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Tricuspid valve biopsy: a potential source of cardiac myofibroblast cells for tissue-engineered cardiac valves.

BACKGROUND AND AIMS OF THE STUDY: As progress is made in the development of a tissue-engineered cardiac valve, the need for a reliable cell source is particularly important. A technique has been developed for the reliable biopsy of tricuspid valve leaflets. Expanding the harvested cells in culture is feasible and provides a source of leaflet cells that are structurally and functionally similar to the pulmonary and aortic valve leaflet cells that they may replace. METHODS: Thirteen sheep underwent tricuspid valve biopsy. Transthoracic echocardiography (TTE) was performed to evaluate function and guide the subsequent biopsy. Myofibroblasts were isolated from the biopsy samples, expanded in culture through 10 passages, and evaluated with immunocytochemistry for valve cell markers. Two animals were sacrificed acutely, two animals died during the immediate postoperative period, and nine animals survived for four weeks or more. RESULTS: All preoperative and pre-explantation echocardiograms were normal. Both animals sacrificed acutely showed that the tricuspid valve leaflet was indeed biopsied with this technique. Two perioperative deaths occurred; one animal died secondary to injury of the chorda tendinea with subsequent destruction of the posterior leaflet; another died from disruption of the superior vena cava that led to irreversible cardiac tamponade. At sacrifice (2 to 17 weeks), all other animals showed intact tricuspid valves with normal leaflet anatomy. All cultured biopsies generated myofibroblasts that were immunocytochemically positive for alpha smooth muscle actin, chondroitin sulfate, vimentin and fibronectin. CONCLUSION: Biopsy of the tricuspid valve to obtain recipient cardiac valve leaflet cells is possible, and the technique is simple and reliable. Biopsy of the leaflet does not compromise function. Interstitial cells can be harvested and expanded in culture. Cellular structure and function is preserved and is similar to that of other cardiac leaflet cells. Tricuspid valve leaflet biopsies are a potential source for harvesting cells to be used in the development of a tissue-engineered cardiac valve.

Actins↗

Differences in accumulation of elements in human cardiac valves.

To elucidate changes of human cardiac valves with aging, the authors determined age-related changes of element contents in the four human cardiac valves by inductively coupled plasma-atomic emission spectrometry and attempted to examine the relationships in the element contents among the four cardiac valves. The subjects consisted of 10 men and 15 women, ranging in age from 65 to 102 yr. The accumulation of calcium and phosphorus was the highest in the aortic valve, and decreased in the order mitral, pulmonary, and tricuspid valves. The contents of calcium and phosphorus in the aortic valves corresponded to about 12 and 19 times the amounts of those in the tricuspid valves, in which the contents were very low. The contents of calcium and phosphorus in the aortic valves were about 2.5-fold the amounts of those in the mitral valves. An examination was attempted to determine whether or not there were relationships in element contents among the four cardiac valves. As for the aortic and mitral valves, there were no relationships in the contents of calcium and phosphorus between them, but there were relationships in the contents of sulfur and magnesium between them. Three out of 24 cases contained high contents of calcium and phosphorus in both the mitral and aortic valves, whereas 16 out of 24 cases contained high contents of calcium and phosphorus in the aortic valves alone, without the high contents in the mitral valves. Likewise, there were no relationships in the element contents, such as calcium, phosphorus, sulfur, and magnesium, between the mitral and pulmonary valves or between the mitral and tricuspid valves. It is suggested that the accumulation of calcium and phosphorus in the cardiac valve occurs independent of the other cardiac valves.

Aged↗

The cardiac valve interstitial cell.

Cardiac valve interstitial cells (ICs) are a heterogeneous and dynamic population of specific cell types that have many unique characteristics. They are responsible for maintaining the extracellular scaffold that provides the mechanical characteristics vital for sustaining the unique dynamic behaviour of the valve. A number of cellular phenotypes can be distinguished: some are sparsely arranged throughout the valve leaflets, whilst others are arranged in thin bundles. These cells express molecular markers similar to those of skeletal, cardiac and smooth muscle cells (SMCs) and in particular, many ICs express smooth muscle (SM) alpha-actin, a marker of myofibroblasts. In this respect, these cells exhibit a profile unlike skin fibroblasts, which may allude to their role in valve function.

