Reply to the Letter to the Editor by Yi et al

We thank Yi et al for the interest in our study and for the questions raised, which help to stimulate the discussion and to conceive further studies.

Regarding their doubt about potential differences in response to cardiac resynchronization therapy (CRT) between ischemic and nonischemic patients despite interventricular pacing interval (V-V) optimization, we strongly believe that the effect of CRT may be influenced by the underlying myocardial disease. The cited study of Molhoek et al was a preliminary report on 74 patients that could not demonstrate significant differences in outcome between ischemic and nonischemic patients. However, data from clinical trials suggested that at mid- and long-term follow-up after CRT, the improvement in left ventricular (LV) size and function is significantly larger in non-ischemic patients as compared to ischemic patients.1, 2 In a recent study,3 we also demonstrated that acutely after CRT the reduction of LV end-systolic volume is significantly greater in nonischemic as compared to ischemic patients. With the current study we suggested that V-V optimization might compensate for the conduction abnormalities due to the presence of scar tissue and lead to a more favorable response to CRT at short-term follow-up. In our opinion, these findings are of great pathophysiologic and clinical interest, but larger studies are needed to confirm these results.

To answer their question about which parameter among LV outflow-tract velocity-time integral (LVOT VTI) and LV dyssynchrony should be preferred during V-V optimization, no evidence so far is available on the superiority of one approach over the other. In our study, we have chosen to define the optimal V-V interval as the one with the highest LVOT VTI, since it is a simple measure that should promptly reflect the acute changes in LV systolic performance. The assessment of LV dyssynchrony in turn, requires advanced skills and specific software that may not be widely available. In addition, there is still no consensus on which is the best method for LV dyssynchrony assessment. In our study, LV dyssynchrony was measured calculating the maximum delay in peak systolic-velocity within 4 basal segments. An excellent agreement was found between V-V intervals yielding the highest LVOT VTI and the lowest LV dyssynchrony. However, as mentioned by Yi et al, not in all cases the 2 approaches were coincident, probably due to different substrates and to the intrinsic difference between the 2 measures.

Finally, regarding their question whether the localization rather than the total extent of transmural scar tissue might be related to the optimal V-V setting, further studies are needed to explore this issue. In particular, it would be interesting to evaluate the relationship between LV lead position, scar localization, and LV site of latest activation. These 3 factors showed to play an important role in response to CRT.4, 5