Prognostic impact of cancer history in patients undergoing transcatheter mitral valve repair.

BACKGROUND: History of cancer is common in patients undergoing transcatheter mitral valve repair (TMVR). OBJECTIVES: Aim was to examine the impact of cancer history on outcomes after TMVR. METHODS: In patients of a monocentric prospective registry of TMVR history of cancer was retrospectively assessed from records. Associations with 6-week functional outcomes and clinical outcomes during a median follow-up period of 594 days were examined. RESULTS: Of 661 patients (mean age 79 years; age-range 37-101 years; 56.1% men), 21.6% had a history of cancer with active disease in 4.1%. Compared with non-cancer patients, cancer patients had a similar procedural success rate (reduction of mitral regurgitation to grade 2 or lower 91.6% vs. 88%; p = 0.517) and similar relevant improvement in 6-min walking distance, NYHA class, Minnesota Living with Heart Failure Questionnaire score and Short Form 36 scores. 1-year survival (83% vs. 82%; p = 0.813) and 1-year survival free of heart failure decompensation (75% vs. 76%; p = 0.871) were comparable between cancer and non-cancer patients. Patients with an active cancer disease showed significantly higher mortality compared with patients having a history of cancer (hazard ratio 2.05 [95% CI 1.11-3.82; p = 0.023]) but similar mortality at landmark analysis of 1 year. CONCLUSION: TMVR can be performed with equal efficacy in patients with and without cancer and symptomatic mitral regurgitation. Cancer patients show comparable clinical outcome and short-term functional improvement as non-cancer patients. However, longterm mortality was increased in patients with active cancer underlining the importance of patient selection within the heart-team evaluation.

Frailty, periinterventional complications and outcome in patients undergoing percutaneous mitral and tricuspid valve repair.

BACKGROUND: Frailty is common in elderly and multimorbid patients and associated with increased vulnerability to stressors. METHODS: In a single centre study frailty according to Fried criteria was assessed in consecutive patients before transcatheter mitral and tricuspid valve repair. Postprocedural infections, blood transfusion and bleeding and renal failure were retrospectively assessed from records. Median follow-up time for survival was 560 days (IQR: 363 to 730 days). RESULTS: 90% of 626 patients underwent mitral valve repair, 5% tricuspid valve repair, and 5% simultaneous mitral and tricuspid valve repair. 47% were classified as frail. Frailty was associated with a significantly increased frequency of bleeding (16 vs 10%; p = 0.016), blood transfusions (9 vs 3%; p = < 0.001) and infections (18 vs 10%; p = 0.006), but not with acute kidney injury (20 vs 20%; p = 1.00). Bleeding and infections were associated with longer hospital stays, with a more pronounced effect in frail patients (interaction test p < 0.05, additional 3.2 and 4.1 days in frail patients, respectively). Adjustment for the occurrence of complications did not attenuate the increased risk of mortality associated with frailty (HR 2.24 [95% CI 1.62-3.10]; p < 0.001). CONCLUSIONS: Bleeding complications and infections were more frequent in frail patients undergoing transcatheter mitral and tricuspid valve repair and partly explained the longer hospital stay. Albeit some of the complications were associated with higher long-term mortality, this did not explain the strong association between frailty and mortality. Further research is warranted to explore interventions targeting periprocedural complications to improve outcomes in this vulnerable population.

Comparison of transcatheter leaflet-approximation and direct annuloplasty in tricuspid regurgitation.

BACKGROUND: Transcatheter repair emerges as a treatment option in patients with tricuspid regurgitation (TR) and high surgical risk. AIMS: This study aimed to compare leaflet-based and annuloplasty-based transcatheter repair in patients with TR. METHODS: In a retrospective analysis consecutive patients undergoing either transcatheter edge-to-edge repair (TEER) or direct annuloplasty (AP) for relevant TR at 2 centers were compared with respect to baseline characteristics, procedural efficacy and safety (death, myocardial infarction, procedure or device-related cardiothoracic surgery, or stroke at 30 days). RESULTS: 161 patients (57% female, median age 79 [75-82] years) with comparable clinical baseline characteristics in the TEER (n = 87) and AP (n = 74) group were examined. Baseline TR grade was significantly less severe in the TEER compared to the AP group (torrential 9.2 vs. 31.1%, p = 0.001). Technical success and improvement of TR grades were not significantly different across groups. In analysis matched for baseline TR severity, reduction of TR grade to less than moderate was significantly more common in the AP group (47.8 vs. 26.1%, p = 0.031). Major or more severe bleeding occurred in 9.2% of TEER and 20.3% of AP patients (p = 0.049) without any fatal bleedings. Major adverse events (MAE) were similar across groups with four patients (4.7%) in the TEER group and five patients (6.9%) in the AP group (p = 0.733) and 6-month survival did not differ significantly. CONCLUSIONS: Differences observed between patients treated with TEER and AP provide first evidence for tailoring distinct transcatheter treatment techniques to individual patient characteristics.

