Incidence, Timing, Causes and Predictors of Early and Late Re-Hospitalization in Patients Who Underwent Percutaneous Mitral Valve Repair With the MitraClip System.

The pattern and reasons for re-hospitalization (RH) after MitraClip implantation are not well characterized. A total of 322 consecutive MitraClip patients were included, with data stratified by RH status. Multivariate analyses were conducted to identify predictors of early (30-day) and late (30-day to 12-month) RH. Eighty-nine patients (27.6%) were readmitted to hospital during the study period and early RH occurred in 27%. The median time from MitraClip to RH was 99 days. RH was mostly related to cardiovascular causes (66.3%). Anemia and gastrointestinal bleeding were the most frequent noncardiovascular causes. Independent predictors of early RH were length of stay ≥3 days during the index procedure (odds ratio [OR] 4.13, 95% confidence interval [CI] 1.32 to 12.91), reduction of left ventricular ejection fraction ≥5% after MitraClip implantation (OR 4.88, 95% CI 1.36 to 18.91), and severe systolic pulmonary artery pressure ≥60 mm Hg at discharge (OR 3.72, 95% CI 1.23 to 11.26). Conversely, the independent predictors of late RH were device failure (OR 4.02, 95% CI 1.22 to 13.25) and systolic pulmonary artery pressure ≥60 mm Hg at discharge (OR 2.34, 95% CI 1.01 to 5.44). In patients with early RHs, survival was significantly worse at 12 months compared with patients with late RH and no-RH (69.3% vs 82.6% vs 86%, p <0.001). In conclusion, RH is not uncommon after MitraClip implantation and cardiovascular causes represent its most frequent etiology. Clinical and echocardiographic predictors of early and late RH can be identified at discharge. Early RH carries a worse prognosis than late RH.

HbA1c Identifies Subjects With Prediabetes and Subclinical Left Ventricular Diastolic Dysfunction.

Context: Prediabetes is associated with subclinical cardiac changes associated with heart failure development. Objective: We investigated diastolic function and its association with markers of glycation and inflammation related to cardiovascular disease in patients with prediabetes. We focused on individuals with prediabetes identified only by glycated hemoglobin A1c [HbA1c; 5.7% to 6.4% and normal fasting glucose (NFG) and normal glucose tolerance (NGT) after an oral glucose tolerance test (OGTT)]. Design: Cross-sectional study. Setting: Departments of Clinical and Experimental Medicine and Cardiology, University of Catania, Catania, Italy. Main Outcome Measures: HbA1c, OGTT, Doppler echocardiography, soluble receptor for advanced glycation end products (sRAGEs), and endogenous secretory RAGE (esRAGE) were evaluated. Patients: We recruited 167 subjects with NFG/NGT who were stratified according to HbA1c level: controls (HbA1c <5.7%) and HbA1c prediabetes (HbA1c 5.7% to 6.4%). Results: Patients with HbA1c prediabetes (n = 106) showed a lower peak mitral inflow in early diastole (E wave) to late diastolic atrial filling velocity (A wave) ratio (E/A ratio) than controls (n = 61) (1.10 ± 0.24 vs 1.18 ± 0.23; P < 0.05). They showed a higher left atrium volume (LAV) (28.4 ± 5 vs 22.1 ± 3; P < 0.05) and sphericity index (SI) (0.6 ± 0.06 vs 0.5 ± 0.05; P < 0.05). After multiple regression analyses, HbA1c, sRAGE, and esRAGE were the major determinants of E/A ratio, LAV, and SI. Conclusions: Subjects with HbA1c prediabetes exhibited subclinical cardiac alterations associated with sRAGE, esRAGE, and HbA1c. These subjects would not have been classified as having prediabetes on the basis of fasting glycemia or post-OGTT values.

Transcatheter Mitral Valve Implantation Using the HighLife System.

