivity of 91% with a specificity of 75% to predict acute response to CRT were obtained using a cut-off value ⩾130 ms for LV dyssynchrony.25

Figure 9 (A) Speckle tracking derived radial strain imaging in the parasternal short-axis view at the mid-left ventricular (LV) level. In this example, peak radial strain (arrow) occurs simultaneously in all six segments, indicating a synchronous LV contraction (the curves are colour-coded in accordance with the segments on the short-axis view). (B) Example of radial time–strain curves from speckle tracking in a patient with heart failure with LV dyssynchrony. The septal regions reach peak strain early in systole (blue/yellow curves), whereas the lateral segments reach peak strain late in systole (red/green curves, arrows indicate peak systolic strain).

Three-dimensional echocardiography

The main advantage of real-time three-dimensional echocardiography (RT3DE; Philips Medical Systems, Andover, Massachusetts, USA) for the quantification of LV dyssynchrony compared with two-dimensional echocardiographic techniques is that it provides simultaneous information on the timing of contraction of a large number of LV segments (fig 10). With an excellent spatial resolution RT3DE can provide detailed information on both global and regional LV function. When this technique is used, regional volume–time curves can be derived for each of the LV segments; LV dyssynchrony is assessed by comparing the times to reach minimal regional volume for each LV segment. The systolic dyssynchrony index is used as a marker of global LV dyssynchrony and is defined as the standard deviation of the time taken to reach minimal regional volume for each of the LV segments. In addition, the regional time differences between different segments allow the identification of the area of latest LV activation, even when these areas are located in the most distal LV regions the apex, or both.

Figure 10 Global (top) and regional (bottom) left ventricular (LV) volume curves derived from a three-dimensional dataset. The regional volume curves for each segment allow the calculation of the systolic dyssynchrony index, which is defined as the standard deviation of the time taken to reach minimum regional volume for each segment.

Recently, Kapetanakis et al demonstrated the feasibility of RT3DE to assess LV dyssynchrony in 174 unselected patients referred for routine echocardiography and concluded that it can rapidly quantify global LV dyssynchrony.

In addition, the authors used RT3DE to calculate global LV dyssynchrony in 26 additional patients undergoing CRT and demonstrated a significant difference in the systolic dyssynchrony index between responders and non-responders (16.6 (1.1)% vs 7.1 (2)%, p<0.001).26 An optimal cut-off value for prediction of response, however, was not reported and remains to be defined in future studies.

Which echo technique?

As discussed above, a large number of different echocardiographic techniques have been tested recently for quantification of the extent of (pre-implantation) LV dyssynchrony in patients with heart failure, to select the patients with a high likelihood of response to CRT. The echocardiographic techniques ranged from simple M-mode echocardiography (four studies, 257 patients),1619 pulsed-wave TDI (four studies, 123 patients),8 22 27 28 to more sophisticated techniques including colour-coded TDI (eight studies, 290 patients),4 5 12 20 21 2931 SRI (seven studies, 206 patients),21 24 3034 TSI (four studies, 177 patients)23 24 35 36 and three-dimensional echocardiography (two studies, 39 patients).26 37 At present, no consensus exists on which technique is optimal to predict response to CRT, and the large number of different echocardiographic techniques that have been published (without direct comparisons between techniques) further contribute to the confusion about the optimal technique. Moreover, the different techniques employ varying numbers of segments to determine LV dyssynchrony (ranging from two to 16 segments) and different cut-off values to define substantial LV dyssynchrony (ranging from 65 ms to 130 ms). Consequently, larger multicentre studies, directly comparing different echocardiographic techniques, are needed to identify the optimal technique, with the optimal number of segments and the optimal extent of LV dyssynchrony to predict response to CRT. The prospective, multicentre PROSPECT trial is specifically designed to answer these questions. The study will include about 300 patients with a clinical follow-up of 6 months and the results are expected in 2007.38

Finally, an emerging approach is the measurement of global, rather than segmental, markers of LV dyssynchrony. One of the proposed parameters for measurement of global LV dyssynchrony is the total isovolumic time derived from the transmitral and subaortic pulsed-wave signals as recently proposed by Duncan et al.39

IMMEDIATE FOLLOW-UP

Echocardiography can be used to assess the immediate benefits from CRT. In the acute setting, echocardiographic studies have demonstrated that CRT immediately improved LV systolic function (LV ejection fraction), with direct disappearance of this effect when CRT was switched off. The acute improvement in LV systolic function was reflected in a reduction in LV end-systolic volume, whereas LV end-diastolic volume remained unchanged (resulting in an increased LV ejection fraction.40 In addition, echocardiographic studies demonstrated that some patients exhibit an immediate reduction in mitral regurgitation after CRT. Kanzaki et al studied 26 patients and reported an acute reduction in regurgitant volume from 40 (20) ml to 24 (17) ml (p<0.001) acutely after CRT. The mechanism underlying the reduction in mitral regurgitation was evaluated using strain imaging. A significant mechanical delay was demonstrated between the posteromedial and anterolateral papillary muscles at baseline (106 (74) ms), which was reduced immediately after CRT implantation (12 (8) ms, p<0.001),41 42 indicating that resynchronisation of the dyssynchronous papillary muscles acutely restored valvular competency.