Performance of Transcatheter Direct Annuloplasty in Patients With Atrial and Nonatrial Functional Tricuspid Regurgitation.

BACKGROUND: A novel echocardiography-based definition of atrial functional tricuspid regurgitation (A-FTR) has shown superior outcomes in patients undergoing conservative treatment or tricuspid valve transcatheter edge-to-edge repair. Its prognostic significance for transcatheter tricuspid valve annuloplasty (TTVA) outcomes is unknown. OBJECTIVES: This study sought to investigate prognostic, clinical, and technical implications of A-FTR phenotype in patients undergoing TTVA. METHODS: This multicenter study investigated clinical and echocardiographic outcomes up to 1 year in 165 consecutive patients who underwent TTVA for A-FTR (characterized by the absence of tricuspid valve tenting, midventricular right ventricular [RV] dilatation, and impaired left ventricular ejection fraction) and nonatrial functional tricuspid regurgitation (NA-FTR). RESULTS: A total of 62 A-FTR and 103 NA-FTR patients were identified, with the latter exhibiting more pronounced RV remodeling. Compared to baseline, the tricuspid regurgitation (TR) grade at discharge was significantly reduced (P < 0.001 for both subtypes), and TR ≤II was achieved more frequently in A-FTR (85.2% vs 60.8%; P = 0.001). Baseline TR grade and A-FTR phenotype were independently associated with TR ≤II at discharge and 30 days. In multivariate analyses, A-FTR phenotype was a strong predictor (OR: 5.8; 95% CI: 2.1-16.1; P < 0.001) of TR ≤II at 30 days. At 1 year, functional class had significantly improved compared to baseline (both P < 0.001). One-year mortality was lower in A-FTR (6.5% vs 23.8%; P = 0.011) without significant differences in heart failure hospitalizations (13.3% vs 22.7%; P = 0.188). CONCLUSIONS: Direct TTVA effectively reduces TR in both A-FTR, which is a strong and independent predictor of achieving TR ≤II, and NA-FTR. Even though NA-FTR showed more RV remodeling at baseline, both phenotypes experienced similar symptomatic improvement, emphasizing the benefit of TTVA even in advanced disease stages. Additionally, phenotyping was of prognostic relevance in patients undergoing TTVA.

Multiparametric Monitoring of Disease Progression in Contemporary Patients with Wild-Type Transthyretin Amyloid Cardiomyopathy Initiating Tafamidis Treatment.

BACKGROUND: Recently, a disease modifying therapy has become available for transthyretin amyloid cardiomyopathy (ATTR-CM). A validated monitoring concept of treatment is lacking, but a current expert consensus recommends three clinical domains (clinical, biomarker and ECG/imaging) assessed by several measurable features to define disease progression. METHODS: We retrospectively analyzed data of wild-type ATTR-CM patients initiating tafamidis therapy assessed within our local routine protocol at baseline and 6-months follow-up with respect to the frequency of values beyond the proposed thresholds defining disease progression. Additionally, associations of cardiac magnetic resonance (CMR) tomography with clinical domains were examined within a subgroup. RESULTS: Sixty-two ATTR-CM patients were included (88.7% male, mean age 79 years). In total, 16.1% of patients had progress in the clinical and functional domain, 33.9% in the biomarker domain and 43.5% in the imaging/electrocardiography (ECG) domain, with the latter driven by deterioration of the diastolic dysfunction grade and global longitudinal strain. In total, 35.5% of patients showed progress in none, 35.5% in one, 29.0% in two and no patient in three domains, the latter indicating overall disease progression. A subgroup analysis of twenty-two patients with available baseline and follow-up CMR data revealed an increase in CMR-based extracellular volume by more than 5% in 18.2% of patients, with no significant correlation with progress in one of the clinical domains. CONCLUSIONS: We provide first frequency estimates of the markers of disease progression according to a recent expert consensus statement, which might help refine the multiparametric monitoring concept in patients with ATTR-CM.

Disentangling Heart Failure and Physical Frailty: Prospective Study of Patients Undergoing Percutaneous Mitral Valve Repair.

