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Structural changes in porcine xenografts used as substitute cardiac valves. Gross and histologic observations in 51 glutaraldehyde-preserved Hancock valves in 41 patients.

Gross and histologic changes are described in 51 Hancock glutaraldehyde-preserved porcine heterograft bioprostheses from 41 patients: 33 valves from 25 patients had been in place for less than 2 months ("early") and 18 valves from 17 patients were examined at later periods up to 75 months ("late") after implantation. The major gross changes were thrombosis (five bioprostheses) and degeneration (three bioprotheses) of the cusps. Major histologic changes observed in 44 bioprostheses (26 early and 18 late) examined histologically were: (1) fibrin deposits on inflow and outflow surfaces of the cusps; (2) inflammatory cell infiltrates; (3) histiocyte deposition; (4) giant cell formation, and (5) focal disruption of the fibrocollagenous structure of the cusps. These observations indicate that porcine bioprostheses are not biologically inert in the human circulation. However, valve failure is rare at the implantation periods studied.

Animals↗

Structural changes in glutaraldehyde-treated porcine heterografts used as substitute cardiac valves. Transmission and scanning electron microscopic observations in 12 patients.

Scanning and transmission electron microscopic studies were made of (1) 12 glutaraldehyde-treated porcine valvular heterografts that had been implanted in patients for 2 days to 76 months; (2) 3 unimplanted commercially processed porcine aortic valves; and (3) 1 unprocessed porcine aortic valve. Comparison of unprocessed porcine valves and unimplanted commercially processed valves showed loss of endothelium and acid mucopolysaccharides during preimplantation processing. Short-term (less than 2 months) changes after implantation consisted of insudation of plasma proteins, penetration of erythrocytes into surface crevices, formation of a thin surface layer of fibrin, and deposition of macrophages, giant cells and a few platelets. Longer-term (more than 2 months) changes were proportional to the time interval after implantation and consisted of progressive disruption of collagen, erosion of the valve surfaces, formation of aggregates of platelets and accumulation of lipid. The surfaces of the leaflets did not become covered with endothelium or with a fibrous sheath. Calcific deposits were found in one valve and bacterial organisms in another. Thus, progressive breakdown of collagen appears to be a critical factor in determining the long-term durability of glutaraldehyde-treated porcine valvular heterografts.

Adult↗

Structure and classification of cuspal tears and perforations in porcine bioprosthetic cardiac valves implanted in patients.

Morphologic studies were made of cuspal tears and perforations in 16 porcine valve bioprostheses that had been implanted in 14 patients (9 male and 5 female) ranging in age from 2 to 65 years. Eleven bioprostheses had been in the mitral position for 30 to 123 months, four in the aortic position for 15 to 40 months and one in a varied pulmonary conduit for 96 months. The cuspal lesions were classified into four types. Type I lesions, which involved the free edges of the cusps, were the most common of all lesions and occurred with equal frequency in mitral and aortic bioprostheses. Regardless of position of implantation, type I lesions were more frequent in the right coronary cusp than in the other cusps. Ultrastructural study showed that these lesions develop as consequences of breakdown of collagen at the free edges of the cusps, usually near the commissures. Type II lesions consisted of linear perforations that extended along the basal regions of the cusps, forming an arc parallel to the sewing ring. These lesions were uncommon an resulted from separation of bundles of collagen. Type III lesions, which were large, round or oval perforations that occupied central regions of the cusps, were more common in aortic than in mitral bioprostheses. They were characterized by marked destruction of cuspal tissue and were most frequently associated with infection. Type IV lesions were small pinhole-like perforations; they usually were multiple, localized in central regions of the cusps and associated with calcific deposits. Type IV lesions were more common in mitral than in aortic bioprostheses. Regardless of position, they were more frequent in the left and noncoronary cusps than in the right coronary cusp (which may be protected by its muscle shelf against this type of perforation). It is concluded that cuspal tears and perforations develop in implanted bioprostheses as consequences of structural failure of connective tissue components.

Adolescent↗

Formation of cartilage in bioprosthetic cardiac valves implanted in sheep: a morphologic study.

