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.

Impact of left atrial diameter on outcome in patients undergoing edge-to-edge mitral valve repair: results from the German TRAnscatheter Mitral valve Interventions (TRAMI) registry.

BACKGROUND: Left atrial (LA) dimension is a marker of disease severity and outcome in primary and secondary mitral regurgitation. In transcatheter mitral valve repair, LA enlargement might additionally impact on device handling and technical success through an altered anatomy and atrial annular dilatation. METHODS AND RESULTS: Data from the multicentre German TRAnscatheter Mitral valve Interventions registry (TRAMI) were used to analyse the association of baseline LA diameter by tertiles with efficacy, safety and long-term clinical outcome in patients undergoing edge-to-edge repair with MitraClip. In 520 of 843 patients prospectively enrolled in TRAMI, baseline LA diameter were reported [median (interquartile range) LA diameter in tertiles: 44 (40-46) mm, 51 (48-53) mm and 60 (55-66) mm]. Larger LA diameters were significantly associated with secondary aetiology of mitral regurgitation, lower ejection fraction, larger left ventricle, male sex and atrial fibrillation (all P < 0.05). Technical success was not different across tertiles (96%, 95.4% and 98.4%, respectively; P = 0.43) as were major in-hospital cardiovascular and cerebral adverse events (mortality, myocardial infarction or stroke: 1.8%, 1.2% and 4.4%, respectively; P = 0.11 across tertiles). However, 4-year mortality significantly increased with larger LA diameter (32.9%, 46.4% and 51.7%, respectively; P < 0.01), as did hospitalization in survivors (60%, 67.6% and 78.9%, respectively; P < 0.05). The association between LA diameter and outcome remained significant after multivariable adjustment including baseline left ventricular end-diastolic diameter. CONCLUSION: Left atrial enlargement is a strong and independent predictor of adverse long-term outcome after transcatheter mitral valve repair. Further study is warranted to examine whether timely intervention may have the potential to modify outcome.

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.

Left atrial appendage occlusion for stroke despite oral anticoagulation (resistant stroke). Results from the Amplatzer Cardiac Plug registry.

INTRODUCTION AND OBJECTIVES: Despite the efficacy of oral anticoagulant (OAC) therapy, some patients continue to have a high residual risk and develop a stroke on OAC therapy (resistant stroke [RS]), and there is a lack of evidence on the management of these patients. The aim of this study was to analyze the safety and efficacy of left atrial appendage occlusion (LAAO) as secondary prevention in patients with nonvalvular atrial fibrillation who have experienced a stroke/transient ischemic attack despite OAC treatment. METHODS: We analyzed data from the Amplatzer Cardiac Plug multicenter registry on 1047 consecutive patients with nonvalvular atrial fibrillation undergoing LAAO. Patientes with previous stroke on OAC therapy as indication for LAAO were identified and compared with patients with other indications. RESULTS: A total of 115 patients (11%) with RS were identified. The CHA2DS2-VASc and the HAS-BLED score were significantly higher in the RS group (respectively 5.5±1.5 vs 4.3±1.6; P <.001; 3.9±1.3 vs 3.1±1.2; P <.001). No significant differences were observed in periprocedural major safety events (7.8 vs 4.5%; P=.1). With a mean clinical follow-up of 16.2±12.2 months, the observed annual stroke/transient ischemic attack rate for the RS group was 2.6% (65% risk reduction) and the observed annual major bleeding rate was 0% (100% risk reduction). CONCLUSIONS: Patients with RS undergoing LAAO showed similar safety outcomes to patients without RS, with a significant reduction in stroke/transient ischemic attack and major bleeding events during follow-up. Adequately powered controlled trials are needed to further investigate the use of LAAO in RS patients.

Implantation of one versus two MitraClips in the German TRAMI registry: Is more always better?

