Macrophage Migration Inhibitory Factor Promotes Thromboinflammation and Predicts Fast Progression of Aortic Stenosis.

BACKGROUND: Aortic stenosis (AS) is driven by progressive inflammatory and fibrocalcific processes regulated by circulating inflammatory and valve resident endothelial and interstitial cells. The impact of platelets, platelet-derived mediators, and platelet-monocyte interactions on the acceleration of local valvular inflammation and mineralization is presently unknown. METHODS: We prospectively enrolled 475 consecutive patients with severe symptomatic AS undergoing aortic valve replacement. Clinical workup included repetitive echocardiography, analysis of platelets, monocytes, chemokine profiling, aortic valve tissue samples for immunohistochemistry, and gene expression analysis. RESULTS: The patients were classified as fast-progressive AS by the median ∆Vmax of 0.45 m/s per year determined by echocardiography. Immunohistological aortic valve analysis revealed enhanced cellularity in fast-progressive AS (slow- versus fast-progressive AS; median [interquartile range], 247 [142.3-504] versus 717.5 [360.5-1234]; P<0.001) with less calcification (calcification area, mm2: 33.74 [27.82-41.86] versus 20.54 [13.52-33.41]; P<0.001). MIF (macrophage migration inhibitory factor)-associated gene expression was significantly enhanced in fast-progressive AS accompanied by significantly elevated MIF plasma levels (mean±SEM; 6877±379.1 versus 9959±749.1; P<0.001), increased platelet activation, and decreased intracellular MIF expression indicating enhanced MIF release upon platelet activation (CD62P, %: median [interquartile range], 16.8 [11.58-23.8] versus 20.55 [12.48-32.28], P=0.005; MIF, %: 4.85 [1.48-9.75] versus 2.3 [0.78-5.9], P<0.001). Regression analysis confirmed that MIF-associated biomarkers are strongly associated with an accelerated course of AS. CONCLUSIONS: Our findings suggest a key role for platelet-derived MIF and its interplay with circulating and valve resident monocytes/macrophages in local and systemic thromboinflammation during accelerated AS. MIF-based biomarkers predict an accelerated course of AS and represent a novel pharmacological target to attenuate progression of AS.

Optimal Antithrombotic Strategies in Cardiogenic Shock.

Cardiogenic shock (CS) represents a critical condition with a high mortality rate. The most common cause of CS is coronary artery disease, and patients typically present with myocardial infarction, necessitating immediate treatment through percutaneous coronary intervention (PCI) and often requiring mechanical circulatory support. CS is associated with a prothrombotic situation, while on the other hand, there is often a significant risk of bleeding. This dual challenge complicates the selection of an optimal antithrombotic strategy. The choice of antithrombotic agents must be personalized, taking into consideration all relevant conditions. Repeated risk assessment, therapeutic monitoring, and adjusting antithrombotic therapy are mandatory in these patients. This review article aims to provide an overview of the current evidence and practical guidance on antithrombotic strategies in the context of CS.

Pacemaker Lead Entanglement during Interventional PFO Occlusion: Salvage Using a Sizing Balloon.

We present a case of a patient with a transient ischaemic attack (TIA) likely due to paradoxical embolism through a patent foramen ovale (PFO). Her medical history included 2nd-degree heart block Mobitz II, which manifested with recurrent syncopes and was treated with a dual chamber pacemaker. During the interventional PFO closure procedure, we noted entrapment of the atrial pacemaker lead between the right-sided occluder disc and the interatrial septum. We were able to successfully move the lead aside using a 24 mm sizing balloon and subsequently developed the right-sided occluder disc in the correct position. In conclusion, pacemaker-lead entrapment between a PFO occluder disc and the interatrial septum can be prevented using a sizing balloon.

Leaving Your Buddy in Jail: A Simplified Approach to the Jailed Buddy Wire Technique.

