Clinical and Hemodynamic Outcomes of Balloon-Expandable Mitral Valve-in-Valve Positioning and Asymmetric Deployment: The VIVID Registry.

BACKGROUND: Mitral valve-in-valve (ViV) is associated with suboptimal hemodynamics and rare left ventricular outflow tract (LVOT) obstruction. OBJECTIVES: This study aimed to determine whether device position and asymmetry are associated with these outcomes. METHODS: Patients undergoing SAPIEN 3 (Edwards Lifesciences) mitral ViV included in the VIVID (Valve-in-Valve International Data) Registry were studied. Clinical endpoints are reported according to Mitral Valve Academic Research Consortium definitions. Residual mitral valve stenosis was defined as mean gradient ≥5 mm Hg. Depth of implantation (percentage of transcatheter heart valve [THV] atrial to the bioprosthesis ring) and asymmetry (ratio of 2 measures of THV height) were evaluated. RESULTS: A total of 222 patients meeting the criteria for optimal core lab evaluation were studied (age 74 ± 11.6 years; 61.9% female; STS score = 8.3 ± 7.1). Mean asymmetry was 6.2% ± 4.4%. Mean depth of implantation was 19.0% ± 10.3% atrial. Residual stenosis was common (50%; mean gradient 5.0 ± 2.6 mm Hg). LVOT obstruction occurred in 7 cases (3.2%). Implantation depth was not a predictor of residual stenosis (OR: 1.19 [95% CI: 0.92-1.55]; P = 0.184), but more atrial implantation was protective against LVOT obstruction (0.7% vs 7.1%; P = 0.009; per 10% atrial, OR: 0.48 [95% CI: 0.24-0.98]; P = 0.044). Asymmetry was found to be an independent predictor of residual stenosis (per 10% increase, OR: 2.30 [95% CI: 1.10-4.82]; P = 0.027). CONCLUSIONS: Valve stenosis is common after mitral ViV. Asymmetry was associated with residual stenosis. Depth of implantation on its own was not associated with residual stenosis but was associated with LVOT obstruction. Technical considerations to reduce postdeployment THV asymmetry should be considered.

5-Year Prospective Evaluation of Mitral Valve-in-Valve, Valve-in-Ring, and Valve-in-MAC Outcomes: MITRAL Trial Final Results.

BACKGROUND: The MITRAL (Mitral Implantation of Transcatheter Valves) trial is the first prospective trial to evaluate the safety and feasibility of balloon-expandable aortic transcatheter heart valves in patients with failed surgical bioprostheses or annuloplasty rings and severe mitral annular calcification treated with mitral valve-in-valve (MViV), valve-in-ring (MViR), or valve-in-mitral annular calcification (ViMAC). OBJECTIVES: The aim of this study was to evaluate 5-year outcomes among these patients. METHODS: A multicenter prospective study was conducted among patients at high surgical risk at 13 U.S. sites. Patients underwent MViV (n = 30), MViR (n = 30), or ViMAC (n = 31) and were followed annually for 5 years. Kansas City Cardiomyopathy Questionnaire scores were obtained at baseline and follow-up visits. Echocardiograms were analyzed at independent core laboratories. RESULTS: A total of 91 patients underwent transcatheter mitral valve replacement (February 2015 to December 2017). The mean age was 74.3 ± 8.9 years. At 5-year follow-up, the lowest all-cause mortality was observed in the MViV group (21.4%), 94.7% of patients were in NYHA functional class I or II, and the mean mitral gradient was 6.6 ± 2.5 mm Hg. The MViR and ViMAC groups had higher all-cause mortality (65.5% and 67.9%), most survivors were in NYHA functional classes I and II (50% and 55.6%), and mean mitral gradients remained stable (5.8 ± 0.1 and 6.7 ± 2.5 mm Hg). Significant improvements in Kansas City Cardiomyopathy Questionnaire scores were observed when all 3 arms were pooled. CONCLUSIONS: MViV, MViR, and ViMAC procedures were associated with sustained improvement of heart failure symptoms and quality of life among survivors at 5 years. Transcatheter heart valve function remained stable in all 3 groups. Patients treated with MViV had excellent survival at 5 years, whereas survival was lower in the MViR and ViMAC groups, consistent with underlying disease severity. Patients with more residual mitral regurgitation had higher mortality.

