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Right ventricular dysfunction (RVD), as expressed by right ventricular to pulmonary artery coupling, has recently been identified as a strong outcome predictor in patients undergoing mitral valve edge-to-edge repair (M-TEER) for secondary mitral regurgitation (MR). The aim of this study was to define RVD in patients undergoing M-TEER for primary MR (PMR) and to evaluate its impact on procedural MR reduction, symptomatic development and 2-year all-cause mortality.This multicentre study included patients undergoing M-TEER for symptomatic PMR at nine international centres. The study cohort was divided into a derivation (DC) and validation cohort (VC) for calculation and validation of the best discriminatory value for RVD. A total of 648 PMR patients were included in the study. DC and VC were comparable regarding procedural success and outcomes at follow-up. Sensitivity analysis identified RVD as an independent predictor for 2-year mortality in the DC (hazard ratio [HR] 2.37, 95% confidence interval [CI] 1.47-3.81, p 0.001), which was confirmed in the VC (HR 2.06, 95% CI 1.36-3.13, p 0.001). Procedural success (MR ≤2+) and symptomatic improvement at follow-up (New York Heart Association [NYHA] class ≤II) were lower in PMR patients with RVD (MR ≤2+: 82% vs. 93%, p = 0.002; NYHA class ≤II: 57.3% vs. 66.5%, p = 0.09 for with vs. without RVD). In all PMR patients, the presence of RVD significantly impaired 2-year survival after M-TEER (HR 2.23, 95% CI 1.63-3.05, p 0.001).Mitral valve edge-to-edge repair is an effective treatment option for PMR patients. The presence of RVD is associated with less MR reduction, less symptomatic improvement and increased 2-year mortality. Accordingly, RVD might be included into pre-procedural prognostic considerations.

The aim of this study was to evaluate the prevalence and prognostic implications of cardiohepatic syndrome (CHS) in patients with tricuspid regurgitation (TR) treated with tricuspid transcatheter edge-to-edge valve repair (T-TEER).The role of CHS in patients undergoing T-TEER for severe TR has not been studied.This study included patients who underwent T-TEER for TR between 2016 and 2020 at 2 high-volume academic centers. CHS was defined as elevation of at least 2 of 3 cholestatic hepatic enzymes. The impact of CHS on 1-year all-cause mortality and clinical outcomes after T-TEER was investigated.T-TEER reduced TR severity to ≤2+ in 257 of 305 included patients (86.2%). CHS was present in 45.2% of patients and was associated with a higher rate of mortality and of first hospitalization for heart failure (HHF) (CHS vs no CHS: estimated 1-year mortality, 34.0% vs 15.9% [P 0.01]; HHF, 23.0% vs 12.2% [P = 0.01]). CHS was identified as an independent predictor of 1-year all-cause mortality (HR: 1.86; 95% CI: 1.10-3.14; P 0.05). Irrespective of CHS, T-TEER improved New York Heart Association functional class and 6-minute walk distance in the majority of patients. In patients with impaired baseline hepatic function, laboratory liver parameters improved after T-TEER.CHS is a strong predictor of mortality and HHF after T-TEER and should be evaluated in the process of procedural decision making for T-TEER. Nevertheless, T-TEER is associated with relevant symptomatic alleviation irrespective of CHS.

