Comparison of a Pure Plug-Based Versus a Primary Suture-Based Vascular Closure Device Strategy for Transfemoral Transcatheter Aortic Valve Replacement: The CHOICE-CLOSURE Randomized Clinical Trial.

BACKGROUND: Transcatheter aortic valve replacement is an established treatment option for patients with severe symptomatic aortic stenosis and is most commonly performed through the transfemoral access route. Percutaneous access site closure can be achieved using dedicated plug-based or suture-based vascular closure device (VCD) strategies, but randomized comparative studies are scarce. METHODS: The CHOICE-CLOSURE trial (Randomized Comparison of Catheter-based Strategies for Interventional Access Site Closure during Transfemoral Transcatheter Aortic Valve Implantation) is an investigator-initiated, multicenter study, in which patients undergoing transfemoral transcatheter aortic valve replacement were randomly assigned to vascular access site closure using either a pure plug-based technique (MANTA, Teleflex) with no additional VCDs or a primary suture-based technique (ProGlide, Abbott Vascular) potentially complemented by a small plug. The primary end point consisted of access site- or access-related major and minor vascular complications during index hospitalization, defined according to the Valve Academic Research Consortium-2 criteria. Secondary end points included the rate of access site- or access-related bleeding, VCD failure, and time to hemostasis. RESULTS: A total of 516 patients were included and randomly assigned. The mean age of the study population was 80.5±6.1 years, 55.4% were male, 7.6% of patients had peripheral vascular disease, and the mean Society of Thoracic Surgeons score was 4.1±2.9%. The primary end point occurred in 19.4% (50/258) of the pure plug-based group and 12.0% (31/258) of the primary suture-based group (relative risk, 1.61 [95% CI, 1.07-2.44], P=0.029). Access site- or access-related bleeding occurred in 11.6% versus 7.4% (relative risk, 1.58 [95%CI: 0.91-2.73], P=0.133) and device failure in 4.7% versus 5.4% (relative risk, 0.86, [95% CI, 0.40-1.82], P=0.841) in the respective groups. Time to hemostasis was significantly shorter in the pure plug-based group (80 [32-180] versus 240 [174-316] seconds, P<0.001). CONCLUSIONS: Among patients treated with transfemoral transcatheter aortic valve replacement, a pure plug-based vascular closure technique using the MANTA VCD is associated with a higher rate of access site- or access-related vascular complications but a shorter time to hemostasis compared with a primary suture-based technique using the ProGlide VCD. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04459208.

Budesonide Inhibits Intracellular Infection with Non-Typeable Haemophilus influenzae Despite Its Anti-Inflammatory Effects in Respiratory Cells and Human Lung Tissue: A Role for p38 MAP Kinase.

BACKGROUND: Inhaled corticosteroids (ICS) are widely used in the treatment of obstructive lung diseases. Recent data suggest a higher pneumonia risk in chronic obstructive pulmonary disease (COPD) patients treated with ICS. OBJECTIVE: Since non-typeable Haemophilus influenzae (NTHi) is the most common pathogen associated with acute exacerbations of COPD, we investigated the effects of budesonide (BUD) on NTHi-induced inflammation and invasive infection. METHODS: The alveolar epithelial cell line A549 and specimens of human lung tissue (HLT) were used in our experiments. Intracellular infection was determined by a lysis/culture assay of infected cells. Activated p38 mitogen-associated protein kinase (MAPK) was assessed using Western blotting and immunohistochemistry, expression of toll-like receptor 2 (TLR2) was determined by PCR, and CXCL-8 levels were measured using ELISA. Immunohistochemistry was used for detection of CXCL-8, platelet-activating factor receptor (PAF-R) and NTHi. RESULTS: BUD significantly reduced CXCL-8 secretion in A549 cells and lung tissue infected with NTHi. Furthermore, BUD decreased the expression of PAF-R in HLT and A549 cells. In A549 cells and HLT, BUD inhibited intracellular infection and - synergistically with NTHi - increased the expression of TLR2 (in A549 cells). TLR2 stimulation did not influence the intracellular infection of A549 cells, but p38 MAPK inhibition resulted in a significant reduction of infection. CONCLUSION: The present study adds new insights into the effects of glucocorticoids on pulmonary host defence after NTHi infection. Although the inflammatory response to infection is suppressed by BUD, interestingly, the intracellular infection is also inhibited. This effect seems to depend on the inhibition of p38 MAPK - a key enzyme in many pro-inflammatory pathways - as well as of PAF-R expression.

