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Secondary mitral regurgitation (SMR) occurs as a result of multifactorial left atrioventricular dysfunction and maleficent remodelling. It is the most common and undertreated form of mitral regurgitation (MR) and is associated with a very poor prognosis. Whether SMR is a bystander reflecting the severity of the cardiomyopathy disease process has long been the subject of debate. Studies suggest that SMR is an independent driver of prognosis in patients with an intermediate heart failure (HF) phenotype and not those with advanced HF. There is also no universal agreement regarding the quantitative thresholds defining severe SMR and indeed there are challenges with echocardiographic quantification. Until recently, no surgical or transcatheter intervention for SMR had demonstrated prognostic benefit, in contrast with HF medical therapy and cardiac resynchronisation therapy. In 2018, the first two randomised controlled trials (RCTs) of edge-to-edge transcatheter mitral valve repair versus guideline-directed medical therapy in HF (Percutaneous Repair with the MitraClip Device for Severe (MITRA-FR), Transcather mitral valve repair in patients with heart failure (COAPT)) reported contrasting yet complimentary results. Unlike in MITRA-FR, COAPT demonstrated significant prognostic benefit, largely attributed to the selection of patients with disproportionately severe MR relative to their HF phenotype. Consequently, quantifying the degree of SMR in relation to left ventricular volume may be a useful discriminator in predicting the success of transcatheter intervention. The challenge going forward is the identification and validation of such parameters while in parallel maintaining a heart-team guided holistic approach.

ObjectivesDifferences in terms of safety and efficacy of percutaneous edge-to-edge mitral repair between patients with functional and degenerative mitral regurgitation (MR) are not well established. We performed a systematic review and meta-analysis to clarify these differences.MethodsPubMed, EMBASE, Google scholar database and international meeting abstracts were searched for all studies about MitraClip. Studies with <25 patients or where 1-year results were not delineated between MR aetiology were excluded. This study is registered with PROSPERO.ResultsA total of nine studies investigating the mid-term outcome of percutaneous edge-to-edge repair in patients with functional versus degenerative MR were included in the meta-analysis (n=2615). At 1 year, there were not significant differences among groups in terms of patients with MR grade≤2 (719/1304 vs 295/504; 58% vs 54%; risk ratio (RR) 1.12; 95% CI: 0.86 to 1.47; p=0.40), while there was a significantly lower rate of mitral valve re-intervention in patients with functional MR compared with those with degenerative MR (77/1770 vs 80/818; 4% vs 10%; RR 0.60; 95% CI: 0.38 to 0.97; p=0.04). One-year mortality rate was 16% (408/2498) and similar among groups (RR 1.26; 95% CI: 0.90 to 1.77; p=0.18). Functional MR group showed significantly higher percentage of patients in New York Heart Association class III/IV (234/1480 vs 49/583; 16% vs 8%; p<0.01) and re-hospitalisation for heart failure (137/605 vs 31/220; 23% vs 14%; p=0.03). No differences were found in terms of single leaflet device attachment (25/969 vs 20/464; 3% vs 4%; p=0.81) and device embolisation (no events reported in both groups) at 1 year.ConclusionsThis meta-analysis suggests that percutaneous edge-to-edge repair is likely to be an efficacious and safe option in patients with both functional and degenerative MR. Large, randomised studies are ongoing and awaited to fully assess the clinical impact of the procedure in these two different MR aetiologies.

Functional or secondary mitral regurgitation is linked to increased cardiovascular morbidity and mortality. From a mechanical perspective, secondary mitral regurgitation occurs due to an imbalance between the forces that tether the mitral leaflets and those that close them. This results in incomplete coaptation. Most commonly, functional mitral regurgitation, which occurs in both ischaemic and non-ischaemic disease states, is usually caused by dysfunction and changes in the left ventricle. Atrial functional mitral regurgitation (AFMR) is a disease state that has been more recently recognized. It occurs when mitral annular enlargement is associated with left atrial dilatation, preserving left ventricular geometry and function. AFMR is typically seen in patients with chronic atrial fibrillation or heart failure who have a conserved ejection fraction. Published reports and ongoing investigations vary in how they define AFMR. This publication examines the pathophysiology of AFMR and highlights the importance of having a common working standard for the definition of AFMR to ensure consistency in the data reported and to drive forward the much needed research into the outcomes and treatment strategies in this area. Several studies have reported that restrictive annuloplasty and transcatheter edge-to-edge repair can reduce mitral regurgitation and improve symptoms. This narrative review will explore the pathophysiology, echocardiographic diagnosis and treatment of AFMR.

