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PubMed1991

An audit of anticoagulation and endocarditis prophylaxis after heart valve surgery.

OBJECTIVE: to audit anticoagulant control and endocarditis prophylaxis following heart valve surgery. DESIGN: retrospective review of all 190 patients living in Canterbury who had heart valve surgery between January 1981 and December 1986 to determine the incidence of endocarditis and complications of anticoagulation. RESULTS: there were 35 late deaths, of which nine were attributed to thromboembolism (3), major bleeding (2), or endocarditis (4). The rate of thromboembolic events, and major bleeding was 4.6 and 3.3/100 patient years of warfarin therapy respectively, while the incidence of late endocarditis was 0.96/100 patient years. Two episodes of endocarditis occurred after minor dental procedures performed without antibiotic prophylaxis. Many dentists indicated that they would not have recommended prophylactic therapy for these procedures. Some patients had inadequate recall of important details of anticoagulant control or endocarditis prophylaxis. Only 24% knew their latest prothrombin ratio, yet a survey of general practitioners revealed that, in their view, the majority of patients may be capable of monitoring their own anticoagulant therapy. CONCLUSION: the incidence of potentially preventable long term complications of heart valve surgery is comparable to other series. Nevertheless, these complications could be reduced by better patient education possibly enhanced by greater involvement of the patient in their anticoagulant control. The indications for antibiotic prophylaxis for dental procedures should be broadened for this group of patients.

Adolescent↗
PubMed2002

Collagen fiber disruption occurs independent of calcification in clinically explanted bioprosthetic heart valves.

The durability of bioprosthetic heart valves (BHV) is severely limited by tissue deterioration, manifested as calcification and mechanical damage to the extracellular matrix. Extensive research on mineralization mechanisms has led to prevention strategies, but little work has been done on understanding the mechanisms of noncalcific matrix damage. The present study tested the hypothesis that calcification-independent damage to the valvular structural matrix mediated by mechanical factors occurs in clinical implants and could contribute to porcine aortic BHV structural failure. We correlated quantitative assessment of collagen fiber orientation and structural integrity by small angle light scattering (SALS) with morphologic analysis in 14 porcine aortic valve bioprostheses removed from patients for structural deterioration following 5-20 years of function. Calcification of the explants varied from 0 (none) to 1+ (minimal) to 4+ (extensive), as assessed radiographically. SALS tests were performed over entire excised cusps using a 0.254-mm spaced grid, and the resultant structural information used to generate maps of the local collagen fiber damage that were compared with sites of calcific deposits. All 42 cusps showed clear evidence of substantial noncalcific structural damage. In 29 cusps that were calcified, structural damage was consistently spatially distinct from the calcification deposits, generally in a distribution similar to that noted in porcine BHV subjected to in vitro durability testing. Our results suggest a mechanism of noncalcific degradation dependent on cuspal mechanics that could contribute to porcine aortic BHV failure.

Animals↗
PubMed1998

Antithrombotic therapy in patients with mechanical and biological prosthetic heart valves.

Permanent therapy with oral anticoagulants offers the most consistent protection in patients with mechanical heart valves. Antiplatelet agents alone do not consistently protect patients with mechanical prosthetic heart valves, including patients in sinus rhythm with St. Jude valves in the aortic position. Levels of oral anticoagulants that prolong the INR to 2.0 to 3.0 appear satisfactory for patients with bileaflet mechanical valves in the aortic position, provided they are in sinus rhythm and the left atrium is not enlarged. Oral anticoagulant levels that prolong the INR to 2.5 to 3.2 are satisfactory for patients with bileaflet mechanical aortic valves and atrial fibrillation. Oral anticoagulant levels that prolong the INR to 2.5 to 3.5 are satisfactory for tilting disk valves and bileaflet prosthetic valves in the mitral position. Experience is sparse in patients with caged ball valves who had prothrombin time ratios reported in terms of INR. It has been suggested that the most advantageous INR level in patients with caged ball or caged disk valves should be as high as 4.0 to 4.9. However, others have shown a high rate of major hemorrhage with an INR that is even somewhat lower (3.0 to 4.5). The problem is self-limited, however, because few such valves are being inserted. Aspirin, in addition to oral anticoagulants, in patients with mechanical heart valves has been shown to diminish the frequency of thromboemboli. The risk of bleeding may not be increased if the INR is low. A low rate of both thromboemboli and bleeding has been shown with an INR of 2.5 to 3.5 in combination with aspirin at a dose of 100 mg/d. There are no investigations in which an aspirin dose of 81 mg/d in combination with oral anticoagulants was evaluated. Dipyripdamole may be effective in reducing the rate of thromboemboli without increasing the rate of bleeding, but data are insufficient to recommend dipyridamole over low doses of aspirin. Patients with bioprosthetic valves in the mitral position, as well as patients with bioprosthetic valves in the aortic position, may be at risk for thromboemboli during the first 3 months after surgery. Among patients during the first 3 months after surgery with bioprosthetic valves in the mitral position, oral anticoagulants administered at an INR of 2.0 to 2.3 were as effective as at an INR of 2.5 to 4.5: additionally, fewer bleeding complications were seen.

