The impact of increased pulmonary arterial pressure on outcomes after transcatheter aortic valve replacement.

OBJECTIVE: To evaluate the impact of increased pulmonary artery systolic pressure (PASP) on outcomes after transcatheter aortic valve replacement (TAVR). METHODS: A total of 242 patients who underwent TAVR were retrospectively reviewed. Transthoracic echocardiography estimated PASP. The cohorts were divided into three groups according to the numerical change of PASP; Increased (post-TAVR PASP at 1 month minus pre-TAVR PASP, ≥ + 5 mmHg; n = 52), No change (-5 to +5 mmHg; n = 86) and Decreased (≤ -5 mmHg; n = 104). Patient demographics and clinical outcomes until 1 year were evaluated. Logistic regression model was used for multivariate risk analysis. RESULTS: At 1 year, the Increased group showed higher mortality (21 ± 6%) than the No change group (5 ± 2%) (hazard ratio [HR]: 4.8, 95% confidence interval [CI]: 1.7-13.5; p < .01) and the Decreased group (8 ± 3%) (HR: 2.8, 95% CI: 1.1-6.7; p = .02). Rehospitalization rate for valve-related or heart failure was also higher in the Increased group (21 ± 6%) than the No change group (10 ± 3%) (HR: 2.4, 95% CI: 1.1-6.0; p = .04). Predictors of PASP deterioration were hypertension (odds ratio [OR]: 3.9, 95% CI: 1.1-13.8; p = .04) and left ventricular end-diastolic diameter >50 mm (OR: 2.2, 95% CI: 1.1-4.6; p = .04), and the increased PASP remained an independent predictor of 1-year all-cause mortality (HR; 2.7, 95% CI: 1.0-6.8; p = .04). CONCLUSIONS: Regardless of the baseline PASP, patients with increased PASP at 1 month after successful TAVR were at higher risk of mortality and rehospitalization within 1 year. Strict medical management should be considered for patients who showed dilated left ventricle preoperatively.

Percutaneous closure of left ventricle pseudoaneurysm using 3D printed heart model for procedure planning: A novel approach.

Left ventricle pseudoaneurysm is a rare complication of myocardial infarction that carries a high risk of mortality. In this report, we present a case of successful percutaneous closure of left ventricle pseudoaneurysm using 3D printing for procedure guidance.

Lipopolysaccharide Density and Structure Govern the Extent and Distance of Nanoparticle Interaction with Actual and Model Bacterial Outer Membranes.

Design of nanomedicines and nanoparticle-based antimicrobial and antifouling formulations and assessment of the potential implications of nanoparticle release into the environment requires understanding nanoparticle interaction with bacterial surfaces. Here we demonstrate the electrostatically driven association of functionalized nanoparticles with lipopolysaccharides of Gram-negative bacterial outer membranes and find that lipopolysaccharide structure influences the extent and location of binding relative to the outer leaflet-solution interface. By manipulating the lipopolysaccharide content in Shewanella oneidensis outer membranes, we observed the electrostatically driven interaction of cationic gold nanoparticles with the lipopolysaccharide-containing leaflet. We probed this interaction by quartz crystal microbalance with dissipation monitoring (QCM-D) and second harmonic generation (SHG) using solid-supported lipopolysaccharide-containing bilayers. The association of cationic nanoparticles increased with lipopolysaccharide content, while no association of anionic nanoparticles was observed. The harmonic-dependence of QCM-D measurements suggested that a population of the cationic nanoparticles was held at a distance from the outer leaflet-solution interface of bilayers containing smooth lipopolysaccharides (those bearing a long O-polysaccharide). Additionally, smooth lipopolysaccharides held the bulk of the associated cationic particles outside of the interfacial zone probed by SHG. Our results demonstrate that positively charged nanoparticles are more likely to interact with Gram-negative bacteria than are negatively charged particles, and this interaction occurs primarily through lipopolysaccharides.

Attachment of pathogenic prion protein to model oxide surfaces.