Stent delivery into highly tortuous and/or calcified coronary lesions represents a challenging problem during PCI. In this case series of 7 patients with complex coronary lesions, we had a hard time delivering larger and thus bulkier stents. We used a buddy wire and delivered a stent into the most distal lesion and jailed the buddy wire. We left the wire jailed during the whole procedure and were easily able to deliver large and long stents to the more proximal lesions. Retrieval of the buddy wire was possible without problems in all cases. The "leaving your buddy in jail" technique provides an excellent support and allows facilitated delivery and deployment of multiple stents, if necessary overlapping stents, into challenging coronary lesions.

Modifiable risk factors for permanent pacemaker after transcatheter aortic valve implantation: CONDUCT registry.

OBJECTIVE: The onset of new conduction abnormalities requiring permanent pacemaker implantation (PPI) after transcatheter aortic valve implantation (TAVI) is still a relevant adverse event. The main objective of this registry was to identify modifiable procedural risk factors for an improved outcome (lower rate of PPI) after TAVI in patients at high risk of PPI. METHODS: Patients from four European centres receiving a balloon-expandable TAVI (Edwards SAPIEN 3/3 Ultra) and considered at high risk of PPI (pre-existing conduction disturbance, heavily calcified left ventricular outflow tract or short membranous septum) were prospectively enrolled into registry. RESULTS: A total of 300 patients were included: 42 (14.0%) required PPI after TAVI and 258 (86.0%) did not. Patients with PPI had a longer intensive care unit plus intermediate care stay (65.7 vs 16.3 hours, p<0.001), general ward care stay (6.9 vs 5.3 days, p=0.004) and later discharge (8.6 vs 5.0 days, p<0.001). Of the baseline variables, only pre-existing right bundle branch block at baseline (OR 6.8, 95% CI 2.5 to 18.1) was significantly associated with PPI in the multivariable analysis. Among procedure-related variables, oversizing had the highest impact on the rate of PPI: higher than manufacturer-recommended sizing, mean area oversizing as well as the use of the 29 mm valve (OR 3.4, 95% CI 1.4 to 8.5, p=0.008) all were significantly associated with PPI. Rates were higher with the SAPIEN 3 (16.1%) vs SAPIEN 3 Ultra (8.5%), although not statistically significant but potentially associated with valve sizing. Implantation depth and postdelivery balloon dilatation also tended to affect PPI rates but without a statistical significance. CONCLUSION: Valve oversizing is a strong procedure-related risk factor for PPI following TAVI. The clinical impact of the valve type (SAPIEN 3), implantation depth, and postdelivery balloon dilatation did not reach significance and may reflect already refined procedures in the participating centres, giving attention to these avoidable risk factors. TRIAL REGISTRATION NUMBER: NCT03497611.

Molecular Fingerprinting and Microbiological Characterisation of Selected Vitis vinifera L. Varieties.

The aim of the study was to analyse selected aspects of the natural variability of selected varieties of Vitis vinifera. Grapevine is one of the most popular and desirable crops in the world due to the great tradition of wine production, but grape extracts also have a wide range of pharmaceutical effects on the human body. It is important to identify different varieties for the conservation of genetic resources, but also for commercial and cultivation purposes. The variability of conserved DNA-derived polymorphism profiles, as well as microbial characteristics, were analysed in this study. Six different varieties of Vitis vinifera L. were used in the study: Cabernet Savignon, Chardonney, Welschriesling, Weisser Riesling, Gewurztramines and Gruner Veltliner. Genetic polymorphism was analysed by CDDP markers for WRKY genes. Polymorphic amplicon profiles were generated by all primer combinations used in the study. Gruner Veltliner and Welschriesling were the most similar, with a similarity value at 0.778. Microbiological quality of grape and antimicrobial activity against Gram-positive and Gram-negative bacteria and yeasts were analysed further. The plate diluting method for microbial quality and the disc diffusion method for antimicrobial activity were evaluated. The number of total count of bacteria ranged between 3.12 in Cabernet Sauvignon to 3.62 log cfu/g in Gruner Veltliner. The best antimicrobial activity showed Gewurztramines against Salmonella enterica, Yersinia enterocolitica, Pseudomonas aeroginosa, Staphylococcus aureus, Listeria monocytogenes, Candida albicans, Candida krusei, and Candida tropicalis. The best antimicrobial activity was found against Enterococcus faecalis in variety Weisser Riesling.

