Impact of glutaraldehyde on calcification of pericardial bioprosthetic heart valve material

BACKGROUND: This study was conducted to investigate the impact of the preservation method of bioprosthetic heart valve materials on calcification rates and biocompatibility of the biologic tissue. METHODS: In subcutaneous rat implants, conventionally preserved bioprosthetic heart valve material was compared with bovine pericardium that was treated with L-glutamic acid to reduce residual glutaraldehyde released from the fixed tissue. Both these methods were compared with bovine pericardium that was stabilized by a dye-mediated photooxidation reaction without glutaraldehyde. Biocompatibility of these biomaterials was tested in vitro using human endothelial cell cultures. RESULTS: Conventionally preserved bovine pericardium with a high amount of glutaraldehyde incorporated into the tissue resulted in severe calcification 63 days after subcutaneous implantation in rats (165.4 +/- 20 mg Ca2+/g dry weight). Postfixation treatment with L-glutamic acid, which reduces free, unbound aldehyde groups, showed a significant decrease in calcification (89.6 +/- 14 mg Ca2+/g dry weight). Glutaraldehyde-free preservation by dye-mediated photooxidation showed no calcification after 63 days of subcutaneous implantation (1.0 +/- 0.4 mg Ca2+/g dry weight). Regular endothelial cell proliferation was observed on photooxidized and L-glutamic acid-treated tissue, whereas conventionally treated tissue caused endothelial cell death. CONCLUSIONS: This study underlines the detrimental role of glutaraldehyde in the calcification process of bioprosthetic heart valve materials and emphasizes alternative preservation methods that reduce or avoid the use of glutaraldehyde.     

Twelve-year experience with the 19 mm Carpentier-Edwards pericardial aortic valve

BACKGROUND: The purpose of the present study was to investigate the therapeutic effectiveness of interleukin-2 (IL-2) and interferon (IFN), either alone or in combination, in comparable groups of patients affected by advanced renal cell carcinoma (RCC). PATIENTS AND METHODS: In order to limit selection biases, treatment was allocated on a random basis. Patients randomized to IL-2 alone were scheduled to receive eight rlL-2 24-hour i.v. infusion cycles, days 1 to 4, at a daily dose of 18 x 10(6) lU/m2 for a total of 25 weeks. Patients randomized to IFN alone were scheduled to receive rIFN-alpha at a daily dose of 6 x 10(6) IU/m2, days 1, 3 and 5, every week for a total of 52 weeks. Patients randomized to the combination of IFN and IL-2 were given the same drugs at the same daily doses for a total of 24 weeks. Drug dose was modified according to toxicity. RESULTS: Twenty-three percent (95% CI:+/-17.5) of patients treated with IL-2 alone showed an objective response to treatment (9% CR). The corresponding figures in patients treated with IFN alone or IFN plus IL-2 were 9% (95% CI:+/-11.9) and 9% (95% CI:+/-11.9), respectively. Complete responses were observed only in patients treated with IL-2. The median duration of response in the IL-2 arm was 18 months (range, 9.5-24). The duration of the two responses achieved by IFN alone was seven and nine months, respectively. The corresponding figures in the two patients responding to the combination of IFN with IL-2 were 19 and 27 months, respectively. Total IL-2 dose appeared to be a major predictor of response. Only a minority of patients experienced grade 3-4 toxicity, the incidence being higher in those treated with IL-2 or IL-2 plus IFN. CONCLUSIONS: Neither IFN nor IL-2 or the combination of the two appear to be very active in patients with advanced RCC, even when trial entry was restricted to patients with relatively indolent disease. This stresses the need for the development of new approaches.     