Purpose The ValveClamp system is a novel edge-to-edge mitral valve repair system designed for the ease of operation. We report the outcomes of our initial experience of treating functional mitral regurgitation (MR) with the ValveClamp system. Methods The subjects of this study were patients with symptomatic functional MR despite standard medical therapy, who were treated with transapical ValveClamp implantation. The patients were divided into an atrial functional mitral regurgitation (AFMR) group and a ventricular functional mitral regurgitation (VFMR) group. Clinical and echocardiographic outcomes were evaluated at baseline and then at the 3-month follow up. Results Twelve patients, with a median age of 71 years (range 65–78 years), were assigned to the AFMR group ( n  = 5) or the VFMR group ( n  = 7). The device implantation rate was 100%, and 10 (83.3%) patients required implantation of only one clamp. The catheter time was less than 10 min in half of the patients, the fastest time being 5 min. There were no procedure-related complications. At the 3-month follow up, all patients were free from all-cause mortality, surgery, and rehospitalization. MR improved to ≤ 2 + in all 12 patients with MR grade 3 + or 4 + at baseline, (100%) and to ≤ 1 + in 9 of these patients (75%), with a low-pressure gradient. The left atrial diameter and the left ventricular end diastolic diameter decreased significantly in both the AFMR and VFMR groups. The left ventricular eject fraction at the 3-month follow up showed a rising trend in both the AFMR and VFMR groups, whereas PASP decreased remarkably. All 12 patients with baseline NYHA functional class III/IV (100%) showed improvement of at least 1 class, and 2 of these patients (16.7%) showed improvement of at least 2 classes. Conclusions The ValveClamp system is simple and effective for transapical transcatheter edge to edge repair in patients with functional MR.

It has been suggested that the disparity of outcomes between the studies of transcutaneous edge-to-edge repair (TEER) for functional mitral regurgitation (FMR) in heart failure with reduced ejection fraction (HFrEF) could be due to systematic differences in the populations studied. One proposal is that there are 2 broad groups: those with proportional FMR who respond less favorably, and those in whom the FMR is greater than expected (disproportionate) FMR where edge-to-edge TEER seems to be more effective. Whether this grouping is relevant for other percutaneous interventions for FMR is unknown. We sought to compare clinical and echocardiographic outcomes of patients with HFrEF and proportionate and disproportionate FMR treated with indirect annuloplasty using the Carillon device. This is a pooled analysis from 3 trials of patients with FMR. Key patient eligibility in these trials specified persistent grade 2+ to 4+ FMR with >5.5 cm left ventricular (LV) end-diastolic diameter (LVEDD) and reduced ejection fraction. Patients with an effective regurgitant orifice area/LV end-diastolic volume (EROA/LVEDV) ratio under 0.15 were assigned to the proportionate FMR group (n = 74;65%) and those with a ratio above 0.15 were classed as having disproportionate FMR (n = 39;35%). At 12 months following treatment, both groups showed improvements in all MR variables including regurgitation volume, EROA and vena contracta. Moreover, in patients with proportionate MR there were clinically relevant and statistically significant improvements in LV volumes and diameters. There was no independent relationship between the degree of proportionality as a continuous variable and the remodeling response to Carillon therapy (change in LVEDV r = 0.17; change in LVESV r = 0.14). Percutaneous mitral annuloplasty with the Carillon device reduces MR in patients with both proportionate and disproportionate FMR, and also results in LV reverse remodeling in those with proportionate FMR. The effect on remodeling remains to be verified in a large-scale trial. [Display omitted]