Prions are the infectious agents in the class of fatal neurodegenerative diseases known as transmissible spongiform encephalopathies, which affect humans, deer, sheep, and cattle. Prion diseases of deer and sheep can be transmitted via environmental routes, and soil is has been implicated in the transmission of these diseases. Interaction with soil particles is expected to govern the transport, bioavailability and persistence of prions in soil environments. A mechanistic understanding of prion interaction with soil components is critical for understanding the behavior of these proteins in the environment. Here, we report results of a study to investigate the interactions of prions with model oxide surfaces (Al2O3, SiO2) using quartz crystal microbalance with dissipation monitoring and optical waveguide light mode spectroscopy. The efficiency of prion attachment to Al2O3 and SiO2 depended strongly on pH and ionic strength in a manner consistent with electrostatic forces dominating interaction with these oxides. The presence of the N-terminal portion of the protein appeared to promote attachment to Al2O3 under globally electrostatically repulsive conditions. We evaluated the utility of recombinant prion protein as a surrogate for prions in attachment experiments and found that its behavior differed markedly from that of the infectious agent. Our findings suggest that prions would tend to associate with positively charged mineral surfaces in soils (e.g., iron and aluminum oxides).

Classification of left ventricular diastolic function using American Society of Echocardiography Guidelines: agreement among echocardiographers.

Guidelines for assessing diastolic function by echocardiography are continually being updated. Our ability to use available guidelines effectively has not been completely investigated. Six trained echocardiographers were asked to interpret 105 echocardiograms using current American Society of Echocardiography (ASE) algorithms for interpretation of diastolic grade and estimation of left atrial (LA) pressure. Diastolic grade was categorized as normal, mild, moderate, or severe dysfunction. The presence or absence of elevated LA pressure was determined using a second ASE algorithm. As a reference comparison for level of agreement, left ventricular ejection fraction was visually determined. By the ASE algorithm, 29 subjects (28%) met all measurement criteria in their assigned grade and 57 subjects (55%) met all or all but one criterion of their assigned grade. Of the 45 subjects (43%) for whom the guidelines disagreed by more than 1 criterion, the readers debated between normal and moderate dysfunction in 22% or mild and moderate diastolic dysfunction in 31%. Percent inter-reader agreement and kappa values were 76% (0.7) for determining diastolic grade, 84% (0.67) for determining elevated LA pressure, and 84% (0.67) for estimation of ejection fraction, the reference standard. For all subjects, if multiple echocardiographic criteria failed to fit into the proposed guidelines, agreement fell to 66% (0.58) for determining diastolic grade and 74% (0.48) for determining LA pressure. There is reasonable agreement estimating diastolic grade and LA pressure using current guidelines. Further refinements in the definition of mild and moderate dysfunction may improve agreement.

Cardiopulmonary Exercise Testing, Rehabilitation, and Exercise Training in Postpulmonary Embolism.

Long-term exercise intolerance and functional limitations are common after an episode of acute pulmonary embolism (PE), despite 3 to 6 months of anticoagulation. These persistent symptoms are reported in more than half of the patients with acute PE and are referred as "post-PE syndrome." Although these functional limitations can occur from persistent pulmonary vascular occlusion or pulmonary vascular remodeling, significant deconditioning can be a major contributing factor. Herein, the authors review the role of exercise testing to elucidate the mechanisms of exercise limitations to guide next steps in management and exercise training for musculoskeletal deconditioning.

Prognosis of paradoxical low-flow low-gradient aortic stenosis after transcatheter aortic valve replacement.