The effect of prosthesis-patient mismatch on aortic bioprosthetic valve hemodynamic performance and patient clinical status

BACKGROUND: High pressure gradients occurring through normally functioning prosthetic valves appear to be related to a mismatch between the effective orifice area of the prosthesis and the patient's body surface area. OBJECTIVE: To determine whether prosthesis-patient mismatch affects clinical and hemodynamic status, a group of patients with a bioprosthetic heart valve in the aortic position was prospectively evaluated at 6.2+/-4.4 years after implantation by transthoracic Doppler echocardiography. METHODS: Manufacturer-derived in vitro valve areas were available in 61 patients allowing classification into two subgroups, with or without mismatch, based on a valve area at implantation indexed for body surface area 0.85 cm2/m2 or less, or greater than 0.85 cm2/m2. Clinical and hemodynamic parameters evaluated at follow-up included New York Heart Association (NYHA) class distribution, mean transprosthetic gradient, prosthetic valve area and cardiac index. RESULTS: Prosthesis-patient mismatch was present in 32 of 61 patients (52%). Although NYHA class of the patients was similar in both groups, hemo-dynamic performance of the aortic bioprostheses was worse in patients with mismatch than in patients with no mismatch, as indicated by a higher mean gradient (22+/-9 versus 15+/-8 mm Hg, P=0.002) and a lower cardiac index (3.0+/-0.7 versus 3.4+/-0.7 L/min/m2, P=0.04). The prevalence and severity of intrinsic prosthetic dysfunction were similar in both groups. Despite similar NYHA functional class distribution in both groups, the occurrence of syncope, acute pulmonary edema and angina pectoris was significantly higher in patients with mismatch (50% versus 21%, P=0.017). CONCLUSIONS: Prosthesis-patient mismatch is associated with worse hemodynamic performance and higher prevalence of adverse clinical events. However, mismatch did not promote accelerated hemodynamic or structural deterioration of the bioprosthesis.     

Hemodynamic function of the Hancock standard orifice aortic valve bioprosthesis

Reports that the hemodynamic performance of the standard orifice aortic bioprosthesis in less than optimal have prompted recommendations that mechanical prosthesis or anulus-enlarging procedures be used in adult patients with a small aortic root. The hemodynamic function of the Hancock bioprosthesis was evaluated in 77 patients who underwent cardiac catheterization of rest and with isoproterenol infusion (15 patients) an average of 6 months after operation. The average peak systolic gradient (basal conditions) was 7 mm Hg (range 0 to 37 mm Hg); 35 patients had no resting gradient. Fifteen patients received 21 mm diameter valves and had an average systolic valve gradient of 10 mm Hg (range 0 to 30 mm Hg); the average effective valve orifice area was 1.27 +/- 0.17 cm2 for 21 mm, 1.46 +/- 0.11 cm2 for 23 mm, 1.72 +/- k0.20 cm2 for 25 mm, and 1.97 +/- 0.06 for 27 mm bioprostheses. Isoproterenol infusion, elevating cardiac output 66%, increased the peak systolic gradient from an average of 11 mm Hg (range 0 to 37 mm Hg) to 44 mm Hg (range 10 to 85 mm Hg). It is concluded that small-diameter (21 and 23 mm) Hancock bioprostheses can be used with acceptable clinical and hemodynamic function in patients with a small body surface area.     

Mid-diastolic aortic valve opening in bacterial endocarditis of aortic valve

Echocardiographic features of acute aortic regurgitation resulting from bacterial endocarditis have been well documented (Nathan et al., 1980; Weaver et al., 1977; Wray, 1975a), and include thick shaggy echoes from aortic valve in diastole, fine diastolic flutter of aortic valves suggestive of rupture of cusps, and premature closure of mitral valves. Echocardiography being a sensitive noninvasive technique for detecting aortic valve vegetations is heavily relied on for earlier diagnosis and prompt therapy of these patients. Prognosis of echocardiographically positive endocarditis is known to be worse than for echo-negative patients. The following case is being presented because of an unusual echocardiographic manifestation with mid-diastolic aortic valve opening secondary to flail aortic valve from staphylococcal endocarditis of the aortic valve.     