Thus, the beneficial effects of CRT appear related to an acute resynchronisation of the left ventricle and papillary muscles. Echocardiography can be used to assess the LV resynchronisation immediately after CRT. Figure 11 shows an example of a patient without resynchronisation after CRT is demonstrated. Indeed, recent data suggest that CRT may not always result in resynchronisation (despite the presence of pre-implantation LV dyssynchrony).43 The mechanisms underlying failure to restore LV synchrony are not entirely clear, but recent data demonstrated that patients with scar tissue in the posterolateral LV segments (usually the area where the LV lead is located) failed to resynchronise after CRT, associated with clinical and echocardiographic non-response (fig 12). In particular, the response rate to CRT was excellent (95%) in patients with severe baseline LV dyssynchrony without posterolateral scar tissue; in patients with posterolateral scar tissue, however, the response rate was low (11%).43 Not only the location but also the extent of scar tissue is important for the response to CRT. Hummel et al showed that the extent of scar tissue was inversely related to the response to CRT.44

Figure 11 Example of a patient without left ventricular (LV) resynchronisation. Despite the presence of severe baseline LV dyssynchrony (120 ms) between the basal septum (yellow curve) and the basal lateral wall (green curve), cardiac resynchronisation therapy was unable to reduce LV dyssynchrony (after implantation 110 ms). As a result, no LV reverse remodelling was seen at 6 months’ follow-up (LV end-systolic volume from 245 ml to 250 ml) and LV ejection fraction remained unchanged (from 23% to 20%). In addition, the patient showed no change in clinical parameters.
Figure 12 In patients with posterolateral scar tissue (usually the location of the left ventricular (LV) pacing lead), cardiac resynchronisation therapy (CRT) is unable to restore LV synchrony. In patients without scar tissue, LV dyssynchrony was reduced from 93 (41) ms to 31 (27) ms (p<0.05), whereas in patients with scar tissue LV dyssynchrony remained unchanged (84 (46) ms at baseline versus 78 (41) ms after CRT, p = NS. (Adapted from reference 33.)

Failure to resynchronise can also be related to a mismatch between the site of latest activation and the position of the LV lead. Using colour-coded TDI, Ansalone et al demonstrated that the response to CRT was minimal when the LV lead was not located near the area of latest activation.27 Similarly, Suffoletto et al recently reported that patients with the LV lead positioned outside the area of latest activation had a significantly smaller response to CRT.25

TSI may be the ideal technique to visualise the area of latest activation and thus guide LV lead positioning. This principle was applied recently by Murphy et al, who used TSI to evaluate the interaction between the LV lead position and the area of latest activation, on the one hand, and LV reverse remodelling after CRT, on the other.36 The authors observed a larger reduction in LV end-systolic volume in patients with the LV lead positioned in the area of latest activation (23% reduction in LV end-systolic volume) than in patients with the lead positioned in an adjacent (15% reduction) or a remote region (9% increase). Although the area of latest activation is most often located in the posterolateral LV segments, a wide variation between patients has been reported.45 Accordingly, echocardiography (in particular, TSI) may provide a patient-tailored approach for LV lead positioning, which targets the area of latest LV activation. In the past, this approach has been hampered by the lack of (echocardiographic) techniques that could provide an accurate three-dimensional representation of regional LV dyssynchrony.

One needs to realise, however, that not all areas of the left ventricle are suitable for endocardial (via the coronary sinus) LV lead placement owing to the absence of suitable veins in the targeted area. It has recently been shown that multislice CT scanning can be helpful in assessing the venous anatomy before CRT implantation.46 Information about the venous anatomy can then be combined with information about the area of latest LV activation, and if suitable branches of the coronary sinus are absent, epicardial (surgical) LV lead placement should be considered.

