Papillary Muscle Infarction by Cardiac MRI in Patients With Mitral Regurgitation.

BACKGROUND: Papillary muscle (PM) infarction (PMI) detected by cardiac magnetic resonance imaging (CMR) is associated with poor outcomes. Whether PM parameters provide more value for mitral regurgitation (MR) management currently remains unclear. Therefore, we examined the prognostic value of PMI using CMR in patients with MR. METHODS: Between March 2018 and July 2023, we retrospectively enrolled 397 patients with MR undergoing CMR. CMR was used to detect PMI qualitatively and quantitively. We also collected baseline clinical, echocardiography, and follow-up data. RESULTS: Of the 397 patients with MR (52.4 ± 13.9 years), 117 (29.5%) were assigned to the PMI group, with 280 (70.5%) in the non-PMI group. PMI was demonstrated more in the posteromedial PM (PM-PM, 98/117) than in the anterolateral PM (AL-PM, 45/117). Compared with patients without PMI, patients with PMI had a decreased AL-PM (41.5 ± 5.4 vs. 45.6 ± 5.3)/PM-PM diastolic length (35.0 ± 5.2 vs. 37.9 ± 4.0), PM-longitudinal strain (LS, 20.4 ± 6.1 vs. 24.9 ± 4.6), AL-PM-LS (19.7 ± 6.8 vs. 24.7 ± 5.6)/PM-PM-LS (21.2 ± 7.9 vs. 25.2 ± 6.0), and increased inter-PM distance (25.7 ± 8.0 vs. 22.7 ± 6.2, all p < 0.001). Multiple logistic regression analyses identified male sex (odds ratio [OR] = 3.65, 95% confidence interval = 1.881-7.081, p < 0.001) diabetes mellitus (OR/95% CI/p = 2.534/1.13-5.68/0.024), AL-PM diastolic length (OR/95% CI/p = 0.841/0.77-0.92/< 0.001), PM-PM diastolic length (OR/95% CI/p = 0.873/0.79-0.964/0.007), inter-PM distance (OR/95% CI/p = 1.087/1.028-1.15/0.003), AL-PM-LS (OR/95% CI/p = 0.892/0.843-0.94/< 0.001), and PM-PM-LS (OR/95% CI/p = 0.95/0.9-0.992/0.021) as independently associated with PMI. Over a 769 ± 367-day follow-up, 100 (25.2%) patients had arrhythmia. Cox regression analyses indicated that PMI (hazard ratio [HR]/95% CI/p = 1.644/1.062-2.547/0.026), AL-PM-LS (HR/95% CI/p = 0.937/0.903-0.973/0.001), and PM-PM-LS (HR/95% CI/p = 0.933/0.902-0.965/< 0.001) remained independently associated with MR. CONCLUSIONS: The CMR-derived PMI and LS parameters improve the evaluation of PM dysfunction, indicating a high risk for arrhythmia, and provide additive risk stratification for patients with MR.

Guideline-Directed Medical Therapy and Survival After TEER for Secondary Mitral Regurgitation With Right Ventricular Impairment.

BACKGROUND: Right ventricular impairment is common among patients undergoing transcatheter edge-to-edge repair for secondary mitral regurgitation (SMR). Adherence to guideline-directed medical therapy (GDMT) for heart failure is poor in these patients. OBJECTIVES: The aim of this study was to evaluate the impact of GDMT on long-term survival in this patient cohort. METHODS: Within the EuroSMR (European Registry of Transcatheter Repair for Secondary Mitral Regurgitation) international registry, we selected patients with SMR and right ventricular impairment (tricuspid annular plane systolic excursion ≤17 mm and/or echocardiographic right ventricular-to-pulmonary artery coupling <0.40 mm/mm Hg). Titrated guideline-directed medical therapy (GDMTtit) was defined as a coprescription of 3 drug classes with at least one-half of the target dose at the latest follow-up. The primary outcome was all-cause mortality at 6 years. RESULTS: Among 1,213 patients with SMR and right ventricular impairment, 852 had complete data on medical therapy. The 123 patients who were on GDMTtit showed a significantly higher long-term survival vs the 729 patients not on GDMTtit (61.8% vs 36.0%; P < 0.00001). Propensity score-matched analysis confirmed a significant association between GDMTtit and higher survival (61.0% vs 43.1%; P = 0.018). GDMTtit was an independent predictor of all-cause mortality (HR: 0.61; 95% CI: 0.39-0.93; P = 0.02 for patients on GDMTtit vs those not on GDMTtit). Its association with better outcomes was confirmed among all subgroups analyzed. CONCLUSIONS: In patients with right ventricular impairment undergoing transcatheter edge-to-edge repair for SMR, titration of GDMT to at least one-half of the target dose is associated with a 40% lower risk of all-cause death up to 6 years and should be pursued independent of comorbidities.

