Randomized investigation of the MitraClip device in heart failure: Design and rationale of the RESHAPE-HF2 trial design.

AIMS: The safety and effectiveness of the MitraClip device to treat functional mitral regurgitation (FMR) has been tested in previous clinical trials yielding somewhat heterogeneous results in heart failure (HF) patients. Over time, the MitraClip device system has been modified and clinical practice evolved to consider also less severely diseased HF patients with FMR for this therapeutic option. The RESHAPE-HF2 trial aims to assess the safety and effectiveness of the MitraClip device system on top of medical therapy considered optimal in the treatment of clinically significant FMR in symptomatic patients with chronic HF. METHODS: The RESHAPE-HF2 is an investigator-initiated, prospective, randomized, parallel-controlled, multicentre trial designed to evaluate the use of the MitraClip device (used in the most up-to-date version as available at sites) plus optimal standard of care therapy (device group) compared to optimal standard of care therapy alone (control group). Eligible subjects have signs and symptoms of HF (New York Heart Association [NYHA] class II-IV despite optimal therapy), and have moderate-to-severe or severe FMR, as confirmed by a central echocardiography core laboratory; have an ejection fraction between ≥20% and ≤50% (initially 15-35% for NYHA class II patients, and 15-45% for NYHA class III/IV patients); have been adequately treated per applicable standards, and have received appropriate revascularization and cardiac resynchronization therapy, if eligible; had a HF hospitalization or elevated natriuretic peptides (B-type natriuretic peptide [BNP] ≥300 pg/ml or N-terminal proBNP ≥1000 pg/ml) in the last 90 days; and in whom isolated mitral valve surgery is not a recommended treatment option. The trial has three primary endpoints, which are these: (i) the composite rate of total (first and recurrent) HF hospitalizations and cardiovascular death during 24 months of follow-up, (ii) the rate of total (i.e. first and recurrent) HF hospitalizations within 24 months, and (iii) the change from baseline to 12 months in the Kansas City Cardiomyopathy Questionnaire overall score. The three primary endpoints will be analysed using the Hochberg procedure to control the familywise type I error rate across the three hypotheses. CONCLUSIONS: The RESHAPE-HF2 trial will provide sound evidence on the MitraClip device and its effects in HF patients with FMR. The recruitment was recently completed with 506 randomized patients.

Combined Tricuspid and Mitral Versus Isolated Mitral Valve Repair for Severe MR and TR: An Analysis From the TriValve and TRAMI Registries.

OBJECTIVES: The aim of this study was to retrospectively compare the characteristics, procedural courses, and outcomes of patients presenting with concomitant mitral regurgitation (MR) and tricuspid regurgitation (TR) in the TriValve (Transcatheter Tricuspid Valve Therapies) and TRAMI (Transcatheter Mitral Valve Interventions) registries. BACKGROUND: Transcatheter mitral edge-to-edge valve repair (TMVR) has been shown to be successful in patients with severe MR. Lately, edge-to-edge repair has also emerged as a possible treatment for severe TR in patients at high risk for cardiac surgery. In patients with both severe MR and TR, the yield of concomitant transcatheter mitral and tricuspid valve repair (TMTVR) for patients at high surgical risk is unknown. METHODS: The characteristics, procedural data, and 1-year outcomes of all patients in the international multicenter TriValve registry and the German multicenter TRAMI registry, who presented with both severe MR and TR, were retrospectively compared. Patients in TRAMI (n = 106) underwent isolated TMVR, while those in TriValve (n = 122) additionally underwent concurrent TMTVR in compassionate and/or off-label use. RESULTS: All 228 patients (mean age 77 ± 8 years, 44.3% women) presented with significant dyspnea at baseline (New York Heart Association functional class III or IV in 93.9%), without any differences in the rates of pulmonary hypertension and chronic pulmonary disease. The proportion of patients with left ventricular ejection fraction <30% was higher in the TMVR group (34.9% vs. 18.0%; p < 0.001), while patients in the TMTVR group had lower glomerular filtration rates. At discharge, MR was comparably reduced in both groups. At 1 year, overall all-cause mortality was 34.0% in the TMVR group and 16.4% in the TMTVR group (p = 0.035, Cox regression). On multivariate analysis, TMTVR was associated with a 2-fold lower mortality rate (hazard ratio: 0.52; p = 0.02). The rate of patients in New York Heart Association functional class ≤II at 1 year did not differ (69.4% vs. 67.0%; p = 0.54). CONCLUSIONS: Concurrent TMTVR was associated with a higher 1-year survival rate compared with isolated TMVR in patients with both MR and TR. Further randomized trials are needed to confirm these results.

