Redefining response to CRT: insights from REVERSE
The REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) study, one of the pivotal trials of cardiac resynchronisation therapy (CRT), showed that CRT improved the clinical composite score and resulted in reverse remodelling in patients with mild HF, reduced left ventricular (LV) ejection fraction and QRS prolongation.1 Professor Michael Gold (Medical University of South Carolina, Charleston, USA) described a new analysis from REVERSE that sought to answer further questions about response to CRT.
“One of the major concerns with CRT is the lack of improvement in about one-third of patients,” he says. “As HF is a progressive disease, it may not be appropriate to use the term ‘non-responder’ for everyone who does not objectively improve. In some patients, a clear response is not observed, but CRT may have prevented deterioration. We evaluated long-term mortality from REVERSE in three groups of patients, ‘responders’, ‘non-progressors’ and ‘progressors,’ with classification based on the two major endpoints of the trial.”
In REVERSE, patients with LV ejection fraction <40% and QRS duration >120 ms were randomised to CRT ON and CRT OFF. After the 12-month randomised phase in the US and 24 months in Europe, all patients were programmed to CRT ON and prospectively followed for 5 years from device implantation. The current analysis included 353 patients with full echocardiographic data who were initially assigned to CRT ON.
The primary endpoint of REVERSE was the clinical composite score at 12 months, which classified patients as improved (56%), unchanged (30%) or worsened (14%).
“There was no difference in 5-year mortality between patients classified as improved or unchanged, analogous to responders and non-progressors, but there was dramatically higher mortality in patients who exhibited worsening at 12 months,” comments Prof. Gold.
Response was also analysed based on the independently powered secondary endpoint of the change in LV end-systolic volume index (LVESVi) at 6 months. Responders were classified as those with a ≥15% reduction, non-progressors as those with a 0–15% reduction and progressors as those with a >0% increase. As with the clinical composite score, those patients who progressed according to LVESVi had a much higher 5-year mortality than patients classified as non-progressors or responders.
Discussing the implications of the findings, Prof. Gold explains, “The consistency between the two different endpoints used for measuring response gives credence and validity to the concept that patients who progress are at much higher risk than non-responders with stabilisation or those who improve. Progressors identified by LVESVi at 6 months or by clinical composite score at 12 months should receive early intervention due to their very poor prognosis. We are now trying to identify factors associated with progression, and, if we can identify likely progressors ahead of the procedure, then we can consider if alternative therapies would be a better approach.”
- Linde C, et al. J Am Coll Cardiol 2008;52:1834–1843.