Surface electrocardiogram to predict outcome in candidates for cardiac resynchronization therapy: a sub‐analysis of the CARE‐HF trial

Abstract

AimsIn CARE-HF, cardiac resynchronization therapy (CRT) lowered morbidity and mortality in patients with moderate to severe heart failure. We examined whether baseline and follow-up electrocardiographic characteristics might predict long-term outcome. Methods and resultsCARE-HF randomly assigned 409 patients to medical therapy (MT) plus CRT, and 404 patients to MT alone. Electrocardiographic measurements were made at baseline during sinus rhythm, and at 3 months during paced or spontaneous rhythm depending on treatment assignment. Favourable outcome was defined as freedom from death, urgent transplantation, or cardiovascular hospitalization. Among patients assigned to CRT, 39% had unfavourable outcomes including 55 deaths. By single variable analysis, (i) prolonged PR interval, left QRS axis (but not QRS duration), and left bundle branch block (BBB) at baseline, and (ii) heart rate, PR, and QRS duration at 3 months predicted unfavourable outcome. By multiple variable analysis, treatment assignment (P ¼ 0.0001), PR (P ¼ 0.0004), and right BBB (P , 0.00013) at baseline predicted outcome, whereas baseline JTc and QRS duration at 3 months predicted all-cause mortality and heart failure hospitalization (P ¼ 0.0071). ConclusionIn CARE-HF, QRS duration at baseline did not predict outcome, but QRS at 3 months was a predictor by single variable analysis. Patients with prolonged PR interval and the 5% of patients with right BBB had a particularly high event rate.--

QRS duration versus morphology and survival after cardiac resynchronization therapy

“…A recent meta‐analysis, pooling data from 5813 patients included in five randomized trials, showed that QRS duration ≥150 ms was associated with clinical benefit from CRT (risk ratio 0.60, 95% CI 0.53–0.67; P  < 0.001) whereas patients with QRS duration between 120 and 143 ms did not benefit from CRT (risk ratio 0.95, 95% CI 0.82–1.10; P  = 0.49) 8. In contrast, the substudy of the CARE‐HF trial demonstrated that QRS duration was not associated with the composite primary outcome of all‐cause mortality and unplanned hospitalization for management of major cardiovascular event 6. Of note, only 11% of patients had a QRS duration <150 ms, which may explain the lack of statistically significant association between QRS duration and outcome.…”

“…QRS morphology (LBBB vs. non‐LBBB) has been consistently associated with better outcomes in patients treated with CRT. For example, in the Cardiac Resynchronization‐Heart Failure (CARE‐HF) trial, which randomized 813 patients to CRT + optimal medical therapy or optimal medical therapy alone, 94% of patients had LBBB morphology while only 5% of patients had right bundle branch block QRS configuration 6. The presence of right bundle branch block morphology was independently associated with the composite primary outcome of all‐cause mortality and unplanned hospitalization for management of major cardiovascular events (HR 2.043, 95% CI 1.332–3.157; P  = 0.001) 6.…”

“…For example, in the Cardiac Resynchronization‐Heart Failure (CARE‐HF) trial, which randomized 813 patients to CRT + optimal medical therapy or optimal medical therapy alone, 94% of patients had LBBB morphology while only 5% of patients had right bundle branch block QRS configuration 6. The presence of right bundle branch block morphology was independently associated with the composite primary outcome of all‐cause mortality and unplanned hospitalization for management of major cardiovascular events (HR 2.043, 95% CI 1.332–3.157; P  = 0.001) 6. In addition, the sub‐study of the Multicenter Automatic Defibrillator Implantation Trial‐Cardiac Resynchronization Therapy (MADIT‐CRT) trial, including 1817 patients with sinus rhythm at baseline ECG, showed that the presence of LBBB morphology was associated with a 53% reduction in the risk of heart failure events or all‐cause mortality of patients randomized to CRT with defibrillator compared with patients treated with implantable cardioverter defibrillator (ICD) alone whereas patients with non‐LBBB QRS morphology did not show clinical benefit from CRT 7.…”

“…However, the individual prognostic benefit is not consistent, and selection of patients who will benefit from CRT remains challenging. Sub‐analyses from randomized controlled trials and meta‐analyses pointed out that QRS duration and morphology are relevant for prognosis of patients treated with CRT 5, 6, 7, 8, 9. Patients with shorter QRS duration and/or non‐left bundle branch block (LBBB) morphology appear to benefit less than patients with longer QRS duration and/or LBBB morphology 5, 6, 7, 8, 9.…”

“…Sub‐analyses from randomized controlled trials and meta‐analyses pointed out that QRS duration and morphology are relevant for prognosis of patients treated with CRT 5, 6, 7, 8, 9. Patients with shorter QRS duration and/or non‐left bundle branch block (LBBB) morphology appear to benefit less than patients with longer QRS duration and/or LBBB morphology 5, 6, 7, 8, 9. However, the patients included in randomized trials with non‐LBBB configuration represent a minority (5–30%), and approximately one third has a QRS duration between 120–150 ms 1, 2, 3, 4.…”