OBJECTIVES: This study is the first report of 2 cases of HighLife (HighLife, Paris, France) implantation in humans. BACKGROUND: Transcatheter mitral valve implantation represents a promising approach to treating mitral regurgitation in patients at increased risk of perioperative mortality. The HighLife transcatheter mitral valve is a 2-component system. The valve is implanted in the mitral position and is anchored by interacting and then reaching an equilibrium position with a previously positioned subannular implant. METHODS: The procedures were successfully performed in a 69-year-old man and a 65-year-old woman with severe functional mitral regurgitation. Both patients were in New York Heart Association functional class IV heart failure with depressed left ventricular ejection fraction and additional comorbidities. RESULTS: The valve was implanted uneventfully in both patients. General anesthesia was used. The subannular implant was deployed through the transfemoral access, whereas the transcatheter mitral valve was released using the transapical access. Patients maintained hemodynamically stable. There were no intraoperative complications. Acutely, post-procedural echocardiograms demonstrated excellent prosthetic valve function with a low transvalvular gradient and no paravalvular leak and left ventricular outflow tract obstruction. Both patients had mild intraprosthetic regurgitation. Patient #1 survived at 5-months follow-up in New York Heart Association functional class II with excellent prosthesis performance. Patient #2 expired 4 days after a technically successful procedure, because the left ventricle did not tolerate the reduction of mitral regurgitation and despite a high dose of inotropic agents the left ventricular function rapidly deteriorated. CONCLUSIONS: Transcatheter mitral valve implantation using the 2-component HighLife system is technically feasible and can be performed safely. Early hemodynamic performance of the prosthesis was excellent.

Unusual interatrial membrane in the left atrium: A newer obstacle for transseptal-based percutaneous mitral valve repair techniques?

We present a case of a patient with severe mitral regurgitation referred to our Institution for an echocardiographic examination as part of the routine workup to assess the eligibility for mitral valve percutaneous repair with either the MitraClip or Cardioband systems. Echocardiography showed the presence of an unusual interatrial membrane in the left atrium that represented a contraindication for the puncture of the interatrial septum. The patient was finally deferred to percutaneous mitral valve replacement using transapical access.

A Risk Model for Prediction of 1-Year Mortality in Patients Undergoing MitraClip Implantation.

There is a lack of specific tools for risk stratification in patients who undergo MitraClip implantation. We aimed at combining preprocedural variables with prognostic impact into a specific risk model for the prediction of 1-year mortality in patients undergoing MitraClip implantation. A total of 311 consecutive patients who underwent MitraClip implantation were included. A lasso-penalized Cox-proportional hazard regression model was used to identify independent predictors of 1-year all-cause mortality. A nomogram (GRASP [Getting Reduction of mitrAl inSufficiency by Percutaneous clip implantation] nomogram) was obtained from the Cox model. Validation was performed using internal bootstrap resampling. Forty-two deaths occurred at 1-year follow-up. The Kaplan-Meier estimate of 1-year survival was 0.845 (95% confidence interval, 0.802 to 0.895). Four independent predictors of mortality (mean arterial blood pressure, hemoglobin natural log-transformed pro-brain natriuretic peptide levels, New York Heart Association class IV at presentation) were identified. At internal bootstrap resampling validation, the GRASP nomogram had good discrimination (area under receiver operating characteristic curve of 0.78, Somers' Dxy statistic of 0.53) and calibration (le Cessie-van Houwelingen-Copas-Hosmer p value of 0.780). Conversely, the discriminative ability of the EuroSCORE II (the European System for Cardiac Operative Risk Evaluation II) and the STS-PROM (the Society of Thoracic Surgeons Predicted Risk of Mortality score) was fairly modest with area under the curve values of 0.61 and 0.55, respectively. A treatment-specific risk model in patients who undergo MitraClip implantation may be useful for the stratification of mortality at 1 year. Further studies are needed to provide external validation and support the generalizability of the GRASP nomogram.

Strategies and Outcomes of Repeat Mitral Valve Interventions after Failed MitraClip Therapy.