OBJECTIVES: To compare baseline characteristics and outcomes in patients treated with either 1 or 2 MitraClips in the German TRAMI (Transcatheter Mitral Valve Interventions) registry. BACKGROUND: The MitraClip community seems to silently assume that results should intrinsically be better after implantation of more than one clip, although data is still sparse. METHODS: In 2010-2013, 803 patients were enrolled prospectively into TRAMI (461 one-clip and 312 two-clip procedures). Follow-up was performed centrally at 30 days and 1 year. RESULTS: Baseline characteristics of TRAMI-patients with two clips differed significantly from single-clip patients regarding constitutional (more men, taller body height) and heart failure-related factors (larger left ventricular dimensions, reduced left ventricular ejection fraction, more severe heart failure). Also, a significant increase in two-clip procedures over time was present. After propensity score matching for differing baseline characteristics, residual moderate mitral regurgitation (MR) occurred more frequently after implantation of two clips, whereas residual severe MR could more frequently be observed after one-clip procedures. However, no or mild residual MR at discharge was present in 71.6% after single-clip and in 70.1% after two-clips implantation (p = .81). After 1 year, no significant differences regarding mortality or New York Heart Association status could be detected in the propensity matched cohorts. However, TRAMI-patients treated with two clips had a significantly higher incidence of cerebral-vascular events (p = .02). CONCLUSIONS: TRAMI data cannot support the theory that implantation of more than one clip is associated with better clinical outcomes. The finding of more cerebral-vascular events after two-clip procedures might be hypothesis-generating.

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.

Percutaneous treatment of mitral regurgitation in patients with impaired ventricular function: Impact of intracardiac electronic devices (from the German Transcatheter Mitral Valve Interventions Registry).

OBJECTIVES: To identify prevalence/impact of previous implantation of cardiac electronic devices (CEDs), such as cardioverter defibrillator (ICD) and cardiac resynchronization (CRT), in a group of MitraClip (MC) candidates with LVEF < 30%. BACKGROUND: MC therapy is nowadays often considered in patients with depressed left ventricular ejection fraction (LVEF%) and symptomatic severe secondary MR. METHODS: Data from the German Transcatheter Mitral Valve Interventions (TRAMIs) registry were analyzed. Patients with pre-procedural LVEF <30% were selected and divided according to the presence of CEDs. Pre-procedural, peri-procedural, and 1-year follow-up data were analyzed. RESULTS: Out of 689 MC patients, 235 had LVEF<30%. Of these, 23% (54/235) had CRT, 36.6% (86/235) ICD, and 40.4% (95/235) had no CEDs. Risk profile was similar (median STS score CRT 6.0 (IQR: 3.0-12.0); ICD 7.0 (IQR: 4.0-12.0); No-CED 6.5 (IQR: 2.0-10.0); p = 0.8). No procedural mortality was observed and hospital mortality was 5.6% in CRT, 2.3% in ICD, and 3.2% in No-CED (p = 0.5). At discharge, severe MV regurgitation was reported in 3.8% of CRT, 3.7% of ICD, and 1.1% of No-CED (p = 0.9). One year estimated survival (CRT 75.7%; ICD 75.8%; No-CED 78%; p = 0.94) and freedom from MACCE (CRT 73.6%; ICD 75.8%; No-CED 74.5%; p = 0.88) were similar. CONCLUSIONS: A third of patients have been already submitted to CEDs implantation at time of referral for MC therapy and 40% of those with severely depressed LVEF% arrive to MC therapy before ICD/CRT implantation. The presence of CED does not impair acute MC therapy success. Mid-term follow-up outcomes are similar in patients with and without CEDs.

Long-term outcome, survival and predictors of mortality after MitraClip therapy: Results from the German Transcatheter Mitral Valve Interventions (TRAMI) registry.

BACKGROUND: MitraClip therapy is increasingly used in patients deemed inoperable to treat severe mitral regurgitation (MR), but long-tern data is scarce. AIMS: The multicentre, industry-independent German Transcatheter Mitral Valve Interventions (TRAMI) registry comprises the largest prospectively enrolled cohort of patients treated by MitraClip therapy. The current analysis is focusing on long-term mortality rates, cardiac rehospitalization and reintervention. METHODS AND RESULTS: Long-term follow-up (median time 1037 days) in the TRAMI registry was available for 722 patients treated at 20 German centres. Improvements in New York Heart Association (NYHA) functional class (I/II long-term: 65% vs. 1-year follow-up: 63.3%) and self-rated health-status (EuroQuol visual analogue scale [EQ VAS] long-term: 60 [50-70] vs. 1-year follow-up: 60 [50; 70]) were pertained over time. Estimated mortality rates by Kaplan-Meier method were 19.7% for 1-year, 31.9% for 2-year and 53.1% for 4-year follow-up without differences found for MR aetiology. Multivariable Cox-regression analysis identified previous aortic valve implantation (hazard ratio [HR] = 2.21; p < 0.0001), NYHA class IV (HR = 1.78; p < 0.001), prior cardiac decompensation (HR = 1.63; p < 0.001), creatinine > 1.5 mg/dl (HR = 1.63; p < 0.0001) and left ventricular ejection fraction < 30% (HR = 1.60; p < 0.001) as most predictive for long-term mortality. CONCLUSIONS: Long-term outcome in the TRAMI registry confirmed lasting clinical improvements and low intervention rates. Long-term mortality was strongly influenced by cardiac and non-cardiac co-morbidities and was found comparable for both MR aetiologies.

