Implantation Of Bioprosthetic Heart Valves Research Articles

The α-Gal KO Mouse Animal Model is a Reliable and Predictive Tool for the Immune-Mediated Calcification Assessment of Heart Valve Bioprostheses.

Recent studies highlighted the presence of anti-α-Gal antibodies in patients implanted with commercial bioprosthetic heart valves (BHVs). BHVs expose residual α-Gal xenoantigen and their recognition by the circulating anti-Gal antibodies leads to opsonization of the device's tissue component with the consequent triggering of a deterioration pathway that culminates with calcification. Small animal models such as mice and rats have been broadly involved in the in vivo testing of biomaterials by subcutaneous implantation, especially for the effectiveness of BHVs anti-calcific treatments. However, since models employed for this purpose express α-Gal antigen, the implantation of BHVs' leaflets does not elicit a proper immunological response, so the calcification propensity may be dramatically underestimated. An α-Gal knockout (KO) mouse model has been created, using the CRISP/Cas9 approach, and adopted to assess the calcification potential of commercial BHVs leaflets through the surgical implantation in the back subcutis area. Calcium quantification was performed by inductively coupled plasma analysis; immune response against the BHVs leaflets and α-Gal silencing was evaluated through immunological assays. Two months after the implantation of commercial BHV leaflets, the anti-Gal antibody titers in KO mice doubled when compared with those found in wild-type (WT) ones. Leaflets explanted from KO mice, after one month, showed a four-time increased calcium deposition concerning the ones explanted from WT. The degree of silencing of α-Gal varied, depending on the specific organ that was assessed. In any case, the animal model was suitable for evaluating implanted tissue responses. Such mouse model proved to be an accurate tool for the study of the calcific propensity of commercial BHVs leaflets than those hitherto used. Given its reliability, it could also be successfully used to study even other diseases in which the possible involvement of α-Gal has been observed.

Recent progress in functional modification and crosslinking of bioprosthetic heart valves.

Valvular heart disease (VHD), clinically manifested as stenosis and regurgitation of native heart valve, is one of the most prevalent cardiovascular diseases with high mortality. Heart valve replacement surgery has been recognized as golden standard for the treatment of VHD. Owing to the clinical application of transcatheter heart valve replacement technic and the excellent hemodynamic performance of bioprosthetic heart valves (BHVs), implantation of BHVs has been increasing over recent years and gradually became the preferred choice for the treatment of VHD. However, BHVs might fail within 10-15 years due to structural valvular degeneration (SVD), which was greatly associated with drawbacks of glutaraldehyde crosslinked BHVs, including cytotoxicity, calcification, component degradation, mechanical failure, thrombosis and immune response. To prolong the service life of BHVs, much effort has been devoted to overcoming the drawbacks of BHVs and reducing the risk of SVD. In this review, we summarized and analyzed the research and progress on: (i) modification strategies based on glutaraldehyde crosslinked BHVs and (ii) nonglutaraldehyde crosslinking strategies for BHVs.

Visible light-induced cross-linking of porcine pericardium for the improvement of endothelialization, anti-tearing, and anticalcification properties.

Population aging and the development of transcatheter aortic valve replacement boost the implantation of bioprosthetic heart valves (BHVs) in patients worldwide. However, the traditional glutaraldehyde cross-linked BHVs fail within 12-15 years mainly due to leaflet tear and calcification defects. In this study, a novel visible light-induced cross-linking of the porcine pericardium (PP) was realized by the photo-oxidation of the furfuryl-modified PP in the presence of Rose Bengal. The resulting material showed comparable collagen stability with the glutaraldehyde cross-linked PP and appropriate biomechanical properties such as tensile strength, modulus, and elongation, suggesting that this material could meet the general requirement for BHVs. Besides, this cross-linked PP showed significantly improved cytocompatibility compared with the Glut-cross-linked PP, with no cytotoxicity to L929 cells and the ability to support HUVECgrowth. Meanwhile, this material showed superior anti-tearing performance and much less calcification than the Glut-cross-linked PP in hope of reducing the risk of BHV failure. Considering these results, the visible light-induced cross-linking method proposed in this study could provide a promising way to construct a biocompatible and robust biomaterial for the fabrication of the BHV.