Pulmonary Hypertension and COVID-19.

Coronavirus disease 2019 (COVID-19) is a primary respiratory infectious disease, which can result in pulmonary and cardiovascular complications. From its first appearance in the city of Wuhan (China), the infection spread worldwide, leading to its declaration as a pandemic on March 11, 2020. Clinical research on SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) suggests that the virus may determine changes in the pulmonary hemodynamics through mechanisms of endothelial dysfunction, vascular leak, thrombotic microangiopathy, and venous thromboembolism that are similar to those leading to pulmonary hypertension (PH). Current available studies report echocardiographic signs of PH in approximately 12 to 13% of hospitalized patients with COVID-19. Those with chronic pulmonary obstructive disease, congestive heart failure, pulmonary embolism, and prior PH are at increased risk to develop or worsen PH. Evidence of PH seems to be associated with increased disease severity and poor outcome. Because of the importance of the pulmonary hemodynamics in the pathophysiology of COVID-19, there is growing interest in exploring the potential therapeutical benefits of inhaled vasodilators in patients with COVID-19. Treatment with inhaled nitric oxide and prostacyclin has shown encouraging results through improvement of systemic oxygenation, reduction of systolic pulmonary arterial pressure, and prevention of right ventricular failure; however, data from randomized control trials are still required.

C5 Variant rs10985126 is Associated with Mortality in Patients with Symptomatic Coronary Artery Disease.

BACKGROUND: Complement component 5a (C5a) is a highly potent anaphylatoxin with a variety of pro-inflammatory effects. C5a contributes to progression of atherosclerosis and inhibition of the receptor (C5aR) might offer a therapeutic strategy in this regard. Single nucleotide polymorphisms (SNPs) of the C5 gene may modify protein expression levels and therefore function of C5a and C5aR. This study aimed to examine associations between clinically relevant C5a SNPs and the prognosis of patients with symptomatic coronary artery disease (CAD). Furthermore, we sought to investigate the influence of C5 SNPs on C5aR platelet surface expression and circulating C5a levels. METHODS: C5 variants (rs25681, rs17611, rs17216529, rs12237774, rs41258306, and rs10985126) were analyzed in a consecutive cohort of 833 patients suffering from symptomatic coronary artery disease (CAD). Circulating C5a levels were determined in 116 patients whereas C5aR platelet surface expression was measured in 473 CAD patients. Endpoints included all-cause mortality, myocardial infarction (MI), and ischemic stroke (IS). Homozygous carriers (HC) of the minor allele (rs10985126) showed significantly higher all-cause mortality than major allele carriers. While we could not find significant associations between rs10985126 allele frequency and C5aR platelet surfazl ce expression, significantly elevated levels of circulating C5a were found in HC of the minor allele of the respective genotype. rs17216529 allele frequency correlated with the composite combined endpoint and bleeding events. However, since the number of HC of the minor allele of this genotype was low, we cannot draw a robust conclusion about the observed associations. CONCLUSION: In this study, we provide evidence for the prognostic relevance of rs10985126 in CAD patients. C5 rs10985126 may serve as a prognostic biomarker for risk stratification in high-risk CAD patients and consequently promote tailored therapies.

Risk factors for permanent pacemaker implantation in patients receiving a balloon-expandable transcatheter aortic valve prosthesis.