Double cryoenergy application (freeze-thaw-freeze) at growing myocardium: Lesion volume and effects on coronary arteries late after energy application. Implications for efficacy and safety in pediatric patients.

INTRODUCTION: Cryoenergy is accepted as an alternative to radiofrequency ablation (RFA) in childen for ablation of supraventricular tachycardia substrates. Single cryoenergy application has been shown to be inferior to RFA. Double cryoenergy application has therefore been introduced into clinical practice, but experience concerning efficacy is limited. Coronary artery stenosis has been reported as serious complication after RFA for arrhythmia substrates but not after single cryoablation. The purpose of the study was to assess lesion volume (efficacy) and risk of coronary artery damage (safety), late, that is, 6 months, after double cryoenergy application in a piglet model. METHODS: Two sequential cycles of cryoenergy were delivered at -75°C for 4 minutes at the atrioventricular groove in five piglets. Animals were restudied after 6 months by coronary angiography and intracoronary ultrasound (ICUS). Ablation lesions were examined histologically and lesion volume was determined by three-dimensional morphometric analysis. RESULTS: Cryolesion volume was 174.04 ± 67.18 mm3 for atrial and 238.69 ± 112.1 mm3 for ventricular lesions (P > .05). Ventricular lesions, 4.06 ± 1.05 mm, were significantly deeper than atrial lesions, 3.58 ± 0.78 mm, (P < .05). In two of the 29 lesions, cryoenergy induced minor coronary artery injury with mild medial and adventitial thickening as well as minimal intimal proliferation, which had neither been detected by coronary angiography nor by ICUS. CONCLUSION: Late after double cryoenergy application at growing myocardium, subclinical minor affection of the coronary artery wall could be detected with minimal intimal proliferation. As lifetime sequelae of this finding remains unknown, further studies are warranted to address safety of repeated cycles of cryoenergy application for tachycardia substrates in children.

[Surgical and Interventional Therapy of Mitral Valve Regurgitation]. / Operative und interventionelle Therapie der Mitralinsuffizienz.

Depending from the etiology of mitral valve pathology and surgical risk, mitral valve surgery is the therapy of choice for most degenerative mitral valve diseases. In isolated secondary mitral valve regurgitation, the indication for interventional or conservative therapy becomes more important. In severe left ventricular dysfunction heart transplantation has to be taken into consideration. If relevant coronary artery disease is present and bypass surgery is indicated, mitral valve surgery is mandatory in severe regurgitation and is subject to a benefit-risk evaluation in moderate regurgitation. Decision pathways take multiple aspects into consideration (fig. 4) like comorbidities and physical status of the patient as well as anatomy of the mitral valve and pathology of regurgitation. The choice of they should found after inspection of the patient by a multidisciplinary team consisting of a cardiologist, a cardiac surgeon, an echocardiographer and a cardiac anesthesiologist.

Incidence and Clinical Impact of Device-Associated Thrombus and Peri-Device Leak Following Left Atrial Appendage Closure With the Amplatzer Cardiac Plug.