LATE FOLLOW-UP

Echocardiography is the preferred technique to evaluate improvement in LV ejection fraction after CRT. In 125 patients with heart failure, a significant improvement in LV ejection fraction from 23 (8)% to 32 (9)% was demonstrated after 6 months of CRT.47

Yu et al demonstrated that the improvement in LV ejection fraction is a gradual process, with further improvements occurring over time (fig 13).4 St John Sutton et al recently evaluated a cohort of 228 patients included in the MIRACLE trial and demonstrated that the gradual improvement in LV ejection fraction was (in part) related to the aetiology of heart failure. Patients with non-ischaemic cardiomyopathy exhibit an immediate improvement in LV ejection fraction, whereas the improvement occurs more gradually in patients with ischaemic cardiomyopathy.11

Figure 13 Changes in LV ejection fraction after CRT in 25 patients studied by Yu et al. A gradual increase in LV ejection fraction was observed (*p<0.05 vs baseline). Interestingly after cessation of CRT at 3 months’ follow-up a gradual decline in LV ejection fraction was seen (†p<0.05 vs 3 months of CRT. (Adapted from reference 4.)

In addition to improvement in LV ejection fraction, echocardiography permits measurement of LV reverse remodelling, with a reduction in both LV end-systolic and end-diastolic volumes. Reverse remodelling is clinically relevant, as reported recently by Yu et al, who demonstrated in 141 patients that a reduction of >10% in LV end-systolic volume after 3-6 months of CRT was the most important predictor of event-free survival at 12 months follow-up.10 This important observation underlines that LV reverse remodelling as measured by echocardiography provides the most clinically meaningful definition of response to CRT (fig 14).

Figure 14 Echocardiographic demonstration of LV reverse remodelling after 6 months of CRT; the LV end-diastolic volume decreased from 237 ml at baseline (A) to 118 ml at 6 months (B).

In combination with the LV reverse remodelling a reduction in mitral regurgitation may also be seen (fig 15), which can be explained by a further reduction in annular dimensions, resulting in a smaller regurgitant orifice.

Figure 15 (A) Patient with severe mitral regurgitation before CRT implantation. (B) No significant change in severity of mitral regurgitation was seen immediately after CRT implantation. (C) At 6 months’ follow-up, however, a significant reduction in mitral regurgitation was seen, secondary to the LV reverse remodelling.

In addition to the effects of CRT on the left ventricle, CRT may also affect right ventricular size and function. Bleeker et al demonstrated the beneficial effects of CRT at 6-months’ follow-up, including right ventricular reverse remodelling, a reduction in tricuspid regurgitation and a decrease in pulmonary artery pressure.48

OPTIMISATION OF PACEMAKER SETTINGS

AV optimisation

The aim of AV optimisation is to select an “optimal” AV delay that results in an increase in diastolic filling time and a reduction of presystolic mitral regurgitation. This may lead to an improvement of stroke volume, symptoms and LV reverse remodelling. Several acute invasive studies have shown that LV dP/dt can be increased by 13%–34% during AV optimisation.4952 Similar acute improvements have been documented in stroke volume during echocardiography-guided AV delay optimisation.53 However, the effect on exercise performance is unclear54 and the effects on heart failure morbidity, hospitalisations and mortality have not been studied.

AV delay optimisation can be performed by measuring LV diastolic filling time intervals or indices of LV systolic function, or both.

The most commonly used echocardiographic method is the iterative method, which uses both transmitral pulsed-wave Doppler (to assess A wave truncation and the diastolic filling time) and aortic continuous wave Doppler (to assess the velocity time integral (VTI), as an index of LV stroke volume). A long sensed AV delay (shorter than the intrinsic PR to ensure capture) is programmed (usually between 160 and 200 ms). This AV delay is shortened in steps of 20 ms until the A wave begins to truncate (visualised on the transmitral Doppler flow registration). Once A-wave truncation is noted, the AV delay is lengthened in steps of 20 ms until truncation no longer occurs. The optimal AV delay is characterised by the longest diastolic filling time or the highest aortic VTI. To obtain an optimal aortic VTI it is advised to use a fast sweep speed, a large velocity scale and a low filter. An example of the effect of changing the AV delay on aortic VTI in a patient after CRT implantation is provided in (fig 16). Since several measurements are needed and one has to wait at least 10 beats before recording the different flows during the different programmed AV delays, this method is time consuming.

Figure 16 Example of the effect of changing the AV delay on aortic velocity time integral (VTI) in a patient after cardiac resynchronisation therapy implantation. The optimal AV delay is derived at 100–120 ms yielding the highest aortic VTI.