Percutaneous mitral valve repair (PMVR) with the MitraClip system (Abbott Vascular, Santa Clara, CA, USA) is a valid therapeutic option for patients with severe mitral regurgitation (MR) deemed to be at high or prohibitive surgical risk. Despite the reassuring data on efficacy and long-term durability of the procedure, the proportion of patients with residual or relapsing severe MR after MitraClip therapy is not negligible. In light of the detrimental prognostic impact of severe MR, repeat interventions are increasingly performed in clinical practice using different techniques. In high-risk settings, percutaneous procedures have proven to be effective and safe at reducing MR. Building on this, we sought to summarize the current landscape and clinical experience of reinterventions after failed MitraClip therapy, so as to assist physicians facing the clinical hurdle of proper treatment management after failed PMVR.

Feasibility and predictors of early discharge after percutaneous edge-to-edge mitral valve repair.

BACKGROUND: Percutaneous edge-to-edge mitral valve repair (PMVR) recently emerged as an effective treatment modality for patients with severe mitral regurgitation (MR). Length of postprocedural hospital stay may represent a modifiable cost associated with percutaneous treatment. We looked at feasibility, predictors and safety of early discharge (ED), defined as hospital discharge within 72 hours, in patients undergoing PMVR. METHODS AND RESULTS: Consecutive patients treated with MitraClip from October 2008 to December 2015 were analysed. Primary outcomes of interest were cardiovascular and non-cardiovascular mortality, rehospitalisation for heart failure and major adverse events at 30 days and 90 days. A total of 269 patients were included. Of these, 115 patients were early discharged (ED group). Rates of ED increased from 25.9% for the biennium 2008-2009 to 59.1% in 2014-2015 (p<0.001 for trend). In a penalised logistic regression model, male gender (OR=2.13, 95% CI 1.17 to 3.95) and procedural year (OR=2.13, 95% CI 1.51 to 3.11) were associated with higher probability of ED. Conversely, atrial fibrillation (OR=0.48, 95% CI 0.27 to 0.85), any Mitral Valve Academic Research Consortium bleeding (OR=0.07, 95% CI 0.01 to 0.60), log-transformed N-terminal pro-brain natriuretic peptide levels (OR=0.79, 95% CI 0.63 to 0.99) and postimplant MR grade (OR=0.60, 95% CI 0.37 to 0.94) conferred a lower likelihood of ED. In propensity score-weighted analyses, overall survival, freedom from heart failure and major adverse events at 30 days and 90 days were not different in ED and non-ED groups (all weighted log-rank p value>0.05). CONCLUSIONS: In selected patients undergoing PMVR, ED may be feasible and safe.

MitraClip Implantation for the Treatment of New-Onset Systolic Anterior Motion of the Mitral Valve After Transcatheter Aortic Valve Replacement.

New-onset systolic anterior motion of the anterior mitral valve leaflet in patients undergoing transcatheter aortic valve replacement is a rare pathophysiologic mechanism leading to postprocedural development of mitral regurgitation and, eventually, left ventricular outflow obstruction. We report the first human case of successful MitraClip implantation to treat new-onset systolic anterior motion of the mitral valve after transcatheter aortic valve replacement causing severe obstruction to left ventricular outflow that was unresponsive to standard medical therapy.

Percutaneous mitral valve repair with the MitraClip system in the elderly: One-year outcomes from the GRASP registry.

BACKGROUND: Although mitral regurgitation (MR) affects a relevant and increasing number of elderly, an optimal management of this high-risk population is challenging. METHODS AND RESULTS: The aim of this prospective, observational study was to compare one-year outcomes of MitraClip therapy in high surgical risk patients with moderate-to-severe or severe MR between patients aged <75 versus ≥75years. A total of 180 patients were included: 92 were <75years and 88 were ≥75years old. At one-year follow-up the primary efficacy endpoint (composite of death, surgery for mitral valve dysfunction and grade 3+ or 4+ MR) occurred in 41 patients (24.5%), with similar rates between those aged <75years (23.9%) and those ≥75years (25.2%), p=0.912. A total of 21 (12.2%) deaths were observed within 1year after the MitraClip procedure, without significant differences in cumulative mortality rates between elderly and younger patients (10.8% vs. 13.3%, respectively, p=0.574). Compared with baseline, the significant reduction in MR severity achieved after the procedure was sustained at one-year follow-up, in both elderly and younger patients and a significant improvement in NYHA functional class was observed in both groups. A total of 18 (10.0%) patients experienced a re-hospitalization for acute heart failure within one-year after the MitraClip procedure, with no significant differences between elderly and younger. At one-year follow-up both elderly and younger patients showed significant reductions in left ventricular volumes, with changes of similar extent between the two subgroups. CONCLUSIONS: MitraClip therapy can be considered a viable option also among subsets with more advanced age.