OBJECTIVES: Routine device surveillance after successful left atrial appendage closure is recommended to evaluate for intermediate to late complications. The aim of this study was to assess the incidence and clinical impact of these complications on cardiovascular events. METHODS: Centers participating in the Amplatzer Cardiac Plug multicenter study were requested to submit their post-procedural transesophageal echocardiograms for independent adjudication. Thirteen of 22 centers contributed all their post-procedural echocardiograms, which included 344 from 605 consecutive patients. These images were submitted to a core laboratory and reviewed by 2 independent experts for peri-device leak, device-associated thrombus, device embolization, device migration, left atrial appendage thrombus, and left atrial thrombus. Clinical events were prospectively collected by each center. RESULTS: Of the 344 transesophageal echocardiograms, 339 were deemed analyzable. Patients' mean age was 74.4 ± 7.5 years, and 67.3% were men. The mean CHADS2 score was 2.7 ± 1.3, the mean CHA2DS2-VASc score was 4.3 ± 1.5, and the mean HAS-BLED score was 3.0 ± 1.2. Amplatzer Cardiac Plug implantation was successful in all patients. Periprocedural major adverse events occurred in 2.4%. Median clinical follow-up duration was 355 days (range 179 to 622 days). Follow-up transesophageal echocardiography was performed after a median of 134 days (range 88 to 227 days). Device-associated thrombus was observed in 3.2% and peri-device leak in 12.5% (5.5% minimal, 5.8% mild, 0.6% moderate, 0.6% severe). Neither device-associated thrombus nor peri-device leak was associated with an increased risk for cardiovascular events. Independent predictors of device-associated thrombus were smoking (odds ratio: 5.79; p = 0.017) and female sex (odds ratio: 4.22; p = 0.027). CONCLUSIONS: Following successful left atrial appendage closure with the Amplatzer Cardiac Plug, the presence of peri-device leak was relatively low, and device-associated thrombus was infrequent. Neither was associated with increased risk for thromboembolism.

Impact of cardiac comorbidities on early and 1-year outcome after percutaneous mitral valve interventions: data from the German transcatheter mitral valve interventions (TRAMI) registry.

AIMS: The use of the MitraClip system has gained widespread acceptance for the treatment of patients with mitral regurgitation (MR) who are not suitable for the conventional surgery. This study sought to investigate the early and 1-year outcome after MitraClip therapy of patients with MR and cardiac comorbidities. METHODS AND RESULTS: Outcomes through 12-month follow-up of patients (n = 528) who underwent MitraClip implantation were obtained from the German transcatheter mitral valve interventions (TRAMI) registry. The majority of these patients (n = 409, 77.5 %) also suffered from coronary artery disease (CAD). Patients with a dilated cardiomyopathy (DCM, n = 65, 12.3 %) or concomitant valvular aortic disease (AV, n = 54, 10.2 %) were less frequent. Although the prevalent pathogenesis was functional MR, patients with DCM had significantly more frequent a functional MR (96.9 %) compared to patients with CAD (74.9 %) or AV (62.5 %, p < 0.001). Technical success was achieved in 97.5 % of patients. Procedural echocardiograms demonstrated in the vast majority of patients a reduction from severe MR III to mild MR I with no difference between the groups (p = 0.83). The peri-procedural complication rate was very low. At 30-day and 12-month follow-up, the majority of patients were in NYHA functional class II or lower. The rate of death, stroke, and myocardial infarction (MACCE) was comparable in the three patient groups during 12-month follow-up (DCM 26.9 %, CAD 30.3 % and AV 27.5 %, p = 0.85). CONCLUSIONS: The MitraClip implantation is feasible and safe even in high-risk patients with MR and cardiac comorbidities.

Predictors of High Post-Procedural Gradients after Catheter-Based Aortic Valve Implantation Using Direct Flow Medical Bioprostheses.

BACKGROUND: The Direct Flow Medical (DFM) valve is a new non-metallic and repositionable bioprosthesis used for transcatheter aortic valve implantation (TAVI). The study aim was to investigate procedural and post-implant valve data in patients receiving differently sized DFM bioprostheses. METHODS: Procedural, echocardiographic and computed tomography findings of 28 patients receiving either a 25, 27 or 29 mm DFM bioprosthesis were analyzed. RESULTS: Implantation of a 29 mm bioprosthesis was associated with longer procedure (p <0.05) and radiation (p <0.05) times, and a higher dose-area product (p <0.01) compared to the 25 mm valve. A high mean post-interventional aortic gradient indicating a suboptimal result was found in 44% patients receiving a 29 mm bioprosthesis, whereas none of the patients with a 25 or 27 mm valve had a high gradient (p <0.05). Aortic valve calcification was greatest in the 29 mm group and correlated with a higher dose-area product (p <0.01). CONCLUSIONS: DFM bioprosthesis size significantly influences the TAVI procedure and post-implant valve function. Valve calcification and use of the 29 mm DFM bioprosthesis per se possibly predict a more complicated procedure. Therefore, annulus size and valve calcification severity should be taken into consideration when deciding which bioprosthesis type might be best suited for individual patients.