Impact of commissural calcification on clinical outcome of percutaneous balloon mitral valvuloplasty; a retrospective cohort study of 876 patients.

BACKGROUND: Percutaneous balloon mitral valvuloplasty (PBMV) is the ACC/AHA class I recommendation for treating symptomatic rheumatic mitral stenosis with suitable valve morphology, less than moderate MR and absence of left atrium clot. The mitral valve restenosis and significant mitral regurgitation (MR) are known adverse outcomes of PBMV. This study aimed to evaluate the outcomes of PBMV in patients with severe mitral stenosis and the effect of Commissural Calcification (CC) on the outcomes. METHODS: In this single-center retrospective cohort study, 876 patients who underwent PBMV were categorized into three groups based on their Wilkins score (Group I: score ≤ 8, Group II: score 9-10, and Group III: score 11-12). Patients were evaluated before, early after PBMV and at 6- and 24-month follow-ups. Main clinical outcomes were defined as significant restenosis and or symptomatic significant MR (moderate to severe and severe MR) or candidate for mitral valve replacement (MVR). The outcomes were compared between patients with and without CC. RESULTS: A total of 876 patients with mean age 46.4 ± 12.3 years (81.0% females) were categorized based on Wilkins score. 333 (38.0%) were in Group I, 501 (57.2%) were in Group II, and 42 (4.8%) were in Group III. CC was present in 175 (20.0%) of the patients, among whom 95 (54.3%) had calcification of the anterolateral commissure, 64 (36.6%) had calcification of the posteromedial commissure, and in 16 (9.1%) patients both commissures were calcified. There was a significant difference in Wilkins score between patients with and without CC (P < 0.001). CC was associated with higher odds of significant symptomatic MR at early and mid-term follow up (OR: 1.69, 95%CI 1.19-2.41, P = 0.003; and OR: 3.90, 95%CI 2.61-5.83, P < 0.001, respectively), but not with restenosis (P = 0.128). Wilkins Groups II and III did not show higher odds of significant symptomatic MR compared to Group I at early (II: P = 0.784; III: P = 0.098) and mid-term follow up (II: P = 0.216; III: P = 0.227). Patients in Wilkins Group II had higher odds of restenosis compared to Group I (OR: 2.96,95%CI: 1.35-6.27, P = 0.007). CONCLUSION: Commissural calcification (CC) is an independent predictor of the significant symptomatic MR (an important determinant of adverse outcome) following PBMV in the early and mid-term follow-up. Mitral valve restenosis occurs more in patients with higher Wilkins score compared to group I with score ≤ 8. Combined Wilkins score and CC should be considered for patient suitability for PBMV.

Primary Atriopathy in Mitral Valve Prolapse: Echocardiographic Evidence and Clinical Implications.

BACKGROUND: Prominent multi-scallop systolic leaflet displacement toward the left atrium (atrialization) is typically observed in bileaflet mitral valve prolapse (MVP) with mitral annular disjunction. We hypothesized that mitral leaflet atrialization is associated with an underlying left atrial (LA) myopathy characterized by progressive structural and functional abnormalities, irrespective of mitral regurgitation (MR) severity. METHODS: We identified 334 consecutive patients with MVP, no prior atrial fibrillation, and comprehensive clinical and echocardiographic data. LA function was assessed by LA reservoir strain, LA function index, and LA emptying fraction. We also classified the stage of LA remodeling based on LA enlargement and LA reservoir strain (stage 1: no remodeling; stage 2: mild remodeling; stage 3: moderate remodeling; and stage 4: severe remodeling). The primary end point was the composite risk of sudden arrhythmic death, heart failure hospitalization, or the new onset of atrial fibrillation. RESULTS: Bileaflet MVP with no or mild MR had a lower LA reservoir strain (P=0.04) and LA function index (P<0.001) compared with other MVP subtypes. In multivariable linear regression adjusted for cardiovascular risk factors and MR ≥moderate, bileaflet MVP remained significantly associated with lower LA function parameters (all P<0.05). There was a significant increase in the risk of events as the LA reservoir strain and LA remodeling stage increased (P<0.001). In multivariable analysis, stage 4 of LA remodeling remained significantly associated with a higher risk of events compared with stage 1 (hazard ratio, 6.09 [95% CI, 1.69-21.9]; P=0.006). CONCLUSIONS: In a large MVP registry, bileaflet involvement is associated with reduced LA function regardless of MR severity, suggesting a primary atriopathy in this MVP subtype. Abnormal LA function, particularly when assessed through a multiparametric approach, is linked to a higher risk of cardiovascular events and may improve risk stratification in MVP, even in those without significant MR.