BACKGROUND: Frailty and heart failure share pathophysiology and clinical characteristics. OBJECTIVES: The aim of this study was to analyze the contribution of heart failure to the physical frailty phenotype by examining patients with heart failure before and after percutaneous mitral valve repair (PMVR). METHODS: Frailty according to the Fried criteria (weight loss, weakness, exhaustion, slowness, and low activity) was assessed in consecutive patients before and 6 weeks after PMVR. RESULTS: A total of 118 of 258 patients (45.7%) (mean age: 78 ± 9 years, 42% female, 55% with secondary mitral regurgitation) were frail at baseline, which significantly decreased to 74 patients (28.7 %) at follow-up (P < 0.001). The frequency of frailty domains slowness, exhaustion, and inactivity significantly decreased, whereas weakness remained unchanged. Baseline frailty was significantly associated with comorbidities, N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, and functional capacity, whereas frailty after PMVR was not associated with NT-proBNP levels. Predictors of postprocedural reversibility of frailty were NYHA functional class 

Prevalence of left ventricular thrombus formation after mitral valve edge-to-edge repair.

The prevalence of left ventricular (LV) thrombus formation following percutaneous mitral valve edge-to-edge repair (TMVR) with the MitraClip system is unclear. Decreased total stroke volume and perfusion of the LV apex after mitral valve repair may facilitate thrombus formation especially in the context of reduced LV function. LV thrombus may cause disabling stroke or other thromboembolic events in this elderly and multimorbid patient cohort. Analyses of the prevalence of and risk factors for left ventricular thrombus formation in patients treated with the MitraClip system due to severe mitral valve regurgitation. All discharge and follow-up transthoracic echocardiographic examinations up to 6 months of 453 consecutive patients treated with the MitraClip system were screened for the presence of LV thrombus. Prevalence of LV thrombus formation was 1.1% (5/453). Importantly, LV thrombi were exclusively found in patients with severely depressed left ventricular systolic function (LV-EF < 30%), comprising a prevalence of 4.4% in this subgroup (5/113). Importantly, two of these patients were under active DOAC therapy with Rivaroxaban and Apixaban, respectively. Apart from LV-EF, we did not identify other factors that might have facilitated LV thrombus formation. LV thrombus formation following percutaneous mitral valve repair occurred exclusively in patients with severely depressed LV-EF. As two patients developed LV thrombus despite of DOAC therapy, anticoagulation with a Vitamin K antagonist should be considered in patients with an indication for oral anticoagulation following TMVR.

Guideline-directed medical therapy after transcatheter edge-to-edge mitral valve repair.

OBJECTIVE: A sizeable proportion of patients with secondary mitral regurgitation (SMR) do not receive guideline-directed medical therapy (GDMT) for heart failure (HF). We investigated the association between the use of GDMT and mortality in patients with SMR who underwent transcatheter edge-to-edge repair (TEER). METHODS: We retrospectively analysed patients with SMR and a left ventricular ejection fraction of <50% who underwent TEER at three centres. According to current HF guidelines, GDMT was defined as triple therapy consisting of beta-blockers, renin-angiotensin system (RAS) inhibitors and mineralocorticoid receptor antagonists (MRAs). Patients were divided into two groups: GDMT and non-GDMT groups. We calculated the propensity scores and carried out inverse probability of treatment weighting (IPTW) analyses to compare 2-year mortality between the two groups. RESULTS: Of 463 patients, 228 (49.2%) were treated with GDMT upon discharge. IPTW-adjusted Kaplan-Meier curve showed patients with GDMT had a lower incidence of mortality than those without GDMT (19.8% vs 31.1%, p=0.011). In IPTW-adjusted Cox proportional hazards analysis, GDMT was associated with a reduced risk of 2-year mortality (HR: 0.58; 95% CI: 0.35 to 0.95; p=0.030), which was consistent among clinical subgroups. Moreover, patients with GDMT had a higher rate of left ventricular reverse remodelling at 1 year after TEER than those without GDMT. CONCLUSION: GDMT, defined as triple therapy consisting of beta-blockers, RAS inhibitors and MRAs, was associated with a reduced risk of 2-year mortality after TEER for SMR. Optimisation of medical therapy is crucial to improve clinical outcomes in patients undergoing TEER for SMR.

Periinterventional inflammation and blood transfusions predict postprocedural delirium after percutaneous repair of mitral and tricuspid valves.

