INTRODUCTION:The impact of coexisting left-sided valvular heart disease (VHD) on clinical outcomes following tricuspid valve edge-to-edge repair (T-TEER) for tricuspid regurgitation (TR) remains unclear, particularly under real-world conditions. To evaluate the prevalence and prognostic impact of concomitant left-sided VHD in patients undergoing T-TEER. METHODS:This study included all patients undergoing T-TEER from the European Registry of Transcatheter Repair for Tricuspid Regurgitation (EuroTR; NCT06307262) with complete echocardiographic data on left-sided valve disease. Study endpoints included survival and heart failure hospitalizations (HFH) at 2 years, NYHA functional class, and TR reduction. RESULTS:Among a total of 1647 eligible patients, 95.8%, 35.6%, and 3.8% had ≥mild, moderate, and severe concomitant VHD, respectively. Moderate or higher VHD was associated with a significantly reduced 2-year survival (P < .001) and reduced 2-year HFH-free survival (P = .005). Multivariate regression analysis confirmed ≥ moderate VHD to be an independent predictor of mortality (hazard ratio 1.54, 95% CI 1.21-1.96, P < .001). Despite worse TR and NYHA functional class at baseline in patients with ≥moderate VHD, T-TEER was associated with a significant TR reduction (P < .001) and symptomatic improvement (P < .001). CONCLUSION:Concomitant left-sided VHD is common among patients undergoing T-TEER and is independently associated with worse survival and higher rates of HFH. Nevertheless, T-TEER provides meaningful symptomatic benefit and durable TR reduction in patients with and without VHD burden.

BACKGROUND:Transcatheter aortic valve implantation (TAVI) is increasingly performed in younger and lower-risk patients. Since many of these patients will outlive their transcatheter heart valve (THV), redo-TAVI procedures are expected to rise in number. Yet, real-world evidence on the procedural safety and efficacy of redo-TAVI remains limited. AIMS:We aimed to evaluate the 30-day procedural and clinical outcomes of redo-TAVI using the balloon-expandable SAPIEN 3 platform. METHODS:The ReTAVI registry is a prospective, international study enrolling consecutive patients with a failed aortic THV undergoing redo-TAVI with a balloon-expandable SAPIEN 3 THV. Data were collected across 59 international centres. All imaging was centrally analysed, and major clinical events were adjudicated by an independent committee. RESULTS:â¨A total of 143 patients (median age 84 years; 40.6% female; median Society of Thoracic Surgeons risk score 7.0%) were enrolled. The predominant failing THVs were balloon-expandable SAPIEN 3 (30.1%), self-expanding CoreValve/Evolut (53.1%), and ACURATE (14.0%) platforms. The most common failure mode was isolated regurgitation (48.6%), followed by stenosis (35.2%) and a mixed pathology (16.2%). The replacement valve was successfully implanted in 95.1% of patients, with a 30-day mortality rate of 3.5%. The 30-day stroke and pacemaker implantation rates were 0.7% and 6.3%, respectively. Redo-TAVI significantly improved valve haemodynamics, with mean gradients decreasing overall (Δ=-12.0 mmHg), and a more pronounced reduction in stenotic failures (Δ=-29.0 mmHg). Coronary obstruction was observed in 1.4% of cases. CONCLUSIONS:Redo-TAVI with a balloon-expandable SAPIEN 3 THV platform is a safe and effective reintervention strategy across diverse failed THV types, when guided by the Heart Team, standardised procedural planning, and comprehensive imaging. CLINICALTRIALS:gov: NCT05601453.