Gender and Sex Differences in the Management, Intervention, and Outcomes of Patients With Severe Primary Mitral Regurgitation.

BACKGROUND: Gender- and sex-based disparities in mitral valve disease exist; however the factors associated with these differences are unknown. Identifying these differences is essential in devising mitigating strategies. We evaluated gender and sex differences among patients with severe primary mitral regurgitation (MR) across treatment phases. METHODS AND RESULTS: We conducted a retrospective cohort study of patients with new diagnoses of severe primary MR between 2016 and 2020. We compared multidisciplinary evaluation incidence and 2-year survival between men and women. We analyzed a subgroup meeting class 1 indications for intervention, which includes severe symptomatic MR or severe asymptomatic MR with ejection fraction <60% or left ventricular end-systolic diameter >40 mm. Logistic regression models identified predictors associated with the likelihood of multidisciplinary evaluation. Among 330 patients meeting class 1 indications, women were older (79 versus 76 years, P=0.01) and had higher Society of Thoracic Surgeons risk scores for mitral valve repair than men (2.5% versus 1.4%, P=0.003). Women were less likely to undergo multidisciplinary evaluation (57% versus 84%, P<0.001) and intervention (47% versus 69%, P<0.001) than men. Median days to intervention for women and men were 77 and 43, respectively. Women had a higher 2-year mortality rate than men (31% versus 21%, P=0.035). On a multivariable model, female sex and older age were associated with lower odds of undergoing multidisciplinary evaluation (odds ratio, 0.26; P<0.001; odds ratio, 0.95; P<0.001, respectively). CONCLUSIONS: Women with severe primary MR with class 1 indication for intervention were less likely to undergo multidisciplinary evaluation and intervention and had a longer interval to intervention than men. Survival was comparable after accounting for age and comorbidity differences.

2-year results and myocardial impact of transapical mitral valve repair in patients with primary mitral regurgitation: an echocardiographic study.

BACKGROUND: There is limited data on the 2-year outcomes of transapical transcatheter edge-to-edge repair (TA-TEER) using the ValveClamp in patients with severe primary mitral regurgitation (MR) and its impact on myocardial deformation. METHODS: From July 2018 to March 2021, 53 patients with symptomatic severe primary MR underwent TA-TEER were enrolled. The endpoint was the composite of all-cause mortality, recurrent 3 + or 4 + MR, or need for mitral surgery. RESULTS: Among the 53 patients who had successfully ValveClamp implantation, 8(15.1%) reached the composite endpoint. Significant improvement in left ventricular (LV) end-diastolic volume, pulmonary artery systolic pressure, NYHA functional class, and MR severity were observed (P < 0.05 for all). Univariate Cox's regression analysis revealed that LV end-diastolic volume index, LV end-systolic volume index, left atrial volume index, and pulmonary artery systolic pressure were associated with adverse events (P < 0.05 for all). On multivariate Cox regression analysis, left atrial volume index was independently associated with the endpoint (hazard ratio, 1.049; 95% CI, 1.009-1.091; P < 0.001) after adjustment for above echocardiographic parameters. LV global longitudinal strain and apical longitudinal strain in global and regional segments decreased at 30 days, but showed a recovery at 2 years with no significant difference compared to the baseline. CONCLUSION: TA-TEER using the ValveClamp presented favorable safety and efficacy at 2-year. Myocardial deformation impairment was observed at 30 days post-procedure, but did not persist at 2 years.

Mitral regurgitation carries greater prognostic significance than mitral stenosis in patients undergoing transcatheter aortic valve replacement.

