Daniel Braun

Transcatheter Treatment of Severe Tricuspid Regurgitation with the Edge-to-Edge: MitraClip Technique.

Background: Current surgical and medical treatment options for severe tricuspid regurgitation (TR) are limited, and additional interventional approaches are required. In the present observational study, the safety and feasibility of transcatheter repair of chronic severe TR with the MitraClip system were evaluated. In addition, the effects on clinical symptoms were assessed. Methods: Patients with heart failure symptoms and severe TR on optimal medical treatment were treated with the MitraClip system. Safety, defined as periprocedural adverse events such as death, myocardial infarction, stroke, or cardiac tamponade, and feasibility, defined as successful implantation of 1 or more MitraClip devices and reduction of TR by at least 1 grade, were evaluated before discharge and after 30 days. In addition, functional outcome, defined as changes in New York Heart Assocation class and 6-minute walking distance, were assessed. Results: We included 64 consecutive patients (mean age 76.6±10 years) deemed unsuitable for surgery who underwent MitraClip treatment for chronic, severe TR for compassionate use. Functional TR was present in 88%; in addition, 22 patients were also treated with the MitraClip system for mitral regurgitation as a combined procedure. The degree of TR was severe or massive in 88% of patients before the procedure. The MitraClip device was successfully implanted in the tricuspid valve in 97% of the cases. After the procedure, TR was reduced by at least 1 grade in 91% of the patients, thereof 4% that were reduced from massive to severe. In 13% of patients, TR remained severe after the procedure. Significant reductions in effective regurgitant orifice area (0.9±0.3cm2 versus 0.4±0.2cm2; P<0.001), vena contracta width (1.1±0.5 cm versus 0.6±0.3 cm; P=0.001), and regurgitant volume (57.2±12.8 mL/beat versus 30.8±6.9 mL/beat; P<0.001) were observed. No intraprocedural deaths, cardiac tamponade, emergency surgery, stroke, myocardial infarction, or major vascular complications occurred. Three (5%) in-hospital deaths occurred. New York Heart Association class was significantly improved (P<0.001), and 6-minute walking distance increased significantly (165.9±102.5 m versus 193.5±115.9 m; P=0.007). Conclusions: Transcatheter treatment of TR with the MitraClip system seems to be safe and feasible in this cohort of preselected patients. Initial efficacy analysis showed encouraging reduction of TR, which may potentially result in improved clinical outcomes.

Meta-Analysis of the Usefulness of Mitraclip in Patients With Functional Mitral Regurgitation

Midterm outcomes for patients presenting with heart failure and functional mitral regurgitation (MR) treated with Mitraclip remain unclear. Pubmed, Medline, and Google Scholar were systematically searched for studies enrolling patients with severe-moderate MR who underwent Mitraclip implantation. All events after at least 6 months were the primary safety end point (including death, rehospitalization for heart failure, and reinterventions), whereas change in the ejection fraction, left ventricular volumes, arterial pulmonary pressure, and left atrial diameters were considered as secondary end points. Meta-regression analysis was performed to evaluate the effect of baseline clinical and echocardiographic parameters on efficacy outcomes: 875 patients were included in 9 studies; 1.48 clips (1.3 to 1.7) for patients were implanted, and after a median follow-up of 9 months (6 to 12), 409 patients (78% [75% to 83%]) were in class New York Heart Association I/II and 57 (11% [8% to 14%]) still had moderate-to-severe MR. Overall adverse events occurred in 137 (26% [20% to 31%]) of the patients and 78 (15% [1% to 17%]) of them died; 6-minute walk test improved by 100 m (83 to 111), whereas a significant reduction in left ventricular volumes and systolic pulmonary pressure was reported. At meta-regression analysis, an increase in left ventricle systolic volumes positively affected reduction of volumes after Mitraclip, whereas atrial fibrillation reduced the positive effect of the valve implantation on ejection fraction on end-diastolic and -systolic volumes. In conclusion, Mitraclip represents an efficacious strategy for patients with heart failure and severe MR. It offers a significant improvement in functional class and in cardiac remodeling, in patients with severely dilated hearts as well, although its efficacy remains limited in the presence of atrial fibrillation.

Transcatheter treatment of severe tricuspid regurgitation using the edge-to-edge repair technique.

AIMS The aim of this study was to investigate the procedural feasibility and short-term durability of the transcatheter tricuspid valve edge-to-edge repair technique in highly symptomatic patients with severe tricuspid regurgitation (TR). METHODS AND RESULTS Eighteen consecutive patients suffering from severe right-sided heart failure (NYHA Class III-IV), primarily due to moderate to severe tricuspid regurgitation, were included in the study. Applying a modified steering technique for the clip delivery system, six patients were treated for isolated severe TR, while 12 patients were treated for moderate to severe TR and concomitant severe mitral regurgitation. The primary objectives were procedural success, defined as reduction of at least one TR grade, and 30-day echocardiographic and clinical outcomes. A total of 41 clips (2.3±0.7 per patient) were placed into the tricuspid valve of high surgical risk patients (EuroSCORE II: 10±8%). Procedural success was achieved in all patients; no MACCE occurred in hospital. The presence of a TR grade ≥3 was reduced from 94% (17 patients) before the procedure to 33% (six patients) at 30-day follow-up (p<0.001). Sixteen patients (89%) reported an improvement in NYHA functional class at 30 days. CONCLUSIONS Applying a modified steering technique, the edge-to-edge repair technique can be successfully used for the treatment of TR. At 30-day follow-up, the short-term durability of TR reduction appeared promising and the majority of patients improved clinically. Further studies with larger patient populations and longer follow-up have to define the role of this novel treatment option for patients with right-sided heart failure and severe TR.