Association of Depression and Cognitive Dysfunction With Patient-Centered Outcomes After Transcatheter Aortic Valve Replacement.

BACKGROUND: Depression and cognitive dysfunction (CD) are not routinely screened for in patients before transcatheter aortic valve replacement (TAVR) and their association with postprocedural outcomes is poorly understood. The objectives of this study are to determine the prevalence of depression and CD in patients with aortic stenosis undergoing TAVR and evaluate their association with mortality and quality of life. METHODS: We analyzed a prospective, multicenter TAVR registry that systematically screened patients for preexisting depression and CD with the Patient Health Questionnaire-2 and Mini-Cog, respectively. The associations with mortality were assessed with Cox proportional hazard models and quality of life (Kansas City Cardiomyopathy Questionnaire and EuroQol visual analogue scale) were evaluated using multivariable ordinal regression models. RESULTS: A total of 884 patients were included; median follow-up was 2.88 years (interquartile range=1.2-3.7). At baseline, depression was observed in 19.6% and CD in 31.8%. In separate models, after adjustment, depression (HR, 1.45 [95% CI, 1.13-1.86]; P<0.01) and CD (HR, 1.27 [95% CI, 1.02-1.59]; P=0.04) were each associated with increased mortality. Combining depression and CD into a single model, mortality was greatest among those with both depression and CD (n=62; HR, 2.06 [CI, 1.44-2.96]; P<0.01). After adjustment, depression was associated with 6.6 (0.3-13.6) points lower on the Kansas City Cardiomyopathy Questionnaire 1-year post-TAVR and 6.7 (0.5-12.7) points lower on the EuroQol visual analogue scale. CD was only associated with lower EuroQol visual analogue scale. CONCLUSIONS: Depression and CD are common in patients that undergo TAVR and are associated with increased mortality and worse quality of life. Depression may be a modifiable therapeutic target to improve outcomes after TAVR.

Incidence, Predictors, and Outcomes Associated With Worsening Renal Function in Patients With Heart Failure and Secondary Mitral Regurgitation: The COAPT Trial.

Background The incidence and implications of worsening renal function (WRF) after mitral valve transcatheter edge-to-edge repair (TEER) in patients with heart failure (HF) are unknown. Therefore, the aim of this study was to determine the proportion of patients with HF and secondary mitral regurgitation who develop persistent WRF within 30 days following TEER, and whether this development portends a worse prognosis. Methods and Results In the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial, 614 patients with HF and severe secondary mitral regurgitation were randomized to TEER with the MitraClip plus guideline-directed medical therapy (GDMT) versus GDMT alone. WRF was defined as serum creatinine increase ≥1.5× or ≥0.3 mg/dL from baseline persisting to day 30 or requiring renal replacement therapy. All-cause death and HF hospitalization rates between 30 days and 2 years were compared in patients with and without WRF. WRF at 30 days was present in 11.3% of patients (9.7% in the TEER plus GDMT group and 13.1% in the GDMT alone group; P=0.23). WRF was associated with all-cause death (hazard ratio [HR], 1.98 [95% CI, 1.3-3.03]; P=0.001) but not HF hospitalization (HR, 1.47 [ 95% CI, 0.97-2.24]; P=0.07) between 30 days and 2 years. Compared with GDMT alone, TEER reduced both death and HF hospitalization consistently in patients with and without WRF (Pinteraction=0.53 and 0.57, respectively). Conclusions Among patients with HF and severe secondary mitral regurgitation, the incidence of WRF at 30 days was not increased after TEER compared with GDMT alone. WRF was associated with greater 2-year mortality but did not attenuate the treatment benefits of TEER in reducing death and HF hospitalization compared with GDMT alone. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01626079.

Cerebrovascular Events After Transcatheter Edge-to-Edge Repair and Guideline-Directed Medical Therapy in the COAPT Trial.