Administration, Oral↗
PubMedDate not supplied

Statistical correlation between transient pressure drop and cavitation at closure of a mechanical heart valve.

Cavitation on a mechanical heart valve (MHV) is attributable to transient regional pressure drop at the instant of valve closure. As a cavitation bubble collapses, it emits shock waves, which have the characteristics of high frequency oscillations (HFO) on a pressure time trace. The potential for such HFO bursts to cause material damage on an MHV can be measured by the cavitation impulse I, which is defined as the area under the trace of the HFO bursts. In the present study, experiments were conducted on a bileaflet MHV in a durability tester, operated at pulse rates from 300-1,000 bpm. In each case, the transient pressure near an occluder was monitored for 60,000 beats via a transducer. The peak pressure drop Pm and the corresponding cavitation impulse I obtained for the 60,000 beat sequence are found to resemble sample records of two stationary stochastic processes, each of which follows a log normal distribution. Their first order probability density functions are estimated from the records. The correlation is investigated between I and Pm associated with each beat, which is found to be of statistical significance.

Biomedical Engineering↗
PubMed1985

Community-acquired febrile illness in patients with prosthetic heart valves.

We prospectively studied 40 patients with prosthetic heart valves and community-acquired febrile illness. The mean age of the group studied was 35.2 +/- 12.8 years, and the mean length of time that the prosthetic valve had been in place was 53.4 +/- 43.7 months. There was a high incidence (37.5%) of infectious endocarditis in the patients studied, with a total mortality of 15% in the group. The presence of a new regurgitant murmur, skin or retinal lesions, splenomegaly, vegetations shown on echocardiograms, and persistent bacteremia was associated with infectious endocarditis (P less than .05). The patients with mechanical Starr-Edwards valves had a significantly higher incidence (P less than .001) of infectious endocarditis than those with other types of prosthetic valves implanted in our hospital. Complete evaluation is mandatory in febrile patients with prosthetic heart valves because of the high risk of prosthetic valve endocarditis as the cause of the fever.

Adult↗
PubMed2000

Early in vivo experience with tissue-engineered trileaflet heart valves.

BACKGROUND: Tissue engineering is a new approach in which techniques are being developed to transplant autologous cells onto biodegradable scaffolds to ultimately form new functional autologous tissue. Workers at our laboratory have focused on tissue engineering of heart valves. The present study was designed to evaluate the implantation of a whole trileaflet tissue-engineered heart valve in the pulmonary position in a lamb model. METHODS AND RESULTS: We constructed a biodegradable and biocompatible trileaflet heart valve scaffold that was fabricated from a porous polyhydroxyalkanoate (pore size 180 to 240 microm; Tepha Inc). Vascular cells were harvested from ovine carotid arteries, expanded in vitro, and seeded onto our heart valve scaffold. With the use of cardiopulmonary bypass, the native pulmonary leaflets were resected, and 2-cm segments of pulmonary artery were replaced by autologous cell-seeded heart valve constructs (n=4). One animal received an acellular valved conduit. No animal received any anticoagulation therapy. Animals were killed at 1, 5, 13, and 17 weeks. Explanted valves were examined histologically with scanning electron microscopy, biochemically, and biomechanically. All animals survived the procedure. The valves showed minimal regurgitation, and valve gradients were <20 mm Hg on echocardiography. The maximum gradient was 10 mm Hg with direct pressures. Macroscopically, the tissue-engineered constructs were covered with tissue, and there was no thrombus formation on any of the specimens. Scanning electron microscopy showed smooth flow surfaces during the follow-up period. Histological examination demonstrated laminated fibrous tissue with predominant glycosaminoglycans as extracellular matrix. 4-Hydroxyproline assays demonstrated an increase in collagen content as a percentage of native pulmonary artery (1 week 45.8%, 17 weeks 116%). DNA assays showed a comparable number of cells in all explanted samples. There was no tissue formation in the acellular control. CONCLUSIONS: Tissue-engineered heart valve scaffolds fabricated from polyhydroxyalkanoates can be used for implantation in the pulmonary position with an appropriate function for 120 days in lambs.