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BACKGROUND:Atrial secondary mitral regurgitation (aSMR) is a distinct subtype of SMR characterized by normal leaflets, annular dilatation, left atrial (LA) enlargement, and preserved left ventricular function. Treatment pathways for aSMR are undefined, and limited data exist regarding outcomes following mitral transcatheter edge-to-edge repair (MTEER). The analysis aimed to evaluate outcomes in patients with aSMR treated with MTEER from the EXPANDed (Evaluation of the MitraClip X System Post-MArket Real-World CliNical Outcomes Database ) studies. METHODS:One-year outcomes were assessed in patients from the EXPANDed studies (EXPAND and EXPAND G4 [Evaluation of the MitraClip X System Post-MArket Real-World CliNical Outcomes Database Generation 4 ]) who met criteria for aSMR. aSMR was defined by the presence of atrial fibrillation, left ventricular ejection fraction ≥45%, and at least 1 dilated LA parameter per echocardiographic core laboratory assessment: LA volume index, LA diameter, or LA diameter index. RESULTS:Of the 967 patients with SMR treated with MTEER in the EXPANDed data set, 160 (17%) met criteria for aSMR. Patients with aSMR were elderly (78±8 years), symptomatic (Kansas City Cardiomyopathy Questionnaire Overall Summary score, 48±27 pts), and had small left ventricular and large LA dimensions at baseline. Acute procedural success was achieved in 97.5% of patients with aSMR, with MR reduction to ≤1+ in 95.2% at 1 year. There were significant 1-year improvements in quality of life (+19 pt Kansas City Cardiomyopathy Questionnaire Overall Summary) and functional capacity (New York Heart Association I/II 80%). The 1-year all-cause mortality rate was 9%, with patients experiencing a 56% reduction in 1-year heart failure hospitalization rates from pre- to post-MTEER. CONCLUSIONS:In the largest population of patients with aSMR assessed by an echocardiographic core laboratory, MTEER safely and significantly reduced MR with improvements in quality of life and reduction in heart failure hospitalization through 1 year.

Background and Aims The coexistence of moderate mitral regurgitation (MR) and severe tricuspid regurgitation (TR) is common, yet evidence guiding optimal management remains limited. Transcatheter edge-to-edge repair (TEER) of both valves-performed either sequentially or in combination-has emerged as a potential therapeutic strategy. This study aimed to assess the prognostic impact of moderate MR in patients undergoing tricuspid TEER (T-TEER) for severe TR and to evaluate whether concomitant mitral TEER (M-TEER) improves clinical outcomes. Methods Data from the EuroTR registry (2016-25) were analysed, including patients with severe TR treated with T-TEER. Outcomes were compared between patients with untreated moderate MR and those who underwent concomitant M-TEER using propensity score matching (PSM). The primary endpoint was all-cause mortality at 2 years. Secondary endpoints included New York Heart Association (NYHA) class, 6 min walk distance (6MWD), TR severity, and heart failure rehospitalizations. Results Among 3100 patients, 30% had moderate MR, which was associated with higher 2-year mortality (23% vs 37%, p<0.0001). After PSM, 217 matched patients treated with concomitant M-TEER had greater TR reduction (-1.9 vs -1.6 grades, P = .001), better NYHA improvement, and increased 6MWD at follow-up. Survival was higher in the combined treatment group (87% vs 76% at 1 year; 81% vs 70% at 2 years, P = .005). In a multivariable analysis, moderate MR predicted increased mortality [hazard ratio (HR) 1.81, P = .005), while combined M-TEER predicted better survival (HR 0.46, P < .0001). Conclusions Moderate MR predicts impaired prognosis in patients undergoing T-TEER for treatment of severe TR. Concomitant M-TEER is associated with improved survival and functional outcomes in this population with multivalve disease. These findings are hypothesis-generating and need to be tested in a dedicated randomized controlled trial.