OBJECTIVES: The aim of this study was to examine predictors and impact of postoperative delirium (POD) on outcome after percutaneous repair of mitral and tricuspid valves. BACKGROUND: POD is common in elderly patients and contributes to increased health care costs and worse outcome. Predictors of POD in percutaneous mitral or tricuspid valve procedures are unclear. METHODS: In a prospective single-center study, patients were screened for POD using the Confusion Assessment Method on the first and second postprocedural days, and up until 7 days in patients with clinical suspicion of delirium. Associations of POD with baseline characteristics, periprocedural outcome and mid-term mortality were examined. RESULTS: One hundred and seventy-seven patients were included (median age 78 years [72-82], 41.8% female) and median (IQR) follow-up was 489 (293-704) days. Patients developing POD (n = 16, 9%) did not differ in baseline and procedural characteristics but more often received postinterventional blood transfusions (37.5% vs. 9.9%, p value = 0.007) and suffered from infections (43.8% vs. 9.9%, p value = 0.001). Patients with POD showed worse survival (HR: 2.71 [1.27-5.78]; p = 0.01), with an estimated 1-year survival of 46 ± 13% compared to 80 ± 3% in patients without POD (log-rank p value 0.007). In multivariate Cox regression, POD remained a significant predictor of mid-term mortality (HR 4.75 [1.97-11.5]; p = 0.001). CONCLUSION: After percutaneous mitral or tricuspid valve repair, POD was independently associated with worse mid-term survival. Procedure- rather than patient-associated characteristics such as blood transfusions and infections emerged as important risk factors for development of POD. Considering the substantial prognostic impact of POD, further studies on its prevention are warranted to improve patient outcome.

"Get with the Guidelines Heart Failure Risk Score" for mortality prediction in patients undergoing MitraClip.

BACKGROUND: Reliable risk scores in patients undergoing transcatheter edge-to-edge mitral valve repair (TMVR) are lacking. Heart failure is common in these patients, and risk scores derived from heart failure populations might help stratify TMVR patients. METHODS: Consecutive patients from three Heart Centers undergoing TMVR were enrolled to investigate the association of the "Get with the Guidelines Heart Failure Risk Score" (comprising the variables systolic blood pressure, urea nitrogen, blood sodium, age, heart rate, race, history of chronic obstructive lung disease) with all-cause mortality. RESULTS: Among 815 patients with available data 177 patients died during a median follow-up time of 365 days. Estimated 1-year mortality by quartiles of the score (0-37; 38-42, 43-46 and more than 46 points) was 6%, 10%, 23% and 30%, respectively (p < 0.001), with good concordance between observed and predicted mortality rates (goodness of fit test p = 0.46). Every increase of one score point was associated with a 9% increase in the hazard of mortality (95% CI 1.06-1.11%, p < 0.001). The score was associated with long-term mortality independently of left ventricular ejection fraction, NYHA class and NTproBNP, and was equally predictive in primary and secondary mitral regurgitation. CONCLUSION: The "Get with the Guidelines Heart Failure Risk Score" showed a strong association with mortality in patients undergoing TMVR with additive information beyond traditional risk factors. Given the routinely available variables included in this score, application is easy and broadly possible.

Prognostic value of hepatorenal function following transcatheter edge-to-edge mitral valve repair.

BACKGROUND: Hepatorenal dysfunction is a strong prognostic predictor in patients with heart failure. However, the prognostic impact of the hepatorenal dysfunction in patients undergoing transcatheter mitral valve repair (TMVR) has not been well studied. METHODS: In consecutive patients who underwent edge-to-edge TMVR at three German centers, the model for end-stage liver disease excluding international normalized ratio (MELD-XI) score was calculated as 5.11 × ln [serum total bilirubin (mg/dl)] + 11.76 × ln [serum creatinine (mg/dl)] + 9.44. Patients were stratified into high (> 11) or low (≤ 11) MELD-XI score of which an incidence of the composite outcome, consisting of all-cause mortality and heart failure hospitalization, within 2 years after TMVR was assessed. RESULTS: Of the 881 patients, the mean MELD-XI score was 11.0 ± 5.9, and 415 patients (47.1%) had high MELD-XI score. The MELD-XI score was correlated with male, effective regurgitant orifice area, and tricuspid regurgitation severity and inversely related to left ventricular ejection fraction. Patients with high MELD-XI score had a higher incidence of the composite outcome than those with low MELD-XI score (47.7% vs. 29.8%; p < 0.0001), and in multivariable analysis, the high MELD-XI score was an independent predictor of the composite outcome [adjusted hazard ratio (HR) 1.34; 95% confidence interval (CI) 1.02-1.77; p = 0.04). Additionally, the MELD-XI score as a continuous variable was also an independent predictor (adjusted HR 1.02; 95% CI 1.00-1.05; p = 0.048). CONCLUSIONS: The MELD-XI score was associated with clinical outcomes within 2 years after TMVR and can be a useful risk-stratification tool in patients undergoing TMVR.

