News:Cardiac Resynchronization Therapy and Optimal Medical Therapy May Reverse Left Ventricular Remodeling in the REVERSE trial

April 1st, 2008 By Katherine Ogando [mailto:kogando@perfuse.org]

ACC 08-Chicago, IL: Cardiac resynchronization therapy (CRT) along with optimal medical therapy (OMT), may improve left ventricular remodeling in patients with mild or no heart failure symptoms according to the REVERSE study. This study was presented today at the ACC 08 by Dr. Cecilia Linde from Sweden.

Cardiac resynchronization therapy has been demonstrated to improve outcomes in patients with severe heart failure (NYHA class III and IV). The authors of the study hypothesized that patients with milder symptoms of heart failure could potentially benefit from CRT as well.

The REVERSE (Resynchronization reverses Remodeling in Systolic left vEntricular dysfunction) study compared the effect of CRT combined with OMT (CRT ON) against OMT alone (CRT OFF) in a randomized, double-blind, controlled multicenter trial. Their was participation by 73 centers in the US, Canada, and Europe. It enrolled a total of 610 patients meeting the criteria for NYHA class II or I (previously symptomatic), with QRS duration > 120 ms, an LV ejection fraction (LVEF) <40%, and a left ventricular end-diastolic dimension (LVEDD) >55 mm. In addition, study participants had to be managed with optimal medical therapy, such as ACE inhibitors, angiotensin receptor blockers, and on stable doses for beta-blockers for at least a month prior to study enrollment. The patients could not have undergone prior permanent cardiac pacing, and could participate with or without an ICD indication.

The primary endpoint was defined as the heart failure clinical composite response, which compares the percent of patients whose condition worsened in the CRT OFF group versus the CRT ON group. This endpoint includes all-cause mortality, heart failure hospitalizations, crossover due to worsening heart failure, NYHA class, and the patient global assessment. The secondary endpoint consists of assessment of the ventricular end systolic volume index (LVESVi) between the CRT OFF and the CRT ON groups.

Patients were randomized in a 2:1 ratio to the CTR ON group (n=419) and CTR OFF (n=191) groups, respectively. The mean age was 61.8 ± 11.6 vs. 62.9 ± 10.6 (p=0.26), the mean LVEF was 26.4 ± 7.0 vs. 26.8 ± 7.0 (p=0.50) and 83% vs. 82% of patients were in NYHA class II in the CRT OFF group compared with the CRT ON group.

There was no significant difference in the primary endpoint between the two groups. The CRT OFF group observed a higher proportion of patients whose condition worsened than the CRT ON, with 21% vs. 16%, p=0.10. The distribution between improved, unchanged, and worsened also favored the CRT ON group versus the CRT OFF group respectively as follows: Worsened, 16% vs. 21%; unchanged, 30% vs. 39%; improved, 54% vs. 40% (p=0.004).

For the secondary endpoint, there was a decrease in the LVESVi of 18.4 ml/m² in the CRT ON group, compared to the more moderate 1.3 ml/m² decrease in the CRT OFF group after 12 months, (n=487, p<0.0001). There was also a steeper decrease in LVEDVi, 20.5 ml/m² in the CRT ON group compared against 1.4 ml/m² in the CRT OFF group (p<0.0001, n=487). Similarly, the LVEF of the CRT ON group increased by 3.8%, versus the 0.6% increase in the CRT OFF group (p<0.0001, n=487). Finally, a 6 minute hall walk test did not demonstrate any significant difference between the two groups (p=0.26).

The study findings suggest that CRT has a beneficial effect on the outcomes of patients with mild heart failure as there is a higher proportion of patients whose condition improved in the CRT ON group compared to the CRT OFF group. The LVEDVi and LVEF results indicate that CRT was associated with an improvement in LV modeling. The hall walk test, however, signifies that although CRT may be associated with positive outcomes, the overall quality of life of patients undergoing the therapy does not change in the short-term.

Future studies may explore the long-term effects of CRT and OMT in patients with mild or no heart failure symptoms.

In addition to the primary and secondary endpoint results, the authors reported no significant improvement between the two groups in the 6 minute hall walk distance.

The results of this study have yet to be reviewed by the FDA to determine efficacy and safety in this patient population. This study was sponsored by Medtronic Inc.