Association of QRS Duration and Reduction in Clinical Events with CRT

In 2010 in the United States, costs related to heart failure were >$39 billion; heart failure affects approximately 6 million people in the United States and an additional 6.5 million in Europe. Cardiac resynchronization therapy (CRT) added to medical therapy has become the cornerstone of treatment for heart disease. CRT, also known as biventricular pacing, has been shown to reduce clinical events (including death) in patients with prolonged QRS duration on the electrocardiogram. Current treatment guidelines call for CRT for patients with systolic heart failure, New York Heart Association (NYHA) class 3 or 4 symptoms, and a QRS duration of ≥120 milliseconds. However, according to researchers, approximately one-third to one-half of patients receiving CRT did not respond to treatment with CRT. Based on an analysis of a study subgroup in which patients with a QRS interval <150 milliseconds had no reduction in heart failure events with CRT, the guidelines have been revised to include a new recommendation for CRT in NYHA 1 and/or NYHA 2 systolic heart failure, with a QRS cutoff of >150 milliseconds. To determine whether the impact of CRT on clinical end points is affected by the degree of baseline QRS prolongation, researchers recently conducted a meta-analysis of randomized trials testing CRT in heart failure. They reported results in Archives of Internal Medicine [2011;171(16):1454-1462]. The researchers searched MEDLINE, SCOPUS (covering EMBASE), and Cochrane Central Register of Controlled Trials databases to identify randomized controlled CRT trials. The analysis included trials that reported clinical outcomes of subgroups stratified by QRS duration. Exclusion criteria were nonrandomized studies, studies lacking a non-CRT control group, enabled an implantable cardioverter-defibrillator (ICD) only in 1 study and not in the other(s) (trials enabling ICD implantation in both arms were eligible), crossover study design, lack of data regarding clinical outcomes of interest (death and hospitalization), and/or reported clinical outcomes without any relation to specific limited QRS ranges. The final meta-analysis included 5 randomized trials representing 5813 patients. In patients with severely prolonged QRS, there was a statistically significant reduction in risk for composite clinical events with CRT in each individual trial (risk ratio [RR], 0.60; 95% confidence interval [CI], 0.53-0.67; P<.001). Conversely, there was no benefit of CRT in patients with moderately prolonged QRS (RR, 0.95; 95% CI, 0.82-1.10; P=.49). The differences in RR resulted in significantly different CRT in the 2 QRS groups (severely prolonged and moderately prolonged) (P<.001). In terms of the association of the magnitude of QRS prolongation and the impact of CRT on the risk of composite clinical events determined by meta-regression analysis, there was a statistically significant relationship between the QRS duration and log RR (slope, –0.07 [95% CI, –0.10 to –0.04; z=–4.60; P<.001). Accordingly, groups with QRS duration levels <150 milliseconds did not benefit from CRT. The differential response of the 2 QRS groups was evident for all NYHA classes. Study limitations cited by the authors included variation in composite outcome across the included trials, using ranges of QRS duration to determine a cutoff, and including trials that dealt with 2 types of outcome measures (hazard ratio and odds ratio). In summary, the researchers noted that “cardiac resynchronization therapy was effective in reducing adverse events in patients with heart failure and a baseline QRS interval of 150 milliseconds or greater, but CRT did not reduce events in patients with a QRS of less than 150 milliseconds. These findings have implications for the selection of patients for CRT.”