Limited but encouraging evidence has demonstrated the safety and efficacy of the MitraClip device. However, only 1 randomized controlled trial has been performed comparing MitraClip to surgical repair: the EVEREST II (Endovascular Valve Edge-to-Edge Repair Study) trial.
After demonstrating the safety and efficacy of the MitraClip system in the Phase 1 EVEREST I trial,18 the prospective EVEREST II trial compared the MitraClip system to surgical repair in a randomized controlled trial of 279 patients with severe grade 3 to 4+ degenerative MR.9,19 Results of the study demonstrated similar mortality rates at 1 and 4 years, as well as rates of grade 3+ or 4+ MR. Adverse events were significantly lower in the group undergoing a transcutaneous approach, although surgery for MV dysfunction was significantly higher in the transcutaneous group at 4 years (24.8% vs 5.5%). In the majority of patients, sustained reduction in MR and reduction of NYHA class III to IV HF—defined as MR ≤ grade 2+—was demonstrated with the transcutaneous repair approach. Additionally, functional status and quality-of-life metrics significantly improved. However, MR ≥ 2+ persisted in 58% of patients in the percutaneous arm compared with 18% in the surgical group. Recently reported data from EVEREST II for 4-year outcomes again demonstrated long-term noninferiority compared to surgical repair. Although rates of significant MR have improved in subsequent trials with the device, possibly reflective of increased experience, these higher residual MR rates have persisted above surgical repair rates.19-21 A recent meta-analysis conducted by Wan et al showed similar clinical outcomes between MitraClip and surgical intervention, despite a higher clinical risk profile (eg, older age, lower left ventricular ejection fraction [LVEF], higher EuroSCORE) among MitraClip patients.6 Although a significantly higher number of patients had residual MR >2, 30-day and 1-year mortality and number of re-operations were noninferior in the MitraClip group.
Several other registries and observational studies have demonstrated long-term efficacy of transcatheter repair in reducing MR severity and improving functional outcomes, despite typically increased patient risk profiles by EuroSCORE.20,21 These studies demonstrated high levels of initial procedural success, as well as improvement in functional status and residual MR at 1 year. The EVEREST II High Risk Registry evaluated percutaneous repair in patients at prohibitive risk (surgical mortality rate >12%) and demonstrated comparable procedural success and 1-year efficacy in LV reverse remodeling to prior trials, including the EVEREST II trial.22 Additionally, a recent comprehensive systematic analysis of 21 studies of high-risk patients comparing MitraClip to MV surgery further demonstrated high rates of technical success in both interventions with slightly lower rates of 30-day mortality and stroke risk after MitraClip and significant 1-year efficacy in reduction of MR and NYHA class HF (70% MR>2+ or NYHA> class II to 5 % at one year).23
Interestingly, studies in Europe have generally included both degenerative and functional MR in their analyses and have shown similarly high success rates and improvement in MR severity and clinical HF in both types. Patients with functional MR have been known to have more severe comorbidities, a higher interventional risk, and lesser efficacy in response to surgical intervention.24 A recent meta-analysis of MitraClip in 9 studies of patients with severe functional MR further demonstrated promising efficacy in improvement of functional status (20% NYHA I/II to 80% at 9 months), reduction in moderate to severe MR (95% to 11%), and cardiac remodeling.24 Restoration of life expectancy has been similar in subgroup analyses of young and old patients with similar procedure risk and 30-day mortality.14,25 Small prospective observational studies have demonstrated efficacy in patients with severe HF (LVEF <30%) with chronic MR, an area where MitraClip use may expand with further study.26,27 Correction of MR to less than 2+ is associated with reverse LV remodeling and normalization of chamber size, despite residual MR often present in transcatheter intervention and particularly in functional MR.9,26,28
Systematic reviews have demonstrated safety and noninferior rates of complications, even in high-risk patients, as well as reproducibility and efficacy.17,29 Given these ongoing rates of significant MR and its known detrimental effect on survival,30 studies have yet to compare percutaneous intervention to optimization of medical therapy. The upcoming COAPT (Clinical Outcomes Assessment of the MitraClip Percutaneous Therapy) and RESHAPE-HF (A Randomized Study of the MitraClip Device in Heart Failure Patients with Clinically Significant Functional Mitral Regurgitation) trials will assess the effectiveness of mitral clipping in high-risk surgical patients and advanced HF, respectively, compared with medical therapy alone. In addition to the MitraClip, other percutaneous technologies such as transcatheter MV replacement, annuloplasty, and chordal implantation are in development for future study.31