Does Surgical Ablation of Atrial Fibrillation Benefit Patients Undergoing Bioprosthetic Valve Replacement?

The benefit of avoiding lifelong anticoagulation therapy in patients with bioprosthetic heart valve implantation may potentially be offset by atrial fibrillation (AF); however, clinical impact of surgical AF ablation in such patients remains controversial. We enrolled 426 patients (aged 72.0 ± 7.8 years) with AF who underwent left-side valve replacement with bioprostheses between 2001 and 2018. Of these, 297 underwent concomitant surgical ablation (ablation group) and 129 underwent valve replacement alone (non-ablation group). Clinical outcomes were compared, and mortality was considered as a competing risk factor against valve-related complications. Inverse-probability weighting (IPTW) was adopted to reduce selection bias. The ablation group had lower baseline risk profiles than the non-ablation group. In crude analysis, early mortality rates were 3.4% and 7.0% in the ablation and non-ablation groups, respectively (P=0.104). During follow-up (1521.9 patient-years), the ablation group showed lower AF-recurrence (P < 0.001) and anticoagulant medication rate (P=0.021), and lower overall mortality risk (subdistribution hazard ratio [SHR], 0.63; 95% confidence interval [CI], 0.42-0.94), but higher risk of permanent pacemaker implantation (SHR, 4.67; 95% CI, 1.36-16.05). No significant difference in the risk of stroke (SHR, 1.27; 95% CI, 0.55-2.95) was observed between the groups. After baseline IPTW-adjustment, findings of the clinical outcomes were analogous to those from crude analyses. In patients undergoing bioprosthetic valve replacement, the addition of surgical ablation was associated with improved rhythm outcomes and survival but at the expense of a higher risk of pacemaker implantation. The underlying mechanism of improved survival by AF ablation needs further investigation.

A method for simultaneously crosslinking and functionalizing extracellular matrix-based biomaterials as bioprosthetic heart valves with enhanced endothelialization and reduced inflammation

With the coming of an aging society and the emergence of transcatheter valve technology, the implantation of bioprosthetic heart valves (BHVs) in patients with valvular disease has significantly increased worldwide. Currently, most clinically available BHVs are crosslinked with glutaraldehyde (GLUT). However, the GLUT treated BHV is less durable due to the combined effect of multiple factors such as cytotoxicity, immune responses, and calcification. In this study, the in-situ polymerization of sulfonic monomers with a decellularized extracellular matrix (ECM) was performed to simultaneously achieve the crosslinking and functionalization of ECM. Subsequently, the feasibility of the hybrid ECM used as leaflet material of BHV was evaluated. In in-vitro tests, the results indicated that the hybrid ECM fixed collagen efficiently and the introduction of sulfonic polymer promoted the proliferation and migration of human umbilical vein endothelial cells (HUVECs). In in-vivo tests, after being implanted in SD rats and mice, the hybrid ECM significantly inhibited immune response and calcification compared with the non-hybrid counterpart and GLUT crosslinked tissue. These results indicated that the hybrid ECM exhibited more competitive stability and better biocompatibility compared to these features in GLUT-crosslinked valve. Therefore, the sulfonic polymer hybrid ECM provides a potential material for more durable BHV and the in-situ polymerization strategy can serve as a general treatment method for tissue crosslinking as well as tailoring the biophysical properties of ECM.