Permanent pacemaker implantation (PPI) is a widely recognized complication associated with TAVI (incidence up to 20%). Smaller registries have identified several variables associated with PPI. The objective was to validate patient- and transcatheter aortic valve implantation (TAVI)-related procedural variables associated with PPI. We performed a retrospective analysis of patients from six European centers undergoing TAVI with the Edwards SAPIEN 3 prosthesis. Baseline variables and pre-procedural ECG characteristics and CT-scans were taken into account. Data for 1745 patients were collected; 191 (10.9%) required PPI after TAVI. The baseline variables pulmonary hypertension (OR 1.64; 95% CI 1.01-2.59), QRS duration > 117 ms (OR 2.58; 95% CI 1.73-3.84), right bundle branch block (RBBB; OR 5.14; 95% CI 3.39-7.72), left anterior hemi block (OR 1.92; 95% CI 1.19-3.02) and first-degree atrioventricular block (AVB, OR 1.63; 95%CI 1.05-2.46) were significantly associated with PPI. RBBB (OR 8.11; 95% CI 3.19-21.86) and first-degree AVB (OR 2.39; 95% CI 1.18-4.66) remained significantly associated in a multivariate analysis. Procedure-related variables included access site (TF; OR 1.97; 95% CI 1.07-4.05), implanted valve size (29 mm; OR 1.88; 95% CI 1.35-2.59), mean TAVI valve implantation depth below the annulus > 30% (OR 3.75; 95% CI 2.01-6.98). Patients receiving PPI had longer ICU stays and later discharges. Acute kidney injury stage 2/3 was more common in patients with PPI until discharge (15.2 vs. 3.1%; p = 0.007), but was not statistically significant thereafter. Further differences in outcomes at 30 days did not reach significance. The data will aid pre- and post-procedural patient management and prevent adverse long-term outcomes.Clinical Trial: NCT03497611.

Thrombogenicity and Antithrombotic Strategies in Structural Heart Interventions and Nonaortic Cardiac Device Therapy-Current Evidence and Practice.

As the number of, and the indications for, structural heart interventions are increasing worldwide, the optimal secondary prevention to reduce device thrombosis is becoming more important. To date, most of the recommendations are empiric. The current review discusses mechanisms behind device-related thrombosis, the available evidence with regard to antithrombotic regimen after cardiac device implantation, as well as providing an algorithm for identification of risk factors for device thrombogenicity and for management of device thrombosis after implantation of patent foramen ovale and left atrial appendage occluders, MitraClips/transcatheter mitral valve replacement, pacemaker leads, and left ventricular assist devices. Of note, the topic of antithrombotic therapy and thrombogenicity of prostheses in aortic position (transcatheter aortic valve replacement, surgical, mechanical, and bioprostheses) is not part of the present article and is discussed in detail in other contemporary focused articles.

Cangrelor in cardiogenic shock and after cardiopulmonary resuscitation: A global, multicenter, matched pair analysis with oral P2Y12 inhibition from the IABP-SHOCK II trial.

AIMS: Cangrelor has a potentially favorable pharmacodynamic profile in cardiogenic shock (CS). We aimed to evaluate the clinical course of CS patients undergoing percutaneous coronary intervention (PCI) treated with cangrelor. METHODS AND RESULTS: We retrospectively identified 136 CS patients treated with cangrelor. Patients were 1:1 matched to CS patients from the IABP-SHOCK II trial not receiving cangrelor by age, sex, cardiac arrest, type of myocardial infarction, culprit lesion, glycoprotein IIb/IIIa inhibitor, and oral P2Y12-receptor inhibitor and followed-up for 12 months. The study cohort consisted of 88 matched pairs. Thirty-day and 12-month mortality was 29.5% and 34.1% in cangrelor-treated patients and 36.4% and 47.1% in control group (P = 0.34 and P = 0.08, respectively). The rate of definite acute stent thrombosis was 2.3% in both groups. Moderate and severe bleeding events occurred in 21.6% in the cangrelor and 19.3% in the control group (P = 0.71). Patients treated with cangrelor more frequently experienced ≥1 TIMI flow grade improvement during PCI (92.9% vs. 81.2%, P = 0.02). CONCLUSION: Cangrelor treatment was associated with similar bleeding risk and significantly better TIMI flow improvement compared with oral P2Y12 inhibitors in CS patients undergoing PCI. The use of cangrelor in CS offers a potentially safe and effective antiplatelet option and should be evaluated in randomized trials.

Comparison of safety and periprocedural complications of transfemoral aortic valve replacement under local anaesthesia: minimalist versus complete Heart Team.