A study of bailout plug-based closure after failed suture-based closure in patients undergoing transfemoral TAVI.

BACKGROUND: Percutaneous suture-based arterial access site closure (ProGlide) is commonly applied in patients undergoing transfemoral transcatheter aortic valve implantation (TAVI). However, the failure of a suture-based vascular closure device (VCD) may require additional treatment. AIMS: We aimed to evaluate the efficacy and safety of bailout access site closure using a large-bore plug-based device (MANTA) in patients with failed suture-based closure during transfemoral TAVI. METHODS: Patients undergoing a bailout attempt with the MANTA VCD were identified from a prospectively enrolling, institutional registry. Efficacy was defined as haemostasis at the access site without the need for alternative treatment other than manual compression or endovascular ballooning. Safety was defined as freedom from vascular dissection, stenosis and occlusion requiring intervention. RESULTS: Of 2,505 patients, 66 underwent a bailout attempt with MANTA as a result of ProGlide failure, which occurred before the large-bore sheath insertion in 16.7% of patients and after the sheath removal in 83.3% of patients. Bailout MANTA was deemed effective in 75.8% of patients (50/66), and the technique was considered safe in 86.4% (57/66) of patients. Failure of bailout MANTA occurred because of its superficial application, resulting in persistent bleeding in 18.2% of patients (12/66), and because of its deep application, resulting in stenosis or occlusion in 6.1% of patients (4/66). Operator experience with the technique (odds ratio [OR] 12.29, 95% confidence interval [CI]: 1.99-75.99; p=0.007) and prior use of three ProGlides (OR 0.02, 95% CI: <0.01-0.39; p=0.010) were the only independent predictors of the efficacy endpoint. CONCLUSIONS: Bailout MANTA after ProGlide failure was effective and safe, but operator experience seems to be crucial. Further technological refinements to facilitate accurate placement appear necessary.

Prognostic significance and clinical utility of left atrial reservoir strain in transcatheter aortic valve replacement.

AIMS: Patients with diastolic dysfunction (DD) experience worse outcomes after transcatheter aortic valve replacement (TAVR). We investigated the prognostic value and clinical utility of left atrial reservoir strain (LARS) in patients undergoing TAVR for aortic stenosis (AS). METHODS AND RESULTS: All consecutive patients undergoing TAVR between January 2018 and December 2018 were included if discharge echocardiography and follow-up were available. LARS was derived from 2D-speckle-tracking. Patients were grouped into three tertiles according to LARS. DD was analysed using the ASE/EACVI-algorithm. The primary outcome was a composite of all-cause death and readmission for worsening heart failure 12 months after TAVR. Overall, 606 patients were available [age 80 years, interquartile range (IQR) 77-84], including 53% women. Median LARS was 13.0% (IQR 8.4-18.3). Patients were classified by LARS tertiles [mildly impaired 21.4% (IQR 18.3-24.5), moderately impaired 13.0% (IQR 11.3-14.6), severely impaired 7.1% (IQR 5.4-8.4), P < 0.0001]. The primary outcome occurred more often in patients with impaired LARS (mildly impaired 7.4%, moderately impaired 13.4%, and severely impaired 25.7%, P < 0.0001). On adjusted multivariable Cox regression analysis, LARS tertiles [hazard ratio (HR) 0.62, 95% confidence interval (CI) 0.44-0.86, P = 0.005] and higher degree of tricuspid regurgitation (HR 1.82, 95% CI 1.23-2.98, P = 0.003) were the only significant predictors of the primary endpoint. Importantly, DD was unavailable in 56% of patients, but LARS assessment allowed for reliable prognostication regarding the primary endpoint in subgroups without DD assessment (HR 0.64, 95% CI 0.47-0.87, P = 0.003). CONCLUSION: Impaired LARS is independently associated with worse outcomes in patients undergoing TAVR. LARS allows for risk stratification at discharge even in patients where DD cannot be assessed by conventional echocardiographic means.