Absorbable Implants↗
PubMed1991

Validation of the orifice formula for estimating effective heart valve opening area.

Interest in the Gorlin formula for estimating heart valve effective orifice area (EOA) has recently been rekindled and the formula itself has been challenged. In this validation study, explanted native heart valves, unimplanted mechanical prostheses, unimplanted bioprostheses and explanted bioprostheses have been tested in vitro in a pulsatile flow simulator. Pressures have been measured 30 mm upstream and 100 mm downstream from the plane of the valve sewing ring (to give pressure drop, pd in kPa). Flow (Q in 1 min-1) has been measured directly by electromagnetic flowmeter and orifice areas have either been taken from manufacturer supplied data (mechanical valves) or have been digitised from video images at maximum orifice (biological valves). The formula EOA = Q/(6.96 x pd 1/2) - 0.7 fitted the data with good correlation, r = 0.96 (n = 179). The orifice assumption on which this formula is based (cf. Gorlin formula) is confirmed though it is recommended that the formula should be modified to account for (i) the pressure recovery phenomenon and (ii) the fact that forward flow through a valve only occurs over a portion of the cycle in pulsatile flow. Heart rates used in the study ranged from 40 to 140 min-1, stroke volumes ranged from 20 to 114.3 ml, cardiac outputs from 2.0 to 8.0 1 min-1 and peripheral resistance from 0.1 to 1.6 kPa 1-1 min (1 - 12 mmHg l-1 min). Application of the formula was independent of the flow conditions.

Adult↗
PubMed1988

An emergency physician's guide to prosthetic heart valves: identification and hemodynamic function.

We describe methods for identifying the type and size of seven commonly used prosthetic heart valves and how these features influence the hemodynamics of flow through the valve. The four mechanical heart valves reviewed are Starr-Edwards silicone rubber ball valves (Models 1200/1260 aortic and 6120 mitral valves), Bjork-Shiley tilting disc valves (60 degrees standard spherical model and the 60 degrees convexo-concave model), Medtronic-Hall (Hall-Kaster) tilting disc valve, and St Jude Medical bileaflet valve. The three bioprostheses reviewed are Hancock porcine valve, Carpentier-Edwards porcine valve, and Ionescu-Shiley bovine pericardial valve. These valves were chosen because of their past or present popularity and therefore are the ones most apt to be implanted in patients seen in the emergency department.

Bioprosthesis↗
PubMed1996

In vitro testing of artificial heart valves: comparison between Newtonian and non-Newtonian fluids.

The in vitro testing of artificial heart valves is often performed with simple fluids like glycerol solutions. Blood, however, is a non-Newtonian fluid with a complex viscoelastic behavior, and different flow fields in comparable geometries may result. Therefore, we used different polymer solutions (Polyacrylamid, Xanthan gum) with blood-like rheological properties as well as various Newtonian fluids (water, glycerol solutions) in our heart valve test device. Hydrodynamic parameters of Björk-Shiley heart valves with a tissue annulus diameter (TAD) of 21-29 mm were investigated under aortic flow conditions. Major results can be summarized as follows. The mean systolic pressure differences depend on the model fluids tested. Closing time and closing volume are not influenced by the rheological behavior of fluids. These parameters depend on TAD and the pressure differences across the valve. In contrast, rheological behavior has a pronounced influence upon leakage flow and leakage volume, respectively. Results show furthermore that the apparent viscosity data as a function of shear rate are not sufficient to characterize the rheological fluid behavior relevant to hydrodynamic parameters of the heart valves investigated. Therefore, similarity in the yield curves of non-Newtonian test fluids mimicing blood is only a pre-requisite for a suitable test fluid. More information about the viscous and elastic component of the fluid viscosity is required, especially in geometries where a complex flow field exists as in the case of leakage flow.