Machine Learning Identifies Clinical Parameters to Predict Mortality in Patients Undergoing Transcatheter Mitral Valve Repair.

OBJECTIVES: The aim of this study was to develop a machine learning (ML)-based risk stratification tool for 1-year mortality in transcatheter mitral valve repair (TMVR) patients incorporating metabolic and hemodynamic parameters. BACKGROUND: The lack of appropriate, well-validated, and specific means to risk-stratify patients with mitral regurgitation complicates the evaluation of prognostic benefits of TMVR in clinical trials and practice. METHODS: A total of 1,009 TMVR patients from 3 university hospitals within the Heart Failure Network Rhineland were included; 1 hospital (n = 317) served as external validation. The primary endpoint was all-cause 1-year mortality. Model performance was assessed using receiver-operating characteristic curve analysis. In the derivation cohort, different ML algorithms were tested using 5-fold cross-validation. The final model, called MITRALITY (transcatheter mitral valve repair mortality prediction system) was tested in the validation cohort with respect to existing clinical scores. RESULTS: Extreme gradient boosting was selected for the MITRALITY score, using only 6 baseline clinical features for prediction (in order of predictive importance): urea, hemoglobin, N-terminal pro-brain natriuretic peptide, mean arterial pressure, body mass index, and creatinine. In the external validation cohort, the MITRALITY score's area under the curve was 0.783 (95% CI: 0.716-0.849), while existing scores yielded areas under the curve of 0.721 (95% CI: 0.63-0.811) and 0.657 (95% CI: 0.536-0.778) at best. CONCLUSIONS: The MITRALITY score is a novel, internally and externally validated ML-based tool for risk stratification of patients prior to TMVR, potentially serving future clinical trials and daily clinical practice.

Mitral Regurgitation International Database (MIDA) Score Predicts Outcome in Patients With Heart Failure Undergoing Transcatheter Edge-to-Edge Mitral Valve Repair.

Background Optimizing risk stratification in patients undergoing transcatheter mitral valve repair is an ongoing challenge. The Mitral Regurgitation International Database (MIDA) score represents a user-friendly mortality risk stratification tool that is validated on a large-scale registry of patients with degenerative mitral regurgitation (MR). We here assessed the potential benefit of the MIDA risk score for patients with functional or degenerative MR undergoing transcatheter mitral valve repair. Methods and Results In total, 680 patients undergoing MitraClip implantation were stratified according to MIDA score tertiles into a low (0-7), intermediate (8-9), and a high (10-12) MIDA score group. MR was assessed in follow-up echocardiograms in 416 patients at 323±169 days after transcatheter mitral valve repair. During 2-year follow-up, 8.2% (15/182) of patients with low, 21.3% (64/300) with intermediate, and 26.3% (52/198) with high MIDA score died (log-rank test P<0.001). Hazard of all-cause mortality increased by 13% (95% CI, 3%-25%) with every additional point of the MIDA score. Subanalysis of 431 patients with functional MR showed similar results. Furthermore, rates of a combined end point of mortality and hospitalization for heart failure were higher with increasing MIDA score (30% [54/182], 38% [113/300] and 48% [94/198], respectively, log-rank test P=0.001). Frequency of residual MR ≥II at follow-up increased with increasing MIDA score group (33%, 44%, and 59%, respectively, P<0.001). Conclusions The MIDA mortality risk score maintains its predictive utility in patients undergoing transcatheter mitral valve repair, regardless of MR cause. Moreover, it was predictive of worse event-free survival regarding a combined end point of mortality and hospitalization for heart failure, and was associated with postprocedural residual MR ≥II and MR recurrence.

Risk Stratification of Patients Undergoing Percutaneous Repair of Mitral and Tricuspid Valves Using a Multidimensional Geriatric Assessment.