Impact of Preprocedural Left Ventricular Ejection Fraction on 1-Year Outcomes After MitraClip Implantation (from the ACCESS-EU Phase I, a Prospective, Multicenter, Nonrandomized Postapproval Study of the MitraClip Therapy in Europe).

This report describes the 12-month outcomes of the a prospective, multicenter, nonrandomized post-approval study of the MitraClip therapy in Europe (ACCESS-EU postapproval study of MitraClip therapy) with respect to preprocedural left ventricular ejection fraction (LVEF). Transcatheter deployment of the MitraClip device may be considered for patients who are not suitable for conventional surgery. A total of 567 patients with significant mitral regurgitation (MR) underwent MitraClip therapy. Of those, 393 had functional MR (FMR) and were subdivided by preprocedural LVEF (A: 10% to 20%, B: >20% to 30%, C: >30% to 40%, D: >40%). Procedural safety and efficacy and treatment outcomes including MR grade, New York Heart Association (NYHA) functional class, 6-minute walk test, and the Minnesota Living with Heart Failure Questionnaire were analyzed at baseline, 30 days, and 12 months. Baseline mean logistic EuroSCORE was 25 ± 19; 87% of patients were in NYHA classes III or IV (A: 96%, B: 83%, C: 90%, D: 86%). There was no incidence of death or stroke intraprocedurally. Eleven patients died within 30 days with no differences among subgroups. Kaplan-Meier survival at 12 months was 81.8% (A: 71%, B: 79%, C: 87%, D: 86%). There was a significant improvement in MR severity at 30 days and 12 months (p <0.0001). At 12 months, all subgroups experienced similar improvements in NYHA class, 6-minute walk test, and Minnesota Living with Heart Failure Questionnaire. This real-world registry reports promising results of MitraClip therapy in patients with FMR. In conclusion, the low rates of hospital mortality and adverse events in patients with FMR-even in patients with severely reduced LVEF-provide additional evidence of substantial benefits after MitraClip implantation.

Gender in the ACCESS-EU registry: a prospective, multicentre, non-randomised post-market approval study of MitraClip® therapy in Europe.

AIMS: Gender has been an important factor in outcomes after mitral valve surgery; however, its effect on percutaneous mitral valve repair is not well known. We aimed to report the effect of gender on outcomes in a large European prospective, multicentre, non-randomised post-approval study of percutaneous mitral valve repair. METHODS AND RESULTS: Two hundred and five female and 362 male patients with significant mitral regurgitation underwent percutaneous repair at 14 European sites from October 2008 to April 2011. Women and men had similar baseline risk scores, but women had a higher rate of degenerative disease (32% vs. 18%). Women were more likely to have one clip implanted (72% vs. 54%), but had a similar length of stay in the intensive care unit (2.6±4.1 days) and overall length of stay (8.0±6.9 days) compared to men. They were also less likely to be discharged home: more women than men went to skilled nursing facilities (25% vs. 15%) and fewer women went home compared to men (71.9% vs. 83.9%). Thirty-day and 12-month safety results were similar between genders, as was 12-month efficacy (echocardiographic and clinical). Multivariate analysis showed no effect of gender on 12-month survival. CONCLUSIONS: In a real-world, post-approval experience in Europe, female patients who underwent percutaneous mitral valve repair experienced safety and efficacy results similar to those of males. However, the discharge rates to skilled nursing facilities rather than home may indicate a need for better optimisation of the female patient's physical and social comorbidities prior to intervention and during the hospitalisation period.

One-year outcomes and predictors of mortality after MitraClip therapy in contemporary clinical practice: results from the German transcatheter mitral valve interventions registry.