Actins↗

Age-dependent decreases of calcium, phosphorus, sulfur, and zinc in the cardiac valves of monkeys.

To elucidate compositional changes of the cardiac valves in monkey with aging, the authors investigated age-related changes of elements in the four cardiac valves of rhesus and Japanese monkeys and the relationships among elements by inductively coupled plasma-atomic emission spectrometry (ICP-AES). The four cardiac valves of the aortic, pulmonary, mitral, and tricuspid valves were resected from 19 rhesus and 11 Japanese monkeys, ranging in age from 10 d to 33 yr. The element contents were determined by ICP-AES. It was found that the Ca, P, S, and Zn contents were high in the four cardiac valves of the monkeys below 1 yr and thereafter decreased significantly with aging, except for Ca in the mitral valve, for which no significant correlation was found between age and Ca content. The Ca and P contents did not increase in the four cardiac valves at old age. This result revealed that calcification scarcely occurred in the four cardiac valves at old age. With regard to the relationships among elements, it was found that there were significant direct correlations among the Ca, P, S, and Zn contents in all of the four cardiac valves of the monkeys, with two exceptions between P and Zn contents in both the aortic and pulmonary valves. Therefore, as Ca decreased in the four cardiac valves, P, S, and Zn decreased simultaneously in the same cardiac valves.

Aging↗

Midterm results after aortic valve replacement with the autologous tissue cardiac valve.

OBJECTIVE: To assess midterm results after aortic valve replacement (AVR) with an autologous tissue cardiac valve (ATCV). This new technique was developed to construct a tissue prosthesis for AVR using the patients pericardium, harvested at the time of operation with negligible effect on operating time. METHODS: Briefly, glutaraldehyde tanned pericardium is mounted on a stent requiring no suturing. Between March 1994 and December 1996, 87 patients, 44/43 M/F and aged 70 +/- 6 years had AVR for aortic stenosis (80%), aortic insufficiency (6%) and combined lesions (14%), one patient suffered from endocarditis. Additional coronary artery bypass was done in 25%, aortic root enlargement in 7%. Aortic cross clamp and cardiopulmonary bypass times were 69 +/- 21 and 93 +/- 29 min. All patients were followed by clinical examination and color flow Doppler echocardiography in 3-12 months interval. Follow up was 99% complete. RESULTS: There were five perioperative deaths (6%), none of them valve related. Eighty-one patients were followed up to a period of 52 months (mean interval 37.5 +/- 1.3 months), one patient was lost for follow up. Overall survival was 86, 81, 79 and 71% at 12, 24, 36 and 48 months, respectively. There were 14 late deaths with eight (10%) valve related (four cerebral deaths, four sudden deaths). Sixteen patients (20%) had to be re-operated due to severe valve incompetence. Freedom from reoperation was 98, 97, 90 and 63% at 12, 24, 36, and 48 months, respectively. Valve incompetence occurred suddenly, without previous signs in the follow-up examinations. Selection and preparation of the pericardium, the way of fixation of the tissue--brief immersion in glutaraldehyde--and engineering problems might be responsible for this disastrous outcome. CONCLUSION: Due to these results we must state, that the ATCV did not fulfill our expectations and presently we can not recommend it as an aortic valve substitute.

Aged↗

Choosing a substitute cardiac valve: type, size, surgeon.

Certain ideal characteristics of substitute cardiac valves are analyzed for each of the four basic types of available substitute cardiac valves. Of the four, the caged disc prosthesis is the least desirable: it obstructs, it clots and it degenerates. Each of the other three types of substitute cardiac valves has more favorable characteristics. Ideally, the caged ball prosthesis might be limited to patients with predominantly regurgitant lesions because of the problem of prosthetic disproportion. The tilting disc has favorable hemodynamic and wear characteristics, but long-term anticoagulant therapy is essential, as with the caged ball and caged disc types of prosthesis. The porcine xenograft appears to be desirable, but patients with sufficient implantation time (more than 5 years) for proper evaluation are just beginning to be studied and, therefore, final judgment must be reserved. Assuming that valve replacement is to be carried out in a large medical center by a surgical team experienced in this procedure, the results of this operation today are dependent more on the type and size of substitute valve inserted than on the surgeon who inserts the valve. It is therefore important for the cardiologist to become more informed about the various types of prosthetic cardiac valves and to become a member of the team deciding which type and size of cardiac valve are most suitable for his (or her) patient.