BACKGROUND: Little is known regarding the risk of cerebrovascular events (CVE) in patients with heart failure and severe secondary mitral regurgitation treated with transcatheter edge-to-edge repair (TEER). OBJECTIVES: The study sought to examine the incidence, predictors, timing, and prognostic impact of CVE (stroke or transient ischemic attack) in the COAPT (Cardiovascular Outcomes Assessment of the Mitraclip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial. METHODS: A total of 614 patients with heart failure and severe secondary mitral regurgitation were randomized to TEER plus guideline-directed medical therapy (GDMT) vs GDMT alone. RESULTS: At 4-year follow-up, 50 CVEs occurred in 48 (7.8%) of the 614 total patients enrolled in the COAPT trial; Kaplan-Meier event rates were 12.3% in the TEER group and 10.2 in the GDMT alone group (P = 0.91). Within 30 days of randomization, CVE occurred in 2 (0.7%) patients randomized to TEER and 0% randomized to GDMT (P = 0.15). Baseline renal dysfunction and diabetes were independently associated with increased risk of CVE, while baseline anticoagulation was associated with a reduction of CVE. A significant interaction was present between treatment group and anticoagulation such that TEER compared with GDMT alone was associated with a reduced risk of CVE among patients with anticoagulation (adjusted HR: 0.24; 95% CI: 0.08-0.73) compared with an increased risk of CVE in patients without anticoagulation (adjusted HR: 2.27; 95% CI: 1.08-4.81; Pinteraction = 0.001). CVE was an independent predictor of death within 30 days after the event (HR: 14.37; 95% CI: 7.61, 27.14; P < 0.0001). CONCLUSIONS: In the COAPT trial, the 4-year rate of CVE was similar after TEER or GDMT alone. CVE was strongly associated with mortality. Whether anticoagulation is effective at reducing CVE risk after TEER warrants further study. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Trial] and COAPT CAS [COAPT); NCT01626079).

Emerging Approaches to Management of Left Ventricular Outflow Obstruction Risk in Transcatheter Mitral Valve Replacement.

An increasing number of patients with mitral valve disease are high risk for surgery and in need of less invasive treatments including transcatheter mitral valve replacement (TMVR). Left ventricular outflow tract (LVOT) obstruction is a predictor of poor outcome after TMVR, and its risk can be accurately predicted using cardiac computed tomography analysis. Novel treatment strategies that have shown efficacy in reducing risk of LVOT obstruction after TMVR include pre-emptive alcohol septal ablation, radiofrequency ablation, and anterior leaflet electrosurgical laceration. This review describes recent advances in the management of LVOT obstruction risk after TMVR, provides a new management algorithm, and explores forthcoming studies that will further advance the field.

SCAI/HRS Expert Consensus Statement on Transcatheter Left Atrial Appendage Closure.

Exclusion of the left atrial appendage to reduce thromboembolic risk related to atrial fibrillation was first performed surgically in 1949. Over the past 2 decades, the field of transcatheter endovascular left atrial appendage closure (LAAC) has rapidly expanded, with a myriad of devices approved or in clinical development. The number of LAAC procedures performed in the United States and worldwide has increased exponentially since the Food and Drug Administration approval of the WATCHMAN (Boston Scientific) device in 2015. The Society for Cardiovascular Angiography & Interventions (SCAI) has previously published statements in 2015 and 2016 providing societal overview of the technology and institutional and operator requirements for LAAC. Since then, results from several important clinical trials and registries have been published, technical expertise and clinical practice have matured over time, and the device and imaging technologies have evolved. Therefore, SCAI prioritized the development of an updated consensus statement to provide recommendations on contemporary, evidence-based best practices for transcatheter LAAC focusing on endovascular devices.

SCAI/HRS expert consensus statement on transcatheter left atrial appendage closure.

Exclusion of the left atrial appendage to reduce thromboembolic risk related to atrial fibrillation was first performed surgically in 1949. Over the past 2 decades, the field of transcatheter endovascular left atrial appendage closure (LAAC) has rapidly expanded, with a myriad of devices approved or in clinical development. The number of LAAC procedures performed in the United States and worldwide has increased exponentially since the Food and Drug Administration approval of the WATCHMAN (Boston Scientific) device in 2015. The Society for Cardiovascular Angiography & Interventions (SCAI) has previously published statements in 2015 and 2016 providing societal overview of the technology and institutional and operator requirements for LAAC. Since then, results from several important clinical trials and registries have been published, technical expertise and clinical practice have matured over time, and the device and imaging technologies have evolved. Therefore, SCAI prioritized the development of an updated consensus statement to provide recommendations on contemporary, evidence-based best practices for transcatheter LAAC focusing on endovascular devices.