Impact of chronic kidney disease on outcomes after percutaneous mitral valve repair with the MitraClip system: insights from the GRASP registry.

AIMS: Our aim was to evaluate the impact of baseline chronic kidney disease (CKD) on clinical outcomes after percutaneous edge-to-edge mitral valve repair (PMVR). METHODS AND RESULTS: Two hundred and fourteen consecutive patients dichotomised by the presence of baseline CKD (n=113) or no-CKD (n=101) had their clinical outcomes compared up to 12-month follow-up. The primary safety endpoint was the incidence of major adverse events and the primary efficacy endpoint was freedom from death, surgery for MV dysfunction, or grade ≥3+ MR. The primary safety endpoint was demonstrated in 12.4% vs. 2.0% in CKD and no-CKD patients, respectively (p=0.003). The primary efficacy endpoint at 12 months was significantly lower in CKD patients (65.8% vs. 84.2%, respectively, log-rank p=0.005). While MR reduction and NYHA functional class improvement were mostly sustained and equivalent up to 12 months in no-CKD patients, they were impaired in CKD patients. Baseline CKD was an independent predictor of the primary efficacy endpoint (adjusted HR 2.48, 95% CI: 1.29 to 4.79, p=0.006) and calcified leaflet predicted grade ≥3+ MR at 12 months (adjusted HR 6.56, 95% CI: 2.71 to 15.88, p<0.001). CONCLUSIONS: CKD patients had worse clinical outcomes compared with no-CKD patients post PMVR. CKD was an independent predictor of the primary efficacy endpoint, whereas calcified leaflet was an independent predictor of grade ≥3+ MR at 12 months.

Early results of MitraClip system implantation by real-time three-dimensional speckle-tracking left ventricle analysis.

AIMS: To appraise the early effect of percutaneous mitral valve repair with the MitraClip system on myocardial function using real-time three-dimensional speckle-tracking echocardiography (3D-STE). METHODS: Consecutive patients with moderate-to-severe or severe mitral regurgitation, undergoing mitral valve repair with the MitraClip system, were prospectively evaluated during the peri-procedural workout and follow-up. Left ventricular deformation was evaluated by a two-dimensional and 3D speckle-tracking analysis. 3D-STE acquisitions were elaborated obtaining real-time 3D global longitudinal strain evaluation, and by appraising both volumetric and hemodynamic parameters (i.e. left ventricular end-diastolic volume, left ventricular end-systolic volume, left ventricular ejection fraction, cardiac output, and stroke volume). RESULTS: In all, 30 patients were included. At 1-month follow-up, 3D-STE analysis revealed no changes in left ventricular end-diastolic volume (162.6 ±â€Š73.7 ml at baseline vs. 159.8 ±â€Š64.5 ml at 1-month follow-up; P = 0.63) and a downward trend in left ventricular end-systolic volume (104.7 ±â€Š52.0 vs. 100.1 ±â€Š50.4 ml, respectively; P = 0.06). Left ventricular ejection fraction did not significantly increase (38.1 ±â€Š11.3% at baseline vs. 39.4 ±â€Š11.0% at 1-month follow-up; P = 0.20). No significant changes were reported in cardiac output (4.3 ±â€Š2.0 l/min at baseline vs. 4.0 ±â€Š1.5 l/min at follow-up; P = 0.377) and in stroke volume (59.5 ±â€Š25.5 ml at baseline vs. 59.9 ±â€Š20.7 ml at follow-up; P = 0.867). On the contrary, left ventricular deformation capability significantly improved, with the real-time 3D global longitudinal strain value changing from -9.8 ±â€Š4.1% at baseline to -11.0 ±â€Š4.4% at follow-up (P = 0.018). CONCLUSIONS: Accurately assessing myocardial function by the use of 3D-STE, this study reported irrelevant early changes in left ventricular size, but a positive effect on left ventricular deformation capability following mitral valve repair with the MitraClip system. These preliminary results need to be confirmed in larger series and extended to long-term follow-up.

