Mechanical dyssynchrony—resurrected as a flashing and rocking parameter to predict prognosis after cardiac resynchronization therapy

Clinicians want to implant those patients with cardiac resynchronization therapy (CRT) who can benefit from it in terms of quality of life, symptoms, and survival. Still, selection of these patients is not straight forward. We are continuously trying to improve the treatment by looking for new techniques, new parameters, new indices, to select the correct patients, to select the correct lead position and pacing site(s), to select the correct device programming and to select the correct response parameters. Among a myriad of response parameters to CRT, the reduction of end-systolic volume (ESV) is widely in use and has been used in several trials.1,2 The Leuven group led by Voigt explore CRT response parameters in a new publication from the multicentre PREDICT-CRT study.3 The authors present the association between volumetric response and long-term survival in 356 CRT patients and show, not unexpectedly, that reverse remodelling by volumetric response was strongly associated with long-term survival. Importantly however, it seemed impossible to find a meaningful cut-off value to predict survival when exploring the ESV reduction after CRT implantation. Survival analyses showed better survival in those with more ESV reduction compared with those with less reduction regardless of which cut-off value that was chosen to separate responders from non-responders. This was nicely displayed as six different Kaplan–Meier plots with different ESV cut-offs and with convincing separation of all curves. This is an intriguing observation. Imagine, the authors would have been happy with just one of these plots, and built the story on that finding. These authors went further and showed that the association between survival and ESV change is a true continuum and that a categorical cut-off using reduction in ESV > 15% is as correct or as incorrect as an ESV reduction of 10% or 5%. Therefore, categorical ESV cut-offs for CRT response should be discussed and may need to be adjusted. This finding is important when interpreting other studies which have used ESV > 15% or other volumetric cut-offs for definition of CRT response. How many patients were clinical responders, but did not reach 15% ESV reduction? How many patients were inappropriately categorized as non-responders because they had limited or no reduction in ESV although the CRT prevented a further deterioration of heart failure? What about the correlations to other parameters and to long-term survival when dichotomizing at a specified cut-off? These points are important to bear in mind and to remind us that response parameters, others than survival, are only surrogate markers. Before redefining ESV criteria for positive CRT response, there is need for comparison to an untreated control group since progression of underlying heart disease also contributes to changes in ESV, although this study may be difficult to conduct. Furthermore, methodological challenges with measuring LV volumes restrict what can be a robust minimum change in ESV to serve as a reliable marker of positive response to CRT. On the other hand, the problems with using volumetric cut-offs for response to CRT are probably bigger in research than in clinical practice. It is reassuring that the results from this study support that all volumetric reduction after CRT counts, independently of where on the scale you start and independently of the magnitude of reduction. Patients and doctors are happy with any decrease in ESV either if decreased by 3% or 30% if symptoms improve or even if symptoms remain stable. The next topic the authors address is the role of mechanical dyssynchrony and long-term survival. The authors used visual assessment of mechanical dyssynchrony by septal flash and apical rocking retrospectively as a possible marker of CRT response and predictor of prognosis. These methods have been explained previously4 and have been both embraced for the simplicity and criticized for the subjectivity and inaccuracy. The authors evaluated the presence of septal flash and apical rocking before CRT and 12 months after CRT and categorized mechanical dyssynchrony as corrected, uncorrected or as no dyssynchrony at baseline. As expected, patients with corrected dyssynchrony had most favourable outcome and patients with uncorrected or no dyssynchrony had the worst outcome. Unfortunately, they did not report if any patients with no mechanical dyssynchrony before CRT developed dyssynchrony after CRT, i.e. ‘increased dyssynchrony’. This very unwanted development, either due to lack of CRT effect and natural disease progression or as an active effect of CRT, has been shown to be associated with most unfavourable prognosis.5 The possibility that CRT may not only be neutral, but in some patients even harmful is concerning and should always be considered and carefully examined. The authors showed a strong association between corrected mechanical dyssynchrony and survival and claimed that this association was stronger than for ESV change. The idea that correction of dyssynchrony is beneficial has been the intuitive thought all since start of the CRT era as also captured in the name of CRT. Corrected mechanical dyssynchrony has previously been associated with beneficial outcome after CRT using other techniques. Time difference between segments by radial strain6 or mechanical dispersion by longitudinal strain7 have been used as markers of dyssynchrony. A reduction of dyssynchrony by these methods after CRT was beneficial for prognosis, while persistence or worsening of dyssynchrony was unfavourable.5,8 So, should we rethink and use mechanical dyssynchrony as a response parameter after CRT? The failure of mechanical dyssynchrony as a parameter to select patients for CRT2,9 should not oppose the idea of mechanical dyssynchrony as a response parameter after CRT. CRT is a powerful therapy and can change cardiac timing and mechanics completely. Synchronicity can be restored by CRT, but also worsened. Therefore, mechanical dyssynchrony not before CRT, but after CRT is most important and plays a key role for prognosis in the individual patient. Septal flash and apical rocking as diagnostic approaches are promising, but are limited by their subjective and dichotomous nature and development of objective methods to quantify these motion disturbances are welcomed. We need further prospective studies to explore if other echocardiographic parameters can assess response to CRT. Studies should investigate if parameters of mechanical dyssynchrony which are closely related to the electrical conduction delay, such as wasted myocardial work,10 septal flash and apical rocking may be used to identify CRT responders in line with the notion that markers of dyssynchrony are good predictors of CRT response if they reflect electrical conduction delay.11 In summary, this study supports recent reports and the simple idea that correcting dyssynchrony is the main target for CRT. Mechanical dyssynchrony has failed as a selection parameter for CRT, but seems to be an excellent response parameter after CRT implantation to predict prognosis. Conflict of interest: None declared.