Use of the MitraClip in High-Risk Patients with Severe Heart Failure: Are we Ready to Identify the Right Candidate?

This editorial refers to ‘Patient selection criteria and midterm clinical outcome for MitraClip therapy in patients with severe mitral regurgitation and severe congestive heart failure,’ by M. Neuss et al., published in this issue on pages 786–795. Mitral regurgitation is common in patients with advanced heart failure, and is associated with poor outcome. Mitral valve surgery has traditionally been the treatment of choice, but a proportion of patients with severe mitral regurgitation and severe heart failure are inoperable or their operative risk is considered too high. Such patients will in general be treated with conventional heart failure drug treatment, while the role of mitral valve surgery is questionable, particularly in those in whom no additional coronary surgery is performed.1 Use of CRT is another treatment option in severe heart failure patients who have significant mitral regurgitation, but only in those with a broad QRS complex.1 Percutaneous valvular repair using the MitraClip system has been available in Europe since 2008, when it gained a CE Mark.2 Its use has rapidly increased in recent years, and >7500 procedures have now been performed worldwide. In the USA, the MitraClip only recently (March 2013) received a cautious green light from the US Food and Drug Administration Circulatory System Devices advisory panel, although the device is not yet approved in the USA. The discussion within the panel focused primarily on the identification of a high-risk patient population that would receive benefit from the correction of mitral regurgitation with the MitraClip. In the EVEREST II study, the MitraClip was shown to be similarly effective in improving clinical outcome compared with surgery, albeit with a safer procedural profile, in selected patients with severe mitral regurgitation and mild to moderate heart failure.3 Since 2012, the MitraClip has an European Society of Cardiology (ESC) guideline recommendation.4 Ongoing registries such as REALISM and ACCES-EU continue to report data supportive of the MitraClip system as a safe option in selected patients who are not eligible for surgery, be it conventional or even by minimally invasive techniques. In the present issue of the journal, Neuss et al.5 report retrospective results of 157 patients who underwent percutaneous mitral valve repair with one or more MitraClips in a single centre. Follow-up was performed using echocardiography, NT-proBNP, 6 min walk test, and a quality of life questionnaire at 6 and 12 months. Exclusions were generally based on morphological EVEREST II criteria3 and co-morbidities with a poor prognosis. The proportion of LVEF <35% and functional NYHA class IV (31%) in this study shows a more liberal selection than in the EVEREST II, indicative of a more realistic everyday population. Reasons in daily practice for denying surgery in as many as 50% of patients with an indication for mitral valve surgery are reported to be severe impairment of LVEF, multiple co-morbidities, and advanced age.5 Of the patients included, 20% already had a CRT device implanted and despite this had NYHA functional class >III and significant mitral regurgitation. The study by Neuss et al. showed that NT-proBNP was a powerful predictor for the (composite) primary endpoint of all-cause mortality, LV assist device (LVAD) implantation, mitral valve surgery, and unsuccessful implantation (hazard ratio 4.6, 95% confidence interval 2.6–8.2 for NT-proBNP >10 000 pg/mL). Although the natriuretic peptides BNP and NT-proBNP are important prognostic markers, independent of LVEF,6 (NT-pro)BNP-guided therapy has not (yet) been shown to improve outcome.1 In some patients in the high NT-proBNP group, worsening afterload mismatch caused immediate detoriation of LV function. Subgroup analysis from EVEREST I7 has shown that, within EVEREST inclusion criteria, this might be of less concern since MitraClip implantation improved haemodynamics in patients with reduced cardiac index and elevated pulmonary arterial pressure and LV filling pressures.7 In the study by Neuss et al., the use of tricuspid annular plane excursion (TAPSE) was also examined, and this showed that TAPSE as a predictor of adverse outcome in this study could well be a sign of the prognosis of heart failure. A low TAPSE itself is associated with increased mortality in patients admitted with heart failure,8 and, with a pulmonary artery systolic pressure (PASP) of >40 mmHg combined with a TAPSE of <14 mmHg, outpatients had a poorer prognosis, but a normal PASP combined with a TAPSE of <14 mmHg did not have additional risk in terms of survival.9 The study by Neuss et al. suggests that the use of the MitraClip may be a treatment option in patients with severe mitral regurgitation and severe heart failure, in particular since conventional mitral valve surgery is questionable in these patients. The authors suggest in their proposed algorithm that beside optimal pharmacological treatment, CRT should be seriously considered before MitraClip implantation. Van Bommel et al. have studied CRT as an alternative to surgery for mitral regurgitation.10 In 49% (n = 42) of patients there was a reduction of ≥1 grade mitral regurgitation by the ESC four-grade scale. Furthermore, there was a clear correlation between the degree of mitral regurgitation reduction and survival. The group of patients in whom CRT leads to a significant reduction of mitral regurgitation beyond current guideline indication would thus be spared unnecessary surgery. The remaining group with persistent symptomatic mitral regurgitation (after CRT implantation) would then be candidates for MitraClip implantation. Currently there are no prospective data on timing or outcome of the combined device therapy (CRT and MitraClip). The ongoing RESHAPE and COAPT trials comparing best medical treatment with best medical treatment and MitraClip therapy will give us more insights into the additional value of Mitraclip in the treatment of heart failure.11 Until their finalization, retrospective observational studies such as reported by Neuss et al. may help us to identify those vulnerable patients with heart failure and mitral regurgitation that will benefit from MitraClip implantation at a low procedural risk. Conflict of interest: none declared.