Recurrent mitral regurgitation (MR) is typically defined as MR that is moderate or severe on follow-up echocardiography after the intervention. This meta-analysis summarizes the results of all available studies on the impact of recurrent MR on clinical outcomes after the intervention. Medline, EMBASE, PubMed and Web of Science were searched from January 2000 to August 2024 for original studies reporting outcomes about the clinical impact of recurrent MR. Five clinical outcomes were analysed: reoperation, cardiovascular deaths, readmission, heart failure and New York Heart Association (NYHA) functional classification. The summary odds ratio (OR) with the 95% confidence interval (CI) was used to assess the risk of clinical outcomes. A total of 22 studies were included in the final analysis, involving 5,804 patients, of which 960 had recurrent MR. The overall pooled incidence of recurrent MR is 16.54%. Secondary or primary patients with MR with recurrent MR after an intervention had higher rates of reoperation [(OR = 6.25, 95% CI, 2.95-14.41; P < 0.001) or (OR = 22.54, 95% CI, 14.96-33.98; P < 0.001)]or of cardiovascular death [(OR = 5.26, 95% CI, 2.35-11.77; P < 0.001) or (OR = 1.68, 95% CI, 1.32-2.14; P < 0.001)]. The rates were also high for readmission (OR = 3.95, 95% CI, 2.56-6.10; P < 0.001), heart failure incidence (OR = 2.87, 95% CI, 1.75-5.11; P < 0.001) and the number of NYHA functional class III/IV (OR = 5.40, 95% CI, 3.01-9.70; P < 0.001) for recurrent MR of secondary MR. However, no significant association was found between recurrent MR of primary MR and the incidence of NYHA functional class III/IV (OR = 1.02, 95% CI, 0.47-2.22; P = 0.96). Recurrent MR is associated with higher rates of reoperations, readmissions, cardiovascular deaths, incidences of heart failure and NYHA functional class III/IV numbers. However, recurrent MR of primary MR is not correlated with NYHA functional class III/IV.

Conventional echocardiographic assessment may overestimate the left ventricular (LV) function in mitral regurgitation (MR). LV global longitudinal strain (GLS) is more sensitive marker to detect subclinical LV dysfunction. Multiple studies have investigated the prognostic value of LV-GLS in MR to examine its potential to determine the timing and indication of intervention. This systematic review aimed to assess the prognostic value of LV-GLS in patients with mitral regurgitation (MR) to define its clinical applicability. PUBMED and EMBASE were queried through July 2021 to identify studies investigating the prognostic value of LV-GLS in MR. A total of 24 observational studies with 5267 patients were identified. Sixteen studies investigated for primary MR, 7 studies for secondary MR, and 1 study for both. Most studies included patients who underwent intervention. There was significant heterogeneity in patient population, intervention status, follow-up period, LV-GLS cutoff value, outcomes, and statistical methods among the studies. Meta-analysis was not performed considering the significant variability. With exception to 1 study, all studies demonstrated significant association between impaired LV-GLS and worse clinical and echocardiographic outcomes in primary MR. Prognostic value of LV-GLS in secondary MR was less certain due to inconsistent findings and limited reporting. LV-GLS is a promising parameter of prognostication in primary MR and can be considered as alternative to determine the timing of intervention. However, the optimal cutoff value remains unclear. The prognostic value of LV-GLS in secondary MR is less clear. Further large-scale prospective study is warranted before its routine clinical application.

IntroductionTranscatheter edge-to-edge mitral valve repair using the MitraClip has been widely performed in surgical high-risk patients with reduced left ventricular systolic function and severe functional mitral regurgitation (FMR). Ischaemic heart disease is the leading aetiology of heart disease worldwide. We aimed to assess the clinical implications of ischaemic aetiology in patients with severe FMR who underwent MitraClip implantation.Methods and resultsFrom two high-volume centres in Germany, we retrospectively compared the clinical outcomes and clinical predictors of all-cause mortality after MitraClip implantation in patients with ischaemic (I-FMR) and non-ischaemic FMR (NI-FMR). In the overall FMR cohort (n = 575), there were 336 (58%) patients with I-FMR and 239 (42%) with NI-FMR. There was no significant difference in survival between the two groups (log-rank p = 0.78). In a multivariable Cox regression analysis of all-cause mortality, different predictors were observed for either group. In I-FMR patients, decreasing tricuspid annular systolic excursion [adjusted hazard ratio (HRadj) 1.06, 95% confidence interval (95% CI) 1.01–1.14 /1 mm, p = 0.028] and increasing logistic EuroSCORE (HRadj 1.02, 95% CI 1.00–1.03, p = 0.037) were independent predictors, whereas in NI-FMR patients, NT-pro BNP (HRadj 1.05, 95% CI 1.02–1.08, p = 0.001) and age (HRadj 1.06, 95% CI 1.01–1.11, p = 0.013) were independently predictive of mortality.ConclusionsDespite the similar survival between ischaemic and non-ischaemic FMR, different predictors of all-cause mortality were demonstrated. Further clinical studies are mandated to focus on each FMR subgroup with stratification by ischaemic origin.