Animals↗

Pathological mineralization of cardiac valves: causes and mechanism.

OBJECTIVE: Mechanism of calcification of cardiac valves was investigated through a comparative characterization of structure, morphology, and size of hydroxyapatite (HAP) crystals formed in mineral deposit on cardiac valves, bone tissue, and crystals synthesized from aqueous solutions under definite conditions. METHODS: All deposits on cardiac valves and bone samples were characterized by scanning electron microscopy (SEM) and energy dispersive X-ray microanalysis (EDS) in a Philips XL30 FEG microscope to evaluate their overall view and structure, to estimate the sizes of particles, and to carry out the chemical analysis. High resolution transmission electron microscopy (HRTEM) and electron micro diffraction was done for precise phase identification of individual crystals and measurements of their sizes. RESULTS: Mineral deposit on cardiac valves contained hydroxyapatite crystals (HAP) crystals with lengths from a few nanometers to a few hundred nanometers. Similar to the HAP precipitation in aqueous solutions, crystals in deposit were randomly oriented relative to each other and without the substrate effect on their orientation. Octacalcium phosphate (OCP) phase was also detected in the form of large (up to a few microns) crystals. The quantity of the OCP crystals was quite low in comparison with the amount of the HAP crystals. HAP crystals in bone samples were no more than 20 nm in length and textured in the HAP [0001] direction along collagen fibers. The HAP crystals from cardiac valves and bones were of uniform thickness comparable with the crystallographic unit cell. CONCLUSIONS: Mass crystallization model and hemodynamics in heart and arteries determine the mechanism of pathological calcification through the mediation of hydroxyapatite nanocrystals perpetually circulating with the bloodstream.

Adult↗

Long-term survival and valve-related complications in young women with cardiac valve replacements.

BACKGROUND: The type of cardiac valve replacement associated with the lowest health risks for young women who may undergo pregnancies is unknown. We investigated which valve type was associated with greatest patient and valve survival and the effect of pregnancy on valve loss. METHODS AND RESULTS: In this retrospective study, all women 12 to 35 years old who underwent valve replacements between 1972 and 1992 at Greenlane Hospital were identified, and follow-up was available in 93%. The 232 women were followed up for 1499 patient-years. Ten-year survival of women with mechanical (n=178), bioprosthetic (n=73), and homograft (n=72) valves was 70% (95% CI, 59% to 83%), 84% (95% CI, 72% to 99%), and 96% (95% CI, 91% to 100%), P=0.002. After adjustment for confounding variables, the relative risk (RR) of death with mechanical compared with bioprosthetic valves was 2.17 (95% CI, 0.78 to 5.88). Thromboembolic events occurred in 45% of women with mechanical valves within 5 years, compared with 13% with bioprosthetic valves, P=0.0001. Valve loss at 10 years was higher in bioprosthetic valves [82% (95% CI, 62% to 92%)] than in mechanical [29% (95% CI, 17% to 39%)] or homograft [28% (95% CI, 12% to 41%)] valves, P=0.0001. Pregnancy was not associated with increased bioprosthetic (RR, 0.96; 95% CI, 0.68 to 1. 35), homograft (RR, 0.65; 95% CI, 0.37 to 1.13), or mechanical (RR, 0.54; 95% CI, 0.27 to 1.08) valve loss. CONCLUSIONS: Although 10-year valve survival was greater with mechanical than bioprosthetic valves, mechanical valves may be associated with reduced patient survival in young women. Thromboembolic complications, often with long-term sequelae, were common with mechanical valves. Pregnancy did not increase structural deterioration or reduce survival of bioprosthetic valves.

Adult↗

Cardiac valve replacement in elderly patients.

