Although the Mississippi delta is a long way from the high peaks of the Himalayas, the contours of EVEREST II were unveiled in New Orleans on Monday at the 60th annual American College of Cardiology (ACC) Scientific Sessions. If you weren’t in attendance, you might be left wondering: Did percutaneous repair for mitral regurgitation come out on top? And how will I find out?
Never fear, dear readers! Thanks to coordinated publication of the full study this week in NEJM, you, too, can follow along with Dr Ted Feldman and the EVEREST II Investigators as they scale the lofty heights of catheter-based cardiac valve repair.
Traditional surgical repair of MR involves the placement of an annuloplasty ring. It produces durable improvement, but comes with the recovery time and potential complications of a median sternotomy. The study sponsor’s percutaneous MR repair system is a catheter-delivered clip that aspires to improve the systolic apposition of the mitral leaflets by clasping them together (a worthwhile video illustrating the procedure is available here on NEJM.org). General anesthesia, with its attendant risks, is still required, but median sternotomy is avoided. The study investigators hypothesized that the gains in periprocedural safety with percutaneous repair would more than offset any loss of procedural efficacy.
The EVEREST II study began by recruiting subjects with 3+ or 4+ mitral regurgitation (MR) plus evidence of left ventricular dysfunction. Subjects were then randomized to percutaneous mitral repair (n=184) or to surgery (n=95). Treatment assignment was not blinded. Results were analyzed by intention-to-treat, as subjects with unsuccessful percutaneous repair often went on to receive surgery. Patients were then followed for two years, with the primary outcome measured at 12 months.
So which technique got to plant a flag on the peak of EVEREST II? On the primary effectiveness endpoint (freedom from death, surgery for mitral valve dysfunction, and 3-4+ MR at 12 months), the surgical arm emerged as clearly superior (73% vs. 55%, p=0.007), a result primarily driven by the subsequent need to proceed to a traditional surgical approach. On the primary safety endpoint (major adverse events at 30 days), the percutaneous repair was victorious (15% vs. 48%, p<0.001), a result driven in part by the need for perioperative blood transfusion in the surgical group.
The percutaneous repair was safer, but it clearly wasn’t as effective: 21% of subjects in the percutaneaous repair arm required surgery within 12 months, and individuals with a percutaneous repair had more residual MR than those undergoing surgery. So what’s best for your patients with MR?
In an accompanying editorial, Drs. Catherine Otto and Edward Verrier (University of Washington, WA) bring a 29, 029 foot perspective to exactly this question. They worry that the long-term effectiveness of percutaneous repair may not be very durable, and seem to feel that percutaneous repair isn’t ready for broad use. Interventionalists might argue that a ‘percutaneous-first’ strategy allowed 78% of patients in the clipping arm to avoid surgery at the two-year follow-up. Ongoing technical innovations may make the percutaneous procedure safer and more effective – although the same is true for surgery as well.
“Patients want treatments that are as safe and effective as possible,” says cardiologist and NEJM executive editor Dr. Gregory Curfman, “Rigorously performed trials like EVEREST II are needed to carefully examine whether technical innovations actually improve meaningful outcomes for patients, and the investigators are to be commended for their efforts.”
The pinnacle of therapy for severe MR that is a treatment that is both perfectly effective and perfectly safe. We’re not there yet. But progress in medicine is like progress in mountaineering: Persistence is key.
“No, it is not remarkable that Everest did not yield to the first few attempts; indeed, it would have been very surprising and not a little sad if it had, for that is not way of great mountains.” – Eric Shipton, Upon That Mountain