Acrylic Resins↗
PubMed2003

Diagnostic value of D-dimer and antithrombin-III levels in predicting prosthetic heart valve thrombosis.

The aim of this prospective study was to investigate the diagnostic value of plasma D-dimer levels and antithrombin-III activity in predicting prosthetic valve thrombus. The study group comprised 97 consecutive patients with prosthetic heart valves (59 with mitral, 21 with aortic, and 17 with both mitral and aortic prostheses) and 35 healthy control subjects. Six patients presented with symptoms of obstruction; the remaining 91 were asymptomatic. Patients were evaluated by both transthoracic and transesophageal echocardiography. Asymptomatic nonobstructive thrombus was detected in 13 patients (13%), whereas obstructive thrombus was demonstrated in all symptomatic patients. Plasma antithrombin-III levels of patients with prosthetic valve thrombi were slightly lower than those of patients without thrombus and of the control group, but the difference was not statistically significant. However, significantly higher plasma D-dimer levels were observed in patients with prosthetic valve thrombi, compared with patients without thrombus and the control group (735 +/- 633 microg/L, 372 +/- 342 microg/L, and 228 +/- 219 microg/L, respectively). Valve thrombus, the prosthetic heart valve itself, and INR levels were identified as major determinants of plasma D-dimer levels. A plasma D-dimer level of >445 microg/L predicted the presence of a prosthetic valve thrombus with 57.8% sensitivity and 83.3% specificity (positive predictive value, 47.8%; negative predictive value, 87.8%). Current data suggest that increased plasma D-dimer levels can be clinically helpful in predicting the presence of prosthetic valve thrombus. Plasma antithrombin-III activity does not seem to have a diagnostic value in predicting prosthetic valve thrombi.

Adult↗
PubMed2001

In vitro investigation of prosthetic heart valves in magnetic resonance imaging: evaluation of potential hazards.

BACKGROUND AND AIM OF THE STUDY: Magnetic resonance (MR) imaging is used in an increasing number of patients, and not only after cardiac valve replacement. However, ferromagnetic biomedical implants are often considered a contraindication for MR imaging because of the potential hazards with respect to their movement, dislodgement, or heating effects during the procedure. The purpose of this study was to assess ferromagnetism, attraction forces, heating effects, and artifacts associated with prosthetic heart valve implants. METHODS: Seventeen common heart valve prostheses (12 mechanical, five biological) were examined in vitro using a high-field-strength 1.5 Tesla (T) MR system. Attractive forces, temperature changes and the amount of artifacts were assessed by applying turbo-spin and gradient-echo sequences. RESULTS: The maximal calculated corresponding ferromagnetic force was (0.22 x 10(-3) N) in the static magnetic field. The temperature changes ranged from 0 to 0.5 degrees C maximum. Artifacts produced by the presence of the heart valve prostheses were less evident using a spin-echo sequence than a gradient-echo sequence. CONCLUSION: MR imaging exerted no significant force on the examined heart valve prostheses, and did not result in significant biological relevant temperature increase. None of the associated artifacts is considered to pose a substantial risk on MR imaging. MR procedures performed with a 1.5 T MR system can be applied safely in patients with heart valve prostheses evaluated in this study.

Artifacts↗
PubMed1985

Clinical performance of the omniscience prosthetic heart valve with Dacron sewing ring.

The Omniscience prosthetic heart valve has been clinically evaluated in 44 patients operated on between January and July, 1981. There were 23 aortic valve replacements (AVR), 18 mitral valve replacements (MVR) and 3 double valve replacements (DVR). Mean age was 48 +/- 11 years. Preoperatively, 61% patients were in New York Heart Association (NYHA) functional class IV, 36% in class III and 2% in class II. The hospital mortality rate was 4.5%. Actuarial freedom from thromboembolic events was 97.4 +/- 2.6% (3 1/2 years of follow-up). Postoperatively, 93% of the patients were in NYHA class I and 7% in class II. There were 7 cases of periprosthetic leak requiring reoperation (6 AVR, 1 MVR) for an overall incidence of 6.3% per patient year. In all these cases the causative factor was considered to be the Dacron sewing ring. All patients survived the reoperation. The actuarial survival rate was 93.9 +/- 5.9% for AVR and 93.7 +/- 6.1% for MVR. These data would suggest that the Omniscience prosthesis represents an acceptable device for heart valve replacement, except for the high incidence of periprosthetic leakage, related to the Dacron sewing ring. Recent modification of the valve-construction including a Teflon sewing ring may avoid the relatively high rates of periprosthetic leakage following implantation of this mechanical valve.

