New Model for the Assessment of Transcatheter Aortic Valve Replacement Devices in Sheep.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is an effective therapy in treating high-risk patients suffering from aortic stenosis. Animal models used to evaluate safety and efficacy of TAVR devices prior to clinical use lack a stenotic aortic annulus, a critical impediment to long-term TAVR device evaluation. We sought to create a reproducible model of aortic stenosis using a modified aortic annuloplasty (MAA) procedure in sheep, followed by deployment and long-term evaluation of TAVR devices using this model. METHODS: Twelve sheep underwent the MAA procedure and were recovered. Transthoracic echocardiography (TTE) was used to monitor changes in the aortic annulus in the postoperative period. At 60 days post-MAA, Test group animals were anesthetized for TAVR insertion and Control animals underwent a necropsy. Test animals were recovered following TAVR insertion and observed for a postoperative period of 140 days. RESULTS: Twelve sheep survived the annuloplasty procedure and the 60-day recovery period. Gross examination of seven Control group animals revealed the implanted annuloplasty ring segments formed hard protrusions into the aortic annulus. Five sheep in the Test group underwent successful deployment of Abbott's experimental TAVR device without evidence of migration. Examination at 140 days post-TAVR insertion showed all devices tightly anchored within the modified aortic annulus. CONCLUSIONS: The MAA procedure creates stenotic segments in the aortic annulus with adequate rigidity for anchorage and long-term evaluation of TAVR devices. This represents the first model that successfully mimics human aortic stenosis and provides a clinically relevant TAVR deployment platform for long-term evaluation in sheep.

Skull base oncocytoma presenting as epistaxis: an unusual presentation of a rare tumour successfully managed with active surveillance.

Oncocytomas are rare tumours, usually occurring in the salivary glands, but may very occasionally occur in other sites. The authors present a skull base oncocytoma as a rare cause of spontaneous epistaxis. Following diagnosis through imaging and intranasal biopsy, the patient opted for annual surveillance instead of active treatment and made a full recovery nonetheless. Skull base oncocytoma is a rare tumour that may result in otherwise common symptomatology. While excision is the mainstay of management, active surveillance may be a viable alternative for select patients.

Triglycidyl amine crosslinking combined with ethanol inhibits bioprosthetic heart valve calcification.

BACKGROUND: One of the most important factors responsible for the calcific failure of bioprosthetic heart valves is glutaraldehyde crosslinking. Ethanol (EtOH) incubation after glutaraldehyde crosslinking has previously been reported to confer anticalcification efficacy for bioprostheses. The present studies investigated the anticalcification efficacy in vivo of the novel crosslinking agent, triglycidyl amine (TGA), with or without EtOH incubation, in comparison with glutaraldehyde. METHODS: The TGA crosslinking (±EtOH) was used to prepare porcine aortic valves for both rat subdermal implants and sheep mitral valve replacements, for comparisons with glutaraldehyde-fixed controls. Thermal denaturation temperature, an index of crosslinking, cholesterol extraction, and hydrodynamic properties were quantified. Explant endpoints included quantitative and morphologic assessment of calcification. RESULTS: Thermal denaturation temperatures after TGA were intermediate between unfixed and glutaraldehyde-fixed. EtOH incubation resulted in almost complete extraction of cholesterol from TGA or glutaraldehyde-fixed cusps. Rat subdermal explants (90 days) demonstrated that TGA-EtOH resulted in a significantly greater level of inhibition of calcification than other conditions. Thus, TGA-ethanol stent mounted porcine aortic valve bioprostheses were fabricated for comparisons with glutaraldehyde-pretreated controls. In hydrodynamic studies, TGA-EtOH bioprostheses had lower pressure gradients than glutaraldehyde-fixed. The TGA-ethanol bioprostheses used as mitral valve replacements in juvenile sheep (150 days) demonstrated significantly lower calcium levels in both explanted porcine aortic cusp and aortic wall samples compared with glutaraldehyde-fixed controls. However, TGA-EtOH sheep explants also demonstrated isolated calcific nodules and intracuspal hematomas. CONCLUSIONS: The TGA-EtOH pretreatment of porcine aortic valves confers significant calcification resistance in both rat subdermal and sheep circulatory implants, but with associated structural instability.