AIMS: This study assessed the outcomes of concomitant mitral valve disease and severe aortic stenosis in patients undergoing transcatheter aortic valve replacement (TAVR). METHODS: Echocardiographic data of 813 patients with severe aortic stenosis undergoing transfemoral TAVR were collected, and clinical outcomes were analyzed for individuals with mitral stenosis and mitral regurgitation. RESULTS: The final cohort includes 788 patients with severe calcific aortic stenosis. Among single parameters of mitral stenosis, a smaller baseline mitral valve area (MVA) by the continuity equation and higher postprocedural mean mitral gradients (MMG) were associated with an increased risk of death at 1 year (P-values 0.02 and <0.01, respectively), but no correlation with outcomes was demonstrated after multivariate adjustment for major prognosticators. Mitral stenosis (based on MVA + MMG) was not associated with complications or mortality. Mitral regurgitation was present in 94.6% of the population at baseline and regressed by at least one grade post-TAVR in 28% of the patients. The improvement in mitral regurgitation was associated with a greater prosthetic effective orifice area (P-value 0.03). Significant (at least moderate) residual mitral regurgitation was correlated with short-term complications and shown to be an independent predictor of 1-year mortality (P-value 0.02, odds ratio (OR) 5.37, confidence interval 1.34-21.5). CONCLUSION: Mitral regurgitation has a greater impact on TAVR patients than mitral stenosis as assessed by functional methods.

Transcatheter Mitral Valve Repair With the MitraClip Device for Prior Mitral Valve Repair Failure: Insights From the GIOTTO-FAILS Study.

BACKGROUND: Minimally invasive mitral valve repair has a favorable risk-benefit profile in patients with significant de novo mitral regurgitation. Its role in patients with prior mitral valve repair is uncertain. We aimed to appraise the outcome of patients undergoing transcatheter edge-to-edge repair (TEER) with prior transcatheter or surgical mitral valve repair (SMVR). METHODS AND RESULTS: We queried the Italian multicenter registry on TEER with MitraClip, distinguishing naïve patients from those with prior TEER or (SMVR). Inhospital and long-term clinical/echocardiographic outcomes were appraised. The primary outcome was the occurrence of death or rehospitalization for heart failure. A total of 2238 patients were included, with 2169 (96.9%) who were naïve to any mitral intervention, 29 (1.3%) with prior TEER, and 40 (1.8%) with prior SMVR. Several significant differences were found in baseline clinical and imaging features. Respectively, device success was obtained in 2120 (97.7%), 28 (96.6%), and 38 (95.0%, P=0.261) patients; procedural success in 2080 (95.9%), 25 (86.2%), and 38 (95.0%; P=0.047); and inhospital death in 61 (2.8%), 1 (3.5%), and no (P=0.558) patients. Clinical follow-up after a mean of 14 months showed similar rates of death, cardiac death, rehospitalization, rehospitalization for heart failure, and their composite (all P>0.05). Propensity score-adjusted analysis confirmed unadjusted analysis, with lower procedural success for the prior TEER group (odds ratio, 0.28 [95% CI, 0.09-0.81]; P=0.019) but similar odds ratios and hazard ratios for all other outcomes in the naïve, TEER, and SMVR groups (all P>0.05). CONCLUSIONS: In carefully selected patients, TEER can be performed using the MitraClip device even after prior TEER or SMVR.

The hybrid (physical-computational) cardiovascular simulator to study valvular diseases.

To better understand the impact of valvular heart disease (VHD) on the hemodynamics of the circulatory system, investigations can be carried out using a model of the cardiovascular system. In this study, a previously developed hybrid (hydro-numerical) simulator of the cardiovascular system (HCS) was adapted and used. In our HCS Björk-Shiley mechanical heart valves were used, playing the role of mitral and aortic ones. In order to simulate aortic stenosis (AS) and mitral regurgitation (MR), special mechanical devices have been developed and integrated with the HCS. The simulation results proved that the system works correctly. Namely, in the case of AS - the mean pulmonary arterial pressure was increased due to increased preload of the left ventricle and the decrease in right ventricular preload was caused by a decrease in systemic arterial pressure. The severity of AS was performed based on the transaortic pressure gradient as well as using the Gorlin and Aaslid equations. In the case of severe AS, when the mean gradient was above 40 mmHg, the aortic valve orifice area was 0.5 cm2, which is in line with ACC/AHA guidelines. For the case of MR - with increasing severity of MR, there was a decrease in the left ventricular pressure and an increase in left atrial pressure. Using mechanical heart valves to simulate VHD by the HCS can be a valuable tool for biomedical research, providing a safe and controlled environment to study and understand the pathophysiology of VHD.