Outcomes of Bioprosthetic Valve Fracture in Patients Undergoing Valve-in-Valve TAVR.

BACKGROUND: Valve-in-valve (VIV) transcatheter aortic valve replacement (TAVR) is increasingly used to treat degenerated surgical bioprostheses. Bioprosthetic valve fracture (BVF) has been shown to improve hemodynamic status in VIV TAVR in case series. However, the safety and efficacy of BVF are unknown. OBJECTIVES: The primary objective of this study was to assess the safety and efficacy of VIV TAVR using SAPIEN 3 and SAPIEN 3 Ultra valves with or without BVF using data from the Society of Thoracic Surgeons/American College of Cardiology TVT (Transcatheter Valve Therapy) Registry. METHODS: The primary outcome was in-hospital mortality. Secondary outcomes included echocardiography-derived valve gradient and aortic valve area. Inverse probability of treatment weighting was used to adjust for baseline characteristics. RESULTS: A total of 2,975 patients underwent VIV TAVR from December 15, 2020, to March 31, 2022. BVF was attempted in 619 patients (21%). In adjusted analyses, attempted BVF was associated with higher in-hospital mortality (OR: 2.51; 95% CI: 1.30-4.84) and life-threatening bleeding (OR: 2.55; 95% CI: 1.44-4.50). At discharge, VIV TAVR with attempted BVF was associated with larger aortic valve area (1.6 cm2 vs 1.4 cm2; P < 0.01) and lower mean gradient (16.3 mm Hg vs 19.2 mm Hg; P < 0.01). When BVF was compared with no BVF according to timing (before vs after transcatheter heart valve implantation), BVF after transcatheter heart valve implantation was associated with improved hemodynamic status and similar mortality. CONCLUSIONS: BVF as an adjunct to VIV TAVR with the SAPIEN 3 and SAPIEN 3 Ultra valves is associated with a higher risk for in-hospital mortality and significant bleeding and modest improvements in echocardiography-derived hemodynamic status. The timing of BVF is an important determinant of safety and efficacy.

Residual or recurrent mitral regurgitation predicts mortality following transcatheter edge-to-edge mitral valve repair.

Objective: Although regurgitant mitral valves can be repaired through surgical or transcatheter approaches, contemporary comparative outcomes are limited with the impact of residual and recurrent mitral regurgitation (MR) on clinical outcomes being poorly defined. We hypothesized that moderate (2+) or greater residual or recurrent (RR) MR-regardless of type of repair-predicts worse clinical outcomes. Methods: Our institutional experience of 660 consecutive patients undergoing mitral valve repair (2015-2021) consisting of 393 surgical mitral valve repair (SMVr) and 267 transcatheter edge-to-edge mitral valve repair (TEER) was studied. The echocardiographic impact of RRMR (2+) following both SMVr and TEER on death and reintervention was evaluated. Results: Patients averaged 67.8 ± 14.2 years (SMVr = 63.8 ± 13.3 vs 73.6 ± 13.6, P < .0001) and 62.1% were male. Baseline clinical and demographic data were vastly different between the 2 groups. Residual or recurrent 2+ or greater MR developed in 25% (n = 68) of patients who received TEER compared with 6% (n = 25) of SMVr (P < .0001). Reintervention (9.3% vs 2.4%, P = .002) and death (37.9% vs 10.4%, P < .0001) rates at 3-years were greater among the TEER group versus SMVr group. Given the heterogeneity in baseline characteristics and difference in survival, each cohort was analyzed separately, stratified by RRMR, using multivariable modeling to identify predictors of repeat reintervention and death. There were too few events of RRMR in the SMVr cohort for evaluation. For the TEER subgroups, we observed greater long-term mortality, but not reintervention among those with RRMR., Hypertension was the strongest predictor of death and obesity was for reintervention. Conclusions: Patients undergoing SMVr and TEER are vastly different with respect to baseline patient characteristics and clinical outcomes, with patients who undergo TEER being much greater risk with poorer prognosis. Moderate or greater RRMR predicted worse long-term survival but not reintervention among patients who received TEER. Given the difference in survival among patients with RRMR following TEER, care must be taken to ensure that patients entering clinical trials and receiving TEER should have a high probability of achieving mild or less MR as seen in contemporary surgical results.