AIMS: In paradoxical low-flow low-gradient severe aortic stenosis (PLFLG AS) patients, stroke volume index (SVI) is reduced despite preserved left ventricular ejection fraction (LVEF). Although reduced SVI is already known as a poor prognostic predictor, the outcomes of PLFLG AS patients after transcatheter aortic valve replacement (TAVR) have not been clearly defined. We retrospectively investigated the post-TAVR outcomes of PLFLG AS patients in comparison with normal-flow high-gradient aortic stenosis (NFHG AS) patients. METHODS: The current observational study included 245 patients with NFHG AS (mean transaortic pressure gradient ≥40 mmHg and LVEF ≥ 50%) and 48 patients with PLFLG AS (mean transaortic pressure gradient <40 mmHg, LVEF ≥ 50% and SVI < 35 ml/m2). The endpoints were all-cause mortality, hospitalization for valve-related symptoms or worsening congestive heart failure and New York Heart Association functional class III or IV. RESULTS: PLFLG AS patients had a significantly higher proportion with a history of atrial fibrillation/flutter as compared with NFHG AS patients. All-cause mortality of PLFLG AS patients was worse than that of NFHG AS patients (P = 0.047). Hospitalization for valve-related symptoms or worsening congestive heart failure was more frequent in PLFLG AS patients than in NFHG AS patients (P = 0.041). New York Heart Association functional class III-IV after TAVR was more frequently observed in PLFLG AS patients (P = 0.019). CONCLUSION: The outcomes of PLFLG AS patients were worse than those of NFHG AS patients in this study. Preexisting atrial fibrillation/flutter was frequent in PLFLG AS patients, and may affect their post-TAVR outcomes. Therefore, closer post-TAVR follow-up should be considered for these patients.

The Prognosis of Elderly Patients with Aortic Stenosis after Transcatheter Aortic Valve Replacement.

Objective Aortic stenosis (AS) is common among elderly patients. Since transcatheter aortic valve replacement (TAVR) is a less invasive procedure than surgical aortic valve replacement for symptomatic severe AS, super-elderly patients have tended to undergo TAVR. We retrospectively investigated the post-TAVR outcome in super-elderly patients with severe AS. Methods This analysis included 433 patients who underwent TAVR in the University of Wisconsin Hospital and Clinics from 2012 to 2017. Post-TAVR mortality, complications in-hospital, rehospitalization, the New York Heart Association (NYHA) functional class and echocardiographic parameters were compared between patients <85 years old (n = 290) and ≥85 years old (n = 143). Results The patients ≥85 years old less frequently had a history of coronary artery disease (73.1% vs. 62.2%, p=0.026) and hypertension (87.2% vs. 77.6%, p=0.012) than younger patients. Furthermore, the patients ≥85 years old had moderate-severe mitral regurgitation more frequently (19.3% vs. 28.7%, p=0.037) at baseline than younger patients. There was no significant difference in in-hospital outcomes between the age groups. The 30-day mortality was worse in patients ≥85 years old than in younger ones (0.7% vs. 3.5%, p=0.042). While there was no significant difference in the long-term mortality between the 2 groups, the estimated 1-year mortality from Kaplan-Meier curves were 9.6% in patients <85 years old and 14.9% in patients ≥85 years old. The rate of in-hospital complications, rehospitalization rate, improvement in the NYHA functional class and echocardiographic parameters were comparable between the two groups. Conclusion The outcomes of super-elderly patients after TAVR were acceptable, suggesting that these patients could benefit from TAVR.

Transport of the pathogenic prion protein through soils.

Transmissible spongiform encephalopathies (TSEs) are progressive neurodegenerative diseases and include bovine spongiform encephalopathy of cattle, chronic wasting disease (CWD) of deer and elk, scrapie in sheep and goats, and Creutzfeldt-Jakob disease in humans. An abnormally folded form of the prion protein (designated PrP(TSE)) is typically associated with TSE infectivity and may constitute the major, if not sole, component of the infectious agent. Transmission of CWD and scrapie is mediated in part by an environmental reservoir of infectivity. Soil appears to be a plausible candidate for this reservoir. The transport of TSE agent through soil is expected to influence the accessibility of the pathogen to animals after deposition and must be understood to assess the risks associated with burial of infected carcasses. We report the results of saturated column experiments designed to evaluate PrP(TSE) transport through five soils with relatively high sand or silt contents and low organic carbon content. Protease-treated TSE-infected brain homogenate was used as a model for PrP(TSE) present in decomposing infected tissue. Synthetic rainwater was used as the eluent. All five soils retained PrP(TSE); no detectable PrP(TSE) was eluted over more than 40 pore volumes of flow. Lower bound apparent attachment coefficients were estimated for each soil. Our results suggest that TSE agent released from decomposing tissues to soils with low organic carbon content would remain near the site of initial deposition. In the case of infected carcasses deposited on the land surface, this may result in local sources of infectivity to other animals.