BACKGROUND:The effect of transcatheter tricuspid-valve repair on clinical outcomes, including death and hospitalization for heart failure, in patients with severe tricuspid regurgitation remains uncertain. METHODS:We randomly assigned patients with symptomatic severe tricuspid regurgitation and an increased risk of future heart-failure events in a 2:1 ratio to tricuspid-valve repair plus medical therapy (tricuspid-repair group) or medical therapy alone (medical-therapy group). The first primary end point was a hierarchical composite of death from any cause, hospitalization for heart failure, and quality-of-life improvement at 1 year, assessed by win ratio. If the between-group difference was significant, a second primary end point would be tested: a composite of death from any cause or hospitalization for heart failure through 3 years. RESULTS:A total of 360 patients underwent randomization (237 patients were assigned to the tricuspid-repair group and 123 to the medical-therapy group). The mean (±SD) age of the patients was 80.3±6.4 years, and 56.4% were women. The win ratio for the first primary end point was 2.42 (95% confidence interval [CI], 1.76 to 3.33; P<0.001), favoring tricuspid-valve repair. The Kaplan-Meier estimate for freedom from death from any cause or hospitalization for heart failure (second primary end point) through 3 years was 52.4% (95% CI, 43.2 to 63.6) in the tricuspid-repair group and 21.0% (95% CI, 12.7 to 34.6) in the medical-therapy group (hazard ratio for death from any cause or hospitalization for heart failure, 0.40; 95% CI, 0.29 to 0.55; P<0.001). Major adverse events within 30 days occurred in 14 patients (5.9%) in the tricuspid-repair group. CONCLUSIONS:Among patients with symptomatic severe tricuspid regurgitation, transcatheter tricuspid-valve repair plus medical therapy was superior to medical therapy alone with respect to a hierarchical composite of death from any cause, hospitalization for heart failure, and quality-of-life improvement at 1 year and was also associated with a lower risk of a composite of death from any cause or hospitalization for heart failure through 3 years. (Funded by the German Center for Cardiovascular Research and others; TRIC-I-HF ClinicalTrials.gov number, NCT04634266.).

AIMS:Tricuspid regurgitation (TR) frequently coexists with left-sided heart failure (HF). Tricuspid valve transcatheter edge-to-edge repair (T-TEER) has emerged as a treatment for severe TR, yet the prognostic role of coexisting HF phenotypes remains unclear. METHODS AND RESULTS:In the EuroTR registry, we assessed the impact of HF subtypes on 2-year all-cause mortality after T-TEER. Patients were stratified by left ventricular ejection fraction (LVEF) into reduced/mildly reduced (HFmrEF/HFrEF <50%) and preserved (≥50%). Those with preserved LVEF were further divided by pulmonary capillary wedge pressure (PCWP) into HFpEF (>15 mmHg) and non-overt left-sided HF (≤15 mmHg). Among 1,773 patients, 30% had HFmrEF/HFrEF, 44% HFpEF, and 26% non-overt left-sided HF. Procedural success (TR ≤moderate) was highest in non-overt left-sided HF (87%) and lowest in HFmrEF/HFrEF (78%). Symptom burden improved across all groups (p<0.001). Estimated 2-year mortality was 25.0% in HFmrEF/HFrEF, 20.3% in HFpEF, and 13.1% in non-overt left-sided HF. Procedural success was associated with improved outcomes in all groups (p<0.01). Among successfully treated patients, survival was comparable between HFmrEF/HFrEF and HFpEF at 1-year but better in HFpEF at 2-years (p=0.027). Predictors of survival differed by phenotype: right ventricular function for HFmrEF/HFrEF, right-sided pressures for HFpEF, and baseline TR severity for non-overt left-sided HF. CONCLUSION:Consideration of left-sided pathologies in patients with significant TR is important as outcomes and predictors for survival differ. Across HF phenotypes, procedural success is associated with survival but the prognostic impact of TR reduction may unfold over time especially in HFpEF.

Tricuspid regurgitation (TR) frequently coincides with severe mitral regurgitation (MR). Transcatheter mitral valve replacement (TMVR) effectively eliminates MR and may secondarily affect TR severity. This study aimed to assess incidence and prognostic value of TR improvement after TMVR using data from an international multicentre registry. Patients with symptomatic MR and baseline TR undergoing TMVR from the CHOICE-MI international multicentre registry were analysed. TR improvement was defined as a ≥1-grade TR reduction at discharge. The primary endpoint was all-cause mortality or heart failure (HF) hospitalization at 1 year. Stepwise Cox regression was performed to assess the adjusted prognostic impact of TR improvement. Among 309 patients (median age 77 years), TR improvement occurred in 33.0% after TMVR. Patients with TR improvement were younger, had higher EuroSCORE II, less coronary artery disease, and lower baseline TAPSE. MR was durably eliminated in most patients, irrespective of TR evolution. At 1 year, there was no statistically significant difference in all-cause mortality or HF hospitalization between patients with and without TR improvement (27.0% vs. 36.9%; p=0.14). Following stepwise Cox regression, TR improvement was an independent predictor of all-cause mortality or HF hospitalization 1 year after TMVR (HR 0.45, 95% CI 0.23–0.88; p=0.02). TR improvement occurs frequently following TMVR and is associated with favourable 1-year outcomes. These results support the clinical relevance of concomitant TR and the systematic assessment of TR after TMVR.

