EVEREST II Substudy Affirms Feasibility, Efficacy of Percutaneous Mitral Leaflet Repair

Charanjit S. Rihal, MD

This is an exceedingly important study to the CV community for a number of reasons. As patients survive into advanced age due to improvements in surgical, procedural and medical therapies, CV specialists will increasingly be faced with the challenge of dealing with very elderly, symptomatic individuals for whom no simple therapies exist. The EVEREST II High Risk Study addresses an extraordinarily challenging subset of patients: those in their 70s and 80s who are symptomatic due to severe MR and LV dysfunction, who have significant medical comorbidity and are poor candidates for open surgery. The trial introduces a new concept of using the MitraClip to percutaneously perform edge-to-edge stapling of the mitral valve leaflets in an effort to reduce mitral regurgitation, improve symptoms and avoid open surgery. A high degree of technical and cognitive skill on the part of the interventional cardiologist is required in successfully performing this procedure, as is the ability to interpret transesophageal echocardiographic images, in collaboration with imaging specialists.

The EVEREST II High Risk Study prospectively enrolled some of the sickest patients ever reported in a clinical study. STS scores were very high, 14 to 18 depending on how they were calculated. In comparison, these STS values are significantly higher than those reported for the PARTNER cohort B study of inoperable aortic stenosis patients undergoing percutaneous aortic valve implantation (where mean values were in the 11-12 range). In EVEREST II, severe comorbidities were extensive and universal, so much so that many of us would hesitate to consult a CV surgeon on these patients.

In an attempt to identify a control group, 58 patients who were treated medically were identified; unfortunately, 22 of these were not included for various reasons. Thus, only a small, nonrandomized control group of 36 patients was available as a comparator. Remarkably, clips were successfully placed in 96% of patients, which attests to the skill of the interventionalists performing these procedures. On the other hand, bad things happen to elderly, sick patients when they undergo general anesthesia and cardiac procedures, and this study confirms it. The procedures were not without complications and six patients died within 30 days. All deaths were felt to be ultimately related to the procedure, albeit not directly intraprocedural. More disturbing, however, is that a further 13 deaths occurred following hospital discharge to 12 months. The high observed incidence of death raises the question whether many of these patients were too far gone in their disease process to legitimately benefit from any therapeutic intervention.

Nonetheless, the imaging and clinical results at 12 months (among survivors) demonstrated significant improvements in LV remodeling, in the degree of mitral regurgitation and significant improvement in symptom status. Thus, the conclusion could be reached that if one survives the procedure and manages to make it out to 1 year, one’s outlook is brighter. Whether this represents an impact of the intervention, natural selection or some combination of both remains to be determined.

Ultimately, I suspect the MitraClip will be an important addition to our therapeutic armamentarium for both functional and degenerative MR among high-risk patients. Moreover, I believe it will be complementary, and not competitive, with currently available medical and surgical therapies.