Procedural Volume and Outcomes for Transcatheter Aortic-Valve Replacement.

BACKGROUND: During the introduction of transcatheter aortic-valve replacement (TAVR) in the United States, requirements regarding procedural volume were mandated by the Centers for Medicare and Medicaid Services as a condition of reimbursement. A better understanding of the relationship between hospital volume of TAVR procedures and patient outcomes could inform policy decisions. METHODS: We analyzed data from the Transcatheter Valve Therapy Registry regarding procedural volumes and outcomes from 2015 through 2017. The primary analyses examined the association between hospital procedural volume as a continuous variable and risk-adjusted mortality at 30 days after transfemoral TAVR. Secondary analysis included risk-adjusted mortality according to quartile of hospital procedural volume. A sensitivity analysis was performed after exclusion of the first 12 months of transfemoral TAVR procedures at each hospital. RESULTS: Of 113,662 TAVR procedures performed at 555 hospitals by 2960 operators, 96,256 (84.7%) involved a transfemoral approach. There was a significant inverse association between annualized volume of transfemoral TAVR procedures and mortality. Adjusted 30-day mortality was higher and more variable at hospitals in the lowest-volume quartile (3.19%; 95% confidence interval [CI], 2.78 to 3.67) than at hospitals in the highest-volume quartile (2.66%; 95% CI, 2.48 to 2.85) (odds ratio, 1.21; P = 0.02). The difference in adjusted mortality between a mean annualized volume of 27 procedures in the lowest-volume quartile and 143 procedures in the highest-volume quartile was a relative reduction of 19.45% (95% CI, 8.63 to 30.26). After the exclusion of the first 12 months of TAVR procedures at each hospital, 30-day mortality remained higher in the lowest-volume quartile than in the highest-volume quartile (3.10% vs. 2.61%; odds ratio, 1.19; 95% CI, 1.01 to 1.40). CONCLUSIONS: An inverse volume-mortality association was observed for transfemoral TAVR procedures from 2015 through 2017. Mortality at 30 days was higher and more variable at hospitals with a low procedural volume than at hospitals with a high procedural volume. (Funded by the American College of Cardiology Foundation National Cardiovascular Data Registry and the Society of Thoracic Surgeons.).

Effect of Activated Carbon in Thin Sand Caps Challenged with Ongoing PCB Inputs from Sediment Deposition: PCB Uptake in Clams (Mercenaria mercenaria) and Passive Samplers.

Ongoing inputs, in the form of sediment deposition along with associated dissolved contaminants, have challenged the assessment of cap performance at contaminated sediment sites. To address this issue, thin 2-3 cm layer sand caps amended with activated carbon (AC) were investigated for the remediation of polychlorinated biphenyl (PCB) contaminated marine sediments using 90-day mesocosms. All treatments were challenged with (1) ongoing clean or marker-PCB-spiked sediment inputs and (2) bioturbation. Bioaccumulation in hard clams (filter feeding near the cap-water interface) was evaluated to best understand cap effectiveness, relative to sheepshead minnows (confined to the surface water) and sandworms (which burrowed through the caps). All caps (sand and AC amended sand) provided isolation of native bedded PCBs (i.e., PCBs sourced from the bed), reducing uptake in organisms. Total PCB bioaccumulation in clams indicated that AC addition to the cap provided no benefit with spiked influx, or some benefit (56% reduction) with clean influx. Spiked input PCBs, when added to the depositional input sediment, were consistently detected in clams and passive samplers, with and without AC in the cap. PCB uptake by passive samplers located in the caps did not reflect the performance of the remedy, as defined by clam bioaccumulation. However, PCB uptake by passive samplers in the overlying water reasonably represented clam bioaccumulation results.

Self-expanding intra-annular versus commercially available transcatheter heart valves in high and extreme risk patients with severe aortic stenosis (PORTICO IDE): a randomised, controlled, non-inferiority trial.