Acenocoumarol↗
PubMed1986

Bioprosthetic heart valve rupture associated with trauma.

Disruption of a bovine pericardial bioprosthetic aortic heart valve occurred in a motor vehicle accident, and was treated by valve replacement for progressive aortic insufficiency. Leaflet rupture was through areas of noninflammatory tissue degeneration, corresponding to regions of repeated mechanical stress and trauma that occur during the normal function of tissue valves. Patients with bioprosthetic heart valves may be predisposed to traumatic valve injury. Early diagnosis and replacement of these disrupted valves should be accomplished to avoid sudden, unpredictable heart failure.

Accidents, Traffic↗
PubMedDate not supplied

Advances towards understanding heart valve response to injury.

BACKGROUND: Composed of endocardial endothelial, valvular interstitial, cardiac muscle, and smooth muscle cells (SMC), heart valves are prone to various pathologic conditions the morphology of which has been well described. The morphology of diseased valves suggest that the "response to injury" process occurs in these valves, and is associated with an accumulation of interstitial cells and matrix, valvular inflammation and calcification, conditions that lead to dysfunction. The purpose of this study is to describe the current knowledge of the regulation of the valvular "response to injury" process, since we feel that this paradigm is essential to understanding valve disease. METHODS: The pertinent literature relating to the cell and molecular biology of valvular repair, and specifically interstitial cell function in valve repair, is reviewed. RESULTS: The cell and molecular biology of valve interstitial cells are poorly understood. Molecules regulating some of the aspects of the "response to injury" process have been studied, however, the signal transduction pathways, gene activation, and interactions of bioactive molecules with each other, with cells, and with the matrix have not been characterized. Initial studies identify the cell and molecular biology of interstitial cells to be an important area of research. Agents that have been studied include nitric oxide (NO) and FGF-2 and several matrix-related proteins including osteopontin. The present review suggests several directions for future study and a working model of valvular repair is presented. DISCUSSION: The regulation of the "response to injury" process in the human heart valve is still largely unknown. The cell and molecular events and processes that occur in heart valve function and repair remain poorly understood. These events and processes are vital to our understanding of the pathobiology of heart valve disease, and to the successful design of tissue engineered replacement valves.

Endocardium↗
PubMed2000

Phenotypic and functional characterization of interstitial cells from human heart valves, pericardium and skin.

BACKGROUND AND AIM OF THE STUDY: Human heart valve interstitial cells (ICs) have been understudied to date. The aim of this study was to determine whether valve ICs were uniquely different from pericardial ICs and skin fibroblasts by determining their phenotype and investigating their reactivity. METHODS: ICs were cultured from human heart valves (n = 13), pericardium (n = 4) and skin (n = 4). Cell phenotype was determined by immunofluorescence using a panel of antibodies against surface and cytoskeletal components, and intracellular calcium changes were evaluated by loading the cells with fura-2 acetoxymethyl ester. RESULTS: Skin fibroblasts expressed virtually no smooth muscle (SM) alpha-actin, whereas, 56.9+/-8.9% (mean +/- SEM) of ICs from valves and 21+/-7.6% of ICs from pericardium expressed SM alpha-actin. ICs from pericardium and skin fibroblasts always expressed a fibroblast surface antigen, whereas expression was variable on valve ICs (80+/-6.9%). All cells expressed prolyl 4-hydroxylase, beta-tubulin and vimentin, but not desmin. Transient increases in intracellular calcium were induced by vasoactive agents: skin fibroblasts were least responsive to all agents. CONCLUSIONS: ICs cultured from heart valves consist of a mixed population of specific cell types, many of which express SM alpha-actin and may be classified as myofibroblasts. The intracellular calcium responses to vasoactive agents indicated that a number of receptor signaling pathways existed. Evaluation of these may help to elucidate the role of myofibroblasts and other fibroblast phenotypes in valve function/dysfunction, as well as contribute to the development of tissue-engineered valves.

Actins↗
PubMed1999

[Minimally invasive approach for heart valve replacement: report of 73 cases].

