Page 168 - Simplicity is Key in CRT

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CRT and non-LBBB
In chapter 6, we show that in 50% of patients with IVCD delayed activation of the LV lateral wall is present, as measured invasively by electro-anatomical mapping (EAM). 12-lead ECG assessment using QRS duration and other well-established indices were not able to identify the IVCD patients that harbour the electrical substrate amenable to CRT.
These results are important because studies up to now, do not agree on the level of benefit for non-LBBB patients [12-14]. In a substudy of the RAFT trial, Birnie et al. [14] showed no significant benefit of CRT with respect to death or HF hospitalization in 60 RBBB and 83 IVCD patients treated with CRT, compared to similar patients not treated with CRT. Event rate in these small subgroups of patients was low and therefore the analysis was not powered to prove significance. However, using improvement in a composite clinical score, which provides significantly more power to the analysis, did not result in significant improvement in the non-LBBB subgroup of the REVERSE trial (n=238) either [12]. Furthermore, echocardiographic endpoints like improvement in end-systolic volume and LVEF were all non-significant in this study. The largest number of non-LBBB patients (n=327), analysed in the MADIT-CRT substudy by Zareba et al. [13] once again showed no benefit in clinical outcomes when these patients were treated with CRT-D versus ICD. Echocardiographic outcomes however did improve significantly in the non-LBBB groups treated with CRT-D versus ICD. These reductions in end-systolic volume and increase in LVEF were present in both RBBB (n=136) and IVCD (n=183) subgroups.
The results from chapter 6 demonstrate that while on average non-LBBB patients may not benefit from CRT, there may be an important subgroup of responders. This diversity within non-LBBB patients fits with the results from previous studies that showed that non-LBBB patients, especially IVCD patients, are a heterogeneous group of patients with multiple causes of conduction delay among which some can be corrected with CRT and consequently show benefit from therapy [12-14, 16, 17].
As some non-LBBB patients may have the electrical substrate amenable to CRT, they might benefit from therapy. Though it should be noted that although these patients harbour the electrical properties (delayed activation of the LV lateral wall), they might not fulfil LBBB criteria because of the presence of scar or other known factors decreasing the chance of benefit from CRT. As IVCD is common among patients currently being referred for CRT, the search for an ECG marker differentiating those IVCD patients with the electrical substrate present deserves to be intensified.
QRS area in patient selection for CRT
In chapter 7 we try to contribute to the quest for a better 12-lead ECG marker for the substrate amenable to CRT by evaluating the association of QRS area with outcomes in CRT. In the abovementioned MUG cohort, QRS area was associated with echocardiographic as well as clinical outcome in CRT. Furthermore it proved to be associated with both clinical and echocardiographic response to CRT, whereas the combination of QRS duration and LBBB morphology, currently used in patient selection for CRT, was not.
The data adds considerably to the already available data in small single centre studies [18, 19] on the value of vectorcardiographic QRS area in identifying patients able to benefit from CRT. Moreover, Mafi Rad et al. [20] have shown that QRS area has a stronger association with the presence of delayed activation of the left ventricular lateral wall than various LBBB definitions and QRS duration. The recent multicentre prospective Markers of Response