Background The impact of postero-anterior and medio-lateral mitral valve (MV) tethering patterns on outcomes in patients undergoing transcatheter edge-to-edge repair (M-TEER) for secondary mitral regurgitation (SMR) is unknown. Methods The ratio of the posterior to anterior MV leaflet angle (PLA/ALA) in MV segment 2 was defined as postero-anterior tethering asymmetry. Medio-lateral tethering asymmetry was assessed as the ratio of the medial (segment 3) to lateral (segment 1) MV tenting area. We used receiver-operating characteristics and a Cox regression model to identify cut-off values of asymmetric anteroposterior and medio-lateral tethering for prediction of 2 year all-cause mortality after TMVR. Results Among 178 SMR patients, postero-anterior tethering was asymmetric in 67 patients (37.9%, PLA/ALA ratio > 1.54). Asymmetric medio-lateral tethering (tenting area ratio > 1.49) was observed in 49 patients (27.5%). M-TEER reduced MR to ≤ 2 + in 92.1% of patients; MR reduction was less effective in the presence of asymmetric postero-anterior tethering (p = 0.02). A multivariable Cox regression model identified both types of asymmetric MV tethering to be associated with increased all-cause 2-year mortality (postero-anterior tethering asymmetry: HR = 2.77, CI 1.43–5.38; medio-lateral tethering asymmetry: HR = 2.90, CI 1.54–5.45; p Conclusions Asymmetric postero-anterior and medio-lateral MV tethering patterns are associated with increased 2-year mortality in patients undergoing M-TEER for SMR. A detailed echocardiographic analysis of MV anatomy may help to identify patients who profit most from M-TEER. Graphical abstract

Background: Atrial functional tricuspid regurgitation (atrial TR) has received growing recognition as a TR entity with a distinct cause owing to its independence from valvular tethering as the predominant mechanism underlying TR. However, characterization of atrial TR varies, and a universal definition is lacking. Methods: In total, 651 patients with significant functional TR were analyzed, including 438 conservatively treated individuals and 213 patients who received transcatheter tricuspid valve repair (TTVR). Based on a clustering approach, we defined atrial TR as tricuspid valve (TV) tenting height ≤10 mm, midventricular right ventricular diameter ≤38 mm, and left ventricular ejection fraction ≥50%. Results: Patients with atrial TR were more often females, had higher right ventricular fractional area change, higher left ventricular ejection fraction, and lower LV end-diastolic diameter, TV tenting area and height, lower right ventricular and tricuspid annular size, enlarged, but lower right atrial area and lower TV effective regurgitant orifice area (all P P P P P Conclusions: An echocardiography-based atrial TR definition is associated with prognostic relevance in patients with functional TR in conservatively treated TR and after TTVR.

Aims To investigate whether there is evidence for distinct cardiac output (CO) based phenotypes in patients with chronic right heart failure associated with severe tricuspid regurgitation (TR) and to characterize their impact on TR treatment and outcome. Methods and results A total of 132 patients underwent isolated transcatheter tricuspid valve repair (TTVR) for functional TR at two centres. Patients were clustered according to k-means clustering into low [cardiac index (CI) 2.6 L/min/m2) clusters. All-cause mortality and clinical characteristics during follow-up were compared among different CO clusters. Mortality rates were highest for patients in a low (24%) and high CO state (42%, log-rank P

OBJECTIVES This study sought to assess the impact of right ventricular dysfunction (RVD) as defined by impaired right ventricular-to-pulmonary artery (RV-PA) coupling, on survival after edge-to-edge transcatheter mitral valve repair (TMVR) for severe secondary mitral regurgitation (SMR). BACKGROUND Conflicting data exist regarding the benefit of TMVR in severe SMR. A possible explanation could be differences in RVD. METHODS Using data from the EuroSMR (European Registry on Outcomes in Secondary Mitral Regurgitation) registry, this study compared the characteristics and outcomes of SMR patients undergoing TMVR, according to their RV-PA coupling, assessed by tricuspid annular plane systolic excursion-to-systolic pulmonary artery pressure (TAPSE/sPAP) ratio. RESULTS Overall, 817 patients with severe SMR and available RV-PA coupling assessment underwent TMVR in the participating centers. RVD was present in 211 patients (25.8% with a TAPSE/sPAP ratio��

The purpose of this paper was to evaluate the impact of proportionality of secondary mitral regurgitation (SMR) in a large real-world registry of transcatheter edge-to-edge mitral valve repair (TMVr) BACKGROUND: Differences in the outcomes of recent randomized trials of TMVr for SMR may be explained by the proportionality of SMR severity to left ventricular (LV) volume.The ratio of pre-procedural effective regurgitant orifice area (EROA) to LV end-diastolic volume (LVEDV) was retrospectively assessed in patients undergoing TMVr for severe SMR between 2008 and 2019 from the EuroSMR registry. A recently proposed SMR proportionality scheme was adapted to stratify patients according to EROA/LVEDV ratio in 3 groups: MR-dominant (MD), MR-LV-co-dominant (MLCD), and LV-dominant (LD). All-cause mortality was assessed as a primary outcome, secondary heart failure (HF) outcomes included hospitalization for HF (HHF), New York Heart Association (NYHA) functional class, N-terminal pro-B-type natriuretic peptide (NT-proBNP), 6-min-walk distance, quality of life and MR grade.A total of 1,016 patients with an EROA/LVEDV ratio were followed for 22 months after TMVr. MR was reduced to grade ≤2+ in 92%, 96%, and 94% of patients (for MD, MLCD, and LD, respectively; p = 0.18). After adjustment for covariates including age, sex, diabetes, kidney function, body surface area, LV ejection fraction, and procedural MR reduction (grade ≤2+), adjusted rates of 2-year mortality in MD patients did not differ from those for MLCD patients (17% vs. 18%, respectively), whereas it was higher in LD patients (23%; p = 0.02 for comparison vs. MD+MLCD). The adjusted first HHF rate differed between groups (44% in MD, 56% in MLCD, 29% in LD; p = 0.01) as did the adjusted time for first death or HHF rate (66% in MD, 82% in MLCD, 68% in LD; p = 0.02). Improvement of NYHA functional class was seen in all groups (p 0.001). Values for 6-min-walk distances, quality of life and NT-proBNP improved in most patients.MD and MLCD patients had a comparable, adjusted 2-year mortality rate after TMVr which was slightly better than that of LD patients. Patients treated with TMVr had symptomatic improvement regardless of EROA/LVEDV ratio.

To investigate the role of left atrial volume index (LAVi) in patients with secondary mitral regurgitation (SMR) undergoing transcatheter edge-to-edge mitral valve repair (TEER).Outcomes were evaluated in SMR patients of a European multicentre registry according to baseline LAVi. Main analysis was performed for all-cause mortality; residual mitral regurgitation (MR) and New York Heart Association (NYHA) class improvement were analysed for patients available. A total of 1074 patients were included with a median LAVi (interquartile range) of 58 ml/mProcedural success and symptomatic benefit were high throughout the whole range of LAVi. The prognostic impact of left atrial enlargement was relevant in patients with less severe SMR and without pulmonary hypertension, reinforcing the need to identify patients in the early course of backward congestion to achieve good long-term outcome after TEER.

BACKGROUND Body surface area (BSA) has been reported to be the stronger predictor for prognosis than body mass index in heart failure (HF) patients. The sex-specific association of BSA with mortality has been unclear. METHODS EuroSMR, a European multicenter registry, included patients who underwent edge-to-edge repair (TEER) for secondary mitral regurgitation (SMR). The outcome was two-year all-cause mortality. RESULTS The present cohort included 1594 HF patients (age, 74 ± 10 years; male, 66%). Association of calculated BSA with two-year all-cause mortality was evaluated. Patients were classified into three BSA groups: the lowest 10% (S), the highest 10% (L), and intermediate between S and L (M). Mean BSA was 1.87 ± 0.21 m2 (male, 1.94 ± 0.18 m2; female, 1.73 ± 0.18 m2). The association of BSA with the endpoint in females showed a U-shaped curve, indicating worse prognosis for both S and L. The association in males followed a linear regression, demonstrating better prognosis for L. Hazard ratio (HR) of L to S in males was 0.43 (95% confidence interval [CI], 0.25-0.74; p = 0.002), whereas HR of L to M in females was 1.76 (95% CI, 1.11-2.78; p = 0.016) (p for interaction = 0.003). CONCLUSIONS Sex-specific association patterns demonstrate the complex influence of anthropomorphic factors in HF patients scheduled for TEER. Further investigation beyond simple evaluation of weight and height is needed for better comprehension of the obesity paradox and better prediction of the results of transcatheter therapy in HF patients.