2-Year Outcomes of Transcatheter Mitral Valve Replacement in Patients With Annular Calcification, Rings, and Bioprostheses.

BACKGROUND: The MITRAL (Mitral Implantation of Transcatheter Valves) trial is the first prospective study for valve-in-mitral annular calcification (ViMAC), mitral valve-in-ring (MViR), and mitral valve-in-valve (MViV) using balloon-expandable aortic transcatheter heart valves. Procedural outcomes beyond 1 year are not well described. OBJECTIVES: This study evaluated 2-year outcomes in ViMAC, MViR, and MViV in the MITRAL trial. METHODS: This multicenter prospective study enrolled patients with severe MAC, prior failed mitral annuloplasty ring repair, or prior failed bioprosthetic MV replacement who were at high surgical risk at 13 U.S. sites. RESULTS: Between February 1, 2015, and December 31, 2017, 91 patients were enrolled (31 with ViMAC, 30 with MViR, and 30 with MViV). In the ViMAC group, 2-year all-cause mortality was 39.3%, 66.7% were New York Heart Association (NYHA) functional class I-II, and mean MV gradient was 5.6 ± 2.0 mm Hg. In the MViR group, 2-year all-cause mortality was 50%, 65% were NYHA functional class I-II, and mean MV gradient was 6.5 ± 2.7 mm Hg. In the MViV group, 2-year all-cause mortality was 6.7%, 85% were NYHA functional class I-II, and mean MV gradient was 6.9 ± 2.4 mm Hg. At 2 years, all patients had ≤mild mitral regurgitation and survivors in all 3 arms showed sustained improvement in Kansas City Cardiomyopathy Questionnaire scores compared to baseline. CONCLUSIONS: Use of balloon-expandable aortic transcatheter heart valves in selected patients with severe MAC, failed annuloplasty ring, and bioprosthetic MV dysfunction is associated with improvements in symptoms, quality of life, and stable prosthesis function at 2-year follow-up. Between 1 and 2 years, the MViR group experienced higher mortality rates than the MViV and ViMAC groups.

Prediction of Death or HF Hospitalization in Patients With Severe FMR: The COAPT Risk Score.

BACKGROUND: There are limited data on the predictors of death or heart failure hospitalization (HFH) in patients with heart failure (HF) with functional mitral regurgitation (FMR). OBJECTIVES: The aim of this study was to develop a predictive risk score using the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial database. METHODS: In COAPT, 614 symptomatic patients with HF and moderate to severe or severe FMR were randomized to MitraClip implantation plus guideline-directed medical therapy (GDMT) or GDMT alone. A risk score for the 2-year rate of death or HFH was generated from Cox proportional hazards models. The predictive value of the model was assessed using the area under the curve of receiver-operating characteristic plots. Kaplan-Meier curves were generated to estimate the proportion of patients experiencing death or HFH across quartiles of risk. RESULTS: During 2-year follow-up, 201 patients (64.4%) in the GDMT-alone group and 133 patients (44.0%) in the MitraClip group experienced death or HFH (P < 0.001). A risk score containing 4 clinical variables (New York Heart Association functional class, chronic obstructive pulmonary disease, atrial fibrillation or flutter, and chronic kidney disease) and 4 echocardiographic variables (left ventricular ejection fraction, left ventricular end-systolic dimension, right ventricular systolic pressure, and tricuspid regurgitation) in addition to MitraClip treatment was generated. The area under the curve of the risk score model was 0.74, and excellent calibration was present. The relative benefit of MitraClip therapy in reducing the 2-year hazard of death or HFH was consistent across the range of baseline risk. CONCLUSIONS: A simple risk score of clinical, echocardiographic, and treatment variables may provide useful prognostication in patients with HF and severe FMR.

1-Year Outcomes of Cardioband Tricuspid Valve Reconstruction System Early Feasibility Study.