Implication of pulmonary hypertension in patients undergoing MitraClip therapy: results from the German transcatheter mitral valve interventions (TRAMI) registry.

AIMS: We sought to evaluate the impact of pulmonary hypertension on outcomes following MitraClip therapy. METHODS AND RESULTS: The 643 patients in the TRAnscatheter Mitral valve Interventions (TRAMI) registry were divided into three groups according to echocardiographically graded systolic pulmonary artery pressure (sPAP) (Group 1: patients with sPAP of ≤36 mmHg; Group 2: patients with sPAP of 37-50 mmHg; Group 3: patients with sPAP of >50 mmHg) and followed for 1 year. Recent cardiac decompensation, aortic valve disease and tricuspid valve insufficiency were observed more frequently in patients with higher sPAP. Furthermore, logEuroSCORE, Society of Thoracic Surgeons score and age were higher with rising sPAP values. No differences were observed in mitral regurgitation (MR) severity, co-morbidities or clinical findings (New York Heart Association class, 6-min walking distance). Reduction to MR of grade 1 or lower was achieved more often in patients with lower sPAP levels (P = 0.01). In Groups 2 and 3, sPAP was reduced significantly. Major adverse cardiac or cardiovascular events (MACCEs) occurring in hospital (death, myocardial infarction, stroke; <4% in each group), as well as 30-day rates of MACCEs (6.1% in Group 1, 11.9% in Group 2, 12.4% in Group 3) and rehospitalization (18.9% in Group 1, 24.8% in Group 2, 24.8% in Group 3) did not differ significantly. At 1 year, differences in rates of mortality and MACCEs (20.3% in Group 1, 33.1% in Group 2, 34.7% in Group 3; P < 0.01) were significant. Both Groups 2 [hazard ratio (HR) 1.81, P = 0.0122] and 3 (HR 1.85, P = 0.0092) were independently predictive of death. Rehospitalization rates did not differ during follow-up. CONCLUSIONS: Despite higher mortality in patients with elevated sPAP, these data suggest the safety, feasibility and benefit of MitraClip therapy even in advanced stages of disease. An early approach might prevent the progress of pulmonary hypertension and improve outcomes.

Left Atrial Appendage Occlusion in Patients With Atrial Fibrillation and Previous Major Gastrointestinal Bleeding (from the Amplatzer Cardiac Plug Multicenter Registry).

History of major gastrointestinal (GI) bleeding may represent a frequent clinical indication for left atrial appendage occlusion (LAAO) in patients with non-valvular atrial fibrillation (AF). This study aims to investigate the procedural safety and long-term outcome of patients with previous major GI bleeding (MGIB) who underwent LAAO. Data from the Amplatzer Cardiac Plug multicenter registry on 1,047 patients were analyzed. Patients with previous MGIB as indication for LAAO were compared with patients without previous MGIB. A total of 151 patients (14.4%) with previous MGIB were identified. Periprocedural major bleeding events were more frequent in patients with previous MGIB (4.0% vs 0.8%, p = 0.001). With an average follow-up of 1.3 years, the observed annual rate of stroke/transient ischemic attack and major bleeding for patients with previous MGIB were 2.1% (61.4% relative reduction according to the Congestive Heart failure, Hypertension, Age ≥75 (doubled), Diabetes, Stroke (doubled), Vascular disease, Age 65-74, and Sex (female) [CHA2DS2-VASc] score) and 4.6% (20.1% relative reduction according to the expected rate based on the Hypertension, Abnormal renal/liver function (1 point each), Stroke, Bleeding history or predisposition, Labile INR, Elderly (>65 years), Drugs/alcohol concomitantly (1 point each) [HAS-BLED] score), respectively. In conclusion, in patients with non-valvular atrial fibrillation and previous MGIB, LAAO was associated with a low annual rate of stroke/transient ischemic attack. Periprocedural major bleeding events were more frequent in this specific population although the annual major bleeding rate showed a 20.1% relative risk reduction according to the HAS-BLED score.