Femoral Arterial Calcification and Plug- vs. Suture-Based Closure Device Strategies Post-Transcatheter Aortic Valve Implantation: Insights From CHOICE-CLOSURE.

Background: The location and severity of vascular calcification may influence closure device success in transfemoral transcatheter aortic valve implantation. The aim of this study was to analyze effects of vascular access-site calcification on vascular and bleeding outcomes post-transcatheter aortic valve implantation. Methods: The Randomized Comparison of CatHeter-based Strategies fOr Interventional ACcess SitE CLOSURE during Transfemoral Transcatheter Aortic Valve Implantation (CHOICE-CLOSURE) trial assigned 516 patients to access site closure using a pure plug-based technique (MANTA, Teleflex) or a primary suture-based technique (ProGlide, Abbott Vascular). The principal finding of the overall study was that access-site or access-related complications were more common after the plug-based strategy compared to percutaneous closure with a suture-based strategy. In this predefined subgroup analysis, the overall cohort was split into patients with and without anterior calcification at the access site and divided by degree of calcification severity using the classification system developed in the MANTA vs. suture-based vascular closure after transcatHeter aortic valve replacement (MASH) trial. Differences in bleeding and vascular complications were compared. The primary endpoint consisted of access-site- or access-related major and minor vascular complications. Results: There were more access-site-related major and minor vascular complications for patients with anterior wall vascular calcification and MASH severe calcification. No significant interaction with choice of closure technique in terms of access-site-related major and minor vascular complications was observed (odds ratio 1.70, 95% CI 0.77-3.78, p = 0.19 for the primary endpoint in plug- vs. suture-based strategy in patients with anterior calcification, odds ratio 1.78, 95% CI 0.56-5.65, p = 0.33 for primary endpoint in plug- vs. suture-based strategy with MASH severe calcification, pint = 0.97 for anterior calcification, pint = 0.95 for MASH severe calcification). Conclusions: The total number of vascular complications was found to be greater in the presence of anterior and MASH severe calcification. Overall, the presence of anterior or severe calcification does not significantly modify the efficacy of the suture-based strategy compared to the plug-based strategy.

Percutaneous Left Atrial Appendage Occlusion-Current Evidence and Future Directions.

Over the past two decades, percutaneous left atrial appendage occlusion (LAAO) has proven to be a viable alternative to oral anticoagulation (OAC) for stroke prevention in patients with atrial fibrillation (AF), in particular in those patients who are at increased risk for stroke and bleeding complications. This systematic review provides a comprehensive evaluation of anatomical features, patient selection, procedural planning and execution, complications, medical treatment following the procedure, and contemporary outcome data.

Comparison of plug-based versus suture-based vascular closure for large-bore arterial access: a collaborative meta-analysis of observational and randomized studies.

BACKGROUND: Large-bore arteriotomies can be percutaneously closed with suture-based or plug-based vascular closure device (VCD) strategies. The efficacy of both techniques remains controversial. AIMS: We conducted a meta-analysis of comparative studies between both VCD strategies, focusing on the most commonly applied VCDs (MANTA and ProGlide). METHODS: We searched MEDLINE, the Cochrane Central Register of Controlled Trials and Google scholar for observational studies (OS) and randomized controlled trials (RCT) comparing vascular closure with the MANTA-based and the ProGlide-based technique. The principal endpoint of this analysis was access-site related vascular complications. Both study types were analyzed separately. RESULTS: Access-site related vascular complications were less frequent after vascular closure with the MANTA technique in the analysis of OS (RR 0.61 [95%CI 0.43-0.89], p = 0.01, I2 = 0%), but more frequent in the analysis of RCT data (RR 1.70 [95%CI 1.16-2.51], p = 0.01, I2 = 0%). Both data sets provided no significant difference between the VCD techniques in terms of overall bleeding events (OS: RR 0.57 [95%CI 0.32-1.02], p = 0.06, I2 = 70%; and RCT: RR 1.37 [95%CI 0.82-2.28], p = 0.23, I2 = 30%). RCT data showed that endovascular stenting or vascular surgery due to VCD failure occurred more often after MANTA application (RR 3.53 [95%CI 1.07-11.33], p = 0.04, I2 = 0%). CONCLUSIONS: While OS point to favorable outcomes for large-bore vascular closure with the MANTA-based technique, RCT data show that this strategy is associated with more access-site related vascular complications as well as endovascular stenting or vascular surgery due to device failure compared with the ProGlide-based technique.