BACKGROUND: Tricuspid regurgitation (TR) is prevalent and undertreated, with mortality and morbidity increasing with TR severity. Given poor outcomes with medical therapy and high in-hospital mortality for isolated tricuspid valve surgery, emerging transcatheter repair devices offer a promising alternative. OBJECTIVES: The Edwards Cardioband Tricuspid Valve Reconstruction System Early Feasibility study (NCT03382457) evaluates the treatment of functional TR via annular reduction with the Cardioband Tricuspid Valve Reconstruction System (Edwards Lifesciences). METHODS: Patients with ≥ moderate functional TR were eligible for this prospective, single-arm multicenter study. At 1 year, patients were evaluated for echocardiographic parameters, clinical and quality-of-life measures, and major adverse events. RESULTS: The 37 patients enrolled had a mean age of 78 years; 76% were female; and they had ≥ severe functional (97.3%) or mixed (2.7%) TR, atrial flutter/fibrillation (97%), and New York Heart Association functional class III/IV (65%). At 1 year, 73.0% achieved ≤ moderate TR (P < 0.0001), and 73.1% had ≥2 grade reductions. Echocardiography showed significant reductions in the tricuspid annulus diameter (P < 0.0001), mean vena contracta (P < 0.0001), proximal isovelocity surface area effective regurgitant orifice area (P < 0.0001), right ventricular end-diastolic diameter (P < 0.0001), and inferior vena contracta (P = 0.0006). New York Heart Association functional class improved significantly (P < 0.0001), with 92.3% achieving class I/II, and Kansas City Cardiomyopathy Questionnaire scores improved by 19.0 points (P < 0.0001). One-year cardiovascular mortality was 8.1%, reinterventions were necessary in 5.4%, major access site complications occurred in 8.1%, and severe bleeding was noted in 35.1% of patients. Kaplan-Meier estimates of survival and freedom from heart failure rehospitalization were 85.9% and 88.7%, respectively. CONCLUSIONS: One-year experience using the Cardioband system for tricuspid valve repair shows high survival and low rehospitalization rates with durable outcomes in TR reduction and echocardiographic, clinical, and quality-of-life outcomes.

Impact of baseline renal dysfunction on cardiac outcomes and end-stage renal disease in heart failure patients with mitral regurgitation: the COAPT trial.

AIMS: Baseline renal dysfunction (RD) adversely impacts outcomes among patients with heart failure (HF) and severe secondary mitral regurgitation (MR). Heart failure and MR, in turn, accelerate progression to end-stage renal disease (ESRD), worsening prognosis. We sought to determine the impact of RD in HF patients with severe MR and the impact of transcatheter mitral valve repair (TMVr) on new-onset ESRD and the need for renal replacement therapy (RRT). METHODS AND RESULTS: The COAPT trial randomized 614 patients with HF and severe MR to MitraClip plus guideline-directed medical therapy (GDMT) vs. GDMT alone. Patients were stratified into three RD subgroups based on baseline estimated glomerular filtration rate (eGFR, mL/min/1.73 m2): none (≥60), moderate (30-60), and severe (<30). End-stage renal disease was defined as eGFR <15 mL/min/1.73 m2 or RRT. The 2-year rates of all-cause death or HF hospitalization (HFH), new-onset ESRD, and RRT according to RD and treatment were assessed. Baseline RD was present in 77.0% of patients, including 23.8% severe RD, 6.0% ESRD, and 5.2% RRT. Worse RD was associated with greater 2-year risk of death or HFH (none 45.3%; moderate 53.9%; severe 69.2%; P < 0.0001). MitraClip vs. GDMT alone improved outcomes regardless of RD (Pinteraction = 0.62) and reduced new-onset ESRD [2.9 vs. 8.1%, hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.15-0.76, P = 0.008] and the need for new RRT (2.5 vs. 7.4%, HR 0.33, 95% CI 0.14-0.78, P = 0.011). CONCLUSION: Baseline RD was common in the HF patients with severe MR enrolled in COAPT and strongly predicted 2-year death and HFH. MitraClip treatment reduced new-onset ESRD and the need for RRT, contributing to the improved prognosis after TMVr.