Cardiac valve replacement in 65 consecutive elderly patients (aged 65 years and older) revealed that the indications for cardiac valve replacement in the elderly should be the same as those in the general population. These 65 patients represented 16% of the patients undergoing valve replacement. The mortality in the first 30 days after operation was 4.6% in the elderly group, compared with 0.9% in the group under 65 years of age. There were 26 significant but nonfatal early complications in the elderly patients, but their long-term functional status was excellent, most of the survivors ending up in either class I or class II of the New York Heart Association functional classification. The late mortality was 3.9% per patient year for aortic valve replacement and 15.1% for mitral with or without aortic valve replacement. The actuarial survival rates were 88% at 24 months and 55% at 54 months for the total elderly group, 86% at 36 months for those with aortic valve replacement, 85% at 24 months and 64% at 36 months for those with mitral valve replacement, 90% at 24 months and 77% at 42 months for the men, and 82% at 24 months and 68% at 42 months for the women. Aortic valve replacement was more common in the elderly than in the younger group because of the higher prevalence of congenital calcific aortic stenosis in the former, and this operation provided more gratifying results than mitral valve replacement in the elderly patients.

Age Factors↗

Single-shot versus interleaved echo-planar MR imaging: application to visualization of cardiac valve leaflets.

Visualization of the cardiac valves with standard magnetic resonance (MR) imaging is not adequate because of long acquisition times. Echo-planar imaging (EPI) can, however, be performed with a temporal resolution (30-50 msec) comparable to that of echocardiography. The authors evaluated the feasibility of real-time imaging of cardiac valve motion with ultrafast MR techniques. Eight healthy volunteers and three patients with mitral stenosis and regurgitation were studied with a 1.5-T whole-body imager. Two different EPI sequences were assessed: a standard single-shot gradient-echo EPI (GEPI) sequence and a fast imaging technique based on multiple-shot EPI with interleaved k-space acquisition (IGEPI). Fat-suppressed images with an in-plane resolution of 3.7 x 3.7 mm were obtained equally spaced through the cardiac cycle. Half-k-space acquisition was used. Morphologic evaluation was superior with IGEPI, owing to the better intracavitary signal homogeneity (P < .01), and the mitral valve leaflets were easier to identify on systolic images. IGEPI provided adequate valve visibility in all three patients.

Adult↗

In vitro immunogenicity of allogeneic cardiac valves.

The immunogenicity of allogeneic cardiac valves (ACV) has not been previously demonstrated in vitro, though valve failure due to tissue degeneration has been attributed to adverse immunological reactions. A novel in vitro assay has been developed in a Brown Norway (BN; RT1n)-Lewis (RT1; donor-recipient) rat model system that demonstrates the immunogenicity of ACVs. A single cell suspension of viable cardiac valve conduit (CVC) cells was obtained by collagenase treatment of BN rat aortic valve conduits. Brown Norway rat CVC cells (5 x 10(4)) and Lewis responder lymphocytes (10(5)) were co-cultured in 96 well plates in RPMI 1640 plus 2.5% (v/v) non heat-inactivated Lewis rat serum and supplements with appropriate controls. Stimulation of responder lymphocytes by CVC cells was measured by 3H-thymidine incorporation into DNA. The counts obtained between 96-192 h of co-culture in the CVC cell/responder lymphocyte reaction were significantly higher (P < 0.05) than those of responder cell controls as assessed by analysis of variance. These results indicate the presence of potent immunostimulatory cells in viable ACVs and the possibility of using a sensitive and reproducible in vitro assay to evaluate ACV immunogenicity.

Animals↗

Lethal cardiac tamponade due to aortotomy wound dehiscence after cardiac valve replacement: a forensic presentation.

Lethal cardiac tamponade due to aortotomy wound dehiscence after cardiac valve replacement (CVR) are apparently unreported in the recent literature. An uncommon example of delayed non-valvular lethal complication of CVR occurring in the early out-patient period is reported here. The forensic aspects of wound dehiscence in cardiovascular surgery for cardiac valve replacement are discussed, and complemented by a study of the fracture ends of suture material in wound breakdown associated with the suture failure.

Adult↗

Immunohistochemical and pathological characteristics of dystrophic amyloid in surgically excised cardiac valves.