AIMS: The aim of the study was to evaluate peri-interventional complications and in-hospital complications in different team settings when performing transfemoral aortic valve replacement (TAVR) under local anaesthesia. METHODS AND RESULTS: We performed TAVR under local anaesthesia with a minimalist Heart Team consisting of two interventional cardiologists, an echocardiographer and two cardiac catheterisation laboratory nurses. In August 2015, new guidelines for TAVR were issued by the National Federal Joint Committee. In accordance with these guidelines, we began to perform TAVR using a complete Heart Team, consisting of two interventional cardiologists, an echocardiographer, a cardiac surgeon, an anaesthesiologist, a cardiovascular perfusionist, two cardiac catheterisation laboratory nurses, a surgical nurse and an anaesthetist nurse. In this study, we retrospectively analysed periprocedural and in-hospital outcomes. Two hundred and ninety-two (55.1%) patients were treated by the minimalist Heart Team, whereas 238 (44.9%) were treated by the complete Heart Team. There were no significant differences in periprocedural (1.4% vs. 1.3%, p=1.0) and in-hospital mortality (4.8% vs. 5.0%, p=0.9) as well as in conversion to open heart (0.3% vs. 0.8%, p=0.59) or immediate vascular surgery (0.3% vs. 2.1%, p=0.1) for minimalist versus complete Heart Team, respectively. CONCLUSIONS: TAVR under local anaesthesia can be safely performed by a minimalist Heart Team. We did not observe any differences in fatal periprocedural complications and mortality when compared with those of a complete Heart Team.

Clinical and economical impact of the presence of an extended heart team throughout the balloon-expandable transcatheter aortic valve implantation procedure.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a standard therapy for aortic valve stenosis in patients at intermediate-to-high surgical risk. Previously, TAVI at our site was performed by a minimalist heart team (MHT), comprised of two interventional cardiologists, echocardiography staff and two cardiac catheterization laboratory nurses. After revision of German Federal Joint Committee (G-BA) guidelines in September 2015, the presence of an extended heart team (EHT; including a full cardiac surgical team) became mandatory throughout the TAVI procedure. We aimed to evaluate the impact of the EHT on clinical and economical outcomes. METHODS: Data was retrospectively extracted from the medical records of patients receiving an Edwards SAPIEN 3 valve at the University Hospital Tübingen, Germany, between 2014 and 2017 and matched with cost data from the national invoice system of hospitals (InEK). For comparison, patients were grouped according to whether they underwent TAVI with or without the EHT. RESULTS: Overall, data for 341 patients (MHT 233; EHT 118) were analysed. Baseline characteristics were largely similar between groups (mean age 81.0 years; 54.5% female), though EHT patients had a lower mean logEuroSCORE (17.5% vs. 19.8%; p = 0.011) and more prior PCI/stenting (39.0% vs. 26.9%; p = 0.022). The rate of immediate procedural death (1.7%) was comparable between groups, as was mortality at 30 days (4.2%). Overall, 1.2% of patients required conversion to surgery. The cost of the index hospitalisation (minus the prosthesis) was higher in the EHT condition (difference + €1604), largely driven by expenditure on physicians (difference + €581; p < 0.001), medical technicians (difference + €372; p < 0.001) and medical supplies (difference +€244; p = 0.001). CONCLUSION: At our site, the presence of an EHT throughout the TAVI procedure appears to substantially increase hospital expenditure without significantly improving patient outcomes. We suggest that TAVI by a minimalist HT with a surgical team on call in case of emergency may be sufficient.

Previous TAVR in patients undergoing percutaneous edge-to-edge mitral valve repair (PMVR) affects improvement of MR.

BACKGROUND: Patients after transcatheter aortic valve replacement (TAVR) and persistent severe mitral regurgitation (MR) are increasingly treated with percutaneous edge-to-edge mitral valve repair (PMVR). The impact of a former TAVR on PMVR procedures is not clear. METHODS AND RESULTS: We retrospectively analyzed 332 patients undergoing PMVR using the MitraClip system with respect to procedural and clinical outcome. 21 of these 332 patients underwent TAVR before PMVR. Intra-procedural transthoracic (TTE) and transesophageal echocardiograms (TEE) immediately before and after clip implantation as well as invasive hemodynamic measurements were evaluated. At baseline, we found a significantly smaller mitral valve anterior-posterior diameter in the TAVR cohort (p < 0.001). A reduction of MR by at least three grades was achieved in a smaller fraction in the TAVR cohort as compared to the cohort with a native aortic valve (p = 0.02). Accordingly, we observed a smaller post-procedural cardiac output in the TAVR cohort (p = 0.02). CONCLUSION: PMVR in patients who had a TAVR before, is associated with altered MR anatomy before and a reduced improvement of MR after the procedure. Future larger and prospective studies will have to determine, whether a previous TAVR influences long-term clinical outcome of patients undergoing PMVR.