Long-term outcomes after TAVI in patients with different types of aortic stenosis: the conundrum of low flow, low gradient and low ejection fraction.

AIMS: The objective of this study was to examine the impact of guideline-defined subtypes of severe aortic stenosis (AS) on long-term outcomes after TAVI. METHODS AND RESULTS: Four hundred (400) consecutive patients who underwent TAVI (203 transapical, 197 transfemoral) at our institution 8/2008-3/2013 were followed systematically (for up to seven years). One hundred and forty-seven (147) individuals suffered from NEF-HG AS (LV-EF ≥50%, high Pmean ≥40 mmHg), 63 from LEF-HG AS (LV-EF <50%, high gradient), 77 from PLF-LG AS (LV-EF ≥50%, low gradient, stroke volume index [SVI] <35 ml/m²), and 81 from LEF-LG AS (LV-EF <50%, low gradient). LEF-LG status was associated with the highest all-cause and cardiovascular mortality and MACCE rate, whereas NEF-HG patients exhibited the best outcome (i.e., median survival 5.1 years in NEF-HG vs. 1.3 years in LEF-LG, p=0.0006; or vs. 3.3 years in PLF-LG, p=0.02). In multivariate analysis, LEF-LG status emerged as the outcome predictor with the highest hazard ratio for all-cause mortality (HR 2.86, p=0.003), cardiovascular mortality (HR 6.53, p<0.0001), and MACCE (HR 2.44, p=0.007), whereas neither baseline EF nor SVI <35 ml/m² independently predicted these endpoints. CONCLUSIONS: These findings suggest that an assessment of LV-EF alone for outcome prediction after TAVI is inadequate; it is the guideline-defined subtype of AS that determines outcome.

[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.

Combined mitro-aortic pathology: impact of previous aortic valve replacement upon outcomes of MitraClip therapy (from the German transcatheter mitral valve interventions registry).

AIMS: The aim of this study was to identify the impact of previous aortic valve replacement (AVR) in MitraClip (MC) patients. METHODS AND RESULTS: Data from the German transcatheter mitral valve interventions (TRAMI) registry were analysed in the light of previous AVR by means of either standard AVR (SAVR) or transcatheter AVR (TAVR). Out of 791 MC patients, 68 (8.6%) had been submitted to AVR (68.4% SAVR and 31.6% TAVR). The AVR group was significantly older (77.2±8.0 years vs. 75.1±8.6 years; p<0.05) and had a trend towards a higher risk profile (median STS score 10 [8.0-12.0] vs. 6.0 [3.0-11.0]; p=0.1). No procedural mortality was observed. Severe residual MV regurgitation was reported in 6.2% of AVR vs. 3.7% of the no-AVR patients (p=0.1). Thirty-day mortality was 10.6% in the previous AVR group vs. 3.9% in the no-AVR group (p<0.05). One-year estimated survival was lower in the AVR group (AVR 63% vs. no-AVR 81%; p<0.0001; HR 2.25, 95% CI: 1.42-3.55). Estimated survival in TAVR compared to SAVR was lower (TAVR 44.4% vs. SAVR 70%; p=0.039; HR 2.32, 95% CI: 0.99-5.37). AVR was a determinant of follow-up mortality (HR 2.18, 95% CI: 1.4-3.4; p<0.001). CONCLUSIONS: Previous AVR in patients undergoing MC therapy carries a heavy and independent burden of mortality/morbidity.

Mid- to long-term outcome of patients treated with everolimus-eluting bioresorbable vascular scaffolds: Data of the BVS registry Göttingen predominantly from ACS patients.