Percutaneous Vacuum-Assisted Thrombectomy Using AngioVac Aspiration System.

BACKGROUND: Surgical embolectomy and thrombolytic therapy are two common approaches for the treatment of large intra-cardiac or intravascular thrombi to prevent new or worsening pulmonary embolism (PE). Considering high operative mortality with surgical embolectomy and high bleeding risk with thrombolytic therapy, patients who are poor candidates for these treatments may benefit from percutaneous aspiration thrombectomy/Vacuum-assisted thrombectomy (VAT). AngioVac aspiration system was granted 510(k) clearance by the United States Food and Drug Administration (FDA) in April 2009. We present a case series to describe its use and outcomes in evacuating large caval thrombi or intracardiac masses. METHODS: We did a retrospective analysis of AngioVac catheter based thrombectomy in 16 consecutive patients treated between January 2016 and January 2019 to report case characteristics and in-hospital clinical outcomes. RESULTS: Sixteen patients (mean age 48) underwent 16 AngioVac procedures over 48 months. Indications included intracardiac mass (68.8%), caval thrombus (56.3%), and catheter associated thrombus (43.8%). 7 (43.8%) patients had concurrent PE. Peri-procedure mortality was 0% and in-hospital mortality was 12.5% at a mean follow-up of 14 days. There were no pulmonary hemorrhages, strokes or myocardial infarctions. 62.5% had a significant drop in hemoglobin, which required a blood transfusion but there was no episode of overt bleeding. CONCLUSION: The AngioVac aspiration system has been shown to be effective at aspirating large volumes of intravascular and intracardiac thrombus. It is a reasonable alternative to surgical thrombectomy in patients with large central thrombi or masses in-transit who are at risk of complicated PE.

Evaluation and treatment of acute and chronic injuries to the capsular ligaments of the knee.

Injury to the capsular ligaments of the knee commonly occurs in conjunction with cruciate ligament injury. An untreated grade III sprain can lead to recurrent meniscal injury, failure of cruciate ligament reconstruction, and arthrosis. Careful clinical examination is necessary to identify injuries to discrete ligaments and estimate the severity of injuries not discernable on imaging studies. A classification system of capsular injury is useful to link the diagnosis to a treatment algorithm. Anatomically based surgical procedures for acute and chronic sprains of the posteromedial, anterolateral, and posterolateral capsular structures have been proven in long-term outcome studies. The goal is to restore the anatomy by repair (for an acute sprain) or capsular shift (for a chronic sprain), rather than to substitute extra-articular tendon routing.

Endovascular Therapy for Rheumatic Mitral and Aortic Valve Disease: Review Article.

Rheumatic heart disease remains a major cause of significant mortality and morbidity in the developing world. Rheumatic mitral and aortic stenosis are the two most common valvular sequelae of acute rheumatic fever. Open surgical procedures with either valve replacement or surgical commissurotomy have largely been replaced by percutaneous commissurotomy and balloon valvuloplasty for selected patients since the early 1980s. The purpose of our review is to examine the literature for any recent advancement in procedural techniques of balloon valvuloplasty for selected patients with rheumatic mitral and or aortic stenosis. Our search indicates that, in general, the volume of recent publications on this important topic is rather scanty with no major changes in the fundamentals of procedural techniques and or primary indications for balloon valvuloplasty of a rheumatic valve stenosis. Percutaneous balloon valvuloplasty/commissurotomy remains the main stay of therapy for rheumatic valvular stenosis in selected patients with favorable valve anatomy.