Degeneration of Bioprosthetic Heart Valves: Update 2020

The implantation of bioprosthetic heart valves (BHVs) is increasingly becoming the treatment of choice in patients requiring heart valve replacement surgery. Unlike mechanical heart valves, BHVs are less thrombogenic and exhibit superior hemodynamic properties. However, BHVs are prone to structural valve degeneration (SVD), an unavoidable condition limiting graft durability. Mechanisms underlying SVD are incompletely understood, and early concepts suggesting the purely degenerative nature of this process are now considered oversimplified. Recent studies implicate the host immune response as a major modality of SVD pathogenesis, manifested by a combination of processes phenocopying the long‐term transplant rejection, atherosclerosis, and calcification of native aortic valves. In this review, we summarize and critically analyze relevant studies on (1) SVD triggers and pathogenesis, (2) current approaches to protect BHVs from calcification, (3) obtaining low immunogenic BHV tissue from genetically modified animals, and (4) potential strategies for SVD prevention in the clinical setting.

Interfacial Coating Method for Amine-Rich Surfaces using Poly(ethylene glycol) Diacrylate Applied to Bioprosthetic Valve Tissue Models.

Bioprosthetic heart valve implants are beset by calcification and failure due to the interactions between the body and the transplant. Hydrogels can be used as biological blank slates that may help to shield implants from these interactions; however, traditional light-based hydrogel polymerization is impeded by tissue opacity and topography. Therefore, new methods must be created to bind hydrogel to implant tissues. To address these complications, a two-step surface-coating method for bioprosthetic valves was developed. A previously developed bioprosthetic valve model (VM) was used to investigate and optimize the coating method. Generally, this coating is achieved by first reacting surface amine groups with an NHS-PEG-acrylate while also allowing glucose to absorb into the bulk. Then, glucose oxidase, poly(ethylene glycol) diacrylate (PEGDA), and iron ions are added to the system to initiate free-radical polymerization that bonds the PEGDA hydrogel to the acrylates sites on the surface. Results showed a thin (∼8 μm), continuous coating on VM samples that is capable of repelling protein adhesion (2% surface fouling versus 20% on uncoated samples) and does not significantly affect the surface mechanical properties. Based on this success, the coating method was translated to glutaraldehyde-fixed valve tissue samples. Results showed noncontinuous but evident coating on the surface, which was further improved by adjusting the coating solution. These results demonstrate the feasibility of the proposed two-step surface coating method for modifying the surface of bioprosthetic valve replacements.

Nonvitamin K Antagonist Oral Anticoagulants Use in Patients with Atrial Fibrillation and Bioprosthetic Heart Valves/Prior Surgical Valve Repair: A Multicenter Clinical Practice Experience.

This is an observational study to investigate the efficacy and safety of nonvitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF) patients with bioprosthetic valves or prior surgical valve repair in clinical practice. A total of 122 patients (mean age: 74.1 ± 13.2; 54 females) with bioprosthetic heart valve or surgical valve repair and AF treated with NOACs were included in the analysis. The mean CHA2DS2-VASc (Congestive heart failure, Hypertension, Age >75 years, Diabetes mellitus, prior Stroke or transient ischemic attack, Vascular disease) and HAS-BLED (Hypertension, Abnormal renal and liver function, Stroke, Bleeding, Labile INR [international normalized ratio], Elderly, Drugs or alcohol) score values were 3.6 ± 1.2 and 2.6 ± 1.4, respectively. Of the total study population, 28.6% was taking apixaban 5 mg twice daily (BID), 24.5% apixaban 2.5 mg BID, 18% dabigatran 150 mg BID, 13% dabigatran 110 mg BID, 9.8% rivaroxaban 20 mg daily (QD), and 5.7% rivaroxaban 15 mg QD. Also, 92% of the study population previously had warfarin replaced with NOACs due to lack compliance and labile INR control (time in therapeutic range < 60%). NOAC therapy for AF was started on average 934 ± 567 days after bioprosthetic heart valve implantation or surgical repair for an average duration of 835 ± 203 days. The study population included 24 (19.6%) patients with bioprosthetic mitral valve, 52 (43%) patients with bioprosthetic aortic valve, 41 (33.6%) patients with previous surgical mitral repair, 5 (4%) patients with previous surgical aortic repair, and concomitant use of NOACs. All patients were evaluated for thromboembolic events (ischemic stroke, transient ischemic attack, systemic embolism) as well as major bleeding events during the follow-up period. In our study population, we recorded a low mean annual incidence of thromboembolism (0.8%) and major bleeding (1.3%). According to our data, anticoagulation therapy with NOACs seems to be an effective and a safe treatment strategy for nonvalvular AF patients with bioprosthetic valves or prior surgical valve repair.