BACKGROUND: Randomised trial data assessing the safety and efficacy of the self-expanding intra-annular Portico transcatheter aortic valve system (Abbott Structural Heart, St Paul, MN, USA) compared with any commercially available valves are needed to compare performance among designs. METHODS: In this prospective, multicentre, non-inferiority, randomised controlled trial (the Portico Re-sheathable Transcatheter Aortic Valve System US Investigational Device Exemption trial [PORTICO IDE]), high and extreme risk patients with severe symptomatic aortic stenosis were recruited from 52 medical centres experienced in performing transcatheter aortic valve replacement in the USA and Australia. Patients were eligible if they were aged 21 years or older, in New York Heart Association functional class II or higher, and had severe native aortic stenosis. Eligible patients were randomly assigned (1:1) using permuted block randomisation (block sizes of 2 and 4) and stratified by clinical investigational site, surgical risk cohort, and vascular access method, to transcatheter aortic valve replacement with the first generation Portico valve and delivery system or a commercially available valve (either an intra-annular balloon-expandable Edwards-SAPIEN, SAPIEN XT, or SAPIEN 3 valve [Edwards LifeSciences, Irvine, CA, USA]; or a supra-annular self-expanding CoreValve, Evolut-R, or Evolut-PRO valve [Medtronic, Minneapolis, MN, USA]). Investigational site staff, implanting physician, and study participant were unmasked to treatment assignment. Core laboratories and clinical event assessors were masked to treatment allocation. The primary safety endpoint was a composite of all-cause mortality, disabling stroke, life-threatening bleeding requiring transfusion, acute kidney injury requiring dialysis, or major vascular complication at 30 days. The primary efficacy endpoint was all-cause mortality or disabling stroke at 1 year. Clinical outcomes and valve performance were assessed up to 2 years after the procedure. Primary analyses were by intention to treat and the Kaplan-Meier method to estimate event rates. The non-inferiority margin was 8·5% for primary safety and 8·0% for primary efficacy endpoints. This study is registered with ClinicalTrials.gov, NCT02000115, and is ongoing. FINDINGS: Between May 30 and Sept 12, 2014, and between Aug 21, 2015, and Oct 10, 2017, with recruitment paused for 11 months by the funder, we recruited 1034 patients, of whom 750 were eligible and randomly assigned to the Portico valve group (n=381) or commercially available valve group (n=369). Mean age was 83 years (SD 7) and 395 (52·7%) patients were female. For the primary safety endpoint at 30 days, the event rate was higher in the Portico valve group than in the commercial valve group (52 [13·8%] vs 35 [9·6%]; absolute difference 4·2, 95% CI -0·4 to 8·8 [upper confidence bound {UCB} 8·1%]; pnon-inferiority=0·034, psuperiority=0·071). At 1 year, the rates of the primary efficacy endpoint were similar between the groups (55 [14·8%] in the Portico group vs 48 [13·4%] in the commercial valve group; difference 1·5%, 95% CI -3·6 to 6·5 [UCB 5·7%]; pnon-inferiority=0·0058, psuperiority=0·50). At 2 years, rates of death (80 [22·3%] vs 70 [20·2%]; p=0·40) or disabling stroke (10 [3·1%] vs 16 [5·0%]; p=0·23) were similar between groups. INTERPRETATION: The Portico valve was associated with similar rates of death or disabling stroke at 2 years compared with commercial valves, but was associated with higher rates of the primary composite safety endpoint including death at 30 days. The first-generation Portico valve and delivery system did not offer advantages over other commercially available valves. FUNDING: Abbott.

Partnership Between Japan and the United States for Early Development of Pediatric Medical Devices　- Harmonization By Doing for Children.

BACKGROUND: The Harmonization By Doing (HBD) program was established in 2003 as a partnership among stakeholders of academia, industry and regulatory agencies in Japan and the United States, with a primary focus on streamlining processes of global medical device development for cardiovascular medical devices. While HBD has traditionally focused on development of devices intended to treat conditions prevalent in adults, in 2016, HBD established the "HBD-for-Children" program, which focuses on the development of pediatric devices as the development of medical devices for pediatric use lags behind that of medical devices for adults in both countries.Methods and Results:Activities of the program have included: (1) conducting a survey with industry to better understand the challenges that constrain the development of pediatric medical devices; (2) categorizing pediatric medical devices into five categories based on global availability and exploring concrete solutions for the early application and regulatory approval in both geographies; and (3) facilitating global clinical trials of pediatric medical devices in both countries. CONCLUSIONS: The establishment of the HBD-for-Children program is significant because it represents a global initiative for the introduction of pediatric medical devices for patients in a timely manner. Through the program, academia, industry and regulatory agencies can work together to facilitate innovative pediatric device development from a multi-stakeholder perspective. This activity could also encourage industry partners to pursue the development of pediatric medical devices.

