Long-Term Mortality after Transcatheter Edge-to-Edge Mitral Valve Repair Significantly Decreased over the Last Decade: Comparison between Initial and Current Experience from the MiTra Ulm Registry.

(1) Objective: We aimed to assess whether the candidate profile, the long-term outcomes and the predictors for long-term mortality after transcatheter edge-to-edge mitral valve repair (M-TEER) have changed over the last decade; (2) Methods: Long-term follow-up data (median time of 1202 days) including mortality, MACCE and functional status were available for 677 consecutive patients enrolled in the prospective MiTra Ulm registry from January 2010 to April 2019. The initial 340 patients treated in our institution before January 2016 were compared with the following 337 patients; (3) Results: Patients treated after 2016 showed significantly less ventricular dilatation (left ventricular end-systolic diameter of 43 ± 13 mm vs. 49 ± 16 mm, p < 0.007), lower systolic pulmonary pressures (50 ± 15 mmHg vs. 57 ± 21 mmHg, p = 0.01) and a lower prevalence of severe tricuspid regurgitation (27.2% vs. 47.3%, p < 0.001) at baseline than patients treated before 2016. Compared to the cohort treated before 2016, patients treated afterwards showed a significantly lower all-cause 3-year mortality (29.4% vs. 43.8%, p < 0.001) and lower MACCE (38.6% vs. 54.1%, p < 0.001), without differences for MR etiology. While severe tricuspid regurgitation and NYHA class IV remained independently associated with an increased long-term mortality over the last decade, severe left ventricular dilatation (hazard ratio, HR 2.12, p = 0.047) and severe pulmonary hypertension (HR 2.18, p = 0.047) were predictors of long-term mortality only in patients treated before 2016. (4) Conclusions: The M-TEER candidates are currently treated earlier in the course of disease and benefit significantly in terms of a better long-term survival than patients treated at the beginning of the M-TEER era.

Valve unit instead of intensive or intermediate care unit admission following transcatheter edge-to-edge mitral valve repair is safe and reduces postprocedural complications.

BACKGROUND: Transcatheter edge-to-edge mitral valve repair (M-TEER) is often performed in general anesthesia, and postprocedural monitoring is usually warranted on an intensive or intermediate care unit (ICU/IMC). We evaluated the implications of a dedicated valve unit (VU) instead of an ICU/IMC for monitoring after M-TEER. METHODS AND RESULTS: In total, 624 patients were retrospectively analyzed. A total of 312 patients were primarily transferred to either ICU or IMC following M-TEER, and 312 patients were scheduled for the VU in the absence of indications for ICU/IMC treatment. Hospital stay was significantly shorter in VU patients (median 6.0 days (interquartile range (IQR) 5.0 - 8.0) vs. 7.0 days (IQR 6.0 - 10.0), p < 0.001) and their risk for infections (2.9 vs. 7.7%, p = 0.008) and delirium (0.6 vs. 2.6%, p = 0.056) was substantially lower compared to ICU/IMC patients. In-hospital mortality was similar in both groups (0.6% vs. 1.3%, p = 0.41). Fifty patients (16.0%) in the VU group had to cross over to unplanned ICU/IMC admission. The most frequent indication was prolonged need for catecholamines (52.0%). Patients with ICU/IMC crossover had more advanced stages of heart failure (LV-EF < 30% in 36.0 vs. 16.0%, p = 0.001; severe concomitant tricuspid regurgitation in 48.0 vs. 27.8%, p = 0.005) and an LV-EF < 30% was independently associated with unplanned ICU/IMC admission. CONCLUSIONS: Following M-TEER postprocedural monitoring on a VU instead of an ICU/IMC is safe, reduces complications, and spares ICU capacities. Patients with advanced heart failure have a higher risk for unplanned ICU/IMC treatment after M-TEER.

The effect of a smaller spacer in the PASCAL Ace on residual mitral valve orifice area.