One hundred and thirty-six cardiac valves obtained surgically from 124 patients (aged 15-77 years) were examined. Microdeposition of amyloid was present in sclerotic or sclerocalcific lesions of aortic valves in 38 out of 75 (51%) and mitral valves in 21 out of 61 (34%). Amyloid deposition was not significantly related to the age of the patients. An antiserum raised against a low molecular weight protein extracted from amyloid-laden valvular tissues (about 20 g) reacted positively to amyloid in the cardiac valves. It did not react to amyloid deposition containing fibril proteins including light chain related amyloidosis, reactive amyloidosis, systemic senile amyloidosis, isolated atrial amyloidosis, beta-2-microglobulin related amyloidosis and beta protein related amyloidosis. Further, amyloid in the cardiac valves failed to react immunohistochemically to anti-AA, anti-AL, anti-TTR, anti-ANF, anti-beta 2M and anti-beta protein antibodies. These findings suggest that an unknown amyloid protein is involved in the damaged valves.

Adolescent↗

[Clinical assessment of prosthetic valve replacement of the right-sided cardiac valves: mechanical or bioprosthesis?].

Clinical results with mechanical and bioprosthetic valve replacements for tricuspid and/or pulmonary positions were reviewed. Between February 1975 and December 1985, 34 bioprostheses (B) (22 Hancock, 9 Ionescu-Shiley and 3 Carpentier-Edwards pericardial) and 18 mechanical prostheses (M) (St. Jude Medical) were implanted in our institute excluding hospital death. Group with B included 29 tricuspid valve replacements and 5 pulmonary valve replacements. Group with M included 9 tricuspid valve replacements, 7 pulmonary valve replacements and 1 both valve replacements. The cumulative follow-up period was 207.2 patient-years (p-t) in group B and 55.0 p-y in group M. The incidence of valve failure was 0.48 +/- 0.48% per p-y in group B and 7.27 +/- 3.64% per p-y in group M (p less than 0.001). The incidence of valve-related events was 1.93 +/- 0.97% per p-y in group B and 9.09 +/- 4.07% per p-y in group M (p less than 0.001). At 3 years, the percent free of valve failure was 100 +/- 0% in group B and 76.8 +/- 10.2% in group M (p less than 0.05). Fourteen bioprosthetic valves (B') and 10 mechanical valves (M') were implanted at the right-sided cardiac valve position alone. The cumulative follow-up period was 94.2 p-y in group B' and 32.3 p-y in group M'. The incidence of valve-related events was 1.06 +/- 1.06% per p-y in group B' and 12.4 +/- 6.19% per p-y in group M' (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Primary cardiac valve tumors.

To investigate the characteristics of primary cardiac valve tumors, we retrospectively analyzed our multiinstitutional experience from 1932 through 1990. We encountered 56 valvular tumors in 53 patients. The average age of these patients was 52 years (range, 2 to 88 years) and 79% (42/53) were male. Symptoms were present in 38% (20/53) and were neurological in 15% (8/53). Four patients experienced sudden death. Each of the four valves was affected with approximately equal frequency: 16 aortic, 15 mitral, 13 pulmonary, and 12 tricuspid. All but four tumors were benign. The most common histological type was papillary fibroelastoma (41), followed by myxomas (5), fibromas (4), sarcomas (2), hamartoma (1), hemangioma (1), histiocytoma (1), and undifferentiated (1). Average tumor size was 1.15 cm (range, 3 mm to 7 cm), and the average size of fibroelastomas was 8 mm (range, 3 to 15 mm). Mitral valve tumors were more likely than aortic valve tumors to produce serious neurological symptoms or sudden death (8/15 versus 3/16; p less than 0.05). Six patients underwent echocardiography, and results were positive in each. All 6 underwent uncomplicated valve repair or replacement. Compared with a series of 407 nonvalvular tumors, cardiac valve tumors are more likely to occur in male patients (p less than 0.001) and adults (p less than 0.001). Valve tumors are also more commonly benign (p less than 0.001) and asymptomatic (p less than 0.001). These tumors demonstrate somewhat less aggressive behavior compared with non-valvular tumors, but their distinct propensity to produce serious clinical sequelae argues in favor of surgical resection for all cardiac valve tumors.

Female↗