OBJECTIVE: To report a new minimally invasive approach for heart valve operation. METHODS: Through right minimal vertical infra-axillary thoracotomy incision (by intercostal space), 68 patients with rheumatic heart disease, 2 patients with subacute endocarditis, and 3 patients with congenital heart disease underwent heart valve replacement from March 1997 to Spring 1998. RESULTS: 30 double valve replacements, 33 mitral valve replacements, 10 aortic valve replacements and 14 DeVega tricuspid annuloplasty were performed. The length of the incision averaged (8.5 +/- 0.9) cm, arrest times averaged (88.6 +/- 33.8) min, cardiopulmonary bypass times averaged (117.0 +/- 45.9) min. Five mitral valve replacements were performed with ventricular fibrillation. Ventilator periods averaged (9.6 +/- 3.6) h, chest tube drainage averaged (264.5 +/- 184.3) ml. One patient died of cerebral bleeding in hospital. Two patients suffered SBE and one of them died. The results of follow up for other patients were fine. CONCLUSIONS: This minimally incisive valve operation is a new safe, small wounded and cosmetic approach for heart valve replacement.

Adult↗
PubMed1997

Model experimental system for investigation of heart valve calcification in vitro.

A model system was developed for the in vitro quantitative investigation of the calcification process occurring in heart valves. The process of heart valve calcification consists of the formation of calcium phosphates at the heart valve-biological fluid interface. Calcium phosphate deposits may consist of more than one calcium phosphate mineral phase, differing with respect to their physical and chemical properties. The kinetics of the formation of hydroxyapatite, the model inorganic compound for the calcified deposits, was precisely monitored in a reactor containing supersaturated calcium phosphate solutions in which the heart valves were immersed after being treated with glutaraldehyde and mounted on special racks. The precipitation process, accompanied with proton release in the solution, was monitored by a pair of glass-saturated calomel electrodes. Upon initiation of the formation of calcium phosphate deposits, the supersaturation in the working solution was reestablished through the addition of titrant solutions made with the appropriate concentration to compensate for the ions precipitated. With this methodology, not only the rates were measured very precisely but also the nucleation capability of the various substrates could be evaluated. Moreover, it was possible to identify the formation of intermediate calcium phosphate phases formed during the calcification process. Valves previously treated with glutaraldehyde were shown to nucleate octacalcium phosphate, which at lower supersaturations converted to the thermodynamically more stable hydroxyapatite. The rates measured were found to depend on the solution supersaturation, while the apparent order of the precipitation process was found to be 1.

Animals↗
PubMed2000

Tissue engineering of pulmonary heart valves on allogenic acellular matrix conduits: in vivo restoration of valve tissue.

BACKGROUND: Tissue engineering using in vitro-cultivated autologous vascular wall cells is a new approach to biological heart valve replacement. In the present study, we analyzed a new concept to process allogenic acellular matrix scaffolds of pulmonary heart valves after in vitro seeding with the use of autologous cells in a sheep model. METHODS AND RESULTS: Allogenic heart valve conduits were acellularized by a 48-hour trypsin/EDTA incubation to extract endothelial cells and myofibroblasts. The acellularization procedure resulted in an almost complete removal of cells. After that procedure, a static reseeding of the upper surface of the valve was performed sequentially with autologous myofibroblasts for 6 days and endothelial cells for 2 days, resulting in a patchy cellular restitution on the valve surface. The in vivo function was tested in a sheep model of orthotopic pulmonary valve conduit transplantation. Three of 4 unseeded control valves and 5 of 6 tissue-engineered valves showed normal function up to 3 months. Unseeded allogenic acellular control valves showed partial degeneration (2 of 4 valves) and no interstitial valve tissue reconstitution. Tissue-engineered valves showed complete histological restitution of valve tissue and confluent endothelial surface coverage in all cases. Immunohistological analysis revealed cellular reconstitution of endothelial cells (von Willebrand factor), myofibroblasts (alpha-actin), and matrix synthesis (procollagen I). There were histological signs of inflammatory reactions to subvalvar muscle leading to calcifications, but these were not found in valve and pulmonary artery tissue. CONCLUSIONS: The in vitro tissue-engineering approach using acellular matrix conduits leads to the in vivo reconstitution of viable heart valve tissue.

Animals↗