Alpha-Gal Inactivated Heart Valve Bioprostheses Exhibit an Anti-Calcification Propensity Similar to Knockout Tissues.

Glutaraldehyde (GLA) has been used to crosslink bioprosthetic heart valve (BHVs) tissues to enhance their stability, besides ensuring a satisfactory degree of immunological tolerance. Unfortunately, GLA fixation does not guarantee a complete tissue biocompatibility of BHVs in currently used devices. The interaction between preformed human anti-alpha-Gal antibody and alpha-Gal antigens promotes the calcification of GLA-treated alpha-Gal-positive tissue. Recently, an alarming correlation between the presence of the alpha-Gal epitope and a premature BHVs degeneracy was reported. This article presents the results of a novel treatment called FACTA, for the inactivation of the alpha-Gal epitopes in porcine aortic valve tissue and commercial BHVs. Evaluation of the alpha-Gal epitope inactivation was performed through a patented ELISA test, confirmed by western blot, immunofluorescence, and immunohistochemical analyses. Investigations were also conducted to assess the in vitro propensity to trigger thrombosis, calcification, and worsening of FACTA-treated tissue. To explain the mechanism of action through which the FACTA treatment acts, a specific experimental model, based on the mass spectroscopy approach, was performed. The study confirms that GLA is able to ensure the inactivation of approximately half alpha-Gal epitopes originally present in both porcine aortic valve tissue and marketed BHVs. By subjecting tissues to the FACTA procedure, it was possible to obtain an alpha-Gal inactivation degree of about 95% alongside to a reduced propensity from 72.6% to 85.4% to the in vitro calcification for porcine aortic valve tissue and 80.5% for commercial treated BHVs. FACTA was effective in decreasing oxidative tissue damage and protecting collagen from degradation. Finally, FACTA could further mitigate or even abrogate the need for early anticoagulation therapies after BHV implantation. A novel treatment, called FACTA, is effective to produce biological tissues that are less susceptible to enzymatic and oxidative stress and structural degradation, calcification, and thrombus formation. FACTA-treated tissues display a clear improvement of their biocompatibility that is characterized by an almost complete inactivation of the alpha-Gal epitope. FACTA prevents the xenogeneic tissue antigens from reacting with the host immune system, ensuring an effective shield effect that makes the tissue surface less reactive and more biocompatible.

Computational Modeling for Fluid–Structure Interaction of Bioprosthetic Heart Valve with Different Suture Density: Comparison with Dynamic Structure Simulation

In this paper, a parametric geometry model based on elliptic and conic surfaces was developed for bioprosthetic heart valve (BHV) simulation. The valve material was modeled by a hyperelastic nonlinear anisotropic solid model. Different suture densities could be substituted by various bonded points between artery vessel and the leaflets as boundary conditions in the computational modeling. Besides these two assumptions that dynamic structure (DS) and fluid–structure interaction (FSI) both shared, the latter need incompressible viscous Newton fluid model to depict bloodstream passing through the BHV. Immersed boundary (IB) method was introduced to solve the FSI simulation. In addition, the DS analysis applied transvalvular pressure on the valve while FSI had left ventricular pressure on fluid inlet as initials. There was inconsistency between the moments of the maximum deformation and the maximum loading in both simulations. Although a similar trend of deformation lagging the load was viewed, the extent of delay in FSI was much smaller compared with that in DS simulation. The deformed profiles in cross-sectional views were shown in one picture to illustrate different dynamic responses caused by distinct assumptions. Percent of open area at the moments when the maximum deformation occurred was defined to show which calculation achieved better approximation for precise hemodynamics. Fixed point was given as boundaries between BHV and artery in the modeling part. Calculations showed that the more the fixed points in this bonded contact, the lower the principal stress was. The maximum shear stress showed a different trend. It had a different trend. Stress concentration in the conjunction area made it high-risk to be teared. Different suture densities had significant impaction in FSI simulations. With that analysis our work achieved a more comprehensive simulation to describe true hemodynamics of a BHV implanted in artery. The artery vessel had particular dynamic response under such assumptions, gradient existed in the maximum principal stress distribution diagram, from inner wall through which blood passing to the outer wall. Results showed a large suture density was suggested in BHV implantation.

