Patient Risk Factors for Bioprosthetic Aortic Valve Degeneration: A Systematic Review and Meta-Analysis.

The choice of valve type for aortic valve replacement surgery is sometimes challenging. The main risk for bioprostheses is structural valve degeneration (SVD); however, little is known about what the most important risk factors are. We conducted a systematic review and meta-analysis to identify the risk factors and estimate their pooled effect sizes to aid the prosthesis choice for replacement. We followed PRISMA guidelines and systematically searched three electronic databases (PubMed, Scopus, and Web of Science) using appropriate key terms: 'aortic valve', 'bioprosthesis', 'degeneration', 'durability', 'prosthesis failure', etc. Hazard ratio (HR) and odds ratio (OR) and associated 95% confidence intervals (CI) were extracted. Pooled risk estimates were calculated using a random-effects model. Twenty-nine (29) observational studies were included with a total of 25,490 patients, 981 of whom developed SVD over a mean follow-up time of 18.5 years. Four (4) factors influencing bioprosthetic SVD were identified: increasing age was a protective factor (per 1-yr increase, HR: 0.91 [95% CI 0.89, 0.94], p<0.0001), whereas increased body surface area (HR 1.77 [1.04, 3.01], p=0.034), patient-prosthesis mismatch (HR 1.95 [1.56, 2.43], p<0.001), and smoking (HR 2.28 [1.37, 3.79], p=0.0015) were risk factors for SVD. We found younger age, patient-prosthesis mismatch, body surface area, and smoking, as risk factors for aortic SVD, which should be considered for valve selection. This study generates a further hypothesis that accelerated flow across the valve is a shared key component in the pathophysiology of SVD, thus future research should consider other high cardiac output states.

Potentially actionable FGFR2 high-level amplification in thymic sebaceous carcinoma.

Our aim was to investigate sebaceous differentiation in thymus tumours and to identify new actionable genomic alterations. To this end we screened 35 normal and 23 hyperplastic thymuses, 127 thymomas and 41 thymic carcinomas for the presence of sebaceous differentiation as defined by morphology and expression of adipophilin and androgen receptor (AR). One primary thymic carcinoma showed morphology of sebaceous carcinomas (keratinizing and foam cells, calcifications, giant cells), a strong expression of adipophilin and AR together with squamous markers. NGS revealed high-level amplification of fibroblast growth factor receptor 2 (FGFR2). In thymuses and thymomas, no cells with sebaceous morphology were present. Occasionally, macrophages or epithelial cells showed adipophilin-positivity, however, without co-expression of AR. Thymic sebaceous carcinoma should be considered if a thymic carcinoma shows clear or foamy features. Testing for FGFR2 amplification might be warranted when searching for actionable genomic alterations in sebaceous carcinomas in the mediastinum and in other locations.

The natural history of guidelines: the case of aortopathy related to bicuspid aortic valves.

Clinical guidelines represent statements that seek to synthesize the best evidence to guide a course of action to improve health outcomes and more cost-effective use of resources. However, even when the evidence is not definitive, comprehensive documents are still needed to guide clinical decision-making. In these circumstances, guidelines are inevitably affected by perceptions of the problem and their possible solutions. From 1998 to 2014, 10 different international guidelines have focused on the aortopathy related to bicuspid aortic valves. Recommended thresholds for intervention started at a cutoff level of 5.5cm in 1998, reached a nadir of 4 to 4.5cm in 2010, and returned to a 5.5cm cutoff level in 2014. During this time, no conclusive objective proof was published to support either an aggressive or conservative strategy. The consequence was that an undefined number of patients underwent surgery (and potential complications thereof) at an earlier disease stage than might have been necessary. This experience might provide a clue as to how guidelines evolve, and provide insight as to how to avoid a similar process in the future.

Surgical thresholds for bicuspid aortic valve associated aortopathy.