Inter- and intra-observer repeatability of aortic annulus measurements on screening CT for transcatheter aortic valve replacement (TAVR): Implications for appropriate device sizing.

OBJECTIVES: To investigate intra- and inter-observer repeatability of aortic annulus CT measurements for transcatheter aortic valve replacement (TAVR) by readers with different levels of experience and evaluate the impact of different multi-reader paradigms to improve prosthesis sizing. METHODS: 82 TAVR screening CTAs were evaluated twice by three raters with six (R1 = radiologist), three (R2 = 3D-laboratory technician) or zero (R3 = medical student) years of experience. Results were translated into hypothetical TAVR size recommendations. Intra- and inter-observer repeatability between single readers and three different multi-reader paradigms ([A]: two readers, [B]: three readers, or [C]: two readers + an optional third reader) were evaluated. RESULTS: Intra-observer variability did not differ significantly (range: 50.1-67.8mm2). However, we found significant differences in mean inter-observer variance (p = 0.001). Multi-reader paradigms led to significantly increased precision (lower variability) for scenarios [B] and [C] (p = 0.03, p < 0.05). Compared to single readers, all multi-reader strategies clearly lowered the rate of discrepant device size categorization between repeated measurements (22-26% to 5-10%). CONCLUSIONS: Aortic annulus CT measurements for TAVR are highly reproducible. Multi-reader strategies provide higher precision than evaluations from single readers with different levels of experience and could effectively be implemented with two readers and an optional third reader (Paradigm C) in a clinical setting.

Recurrent severe aortic stenosis one year after transcatheter aortic valve-in-valve implantation: Successful treatment with balloon aortic valvuloplasty.

Transcatheter aortic valve-in-valve (VIV) implantation has evolved as one of the primary therapeutic modalities in patients with failed surgical bioprosthesis allowing a reduction in rate of surgical reintervention. We report a case of a 90-year-old woman who had previously undergone aortic valve replacement with 21-mm Carpentier-Edwards valve in 1999 followed by 23 mm Sapien VIV in March 2013. She developed severe recurrent aortic stenosis 1-year post-VIV which was successfully treated with balloon aortic valvuloplasty (BAV). BAV can be a favorable treatment option allowing considerable symptomatic relief and improvement in performance of daily activities in extreme age patients who develop restenosis after VIV implantation and are high-risk candidates for both redo-surgical aortic valve replacement and redo-VIV implantation. .

Posterolateral reconstruction of the knee using capsular procedures for evaluation and treatment of posterolateral instability of the knee.

Posterolateral rotatory instability of the knee causes significant morbidity if unrecognized and left untreated. With both acute and chronic injuries, restoration of the normal anatomy is crucial for a good outcome. During capsular repairs, detailed knowledge of the anatomy will help the surgeon repair the pathoanatomy. To complement the direct approach, an osteotomy of the lateral femoral condyle that includes the attachments of the fibular collateral ligament and popliteal tendon allows superior visualization of the lateral meniscus and its attachments, as well as the associated deep structures. The osteotomy also permits placement of posterior capsular sutures that allow the capsular shift to tighten the injured structures. Fine-tuning the tension of these structures may be accomplished by slightly adjusting the position of the bone block as it is reattached without significantly affecting isometry. The osteotomy is not required for all reconstructions; however, it provides excellent access to the deep structures of the posterolateral corner. The capsular shift can complement the direct repair of structures and may be done as an isolated or staged procedure or in combination with other reconstructive treatment options.

The posteromedial corner of the knee: medial-sided injury patterns revisited.

