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PubMed1998

Exercise-induced fragmentation hemolysis: a simple in vivo test to evaluate heart valve hemolysis.

Differentiating heart valve-related fragmentation hemolysis from other causes of hemolysis can occasionally be difficult, especially when findings on transthoracic or transesophageal echocardiography are minimal. We report a case in which the cause of hemolysis remained in doubt after thorough hematologic and cardiologic evaluations. The decision to reoperate on the valve was finally made, based on the result of exercise-induced increase in serum hemoglobin. Hemolytic anemia promptly resolved after reoperation. We believe this to be the first reported use of this in vivo test to support the diagnosis of valve-related hemolytic anemia.

Anemia, Hemolytic↗
PubMed1996

Structural failure of pyrolytic carbon heart valves.

Pyrolite carbon has been used for the manufacture of mechanical heart valve prostheses for the past 25 years. In general, pyrolytic carbon mechanical heart valves have provided adequate physiological function and satisfactory structural performance. Although rare in occurrence, incidents of valve failure due to fracture of one or more components have been reported. These reports of failure are reviewed and a few representative examples are examined in detail in order to determine the characteristic failure mechanism. Understanding the underlying factors responsible for causing these failures provides a solid basis for improved design and manufacture of future mechanical heart valve prostheses.

Biocompatible Materials↗
PubMed1999

[Study of cytotoxicity of bioprosthetic heart valve material and its store solution].

This study compared the cytotoxicities of bioprosthetic heart valve materials crosslinked by glutaraldehyde, stored in 4% formaldehyde or Hank's solution. Human embryonic pulmonary fibroblasts or L-929 cell culture in vitro were used. Cell proliferative inhibition index(CP II) was calculated for bioprosthetic heart valve materials using different store methods in different rinse periods(before, 10 days, 20 days, 30 days). The results demonstrate: (1) bioprosthetic heart valve materials stored in 4% formaldehyde or in Hank's solution both have significant cytotoxicity, and the longer the rinse time continues, the lower the cytotoxicity declines; (2) HEL cell is more sensitive than L-929 cell in detecting the cytotoxicity of toxic biomaterials but for weak toxic biomaterials the two cell lines are not significanth different; (3) formatldehyde solution increases the cytotoxicity of biomaterials stored in it, but the enhanced cytotoxicity can be easily relieved by rinse. The authors conclude that bioprosthetic heart valve materials have long term significant cytotoxicity and the biomaterial cytotoxicity test using human fibroblasts is more sensitive and precise than other tests.

Animals↗
PubMed2003

Normal values for Doppler echocardiographic assessment of heart valve prostheses.

Assessment of normal and abnormal function of heart valve prostheses remains challenging. Doppler echocardiography has been shown to allow hemodynamic evaluation in various clinical settings and has become the most widely used tool to assess prosthetic valve function. Prosthetic valves, even when they function normally, are to some degree obstructive to the blood flow. The normal values of gradients, pressure half-time, and effective orifice area depend on valve type and valve size. Doppler assessment of prosthetic valve function, thus, requires specification of valve type and valve size, and knowledge of the normal values. This study provides an updated overview on the available data of normal values to facilitate adequate interpretation of Doppler data.

Aortic Valve↗
PubMed2006

Use of breath carbon monoxide to measure the influence of prosthetic heart valves on erythrocyte survival.

First-generation prosthetic heart valves commonly caused sufficient red blood cell (RBC) injury to induce hemolytic anemia. Although multiple studies have shown that new-generation valves are not associated with anemia, the extent to which these valves are injurious to RBCs is not known, because RBC survival not has not been measured in these subjects. Using a technique that uses breath carbon monoxide (CO) to quantify RBC turnover, this study measured RBC life span in 38 subjects with normally functioning, new-generation valves. Erythrocyte survival averaged 98.8 +/- 23 and 103 +/- 15 days, respectively, in 20 subjects with mechanical valves and 18 subjects with bioprosthetic valves (p >0.05). However, these life spans were significantly (p <0.01) less than those of healthy subjects (122 +/- 23 days) and a group of elderly subjects with osteoarthritis (128 +/- 26 days). The mean hemoglobin concentrations of the 2 groups of valve patients were within normal limits. In conclusion, new-generation heart valves commonly are associated with a small degree of hemolysis that is compensated for by increased RBC production.

