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Edge-to-edge mitral valve repair: solid data and a prosperous future
  1. Martin Orban,
  2. Jörg Hausleiter
  1. Medizinische Klinikund Poliklinik I, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany
  1. Correspondence to Dr Martin Orban, Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Campus Innenstadt, Ludwig-Maximilians-Universität München, Ziemssenstr. 1, 80336 München, Germany; MartinOrban{at}

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In recent years, transcatheter edge-to-edge mitral valve repair (E2E-MVR) using the mitral clip approach (MitraClip, Abbott Vascular, Menlo Park, California, USA) has evolved as the predominant alternative non-surgical treatment option for patients with symptomatic mitral regurgitation (MR) who were judged inoperable by a heart team. By now, more than 45 000 patients have been treated with this approach, demonstrating a wide acceptance for this interventional treatment.

MR is classified on the basis of the underlying aetiology as primary (degenerative) or secondary (functional) that constitute markedly different diseases. In patients with primary MR, the mitral valve apparatus per se is diseased and left ventricular ejection fraction (LV-EF) is mostly preserved (mean LV-EF of 58% in Chiarito et al’s Heart manuscript).1 The Endovascular Valve Edge-to-Edge Repair Study (EVEREST) II2—which included predominantly patients with primary MR (in 73% of randomised patients)—E2E-MVR did not reduce MR as effectively as surgical mitral valve repair or replacement in patients who were eligible for surgery, but nevertheless, short-term clinical outcome of patients treated with E2E-MVR showed a similar mortality rate and improvement of New York Heart Association (NYHA) functional class compared with surgical mitral valve repair and replacement. Although the inferior MR reduction was initially thought of as disappointing, the overall results may also be considered favourably due to the fact that the interventional experience with E2E-MVR was negligible in this early trial with a mean experience of less than 10 cases per interventional site. The 5-year result of the EVEREST II trial showed no difference in mortality and a comparable symptomatic improvement between E2E-MVR and surgical mitral valve repair and replacement. Both American and European guidelines advise E2E-MVR for patients with a prohibitive surgical risk due to severe comorbidities with chronic severe primary MR who have favourable anatomy for the repair procedure and a reasonable life expectancy with a class of recommendation IIb, level of evidence B and a class of recommendation IIb, level of evidence C, respectively (figure 1).3 4

Figure 1

Current guideline recommendation of transcatheter edge-to-edge mitral valve repair (E2E-MVR) in patients judged inoperable with primary or secondary MR. The figures depicts the class of recommendation and the level of evidence of American and European guideline recommendations of transcatheter E2E-MVR in patients judged inoperable with primary and secondary MR. IIb, class of recommendation: usefulness/efficacy is less well established by evidence/opinion and E2E-MVR may be considered; B, level of evidence: xata derived from a single randomised clinical trial or large non-randomised studies; C, level of evidence: consensus of opinion of the experts and/or small studies, retrospective studies and registries.; MR, mitral regurgitation.

In contrast, the underlying cause of secondary MR is the disease of the left ventricle, which leads to left ventricular dilatation and restricted leaflet motion, while the leaflets and the subvalvular apparatus is intact. Overall prognosis of these patients is determined by the left ventricular dysfunction (mean LV-EF of 39% in patients with functional MR in  Heart).1 The cornerstone of treatment of this patient population is optimal pharmacotherapy and, if applicable, cardiac resynchronisation therapy. In end-stage heart failure, heart transplantation can be performed or further mechanical circulatory support can be established with ventricular assist devices. As secondary severe MR in patients with heart failure worsens prognosis and accelerates left ventricular failure and dilation, it seems to be reasonable to treat MR. Interestingly, surgical therapies of secondary MR have not proven beneficial in terms of prognosis and tend to be inefficient in sustaining MR reduction. Similar to E2E-MVR, the level of evidence for the surgical approach is weak (evidence C). Here, interventional strategies come into focus due to their considerably lower periprocedural and postprocedural risk. Especially secondary MR usually provides good conditions for the edge-to-edge repair technique, since the leaflets, papillary muscles and chordae are not primarily affected. However, left ventricular and annular dilatation as the cause of MR persists and may lead to subsequent deterioration of MR. Only European guidelines implemented this therapy option as recommendation for the treatment of secondary MR (recommendation class IIb, level of evidence C, figure 1)4, while American guidelines do not despite the fact that in non-randomised studies E2E-MVR improves heart failure symptoms even in selected patients with severely impaired LV-EF,5 6 which is of particular interest of the individual patient.