Among patients with severe functional mitral regurgitation (FMR), atrial functional mitral regurgitation (aFMR) represents an underrecognized entity. Data regarding outcomes after mitral valve transcatheter edge-to-edge repair (M-TEER) in aFMR remain scarce.The objective of this study was to analyze the outcome of aFMR patients undergoing M-TEER.Using patients from the international EuroSMR (European Registry of Transcatheter Repair for Secondary Mitral Regurgitation) registry undergoing M-TEER for FMR, the authors analyzed baseline characteristics and 2-year outcomes in aFMR in comparison to non-aFMR and ventricular FMR. Additionally, the impact of right ventricular dysfunction (RVD) (defined as right ventricular to pulmonary artery uncoupling) on outcome after M-TEER was assessed.Among 1,608 FMR patients treated by M-TEER, 126 (7.8%) were categorized as aFMR. All 126 aFMR patients had preserved left ventricular function without regional wall motion abnormalities, left arterial dilatation and Carpentier leaflet motion type I. Procedural success (defined as mitral regurgitation ≤2+ at discharge) was 87.2% (P 0.001) and New York Heart Association (NYHA) functional class significantly improved during follow-up (NYHA functional class III/IV: 86.5% at baseline to 36.6% at follow-up; P 0.001). The estimated 2-year survival rate in aFMR patients was 70.4%. Two-year survival did not differ significantly between aFMR, non-aFMR, and ventricular FMR. Besides NYHA functional class IV, RVD was identified as a strong independent predictor for 2-year survival (HR: 2.82 [95% CI: 1.24-6.45]; P = 0.014).aFMR is a frequent cause of FMR and can be effectively treated with M-TEER to improve symptoms at follow-up. Advanced heart failure symptoms and RVD were identified as important risk factors for survival in aFMR patients.

BACKGROUND Transcatheter treatment techniques for tricuspid regurgitation (TR) have evolved in recent years, with leaflet repair being the most commonly used, but thus far evidence on the PASCAL and PASCAL Ace system is based mainly on compassionate use data. OBJECTIVES This is the first report on commercial use in a multicenter study with a large patient cohort investigating the safety and efficacy of the PASCAL and PASCAL Ace system in the treatment of TR. METHODS In a retrospective, multicenter, observational setting, data from all consecutive patients undergoing leaflet repair for TR at 8 centers was collected, including a centralized analysis of echocardiographic data. RESULTS A total of 235 high-risk patients (mean age 78 ± 8 years, 49% women, mean Society of Thoracic Surgeons Predicted Risk of Mortality score 8.6% ± 6.8%) were included. TR was functional in 87% of patients and graded severe or higher in 91%. TR was successfully reduced to moderate or less in 78% of patients (P < 0.001). Procedural success was 78% (n = 153). At the latest available follow-up (median 173 days), TR reduction was sustained (78% with TR moderate or less; P < 0.001), and echocardiography showed indications of right ventricular remodeling (mean right ventricular end-diastolic diameter 56 ± 9 mm vs 53 ± 9 mm; P < 0.001). Patients' symptoms diminished significantly (63% were in New York Heart Association functional class I or II at follow-up; P < 0.001). In a device-specific analysis, the PASCAL and PASCAL Ace showed no difference in TR reduction (postprocedural TR moderate or less in 77% vs 78%; P = 0.82). CONCLUSIONS In early clinical experience, the PASCAL (Ace) leaflet repair system has high technical and procedural success rates with efficient TR reduction and significant clinical and echocardiographic improvement at follow-up.