BACKGROUND: Mitral transcatheter edge-to-edge repair (M-TEER) is an established treatment for functional mitral regurgitation (FMR) associated with a risk of creating iatrogenic stenosis. OBJECTIVES: To investigate the impact of the P10 and its larger spacer compared to the narrower Ace and its smaller spacer on reduction of mitral valve orifice area (MVOA) during M-TEER. METHODS: Consecutive patients undergoing M-TEER for treatment of severe FMR were screened retrospectively. Patients with a single PASCAL device implantation within the central segments of the MV leaflets, non-complex anatomy, and baseline MVOA ≥ 3.5cm2 were selected. Intraprocedural transesophageal echocardiography was used to compare MVOA reduction with 3D multiplanar reconstruction and direct planimetry. Device selection did not follow a prespecified MVOA threshold. RESULTS: Seventy-two patients (81.0 years, IQR {74.3-85.0}) were included. In 32 patients, the P10 was implanted (44.4%). MR severity (p = 0.66), MR reduction (p = 0.73), and body surface area (p = 0.56) were comparable. Baseline MVOA tended to be smaller in P10 patients with the larger spacer (5.0 ± 1.1 vs. 5.4 ± 1.3cm2, p = 0.18), however, residual MVOA was larger in these patients (2.7 ± 0.7 vs. 2.3 ± 0.6cm2, p = 0.03). Accordingly, relative MVOA reduction was significantly less in P10 patients (- 45.9 ± 7.6 vs. - 56.3 ± 7.0%, p < 0.01). Indirect annuloplasty was more pronounced in Ace patients whereas mean transmitral gradients were similar. CONCLUSION: In FMR patients with non-complex anatomy, the larger spacer of the P10 maintains greater MVOA with similar MR reduction. Hence, the use of the PASCAL Ace device in patients with small MVOAs might correlate with a risk of both clinically relevant orifice reduction and even iatrogenic stenosis.

Predictors of Improvement in Concomitant Tricuspid Regurgitation Following Transcatheter Edge-to-Edge Mitral Valve Repair.

BACKGROUND: Improvement in concomitant tricuspid regurgitation (TR) after mitral valve transcatheter edge-to-edge repair (M-TEER) for mitral regurgitation (MR) occurs frequently; however factors determining the post-procedural course of TR are not well understood. We investigated the parameters associated with TR improvement after M-TEER. METHODS AND RESULTS: A total of 300 patients were consecutively included in this retrospective analysis. MR and TR severity as well as heart chamber metrics were assessed before the procedure and at follow-up. Device success was achieved in 97.3% of patients. TR decreased in 30.2% of patients. Patients with improved TR were more often female, had more severe TR at baseline, and their right heart dimensions at baseline trended to be smaller. Female sex (odds ratio (OR) 2.997), baseline MR-Grade (OR 3.181) and baseline TR-Grade (OR 2.653) independently predicted TR reduction. More pronounced right heart reverse remodeling was observed in patients with improved TR. TR regression independently predicted lower mortality (hazard ratio (HR) 0.333, 95% confidence interval 0.112-0.996, p = 0.049). CONCLUSIONS: A reduction in concomitant TR severity after M-TEER occurred mainly in females and in patients with high-grade TR and MR at baseline. TR regression is associated with better survival after M-TEER.

Drug-coated balloon: an effective alternative to stent strategy in small-vessel coronary artery disease-a meta-analysis.

Background: Small-vessel coronary artery disease (CAD) is frequently observed in coronary angiography and linked to a higher risk of lesion failure and restenosis. Currently, treatment of small vessels is not standardized while having drug-eluting stents (DES) or drug-coated balloons (DCBs) as possible strategies. We aimed to conduct a meta-analytic approach to assess the effectiveness of treatment strategies and outcomes for small-vessel CAD. Methods: Comprehensive literature search was conducted using PubMed, Embase, MEDLINE, and Cochrane Library databases to identify studies reporting treatment strategies of small-vessel CAD with a reference diameter of ≤3.0 mm. Target lesion revascularization (TLR), target lesion thrombosis, all-cause death, myocardial infarction (MI), and major adverse cardiac events (MACE) were defined as clinical outcomes. Outcomes from single-arm and randomized studies based on measures by means of their corresponding 95% confidence intervals (CI) were compared using a meta-analytic approach. Statistical significance was assumed if CIs did not overlap. Results: Thirty-seven eligible studies with a total of 31,835 patients with small-vessel CAD were included in the present analysis. Among those, 28,147 patients were treated with DES (24 studies) and 3,299 patients with DCB (18 studies). Common baseline characteristics were equally distributed in the different studies. TLR rate was 4% in both treatment strategies [0.04; 95% CI 0.03-0.05 (DES) vs. 0.03-0.07 (DCB)]. MI occurred in 3% of patients receiving DES and in 2% treated with DCB [0.03 (0.02-0.04) vs. 0.02 (0.01-0.03)]. All-cause mortality was 3% in the DES group [0.03 (0.02-0.05)] compared with 1% in the DCB group [0.01 (0.00-0.03)]. Approximately 9% of patients with DES developed MACE vs. 4% of patients with DCB [0.09 (0.07-0.10) vs. 0.04 (0.02-0.08)]. Meta-regression analysis did not show a significant impact of reference vessel diameter on outcomes. Conclusion: This large meta-analytic approach demonstrates similar clinical and angiographic results between treatment strategies with DES and DCB in small-vessel CAD. Therefore, DES may be waived in small coronary arteries when PCI is performed with DCB.