Data on the association of previous cardiac surgery (PCS) with outcomes following tricuspid valve transcatheter edge-to-edge repair (T-TEER) are limited. This study aimed to evaluate the impact of PCS on outcomes after T-TEER. This analysis included patients from the EuroTR registry (European Registry of Transcatheter Repair for Tricuspid Regurgitation; NCT0630726) who underwent T-TEER for clinically relevant tricuspid regurgitation (TR) between 2016 and 2024 and had available information on cardiac surgical history. Study endpoints were procedural TR reduction, improvement in NYHA functional class, all-cause mortality, and the composite of death or heart failure hospitalization (HFH) at 2 years. Among 2929 patients, 27.2

Renal dysfunction might affect outcomes in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease (MVD) undergoing percutaneous coronary intervention (PCI). In MULTISTARS AMI, patients with STEMI and MVD were randomized to immediate or staged PCI of non-culprit lesions. In this pre-specified analysis, patients were stratified according to the presence of renal dysfunction at baseline, defined at an estimated glomerular filtration rate (eGFR) of 60 ml/min/1.73 m2. Patients with an eGFR < 30 ml/min/1.73 m2 were excluded from the trial. The primary endpoint was a composite of death, non-fatal myocardial infarction, stroke, unplanned revascularization, or hospitalization for heart failure at 1 year. In MULTISTARS AMI, 108 (13

The prevalence of mitral regurgitation (MR), particularly degenerative MR (DMR), rises with advancing age. Elderly patients frequently carry increased surgical risk due to frailty and comorbidities, leading to a prohibitive risk of conventional surgery. For such patients, mitral transcatheter edge-to-edge repair (M-TEER) provides a minimally invasive alternative to surgical repair. Data from large registries, including TRAMI (Transcatheter Mitral Valve Interventions) and EXPAND (The MitraClip™ EXPAND Study of the Next Generation of MitraClip™ Devices), demonstrate high procedural success, low 30-day mortality (2-3%) and stroke rates (<1%), and durable improvements in functional status and quality of life (QoL) in elderly cohorts. Although definitions of "elderly" vary between studies (≥75, ≥80, or ≥85 years) and benefits are consistently observed, elderly was defined  ≥75 years within this review. For selected patients unsuitable for M-TEER, transcatheter mitral valve replacement (TMVR) can achieve effective MR elimination, with reported 1-year mortality ranging from 7% to 17% in early transfemoral, transseptal experiences and up to 29% after transapical TMVR. This review summarizes current evidence on safety, functional outcomes, QoL, survival, emerging replacement strategies, and conservative management in elderly patients with MR.

BACKGROUND:Transcatheter mitral valve replacement (TMVR) is an alternative for patients with mitral regurgitation (MR), but data on transfemoral (TF) devices are limited. OBJECTIVES:The aim of this study was to evaluate clinical, echocardiographic, and functional outcomes following TF TMVR in an international registry. METHODS:The CHOICE-MI (Choice of Optimal Transcatheter Treatment for Mitral Insufficiency) Registry included patients undergoing TMVR with dedicated devices at 41 international centers. This analysis included only TF TMVR. Outcomes were assessed per Mitral Valve Academic Research Consortium criteria. Echocardiographic, functional, and clinical outcomes up to 2 years were reported. The primary endpoint was a composite of all-cause mortality or heart failure hospitalization at 2 years. Predictors were identified using multivariable Cox regression. RESULTS:A total of 124 patients (median age 79 years [Q1-Q3: 75-83 years], 50% women, median European System for Cardiac Operative Risk Evaluation II score 5.0% [Q1-Q3: 3.3-8.5]) underwent TF TMVR with 9 different devices. The leading MR etiology was primary MR (n = 49 [39.5%]), with mitral annular calcification in 12.9%. Technical success was achieved in 113 of 124 patients (91.1%), and procedural mortality was low (1 of 124 [0.8%]). Residual MR ≤1+ was achieved in 94.9% at discharge, with stable results at follow-up. The rates of cardiovascular mortality were 14.7% (95% CI: 7.9%-21.5%) and 20.3% (95% CI: 11.4%-29.1%) and of the primary endpoint 44.1% (95% CI: 30.6%-50.0%) and 52.4% (95% CI: 40.2%-62.1%) at 1 and 2 years, respectively, and NYHA functional class had significantly improved at 1- and 2-year follow-up. Atrial fibrillation was an independent predictor of the primary endpoint, whereas technical success was associated with survival. CONCLUSIONS:TMVR using dedicated TF devices demonstrates favorable safety, durable MR reduction, and sustained functional improvement in high-risk patients. (Choice of Optimal Transcatheter Treatment for Mitral Insufficiency Registry [CHOICE-MI Registry]; NCT04688190).