Clinical Trial Principles and Endpoint Definitions for Paravalvular Leaks in Surgical Prosthesis.

The VARC (Valve Academic Research Consortium) for transcatheter aortic valve replacement set the standard for selecting appropriate clinical endpoints reflecting safety and effectiveness of transcatheter devices, and defining single and composite clinical endpoints for clinical trials. No such standardization exists for circumferentially sutured surgical valve paravalvular leak (PVL) closure. This document seeks to provide core principles, appropriate clinical endpoints, and endpoint definitions to be used in clinical trials of PVL closure devices. The PVL Academic Research Consortium met to review evidence and make recommendations for assessment of disease severity, data collection, and updated endpoint definitions. A 5-class grading scheme to evaluate PVL was developed in concordance with VARC recommendations. Unresolved issues in the field are outlined. The current PVL Academic Research Consortium provides recommendations for assessment of disease severity, data collection, and endpoint definitions. Future research in the field is warranted.

Possible Subclinical Leaflet Thrombosis in Bioprosthetic Aortic Valves.

BACKGROUND: A finding of reduced aortic-valve leaflet motion was noted on computed tomography (CT) in a patient who had a stroke after transcatheter aortic-valve replacement (TAVR) during an ongoing clinical trial. This finding raised a concern about possible subclinical leaflet thrombosis and prompted further investigation. METHODS: We analyzed data obtained from 55 patients in a clinical trial of TAVR and from two single-center registries that included 132 patients who were undergoing either TAVR or surgical aortic-valve bioprosthesis implantation. We obtained four-dimensional, volume-rendered CT scans along with data on anticoagulation and clinical outcomes (including strokes and transient ischemic attacks [TIAs]). RESULTS: Reduced leaflet motion was noted on CT in 22 of 55 patients (40%) in the clinical trial and in 17 of 132 patients (13%) in the two registries. Reduced leaflet motion was detected among patients with multiple bioprosthesis types, including transcatheter and surgical bioprostheses. Therapeutic anticoagulation with warfarin, as compared with dual antiplatelet therapy, was associated with a decreased incidence of reduced leaflet motion (0% and 55%, respectively, P=0.01 in the clinical trial; and 0% and 29%, respectively, P=0.04 in the pooled registries). In patients who were reevaluated with follow-up CT, restoration of leaflet motion was noted in all 11 patients who were receiving anticoagulation and in 1 of 10 patients who were not receiving anticoagulation (P<0.001). There was no significant difference in the incidence of stroke or TIA between patients with reduced leaflet motion and those with normal leaflet motion in the clinical trial (2 of 22 patients and 0 of 33 patients, respectively; P=0.16), although in the pooled registries, a significant difference was detected (3 of 17 patients and 1 of 115 patients, respectively; P=0.007). CONCLUSIONS: Reduced aortic-valve leaflet motion was shown in patients with bioprosthetic aortic valves. The condition resolved with therapeutic anticoagulation. The effect of this finding on clinical outcomes including stroke needs further investigation. (Funded by St. Jude Medical and Cedars-Sinai Heart Institute; Portico-IDE ClinicalTrials.gov number, NCT02000115; SAVORY registry, NCT02426307; and RESOLVE registry, NCT02318342.).