Whether E2E-MVR is safe and successful for both groups of MR patients remains to be defined, and a large meta-analysis comparing both aetiologies was still missing in the literature. The present systematic review and meta-analysis by Chiarito et al investigates the outcome (safety and efficacy) after E2E-MVR in patients with primary versus secondary MR.1 The availability of data on 1-year outcome and a study population of at least 25 patients were the prerequisite for this meta-analysis. Thus, nine studies with available 1-year outcome analysing 2615 patients in total (833 patients with primary and 1782 with secondary MR) were included. This meta-analysis highlights again the differences in baseline characteristics between both patient populations.


Single leaflet device attachment rate was low in both groups (primary MR: 4% vs secondary MR: 3%, p=0.81), and no device embolisation occurred within the first year. Patients with primary MR had a significant higher rate of reintervention at 1 year (10% vs 4%, p=0.04).


No difference in the acute procedural success defined as MR grade below or equal 2+ was detected (94% vs 95%, p=0.52). At 1 year, there was no difference in the number of patients with MR grade ≤2+  between both groups (54% vs 58%, p=0.4); however, not all of those studies were core lab adjudicated. Patients with primary MR showed significantly lower rates of NYHA class III and IV at 1 year (8% vs 16%, p<0.001) and rehospitalisation for heart failure (14% vs 23%, p=0.03). Interestingly, there was no difference in 1-year mortality between both groups (14% vs 18%, p=0.18), a fact which is likely explained by the considerably higher age in the primary MR group (5 years older), which might equal the substantially lower left ventricular ejection fraction (39% in secondary vs 58% in primary MR group) and higher frequencies of comorbidities usually seen in the secondary MR group.

This meta-analysis is the largest data collection, which compares patients with primary versus secondary MR who are treated with E2E-MVR. The data suggest that E2E-MVR can be considered as safe and successful in both primary and secondary MR. It represents exceptional data on a large number (n=1782) of patients with secondary MR and provides physicians with a stronger evidence to recommend E2E-MVR to patients with high or prohibitive surgical risk with both primary and especially secondary MR. The data from this meta-analysis support again the need for implementation of E2E-MVR as a treatment option in the standard of care of patients with secondary MR and heart failure. In clinical reality, E2E-MVR already found its way into broad everyday clinical practice for secondary MR in heart failure patients in some countries. This fact is also reflected in this meta-analysis since the majority of patients was treated for secondary MR (68% of patients). Hence, physicians should be equipped with broader guideline recommendations. However, still, large randomised controlled trials are missing to increase the level of evidence.

Open questions

Until now there is no completed randomised controlled trial except the EVEREST trials,2 which investigates safety and outcome of E2E-MVR. Future studies should take into consideration that E2E-MVR treats two different patient populations—primary and secondary MR—and investigators may aim their studies and analyses restricted to one of these populations. It is widely accepted that procedural success of E2E-MVR is considered as a reduction of MR to grade ≤2+. There is a paucity of data comparing clinical outcome of patients according to a postprocedural grade 2+, 1+ or even <1 stratified by primary or secondary MR. The Heart meta-analysis by Chiarito et al does not add data to this field due to the unavailability of data. Especially for secondary MR, the issue of whether maximal reduction of MR represents the best strategy to improve outcome is still unresolved. While complete elimination of MR might appear as the natural approach, it is unclear whether the rapid increase in afterload after complete elimination of MR might be detrimental to a failing left ventricle and increase the risk of contractile failure. However, the available clinical experience so far does not support this theoretical concern. Moreover, reduction of MR by placement of additional clips might cause a progressive reduction of mitral valve orifice area eventually leading to a rise in atrial pressure even during mild exercise or tachycardia limiting the benefit of the procedure for the patient. Finally, the impact of E2E-MVR on prognosis is still unclear. However, multiple retrospective studies already demonstrated that E2E-MVR might be associated with a relevant reduction of mortality, when compared with control patients.7 8 Furthermore, three ongoing prospective randomised trials (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT), A Clinical Evaluation of the Safety and Effectiveness of the MitraClip System in the Treatment of Clinically Significant Functional Mitral Regurgitation 2 (RESHAPE-HF2) and Multicentre Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients With Severe Secondary Mitral Regurgitation (MITRA-FR)) will provide more guideline-relevant evidence within the next few years, which might impact our treatment of heart failure patients with concomitant secondary MR.



  • Competing interests JH received speaker honoraria from Abbott Vascular and Edwards LifeSciences; MO has no conflict of interest.

  • Provenance and peer review Commissioned; internally peer reviewed.

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