Determinants of aortic bioprosthetic valve calcification assessed by multidetector CT

BackgroundCusp calcification is the main mechanism leading to bioprosthetic heart valve (BPV) failure. Recent studies suggest that BPV calcification is an active rather than passive process probably modulated by several...

Abstract 19515: Statin Use is Associated with Reduced All-Cause Mortality Following Bioprosthetic Heart Valve Implantation

Objective: This study examined the impact of statin use on clinical outcomes in patients undergoing bioprosthetic heart valve (BHV) implantation. Background: The medical management of patients undergoing BHV implantation is primarily directed at the management of co-morbid conditions. The anti-atherogenic and anti-inflammatory effects of statin use may contribute to improved clinical outcomes following BHV implantation. Methods: A retrospective analysis of patients (n=1957) undergoing aortic (n=1609) and mitral (n=436) BHV replacement with available data on statin use from 2004 to 2013 was performed. All-cause mortality was assessed using the Social Security Death Index. Association of baseline characteristics and statin use during follow-up with the incidence of events was assessed using a time-dependent covariate Cox regression model. Results: Follow-up was complete in 100% of patients. Total follow-up time was 3.9 ± 2.4 years during which death occurred in 10% of patients. Pre-discharge statin use was not significantly associated with mortality at 30 days or medium-term follow-up. After adjustment for covariates, post-BHV implantation use of statins was associated with a significant reduction in the risk of all-cause mortality in the entire cohort: HR=0.55, 95% CI: 0.40-0.74, P&lt;0.001. In addition, post-BHV statin use was associated with a decreased risk of all-cause mortality in the aortic valve replacement subgroup: HR=0.59, 95% CI: 0.42-0.84, P=0.003, and mitral valve replacement subgroup: HR=0.30, 95% CI: 0.17-0.54, P&lt;0.001. After exclusion of patients with known CAD (43% of the cohort), post-BHV use of statin therapy remained associated with a lower risk of death: HR=0.51, 95% CI: 0.33-0.80, P=0.004. Conclusion: Statin treatment is associated with a significant reduction in medium-term all-cause mortality in patients with and without CAD undergoing aortic and mitral BHV implantation.

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Antithrombotic Strategy in the Three First Months following Bioprosthetic Heart Valve Implantation

Heart valve prosthesis unquestionably improve quality of life and survival of patients with severe valvular heart disease, but the need for antithrombotic therapy to prevent thromboembolic complications is a major challenge to clinicians and their patients. Of the articles analyzed, most were retrospective series of cases or historical cohorts obtained from the database. The few published randomized trials showed no statistical power to assess the primary outcome of death or thromboembolic event. In this article, we decided to perform a systematic literature review, in an attempt to answer the following question: what is the best antithrombotic strategy in the first three months after bioprosthetic heart valve implantation (mitral and aortic)?After two reviewers applying the extraction criteria, we found 1968 references, selecting 31 references (excluding papers truncated, which combined bioprosthesis with mechanical prosthesis, or without follow-up).Based on this literature review, there was a low level of evidence for any antithrombotic therapeutic strategy evaluated. It´s therefore interesting to use aspirin 75 to 100 mg / day as antithrombotic strategy after bioprosthesis replacement in the aortic position, regardless of etiology, for patients without other risk factors such as atrial fibrillation or previous thromboembolic event. In the mitral position, the risk of embolism, although low, is more relevant than in the aortic position, according to published series and retrospective cohorts comprised mostly of elderly non-rheumatic patients.The current evidence is limited to have a consistent and safe level of evidence regarding the best therapeutic strategy. Based on these studies, 75 to 100 mg/day of aspirin is interesting as antithrombotic strategy after implantation of aortic bioprosthesis, regardless of etiology, for patients with no other risk factors such as atrial fibrillation or previous thromboembolic event. As for mitral bioprosthesis, the risk of embolism, although low, is more relevant than in the aortic position, according to published series and retrospective cohorts - usually elderly non rheumatic patients.