Relative survival potential of platelets is associated with platelet CXCR4/CXCR7 surface exposure and functional recovery following STEMI.

BACKGROUND AND AIMS: Platelets are critically involved in tissue repair and regeneration, which depend on their inflammatory properties and survival. SDF-1 ligates to CXCR4 and CXCR7 and contributes to the regulation of platelet survival. Platelet CXCR4/CXCR7 are involved in myocardial regeneration after infarction and are associated with outcomes in patients with symptomatic coronary artery disease. This study investigates the CXCR4/CXCR7 platelet survival axis ex vivo. METHODS: 87 patients with ST-segment elevation myocardial infarction (STEMI) were included and analyzed for platelet surface exposure of CXCR4, CXCR7, Annexin V binding and tetramethylrhodamine ethyl ester (TMRE) response. Serum of 38 patients was analyzed for FasL, TNFα, TNF RI, TNF RII and TRAIL with Bioplex®. The majority of patients received sequential cardiac MRI (intrahospital, 6-month follow-up). RESULTS: We found a strong and positive correlation between surface exposure of CXCR4 and CXCR7 (ρ = 0.856, p<0.001). Relative survival potential correlated significantly with both platelet surface exposure of CXCR4 and CXCR7 (ρ = 0.365, p = 0.019; ρ = 0.417, p = 0.006) and furthermore with improvement of myocardial left ventricular ejection fraction (LVEF) (ρ = 0.490, p = 0.013). High relative survival potential showed significantly higher levels for both CXCR4 and CXCR7 surface exposure (MFI 87.3 vs. 69.0, p = 0.037; MFI 71.4 vs. 59.3, p = 0.045). We found a significant change in absolute LVEF% over the course of 6 months in patients with high CXCR7 platelet surface exposure (LVEF% 44.3 vs. 60.0, p≤0.001). CONCLUSIONS: Platelet survival is associated with platelet surface exposure of CXCR4 and CXCR7 in STEMI patients and contributes to functional recovery after STEMI.

Inhibitory mechanisms of very low-dose rivaroxaban in non-ST-elevation myocardial infarction.

Very low-dose (VLD) factor Xa (FXa) inhibition, in combination with acetylsalicylic acid (ASA) and clopidogrel, is associated with improved outcomes in patients with acute coronary syndrome (ACS) with a tolerable bleeding risk profile. To date, there are no data documenting platelet inhibition and the anticoagulatory effects of VLD FXa inhibition on top of guideline-adherent dual-antiplatelet therapy (DAPT) in patients with ACS. Patients with non-ST-elevation myocardial infarction (NSTEMI) receiving oral DAPT (ASA + clopidogrel, n = 20; or ASA + ticagrelor, n = 20) were prospectively enrolled in a nonrandomized study. Coagulation- and platelet-dependent thrombin generation (TG), measured by means of the calibrated automated thrombogram, were significantly decreased after in vitro and in vivo addition of rivaroxaban. As shown by a total thrombus-formation analysis approach, rivaroxaban treatment led to a significantly decreased coagulation-dependent (AR-chip) thrombus formation in patients treated with ASA plus P2Y12 inhibitor (clopidogrel/ticagrelor), whereas the pure platelet-dependent (PL-chip) thrombus formation was not affected at all. Adjunctive rivaroxaban therapy was not associated with significant differences in platelet aggregation assessed by light-transmission aggregometry (LTA). Nevertheless, according to fluorescence-activated cell sorter analysis, VLD rivaroxaban treatment resulted in a significantly reduced expression of platelet HMGB-1, whereas P-selectin exposure was not affected. Furthermore, an enhanced effect of rivaroxaban on total thrombus formation and TG was observed in particular in clopidogrel nonresponder patients defined as adenosine 5'-diphosphate-induced LTA ≥40%. VLD rivaroxaban reduces thrombus formation and platelet-dependent TG in patients with ACS receiving DAPT, which can be of potential ischemic benefit. This trial was registered at www.clinicaltrials.gov as #NCT01417884.