In-hospital outcomes of transcatheter versus surgical aortic valve replacement in end stage renal disease.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is an alternative to surgical aortic valve replacement (SAVR) for patients with severe symptomatic aortic stenosis (AS) who are at intermediate and high risk for surgery. Commercial use of TAVR has expanded to patients with end stage renal disease (ESRD). OBJECTIVES: Compare in-hospital outcomes of TAVR versus SAVR in ESRD patients requiring hemodialysis (HD). METHODS: ESRD patients on HD undergoing TAVR (n = 328) or SAVR (n = 697) between 2012 and 2014 were identified in the National Inpatient Sample (NIS). Propensity-score matching method was used to minimize selection bias. Baseline characteristics and in-hospital outcomes were compared. RESULTS: TAVR patients were older (75.3 vs. 61.6 years, P < 0.001) and had more comorbidities, including congestive heart failure (16.2% vs. 7.5%), diabetes mellitus (28.4% vs. 22.5%), chronic lung disease (27.7% vs. 20.4%), and peripheral vascular disease (35.1% vs. 21.2%). Propensity-score matching yielded 175 pairs of patients matched on 30 baseline covariates. Overall in-hospital mortality was high (9.9%) and similar between TAVR and SAVR (8% vs. 10.3%, P = 0.58). TAVR was associated with shorter length of stay (LOS) (8 vs. 14 days, P < 0.001), lower hospitalization cost ($276,448 vs. $364,280, P = 0.01), lower in-hospital complications (60.6% vs. 76%, P = 0.003), and higher rate of home discharge (31.4% vs. 17.7%, P = 0.004) compared with SAVR. CONCLUSIONS: Regardless of treatment modality, patients with AS on HD have high in-hospital mortality. TAVR and SAVR have comparable in-hospital mortality in this population. However, TAVR is associated with shorter LOS, lower hospitalization costs, lower in-hospital complications, and higher rates of home discharge.

Hopscotch technique: A novel method for percutaneous closure of paravalvular leaks.

OBJECTIVES: To describe the feasibility and safety of the Hopscotch Technique, a novel method to close paravalvular leaks. BACKGROUND: Successful closure of paravalvular leaks requires the complete seal of irregular defects, frequently interrupted by remaining sutures or tissue that converts a large defect into a complex series of contiguous smaller defects. Successful treatment with devices placed in a single space is impossible with constrained appearance and significant residual leak; therefore, new techniques to deploy smaller devices in the correct location are needed. METHODS: We retrospective analyzed all the patients with mitral PVLs undergoing percutaneous closure with the Hopscotch technique from November 2011 to January 2016. RESULTS: Sixteen procedures were performed in 15 patients (median age 66-year-old, 67% male, STS 3.9%), most of them with biological prostheses (73%). Mean PVL size was 12.5 mm located in the lateral position. Percutaneous transapical access was the final approach in nine procedures and success of the procedure was achieved in 12. Usually, the technique was performed by 1 Hopscotch crossing/jump; however, complex procedures requiring 2 or 3 crossings were utilized in 4 patients, even possible between aortic and mitral leaks along the aortic-mitral continuity. Residual mitral paravalvular regurgitation of ≤mild was achieved in 93% of procedures. CONCLUSIONS: The Hopscotch technique is feasible and safety for patients with mitral paravalvular leak when boundaries prevent full device expansion. © 2017 Wiley Periodicals, Inc.

Percutaneous left atrial appendage occlusion: the Munich consensus document on definitions, endpoints, and data collection requirements for clinical studies.

The increasing interest in left atrial appendage occlusion (LAAO) for ischaemic stroke prevention in atrial fibrillation (AF) fuels the need for more clinical data on the safety and effectiveness of this therapy. Besides an assessment of the effectiveness of the therapy in specific patients groups, comparisons with pharmacological stroke prophylaxis, surgical approaches, and other device-based therapies are warranted. This paper documents the consensus reached among clinical experts in relevant disciplines from Europe and North America, European cardiology professional societies, and representatives from the medical device industry regarding definitions for parameters and endpoints to be assessed in clinical studies. Adherence to these definitions is proposed in order to achieve a consistent approach across clinical studies on LAAO among the involved stakeholders and various clinical disciplines and thereby facilitate continued evaluation of therapeutic strategies available.

The future of transcatheter mitral valve interventions: competitive or complementary role of repair vs. replacement?

Transcatheter mitral interventions has been developed to address an unmet clinical need and may be an alternative therapeutic option to surgery with the intent to provide symptomatic and prognostic benefit. Beyond MitraClip therapy, alternative repair technologies are being developed to expand the transcatheter intervention armamentarium. Recently, the feasibility of transcatheter mitral valve implantation in native non-calcified valves has been reported in very high-risk patients. Acknowledging the lack of scientific evidence to date, it is difficult to predict what the ultimate future role of transcatheter mitral valve interventions will be. The purpose of the present report is to review the current state-of-the-art of mitral valve intervention, and to identify the potential future scenarios, which might benefit most from the transcatheter repair and replacement devices under development.