A faster technique that only requires the mitral inflow has also been proposed. This mitral inflow technique was initially developed by Ritter for patients with complete heart block treated with dual-chamber pacing.55 56 It requires recordings of the mitral inflow by pulsed-wave Doppler at a long and a short AV delay. A long AV delay (AV long, for example, 200 ms) results in premature mitral valve closure before the paced QRS. The time interval “a” is measured from the termination of the mitral A wave to the onset of the paced QRS. A short AV delay (for example, 60 ms) results in closure of the mitral valve due to onset of LV systolic contraction. The electromechanical delay, time interval “b”, is measured from the onset of the paced QRS to the termination of the mitral A wave. The optimal AV delay is then calculated by the equation: AVlong – (b-a). Although attractive, this method has to be used cautiously in patients treated with CRT since loading conditions may significantly alter LV filling pressures. Also, in patients with raised filling pressures (such as CRT patients), the mitral A wave may be severely attenuated or abbreviated which limits visualisation of mitral A wave truncation.

Because of the time efforts and lack of proven clinical benefit, AV optimisation is not routinely performed. Instead, a short AV delay (usually in the range of 100–120 ms) is often programmed and AV optimisation is only performed in patients who do not respond to CRT. In addition, many questions are unresolved about AV optimisation at the present time. For example, the effect of body position (supine versus sitting) on the optimal AV delay is unknown. More importantly, it is largely unknown whether the AV delay should be shortened, kept constant or prolonged as heart rate increases during exercise in CRT patients. In previous multicentre trials the AV delay was programmed fixed or with dynamic shortening. However, Scharf et al reported that the relatively short baseline AV delay should be prolonged and not shortened at increased heart rates to maintain stroke volume in CRT patients.54 If confirmed in future studies, this would imply that dynamic AV lengthening should become available in new CRT devices.

VV optimisation

The aim of VV optimisation is to select an “optimal” interventricular (VV) interval that further improves inter- and intraventricular dyssynchrony and thus mechanical efficiency or stroke volume. Acute invasive studies have shown that VV optimisation resulted in a further improvement of dP/dt.51 52 Sogaard et al showed in 20 patients that sequential VV activation resulted in a further reduction of delayed longitudinal contraction with a further increase of diastolic filling time, as compared with simultaneous biventricular activation.31 Accordingly, Vanderheyden et al reported in 20 patients that VV optimisation resulted in prolongation of LV filling time, reduction of inter- and in intra-LV dyssynchrony, with an increase in stroke volume.57 Although these small studies appear to support VV optimisation, larger studies of the effects on exercise performance, heart failure morbidity/hospitalisations and mortality are not yet available.

Currently, consensus is lacking on which echocardiographic parameters should be measured during VV optimisation. It seems logical, however, that both measures of inter- and intra-LV dyssynchrony as well as stroke volume should be evaluated.

Vanderheyden et al57 and Parreira et al58 used pulsed-wave TDI to assess inter- and intra-LV dyssynchrony as well as the aortic VTI to assess stroke volume. In these studies VV optimisation was performed by advancing the LV stimulus (left ventricle first) or the RV stimulus (right ventricle first) by 20 ms intervals up to 60 ms.

Leon et al evaluated the haemodynamic effects of VV optimisation in 376 patients undergoing CRT implantation by measuring the aortic VTI for each VV interval.59 In 81% of patients, optimisation of the VV timing interval resulted in an increase in stroke volume, with a median increase of 8.6%. Of interest, in the majority of patients the highest aortic VTI was derived when the left ventricle was paced first (fig 17).58

Figure 17 Optimal VV timing settings at pre-hospital discharge. In the majority of patients (55%) the aortic velocity time integral was highest when the left ventricle was paced before the right ventricle. (Adapted from reference 59.)

As with AV optimisation, many questions are unresolved about VV optimisation. There are virtually no published data on the effect of body position, exercise or outcome. Also, it is unclear whether AV optimisation should proceed VV optimisation or vice versa.

SUMMARY

The role of echocardiography in patients with CRT can be defined as follows.

  • Echocardiography can optimise selection of CRT candidates by demonstration of LV dyssynchrony, and many echocardiographic techniques have been proposed. The extent of LV dyssynchrony that is mandatory for response to CRT is not yet defined, but may be derived from the PROSPECT trial.38

  • Echocardiography can be used to assess immediate response to CRT, including detection of acute LV resynchronisation. Also, echocardiography is useful to evaluate long-term benefit from CRT (ie LV reverse remodelling).

  • Echocardiography is important in optimisation of pacemaker settings, including AV and VV optimisation.

REFERENCES

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Footnotes

  • Funding: Dr GB Bleeker is supported by the Dutch Heart Foundation, grant no. 2002B109.

  • Competing interests: None declared.

  • Abbreviations:
    CRT
    cardiac resynchronisation therapy
    LV
    left ventricular
    NYHA
    New York Heart Association
    RT3DE
    real-time three-dimensional echocardiography
    SPWMD
    septal to posterior wall motion delay
    SRI
    strain (rate) imaging
    TDI
    tissue Doppler imaging
    TSI
    tissue synchronisation imaging
    VTI
    velocity time integral

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