Acute myocardial infarction associated with prosthetic valve leaflet thrombosis after transcatheter aortic valve implantation: a case report.

BACKGROUND: Fatal thrombo-embolic events like cerebral stroke or myocardial infarction are rare complications of prosthetic heart valve leaflet thrombosis. Nevertheless, prevention and management of leaflet thrombosis is gaining increased attention, particularly with the widespread adoption of transcatheter heart valves. CASE SUMMARY: We herein present the case of a 79-year-old man who had undergone a transcatheter aortic valve implantation procedure. Seven months later, he presented with a non-ST-segment elevation myocardial infarction. Coronary angiography did not reveal obstructive lesions. A dedicated cardiac computed tomography scan showed thrombosis of both right- and non-coronary leaflets of the prosthetic aortic valve, while prosthetic valve function was normal on echocardiography. Transmural myocardial infarction lesions in the midventricular and apical inferior wall were detected by cardiac magnetic resonance imaging. DISCUSSION: Subclinical leaflet thrombosis of prosthetic aortic valves is a common finding. In this case report, we show that myocardial infarction presumably due to leaflet thrombosis was the first symptom in an otherwise asymptomatic patient. This finding raises the question of the validity in distinguishing between subclinical and clinical leaflet thrombosis based on prosthetic valve function.

Nontypeable Haemophilus Influenzae Infection Upregulates the NLRP3 Inflammasome and Leads to Caspase-1-Dependent Secretion of Interleukin-1ß - A Possible Pathway of Exacerbations in COPD.

RATIONALE: Nontypeable Haemophilus influenzae (NTHi) is the most common cause for bacterial exacerbations in chronic obstructive pulmonary disease (COPD). Recent investigations suggest the participation of the inflammasome in the pathomechanism of airway inflammation. The inflammasome is a cytosolic protein complex important for early inflammatory responses, by processing Interleukin-1ß (IL-1ß) to its active form. OBJECTIVES: Since inflammasome activation has been described for a variety of inflammatory diseases, we investigated whether this pathway plays a role in NTHi infection of the airways. METHODS: A murine macrophage cell line (RAW 264.7), human alveolar macrophages and human lung tissue (HLT) were stimulated with viable or non-viable NTHi and/or nigericin, a potassium ionophore. Secreted cytokines were measured with ELISA and participating proteins detected via Western Blot or immunohistochemistry. MEASUREMENTS AND MAIN RESULTS: Western Blot analysis of cells and immunohistochemistry of lung tissue detected the inflammasome key components NLRP3 and caspase-1 after stimulation, leading to a significant induction of IL-1ß expression (RAW: control at the lower detection limit vs. NTHi 505±111pg/ml, p<0.01). Inhibition of caspase-1 in human lung tissue led to a significant reduction of IL-1ß and IL-18 levels (IL-1ß: NTHi 24 h 17423±3198pg/ml vs. NTHi+Z-YVAD-FMK 6961±1751pg/ml, p<0.01). CONCLUSION: Our data demonstrate the upregulation of the NRLP3-inflammasome during NTHi-induced inflammation in respiratory cells and tissues. Our findings concerning caspase-1 dependent IL-1ß release suggest a role for the inflammasome in respiratory tract infections with NTHi which may be relevant for the pathogenesis of bacterial exacerbations in COPD.