BACKGROUND: Given their advanced age and high comorbidity, individual risk assessment is crucial in patients undergoing transcatheter mitral and tricuspid valve repair. Therefore, we evaluated the use of a comprehensive geriatric assessment score, the multidimensional prognostic index (MPI), for risk stratification in these patients. METHODS: We conducted a prospective, observational single-center study, including 226 patients undergoing percutaneous repair for mitral or tricuspid regurgitation. The MPI was calculated preprocedural and covers 8 domains (activities of daily living, instrumental activities of daily living, mental status, nutrition, risk of pressure ulcers, comorbidity, medication, and marital/cohabitation status). We sought to identify an association of MPI score with procedural outcomes and 6-month mortality. RESULTS: A total of 53.1% of patients were stratified as low risk according to MPI (MPI-1 group), 44.2% as medium risk (MPI-2 group), and 2.7% as high risk (MPI-3 group). Procedural efficacy and safety were similar between groups. The estimated survival rate at 6 months was 97±2% in MPI-1 group, 79±4% in MPI-2 group (hazard ratio, 6.90 [95% CI, 2.36-12.2]; P≤0.001) and 50±20% in MPI-3 group (hazard ratio, 20.3 [95% CI, 4.51-91.3]; P<0.001). An increase in 1 SD of the MPI score (0.14 points, possible range of MPI score 0-1) was associated with a hazard ratio of 2.13 (95% CI, 1.58-2.73; P≤0.001) for death after 6 months. The risk association of the MPI with mortality remained significant in multivariate analysis including risk factors, such as peripheral artery disease and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels. CONCLUSIONS: A comprehensive geriatric assessment with the MPI score provides additional information on mortality risk beyond established cardiovascular risk factors.

Periprocedural changes in natriuretic peptide levels and clinical outcome after transcatheter mitral valve repair.

AIMS: This multicentre study investigated the association of periprocedural changes in the levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) with clinical outcomes after transcatheter edge-to-edge mitral valve repair (TMVR). METHODS AND RESULTS: Patients were retrospectively analysed who underwent TMVR with the MitraClip system (Abbott Vascular, Santa Clara, CA, USA) and had available sequential NT-proBNP testing at baseline and 2 months after TMVR. Periprocedural changes in NT-proBNP following TMVR were assessed as the percent change in NT-proBNP between baseline and the 2 month follow-up, and the significant reduction in NT-proBNP was defined as a decrease of >30% in the follow-up NT-proBNP compared with the pre-procedural NT-proBNP level. Primary outcome was defined as a composite outcome consisting of all-cause mortality and hospitalization due to heart failure from 2 months to 2 years after TMVR. Additionally, we identified the cut-off value of pre-procedural NT-proBNP to predict the composite outcome using a receiver operating characteristic analysis (cut-off: 2485 pg/mL). Of 485 patients undergoing TMVR (age: 76.2 ± 9.2 years, female: 42.1%, secondary mitral regurgitation: 67.2%), 150 patients (30.9%) had the significant reduction in NT-proBNP (>30%) following the procedure. Patients with the NT-proBNP reduction had a lower incidence of the composite outcome, compared with those without the reduction in NT-proBNP (31.4% vs. 40.2%; log-rank P = 0.03). The significant reduction in NT-proBNP was also associated with a lower risk of the composite outcome [adjusted hazard ratio (HR): 0.67; 95% confidence interval (CI): 0.45-0.97; P = 0.04], independently of pre-procedural NT-proBNP levels and other clinical parameters. The percent change in NT-proBNP was associated with a linear trend of the incidence of the composite outcome (adjusted HR per 10% decrease: 0.96; 95% CI: 0.94-0.98; P < 0.001). A stratified analysis revealed that the prognostic impact of the significant reduction in NT-proBNP was consistent among clinical subgroups, including aetiology of mitral regurgitation (P for interaction = 0.99). Higher pre-procedural NT-proBNP level (>2485 pg/mL) was associated with the increased risk of the composite outcome (adjusted HR: 1.50; 95% CI: 1.03-2.17; P = 0.03); however, patients with a higher pre-procedural NT-proBNP who achieved the significant reduction in NT-proBNP had a similar risk of the composite outcome to those with a lower pre-procedural NT-proBNP. CONCLUSIONS: Changes in sequential NT-proBNP measurements were associated with clinical outcomes within 2 years after TMVR. The assessment of NT-proBNP dynamics may be valuable to assess the residual risk for patients undergoing TMVR and could assist with post-procedural management after TMVR.

Predictors and prognostic relevance of tricuspid alterations in patients undergoing transcatheter edge-to-edge mitral valve repair.