TRI-SCORE is superior to EuroSCORE II and STS-Score in mortality prediction following transcatheter edge-to-edge tricuspid valve repair.

BACKGROUND: The development of transcatheter tricuspid edge-to-edge repair for tricuspid regurgitation is a therapeutic milestone but a specific periprocedural risk assessment tool is lacking. TRI-SCORE has recently been introduced as a dedicated risk score for tricuspid valve surgery. AIMS: This study analyzes the predictive performance of TRI-SCORE following transcatheter edge-to-edge tricuspid valve repair. METHODS: 180 patients who underwent transcatheter tricuspid valve repair at Ulm University Hospital were consecutively included and stratified into three TRI-SCORE risk groups. The predictive performance of TRI-SCORE was assessed throughout a follow-up period of 30 days and up to 1 year. RESULTS: All patients had severe tricuspid regurgitation. Median EuroSCORE II was 6.4% (IQR 3.8-10.1%), median STS-Score 8.1% (IQR 4.6-13.4%) and median TRI-SCORE 6.0 (IQR 4.0-7.0). 64 patients (35.6%) were in the low TRI-SCORE group, 91 (50.6%) in the intermediate and 25 (13.9%) in the high-risk groups. The procedural success rate was 97.8%. 30-day mortality was 0% in the low-risk group, 1.3% in the intermediate-risk and 17.4% in the high-risk groups (p < 0.001). During a median follow-up of 168 days mortality was 0%, 3.8% and 52.2%, respectively (p < 0.001). The predictive performance of TRI-SCORE was excellent (AUC for 30-day mortality: 90.3%, for one-year mortality: 93.1%) and superior to EuroSCORE II (AUC 56.6% and 64.4%, respectively) and STS-Score (AUC 61.0% and 59.0%, respectively). CONCLUSION: TRI-SCORE is a valuable tool for prediction of mortality after transcatheter edge-to-edge tricuspid valve repair and its performance is superior to EuroSCORE II and STS-Score. In a monocentric cohort of 180 patients undergoing edge-to-edge tricuspid valve repair TRI-SCORE predicted 30-day and up to one-year mortality more reliably than EuroSCORE II and STS-Score. AUC area under the curve, 95% CI 95% confidence interval.

Transcatheter edge-to-edge-repair of functional mitral regurgitation induces significant remodeling of mitral annular geometry.