Foci of cartilage were found in 12 of 120 bioprostheses implanted in young sheep for 13 to 24 weeks, but in none of 47 bioprostheses implanted for less than 13 weeks. Cartilage was found more frequently (p less than 0.01) in bioprotheses implanted in the tricuspid position than in those implanted in the mitral position. In porcine aortic valvular bioprostheses, the cartilage was preferentially localized in the region of the muscle shelf; in pericardial bioprostheses, it occurred in the fibrous sheaths covering the cusps. In both instances, the cartilage was found to undergo calcification and was considered to be formed by metaplasia of connective tissue cells of host origin.

Animals↗

Modification by the Hancock T6 process of calcification of bioprosthetic cardiac valves implanted in sheep.

The effectiveness of the T6 process (surfactant treatment) to decrease calcification of porcine aortic valvular (PAV) and bovine pericardial (BPV) bioprostheses was investigated. Morphologic and biochemical studies were made of standard and T6-treated PAVs and BPVs that had been implanted for a mean of 20 weeks in the tricuspid position in young sheep. Gross, radiographic, histologic and ultrastructural observations showed that the calcific deposits were less severe in T6-treated (n = 9) than in standard PAVs (n = 7), but were similar in severity in T6-treated (n = 6) and standard BPVs (n = 7). This was confirmed by results of quantitative analyses for calcium in half of each cusp of each explanted valve. Because these results showed large differences in standard deviations in the 4 groups of sheep, natural logarithmic and square-root transformations were used for statistical comparisons. The mean calcium content (milligrams of calcium per gram of dry tissue) of standard PAVs (111 +/- 53) was greater than that of T6-treated PAVs (11 +/- 3) (p = 0.0037). The calcium content of T6-treated PAVs was lower than that of T6-treated BPVs (96 +/- 26) (p = 0.031). However, the calcium content of standard BPVs (35 +/- 13) was not different from that of T6-treated BPVs or standard PAVs. Thus, under conditions of relatively short-term implantation in the sheep model, the T6 process is useful for decreasing the extent of calcification in PAVs, but not in BPVs.

Animals↗

Platelet adherence to bioprosthetic cardiac valves.

Tissue from porcine aortic bioprosthetic valves (Hancock) and bovine pericardial valves (Ionescu-Shiley) were incubated with platelets tagged with chromium-51. There was a significantly decreased platelet-collagen adhesion reaction in both porcine and bovine glutaraldehyde-treated valves compared with reactions in fresh porcine aortic valve and fresh bovine pericardium (p less than 0.001). There was no significant difference in the platelet-collagen reaction between porcine aortic valve and bovine pericardium, whether treated with glutaraldehyde or in the fresh state (p greater than 0.05). The addition of aspirin did not significantly decrease the platelet-collagen reaction on glutaraldehyde-treated or fresh valves (p greater than 0.05). Rinsing fresh valves in plasma appeared to offer more protection against platelet adhesion than rinsing them in saline solution (p less than 0.01). It is concluded that there is no difference in platelet adherence to porcine aortic valve or bovine pericardium and that glutaraldehyde, and perhaps plasma, offers a protective effect against platelet adhesion.

Animals↗

Degeneration in porcine bioprosthetic cardiac valves: incidence of primary tissue failures among 938 bioprostheses at risk.

From June 1974 through December 1980, 938 porcine xenografts were inserted in 794 selected patients who survived surgery and who were considered at risk for primary tissue valve failure. Sixty-three instances of primary tissue valve degeneration occurred in 59 of the 794 patients. In patients operated on 9 years ago, 29% of the valves implanted in the mitral position (5 of 17) and 27% in the aortic position (3 of 11) failed. These percentages decreased to 18% (14 of 80) and 20% (11 of 54) for those implanted in 1975, 8% (6 of 73) and 14% (7 of 51) for those implanted in 1976, 9% (6 of 68) and 5% (4 of 76) for 1977, and 4% (3 of 79) and 3% (2 of 63) for 1978. The average interval between valve placement and explantation or death was 56 months (range 10 to 98) for valves in the mitral position and 68 months (range 12 to 92) for valves in the aortic position. The rate of valve survival without degeneration was 98 +/- 1% at 4 years, 96 +/- 2% at 5 years, 90 +/- 3% at 6 years, 87 +/- 4% at 7 years and 76 +/- 7% at 8 and 9 years. Until 1978, 4 valves failed, 8 failed in 1979 to 1980, 12 in 1981, 25 in 1982, and 14 have already failed from January to May 1983. Our figures show a progressive increase in valve degeneration with the passing of time. No leveling of this failure rate has so far been observed.

