Could exercise unveil the mystery of non-response to cardiac resynchronization therapy?

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Left ventricular mechanical dyssynchrony describes the differences in the timing of contraction between different myocardial segments that are commonly observed in patients with congestive heart failure, particularly in those with depressed LV ejection fraction. Its presence varies with not only the methods of assessment, but also characteristics of the study population including the QRS duration, loading condition, severity of coronary artery disease, LV hypertrophy, and LV remodelling. Therefore, the ECG criteria of QRS width ≥120 ms adopted in the current guidelines may not be optimal for identifying patients who will benefit most from CRT or defining the presence of mechanical dyssynchrony. 6 Analysis of LV dyssynchrony is achieved by different imaging modalities such as echocardiography, from conventional M-mode and Doppler echocardiography to more advanced tissue Doppler imaging (TDI), three-dimensional echocardiography, and speckle tracking imaging, and most of the time, performed at rest. Consequently, lack of mechanical dyssynchrony has been found in about one-third of heart failure patients with QRS duration ≥120 ms. On the other hand, mechanical dyssynchrony occurs in 40‐50% of patients with a narrow QRS complex defined as ,120 ms. 7 Furthermore, numerous studies have suggested that the presence and the extent of LV mechanical dyssynchrony could be a better predictor of response to CRT than QRS duration per se. 5,8 Not until recently, the contribution of exercise to LV mechanical dyssynchrony has been investigated and exercise-induced dyssynchrony has been found to be associated with exacerbation of heart failure symptoms, an increase in mitral regurgitation, and a reduction in exercise capacity. 9‐12 Therefore, it appears that the assessment of LV mechanical dyssynchrony only at rest may not be sufficient in heart failure patients. The landmark study by Lafitte et al. 9 first described how mechanical dyssynchrony was modified by exercise in 65 consecutive patients with LV ejection fraction of ,35% and New York Heart Association class II or III symptoms. Depending on the parameter adopted for assessment and using 20% of change as a cut-off point, LV systolic dyssynchrony increased in 28‐40%, remained the same in 35‐43%, and decreased in 23‐31% of the patients during exercise. On a closer inspection, patients could be categorized into four different groups: patients without dyssynchrony at rest but induced by exercise (exercise-induced dyssynchrony), patients with dyssynchrony at rest which normalized during exercise, patients without dyssynchrony at rest as well as during exercise, and patients with dyssynchrony in both situations. The former two groups warranted further investigation to help understand the relationship with lack of response to CRT, which represented 20‐26% of the study population. In another study in 60 patients with dilated cardiomyopathy and narrow QRS complex (,120 ms), significant mechanical dyssynchrony was observed in 33.3% of patients at rest and in 58.3% during exercise. The dynamic change in standard deviations of the time to peak systolic velocity of the 12 LV segments (Ts-SD or Yu Index) as the dyssynchrony measurement between rest and exercise showed an independent positive association with the change in mitral regurgitation, and an independent inverse correlation with the change in LV stroke volume. 10 Wang et al. 11 reported the occurrence of exercise-evoked systolic dyssynchrony in 11 (33%) of 33 heart failure patients with ejection