Coaptation length (CL) after surgical mitral valve repair (MVr) has been considered an independent predictor of recurrent mitral regurgitation (MR) in patients with functional MR1Maisano F. Falk V. Borger M.A. et al.Improving mitral valve coaptation with adjustable rings: outcomes from a European multicentre feasibility study with a new-generation adjustable annuloplasty ring system.Eur J Cardiothorac Surg. 2013; 44: 913-918Crossref PubMed Scopus (14) Google Scholar (Figure 1a and b). However, its role in degenerative MR has not been fully explored, and there is a scarcity of studies addressing this issue. We systematically reviewed the medical literature to investigate the effect of post-repair mitral CL on surgical MVr durability in patients with degenerative MR and carried out a pooled analysis of Kaplan-Meier-estimated individual patient data (IPD) from studies with late follow-up (beyond the immediate postoperative period). We followed the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Using the PECOS strategy (Population, Exposure, Comparison, Outcome, and Study design), any studies were included if the following criteria were fulfilled:1)The population comprised adults who had degenerative MR treated with surgical MVr;2)There was a group of patients exposed to a short postoperative CL;3)There was a group of patients who had a long CL;4)The study included recurrent MR as outcome with Kaplan-Meier curves;5)The study design was retrospective/prospective, randomized/non-randomized, mono/multicentric, with matched/unmatched populations. The following sources were searched for articles meeting our inclusion criteria and published by October 31, 2022: PubMed/MEDLINE, EMBASE and Google Scholar, and the reference lists of relevant articles. The Medical Subject Headings (MeSH) related to our research question were used. Studies were selected by 2 independent reviewers. When there was disagreement, a third reviewer made the decision to include or exclude the study. Most authors pool their data using random-effects models to produce incidence rate ratios, odds ratios, or risk ratios as summary measures. Time-to-event outcomes are not easily incorporated into traditional meta-analyses. Researchers have resorted to pooling median survival times, incidence rate ratios or event rates estimated from survival estimates at given timepoints or made direct estimates of the hazard ratios (HRs) across the studies. All these approaches have been shown to be limiting and unsatisfactory, as they do not allow the production of pooled Kaplan-Meier curves and fail to recognize some of the central tenets of survival analysis such as censoring and the proportional hazards assumption. In response to inconsistent reporting that resulted from these diverging approaches, the “curve approach” has emerged as the preferred model for meta-analysis of aggregated time-to-event data. This approach reconstructs IPD based on the published Kaplan-Meier graphs from the included studies. We used the two-stage approach based on the R package “IPDfromKM” (version 0.1.10). In the first stage, raw data coordinates (time, survival probability) were extracted from each treatment arm in each of the Kaplan-Meier curves. In the second stage, the data coordinates were processed based on the raw data coordinates from the first stage in conjunction with the numbers at risk at given timepoints, and IPD were reconstructed. Finally, the reconstructed IPD from all studies were merged to create the study data set. The cumulative incidence of recurrent MR at follow-up in both arms (short and long CL after MVr) was visually assessed using Kaplan-Meier estimates with the R packages “survival” (version 3.2-13) and “survminer” (version 0.4.9). HRs with 95% confidence intervals for the difference between both arms were calculated using a Cox regression model with the R package “coxphw” (version 4.0.2). Hereby, a HR > 1 (with p-value<0.05) would indicate a higher risk of recurrent MR. The proportionality of the hazards of each Cox model was checked with the Grambsch-Therneau test and diagnostic plots based on Schoenfeld residuals. All analyses were completed with R Statistical Software (version 4.1.1, Foundation for Statistical Computing, Vienna, Austria). After excluding duplicates and non-eligible studies, we found only 3 studies2Hage F. Hage A. Malik M.I. Tzemos N. Chu M.W.A. Coaptation length predicts early- and intermediate-term durability following degenerative mitral repair.Eur J Cardiothorac Surg. 2022; 62: ezac194Crossref PubMed Scopus (3) Google Scholar, 3Sasaki H. Mahara K. Terada M. Kishiki K. Takanashi S. Kobayashi Y. Short coaptation length is a predictor of recurrent mitral regurgitation after mitral valve plasty.Heart Lung Circ. 2021; 30: 1414-1421Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar, 4Uchimuro T. Tabata M. Saito K. et al.Post-repair coaptation length and durability of