BACKGROUND AND AIMS:Left ventricular reverse remodelling (LVRR) is a key objective of contemporary heart failure (HF) therapies and is characterized by reversal of left ventricular (LV) dilation and dysfunction. OBJECTIVES:To report the incidence and clinical impact of early (30-day) LVRR patients with primary (PMR) and secondary mitral regurgitation (SMR) treated with mitral transcatheter edge-to-edge repair (M-TEER), and to identify independent associations with early LVRR. METHODS:The EXPANDed cohort includes 2205 patients treated with M-TEER from the EXPAND and EXPAND G4 studies. Patients were classified as having early LVRR if they demonstrated a >10% reduction in LV dimension or volume from baseline to 30 days. All LV measurements were assessed by independent echocardiographic core laboratories. RESULTS:Among 527 SMR patients, 338 patients (64.1%) experienced early LVRR after M-TEER. At 1 year, SMR patients with early LVRR had significantly lower rates of death or HF hospitalizations compared with those without (early LVRR: 24.7% vs no early LVRR: 35.9%, P = .009), despite similar MR reduction (MR mild or less ≥93% in both groups) and comparable improvements in functional status (NYHA ≤II ≥78%) and quality of life (∼20-points improvement per KCCQ-OS). Independent associations with early LVRR included hypertension [odds ratio (OR) = 1.96, P = .004], absence of prior cardiac surgeries (OR = 0.51, P = .002), and smaller LV end-systolic volume (OR = 0.81, P = .002).Among 536 PMR patients, 391 (73.0%) experienced early LVRR at 30 days. At 1 year, PMR patients with early LVRR group had similar clinical (composite all-cause mortality or HF hospitalization: early LVRR: 14.5% vs no early LVRR: 17.1%, P = .47) and symptomatic outcomes (≥83% NYHA ≤II; ∼19-point improvement per KCCQ-OS) compared with those without. However, among PMR patients with dilated ventricles, early LVRR group was associated with significantly lower all-cause mortality (early LVRR: 3.8%, no Early LVRR: 14.0%, P = .028). CONCLUSIONS:Regardless of aetiology, most patients experienced early LVRR after M-TEER with significant MR reduction and symptom relief. In SMR patients, early LVRR was associated with lower rates of HF hospitalization and death.