BACKGROUND: Medial-sided knee injury patterns have been poorly defined in the available literature. The lack of definition can be attributed to the differing anatomic perspectives of physician authors and the functional significance they assigned to the posteromedial structures of the knee. HYPOTHESIS: Many so-called medial collateral ligament injuries can involve significant damage to the posteromedial corner structures that may not be appreciated. STUDY DESIGN: Retrospective cohort study. METHOD: The authors reviewed the charts of 93 patients (93 knees) with operatively treated isolated and combined medial-sided knee injuries and described the associated medial injury patterns. RESULTS: Ninety-nine percent of the knees were found to have an injury of the posterior oblique ligament. In the series, 70% of the knees also had an injury of the semimembranosus capsular attachment, and 30% were found to have complete peripheral detachment of the meniscus. Injury to the posterior oblique ligament was the common injury, but other sites of disruption capable of disabling this dynamic meniscocapsular complex were present. CONCLUSIONS: Before assigning function to the various posteromedial structures of the knee, we must better define medial-sided injury patterns, the purpose of the current work. From this review of medial-sided injuries in this series of patients, the authors have come to realize that a subgroup of these knee injuries involves injuries to the posteromedial structures that are under-appreciated.

Elongation kinetics of polyglutamine peptide fibrils: a quartz crystal microbalance with dissipation study.

Abnormally expanded polyglutamine domains in proteins are associated with several neurodegenerative diseases, including Huntington's disease. Expansion of the polyglutamine (polyQ) domain facilitates aggregation of the affected protein, and several studies directly link aggregation to neurotoxicity. Studies of synthetic polyQ peptides have contributed substantially to our understanding of the mechanism of aggregation. In this report, polyQ fibrils were immobilized onto a sensor, and their elongation by polyQ peptides of various length and conformation was examined using quartz crystal microbalance with dissipation monitoring (QCM-D). The rate of elongation increased as the peptide length increased from 8 to 24 glutamines (Q8, Q20, and Q24). Monomer conformation affected elongation rates: insertion of a ß-turn template d-Pro-Gly in the center of the peptide increased elongation rates several-fold, while insertion of Pro-Pro dramatically slowed elongation. Dissipation measurements of the QCM-D provided qualitative information about mechanical properties of the elongating fibrils. These data showed clear differences in the characteristics of the elongating aggregates, depending on the specific identity of the associating polyQ peptide. Elongation rates were sensitive to the pH and ionic strength of the buffer. Comparison of QCM-D data with those obtained by optical waveguide lightmode spectroscopy revealed that very little water was associated with the elongation of fibrils by the peptide containing d-Pro-Gly, but a significant amount of water was associated when the fibrils were elongated by Q20. Together, the data indicate that elongation of polyQ fibrils can occur without full consolidation to the fibril structure, resulting in variations to the aggregate structure during elongation.

Transport of the pathogenic prion protein through landfill materials.

Transmissible spongiform encephalopathies (TSEs, prion diseases) are a class of fatal neurodegenerative diseases affecting a variety of mammalian species including humans. A misfolded form of the prion protein (PrP(TSE)) is the major, if not sole, component of the infectious agent RecentTSE outbreaks in domesticated and wild animal populations have created the need for safe and effective disposal of large quantities of potentially infected materials. Here, we report results of a study to evaluate the potential for transport of PrP(TSE) derived from carcasses and associated wastes in municipal solid waste (MSW) landfills. Column experiments were conducted to evaluate PrP(TSE) transport in quartz sand, two fine-textured burial soils currently used in landfill practice, a green waste residual material (a potential burial material), and fresh and aged MSW. PrP(TSE) was retained by quartz sand and the fine-textured burial soils, with no detectable PrP(TSE) eluted over more than 40 pore volumes. In contrast, PrP(TSE) was more mobile in MSW and green waste residual. Transport parameters were estimated from the experimental data and used to model PrP(TSE) migration in a MSW landfill. To the extent that the PrP(TSE) used mimics that released from decomposing carcasses and the column experiments adequately simulate prion transport through burial soils, burial of CWD-infected materials at MSW landfills could provide secure containment of PrP(TSE) provided reasonable burial strategies (e.g., encasement in fine-grained soil) are used.