Available transcatheter aortic valve replacement technology.

Transcatheter aortic valve replacement (TAVR) is an alternative and now recommended therapy for patients who meet indications for surgical valve replacement and are high or prohibitive surgical risk. Available TAVR technologies are rapidly emerging to treat this complex patient population. This review discusses the specific valve designs of the transcatheter heart valves currently used, newer generation modifications to overcome limitations of earlier valve designs, and novel imaging modalities, such as computed tomographic angiography-fluoroscopy and echocardiography-fluoroscopy fusion imaging, available for pre-procedural planning and intra-procedural guidance.

Novel approach for the percutaneous treatment of left ventricular pseudoaneurysms.

Left ventricular pseudoaneurysm (LVPA) is a rare yet serious complication that may follow cardiac surgery, myocardial infarction, trauma, or infection. If left untreated, reported rates of rupture and sudden cardiac death are high. Although surgical intervention has traditionally been the standard treatment for LVPA, percutaneous closure is now an attractive alternative in the high-risk patient. We report a case of a successful percutaneous LVPA closure using direct chest wall entry into the pseudoaneurysm. This novel approach can be useful when access to the LVPA is a challenge, especially in the setting of small ostial size, dense left ventricular trabeculations, angulated serpiginous tract, and presence of mechanical prostheses.

SCAI/AATS/ACC/STS operator and institutional requirements for transcatheter valve repair and replacement, Part III: Pulmonic valve.

With the evolution of transcatheter valve replacement, an important opportunity has arisen for cardiologists and surgeons to collaborate in identifying the criteria for performing these procedures. Therefore, The Society for Cardiovascular Angiography and Interventions (SCAI), American Association for Thoracic Surgery (AATS), American College of Cardiology (ACC), and The Society of Thoracic Surgeons (STS) have partnered to provide recommendations for institutions to assess their potential for instituting and/or maintaining a transcatheter valve program. This article concerns transcatheter pulmonic valve replacement (tPVR). tPVR procedures are in their infancy with few reports available on which to base an expert consensus statement. Therefore, many of these recommendations are based on expert consensus and the few reports available. As the procedures evolve, technology advances, experience grows, and more data accumulate, there will certainly be a need to update this consensus statement. The writing committee and participating societies believe that the recommendations in this report serve as appropriate requisites. In some ways, these recommendations apply to institutions more than to individuals. There is a strong consensus that these new valve therapies are best performed using a Heart Team approach; thus, these credentialing criteria should be applied at the institutional level. Partnering societies used the ACC's policy on relationships with industry (RWI) and other entities to author this document (http://www.acc.org/guidelines/about-guidelines-and-clinical-documents). To avoid actual, potential, or perceived conflicts of interest due to industry relationships or personal interests, all members of the writing committee, as well as peer reviewers of the document, were asked to disclose all current healthcare-related relationships including those existing 12 months before the initiation of the writing effort. A committee of interventional cardiologists and surgeons was formed to include a majority of members with no relevant RWI and to be led by an interventional cardiology cochair and a surgical cochair with no relevant RWI. Authors with relevant RWI were not permitted to draft or vote on text or recommendations pertaining to their RWI. RWI were reviewed on all conference calls and updated as changes occurred. Author and peer reviewer RWI pertinent to this document are disclosed in the Appendices. In addition, to ensure complete transparency, authors' comprehensive disclosure information (including RWI not pertinent to this document) is available in Appendix AII. The work of the writing committee was supported exclusively by the partnering societies without commercial support. SCAI, AATS, ACC, and STS believe that adherence to these recommendations will maximize the chances that these therapies will become a successful part of the armamentarium for treating valvular heart disease in the United States. In addition, these recommendations will hopefully facilitate optimum quality during the delivery of this therapy, which will be important to the development and successful implementation of future, less invasive approaches to structural heart disease.

Effect of age and maternal antibodies on the systemic and mucosal immune response after neonatal immunization in a porcine model.

