Author + information
- aDepartment of Cardiology, DHU FIRE, Assistance Publique – Hôpitaux de Paris, Bichat Hospital, Paris, France
- bDepartment of Cardiology, INSERM U1148, Bichat Hospital, Paris, France
- cDepartment of Cardiology, University Paris VII, Paris, France
- dDepartment of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada
- ↵∗Address for correspondence:
Prof. Bernard Iung, Department of Cardiology, Bichat Hospital, 46 rue Henri Huchard, 75018 Paris, France.
The paper by Arnold et al. (1) in this issue of the Journal reports the first evaluation of health status derived from a randomized controlled trial evaluating transcatheter mitral valve edge-to-edge repair (TMVr) in patients with secondary mitral regurgitation (MR). This study is derived from the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial (2), which showed improved survival and a reduced number of hospitalizations for heart failure after TMVr at 24 months compared with maximally tolerated medical therapy alone. In line with these results, the investigators observed that TMVr led to a significant benefit in health status using the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the Medical Outcomes Study Short-Form 36 Health Survey (SF-36) that was early and sustained. Importantly, the difference between the 2 arms was large and clinically significant.
The assessment of health status and patient-centered outcomes is particularly relevant in disease such as secondary MR. The presence of secondary MR worsens the already dismal prognosis of patients presenting with heart failure and reduced ejection fraction (3). In addition to clinical events, the possibility to improve functional status and quality of life is of utmost importance in severely disabled patients. The methods used in the paper by Arnold et al. (1) are adapted to patients with secondary MR because the KCCQ was specifically designed for heart failure and consists of 5 components (physical limitation, symptoms, quality of life, social limitation, and self-efficacy). The SF-36 explores with more detail other components of quality of life and psychological status. Competing risk of death, which is high in secondary MR, was appropriately taken into account. Finally, the investigators should be congratulated for the quality of data, as attested by a data completeness rate ≥88% for KCCQ overall summary score (KCCQ-OR) at each time point, which is difficult to obtain for health status questionnaires comprising a number of constituting items.
A relevant finding of the analysis performed by Arnold et al. (1) is the categorization of the improvement of health status. The percentage of patients alive and substantially improved was 58% at 6 months and 39% at 2 years versus 37% and 21%, respectively, in the standard care arm. Despite a significant improvement in health status in the whole population, 10% of patients died, and 26% did not experience any health status improvement or worsened at 6 months in the TMVr arm. Even if these percentages were lower than in the standard care arm (11% and 41%, respectively), it appears that one-third of the patients did not derive a clinical benefit 6 months after TMVr. The same findings have been observed after transcatheter aortic valve replacement in high-risk patients, with a contrast between the benefit observed in randomized trials comparing device therapy with medical therapy alone and the lack of clinical improvement in at least one-third of patients at 6 months (4,5). However, the identification of futile procedures remains difficult in current practice (6). In the present analysis, the improvement in health status after TMVr, as compared with standard care, was consistent across all pre-specified subgroups and it is therefore not possible to identify easily the patient characteristics associated with a high risk of performance of a futile procedure.
Health status, as assessed by KCCQ-OR and SF-36, improved as soon as during the first month after TMVr, which argues in favor of an effect of the correction of MR. There was a subsequent mild decline in the values of KCCQ-OR and SF-36, which remained significantly higher than in the standard care arm. There was also an improvement of health status in the standard care arm, although of small extent, and this is a further illustration of the need for randomized controlled trials for assessing the therapeutic efficacy of the treatment of secondary MR where confounding factors are particularly numerous.
The findings by Arnold et al. (1) represent an important contribution in the knowledge of the treatment of secondary MR. However, considerable challenges remain with regard to clinical practice. The first step is to identify which patients with secondary MR are good candidates for TMVr. In contrast to the COAPT trial, the MITRA-FR (Percutaneous Repair with the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation) trial did not show any benefit on survival free of heart failure hospitalization (7). These contradictory findings have already generated a number of comments. The most frequent hypothesis raised to account for these discrepancies is patient selection, because patients in the COAPT trial presented with more severe degrees of MR and less severe left ventricular remodeling. In this regard, the paper by Grayburn et al. (8) is very insightful. However, it is not possible to derive individual selection criteria from the results of each study at the present time. The second step is to identify the patients who are not likely to derive a benefit from TMVr on health status. The homogeneity of the results of subgroup analyses performed in the paper by Arnold et al. (1) does not provide selection criteria in this field, and further analyses are needed to search for factors which would predict futile TMVr procedures in patients with secondary MR.
↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Prof. Iung has been a consultant for Edwards Lifesciences; and has received speaker fees from Boehringer Ingelheim and Novartis. Dr. Messika-Zeitoun has received consultant fees and grant support from Edwards Lifesciences.
- 2019 American College of Cardiology Foundation
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