Background: Mitral annular alterations in the context of heart failure often lead to severe functional mitral regurgitation (FMR), which should be treated with transcatheter edge-to-edge repair (M-TEER) according to current guidelines. M-TEER's effects on mitral valve (MV) annular remodeling have not been well elucidated. Methods: 141 consecutive patients undergoing M-TEER for treatment of FMR were included in this investigation. Comprehensive intraprocedural transesophageal echocardiography was used to assess the acute effects of M-TEER on annular geometry. Results: Average patient age was 76.2 ± 9.6 years and 46.1% were female patients. LV ejection fraction was reduced (37.0% ± 13.7%) and all patients had mitral regurgitation (MR) grade ≥III. M-TEER achieved optimal MR reduction (MR ≤ I) in 78.6% of patients. Mitral annular anterior-posterior diameters (A-Pd) were reduced by -6.2% ± 9.5% on average, whereas anterolateral-posteromedial diameters increased (3.7% ± 8.9%). Overall, a reduction in MV annular areas was observed (2D: -1.8% ± 13.1%; 3D: -2.7% ± 13.7%), which strongly correlated with A-Pd reduction (2D: r = 0.6, p < 0.01; 3D: r = 0.65, p < 0.01). Patients that achieved A-Pd reduction above the median (≥6.3%) showed significantly lower rates of the composite endpoint rehospitalization for heart failure or all-cause mortality than those with less A-Pd reduction (9.9% vs. 28.6%, p = 0.037, log-rank p = 0.039). Furthermore, patients reaching the composite endpoint had an increase in annular area (2D: 3.0% ± 15.4%; 3D: 1.9% ± 15.3%), whereas those not reaching the endpoint showed a decrease (2D: -2.7% ± 12.4%; 3D: -3.6% ± 13.3%), although residual MR after M-TEER was similar between these groups (p = 0.57). In multivariate Cox regression adjusted for baseline MR, A-Pd reduction ≥6.3% remained a significant predictor of the combined endpoint (OR: 0.35, 95% CI: 0.14-0.85, p = 0.02). Conclusion: Our findings indicate that effects of M-TEER in FMR are not limited to MR reduction, but also have significant impact on annular geometry. Moreover, A-Pd reduction, which mediates annular remodeling, has a significant impact on clinical outcome independent of residual MR.

Diabetes Mellitus in Patients Undergoing Mitral Transcatheter Edge-to-Edge Repair-A Decade Experience in 1000+ Patients.

BACKGROUND: Diabetes mellitus worsens outcomes in patients suffering from heart disease undergoing cardiac procedures. OBJECTIVES: To investigate the impact of diabetes in patients undergoing mitral transcatheter edge-to-edge repair (M-TEER). METHODS: 1118 patients treated with M-TEER for functional (FMR) and degenerative (DMR) mitral regurgitation (MR) between 2010 and 2021 were analyzed using the combined endpoint of death/rehospitalization for heart failure (HFH). RESULTS: Among diabetics (N = 306; 27.4%), comorbidities such as coronary artery disease (75.2% vs. 62.7%; p < 0.001) and progressed (stage III/IV) chronic kidney disease (79.5% vs. 72.6%; p = 0.018) were more frequent. The rate of FMR was higher in diabetics (71.9% vs. 64.5%; p < 0.001). The combined endpoint occurred more frequently in diabetics (40.2% vs. 35.6%; log-rank = 0.035). While no difference was observed in FMR patients (36.8% vs. 37.6%; log-rank p = 0.710), rates of the combined endpoint differed significantly between diabetics and non-diabetics in DMR patients (48.8% vs. 31.9%; log-rank p = 0.001) only. However, diabetes did neither predict the combined endpoint in the overall (OR: 0.97; 95% CI 0.65-1.45; p = 0.890) nor in the DMR cohort (OR: 0.73; 95% CI 0.35-1.51; p = 0.389). Among diabetics treated with M-TEER, troponin (OR: 2.32; 95% CI 1.3-3.7; p = 0.002) and estimated glomerular filtration rate (OR: 0.52; 95% CI 0.3-0.88; p = 0.018) independently predicted the combined endpoint. CONCLUSIONS: Diabetes is associated with adverse outcomes after M-TEER, particularly in DMR patients. However, diabetes does not predict the combined endpoint. In diabetics undergoing M-TEER, biochemical markers associated with organ function and damage independently predict the combined endpoint of death and rehospitalization.

Prevalence of iatrogenic atrial septal defects (iASD) after mitral valve (MV) transcatheter edge-to-edge repair (TEER) in the long-term follow-up.

