Impact of QRS Morphology and Duration on Outcomes Following Cardiac Resynchronization Therapy: Results From the Resynchronization-Defibrillation for Ambulatory Heart Failure Trial (RAFT)
Does QRS duration and/or morphology impact outcomes in patients with heart failure (HF) receiving cardiac resynchronization therapy with defibrillators (CRT-ICD) versus ICDs alone?
This was a secondary analysis of the RAFT (Resynchronization-Defibrillation for Ambulatory Heart Failure Trial) trial. Patients (n = 1,483) with New York Heart Association (NYHA) class II or III HF, an ejection fraction (EF) <30%, and a QRS ≥120 ms with a normal sinus rhythm were randomized to CRT-ICD versus ICD alone. Patients were grouped according to QRS morphology: left bundle branch block (LBBB), right bundle branch block (RBBB), or nonspecific intraventricular conduction delay (NIVCD) patterns. They were further subgrouped by QRS duration. The primary outcome was all-cause mortality or HF hospitalization.
Of 1,483 patients, an LBBB was present in 1,175 (79%), an RBBB in 141 (12%), and a NIVCD in 167 (14%). Patients with an LBBB had a lower EF (EF 22% in LBBB, 24% in RBBB, and 23% in NIVCD) and were less likely to have an ischemic etiology for HF (62% LBBB, 80% RBBB, and 83% NIVCD). In patients with an LBBB, event-free survival was better with CRT-ICD and this was true over all QRS durations studied (hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.52-0.78). Patients with a non-LBBB pattern did not have a significant improvement in event-free survival with CRT-ICD versus ICD therapy (HR, 0.99; 95% CI, 0.70-1.4). However, nonsignificant reductions in death were noted (HR, 0.54; 95% CI, 0.26-1.1) for RBBB and (HR, 0.93; 95% CI, 0.49-1.8) for NIVCD. On subgroup analysis, patients with a QRS ≥160 ms and a non-LBBB pattern had an HR of 0.52 (95% CI, 0.29-0.96) for the primary outcome compared with those receiving ICD alone (p = 0.03). Patients with a QRS <160 ms and non-LBBB pattern did not have improved event-free survival with CRT-ICD therapy (HR, 1.38; 95% CI, 0.88-2.14; p = 0.16).
The authors concluded that patients with an LBBB gain benefit from CRT-ICD compared with ICD alone. Data from this analysis do not support the use of CRT-ICD in those with a QRS <160 ms and non-LBBB morphology.
In this secondary analysis, more data are present to support CRT-ICD therapy in patients with HF and an LBBB pattern. This is now standard of care for HF patients with reduced EFs and an LBBB. However, the data supporting device therapy for those with non-LBBB patterns remain murky. Like noted in other studies, both QRS duration and morphology appear to play a role in benefit, which makes theoretical sense given the location of the resynchronization lead in the branch coronary sinus (CS). Conduction abnormalities arising from within the right ventricle or other regions of the left ventricle may gain less resynchronization benefit, or worsen, with leads placed in the CS. However, this study does not clearly negate benefit of CRT-ICD therapy in all patients with non-LBBB patterns. It just highlights the lack of answers. Power is a significant weakness of this substudy. Only 102 patients had a QRS duration ≥160 ms and a non-LBBB pattern, and only 53 of these were randomized to CRT-ICD. While non-LBBB patients overall did not have a reduction in the primary outcome with CRT-ICD, they did have trends for improved survival, which was most prominent in the RBBB subgroup (HR for death, 0.54). For patients with a QRS <160 ms and non-LBBB, events occurred early after CRT-ICD implant (within 6 months). Was this driven by HF? Should we institute early follow-up to ensure we are not provoking HF in these patients? Were these patients displaying RBBB or NIVCD, or both? At this point, we need to ‘unlump’ the non-LBBB HF patients and perform a well-designed randomized trial of CRT-ICD versus ICD therapy in non-LBBB patients examining the impact of QRS morphology on outcomes.
Keywords: Heart Failure, Defibrillators, Implantable, Cardiac Resynchronization Therapy
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