Mitral regurgitation (MR) is the most common acquired valvular disease globally, with a rising prevalence with age. For primary/degenerative MR, mitral surgery—whether replacement or repair—remains the first-line choice for surgically eligible patients. However, surgical techniques, especially restrictive annuloplasty in secondary or functional MR, have not achieved the same success. In this context, structural intervention, particularly transcatheter edge-to-edge repair (TEER), has emerged as a valid, less invasive option for severe MR patients using devices such as Abbott® MitraClip® and Edwards® Pascal®. Although initially targeted at primary MR, studies have demonstrated the safety and efficacy of TEER in secondary MR compared to optimal medical therapy, as shown in two large randomized trials.
Despite the progressive increase in TEER usage in daily clinical practice across industrialized countries, the current incidence of its use, indications, and comparative evolution with mitral surgery remains undefined. Addressing this, the article under review today leverages data from the national hospitalized patient database in France to provide a global and comparative view of all patients undergoing percutaneous and surgical interventions. The study included 57,030 patients with severe MR, who consecutively underwent one of the two procedures (52,289 surgery vs. 4,741 TEER) between 2012 and 2022. After propensity score matching, 2,160 patients were analyzed in each group. The average patient age was 76 years, with 58% men and an average EuroSCORE II of 3.9. At a 3-year follow-up (average follow-up of 1 year), TEER was associated with significantly lower incidences of cardiovascular death (HR 0.68; p = .001), pacemaker implantation (HR 0.68; p = .00002), and stroke (HR 0.65; p = .03). Non-cardiovascular mortality (HR 1.56; p = .0002), recurrent pulmonary edema, and cardiac arrest were more frequent in the TEER group. No differences were observed between the two groups in all-cause mortality, endocarditis, major bleeding, atrial fibrillation, or myocardial infarction (MI). A significant interaction was noted between age >75 years and EuroSCORE II ≥ 4% in the reduction of cardiovascular and all-cause mortality following TEER compared to surgery.
The authors conclude that these results suggest that TEER was associated with lower cardiovascular mortality compared to mitral surgery during long-term follow-up.
COMMENTARY:
The percutaneous MitraClip® treatment was approved in Europe for primary MR in 2008 (introduced in France in 2010) and in the U.S. in 2013. Since then, its indications have expanded to include functional MR, mainly following the positive outcomes of the COAPT clinical trial. The five-year COAPT study demonstrated benefits of TEER over medical treatment in patients with an LVEF of 20-50% and an LVEDD < 70 mm, as discussed in previous blog entries. However, these findings were not mirrored in the MITRA-FR trial (LVEF 15-40%), which included patients with more significant ventricular dilation.
Current clinical guidelines assign a class I recommendation for mitral surgery in patients with primary MR. However, there is consensus among experts in both the U.S. and Europe that TEER may be considered in non-surgical candidates due to high surgical risk. Regarding functional MR, American guidelines recommend it as class IIa for patients with favorable anatomy and persistent symptoms despite optimal medical treatment. Meanwhile, in European guidelines, based on the COAPT study results, TEER also holds a class IIa recommendation for patients who do not respond to medical treatment and present excessively high surgical risk.
This analysis, led by Deharo et al., is noteworthy primarily for providing an overview of clinical practice in managing severe MR in France rather than for the comparative outcomes between MitraClip® and surgery, which are anecdotal and somewhat biased, as we’ll discuss further.
From my perspective, the two key takeaways are:
- Over a 10-year period, 8.3% of all MR cases treated in France were managed with percutaneous MitraClip® treatment. This transcatheter approach has continued to grow annually without decreasing the number of mitral surgeries performed, thereby consolidating itself as a genuine alternative in a significant percentage of severe MR cases.
- Comparing patients undergoing surgery with those treated with MitraClip® reveals that the benefits of the latter are more pronounced in older patients with higher baseline surgical risk, confirming previous suspicions.
Everything else, including this last statement, should be approached with great caution, as this study has considerable limitations. The most significant limitation is the lack of distinction between mitral repair and replacement and between primary/degenerative and functional MR. This omission alone makes any attempt to match groups difficult to justify and reduces credibility.
The raw data from this study, reflecting the reality of MR treatment in France, are valuable and undoubtedly represent its most significant contribution. It’s clear that patients treated with MitraClip® were older and had more comorbidities. This patient profile theoretically benefits most from MitraClip, a fact now confirmed by a national database.