Gender-related clinical and echocardiographic outcomes at 30-day and 12-month follow up after MitraClip implantation in the GRASP registry.

OBJECTIVES: To assess the influence of patients' gender on the outcomes of percutaneous edge-to-edge mitral valve repair (PMVR) using the MitraClip system. BACKGROUND: Although gender-related differences have been extensively documented in patients who undergo surgery for moderate-to-severe (3+) and severe (4+) mitral regurgitation (MR), studies assessing whether these differences exist after PMVR are lacking. METHODS: Clinical and echocardiographic data through 12-month follow up from 171 consecutive patients whom underwent MitraClip implantation and were dichotomized by the gender (106 males and 65 females) were obtained. The primary safety endpoint was the incidence of major adverse events at 30 days and the primary efficacy endpoint was freedom from death, surgery for mitral valve dysfunction, or grade≥3+ MR at 12-month follow up. RESULTS: The primary safety endpoint was observed in four males (3.8%) and four females (6.2%) (P=0.358). Remarkable reduction in MR postprocedure was revealed in both groups, and these results were mostly sustained. Furthermore, left ventricle reverse remodeling and New York Heart Association (NYHA) functional class improvement were revealed in both groups, but females tended to demonstrate worse results over time (P=0.083). The primary efficacy endpoint obtained by Kaplan-Meier estimates was observed in 76.3 and 70.2%, respectively (log rank P=0.231). CONCLUSIONS: MitraClip implantation in patients with 3+ and 4+ MR is safe and efficacious until mid-term follow up, regardless of patients' gender. Despite improvement in NYHA functional class in both groups, female gender demonstrated a trend toward poorer results. Further validation of our findings is warranted.

Extended use of percutaneous edge-to-edge mitral valve repair beyond EVEREST (Endovascular Valve Edge-to-Edge Repair) criteria: 30-day and 12-month clinical and echocardiographic outcomes from the GRASP (Getting Reduction of Mitral Insufficiency by Percutaneous Clip Implantation) registry.

OBJECTIVES: This study sought to compare, in high-risk patients with 3+ to 4+ mitral regurgitation (MR) dichotomized by baseline echocardiographic features, acute, 30-day, and 12-month outcomes following percutaneous mitral valve repair using the MitraClip. BACKGROUND: The feasibility and mid-term outcomes after MitraClip implantation in patients with echocardiographic features different from the EVEREST (Endovascular Valve Edge-to-Edge Repair) I and II trials have been scarcely studied. METHODS: Clinical and echocardiographic outcomes through 12-month follow-up of consecutive patients who underwent MitraClip implantation were obtained from an ongoing prospective registry. Two different groups, divided according to baseline echocardiographic criteria (investigational group [EVERESTOFF] and control group [EVERESTON]), were compared. RESULTS: Seventy-eight patients were included in EVERESTOFF and 93 patients in EVERESTON groups. Important and comparable acute reductions in MR and no clip-related complications were revealed. The primary safety endpoint at 30 days was comparable between groups (2.6% vs. 6.5%, respectively, p = 0.204); in addition, MR reduction was mostly sustained, whereas equivalent improvement in New York Heart Association functional class were demonstrated. Kaplan-Meier freedom from death, surgery for mitral valve dysfunction, or grade ≥3+ MR at 12 months was demonstrated in 71.4% and 76.2%, respectively, in the EVERESTOFF and EVERESTON groups (log rank p = 0.378). Significant improvements in ejection fraction and reduction in left ventricle volumes were demonstrated in both groups over time, but the baseline between-group differences were sustained. CONCLUSIONS: MitraClip implantation in patients with expanded baseline echocardiographic features, compared with the control group, was associated with similar rates of safety and efficacy through 12-month follow-up. Further validation of our findings is warranted.