Internal shear properties of fresh porcine aortic valve cusps: implications for normal valve function

BACKGROUND AND AIMS OF THE STUDY: Several types of stress act on aortic heart valve tissue during the cardiac cycle. When closed the valve is subjected to primarily tensile stress due to the diastolic pressure, and upon opening bending stress occurs near the attachment with the aortic root and throughout the body of the cusps. Smooth bending requires internal tissue shearing. To measure the internal shear properties of the tissue a testing device was created which combined a high-precision linear actuator with a sensitive load cell. MATERIALS AND METHODS: Circular punch biopsy specimens from fresh porcine aortic valve cusps (n = 32) were examined. The shear stress versus shear strain characteristics were measured both in the circumferential (n = 17) and the radial (n = 13) direction, and the stress relaxation characteristics were also examined circumferentially (n = 15) and radially (n = 15). In addition seven specimens were tested repeatedly in both radial and circumferential directions for tissue isotropy. RESULTS: The results from the shear stress versus strain tests showed the tissue to behave non-linearly over the strain range between -0.9 and 0.9. The average moduli at the near zero strains were less than 300 Pa and increased to over 20 kPa at the extreme strains. The circumferential direction yielded slightly higher average moduli than the radial direction but this difference was not significant. The stress relaxation results indicated that valve tissue relaxation occurs in two distinct phases, an initial low slope region and a second high slope region with respective values of -7.5 log(s)-1 and -15 log(s)-1 and with no significant difference between test directions. CONCLUSIONS: Our results define and describe the pattern of internal shear properties of the aortic valve that are particularly important during the transition between the open and closed positions. This behavior pattern has particular application in the creation of accurate mathematical models of the valve tissue and may be important in understanding the mechanism of tissue failure in bioprosthetic valves.     

Clinical, echocardiographic, and pathologic features of aortic wall dehiscence of porcine bioprosthetic valves: a cause of rapidly progressive mitral regurgitation and heart failure after bioprosthetic mitral valve replacement

The aim of this study was to define the clinical, echocardiographic, and pathologic correlates of commissural dehiscence of aortic wall from the stent post of the porcine bioprostheses in the mitral position. This form of valve degeneration was found in 5 of 23 explanted mitral bioprostheses. A thickened, separated aortic wall at multiple commissural sites along with other evidence of valve degeneration was identified in the three patients who had chronic congestive heart failure. A large dehiscence at a single commissural site with otherwise normal valve morphology was present in the two patients who had acute heart failure. Two dimensional/Doppler echocardiography showed a prolapsing or a flail anteriorly positioned leaflet and an eccentric posteriorly directed mitral regurgitation jet in all patients. These echocardiographic findings in patients with a porcine bioprosthetic mitral valve should suggest commissural dehiscence from the aortic wall as a possible mechanism of valve failure. Exclusive involvement of the porcine aortic bioprosthesis placed in the mitral position along with involvement of strut of the bioprosthesis facing the aortic root in all cases suggests excessive hemodynamic stress on the valve in the mitral position and in particular on the anteriorly placed strut as the potential cause of this form of valve degeneration.     

Complement activation is involved in the structural deterioration of bovine pericardial bioprosthetic heart valves

Disintegrated collagen fibers surrounded with protein deposits are a morphologic feature in torn, folded, and disrupted cusps of pericardial prostheses explanted for clinical dysfunction. New technologies for valve bioprostheses with improved durability require further investigation of molecular mechanisms initiating the deterioration of bioprosthetic valves. The authors' aim was to obtain experimental evidence of biologic factors contributing to the degradation of the bioprosthetic matrix. Clinically failed Mitroflow (22), Hancock (3), Ionescu-Shiley (2), and Sorin (1) valves were explanted after 69-170 months. Non calcific deterioration of the prosthetic matrix was studied with labeled antibodies to plasma proteins and cells. IgG, and complement proteins C1q, C3, and C4 were accumulated close to dissociated collagen bundles (26/28) throughout the prostheses. Fibrin was identified on the cuspal surface and in the deep disrupted areas. The fibrin peptides and proteolytic breakdown products of the complement components, the latter consistent with complement activation and chemotaxis for monocytes, were shown by immunoenzymic assay on Western blots from the valve extracts. The complement activation triggered by the IgG aggregates generates bioactive peptide signals that can activate macrophages (22/28) and neutrophil granulocyte elastase (22/24) able to cooperate with the mechanical stress in the breakdown of the chemically processed, non hemocompatible, and non-self macromolecular matrix.     