Prevention of calcification of bioprosthetic heart valve cusp and aortic wall with ethanol and aluminum chloride.

BACKGROUND: Calcification is frequently associated with device failure of bioprostheses fabricated from either glutaraldehyde pretreated porcine aortic valves or bovine pericardium. It was hypothesized that differential pretreatment with ethanol-aluminum chloride will prove safe and efficacious for inhibiting the calcification of both the porcine aortic valve bioprosthetic cusp and the aortic wall. METHODS: Glutaraldehyde-fixed porcine aortic valves were subjected to differential aluminum chloride (AlCl3) and ethanol pretreatment; aortic wall segments were treated exclusively with AlCl3 (0.1 moles/L) for 45 minutes, 6 hours, or 8 hours (groups 3A, B, and C, respectively), followed by valve cusp incubations in ethanol (80%, pH 7.4). Nontreated control bioprosthetic valves were either stent-mounted porcine aortic valve bioprostheses (Carpentier-Edwards, group 1) (Edwards, Santa Anna, CA) or St. Jude Toronto SPV valves (St. Jude Medical, St. Paul, MN) (group 2). Mitral valve replacements were carried out in juvenile sheep for 150 days. RESULTS: Calcium in cusps from group 3A was 2.84 +/- 0.62 mg calcium/g tissue versus control, 22.79 +/- 8.46 mg calcium/g tissue, p = 0.04. Valves pretreated with AlCl3 for 45 minutes, 6 hours, and 8 hours had significantly lower levels of calcium in the aortic wall compared to controls (40.38 +/- 5.66, 26.77 +/- 4.02, and 28.94 +/- 8.25 mg calcium/g tissue for groups 3A, 3B, and 3C, respectively, vs 95.47 +/- 17.14 mg calcium/g tissue for group 1, p < 0.001, and 133.42 +/- 3.96 mg calcium/g tissue for group 2, p < 0.001). CONCLUSIONS: Differentially applied ethanol and aluminum chloride pretreatment significantly inhibited calcification of both the glutaraldehyde-fixed porcine aortic valve bioprosthetic cusp and the aortic wall.

Inhibition of cusp and aortic wall calcification in ethanol- and aluminum-treated bioprosthetic heart valves in sheep: background, mechanisms, and synergism.

BACKGROUND AND AIM OF THE STUDY: Calcification of bioprosthetic heart valves fabricated from glutaraldehyde (GA)-pretreated heterograft tissue is frequently responsible for the clinical failure of these devices. Stentless bioprostheses fabricated from GA-fixed porcine aortic valves pose an important challenge in this regard, as pathologic calcification can affect not only the bioprosthetic cusps, but also the aortic wall segment. METHODS: A synergistic approach was used to prevent bioprosthetic cusp and aortic wall calcification. Ethanol pretreatment of bioprosthetic heart valves was shown to inhibit cuspal calcification due to multiple mechanisms, including alterations of collagen structure and lipid extraction. AlCl3 pretreatment of bioprostheses to prevent calcification was also investigated; this alters elastin structure, inhibits alkaline phosphatase, and complexes with phosphoesters, thereby inhibiting aortic wall mineralization. RESULTS: Experimental data from rat subdermal implants and sheep mitral replacements showed successful synergism with co-pretreatment of porcine aortic valve bioprostheses with ethanol and AlCl3. Significant inhibition of both cusp and aortic wall calcification was achieved by differential pretreatments that restrict AlCl3 to only the aortic wall, and not the cusp, accompanied by ethanol cuspal exposure. Sequential exposure of bioprostheses, first to AlCl3 and then to ethanol, led to unexpectedly severe cuspal calcification. CONCLUSION: Differential pretreatment of stentless bioprostheses with ethanol and AlCl3 can effectively inhibit both cuspal and aortic wall calcification.