MitraClip in end-stage heart failure: a realistic alternative to surgery?

This editorial refers to ‘MitraClip® therapy in patients with end-stage systolic heart failure’ by O. Franzen et al., published in this issue on page 569–576.

Patients with severe symptomatic mitral regurgitation (MR) have a poor prognosis with an annual mortality rate of 5% without surgical intervention,1,2 and mortality can be as high as 60% at 5 years when associated with significant heart failure.3,4 Medical management of MR is limited to controlling symptoms of heart failure, because no medical strategy has been shown to improve survival.5 Surgery is recommended for patients with symptomatic severe MR or asymptomatic severe MR with evidence of left ventricular (LV) dysfunction or dilatation.6–8 Surgical options include mitral valve (MV) repair or replacement. When feasible, MV repair is the operation of choice. Mitral valve repair is associated with improved clinical outcomes including improved LV function, lower mortality, and avoidance of chronic anticoagulation (mechanical valves) compared with valve replacement surgery.9 However, valve morphology is of critical importance for the success of valve repair, and when surgical repair is not possible, replacement may be the only alternative.10 Reported in-hospital mortality rates for MV surgery range from 1 to 2% for low-risk patients undergoing MV repair to as high as 25% for high-risk or elderly patients undergoing valve replacement.11–13 Co-morbidities such as LV dysfunction, renal failure, or chronic obstructive pulmonary disease increase the risk of surgery significantly. Morbidity and mortality are also significantly higher for repeat operations.

In the 1980s, Alfieri14 developed an MV repair technique by suturing together the middle scallops of the anterior and posterior MV leaflets at the origin of the MR jet, resulting in a double-orifice MV, the so-called ‘edge-to-edge’ technique.15 This approach has been used predominantly for degenerative MR and is usually used in combination with an annuloplasty ring. Isolated edge-to-edge repair has been used in selected patients with durable results reported for up to 12 years. These late results were used as clinical proof of the principle of a novel endovascular approach for MV repair.16–18 This endovascular approach for MV repair aims to approximate the anterior and posterior MV leaflets with a mechanical implant (MitraClip System, Abbott Vascular–Structural Heart, Menlo Park, CA, USA), resulting in a double-orifice MV.19 Implantation of the MitraClip in an animal model showed the clip to be fully covered with tissue and securely attached to the leaflets at 12 months and did not result in the development of MV stenosis or haemolysis.20 The 12-month results of the first 107 non-randomized patients treated with the MitraClip in the EVEREST I clinical trial (Endovascular Valve Edge-to-Edge REpair Study I, feasibility trial) showed that the MitraClip can successfully reduce MR. Furthermore, the EVEREST I trial showed that the MitraClip procedure can be performed safely.21 An important additional finding from the EVEREST I trial was the observation that patients who had a suboptimal MitraClip procedure could subsequently undergo successful open MV surgery safely and effectively. Therefore, even after a suboptimal MitraClip procedure, there may be a benefit in delaying the need for future surgery, with no or negligible incremental risk. Open MV surgery may be avoided altogether in patients with a successful result. This strategy has also been successfully used for many years with balloon valvuloplasty for mitral commissurotomy.

Late breaking data from the landmark EVEREST II trial that were presented at the American College of Cardiology's 59th annual scientific meeting in March 2010, confirmed that the MitraClip can be an effective treatment option for patients with significant MR.22 The EVEREST II trial is the first randomized trial of any minimally invasive MV repair device compared with open MV surgery. For the primary safety endpoint of major adverse events (MAE) at 30 days, the MitraClip system demonstrated a superior safety profile (P < 0.0001) compared with surgical repair or replacement (9.6% of MitraClip patients and 57.0% of surgery patients had an MAE).

For the primary efficacy endpoint, the MitraClip device was non-inferior to surgery at 1 year (clinical success rate of 72.4% for MitraClip patients with successful initial treatment compared with a clinical success rate of 87.8% for surgery patients). With 95% confidence, the clinical success rate of the MitraClip device fell within 25.4% of the clinical success rate of the surgical control.

At 1 year, the MitraClip procedure demonstrated significant clinical benefits for the following secondary endpoints in patients with successful initial treatment. A reduction in the severity of MR, and a reduction in both the volume (LV diastolic volumes) and diameter of the left-ventricle heart chamber (LV diastolic dimensions), indicating an improvement in LV function, were reported. An improvement in symptoms was also reported, with 97.5% of patients having no symptoms [New York Heart Association (NYHA) functional class I] or mild symptoms (NYHA functional class II) [P < 0.0001], whereas at baseline, 52.6% of patients had moderate (NYHA functional class III) or severe symptoms (NYHA functional class IV). Furthermore, patients who underwent successful placement of the MitraClip experienced a significant improvement compared with baseline in both physical and mental quality of life with respect to open MV surgery, as measured by the SF-36 Survey [increase of 4.7 points in the physical quality-of-life score (P < 0.0001) and increase of 5.8 points in the mental quality-of-life score (P < 0.0001)]. In the present issue of the European Journal of Heart Failure, Franzen et al.23 describe the use of the MitraClip in patients with MR and end-stage heart failure with severely reduced LV function. The aim of this study was to assess the feasibility, short-term durability, and clinical outcomes of the MitraClip procedure for MR in patients with end-stage heart failure and severely reduced LV function. Franzen et al. retrospectively analysed data collected from seven European centres. Overall, 50 patients with heart failure, a LV ejection fraction ≤25% and MR of at least grade 3+ were included. All patients were in NYHA functional class III or IV. The patients underwent a total of 53 MitraClip procedures, an acute procedural success rate of 94%. Severity of MR was reduced in all successfully treated patients, 44 (92%) were discharged with MR ≤2+. Thirty-day mortality was 6%; cumulative survival at 6 months was 81.2%. At 6 months, MR ≤2+ was present in 27 (87%) of 31 patients, and 23 (72%) of 32 patients were in NYHA functional class I or II. Six min walk distance improved significantly and a significant reduction in LV volumes indicating reverse LV remodelling, was concordant with a significant reduction in NT-proBNP plasma levels. This study suggests that severe functional MR in patients with end-stage heart failure and marked LV dysfunction can be reduced by the MitraClip and that successful therapy promotes clinical benefit at 6 months. Prospective randomized studies with extended follow-up are warranted to validate the study results and assess the durability of MitraClip therapy in heart failure patients.

Summarizing, based on the positive risk-benefit profile demonstrated in the EVEREST trials and supported by the article of Franzen et al. published in this issue, the MitraClip procedure has the potential to be a valid treatment option for selected patients with significant MR. In particular, based on current evidence, high-risk symptomatic, or otherwise inoperable patients with severe MR (organic or functional) seem the best candidates for the MitraClip, whenever the echocardiographic criteria of eligibility are met. Indications for the MitraClip may increase in the future, since rapid improvements in technology and in imaging modalities are expected. In particular, improvements in first-generation devices may overcome some intrinsic limitations of the current system.

In conclusion, when treating patients with significant MR, clinicians need to consider the benefits of the available treatment options and the individual patient's risk factors when making decisions about therapy. The journey of trans-catheter treatment of the MV has only just begun.

Conflict of interest: none declared.