It's Time for a Paradigm Shift in the Quantitative Evaluation of Left Ventricular Dyssynchrony

The acute adverse effects of left ventricular (LV) dyssynchrony on cardiac performance were first described in 1925 by Carl Wiggers1. In recent years, the accurate diagnosis of LV dyssynchrony has become the focus of a myriad of publications, driven by the advent of cardiac resynchronization therapy (CRT) to treat heart failure due to severe LV dysfunction in the setting of marked prolongation of the QRS interval2–4. In the initial large clinical trials of CRT, QRS duration was used as a measure of dyssynchrony to select patients for treatment2, 3. However, sensitivity5 and specificity6 of QRS duration to predict response to CRT were less than optimal. Subsequently, numerous “time-to-peak” parameters based directly on the motion of the LV walls were developed to diagnose LV mechanical dyssynchrony with echocardiography in an attempt to improve CRT selection criteria7. Echocardiographic mechanical dyssynchrony parameters initially showed promise in predicting response to CRT in single-center studies8–12. However, the multicenter Predictors of Response to CRT (PROSPECT) study recently reported that no echocardiographic dyssynchrony parameter could be recommended to improve patient selection for CRT beyond current guidelines13. In addition, the Resynchronization Therapy in Narrow QRS (RETHINQ) trial recently reported that patients with narrow QRS and evidence of mechanical dyssynchrony do not benefit from CRT14. So where do we go from here? Should selection of patients for CRT based on mechanical dyssynchrony be abandoned in the wake of the negative results from PROSPECT and RETHINQ? We believe that techniques to quantify LV mechanical dyssynchrony need to be refined, not forgotten, and will still play a role in improving CRT selection criteria in the future. This refinement of dyssynchrony quantification requires a paradigm shift. First, time-to-peak methods for quantifying dyssynchrony utilize only a single time point on the velocity or strain curves and should be replaced with more quantitatively sophisticated methods. Utilizing more data reduces variability and increases accuracy. Second, “response to CRT” should no longer be considered synonymous with “presence of left ventricular dyssynchrony”. There is no method based on LV dyssynchrony measures that by itself will predict response to CRT with high accuracy.