What is the Role of Cangrelor in Patients Undergoing PCI?

Dual antiplatelet therapy with aspirin and oral P2Y12-receptor inhibitors prevents ischemic events in patients undergoing Percutaneous Coronary Intervention (PCI). However, oral administration of antiplatelet drugs cause delay of onset of platelet inhibition in P2Y12-inhibitor naïve patients. Cangrelor is a novel P2Y12-receptor inhibitor which is administrated intravenously and thus allows immediate antiplatelet inhibition during PCI. Due to its unique pharmacokinetics with fast onset of platelet inhibition and very short plasma half-life it allows effective and controllable periprocedural platelet inhibition. It could reduce short-term ischemic events in large randomized clinical trials. The present article reviews the available evidence and application on cangrelor use in clinical practice.

Antithrombotic Therapy After TAVR.

Transvascular Aortic Valve Replacement (TAVR) has emerged as a treatment option in patients with severe aortic stenosis who are inoperable and has recently been evaluated in patients with intermediate surgical risk. The number of procedures is increasing worldwide in parallel with the demographic changes in industrial countries. The risk for cerebral embolism is of main concern and represents a major determinant for prognosis and quality of live after TAVR. The empiric antithrombotic therapy consists of Dual Antiplatelet Therapy (DAPT); However the risk-benefit of this approach is lacking evidence from randomized, placebo-controlled trials regarding choice and duration of antithrombotic treatment. Although anticoagulation is generally not recommended in patients with aortic bioprosthesis without atrial fibrillation, there is current uncertainty whether combination of antiplatelet and anticoagulant therapy or anticoagulation alone might represent a more favorable antithrombotic regimen compared to the current empiric standard of DAPT. In addition, so far undetected atrial fibrillation is highly prevalent in the elderly population undergoing TAVR. In particular, the favorable safety profile of Non-Vitamin K Oral Anticoagulants (NOAC) offers an attractive option. A number of trials are currently underway to investigate the benefit of NOAC in patients with and without atrial fibrillation undergoing TAVR. The present article reviews the available evidence concerning stroke risk in TAVR patients and the current and future role of antithrombotic therapy during and after the procedure.

Improved mitral valve coaptation and reduced mitral valve annular size after percutaneous mitral valve repair (PMVR) using the MitraClip system.

Aims: Improved mitral valve leaflet coaptation with consecutive reduction of mitral regurgitation (MR) is a central goal of percutaneous mitral valve repair (PMVR) with the MitraClip® system. As influences of PMVR on mitral valve geometry have been suggested before, we examined the effect of the procedure on mitral annular size in relation to procedural outcome. Methods and results: Geometry of the mitral valve annulus was evaluated in 183 patients undergoing PMVR using echocardiography before and after the procedure and at follow-up. Mitral valve annular anterior-posterior (ap) diameter decreased from 34.0 ± 4.3 to 31.3 ± 4.9 mm (P < 0.001), and medio-lateral (ml) diameter from 33.2 ± 4.8 to 32.4 ± 4.9 mm (P < 0.001). Accordingly, we observed an increase in MV leaflet coaptation after PMVR. The reduction of mitral valve ap diameter showed a significant inverse correlation with residual MR. Importantly, the reduction of mitral valve ap diameter persisted at follow-up (31.3 ± 4.9 mm post PMVR, 28.4 ± 5.3 mm at follow-up). Conclusion: This study demonstrates mechanical approximation of both mitral valve annulus edges with improved mitral valve annular coaptation by PMVR using the MitraClip® system, which correlates with residual MR in patients with MR.