AIMS: The transcatheter mitral valve interventions (TRAMI) registry was established in order to assess safety and efficacy of catheter-based mitral valve interventional techniques in Germany, and prospectively enrolled 828 MitraClip patients (median age 76 years, median log. EuroSCORE I 20.0%) between August 2010 and July 2013. We present the 1-year outcome in this MitraClip cohort-which is the largest published to date. METHODS AND RESULTS: Seven forty-nine patients (90.5%) were available for 1-year follow-up and included in the following analyses. Mortality, major adverse cardiovascular event rates, and New York Heart Association (NYHA) classes were recorded. Predictors of 1-year mortality were identified by multivariate analysis using a Cox regression model with stepwise forward selection. The 1-year mortality was 20.3%. At 1 year, 63.3% of TRAMI patients pertained to NYHA functional classes I or II (compared with 11.0% at baseline), and self-rated health status (on EuroQuol visual analogue scale) also improved significantly by 10 points. Importantly, a significant proportion of patients regained the complete independence in self-care after MitraClip implantation (independence in 74.0 vs. 58.6% at baseline, P = 0.005). Predictors of 1-year mortality were NYHA class IV (hazard ratio, HR 1.62, P = 0.02), anaemia (HR 2.44, P = 0.02), previous aortic valve intervention (HR 2.12, P = 0.002), serum creatinine ≥1.5 mg/dL (HR 1.77, P = 0.002), peripheral artery disease (HR 2.12, P = 0.0003), left ventricular ejection fraction <30% (HR 1.58, P = 0.01), severe tricuspid regurgitation (HR 1.84, P = 0.003), and procedural failure (defined as operator-reported failure, conversion to surgery, failure of clip placement, or residual post-procedural severe mitral regurgitation) (HR 4.36, P < 0.0001). CONCLUSIONS: Treatment of significant MR with MitraClip resulted in significant clinical improvements in a high proportion of TRAMI patients after 12 months. In the TRAMI cohort, the failure of procedural success exhibited the highest hazard ratio concerning the prediction of 1-year mortality.

Impact of the learning curve on outcome after transcatheter mitral valve repair: results from the German Mitral Valve Registry.

AIMS: This analysis from the German Mitral Valve Registry investigates the impact of the learning curve with the MitraClip(®) technique on procedural success and complications. METHODS AND RESULTS: Consecutive patients treated since 2009 in centers that performed more than 50 transcatheter mitral repairs were included. Results of the first half of the patients were compared to those of the second. Altogether 496 patients from 10 centers were included. Patients treated later had less common severe heart failure symptoms (patients with NYHA IV: 22.1 vs. 14.5 %, p < 0.05). The EuroSCORE I (22.0 vs. 23.0 %, p = ns) and Society of Thoracic Surgeons (STS) score (7.5 vs. 9.5 %, p = ns) did not differ between both groups. Procedural success was 95.6 % (238/249) in the first cases and 94.7 % (232/245, p = ns) subsequently. Also procedural time (104.3 vs. 119 min, p = ns) and complications did not decrease over time. CONCLUSION: A learning curve using the MitraClip(®) device does not appear to significantly affect acute MR reduction, hospital and 30-day mortality. Most likely, the proctor system leads to already high initial procedure success and relatively short procedure time.

Failure of acute procedural success predicts adverse outcome after percutaneous edge-to-edge mitral valve repair with MitraClip.

AIMS: MitraClip implantation is evolving as a potential alternative treatment to conventional surgery in high-risk patients with significant mitral regurgitation (MR). However, outcome predictors are under-investigated. The aim of this study was to identify predictors of midterm mortality and heart failure rehospitalisation after percutaneous mitral valve repair with MitraClip. METHODS AND RESULTS: A total of 150 consecutive patients were followed for a median of 463 days. Survival analyses were performed for baseline characteristics, risk scores and failure of acute procedural success (APS) defined as persisting MR grade 3+ or 4+. Univariate significant risk stratifiers were tested in multivariate analyses using a Cox proportional hazards model. Overall survival was 96% at 30 days, 79.5% at 12 months, and 62% at two years. Multivariate analysis identified APS failure (HR 2.13, p=0.02), NYHA Class IV at baseline (HR 2.11, p=0.01) and STS score ≥12 (HR 2.20, p<0.0001) as significant independent predictors of all-cause mortality, and APS failure (HR 2.31, p=0.01) and NYHA Class IV at baseline (HR 1.89, p=0.03) as significant independent predictors of heart failure rehospitalisation. Furthermore, a post-procedural significant decrease in hospitalisation rate could only be observed after successful interventions (0.89±1.07 per year before vs. 0.54±0.96 after implantation, p=0.01). Patients with severely dilated and overloaded ventricles who did not meet EVEREST II eligibility criteria were at higher risk of APS failure. CONCLUSIONS: The failure of acute procedural success proved to have the most important impact on outcome after MitraClip implantation.