OBJECTIVES: This systematic review seeks to present the outcomes of the natural history of aortopathy associated with bicuspid aortic valve (ABAV) and after interventions. BACKGROUND: Aortopathy is common in patients with ABAV, and early intervention has been proposed to reduce the risk of dissection. In asymptomatic patients, the timing of surgical management is based upon imaging of aortic size, but the actual threshold is based upon observational data and expert opinion. As evidence of high risk would justify early intervention, we sought to define the natural history of this condition and after interventions. METHODS: We undertook a systemic review of the evidence from observational studies of ABAV published up to June 2013. The primary outcome was annualized all-cause mortality. Secondary outcomes included acute aortic events, rates of aneurysm enlargement, and peri-operative complications. A random-effects model was used to combine outcomes. A meta-regression was undertaken to assess the impact of potential covariates. RESULTS: The 32 eligible papers involved 11,045 patients (9,441 BAV and 1,604 control subjects, age 46 ± 14 years). There were 3 major groups, nonoperated bicuspid aortic valve (BAV) patients (ages from 30 to 40 years), patients after aortic surgery (generally 40 to 60 years of age) and after isolated valve replacement (>60 years of age). The respective annualized mortality of nonoperated BAV patients was 0.56% (95% confidence interval [CI]: 0.13 to 0.99), compared with 0.78% (95% CI: 0.20 to 1.36) in patients after aortic surgery and 2.39% (95% CI: 1.61 to 3.16) after isolated valve replacement. The annualized acute event rate in nonoperated BAV patients was 0.29% (95% CI: 0.23 to 0.35), this risk being no different from that of a tricuspid aortic valve (risk ratio: 0.68, 95% CI: 0.34 to 1.36). In the post-surgical series, 30-day mortality varied from 0% to 2.5%, and the risk of acute events was 0.16% (95% CI: 0.0 to 0.32) in patients after aortic surgery and 0.68% (95% CI: 0.42 to 0.94) after isolated valve replacement. Aortic dilation was at a rate of 0.16 mm/year over 6 decades in healthy BAV subjects and 1.1 ± 0.15 mm/year in older aortic valve replacement patients. CONCLUSIONS: The risk associated with ABAV varies according to age and clinical setting. Nonetheless, despite aortic dilatation, the acute aortic event risk of ABAV appears low in current practice. Decision-making regarding the timing of intervention needs to be made on the basis of the balance between this low risk and both the morbidity and mortality of surgery.

Intracardiac lipoma arising from the papillary muscle.

Cardiac lipoma is the commonest nonmyxomatous benign primary cardiac tumor. We report a case of lipoma arising from the anterolateral papillary muscle and presenting with a transient ischemic episode and a history of malignant melanoma. The lipoma was removed leaving the mitral apparatus intact.

Human blood vessel-derived endothelial progenitors for endothelialization of small diameter vascular prosthesis.

BACKGROUND: Coronary bypass graft failure as a result of acute thrombosis and intimal hyperplasia has been the major challenge in surgical procedures involving small-diameter vascular prosthesis. Coating synthetic grafts with patients' own endothelial cells has been suggested to improve the patency rate and overall success of bypass surgeries. METHODOLOGY/PRINCIPAL FINDINGS: We isolated endothelial progenitor cells (EPCs) from leftover pieces of human saphenous vein/mammary artery. We demonstrate that EPCs can be expanded to generate millions of cells under low-density culture conditions. Exposure to high-density conditions induces differentiation to endothelial cell phenotype. EPC-derived endothelial cells show expression of CD144high, CD31, and vWF. We then assessed the ability of differentiated endothelial cells to adhere and grow on small diameter expanded polytetrafluoroethylene (ePTFE) tubings. Since ePTFE tubings are highly hydrophobic, we optimized protocols to introduce hydrophilic groups on luminal surface of ePTFE tubings. We demonstrate here a stepwise protocol that involves introduction of hydrophilic moieties and coating with defined ECM components that support adhesion of endothelial cells, but not of blood platelets. CONCLUSION/SIGNIFICANCE: Our data confirms that endothelial progenitors obtained from adult human blood vessels can be expanded in vitro under xenoprotein-free conditions, for potential use in endothelialization of small diameter ePTFE grafts. These endothelialized grafts may represent a promising treatment strategy for improving the clinical outcome of small-caliber vascular grafts in cardiac bypass surgeries.