Ertugliflozin for Functional Mitral Regurgitation Associated With Heart Failure: EFFORT Trial.

BACKGROUND: The morbidity and mortality rates of patients with heart failure (HF) and functional mitral regurgitation (MR) remain substantial despite guideline-directed medical therapy for HF. We evaluated the efficacy of ertugliflozin for reduction of functional MR associated with HF with mild to moderately reduced ejection fraction. METHODS: The EFFORT trial (Ertugliflozin for Functional Mitral Regurgitation) was a multicenter, double-blind, randomized trial to examine the hypothesis that the sodium-glucose cotransporter 2 inhibitor ertugliflozin is effective for improving MR in patients with HF with New York Heart Association functional class II or III, 35%≤ejection fraction<50%, and effective regurgitant orifice area of chronic functional MR >0.1 cm2 on baseline echocardiography. We randomly assigned 128 patients to receive either ertugliflozin or placebo in addition to guideline-directed medical therapy for HF. The primary end point was change in effective regurgitant orifice area of functional MR from baseline to the 12-month follow-up. Secondary end points included changes in regurgitant volume, left ventricular (LV) volume indices, left atrial volume index, LV global longitudinal strain, and NT-proBNP (N-terminal pro-B-type natriuretic peptide). RESULTS: The treatment groups were generally well-balanced with regard to baseline characteristics: mean age, 66±11 years; 61% men; 13% diabetes; 51% atrial fibrillation; 43% use of angiotensin receptor-neprilysin inhibitor; ejection fraction, 42±8%; and effective regurgitant orifice area, 0.20±0.12 cm2. The decrease in effective regurgitant orifice area was significantly greater in the ertugliflozin group than in the placebo group (-0.05±0.06 versus 0.03±0.12 cm2; P<0.001). Compared with placebo, ertugliflozin significantly reduced regurgitant volume by 11.2 mL (95% CI, -16.1 to -6.3; P=0.009), left atrial volume index by 6.0 mL/m2 (95% CI, -12.16 to 0.15; P=0.005), and LV global longitudinal strain by 1.44% (95% CI, -2.42% to -0.46%; P=0.004). There were no significant between-group differences regarding changes in LV volume indices, ejection fraction, or NT-proBNP levels. Serious adverse events occurred in one patient (1.6%) in the ertugliflozin group and 6 (9.2%) in the placebo group (P=0.12). CONCLUSIONS: Among patients with functional MR associated with HF, ertugliflozin significantly improved LV global longitudinal strain and left atrial remodeling, and reduced functional MR. Sodium-glucose cotransporter 2 inhibitors may be considered for patients with functional MR. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04231331.

Predictors of post-operative left atrioventricular valve regurgitation in pediatric patients with complete atrioventricular canal defects.

BACKGROUND: In infants with complete atrioventricular canal (CAVC) defects, post-operative left atrioventricular valve regurgitation (LAVVR) is a known major cause of morbidity and mortality and a common indication for re-operation. However, there is scarce data to identify risk factors for poor outcomes. Our study aims to find echocardiographic characteristics that predict post-operative LAVVR at discharge and 1-year follow-up. METHODS: Retrospective cohort study of patients with initial CAVC repair at our hospital who were followed for 1 year between 2013 and 2022. Patients with major co-morbid conditions were excluded. Serial echocardiograms were reviewed. Anatomic details, quantitative and qualitative measure of LAVVR including the number of regurgitant jets, regurgitant jet length and vena contracta width, and ventricular function were collected. The time points measured include pre-operative transthoracic echocardiogram (TTE), post-operative transesophageal echocardiogram (PO-TEE), routine protocol based post-operative day 1 (POD1) TTE, discharge TTE and 1-year post-operative (1yPO) TTE. Paired t-tests, chi-square analysis, and linear regression analysis were performed comparing measured variables to LAVVR outcomes. RESULTS: Fifty-two patients were included; 92% had Trisomy 21. The majority were classified as Rastelli A (71%), others Rastelli C (29%). Only two patients had moderate or greater LAVVR pre-operatively. The mean age at repair was 125 ± 44 days. Pre-operative LAVVR was the only significant predictor of LAVVR severity at 1 year after backward stepwise regression. Of those with < moderate LAVVR on PO-TEE, 20% had worsening to ≥ moderate at discharge, but only 9% remained that way at 1 year. Of those with ≥ moderate LAVVR on PO-TEE, 40% improved to < moderate by 1 year. Two patients who worsened at 1 year, both secondary to likely cleft suture dehiscence. Only one patient required reoperation in the immediate post-operative period secondary to severe LAVVR due to suture dehiscence. Routine protocol-based POD1 echo did not have any association with altered outcomes. CONCLUSION: Pre-operative LAVVR was the only significant predictor of LAVVR severity at 1 year. A significant percentage (40%) of patient with ≥ moderate LAVVR on PO-TEE improved to < moderate by 1 year. Furthermore, routine protocol-based POD1 echo did not have any association with altered outcomes.