OBJECTIVES The aim of this study was to assess the impact of residual mitral regurgitation (resMR) on mortality with respect to left ventricular dilatation (LV-Dil) or right ventricular dysfunction (RV-Dys) in patients with secondary mitral regurgitation (SMR) who underwent mitral valve transcatheter edge-to-edge repair (TEER). BACKGROUND The presence of LV-Dil and RV-Dys correlates with advanced stages of heart failure in SMR patients, which may impact the outcome after TEER. METHODS SMR patients in a European multicenter registry were evaluated. Investigated outcomes were 2-year all-cause mortality and improvement in New York Heart Association functional class with respect to MR reduction, LV-Dil (defined as LV end-diastolic volume�����159��ml), and RV-Dys (defined as tricuspid annular plane systolic excursion-to-systolic pulmonary artery pressure ratio of��

OBJECTIVES The authors sought to assess sex-based differences in characteristics and outcomes of patients undergoing transcatheter edge-to-edge mitral valve repair (TMVR) for secondary mitral regurgitation (SMR). BACKGROUND Subgroup analysis from the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart��Failure Patients with Functional Mitral Regurgitation) trial indicated potential sex-related differences in outcomes after TMVR. The impact of sex on results after TMVR in a real-world setting is unknown. METHODS The authors assessed clinical outcomes and echocardiographic parameters in women and men undergoing TMVR for SMR between 2008 and 2018 who were included in the large, international, multicenter real-world EuroSMR registry (European Registry of Transcatheter Repair for Secondary Mitral Regurgitation). RESULTS A total of 1,233 patients, including 445 women (36%) and 788 men (64%), were analyzed. Although women were significantly older and had fewer comorbidities than men, TMVR was equally effective in women and men (mitral regurgitation [MR] grade�����2+ at discharge: 93.2% vs. 94.6% for women vs. men; p��=��0.35). All-cause mortality at 1 year (17.9% vs. 18.9%, adjusted hazard ratio: 0.806; p��=��0.46) and at 2-year follow-up (26.5% vs. 26.4%, adjusted hazard ratio: 0.757; p��=��0.26) were similar in women versus men after multivariate regression analysis. Durability of MR reduction, improvement in symptoms, quality of life, and functional capacity did also not differ during follow-up. CONCLUSIONS Results from the EuroSMR registry confirmed effective and similar MR reduction with TMVR in women and men. There were no sex-related differences in clinical outcomes up to 2 years of follow-up.

The goal of this study was to evaluate the effect of transcatheter edge-to-edge tricuspid valve repair (TTVR) for severe tricuspid regurgitation (TR) on hospitalization for heart failure (HHF) and HF-related endpoints.Patients with severe TR need effective therapies beyond conservative treatment. The impact of TTVR on HHF and HF-related endpoints is unknown.Isolated TTVR was performed in 119 patients. Assessments were conducted of New York Heart Association functional class, 6-min walk distance, Minnesota Living with Heart Failure Questionnaire scores, N-terminal pro-B-type natriuretic peptide level, and medication. HHFs were analyzed in the preceding 12 months before and until the longest available follow-up after TTVR. Results were compared with those of 114 patients who underwent combined mitral and tricuspid valve repair.Procedural success with a reduction to moderate or less TR and no in-hospital death was achieved in 82% of patients. With a median follow-up of 360 days (interquartile range: 187 to 408 days), a durable TR reduction to moderate or less was achieved in 72% of patients (p 0.001). TTVR reduced the annual rate of HHF by 22% (1.21 to 0.95 HHF/patient-year; p = 0.02), with concomitant clinical improvement in New York Heart Association functional class (patients in class II or lower: 9% to 67%; p 0.001), 6-min walk distance (+39 m; p = 0.001), and Minnesota Living with Heart Failure Questionnaire score (-6 points; p = 0.02). N-terminal pro-B-type natriuretic peptide level decreased numerically by 783 pg/ml. Diuretic dose before TTVR was increased, but HF medication did not change after TTVR. Procedural success was associated with improved 1-year survival (79% vs. 60%; p = 0.04) and event-free-survival (death + first HHF: 67% vs. 40%; p = 0.001). Transcatheter mitral and tricuspid valve repair-treated patients had comparable outcomes.TTVR for severe TR is associated with a reduction of HHF and improved clinical outcomes.

Transcatheter edge-to-edge tricuspid valve repair (TTVR) is a new treatment option for patients with moderate-to-severe tricuspid regurgitation (TR) and right-sided heart failure who have a prohibitive surgical risk. Efficacy and clinical outcome are promising, but quantitative TR reduction and the