Adolescent↗

Measurement of aortic root size by biplane angiography before cardiac valve replacement.

Aortic valve replacement (AVR) in the patient with a small aortic root demands special consideration because the hemodynamic function of artificial valves with a small external diameter is often poor. In this study, the internal diameter of the aortic root was measured from biplane ventriculography. This measured root diameter was then used to predict the external diameter of the artificial valve. Twelve patients underwent biplane ventriculography followed by AVR with Carpentier-Edwards bioprostheses. The artificial valve diameter was predicted with a correlation coefficient of 0.93, a standard error of estimate of 0.89 mm, and an average absolute difference between preoperative measurement and valve diameter of 0.69 mm. Therefore, the aortic root diameter can be accurately measured from the ventriculogram, thus detecting the patient with a small aortic root before surgery.

Angiography↗

Quantitative anatomic analysis of "stent creep" of explanted Hancock standard porcine bioprostheses used for cardiac valve replacement.

The degree of progressive inward deflection of the stent posts ("stent creep") during function of Hancock standard orifice porcine aortic valve bioprostheses is unknown. The present investigation determines, using a quantitative geometric analysis of clinically removed bioprostheses, the contribution of stent creep to progressive reduction in the outflow orifice area of these valves. Fifty-four Hancock standard orifice porcine aortic valve bioprostheses obtained at reoperation or at autopsy of 50 patients were studied; 47 of these were removed more than 21 months postoperatively. The projected geometric outflow orifice area of each prosthesis was planimetrically measured. To compare prostheses through the entire range of available sizes, this measured area was divided by that of an unimplanted valve of the same size to calculate a ratio designated the "normalized outflow area ratio" (NOAR). Thus, by definition, for all unimplanted standards, NOAR was 1.00. In 7 prostheses in place for less than 1 month, the NOAR was 1.00 +/- 0.03 (mean +/- standard deviation). In 47 prostheses removed 21 to 126 months postoperative, the NOAR was 0.91 +/- 0.08. The relation between NOAR and duration of function determined by linear regression was NOAR = 0.955 - 4.560 X 10(-4) X Duration (in months). The minimum NOAR found was 0.74; the NOAR was less than 0.80 in 4 prostheses (8% of long-term valves). Thus, stent creep is usually not prominent after long-term function of Hancock standard orifice procine bioprostheses and suggests that clinically important progressive reduction of the geometric outflow orifice is infrequent.

Adult↗

Identification of photoproducts liberated by in vitro argon laser irradiation of atherosclerotic plaque, calcified cardiac valves and myocardium.

To determine how laser light effects alterations in cardiovascular tissue, photoproducts liberated as the result of argon laser irradiation of atherosclerotic plaque, myocardium and calcified aortic valve leaflets were analyzed by gas chromatography, gas chromatography-mass spectrometry and absorbance spectroscopy. The products formed in gas phase are those expected when proteins and porphyrins are pyrolyzed--light hydrocarbon fragments, carbon monoxide and water vapor. The laser-generated products dissolved in solution are those expected when a protein chain or porphyrin ring is degraded in a thermal reaction, namely protein fragments and nitrogen heterocyclic ring fragments. These photoproducts are those typical of combustion or thermal degradation, and indicate that the fundamental nature of laser irradiation of coronary plaque, myocardium and calcified valve leaflets is thermal rather than photochemical. Thermal degradation of myocardium is more extensive than thermal degradation of atherosclerotic arteries or calcified valves because the red hue of myoglobin-containing myocardium enhances the absorption of the blue-green argon laser light. In contrast, the yellow-white hue of both atherosclerotic plaque and calcified aortic valve leaflets allows less complete absorbance of the argon laser light, leading to a lesser amount of converted heat and, therefore, less complete thermal degradation.

Arteriosclerosis↗