After a propensity score analysis with 2,160 patients in each group, in which higher-risk surgical patients were selected, and with an average follow-up of 1 year, it was observed that patients over 75 years and those with EuroSCORE II ≥ 4 (intermediate and high risk) treated with MitraClip showed improvement in all-cause and cardiovascular mortality, which aligns with expectations.
Furthermore, by further scrutinizing the data, an attempt was made to differentiate primary and functional MR by classifying as primary those patients without a history of ischemic/dilated cardiomyopathy, coronary artery disease, MI, or revascularization surgery, which, in my opinion, is a stretch. When analyzing functional MR cases, lower all-cause mortality after TEER compared to surgery was observed.
If we delve deeper into the results from Deharo et al., the first thing that stands out is that unmatched percutaneously treated patients exhibited greater frailty and comorbidities compared to those undergoing surgery. In a direct comparison, cardiovascular mortality was 8.75% with TEER versus 3.6% with surgery (figures that could be compared to STS 2020 data, where mortality was 1.2% in mitral repair and 4.5% in mitral replacement). However, after adjustment, cardiovascular mortality became 7.96% with TEER versus 11.4% with surgery, reflecting a higher baseline risk in the surgical group to match the TEER group, illustrating the complexity of matching both groups. Therefore, after analyzing matched subgroups, one could conclude that as surgical risk increases, the comparative outcomes of TEER improve in terms of mortality.
Regarding the observed benefit in functional MR, American guidelines currently favor TEER over surgery, assigning only a class IIb recommendation to the latter (except in cases of concomitant revascularization, where surgery is class I recommended if LVEF >30% and class IIa if <30%). Within this context, if we consider the study results valid, they would support the current recommendation of TEER over surgery for functional MR patients.
In primary MR, where surgery is considered superior to TEER, we await clinical trials to provide further insights. The REPAIR MR study is comparing MitraClip® TEER with surgical mitral repair in patients with severe MR and moderate risk, while the PRIMARY study makes the same comparison in low-risk patients.
Another significant point is the lack of information on technical success rates for the percutaneous intervention in this study. Limited comparative experiences between mitral valve repair surgery and edge-to-edge therapy in functional MR, based on real-world data, such as Okuno et al.’s work previously discussed in this blog, highlight an incidence of mild or no residual MR post-intervention of 72% for percutaneous therapy, far below the 96-98% success rates reported in COAPT and MITRA-FR studies, respectively. This discrepancy could stem from defining “procedure success” as merely a one-grade reduction in MR. Additionally, several studies have shown that residual MR after surgery has significant long-term prognostic implications. In this study, follow-up only extended to 1 year, and no information on residual MR is available, likely not an insignificant factor.
This study does not challenge the excellent and durable outcomes of mitral surgery in younger patients with lower surgical risk but rather evaluates the real-world practice of severe MR treatment in France over the past 10 years. If we consider the propensity analysis valid, it could be inferred that in patients over 75 years and with high surgical risk with severe MR (likely mostly functional), the use of MitraClip® fulfills its intended purpose, confirming what was already known.
Nevertheless, the results from matched groups do not allow for reliable conclusions, as the surgical group is highly heterogeneous regarding MR type and surgery type, invalidating the conclusions for practical purposes. While initial results suggest the validity and efficacy of MitraClip® in high-risk patients in terms of mortality, it is neither fair nor accurate to conclude, as the authors misleadingly suggest, that MitraClip® use in severe MR compared to surgery is associated with lower long-term cardiovascular mortality. Firstly, it isn’t even mentioned that these results were obtained after a propensity subgroup analysis where dissimilar cases are grouped; secondly, if valid, it applies only to certain high-risk patients; and lastly, calling a one-year follow-up “long-term” is inappropriate.
Striking the right balance between the honesty of results and their presentation, considering the economic interests of companies promoting their products, is challenging. Studies like this offer valuable insights, such as a realistic description of clinical practice in the national management of severe MR. However, attempting to draw other conclusions and presenting them in a skewed way through propensity group analysis where anything fits may be a mistake and, above all, unfair.
REFERENCE:
Deharo P, Obadia JF, Guerin P, Cuisset T, Avierinos JF, Habib G, et al. Mitral transcatheter edge to edge repair versus isolated mitral surgery for severe mitral regurgitation: A French nationwide study. Eur Heart J. 2024 Jan 19:ehae046. doi: 10.1093/eurheartj/ehae046.