Systolic aortic valve compression from partial dehiscence of an aortic valve homograft

Implantation of valve prostheses provide improvement of symptoms and prolongation of life in selected patients with valvular heart disease. Meticulous follow-up of patients after valve surgery is essential as complications of valve failure, valve dehiscence, valve thrombosis, and infection may occur. The major mode of failure of aortic valve homografts is valve regurgitation, which is readily detected by physical examination. We report a case of left ventricular outflow obstruction after implantation of an aortic valve homograft.     

Effects of accelerated testing on porcine bioprosthetic heart valve fiber architecture

We undertook the following study to quantitatively assess the changes in porcine bioprosthetic heart valve (PBHV) fiber architecture to increasing levels of fatigue damage using an in vitro accelerated test model. PBHVs were subjected to 0-500 million test cycles at 16 Hz, and small-angle light scattering (SALS) was used to quantify the gross fiber structure of the cusps. The degree of gross fiber alignment remained essentially constant from 0 to 500 million cycles over the entire cusp. Increasing fiber orientation randomness, indicative of local damage, was observed only in the vicinity of the nodulus of Arantii after 50 million cycles. The SALS data from the damaged regions suggested shearing between fiber layers, which may be part of the failure process and accelerates valve failure. Histological analysis revealed a relatively intact gross fiber structure with the collagen fiber crimp remaining, although delamination and de-registration of the crimp was also observed. Accelerated tested PBHVs also demonstrated a pronounced 'sagging', which began at the earliest cycle number tested (1.4 million cycles) and whose rate decreased logarithmically with cycle number. Results of this study suggest that PBHV cusps can alter their shape without any visually apparent material yielding or fiber failure under continual cyclic loading. Further, while most of the 4 mmHg pressure fixed PBHV's gross fiber architecture remains unchanged after 500 million cycles of accelerated testing, localized accumulated fiber damage can occur on a sub-visual structural level as early as 50 million cycles.     

Successful conservative treatment of nontyphoid salmonella endocarditis involving a bioprosthetic valve

We report a case of a 28-yr-old man in whom mastocytosis was diagnosed by fine-needle aspiration (FNA) of enlarged periaortic lymph nodes. FNA cytology revealed numerous mast cells characterized by cells having round to oval eccentrically placed nuclei and associated coarsely granular cytoplasm, most conspicuous on Diff-Quik- and Giemsa-stained smears. Lymphocytes, histiocytes, and occasional plasma cells were present in the background. We believe this paper to be the first reported case of mastocytosis diagnosed by FNA. The case demonstrates the utility of FNA in evaluating lymphadenopathy occurring in mastocytosis.     

Myxoma of the aortic valve

Myxoma of the aortic valve is exceedingly uncommon. In this article, we report a 58-year-old man with myxoma arising from the aortic valve. Aortic valve replacement was performed, and postoperative histologic examination showed myxoma of aortic valve.     

Regression of left ventricular hypertrophy after aortic valve replacement for aortic stenosis with different valve substitutes

OBJECTIVE: Stentless biologic aortic valves are less obstructive than stented biologic or mechanical valves. Their superior hemodynamic performances are expected to reflect in better regression of left ventricular hypertrophy. We compared the regression of left ventricular hypertrophy in 3 groups of patients undergoing aortic valve replacement for severe aortic stenosis. Group I (10 patients) received stentless biologic aortic valves, group II (10 patients) received stented biologic aortic valves, and group III (10 patients) received bileaflet mechanical aortic valves. METHODS: Echocardiographic evaluations were performed before the operation and after 1 year, and the results were compared with those of a control group. Left ventricular diameters and function, left ventricular wall thickness, and left ventricular mass were assessed by echocardiography. RESULTS: Group I patients had a significantly lower maximum and mean transprosthetic gradient than the other valve groups (P = .001). One year after operation there was a significant reduction in left ventricular mass for all patient groups (P < .01), but mass did not reach normal values (P = .05). Although the rate of regression in the interventricular septum and posterior wall thickness differed slightly among groups, their values at follow-up were comparable and still higher than control values (P = .002). The ratio between interventricular septum and posterior wall and the ratio between wall thickness and chamber radius did not change significantly at follow-up. CONCLUSIONS: Because the number of patients was relatively small, we could not use left ventricular mass regression after I year to distinguish among patients undergoing aortic valve replacement for aortic stenosis by means of valve prostheses with different hemodynamic performances.     