Procyanidins‐crosslinked heart valve matrix: Anticalcification effect

Calcification is one of the key factors for short durability of glutaraldehyde-crosslinked bioprosthetic heart valves. We have shown previously that procyanidins (PC)-crosslinked heart valve matrix has low cytotoxicity, perfect mechanical properties, and ideal stability. The aim of this study is to investigate the anticalcification effect of procyanidins and its crosslinked heart valves. Porcine aortic heart valve leaflets were decellularized and crosslinked with PC solution. The inhibition of calcification on PC-crosslinked heart valves was evaluated by soaking valves in simulated body fluid. The anticalcification effect of PC on valvular related cells was evaluated by culturing cells in the presence of PC. The results showed that minerals deposited on non- and glutaraldehyde-crosslinked valvular matrix in simulated body fluid, and PC could inhibit valve matrix mineralization in a dose-dependant manner. In addition, PC inhibited osteodifferentiation and calcification of valvular related cells by suppressing alkaline phosphatase activity and mineral deposition of cells. In conclusion, procyanidins can inhibit calcification of valvular matrix effectively by blocking mineral deposition and suppressing alkaline phosphatase activity and calcification of valvular related cells. Therefore, procyanindins-crosslinked heart valve matrix may be a potential candidate as new bioprosthetic heart valve implants.

Neomycin binding preserves extracellular matrix in bioprosthetic heart valves during in vitro cyclic fatigue and storage

Bioprosthetic heart valve (BHV) cusps have a complex architecture consisting of an anisotropic arrangement of collagen, glycosaminoglycans (GAGs) and elastin. Glutaraldehyde (GLUT) is used as a fixative for all clinical BHV implants; however, it only stabilizes the collagen component of the tissue, and other components such as GAGs and elastin are lost from the tissue during processing, storage or after implantation. We have shown previously that the effectiveness of the chemical crosslinking can be increased by incorporating neomycin trisulfate, a hyaluronidase inhibitor, to prevent the enzyme-mediated GAG degradation. In the present study, we optimized carbodiimide-based GAG-targeted chemistry to incorporate neomycin into BHV cusps prior to conventional GLUT crosslinking. This crosslinking leads to enhanced preservation of GAGs during in vitro cyclic fatigue and storage. The neomycin group showed greater GAG retention after both 10 and 50 million accelerated fatigue cycles and after 1 year of storage in GLUT solution. Thus, additional binding of neomycin to the cusps prior to standard GLUT crosslinking could enhance tissue stability and thus heart valve durability.

Tissue heart valve implantation in India; Indications, results and impact on quality of life

Backgound There is limited experience with bioprosthetic heart valve implantation in India and results and follow-up are not available. This study aims to assess the suitability of the bioprostheses in the Indian population and impact on their quality of life.