BACKGROUND: Mitral valve repair may lead to alterations of tricuspid regurgitation (TR). AIMS: We aimed to investigate alterations, predictors and prognostic relevance of TR evolution in a large-scale multicentre population of patients undergoing transcatheter mitral valve repair (TMVR) via the MitraClip. METHODS: In total, we included 531 TMVR patients with at least one available follow-up echocardiography. TR improvement was defined as a TR ≥II at baseline, which showed a decline of at least one TR categorisation. RESULTS: Distribution of preprocedural TR severity was TR 0/I 41% (220/531), TR II 39% (209/531) and TR ≥III 19% (102/531), respectively. Follow-up echocardiography was at 308±187 days. TR severity improved to TR 0/I 49% (259/531), TR II 35% (183/531) and TR III 17% (89/531), p=0.003. Out of 311 patients with TR ≥II at baseline, 41% (127/311) showed TR improvement. Atrial fibrillation (AF), residual mitral regurgitation ≥II (rMR) and tricuspid annular diameter (TAD) remained variables which prevented TR improvement (odds ratio 0.49 [0.29-0.84], 0.47 [0.27-0.81] and 0.97 [0.93-0.997], respectively). TR improvement was associated with better event-free survival regarding post-procedural heart failure hospitalisation (HHF) (hazard ratio 0.6 [0.38-0.94]). The main changes of TR severity occurred within 3 months post TMVR (p=0.006), while there were only minor TR changes between 3 and 12 months of follow-up (p=0.813). CONCLUSIONS: TR improvement was frequent after TMVR. Predictors preventing TR improvement were AF, post-procedural rMR, and TAD. Furthermore, TR improvement was an early phenomenon occurring primarily within the first three months post TMVR and served as a suitable marker of reduced HHF.

Association of iron deficiency, anaemia, and functional outcomes in patients undergoing edge-to-edge mitral valve repair.

AIMS: Patients undergoing percutaneous mitral valve repair (PMVR) show a substantial heterogeneity of prognostic and symptomatic benefit. Iron deficiency and anaemia are associated with worse outcomes in heart failure patients. We investigated the impact of these comorbidities on functional and clinical outcome after PMVR. METHODS AND RESULTS: Iron deficiency and anaemia were prospectively assessed in 130 patients undergoing PMVR with MitraClip. Associations with functional outcomes at 6 weeks [6 min walking distance (6MWD), Short-Form-36 physical component score, and Minnesota Living with Heart Failure Questionnaire score, New York Heart Association class] and long-term clinical outcome were examined. Iron deficiency and anaemia were frequent with 52% and 50%, respectively. Patients with anaemia showed significant worse baseline functional measures, whereas patients with iron deficiency showed only a trend for lower baseline 6MWD. The benefit in functional outcomes after PMVR was notable and did not differ significantly by iron deficiency or anaemia status (range of median changes in 6MWD 35 to 45 m, physical component score 5.6 to 7.2, Minnesota Living with Heart Failure Questionnaire -8.0 to -10.5; improvement of ≥1 New York Heart Association class 69% to 80%). Anaemia was associated with higher risk for the combined endpoint of mortality and heart failure hospitalization (hazard ratio: 2.51; 95% confidence interval: 1.24-5.1; P = 0.01), whereas iron deficiency showed a trend towards more heart failure hospitalizations (hazard ratio: 2.94; 95% confidence interval: 0.94-9.03; P = 0.09). CONCLUSIONS: The prevalence of iron deficiency and anaemia is high in patients undergoing MitraClip. Clinical baseline status and long-term outcome were worse particularly in patients with anaemia. However, the functional benefit of PMVR was equal in patients with and without iron deficiency and anaemia.

Impact of COAPT trial exclusion criteria in real-world patients undergoing transcatheter mitral valve repair.

BACKGROUND: The generalizability of the COAPT trial results on the benefit of TMVR in patients with secondary mitral regurgitation is unclear. METHODS: Functional and long-term clinical outcome were examined in 122 consecutive patients with secondary mitral regurgitation and reduced ejection fraction undergoing TMVR. "COAPT-like" patients were defined according to principal COAPT inclusion/exclusion criteria if all of the following was fulfilled: symptomatic mitral regurgitation grade 3+ or more according to American guidelines; left ventricular ejection fraction ≥ 20%, left ventricular end-systolic dimension ≤ 70 mm, estimated pulmonary artery systolic pressure ≤ 70 mmHg, mitral valve orifice area ≥ 4 cm2, no prior mitral valve procedure, no right sided congestive heart failure, no COPD requiring home oxygen therapy and NYHA class less than IVb. RESULTS: 51% of 122 patients (mean age 74 ± 10 years, 76% male) showed COAPT-like characteristics. COAPT-like patients showed a significantly lower hazard for the composite endpoint of mortality and heart failure hospitalization (HR 0.51, 95%CI 0.30-0.89, p = .017) during a mean follow-up of 16 ± 6 months, with an estimated 1-year event rate of 20% vs 43%, respectively. The improvement in functional outcomes 6 min walking distance (76 ± 136 m vs. 31 ± 90 m), Minnesota Living with Heart Failure Questionnaire (-6 ± 19 vs. -10 ± 23) and Short Form 36 physical component score (3.8 ± 10 vs. 5.5 ± 11) was similar in COAPT-like and the other patients. CONCLUSION: In this first real world cohort half of the patients undergoing TMVR showed COAPT-like characteristics and these patients showed a substantially better clinical outcome. The mid-term functional benefit was similar in COAPT-like and other patients.