mitral valve repair for posterior mitral valve prolapse.Gen Thorac Cardiovasc Surg. 2014; 62: 221-227Crossref PubMed Scopus (8) Google Scholar with late follow-up which examined the effect of mitral CL on recurrent MR in the context of degenerative MR. All the studies were non-randomized, non-multicentric, and retrospective. All the studies included patients with a mean age of around 60 years and one-third of the overall population was female. The overall mean left ventricle ejection fraction was 65%. While 73.6% of patients had exclusively posterior leaflet prolapse, 9.2% had exclusively anterior leaflet prolapse, and 17.2% had bileaflet prolapse. Ring or band annuloplasty was performed in all cases. Neochords were implanted in 48.6% of cases and posterior leaflet resection was performed in 51.8% of cases. Figure 1c depicts the pooled Kaplan-Meier curves for the cumulative risk of recurrent MR in the presence of short or long CL after surgical MVr. To conduct the analysis for cumulative risk of recurrent MR (Figure 1c), the data of 683 patients (short CL: 118 patients; long CL: 565 patients) from the 3 studies were pooled. Patients with short CL had a significantly higher risk of recurrent MR (HR 13.12, 95% confidence interval 6.68-25.79, p < 0.001). In this Cox model, the proportional hazards assumption was not violated, which means that this effect is likely constant over time. To the best of our knowledge, this is the first and largest meta-analysis of reconstructed time-to-event data with Kaplan-Meier-derived IPD evaluating the impact of short CL on late outcomes of surgical MVr in patients with degenerative MR. We found that those patients with short CL have a higher risk of recurrent MR over time leading to reoperations. Therefore, we could say that CL after MVr as a predictor of recurrent MR goes beyond those patients with functional MR, playing also a role in degenerative MR. A major limitation of our study would be the precise establishment of the cutoffs to define CL as short or long. In our case, we used the cutoffs established in the Kaplan-Meier curves from which we extracted the data. The cutoffs for short CL in the curves used in the original studies which we pooled were <7mm,2Hage F. Hage A. Malik M.I. Tzemos N. Chu M.W.A. Coaptation length predicts early- and intermediate-term durability following degenerative mitral repair.Eur J Cardiothorac Surg. 2022; 62: ezac194Crossref PubMed Scopus (3) Google Scholar <5.6mm,3Sasaki H. Mahara K. Terada M. Kishiki K. Takanashi S. Kobayashi Y. Short coaptation length is a predictor of recurrent mitral regurgitation after mitral valve plasty.Heart Lung Circ. 2021; 30: 1414-1421Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar and <8mm.4Uchimuro T. Tabata M. Saito K. et al.Post-repair coaptation length and durability of mitral valve repair for posterior mitral valve prolapse.Gen Thorac Cardiovasc Surg. 2014; 62: 221-227Crossref PubMed Scopus (8) Google Scholar We might say that 7mm would be the average cutoff in this scenario. However, to stay on the safe side, if surgeons aim for a CL > 10mm in all cases (pending validation in future studies), it is highly unlikely that we would have recurrent MR leading to reoperations, which is clearly visible in the study by Hage et al.2Hage F. Hage A. Malik M.I. Tzemos N. Chu M.W.A. Coaptation length predicts early- and intermediate-term durability following degenerative mitral repair.Eur J Cardiothorac Surg. 2022; 62: ezac194Crossref PubMed Scopus (3) Google Scholar The aforementioned study2Hage F. Hage A. Malik M.I. Tzemos N. Chu M.W.A. Coaptation length predicts early- and intermediate-term durability following degenerative mitral repair.Eur J Cardiothorac Surg. 2022; 62: ezac194Crossref PubMed Scopus (3) Google Scholar revealed that patients with CL in the strata 9-11mm and >11mm had the best (and similar) results compared with the strata 7-9mm and <7mm in terms of recurrent MR after surgical MVr. Although beyond the scope of our study, we should mention that there is evidence showing that mitral CL also predicts optimal MR reduction and better survival in patients undergoing transcatheter edge-to-edge repair5Sato H. Cavalcante J.L. Bae R. et al.Coaptation Reserve predicts optimal reduction in mitral regurgitation and long-term survival with transcatheter edge-to-edge repair.Circ Cardiovasc Interv. 2022; 15: e011562Crossref PubMed Scopus (2) Google Scholar and this may have implications for patient selection and expanded use of the therapy in the future. Such findings support the use of this objective echocardiographic measure (besides assessment of residual MR) to make intraoperative decisions regarding the need of surgical MVr revision before leaving the operation room and also to develop surgical techniques to optimize mitral coaptation in the population with degenerative MR. The research reported has adhered to the relevant ethical guidelines.