New England Journal of Medicine April 14, 2011

Percutaneous Repair or Surgery for Mitral Regurgitation

Ted Feldman, Elyse Foster, Donald D. Glower, Saibal Kar, Michael J. Rinaldi, et al. (EVEREST II Investigators)

Bottom Line

In patients with severe mitral regurgitation, percutaneous repair with the MitraClip was less effective than conventional surgery at reducing regurgitation but demonstrated superior safety and resulted in similar clinical improvements at 12 months.

Key Findings

1. The primary efficacy end point (composite of freedom from death, surgery for mitral-valve dysfunction, and grade 3+ or 4+ MR at 12 months) was achieved in 55% of the percutaneous-repair group compared to 73% of the surgery group (P=0.007) [2.1.2].

2. The primary safety end point (major adverse events at 30 days) occurred in significantly fewer patients in the percutaneous-repair group compared to the surgery group (15% vs. 48%, P<0.001).

3. At 12 months, the rate of required surgery for mitral-valve dysfunction was significantly higher in the percutaneous-repair group (20%) than in the initial surgery group (2%).

4. The individual rates of death (6% in each group) and persistent grade 3+ or 4+ mitral regurgitation (21% vs. 20%) were similar between the percutaneous repair and surgical arms at 12 months.

5. Despite differences in residual mitral regurgitation, both groups demonstrated similar and significant improvements in left ventricular size, New York Heart Association (NYHA) functional class, and quality-of-life measures from baseline to 12 months.

Study Design

Design

Randomized Controlled Trial

Open-Label

Sample

279

Patients

Duration

12 mo

Median

Setting

Multicenter, North America

Population Patients with moderately severe or severe (grade 3+ or 4+) mitral regurgitation who were candidates for conventional mitral valve surgery.

Intervention Percutaneous mitral-valve edge-to-edge repair using the MitraClip device.

Comparator Conventional open-heart surgery for repair or replacement of the mitral valve.

Outcome Efficacy: A composite of freedom from death, from surgery for mitral-valve dysfunction, and from grade 3+ or 4+ mitral regurgitation at 12 months. Safety: A composite of major adverse events within 30 days.

Study Limitations

• The open-label design could introduce bias in patient management, follow-up care, and the assessment of subjective endpoints like quality of life.

• A significant proportion of the major adverse events in the surgical arm were driven by perioperative blood transfusions, which may overstate the clinical safety disparity between the two approaches.

• The trial enrolled patients with both degenerative (primary) and functional (secondary) mitral regurgitation, pooling distinct pathophysiologies that typically respond differently to interventions.

• The relatively short 12-month follow-up of the primary report was insufficient to definitively evaluate the long-term durability of the percutaneous clip.

• Percutaneous repair was associated with a high early failure rate, with 1 in 5 patients requiring subsequent surgical intervention within the first year.

Clinical Significance

The EVEREST II trial was a landmark study that validated transcatheter edge-to-edge repair (TEER) using the MitraClip as a feasible, safe alternative to conventional open-heart surgery. Although percutaneous repair was less effective at definitively eliminating MR and carried a higher risk of needing subsequent surgery, its markedly lower 30-day major adverse event rate and comparable functional benefits established it as a vital therapeutic option—especially for patients at high or prohibitive risk for traditional surgery.

Historical Context

For decades, open-heart surgery (repair or replacement) was the only definitive treatment for severe mitral regurgitation, leaving a vast population of elderly or frail patients unserved due to prohibitive surgical risk. The MitraClip device was engineered to percutaneously replicate the surgical 'Alfieri stitch' (edge-to-edge repair). EVEREST II was the first pivotal randomized controlled trial to directly compare this transcatheter approach to the surgical gold standard, ultimately paving the way for the FDA approval of the MitraClip in 2013 and catalyzing the rapid growth of structural heart disease interventions.

Guided Discussion

High-yield insights from every perspective

Med Student

Medical Student

How does the Alfieri stitch concept, which the MitraClip replicates, alter the hemodynamics and anatomy of the mitral valve to reduce regurgitation, and what basic anatomical criteria are required for it to be successful?

Key Response

This tests the student's understanding of basic valvular anatomy and pathophysiology. The MitraClip essentially fastens the anterior and posterior leaflets together (usually A2 to P2), creating a double-orifice valve that reduces the regurgitant orifice area while ideally maintaining an adequate forward flow area. Anatomically, it requires sufficient leaflet tissue for grasping and pathology that is centrally located.

Resident

Given that the EVEREST II trial showed surgery was more effective at eliminating MR but MitraClip had a better safety profile, what specific clinical and echocardiographic features would lead you to recommend percutaneous repair over surgery for a patient with severe symptomatic MR?

Key Response

Residents must learn to apply trial data to patient selection. Since EVEREST II demonstrated that surgery is more definitive for MR reduction, percutaneous repair is typically reserved for patients with a high STS predicted risk of mortality (e.g., frailty, severe comorbidities) who also possess favorable echocardiographic anatomy (e.g., central pathology, lack of severe calcification) as discussed in multidisciplinary heart team meetings.