Impact of Frailty on Outcomes in Patients Undergoing Percutaneous Mitral Valve Repair.

OBJECTIVES: The aim of this study was to describe the impact of frailty in patients undergoing percutaneous mitral valve repair (PMVR). BACKGROUND: Frailty is common in elderly patients and those with comorbidities and is associated with adverse prognosis. METHODS: Frailty according to the Fried criteria was assessed in consecutive patients admitted for PMVR. Associations of frailty with 6-week (device success, changes in 6-min walking distance and Minnesota Living With Heart Failure Questionnaire and Short Form 36 physical and mental component scores, and improvement ≥1 New York Heart Association functional class) and long-term outcomes during a median follow-up period of 429 days were examined. RESULTS: Of 213 patients admitted for PMVR (median age 78 years; age range 50 to 95 years; 57.3% men), 45.5% were classified as frail. Compared with nonfrail patients, frail patients had a similar device success rate (81.4% vs. 84.5%; p = 0.56) and improvement in 6-min walking distance, New York Heart Association functional class, and Short Form-36 scores but a more pronounced improvement in Minnesota Living With Heart Failure Questionnaire score (mean change -15.9 vs. -11.2 points; p = 0.002). Mortality at 6 weeks was significantly higher in frail (8.3%) compared with nonfrail (1.7%) patients (p = 0.03). Hazards of death (hazard ratio: 3.06; 95% confidence interval: 1.54 to 6.07; p = 0.001) and death or heart failure decompensation (hazard ratio: 2.03; 95% confidence interval: 1.22 to 3.39; p = 0.007) were significantly increased in frail patients during long-term follow-up, which did not change relevantly after adjustment for European System for Cardiac Operative Risk Evaluation score and N-terminal pro-brain natriuretic peptide level. CONCLUSIONS: PMVR can be performed with equal efficacy and is associated with at least similar short-term functional improvement in frail patients. These results support the continued use of PMVR in frail elderly patients with the goal of palliation of heart failure symptoms and improvement in quality of life.

Functional status and quality of life after transcatheter mitral valve repair: a prospective cohort study and systematic review.

BACKGROUND: Estimating the quantitative effect of transcatheter mitral valve repair on functional parameters and quality of life is important for individual treatment decision-making. METHODS: We combined data from a prospective monocentric cohort study (N = 215) with data from a systematic literature review (PubMed search term "mitraclip", till 30.04.2016) on patients undergoing MitraClip with at least mortality after discharge reported as an outcome. Effects on functional parameters were reported as range of mean change. RESULTS: 36 observational studies and 1 randomized controlled trial were identified. Due to substantial heterogeneity of effect estimates (I 2-heterogeneity >75%) and inadequate quality of studies with a lack of comparison group in 97.4% and lack of an independent assessment of outcomes in 86.8%, no pooled estimates were calculated. All studies reported improvements of mean New York Heart Association (NYHA) class (0.5-1.9 classes), Short-Form (SF)-12/36 scores (4.4-9.2 for physical component score, 2.6-8.9 for mental component score), 6-min walk distance [(6MWD) 2-336 m] and Minnesota Living with Heart failure questionnaire (MLWHFQ) score (-7 to -18 points), with improvements regarded as clinically relevant in 20 of 29 studies for NYHA class, in all of 7 studies for SF12/36, in 9 of 15 studies for 6MWD and in all of 8 studies for MLWHFQ. CONCLUSION: MitraClip therapy provides improvements in physical capacity, physical and mental functioning and disease-specific quality of life in the majority of patients. However, more comparative and high-quality studies are required for understanding the heterogeneity of results, which is crucial for optimal patient selection.