IntroductionThe WASH complex regulates endosomal actin dynamics and vesicular trafficking and is essential for neuronal integrity and motor function. Although variants in WASHC4, WASHC5, and WASHC3 are linked to neurodevelopmental abnormalities, the role of WASHC3 beyond the nervous system, particularly in cardiac mitochondrial regulation, remains unclear.MethodsWe modeled WASHC3 loss of function in zebrafish and human cardiomyocytes. Washc3 was suppressed in zebrafish embryos by antisense oligonucleotide-mediated knockdown, and a stable Washc3 knockout line was generated using CRISPR/Cas9. Washc3-deficient zebrafish hearts were analyzed by quantitative LC-MS/MS proteomics with GO/KEGG enrichment and transcript-level assays. Mitochondrial bioenergetics was assessed by Seahorse XF assays in primary zebrafish cardiomyocytes and in human AC16 cardiomyocytes following AAV-shRNA-mediated WASHC3 knockdown.ResultsWashc3 knockdown embryos exhibited neuromuscular degeneration, impaired locomotion, and early cardiac dysfunction. In contrast, Washc3 knockout zebrafish showed normal early development but developed progressive pericardial degeneration and epicardial remodeling in aged animals. Cardiac proteomics revealed downregulation of mitochondrial proteins, particularly oxidative phosphorylation components, supported by pathway enrichment and concordant transcript-level findings. Mitochondrial respiration was significantly impaired in both Washc3-deficient zebrafish cardiomyocytes and WASHC3-depleted human AC16 cardiomyocytes.DiscussionThese findings identify a previously unrecognized role for WASHC3 in maintaining cardiac mitochondrial protein homeostasis and bioenergetic function and provide a framework linking neuromuscular and cardiac phenotypes to impaired mitochondrial bioenergetics in energy-demanding tissues.

Background Hemolytic anemia after surgical valve repair is rare but potentially life-threatening and has mostly commonly been described in the context of paravalvular regurgitation. Case Summary A 78-year-old woman with prior surgical mitral valve (MV) repair presented with progressive dyspnea and severe hemolytic anemia. Echocardiography revealed severe eccentric, valvular mitral regurgitation (MR) caused by anterior leaflet prolapse with a high-velocity regurgitant jet striking the annuloplasty ring. The patient underwent transcatheter mitral edge-to-edge repair (M-TEER), achieving reduction of MR to mild and resolution of hemolysis. Discussion This case highlights hemolysis as a rare complication after surgical MV repair and the utility of M-TEER for patients at prohibitive surgical risk. Take-Home Messages M-TEER may represent a safe and effective option for managing hemolytic anemia due to recurrent MR. Besides paravalvular regurgitation, valvular regurgitation in the context of prior surgical MV repair should be recognized as a potential cause of hemolytic anemia.

BACKGROUND:N-terminal pro-B-type natriuretic peptide (NT-proBNP) is an established marker of myocardial stress, yet its prognostic role in tricuspid valve transcatheter edge-to-edge repair (T-TEER) for tricuspid regurgitation (TR) remains unclear. OBJECTIVES:The aim of this study was to evaluate the prognostic value of baseline NT-proBNP and its early postprocedural trajectory after T-TEER. METHODS:Patients undergoing T-TEER with available baseline NT-proBNP measurements in the EuroTR (European Registry of Transcatheter Repair for Tricuspid Regurgitation) registry were analyzed. NT-proBNP was evaluated continuously and by tertiles, with longitudinal changes assessed when serial measurements were available. Endpoints were the 2-year composite of all-cause mortality or first heart failure hospitalization, changes in NT-proBNP, symptomatic alleviation, and residual TR. RESULTS:In total, 2,282 patients (median age 80 years [Q1-Q3: 76-83 years], 54% women, 86% in NYHA functional class III or IV) with baseline NT-proBNP values (tertile 1, ≤1,674 pg/mL; tertile 2, 1,674-3,743 pg/mL; and tertile 3, >3,743 pg/mL) were included. Higher tertiles were associated with greater comorbidity burden, more advanced biventricular remodeling, and more severe TR. Baseline NT-proBNP was independently associated with the primary endpoint (adjusted HR: 1.62; 95% CI: 1.29-2.04). Residual TR ≤2+ at discharge occurred in 86.3%, 82.9%, and 81.4% across tertiles (P = 0.040), and higher NT-proBNP was associated with a lower likelihood of symptomatic alleviation (adjusted OR per log10 increase: 0.63; 95% CI: 0.48-0.84; P < 0.001). Both baseline NT-proBNP and higher than expected 30-day levels relative to baseline were independently associated with higher subsequent risk for the primary endpoint. CONCLUSIONS:Baseline NT-proBNP was independently associated with 2-year mortality or heart failure hospitalization after T-TEER. Early postprocedural NT-proBNP trajectories provided incremental prognostic information and may identify patients at increased risk.

