European Journal of Echocardiography Advance Access originally published online on March 14, 2008
European Journal of Echocardiography 2008 9(3):320-321; doi:10.1093/ejechocard/jen021
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Echocardiographic selection of candidates for cardiac resynchronization therapy: the lack of evidence! Reply
La Sapienza University
Rome
Italy
E-mail address: vitar{at}tiscali.it
We appreciate the interest in our work,1 in which we have attempted to delineate a possible algorithm to use tissue doppler imaging (TDI)-guided cardiac resynchronization therapy (CRT) as a complement to evidence-based clinical guidelines in the management of patients with severe heart failure.
Dr Soliman et al. suggest that echocardiographic left ventricle (LV) dyssynchrony can be assessed by the ‘spectral’ TDI lateral-to-septal delay whereas ‘colour-encoded’ TDI (regardless of the LV segment model used) is of limited value because several inherited physiological and technical limitations. Thus, they raise the question that in the absence of sound and prospective multi-centre echocardiographic data, any advice to use TDI (colour-encoded TDI?) for patient selection is speculative.
Actually, I believe that ‘scientific’ progress and methods are not only related to ‘multi-centre’ data, even if themselves statistically important.2 Anyway, unpublished reports should be considered as preliminary data3 since analyses may change in the final publication. In addition, we should consider that the guidelines based on large, randomized, controlled studies are not inflexible, and they do provide the best first step. Patients vary in complexity and degree of illness, as they do in their individual responses to medication and other treatment modalities, so statistical data must be gathered properly and then corrected to reflect variations in patient complexity. In common, clinical practice I often realize evident benefits in the individual heart failure (HF) patient after CRT with improved synchronicity by both spectral and colour-encoded TDI (and patients are ‘real world’!). Lastly, although I agree with them about TDI technical limitations, I verify their opinion on colour-encoded TDI is somewhat contradicted by the current literature.
The prognostic importance of systolic dyssynchrony in predicting short-to-medium-term response was initially reported by Bader et al., 4 who examined HF patients with EF of 
45% and prolonged QRS duration who were followed for 1 year. Intraventricular delay was examined by spectral pulsed TDI in the apical four- and two-chamber views to document the LV long-axis motion and was found to be the most important independent predictor of HF events.
The important prognostic value of systolic dyssynchrony was also confirmed in patients with HF and narrow QRS complexes. In a study of HF patients with EF <35% and QRS duration 120 ms,5 intraventricular dyssynchrony was measured from both basal and middle LV segments on apical four- and two-chamber views, and the standard deviation of the time to peak systolic velocity (Ts-SD) was derived from the eight LV segments through off-line analysis. From the receiver-operating characteristic curves, a Ts-SD value of >37 ms had a sensitivity of 68% and specificity of 71% to predict event-free survival.
Other studies suggested that assessment of LV mechanical delay in HF patients provides prognostic information independent of electrical delay on the surface electrocardiogram. In fact, systolic dyssynchrony is a common condition in HF, with a prevalence range from 27 to 43% depending on methodologies. Most of the indices of dyssynchrony with defined cut-off values were derived from TDI or related technologies.6 These parameters mostly examined the time to peak myocardial contraction from 2 (e.g., septal-to-lateral wall delay) to 12 (Ts-SD or Ts-diff) LV segments. The assessment of systolic dyssynchrony by TDI before pacemaker implantation may help to predict short-to-medium-term echocardiographic responders with a reasonably high sensitivity (87–97%), but variable specificity (55–100%).
Apart from predicting responders after CRT, TDI also has a role in predicting the long-term clinical outcome. The link between baseline systolic dyssynchrony and long-term prognosis in HF patients could be explained by the fact that those patients with severe systolic dyssynchrony had early LV reverse remodelling. LV reverse remodelling was the only independent predictor of all-cause or cardiovascular mortality by Cox multivariable regression analysis.7 Currently, the role of dyssynchrony assessment by applying tissue-Doppler or non-Doppler strain to predict CRT response is a topic of further investigation,8,9 although strain rate did not appear to be useful.10 However, the use of the various echo modalities requires sound knowledge of the pathophysiology of dyssynchrony and of the benefits and limitations of each ultrasound technique.
In conclusion, I do believe that although myocardial velocity curves can be constructed either on line from spectral pulsed TDI or off line from two-dimensional colour TDI; the latter approach is preferable, because multiple segments can be compared within the same heart beat. Systolic dyssynchrony assessment not only predicts HF events and mortality, but may also predict favourable LV reverse remodelling and long-term clinical outcome. Although a number of post-processing techniques can be derived from TDI, such as strain and strain rate, the clinical utility of these modalities as prognosticators has not yet been established.
Thus, on the basis of literature and clinical data, I would suggest a more appropriate letter title: Echocardiographic selection of candidates for cardiac resynchronization therapy: ‘A new field still in progress’ instead of ‘The lack of evidence’.
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[Abstract/Free Full Text] - Mele D, Pasanisi G, Capasso F, De Simone A, Morales MA, Poggio D, et al. Left intraventricular myocardial deformation dyssynchrony identifies responders to cardiac resynchronization therapy in patients with heart failure. Eur Heart J (2006) 27:1070–1078.
[Abstract/Free Full Text] - Knebel F, Schattke S, Bondke H, Walde T, Eddicks S, Reibis R, et al. Evaluation of longitudinal and radial two-dimensional strain imaging versus Doppler tissue echocardiography in predicting long-term response to cardiac resynchronization therapy. J Am Soc Echocardiogr (2007) 20:335–341.[CrossRef][Web of Science][Medline]
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[Abstract/Free Full Text]
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