Effectiveness of Cardiac Resynchronization Therapy by QRS Morphology in the Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy (MADIT-CRT)

Abstract

on behalf of the MADIT-CRT InvestigatorsBackground-This study aimed to determine whether QRS morphology identifies patients who benefit from cardiac resynchronization therapy with a defibrillator (CRT-D) and whether it influences the risk of primary and secondary end points in patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT) trial. Methods and Results-Baseline 12-lead ECGs were evaluated with regard to QRS morphology. Heart failure event or death was the primary end point of the trial. Death, heart failure event, ventricular tachycardia, and ventricular fibrillation were secondary end points. Among 1817 patients with available sinus rhythm ECGs at baseline, there were 1281 (70%) with left bundle-branch block (LBBB), 228 (13%) with right bundle-branch block, and 308 (17%) with nonspecific intraventricular conduction disturbances. The latter 2 groups were defined as non-LBBB groups. Hazard ratios for the primary end point for comparisons of CRT-D patients versus patients who only received an implantable cardioverter defibrillator (ICD) were significantly (PϽ0.001) lower in LBBB patients (0.47; PϽ0.001) than in non-LBBB patients (1.24; Pϭ0.257). The risk of ventricular tachycardia, ventricular fibrillation, or death was decreased significantly in CRT-D patients with LBBB but not in non-LBBB patients. Echocardiographic parameters showed significantly (PϽ0.001) greater reduction in left ventricular volumes and increase in ejection fraction with CRT-D in LBBB than in non-LBBB patients. Conclusions-Heart failure patients with New York Heart Association class I or II and ejection fraction Յ30% and LBBB derive substantial clinical benefit from CRT-D: a reduction in heart failure progression and a reduction in the risk of ventricular tachyarrhythmias. No clinical benefit was observed in patients with a non-LBBB QRS pattern (right bundle-branch block or intraventricular conduction disturbances). Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00180271.

QRS duration versus morphology and survival after cardiac resynchronization therapy

“…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. Subsequent meta‐analysis pooling data from 5356 patients enrolled in four randomized trials showed that LBBB morphology was associated with significant reduction in the composite adverse clinical events of patients treated with CRT (risk ratio 0.64, 95% CI 0.52–0.77; P  < 0.0001) whereas patients with non‐LBBB configuration failed to show clinical benefit 9.…”

“…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.…”

2013 ESC Guidelines on Cardiac Pacing and Cardiac Resynchronization Therapy

“…En general, con estimulación cardiaca, el índice de recurrencia del síncope durante el seguimiento osciló entre 0 y el 20%, mientras que las recurrencias del síncope siempre fueron más en los pacientes no tratados, que mostraron tasas de un 20-60%. En un metanálisis de los tres estudios con grupo control de pacientes no tratados [36][37][38] , el síncope se repitió en el 9% de los 85 pacientes tratados con marcapasos y en el 38% de los 91 controles (riesgo relativo [RR] = 0,24; intervalo de confianza del 95% [IC95%], 0, 48). En un registro amplio de 169 pacientes consecutivos tratados con marcapasos 39 , la recurrencia actuarial estimada de síncope fue del 7% a 1 año, el 16% a 3 años y el 20% a 5 años.…”

Biventricular pacing in heart failure: right is not wrong!

“…Those with left bundle branch block (LBBB) and the widest QRS complexes seem to have the highest rate of response [4]. However, a significant percentage of patients with guideline-approved criteria remain "nonresponders."…”