Percutaneous Coronary Intervention as a Non-Surgical Treatment for Ischemic Mitral Regurgitation in Patients with Multi-Vessel Coronary Artery Disease.

BACKGROUND Multi-vessel coronary artery disease (MVD) represents a severe type of coronary artery disease (CAD). Ischemic mitral regurgitation (IMR) is a common mechanical complication in patients with CAD. This study aimed to retrospectively investigate the efficacy of percutaneous coronary intervention (PCI) on moderate/severe IMR in patients with MVD. MATERIAL AND METHODS Clinical data were collected from 15 patients who underwent successful treatment for MVD combined with moderate/severe IMR through the PCI procedure and achieved complete revascularization between January 2014 and December 2022. Cardiac structural and functional parameters were assessed through echocardiographic evaluations. Color flow recordings of MR jets were obtained through an enlarged view of the 4-chamber cut, and the diagnosis of MR was categorized into mild (<4 cm²), moderate (4-8 cm²), and severe (>8 cm²), based on the MR area. RESULTS The common features of the selected cases were advanced age, low body weight, and renal insufficiency. Cardiac echocardiography revealed an augmentation in the left atrial anteroposterior diameter and left ventricular internal diameter at end-systole after PCI, while the left ventricle internal diameter in diastole, left ventricular ejection fraction, and left ventricular fractional shortening were comparable to preoperative values. All patients had moderate/severe MR preoperatively, and MR improved at 1 month (2.73±0.69) and 12 months (2.26±0.58) after PCI. CONCLUSIONS In cases of MVD accompanied by moderate/severe IMR, undergoing PCI can spare certain elderly patients with low body weight and renal insufficiency from high-risk surgery, alleviating the severity of MR without undergoing mitral valve intervention.

Technical and Clinical Outcomes After Transcatheter Edge-to-Edge Repair of Mitral Regurgitation in Male and Female Patients: Is Equality Achieved?

BACKGROUND: Currently, no clear impact of sex on short- and long-term survival following transcatheter edge-to-edge mitral valve repair (TEER) is evident, although no data are available on postprocedural life expectancy. Our aim was to assess sex-specific differences in outcomes of patients with mitral regurgitation (MR) treated by TEER. METHODS AND RESULTS: Short-term and 5-year outcomes in men and women undergoing TEER between 2011 and 2018 who were included in the large, multicenter, real-world MitraSwiss registry were analyzed. Outcomes were compared stratified by sex and according to MR cause (primary versus secondary). The impact of TEER on postprocedural life expectancy was estimated by relative survival analysis. Among 1142 patients aged 60 to 89 years, 39.8% were women. They were older, with fewer cardiovascular risk factors and lower functional capacity compared with men. Thirty-day mortality was higher in men than in women (3.3% versus 1.1%; odds ratio, 3.16 [95% CI, 1.16-10.7]; P=0.020). Five-year survival was comparable in both sexes (adjusted hazard ratio for 5-year mortality in men, 1.14 [95% CI, 0.90-1.44], P=0.275). Both men and women with either primary or secondary MR showed similar clinical efficacy over time. TEER provided high relative survival estimates among all groups, and fully restored predicted life expectancy in women with primary MR (5-year relative survival estimate, 97.4% [95% CI, 85.5-107.0]). CONCLUSIONS: TEER is not associated with increased short-term mortality in women, whereas 5-year outcomes are comparable between sexes. Moreover, TEER completely restored normal life expectancy in women with primary MR. A residual excess mortality persists in secondary MR, independently of sex.