Myocardial deformational adaptations to different forms of training: a real-time three-dimensional speckle tracking echocardiographic study.

The hemodynamic load due to physical activity leads to structural and functional cardiac adaptations known as "Athlete's heart". We aimed to compare myocardial performance in different groups of trained athletes by means of 3D echocardiography and 3D speckle tracking echocardiography (3D-STE). 66 athletes [26 strength-trained athletes (STA) and 40 endurance athletes (ETA)] were prospectively enrolled. A control group of 40 sedentary subjects (sedentary group) was also included. All subjects underwent both standard and 3D evaluation of left ventricular (LV) function including 3D-STE. Left ventricular mass indexed for body surface area, LV end-diastolic (LV Dd) thickness of interventricular septum and posterior wall thickness mean values were significantly increased in athletes (p < 0.001, p < 0.01 and p < 0.001, respectively). LV diastolic diameter index had a significantly higher mean value in ETA in respect to sedentary group (p = 0.001). Despite a preserved mean value of LV ejection fraction (LV EF) in all the groups, subjects in STA group showed a significant reduction of strain in the longitudinal, radial and circumferential directions (p < 0.05 for all). Area strain mean value was also reduced in STA group (p < 0.01). In the overall population, an inverse relationship between longitudinal strain and LV Dd index (r = -0.260, p = 0.008), the E/A ratio (r = -0.249, p = 0.010) and the E' velocity (r = -0.259, p = 0.009) has been identified. Sport-specific patterns of ventricular morphological and functional remodeling are present in athletes performing different kinds of training. 3D-STE is a useful and feasible echocardiographic technique for the assessment of sport-specific pattern of deformational adaptations.

Association of tricuspid regurgitation with clinical and echocardiographic outcomes after percutaneous mitral valve repair with the MitraClip System: 30-day and 12-month follow-up from the GRASP Registry.

AIM: The aim of this study was to evaluate the association of baseline tricuspid regurgitation (TR) on the outcomes after percutaneous mitral valve repair (PMVR) with the MitraClip system. METHODS AND RESULTS: Data from 146 consecutive patients with functional mitral regurgitation (MR) were obtained. Two different groups, dichotomized according to the degree of pre-procedural TR (moderate/severe, n = 47 and none/mild, n = 99), had their clinical and echocardiographic outcomes through 12-month compared. At 30-day, the primary safety endpoint was significantly higher in moderate/severe TR compared with none/mild TR (10.6 vs. 2.0%, P = 0.035). Marked reduction in MR grades observed post-procedure were maintained through 12 months. Although NYHA functional class significantly improved in both groups compared with baseline, it was impaired in moderate/severe TR compared with the none/mild TR group (NYHA > II at 30 day: 33.3 vs. 9.2%, P < 0.001; at 1 year: 38.5 vs. 12.3%, respectively, P = 0.006). Left ventricle reverse remodelling and ejection fraction improvement were revealed in both groups. The primary efficacy endpoint at 12-month determined by freedom from death, surgery for mitral valve dysfunction, or grade ≥ 3+ MR was comparable between groups, but combined death and re-hospitalization for heart failure rates were higher in the moderate/severe TR group. Multivariable Cox regression analysis demonstrated that baseline moderate/severe TR and chronic kidney disease were independent predictors of this combined endpoint. CONCLUSIONS: Although PMVR with MitraClip led to improvement in MR, TR, and NYHA functional class in patients with baseline moderate/severe TR, the primary safety endpoint at 30-day was impaired, while moderate/severe TR independently predicted death and re-hospitalization for heart failure at 12-month.