Newborn mammals are highly susceptible to respiratory infections. Although maternal antibodies (MatAb) offer them some protection, they may also interfere with their systemic immune response to vaccination. However, the impact of MatAb on the neonatal mucosal immune response remains incompletely described. This study was performed to determine the effect of ovalbumin (OVA) -specific MatAb on the anti- OVA antibody response in sera, nasal secretions and saliva from specific pathogen-free Vietnamese miniature piglets immunized at 7 or 14 days of age. Our results demonstrated that MatAb increased antigen-specific IgA and IgG responses in sera, and transiently enhanced an early secretory IgA response in nasal secretions of piglets immunized at 7 days of age. In contrast, we detected a lower mucosal (nasal secretion and saliva) anti- OVA IgG response in piglets with MatAb immunized at 14 days of age, compared with piglets with no MatAb, suggesting a modulatory effect of antigen-specific maternal factors on the isotype transfer to the mucosal immune exclusion system. In our porcine model, we demonstrated that passive maternal immunity positively modulated the systemic and nasal immune responses of animals immunized early in life. Our results, therefore, open the possibility of inducing systemic and respiratory mucosal immunity in the presence of MatAb through early vaccination.

Guidance of post myocardial infarction ventricular septal defect and pseudoaneurysm closure.

Left ventricular pseudoaneurysm and ventricular septal defect are rare but devastating complications of myocardial infarction. With medical treatment alone, the majority of patients will die from these complications. Until recently, the recommended treatment was surgical closure. These surgeries carried extreme risk due to abnormal hemodynamics, necrotic substrates and the comorbidities of these patients. Recently, trans-catheter closure was shown to be an acceptable alternative to open surgical intervention. 3D echocardiography identifies the location, size, and shape of the defect and can assess, guide, and follow up the closure procedure.

Review of surgical prosthetic paravalvular leaks: diagnosis and catheter-based closure.

Paravalvular leak (PVL) is an uncommon yet serious complication associated with surgical prosthetic valve implantation. Paravalvular leak can have significant clinical consequence such as congestive heart failure, haemolytic anaemia, and infective endocarditis. Recently, transcatheter therapy has been applied to the treatment of this disorder with reasonable procedural and clinical success. This review discusses the current state of PVLs, the utilization of multi-modality imaging in their diagnosis and treatment, and the available therapeutic options. Further aim of this review is to examine transcatheter therapy of PVLs including the principles, outcomes, and procedural-related complications.

Toward a universalistic behavioural model of perceived managerial and leadership effectiveness for the health services sector.

Much management and leadership development provision for healthcare professionals has been the subject of considerable criticism, and there have been numerous calls for training programmes explicitly focused on the specific managerial (manager/leader) behaviours healthcare managers, physician leaders and nurse managers need to exhibit to be perceived effective. The aim of our multiple cross-case/cross-nation comparative study has been to: i) identify similarities and differences between the findings of published qualitative critical incident studies of effective and ineffective managerial behaviour observed within British, Egyptian, Mexican and Romanian public hospitals, respectively, and ii) if possible, deduce from the identified commonalities a healthcare-related behavioural model of perceived managerial and leadership effectiveness. Adopting a philosophical stance informed by pragmatism, epistemological instrumentalism and abduction, we used realist qualitative analytic methods to code and classify into a maximum number of discrete behavioural categories empirical source data obtained from five previous studies. We found high degrees of empirical generalization which resulted in the identification of five positive (effective) and four negative (ineffective) behavioural dimensions (BDs) derived, respectively, from 14 positive and 9 negative deduced behavioural categories (BCs). These BDs and underpinning BCs are expressed in the form of an emergent two-factor universalistic behavioural model of perceived managerial and leadership effectiveness. We suggest the model could be used to critically evaluate the relevance and appropriateness of existing training provision for physician leaders, nurse managers and other healthcare managers/leaders in public hospitals or to design new explicit training programmes informed and shaped by healthcare-specific management research, as called for in the literature.

Vacuum thrombectomy of large right atrial thrombus.

We report a novel technique for percutaneous removal of the right heart thrombi using a suction cannula. This method allowed complete en bloc removal of the right atrial thrombus avoiding surgical procedure in a high risk patient.