Impact of size mismatch and left ventricular function on performance of the St. Jude disc valve after aortic valve replacement

BACKGROUND: The hemodynamic function of the St. Jude valve may change relative to changes in left ventricular function after aortic valve replacement for aortic stenosis. From theoretical reasons one may hypothesize that prosthetic valve hemodynamic function is related to left ventricular failure and mismatch between valve size and patient/ventricular chamber size. METHODS: Forty patients aged 24 to 82 years who survived aortic valve replacement for aortic stenosis with a standard St. Jude disc valve (mean size, 23.5 mm; range, 19 to 29 mm) were followed up prospectively with Doppler echocardiography and radionuclide left ventriculography preoperatively and 9 days, 3 months, and 18 months after the operation with assessment of intravascular hemolysis at 18 months. Follow-up to a maximum of 7.4 years (mean, 6.3 years) was 100% complete. RESULTS: Left ventricular muscle mass index decreased from 198 +/- 62 g.m-2 preoperatively to 153 +/- 53 g.m-2 at 18 months (p < 0.001), paralleled by a significant increase in left ventricular ejection fraction, peak ejection rate, and peak filling rate; only 18% of the patients had normal left ventricular muscle mass index and only 32% normal ventricular function (normal left ventricular ejection fraction, peak ejection rate, peak filling rate, early filling fraction, and late filling fraction during atrial contraction) at 18 months. Prosthetic valve peak Doppler gradient dropped from 20 +/- 6 mm Hg at 9 days to 17 +/- 5 mm Hg at 18 months (p < 0.05). Reduction of left ventricular muscle mass index was unrelated to peak gradient and size of the valve. Peak gradient at 18 months rose with valve orifice diameter of 17 mm or less (by 6 mm Hg), orifice diameter/body surface area of 9 mm.m-2 or less (by 5 mm Hg), left ventricular enddiastolic dimension (by 23 mm Hg per 10 mm increase), and impaired ventricular function (by 3 mm Hg). All but 2 patients (5%) had intravascular hemolysis; none had anemia. Two patients with moderate paravalvular leak had the highest serum lactic dehydrogenase levels; 4 patients with trivial leak had higher serum lactic dehydrogenase levels than those without leak. Serum lactic dehydrogenase levels rose with moderate paravalvular leak, impaired ventricular function, and valve orifice diameter. Six patients with trivial or moderate paravalvular leak had a cumulative 7-year freedom from bleeding and thromboembolism of 44% +/- 22% compared with 87% +/- 5% for those without leak (p < 0.05). CONCLUSIONS: The peak gradient of the St. Jude aortic valve dropped marginally over the first 18 postoperative months in association with incomplete left ventricular hypertrophy regression and marginal improvement of ventricular function. Mismatch between valve size and ventricular cavity size or patient size and impaired function of a dilated ventricle significantly compromised the performance of the St. Jude valve. Probably explained by platelet destruction or activation, paravalvular leak was related to bleeding and thromboembolic complications.     

Diagnosis and treatment of aortic valve stenosis

The present review has attempted to summarize the classic symptoms and signs of aortic valve stenosis, especially in an adult. It is emphasized that all the classic signs rarely are present and their absence may mislead an unwary clinician. The diagnostic help provided by noninvasive tests, including echocardiography and phonocardiography, has been emphasized. A need for cardiac catheterization and angiography in most patients prior to corrective surgery is stressed. The natural history of the disease without operative intervention is dim and a significant risk of sudden death exists. The current surgical approach with immediate and long-term results is summarized. Finally, attention has been drawn to the special clinical circumstances when the aortic valve stenosis provides a strinkingly different clinical picture. We cannot find a better way to end this review than by quoting a warning note given by Thomas Lewis in 1920: "It is the faint cry of an anguished and fast failing muscle, which, when it comes, all should strain to hear, for it is not long repeated. A few months, a few years at most, and the end comes."