Percutaneous edge-to-edge repair of the mitral valve in patients with degenerative versus functional mitral regurgitation.

To prospectively assess the outcome of percutaneous edge‐to‐edge repair in patients with degenerative versus functional mitral regurgitation (MR).

Three-dimensional transoesophageal echocardiography for the assessment of clip attachment to the leaflets in percutaneous edge-to-edge repair of the mitral valve

AIMS Single leaflet clip attachment (SLA) is a prevalent complication in percutaneous edge-to-edge repair of the mitral valve, leading to the recurrence of significant mitral regurgitation. The objective of this retrospective analysis was to evaluate a novel 3-D transoesophageal echocardiographic method for the assessment of clip attachment to the mitral leaflets. METHODS AND RESULTS We analysed a total of 87 patients treated for symptomatic mitral regurgitation. In 47 patients, clip attachment to the leaflets was assessed by conventional 2-D transoesophageal echocardiography supported by biplane TEE images (biplane TEE group). In 40 patients, clip attachment to the leaflets was assessed by the intraprocedural 3-D volume method in addition to the conventional method (volumetric TEE group). The primary endpoint was defined as clip complications consisting of SLA and clip displacement at any time after clip implantation. Clip complications occurred in nine patients (19.1%) in the biplane TEE group and in two patients (5%) in the volumetric TEE group (p=0.06). Regarding the grade of mitral regurgitation, in the follow-up period we observed a more pronounced deterioration in the biplane TEE group than in the volumetric TEE group. CONCLUSIONS These findings suggest that the additional use of 3-D volumetric transoesophageal echocardiography for the assessment of clip attachment to the mitral leaflets may contribute to a reduced rate of subsequent clip complications.

Long-term outcome of patients with severe biventricular heart failure and severe mitral regurgitation after percutaneous edge-to-edge mitral valve repair.

OBJECTIVE To assess long-term outcome and parameters associated with poor and favorable outcome in patients with a left ventricular ejection fraction (LV-EF) ≤25% and severe mitral regurgitation (MR) after percutaneous edge-to-edge mitral valve repair (pMVR). BACKGROUND There is no data on long-term outcome in this cohort of patients. METHODS We analyzed all 34 patients with a LV-EF ≤25% and severe MR treated with pMVR in 2 university hospitals from 2009 to 2012. RESULTS Mitral regurgitation could be successfully reduced to grade ≤2 in 30 patients (88%). Long-term follow-up (up to 5 years) revealed a steep decline of the survival curve reaching 50% already 8 month after pMVR. In contrast, estimated survival of the remaining patients showed a favorable long-term outcome. Patients deceased during the first year presented with higher right ventricular tricuspid pressure gradient (RVTG) (44.5 ± 8.4 mmHg vs. 35.2 ± 15.4 mmHg, P = 0.035) and worse RV-function (P = 0.014) prior to the procedure. One-year mortality of patients with pulmonary hypertension and depressed RV-function (n = 22) was very high (77%) compared to the remaining patients (n = 12, mortality rate of 0%, P = 0.0001). CONCLUSIONS Although pMVR lead to a successful reduction of MR in patients with a LV-EF ≤25%, 1-year mortality in this cohort was very high. However, a subgroup of patients showed a favorable long-term outcome after pMVR. Especially the right ventricular parameters sustained RV-function and absence of pulmonary hypertension-easily assessed with echocardiography-might be used to identify this subgroup and encourage pMVR in these patients.

Comparison of Prasugrel and Bivalirudin vs Clopidogrel and Heparin in Patients With ST‐Segment Elevation Myocardial Infarction: Design and Rationale of the Bavarian Reperfusion Alternatives Evaluation (BRAVE) 4 Trial

Primary percutaneous coronary intervention (PCI) is the preferred reperfusion strategy for patients with ST‐segment elevation myocardial infarction (STEMI). Effective and safe adjunct antithrombotic therapy is a major determinant for short‐ and long‐term outcomes after primary PCI. Two separate studies have shown significant benefits vs conventional therapy for 2 recently approved drugs. In the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS‐AMI) trial, bivalirudin after pretreatment with clopidogrel resulted in improved net clinical outcome compared with heparin plus glycoprotein IIb/IIIa inhibitors. However, during the first 24 hours after PCI, there was an increase in stent thrombosis rates with bivalirudin. In the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel—Thrombolysis In Myocardial Infarction (TRITON‐TIMI) 38 trial, prasugrel was superior to clopidogrel in patients with acute coronary syndrome with and without ST‐segment elevation. The synergic actions of prasugrel and bivalirudin may maximize the benefit of antithrombotic therapy for STEMI patients undergoing primary PCI. However, no specifically designed studies have so far compared the combination of prasugrel plus bivalirudin with that of clopidogrel plus unfractionated heparin in these patients. The Bavarian Reperfusion Alternatives Evaluation (BRAVE) 4 study is a randomized, open‐label, multicenter trial aimed to test the hypothesis that a strategy based on prasugrel plus bivalirudin is superior to a strategy based on clopidogrel plus unfractionated heparin in terms of net clinical outcome in STEMI patients with planned primary PCI.