Percutaneous mitral valve repair with the MitraClip system according to the predicted risk by the logistic EuroSCORE: preliminary results from the German Transcatheter Mitral Valve Interventions (TRAMI) Registry.

OBJECTIVE: To evaluate in-hospital and short-term outcomes of percutaneous mitral valve repair according to patients' logistic EuroSCORE (logEuroSCORE) in a multicenter registry BACKGROUND: The logEuroSCORE is an established tool to predict the risk of mortality during cardiac surgery. In high-risk patients percutaneous mitral valve repair with the MitraClip system represents a less-invasive alternative METHODS: Data from 1002 patients, who underwent percutaneous mitral valve repair with the MitraClip system, were analyzed in the German Transcatheter Mitral Valve Interventions (TRAMI) Registry. A logEuroSCORE (mortality risk in %) ≥ 20 was considered high risk RESULTS: Of all patients, 557 (55.6%) had a logEuroSCORE ≥ 20. Implantation of the MitraClip was successful in 95.5 % (942/986) patients. Moderate residual mitral valve regurgitation was more often detected in patients with a logEuroSCORE ≥ 20 (23.8% vs. 17.1%, respectively, P < 0.05). In patients with a logEuroSCORE ≥ 20 the procedural complication rate was 8.9% (vs. 6.4, n.s.) and the in-hospital MACCE rate 4.9% (vs. 1.4% P < 0.01). The in-hospital mortality rate in patients with a logEuroSCORE ≥ 20 and logEuroSCORE < 20 was 4.3 and 1.1%, respectively (P ≤ 0.01) CONCLUSION: Percutaneous mitral valve repair with the MitraClip system is feasible in patients with a logEuroSCORE ≥ 20 with similar procedural results compared to patients with lower predicted risk. Although mortality was four times higher than in patients with logEuroSCORE < 20, mortality in high risk patients was lower than predicted. In those with a logEuroSCORE ≥ 20, moderate residual mitral valve regurgitation was more frequent.

Uncommon delayed and late complications after percutaneous left atrial appendage closure with Amplatzer(®) Cardiac Plug.

AIMS: Percutaneous left atrial appendage closure with Amplatzer(®) Cardiac Plug (St. Jude Medical Inc.) for the prevention of stroke in patients with atrial fibrillation is rapidly propagating. We sought to provide additional safety data. METHODS AND RESULTS: We have screened our database of patients having been treated with Amplatzer(®) Cardiac Plug and found 3 cases with uncommon complications that have not been reported previously. One patient experienced an embolisation of the occluder about 12 months after implantation that potentially resulted from mismatch of occluder size and landing zone. Another patient developed cardiac tamponade 9 days after implantation. This case of delayed effusion was probably not a result of interventional trauma, but might have been provoked by scratching of the inner pericardial membrane. A third patient developed a large thrombus in the left atrium which was considered to be caused by injury of the endothelial wall during implantation. The first two cases could be treated by a percutaneous procedure, the last case by cardiac surgery without any sequelae. CONCLUSIONS: Complications after left atrial appendage closure not related to a device-related thrombus can occur later after implantation. With appropriate percutaneous or surgical management these complications can be handled without sequelae.

Clinical outcomes through 12 months in patients with degenerative mitral regurgitation treated with the MitraClip® device in the ACCESS-EUrope Phase I trial.