Fellow

The EVEREST II trial included patients with both primary (degenerative) and secondary (functional) MR. How does the pathophysiology of functional vs. degenerative MR influence the durability of edge-to-edge repair, and how do the results of later trials like COAPT and MITRA-FR contextualize the functional MR subgroup from EVEREST II?

Key Response

Fellows need to integrate EVEREST II with subsequent landmark literature. Degenerative MR is a primary valve issue, whereas functional MR is a ventricular issue (tethering/dilation). The COAPT and MITRA-FR trials showed that in functional MR, patient selection based on 'proportionate' vs. 'disproportionate' MR relative to left ventricular volume is critical for predicting whether a MitraClip will provide a mortality benefit, a nuance not fully explored in the early EVEREST II cohort.

Attending

When counseling a high-surgical-risk patient about MitraClip based on EVEREST II and subsequent longitudinal data, how do you frame the trade-off between the higher likelihood of residual MR requiring reintervention versus the immediate procedural safety and short-term quality of life improvements?

Key Response

Attendings must navigate complex shared decision-making. The rationale emphasizes translating clinical trial endpoints (like the 20% need for surgery at 1 year in the MitraClip group of EVEREST II) into practical patient expectations, ensuring the patient understands that TEER prioritizes symptom relief and safety over definitive, long-term anatomical correction.

Scholarly Review

Critical appraisal through the lens of expert reviewers and guideline development

PhD

EVEREST II utilized a composite primary efficacy endpoint of freedom from death, surgery for mitral-valve dysfunction, and grade 3+ or 4+ MR at 12 months. How does the inclusion of a highly subjective clinical decision (surgery for valve dysfunction) alongside a core-lab adjudicated metric (MR grade) introduce potential bias, and how would you design an estimand to better isolate the device's true efficacy?

Key Response

This questions the construct validity of the composite endpoint. Combining subjective clinical thresholds for reoperation with objective echocardiographic data can introduce ascertainment bias. A robust methodological critique would explore how competing risks and clinical blinding (or lack thereof) affect the triggering of the 'surgery' component, and suggest using hierarchical win-ratio designs or stricter, purely objective hemodynamic estimands.

Journal Editor

The EVEREST II trial was conducted during the early learning curve of the MitraClip procedure, while surgeons were performing established, highly optimized conventional operations. How does this differential in procedural maturity threaten the internal and external validity of the efficacy endpoints, and how should a reviewer account for this 'learning curve bias'?

Key Response

A seasoned editor must evaluate baseline procedural disparities. Comparing a novel transcatheter device to a decades-old surgical standard often underestimates the future efficacy and safety of the device. Reviewers should look for learning curve analyses within the supplementary data and recognize that both the safety and efficacy estimates for the device are likely to improve significantly in post-market real-world registries.

Guideline Committee

Based on the EVEREST II trial findings of lower MR reduction efficacy but superior safety, how should current guidelines grade the recommendation for transcatheter edge-to-edge repair (TEER) in patients with severe primary MR, and why is surgery still maintained as the Class I recommendation for low-risk patients?

Key Response

This directly informs guideline construction. Because EVEREST II showed that surgery was superior in durably eliminating MR, current ACC/AHA guidelines maintain surgery as a Class I recommendation for severe primary MR in low-to-intermediate risk patients. TEER is given a Class IIa recommendation strictly for symptomatic patients with primary MR who have favorable anatomy but are deemed high or prohibitive surgical risks, reflecting the safety vs. efficacy trade-off established in EVEREST II.

Clinical Landscape

Noteworthy Related Trials

2014

CTSNet Severe Ischemic MR Trial

n = 251 · NEJM

Tested

Mitral-valve replacement

Population

Patients with severe ischemic mitral regurgitation

Comparator

Mitral-valve repair

Endpoint

Left ventricular end-systolic volume index at 12 months

Key result: There was no significant difference in left ventricular reverse remodeling or survival, but repair had a higher rate of MR recurrence.

2018

COAPT Trial

n = 614 · NEJM

Tested

Transcatheter mitral-valve repair (MitraClip) plus medical therapy

Population

Patients with heart failure and severe secondary mitral regurgitation

Comparator

Medical therapy alone

Endpoint

All-cause hospitalizations for heart failure within 24 months

Key result: MitraClip significantly reduced heart failure hospitalizations and all-cause mortality compared to medical therapy alone.

2018

MITRA-FR Trial

n = 304 · NEJM

Tested

Percutaneous mitral-valve repair (MitraClip) plus medical therapy

Population

Patients with severe secondary mitral regurgitation and symptomatic heart failure

Comparator

Medical therapy alone

Endpoint

Composite of all-cause death or unplanned hospitalization for heart failure at 12 months

Key result: There was no significant difference in the composite primary endpoint between the percutaneous repair and medical therapy groups.

Tailored to your role

Want this tailored to you?

Add your specialty or training stage to get role-specific takeaways and more questions.

Personalize this analysis