Heterotopic implantation of a porcine bioprosthetic heart valve in a dog with aortic valve endocarditis

A 5-year-old male German Shepherd Dog was evaluated because of a 5-month history of progressive lethargy, weight loss, and heart failure. On physical examination, bounding femoral pulses and systolic and diastolic murmurs were detected. Echocardiography revealed severe aortic valve insufficiency (AVI) and a large vegetative lesion on the aortic valve consistent with aortic valve endocarditis. The AVI velocity profile half-time was 130 milliseconds; the calculated peak systolic pressure gradient across the aortic valve was 64 mm Hg. Left ventricular diameter during diastole was 63.6 mm (predicted range, 40.2 to 42 mm) and during systole was 42.9 mm (predicted range, 25.4 to 27 mm). Systolic, diastolic, and mean arterial blood pressures were 120, 43, and 65 mm Hg, respectively. To palliate severe AVI, the descending aorta was occluded (duration, 16.75 minutes) and heterotopic implantation of a porcine bioprosthetic heart valve in that vessel was performed. After surgery, systolic, diastolic, and mean arterial blood pressures were 115, 30, and 61 mm Hg, respectively, in the forelimb and 110, 62, and 77 mm Hg, respectively, in the hind limb. Within 6 months, the AVI velocity profile half-time had increased to 210 milliseconds, indicating diminished severity of AVI. After 24 months, the dog was able to engage in vigorous exercise; no pulmonary edema had developed since surgery. Heterotopic bioprosthetic heart valve implantation into the descending aorta during brief aortic occlusion appears feasible in dogs and may provide substantial palliation for dogs with severe AVI.

Aluminum Chloride Pretreatment of Elastin Inhibits Elastolysis by Matrix Metalloproteinases and Leads to Inhibition of Elastin-Oriented Calcification

Calcification of elastin occurs in many pathological cardiovascular diseases including atherosclerosis. We have previously shown that purified elastin when subdermally implanted in rats undergoes severe calcification and aluminum chloride (AlCl(3)) pretreatment of elastin inhibits calcification. In the present study we investigated whether matrix metalloproteinase (MMP) binding to elastin and elastin degradation is prevented by AlCl(3) pretreatment. Subdermal implantation of AlCl(3)-pretreated elastin showed significantly lower MMP-9 and MMP-2 activity surrounding the implant as compared to the control implants. AlCl(3) pretreatment also significantly inhibited elastin implant calcification at the seven-day implant period (AlCl(3)-pretreated 4.07 +/- 1.27, control 23.82 +/- 2.24 microg/mg; p<0.0001). Moreover, elastin gel zymography studies showed that gel pretreatment with AlCl(3) inhibited elastolysis by MMP-9. We also demonstrate significant suppression of MMP-2 activity in aortic wall segments of AlCl(3)-pretreated porcine bioprosthetic heart valve implants as compared to control valve implants in sheep mitral valve replacement studies. AlCl(3) pretreatment also significantly inhibited calcification of elastin in this model. Thus, we conclude that aluminum ion binding to elastin prevents MMP-mediated elastolysis and thus prevents elastin calcification.

Oral Disease Burden in Patients Undergoing Prosthetic Heart Valve Implantation

Background. Valvular heart disease predisposing to endocarditis and requiring prosthetic valve implantation is common among the elderly. Spontaneous bacteremias associated with acute or chronic oral/odontogenic infections may represent a far greater cumulative risk for the development of endocarditis than do occasional health care procedures administered in a professional setting.Methods. To determine the oral disease burden in patients undergoing mechanical or bioprosthetic heart valve implantation, we performed a comprehensive clinical and radiographic regional examination on 156 consecutive patients, with emphasis on identifying acute and chronic oral/odontogenic infections and conditions.Results. The mean number of remaining teeth in the cohort was 19.32; of these, 1.07 were carious, involving a mean number of 2.51 tooth surfaces. In addition, 15.38% of the patients had evidence of acute or chronic periapical abscesses, and 43.6% of the patients had moderate to advanced periodontitis.Conclusions. In view of the substantial morbidity and mortality associated with prosthetic valve endocarditis and based upon the high incidence of dental disease identified in patients undergoing valvular operations, routine preoperative dental assessment should be deemed a “medical necessity” by third-party payors. Appropriate therapeutic intervention should be initiated whenever possible before valve implantation.(Ann Thorac Surg 1997;63:402–4)