**5. Response prediction of new echocardiographic mechanical dyssynchrony markers**

#### **5.1 Eye balling and time-based mechanical dyssynchrony markers**

Accumulation of resynchronization trials knowledge demonstrated clearly that an important proportion of the CRT population is not responding. All-cause mortality combined including heart failure hospitalization, NYHA class, and patient global assessment were used in a heart failure clinical composite score (CCS) in Multicenter InSync Randomized Clinical Evaluation (MIRACLE) and was not able to show improvement in 34% of patients [7, 51]. A special new concern group in today's trials are the non-LBBB subjects. The use of echocardiographic markers before 2008 for this important group was not able to show additive benefit of the use of echocardiographic markers to predict CRT in important landmark trials like PROSPECT (Predictors of Response to Cardiac Resynchronization Therapy), ECHO-CRT, and others [26]. Iatrogenic electropathy has been reported as a possible deleterious effect of biventricular pacing [52]. *New echocardiographic parameters to evaluate ventricular dyssynchrony were made available to provide proper measurement tool for resynchronization therapy* [53, 54]. Two parameters are in clinical use nowadays: first is simple eyeballing to assess the degree of dyssynchrony. The second is more technical demanding based on strain study called strain-based speckle tracking echocardiography (STE). Mechanical dyssynchrony is present when an interventricular mechanical delay of > or = 40 ms and a septal-to-posterior radial peak strain delay of > or = 130 ms assessed with STE-strain curves.

Incorporation of echocardiographic mechanical parameters to evaluate ventricular dyssynchrony contribute significantly to the improvement of the prognostic value of guideline-based patient selection for CRT [54, 55]. Reduction of all-cause mortality was associated with incorporation of the apical rocking and/or septal flash at baseline evaluation for CRT [56, 57]. Incorporation of mechanical dyssynchrony parameters as a selection criterion for CRT was associated with a significant reduction in LV end-systolic pressure in comparison to the old criteria based on QRS duration and morphology alone [55]. Despite those early promising outcome studies, not all non-LBBB with mechanical dyssynchrony have improved outcomes.

*CRT Past, Present, and Future Directions: Toward Intelligent Responders Selection… DOI: http://dx.doi.org/10.5772/intechopen.101608*

Here it is wise to remember that absence of response, especially in the time dyssynchrony-based studies, might be related to a non-electrical disease that is not responding to CRT like myocardial hypocontractility and scaring, which are very frequent pathologies in the heart failure population. Future randomized control trials must consider those important discriminative factors.

## **5.2 Septal rebound stretch analysis for the prediction of volumetric response to cardiac resynchronization therapy**

Utilizing detection of specific wall motion patterns to serve as markers for CRT response is the most recent advance in the investigation toward optimal response prediction for CRT [54, 58–60]. It is promising as a superior ventricular dyssynchrony measure tool compared to timing-based measures. Early septal contraction and delayed lateral wall activation give rise to myocardial stretching of the opposing wall during systole [54, 59, 61, 62]. This stretching is paradoxical systolic LV motion that is not contributing to LV ejection and, will result in waste of energy. This myocardial stretch and the resulting waste of energy can be converted to myocardial shortening when we perform biventricular pacing [58, 63, 64]. Systolic rebound stretch of the septum (SRSsept) refers to the amount of systolic stretching of the septum after initial systolic shortening (**Figure 1**). It is considered as a good indicator to reflect the potential for recovery of LV function with CRT and might be one of the best response indicators for resynchronization therapy [53, 58, 66]. Salden et al. and after their pioneering publication in the strategies to improve the selection of patients without typical LBBB for cardiac resynchronization therapy [67] and in a recent publication, published the first results from the multicenter study that investigated the association of baseline echocardiographic SRSsept with the volumetric response after CRT. They found that SRSsept is independently associated with favorable changes in LVESV post CRT. In addition, they found that for the prediction of volumetric response, assessment of SRSsept implies additional predictive information compared to visual assessment of apical rock alone. For assessment of subjects without strict LBBB criteria, SRSsept is an excellent echocardiographic discriminator to predict response to CRT [65]. We and others recommend incorporation of echocardiographic SRSspet for future prospective validation studies for CRT subjects evaluation.

#### **Figure 1.**

*Septal single wall image acquisition of systolic rebound stretch of the septum (SRSsept)-in red-defined as septal stretching after initial shortening. Speckle tracking echocardiography software was used to deduce strain curves of the focused LV septal wall image. MVC, mitral valve closing; AVC, aortic valve closing [65].*