OBJECTIVES: To investigate prevalence of iatrogenic atrial septal defects (iASDs) after mitral valve (MV) transcatheter edge-to-edge repair (TEER) with the MitraClip in the long-term follow-up. BACKGROUND: MV TEER requires transseptal puncture using a large 22 F sheath. Prevalence, impact and haemodynamic effects of these iASDs remain unknown in the long-term follow-up. METHODS: This prospective study enrolled patients who had undergone first-time TEER at our university hospital between January 2017 and June 2018 for a clinical long-term follow-up study. Prevalence of iASD was investigated 12 months post-TEER using transoesophageal echocardiography (TEE). Study protocol further consisted of transthoracic echocardiography (TTE) and exercise testing. Incidence of all-cause death was compared 12 months post-TEE follow-up. This study was approved by local ethics committee. RESULTS: 48 patients participated in clinical follow-up examinations. Median time between TEER and clinical follow-up examination (TEE, TTE, exercise testing) was 19.5 (IQR: 7.0) months after TEER. Persistent iASD was found in 41.7% of patients. TEER was found to be equally effective in reducing MR and clinical symptoms in both groups at baseline as well as follow-up. Procedural fluoroscopy and device times were significantly longer in the iASD group. MR reduction and functional status (New York Heart Association Class, 6 Minute Walking Test distance) were similar in both groups. Nevertheless, a significant decrease in systolic pulmonary artery pressure (sPAP) and significantly smaller atrial diameters were observed in patients with iASD at follow-up. CONCLUSION: Prevalence of iASDs after TEER in long-term follow-up was about 41%. Although a significant reduction of sPAP and better left atrial reverse remodelling were accomplished in patients with iASD, clinical impact appears low. Manipulation at the atrial septum might play a key role in creating persisting iASD.

Implications of concomitant obstructive or restrictive pulmonary diseases on functional and clinical results after MitraClip.

OBJECTIVES: We investigated the impact of underlying pulmonary limitations (PL) on symptoms and clinical outcomes after transcatheter mitral valve repair (TMVr). BACKGROUND: Patients with pulmonary disease and patients with symptomatic mitral regurgitation (MR) suffer common symptoms like dyspnea and reduced exercise capacity. METHODS: Datasets from the TMVr Ulm registry were retrospectively analyzed by a blinded specialist in pneumology. Patients were dichotomized according to an unambiguous manifestation of concomitant pulmonary disease in a PL-group and a non-PL-group and were analyzed regarding baseline characteristics and clinical follow-up. RESULTS: Overall, 483 patients were included in the study of which 32.3% (n = 156) showed an underlying pulmonary disease. Patients in the PL-group were similar to patients in the non-PL-group, including Euro SCORE II (8.2 vs. 8.4, p = 0.39), New York Heart Association (NYHA) classification (3.2 ± 0.7 in both groups, p = 0.65) and the incidence of moderate-to-severe or severe MR after TMVr (5.8 vs. 8.3%, p = 0.32). Equal and significant symptom relief after TMVr was experienced in both cohorts according to NYHA functional class (2.24 ± 0.84 vs. 2.24 ± 0.86, p = 0.93) and rate of hospitalization during 2 years of follow-up decreased comparably from 61.1 to 19.3%. However, all-cause mortality for 2 year follow-up was significantly higher in the PL-group compared to the non-PL-group (31.4 vs. 21.4%, p = 0.018). CONCLUSION: In patients with MR and concomitant pulmonary disorders, a significant increase of exercise capacity and a significant decrease of rehospitalization rate were observed after TMVr. Nevertheless, all-cause mortality remains significantly increased within a follow-up period of 2 years compared to patients without pulmonary disorders.

Impact of bleeding complications after transcatheter mitral valve repair.

BACKGROUND: Bleeding in the context of cardiac catheterization is frequent and negatively impacts on short- and long-term patient outcome. We evaluated the clinical impact of in-hospital bleeding events after transcatheter mitral valve repair (TMVr) in the long-term follow- up. METHODS: 586 consecutive patients treated with first-time TMVr were enrolled in this registry. In-hospital MVARC (Mitral Valve Academic Research Council) bleedings were assessed and patients were grouped according to the incidence of a bleeding event. Multivariate logistic regression was used to identify significant independent predictors of MVARC bleeding. This study received approval by local ethics committee. RESULTS: 78 patients (13.3%) suffered from an MVARC bleeding event (Access site-related bleedings: 46.2%; GI tract bleeding: 35.9%; Other bleedings: 17.9%). Among these bleeding subgroups, neither relevant differences in baseline characteristics nor in severity of bleeding events were observed. Despite not being an independent predictor for overall death in the multivariate Cox regression analysis, MVARC bleeding was associated with prolonged hospital stay. The ORBIT bleeding score was the best match to predictors of any MVARC bleeding found in our cohort (c-score overall cohort: 0.68; c-score GI bleeding cohort: 0.72). CONCLUSION: MVARC bleedings after TMVr are frequent findings but were only in half of the cases related to the access site. The ORBIT score could be useful for identification of patients at high risk for non-access site bleeding and especially GI bleeding.