OBJECTIVES: Percutaneous treatment with the MitraClip device represents an alternative option for selected patients with degenerative mitral regurgitation (DMR) considered ineligible for surgery due to contraindications or high surgical risk by an inter-disciplinary heart team. We describe 12-month outcomes following treatment with the MitraClip device in DMR patients. METHODS: The MitraClip Therapy Economic and Clinical Outcomes Study Europe (ACCESS-EU) Study has completed the enrolment of 567 patients as of April 2011, 117 of whom were DMR. Baseline demographics, procedural and acute safety results at 30 days and survival at 12 months were evaluated in the DMR subset. Effectiveness results, defined by a reduction in MR, and improvement in clinical outcomes based on changes in New York Heart Association (NYHA) functional Class, 6-min walk test (6MWT) and quality-of-life data were also assessed. Furthermore, DMR patients were stratified into high- and low-risk subgroups (logistic European System of Cardiac Operative Risk Evaluation I (logEuroSCORE I ≥20% or <20%, respectively) and differentially evaluated. RESULTS: One hundred and seventeen DMR patients underwent the MitraClip procedure with a 94.9% rate (111 of 117) of successful clip implantation. Baseline characteristics and comorbidities included NYHA Class III/IV (74%), left ventricular ejection fraction (LVEF) <40% (9%), prior cardiac surgery (24%) and prior myocardial infarction (MI) (22%). Mean logEuroSCORE I was 15.5 ± 13.3%. Mortalities at 30 days and 12 months were 6.0 and 17.1%, respectively. At 12 months, 74.6% (53 of 71) of patients in follow-up achieved MR ≤grade 2+ and 80.8% (63 of 78) were in NYHA functional class I/II. Both Minnesota Living with Heart Failure questionnaire (MLHFQ) scores and 6MWT distance improved significantly at 12 months compared with baseline (P = 0.03 and P < 0.0001, respectively). CONCLUSIONS: The MitraClip procedure resulted in significant reductions in MR and improvements in clinical outcomes at 12 months in selected patients with severe DMR. MitraClip therapy may serve as a complementary non-surgical therapeutic option for DMR patients who are considered at high risk or ineligible for surgery by an inter-disciplinary dedicated heart team. Interventional treatment should be indicated following the discussion of patients in an inter-disciplinary conference of cardiologists and cardiac surgeons as suggested by current international guidelines.

Percutaneous mitral valve interventions in the real world: early and 1-year results from the ACCESS-EU, a prospective, multicenter, nonrandomized post-approval study of the MitraClip therapy in Europe.

OBJECTIVES: The purpose of this article is to report early and mid-term outcomes of the ACCESS-EU study (ACCESS-Europe A Two-Phase Observational Study of the MitraClip System in Europe), a European prospective, multicenter, nonrandomized post-approval study of MitraClip therapy (Abbott Vascular, Inc., Santa Clara, California). BACKGROUND: MitraClip has been increasingly performed in Europe after approval; the ACCESS-EU registry provides a snapshot of the real-world clinical demographic data and outcomes. METHODS: A total of 567 patients with significant mitral valve regurgitation (MR) underwent MitraClip therapy at 14 European sites. Mean logistic European System for Cardiac Operative Risk Evaluation at baseline was 23.0 ± 18.3; 84.9% patients were in New York Heart Association functional class III or IV, and 52.7% of patients had an ejection fraction ≤40%. RESULTS: The MitraClip implant rate was 99.6%. A total of 19 patients (3.4%) died within 30 days after the MitraClip procedure. The Kaplan-Meier survival at 1 year was 81.8%. Intensive care unit and hospital length of stay was 2.5 ± 6.5 days and 7.7 ± 8.2 days, respectively. Single leaflet device attachment was reported in 27 patients (4.8%). There were no MitraClip device embolizations. Thirty-six subjects (6.3%) required mitral valve surgery within 12 months after the MitraClip implant procedure. There was improvement in the severity of MR at 12 months, compared with baseline (p < 0.0001), with 78.9% of patients free from MR, severity of >2+ at 12 months. At 12 months, 71.4% of patients had New York Heart Association functional class II or class I. Six-min-walk-test improved 59.5 ± 112.4 m, and Minnesota-living-with-heart-failure score improved 13.5 ± 20.5 points. CONCLUSIONS: In the real-world, post-approval experience in Europe, patients undergoing the MitraClip therapy are high-risk, elderly patients, mainly affected by functional MR. In this patient population, the MitraClip procedure is effective with low rates of hospital mortality and adverse events.

Acute outcomes after MitraClip therapy in highly aged patients: results from the German TRAnscatheter Mitral valve Interventions (TRAMI) Registry.

