QRSarea as single indicator for selection of patients for resynchronization therapy: subanalysis of the RAFT study

Background Prior retrospective and non-randomized studies indicate that the area under the QRS complex (QRSarea) has a strong association with the response to cardiac resynchronisation therapy (CRT). Purpose To evaluate the strength of QRSarea for selection of patients for CRT using a subanalysis of the RAFT trial, in which heart failure patients were randomized to CRT-D or ICD. Methods RAFT (Resynchronization–Defibrillation for Ambulatory Heart Failure Trial) was a multicenter, double-blind, randomized, controlled study that included patients with heart failure symptoms (NYHA II-III), ejection fraction <30% and QRS duration >120 ms. Data from 1081 patients with sufficient ECG quality was available for QRSarea analysis. Primary endpoint was the combination of all-cause mortality (ACM) and hospitalization for heart failure (HFH). Subgroups were created using QRS duration (QRSd; < and >/= 150 ms), left bundle branch block (LBBB; Y/N) and QRSarea (quartiles). QRSarea was determined from the vectorcardiogram, synthesized from digitized 12-lead ECGs as the sum of the area under the QRS complex in the X, Y and Z leads. CRT benefit was defined as a significant difference in outcome between the CRTD and the ICD group. Results The RAFT QRSarea cohort consisted of 68% patients with ischemic cardiomyopathy (ICM) and 77% patients with LBBB. The highest two QRSarea quartiles consisted for > 90% of patients with LBBB as well as ~50% patients with non-ICM. In contrast, the lower two quartiles consisted of ~50% with LBBB and >80% patients with ICM. Larger QRSarea was also associated with lower age and LVEF as well as hypertension. A significant relation existed between QRSarea and CRT benefit regarding the primary endpoint (HR 0.80 (95% CI 0.69-0.94)), the CRT benefit regarding the primary endpoint being significant in the two higher QRSarea quartiles (figure; dashed =ICD, drawn lines = CRT). CRT patients in all QRSarea quartiles benefited regarding ACM while benefit in HFH occurred only in patients in the upper two quartiles. Conclusions This randomized study demonstrates that QRSarea provides a consistent estimation of the benefit of CRT in patients with heart failure, presumably because QRSarea reflects both electrophysiological and non-electrophysiological factors and can be determined objectively, accurately and in terms of continuous values.