Oral thrombin inhibitor aggravates platelet adhesion and aggregation during arterial thrombosis

Blood treated with an oral thrombin inhibitor demonstrates enhanced thrombus formation under flow conditions in humans and in rodents. The hidden side of an anticoagulant For patients with atrial fibrillation and other conditions that predispose them to thrombosis, long-term anticoagulation treatment is the norm. Surprisingly, oral thrombin inhibitors, one of the types of anticoagulants used in humans, slightly increased the risk of acute coronary syndromes in clinical studies. To understand this apparent paradox, Petzold et al. compared the effects of treatment with oral thrombin inhibitors, treatment with vitamin K antagonists (another class of anticoagulants), or no treatment at all in patients’ blood and in mouse models of arterial thrombosis, confirming the observations from clinical studies and identifying some of the underlying mechanisms. In patients with atrial fibrillation, oral anticoagulation with oral thrombin inhibitors (OTIs), in contrast to vitamin K antagonists (VKAs), associates with a modest increase in acute coronary syndromes (ACSs). Whether this observation is causatively linked to OTI treatment and, if so, whether OTI action is the result of a lower antithrombotic efficacy of OTI compared to VKA or reflects a yet undefined prothrombotic activity of OTI remain unclear. We analyzed platelet function in patients receiving OTI or dose-adapted VKA under static and flow conditions. In vivo, we studied arterial thrombosis in OTI-, VKA-, and vehicle-treated mice using carotid ligation and wire injury models. Further, we examined thrombus formation on human atherosclerotic plaque homogenates under arterial shear to address the relevance to human pathology. Under static conditions, aggregation in the presence of ristocetin was increased in OTI-treated blood, whereas platelet reactivity and aggregation to other agonists were only marginally affected. Under flow conditions, firm platelet adhesion and thrombus formation on von Willebrand factor, collagen, and human atherosclerotic plaque were increased in the presence of OTI in comparison to VKA. OTI treatment was associated with increased thrombus formation in injured carotid arteries of mice. Inhibition or ablation of GPIbα-thrombin interactions abolished the effect of OTI on thrombus formation, suggesting a mechanistic role of the platelet receptor GPIbα and its thrombin-binding site. The effect of OTI was also abrogated in the presence of aspirin. In summary, OTI treatment has prothrombotic activity that might contribute to the increase in ACS observed clinically in patients.

Six-month outcome after transcatheter edge-to-edge repair of severe tricuspid regurgitation in patients with heart failure: Six-month results after edge-to-edge tricuspid valve repair

Severe tricuspid regurgitation (TR) is common in patients with right‐sided heart failure (HF) and causes substantial morbidity and mortality. Treatment options beyond medical therapy are limited for high‐risk patients. Transcatheter edge‐to‐edge tricuspid valve (TV) repair showed procedural safety and short‐term efficacy. Impact on mid‐term outcome is unclear. This dual‐centre observational study evaluates the mid‐term safety, efficacy and clinical outcome after edge‐to‐edge TV repair for severe TR in patients with HF.

Dangerous liaison: successful percutaneous edge-to-edge mitral valve repair in patients with end-stage systolic heart failure can cause left ventricular thrombus formation.

AIMS To evaluate the characteristics and clinical outcome of patients with new formation of left ventricular (LV) thrombus after percutaneous edge-to-edge mitral valve repair. METHODS AND RESULTS Between 2009 and 2012 we intended to treat 150 patients with severe mitral regurgitation (MR) with percutaneous edge-to-edge mitral valve repair in our centre. Post-procedural transthoracic echocardiographic examinations scheduled during the hospital stay revealed the new formation of LV thrombi in three out of 150 patients. All three patients suffered from end-stage systolic heart failure with a LV ejection fraction (LVEF) below 20% and were successfully treated in terms of MR reduction (reduction of at least two MR grades). No thrombus formation was observed in patients with a LVEF >20% treated in our centre (a total of 136 patients). The frequency of new LV thrombus formation in the cohort of patients with a LVEF ≤20% treated in our centre was 21% (three out of 14 patients). CONCLUSIONS New formation of LV thrombus was detected in patients with severely depressed LVEF (≤20%) after successful reduction of MR following percutaneous edge-to-edge mitral valve repair. This phenomenon could be a play of chance, but percutaneous edge-to-edge mitral valve repair using the MitraClip¨ system is a new procedure. Special care is needed when performing new procedures, and the unexpected post-procedural finding of LV thrombus formation in approximately 20% in this cohort is worth reporting.