BACKGROUND: Bioresorbable vascular scaffolds (BVS) are widely used in routine clinical practice. While previous studies reported acceptable short- to midterm outcome after BVS implantation, data on longer-term outcome are rare. METHODS: Patients treated with at least one Absorb®-BVS were consecutively enrolled. Follow-up data were assessed after 834.0 [769.0-1026.0] days. The primary device-oriented composite endpoint (DOCE) was defined as cardiovascular death, myocardial infarction (MI) and/or target lesion revascularization (TLR). RESULTS: Between 2012 and 2014, 195 patients were included into study analysis. Overall, 244 BVS were implanted. Mean patient age was 64.0[54.3-74.0] years. Three-quarter of patients had an ACS; of those 42.9% had ST-elevation-MI and 40.8% had non-ST-elevation-MI. DOCE occurred in 3.1%, 6.7%, 11.8% and 15.4% of patients during hospital stay, within 6-months, 18-months or during the complete follow-up period, respectively. In those patients, median time until DOCE was 211.5[43.25-567.25] days. In 11 (36.7%) patients DOCE occurred after >12months. Using univariable analysis, bifurcation stenting was associated with a hazard ratio (HR) of 11.8[2.38-58.57] for TLR (p=0.002) and 2.1[1.02-4.49] for DOCE (p=0.045). Similarly, in ACS patients, bifurcation stenting was associated with an increased risk for TLR (HR=10.4[2.01-53.56]; p=0.005) and for DOCE (HR=2.4[1.09-5.32]; p=0.029) and in multivariable analysis, it remained an independent predictor of DOCE (HR=3.0; p=0.018). CONCLUSIONS: Although, the rates of (potentially) device-related complications following BVS implantation are acceptable, they are nonetheless not negligible. Interestingly, they did not decline over time. Bifurcation stenting could be found as relevant procedure-related predictor of DOCE, especially in ACS patients. Randomized trials are warranted to confirm these findings.

Patients with intracranial bleeding and atrial fibrillation treated with left atrial appendage occlusion: Results from the Amplatzer Cardiac Plug registry.

BACKGROUND: In patients with non-valvular atrial fibrillation (NVAF), intracranial bleeding (ICB) constitutes a very challenging situation in which the rate of both ischemic and hemorrhagic events is increased. In these patients, left atrial appendage occlusion (LAAO) might represent a very valid alternative. OBJECTIVES: To investigate the procedural safety and long-term outcome of patients undergoing LAAO therapy due to previous ICB. METHODS: Data from the Amplatzer Cardiac Plug multicenter registry on 1047 consecutive patients were analyzed. Patients with previous ICB as indication for LAAO were compared to patients with other indications. RESULTS: A total of 198 patients (18.9%) with previous ICB were identified. The CHA2DS2-VASc score was similar (4.5±1.5 vs. 4.4±1.6, p=0.687) and the HAS-BLED score was higher in patients with previous ICB compared to those without (3.5±1.1 vs. 3.1±1.2, p<0.001). No significant differences in peri-procedural major adverse events were observed (2.5 vs 5.4%, p=0.1). Patients with previous ICB were more frequently on single acetylsalicylic acid therapy after LAAO (42.4% vs. 28.3%; p<0.001). With an average follow-up of 1.3years, the observed annual stroke/TIA rate (procedure and follow-up) for patients with previous ICB was 1.4% (75% relative risk reduction). The observed annual major bleeding rate (procedure and follow-up) for patients with previous ICB was 0.7% (89% relative risk reduction). CONCLUSIONS: In patients with NVAF and previous ICB, LAAO seemed to be a safe procedure and was associated with a significant reduction in stroke/TIA and a remarkably low frequency of major bleeding during follow-up.

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 tricuspid valve regurgitation in surgical high-risk patients undergoing MitraClip implantation: results from the TRAMI registry.

AIMS: We sought to assess the impact of tricuspid regurgitation (TR) severity on patient outcome in a collective with relevant mitral regurgitation undergoing MitraClip implantation.. METHODS AND RESULTS: From August 2010 to July 2013, 766 patients (age 75.3±8.5 years, 61% male, median EuroSCORE 24.3%±18.4) were prospectively enrolled in the TRAMI registry and stratified by echocardiography into no/mild, moderate and severe TR. Overall, the mean number of implanted MitraClips was higher in patients with severe TR but increasing TR severity was not associated with procedural success. In-hospital and one-year mortality as well as MACE and MACCE (death, myocardial infarction±stroke) rates were higher with increasing TR severity. Kaplan-Meier curves indicated a significant difference for mortality (p<0.0001), but not for rehospitalisation for heart failure. After multivariate Cox regression, severe TR proved to be a predictor for one-year mortality (HR 2.01, 95% CI: 1.25-3.26, p=0.004). Higher rates of severe bleeding were more frequent with increasing TR grades. CONCLUSIONS: In patients with MitraClip implantation, increasing TR severity is associated with adverse outcome, higher bleeding rates and decreased survival rates.

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.