AIMS: The influence of age on baseline demographics and outcomes of patients selected for MitraClip has not been previously investigated. METHODS AND RESULTS: Baseline demographics and acute outcomes in 1,064 patients from the German TRAMI registry were stratified by age (525 patients ≥76 years and 539 patients <76 years). In elderly patients, logistic EuroSCORE was higher (25[15-40]% vs. 18[10-31]%, p<0.0001) and the proportion of women was greater (47.2% vs. 29.3%, p<0.0001). Elderly patients were more likely to have preserved left ventricular ejection fraction >50% (40.1% vs. 21.8%, p<0.0001) and degenerative mitral regurgitation (DMR, 35.3% vs. 25.6%, p<0.01). Age was the most frequent reason for non-surgical treatment in the elderly (69.4% vs. 36.1%, p<0.0001). The intrahospital MACCE (death, myocardial infarction, stroke) was low in both groups (3.5% vs. 3.4%, p=0.93) and the proportion of non-severe mitral regurgitation at discharge was similar (95.8% vs. 96.4%, p=0.73). A logistic regression model did not reveal any significant impact of age on acute efficacy and safety of MitraClip therapy. In both groups, the majority of patients were discharged home (81.8% vs. 86.2%, p=0.06). CONCLUSIONS: Elderly and younger patients have similar benefits from MitraClip therapy. Age was the most frequent cause for denying surgery in elderly patients.

Double cryoenergy application (freeze-thaw-freeze) at growing myocardium: lesion volume and effects on coronary arteries early after energy application. Implications for efficacy and safety in pediatric patients.

INTRODUCTION: Data on radiofrequency current application (RFA) at growing myocardium suggest that coronary artery stenosis may occur with a low incidence. Cryoenergy has emerged as an effective alternative to RFA. Although already used in clinical practice, experience with cryoenergy is low due to lack of data concerning effects of a modified double cryoenergy application, a freeze-thaw-freeze cycle, at growing myocardium. Purpose of the study was to assess lesion volume (efficacy) and risk of coronary artery damage (safety) early, 48 hours, after modified double cryoenergy application in a piglet model. METHODS AND RESULTS: In 5 piglets, following selective coronary angiography, two sequential cycles of cryoenergy were delivered at -75 °C for 4 minutes, interrupted by thawing for one minute, at the atrioventricular groove. Piglets were restudied after 48 hours by coronary angiography and intracoronary ultrasound (ICUS). Ablation lesions were examined morphologically and lesion volume was determined by 3-dimensional morphometric analysis. Lesion volume was 109.21 ± 39.61 mm(3) for atrial and 150.30 ± 53.21 mm(3) (P = 0.02) for ventricular lesions. Lesion depth was not significantly different for atrial, 3.07 ± 1.08 mm, versus ventricular lesions, 3.56 ± 1.3 mm. Cryoenergy induced minor coronary artery damage with medial and adventitial necrosis but a preserved intimal layer was present in 2/31 lesions, which had not been detected by coronary angiography or ICUS. CONCLUSION: Early after double cryoenergy application, subclinical minor changes of the coronary artery wall could be detected occasionally whereas the intimal layer remained intact. These findings may have implications on efficacy and safety when cryoenergy is applied for tachycardia substrates in pediatric patients.

Complete interventional heart repair of multiple concomitant cardiac pathologies in a staged approach.

OBJECTIVES AND BACKGROUND: The evidence of multiple percutaneous cardiac procedures in patients with numerous concomitant cardiac pathologies is limited. METHODS AND RESULTS: We report on the case of a 90-year-old male patient presenting with advanced heart failure because of degenerative aortic valve stenosis and degenerative mitral valve regurgitation. Moreover, significant coronary artery disease and intolerance of anticoagulation in atrial fibrillation were present. The patient was rejected from surgery because of age and frailty and underwent a staged interventional procedure with percutaneous coronary intervention, followed by transfemoral aortic valve implantation with Edwards Sapien XT, percutaneous mitral valve repair with MitraClip, and left atrial appendage closure with Amplatzer Cardiac Plug. The last procedure was complicated by pericardial tamponade necessitating pericardial drainage. Eight weeks later, the patient reported on the absence of dyspnea in activities of daily living and a significant gain in quality of live. CONCLUSIONS: The case demonstrates feasibility of a staged interventional approach in a select high-risk patient.