Objectives: The treatment of secondary mitral regurgitation (MR) is still controversial. In 2019, a new conceptual framework was introduced, distinguishing between patients with a degree of MR “proportionate” to the left ventricular (LV) dilatation and patients in whom the severity of MR is “disproportionate” to the LV dilatation. The aim of this study was to compare the long-term outcome of patients with disproportionate vs. proportionate secondary MR who underwent mitral valve (MV) surgery. Methods: From January 2012 to June 2022, 96 patients with a preoperative diagnosis of pure secondary MR and LV dysfunction underwent MV surgery. The patients were divided in two groups, disproportionate vs. proportionate MR, according to echocardiographic parameters. A 5.2 (3.5–7.5) years complete clinical and echocardiographic follow-up was performed. Results: In the study period, 61 patients with disproportionate and 35 patients with proportionate MR underwent surgical MV repair or MV replacement. The thirty-day outcome was comparable in the two groups. At long-term follow-up, mortality was 5% in the disproportionate group vs. 11% in the proportionate group (p = 0.2), and cardiovascular mortality was 3% vs. 9%, respectively (0.5). Rehospitalization for heart failure was 6% vs. 20% (p = 0.04), and the rate of patients with New York Heart Association (NYHA) functional class ≥ III was 8% vs. 26%, respectively (p = 0.01). LV volumes were significantly higher in the proportionate group, thus presenting a lower LV ejection fraction (p < 0.001 and p = 0.03, respectively). No cases of recurrent MR have been observed. Conclusions: In this first exploratory analysis, patients with disproportionate secondary MR seem to present a possible benefit in terms of mortality and cardiovascular mortality, although not ones reaching statistical significance. Nevertheless, significant advantages were observed in terms of rehospitalization for heart failure, clinical status and symptoms, LV volumes, and LV function. Among patients referred to cardiac surgery, identifying the subset of patients with functional MR, who may obtain more significant advantages from surgery, seems relevant for patient selection, risk stratification, and to predict long-term outcomes.

Aims Functional mitral regurgitation (MR) (FMR) is common in heart failure with reduced ejection fraction and worsens morbidity and mortality, even when mild. The CARILLON® mitral contour system (Cardiac Dimensions, Kirkland, WA, USA), a mitral annuloplasty device delivered percutaneously to the coronary sinus, is designed to reduce the mitral annular dimension by virtue of the close anatomic relationship between the coronary sinus and the posterior mitral annulus. We performed a comprehensive individual patient data meta‐analysis of all studies that used CARILLON® device vs. control that have measured mitral regurgitation severity, left ventricular (LV) remodelling, functional status, and heart failure‐related outcomes in heart failure with reduced ejection fraction patients. Methods and results The Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE were searched in July 2020. Primary outcomes of interest were measures of MR severity, LV remodelling, New York Heart Association functional class and heart failure‐related outcomes [mortality and heart failure hospitalization (HFH) during follow up]. All data were received as individual patient and individual time point data‐points. Mean differences and 95% confidence intervals (CIs) were calculated for continuous data using a fixed‐effects model. Three studies (REDUCE FMR, TITAN and TITAN II) enrolling 209 participants were identified and included. Pooled analysis showed that, compared with control, CARILLON® device significantly improved both MR volume (mean difference MD ‐9.20, 95% C.I. −16.11 to −2.29 mL, P = 0.009) and MR grade (MD ‐1.12, 95% CI −1.36 to −0.88, P < 0.00001) and this was associated with a significant reduction in LA volume, MD −7.54 mL, 95% CI −14.90 to − 0.18, P = 0.04. Significant LV reverse remodelling was also seen in terms of EDV (MD −16.53, 95% CI −28.61 to −44.4 mL, P = 0.007), and a trend in ESV (MD −8.68, 95% CI −18.69 to −1.34 mL, P = 0.09) but no significant effect on LVEF (MD 0.88, 95% CI −1.52% to 2.38%, P = 0.47), due presumably to the greater residual MR in the control patients falsely elevating the LVEF. In addition, the CARILLON® device significantly improved New York Heart Association functional Class (MD −0.22, 95% CI −0.24 to −0.16, P < 0.00001), associated with a lower rate of HFH compared with controls (45.3% vs. 64%, respectively, P = 0.04). As a sensitivity analysis we also restricted the analyses to those patients with Class 3+/4+ MR at baseline. In this cohort, the echocardiographic results were similar, and the reduction in HFH rates was even more marked (43.9% vs. 82.9%, respectively, P = 0.04). Conclusions This comprehensive meta‐analysis of individual patient data has shown that CARILLON® device provides statistically significant and clinically meaningful benefits on MR severity, LA and LV volumes, and remodelling and rates of subsequent heart failure hospitalization