Background According to the 2025 ESC/EACTS guidelines for the management of valvular heart disease, transcatheter tricuspid valve interventions (TTVI) have received a Class IIa recommendation (Level of Evidence: A) for the treatment of patients with severe symptomatic tricuspid regurgitation. However, in patients with severe left ventricular dysfunction (LVD) or right ventricular dysfunction (RVD) or precapillary pulmonary hypertension (pcPH), optimal medical therapy (OMT) is preferred because of the potential risk for futility. Objectives The aim of this study was to evaluate clinical and symptomatic outcomes in such “OMT candidate” patients. Methods Using data from EuroTR (European Registry of Transcatheter Repair for Tricuspid Regurgitation), guideline-based thresholds for LVD, RVD, and pcPH were applied to patients undergoing tricuspid valve transcatheter edge-to-edge repair (T-TEER). Patients meeting ≥1 exclusion criterion (“OMT candidates”) were compared with those meeting current recommendations (“TTVI appropriate”) regarding NYHA functional class improvement and 2-year survival free from heart failure hospitalization (HFH). Results Among 1,626 T-TEER patients, 213 (13.1%) met ≥1 exclusion criterion (4.2% of those with LVD, 6.8% of those with RVD, and 3.6% of those with pcPH). Severe LVD, RVD, and pcPH were each associated with significantly lower 1-year HFH-free survival (LVD, 54.6% vs 72.9% [P < 0.001]; RVD, 59.0% vs 73.2% [P = 0.003]; pcPH, 56.2% vs 73.4% [P = 0.021]; median survival follow-up 446 days [Q1-Q3: 192-805 days]). Despite higher NYHA functional class at baseline and follow-up, the rate of ≥1-class improvement was comparable across subgroups (LVD, 51.1% vs 59.4% [P = 0.25]; RVD, 59.7% vs 59.0% [P = 0.90]; pcPH, 51.3% vs 59.4% [P = 0.31]). Overall, “OMT candidates” had lower HFH-free survival than “TTVI-appropriate” patients (58.7% vs 74.3%; P < 0.001) but showed comparable symptomatic relief (≥1 NYHA functional class in 56.2% vs 59.5%; P = 0.68). Conclusions T-TEER may provide symptomatic benefit in selected high-risk patients with severe LVD, RVD, or pcPH. In the absence of randomized evidence, multidisciplinary evaluation at experienced heart valve centers remains essential to balance potential benefit against procedural futility. Further studies are warranted to refine patient selection and optimize outcomes in this challenging cohort.

BACKGROUND:Mitral valve transcatheter edge-to-edge repair (M-TEER) is an established therapy for patients with mitral regurgitation (MR) at high surgical risk. By reducing the mitral valve orifice area (MVOA), M-TEER may increase the risk of iatrogenic mitral stenosis. Data for PASCAL M-TEER according to 3-dimensional (3D)-MVOA remain limited. OBJECTIVES:The objective of the study was to compare procedural, echocardiographic, and clinical outcomes after PASCAL M-TEER according to baseline 3D-MVOA. METHODS:Patients with available baseline 3D-MVOA from the investigator-initiated multicenter REPAIR registry were stratified by 3D-MVOA (<4 vs ≥4 cm2). Outcomes included Mitral Valve Academic Research Consortium-defined technical success, MR ≤1+ at discharge, ≥1 NYHA functional class improvement at 30-days, and 1-year all-cause mortality. RESULTS:Among 1,189 patients (mean age 78 ± 9 years, 44% female, 86% NYHA functional class III/IV, mean 3D-MVOA 4.9 ± 1.6 cm2, 45% secondary MR), 338 (28%) had baseline 3D-MVOA <4 cm2 and 851 (72%) ≥4 cm2. Technical success was achieved in 95.9% vs 98.2% (P = 0.028) and MR reduction to ≤1+ in 72% vs 72% (P > 0.999), respectively. At 30 days, NYHA functional class improved in 61% vs 64% (P = 0.532). One-year all-cause mortality was 13.0% (95% CI: 8.5% to 17.4%) vs 13.6% (95% CI: 10.9% to 16.3%; P = 0.760); adjusted HR (