Aged↗
PubMed2006

Heart valve tissue engineering: concepts, approaches, progress, and challenges.

Potential applications of tissue engineering in regenerative medicine range from structural tissues to organs with complex function. This review focuses on the engineering of heart valve tissue, a goal which involves a unique combination of biological, engineering, and technological hurdles. We emphasize basic concepts, approaches and methods, progress made, and remaining challenges. To provide a framework for understanding the enabling scientific principles, we first examine the elements and features of normal heart valve functional structure, biomechanics, development, maturation, remodeling, and response to injury. Following a discussion of the fundamental principles of tissue engineering applicable to heart valves, we examine three approaches to achieving the goal of an engineered tissue heart valve: (1) cell seeding of biodegradable synthetic scaffolds, (2) cell seeding of processed tissue scaffolds, and (3) in-vivo repopulation by circulating endogenous cells of implanted substrates without prior in-vitro cell seeding. Lastly, we analyze challenges to the field and suggest future directions for both preclinical and translational (clinical) studies that will be needed to address key regulatory issues for safety and efficacy of the application of tissue engineering and regenerative approaches to heart valves. Although modest progress has been made toward the goal of a clinically useful tissue engineered heart valve, further success and ultimate human benefit will be dependent upon advances in biodegradable polymers and other scaffolds, cellular manipulation, strategies for rebuilding the extracellular matrix, and techniques to characterize and potentially non-invasively assess the speed and quality of tissue healing and remodeling.

Animals↗
PubMed2003

Noise levels of closing sounds in vivo are equal for different bileaflet mechanical heart valves.

BACKGROUND AND AIM OF THE STUDY: Patients with mechanical heart valves must endure the valve's closing sounds for the rest of their life. Sound pressure levels (SPLs) recorded show wide patient-to-patient variation, even for the same type of valve. The variation was attributed to body constitution variability and differences in hemodynamic status. It was hypothesized that aortic mechanical valves generate closing clicks which correlate in magnitude with hemodynamic parameters, such as the rate of relaxation of the left ventricle (dp/dt) and potential energy stored in the aortic windkessel. METHODS: Three different aortic mechanical heart valves were investigated in a porcine model (n = 9), namely St. Jude Medical, CarboMedics and ATS. Closing sounds were measured with a microphone placed in a portable anechoic chamber 10 cm above the exposed heart. Left ventricular pressure (LVP) and cardiac output were also measured. Different hemodynamic conditions were produced by intravenous infusion of isotonic saline and dobutamine. Volume regulation and atrial pacing were also applied. RESULTS: Different hemodynamic situations were established (cardiac output, 1.2-6.5 l/min; heart rate, 99-171 bpm). The measured mean SPLs were 49.5-53.9 dB(A), and there were no statistically significant differences in noise between the valves (p = 0.8; one-way ANOVA). Likewise, only a weak relationship was identified between different hemodynamic parameters and the SPLs recorded. CONCLUSION: The SPLs of the investigated bileaflet mechanical heart valves did not differ significantly. Moreover, the SPL was only weakly related to LVP during closure and estimated stroke work.

Adaptation, Physiological↗
PubMed2004

Protocols for thawing and cryoprotectant dilution of heart valves.

PURPOSE: To reduce the time taken for thawing and removal of cryoprotectant from heart valves. METHODS: Three sets of experiments were carried out using porcine heart valves. The valves in all three experiments were first exposed to 10% (v/v) dimethyl sulphoxide (DMSO) by a 2-step protocol. Outcome was determined after the various experimental treatments by monitoring the outgrowth of cells from valve leaflet explants. Experiment 1-Dilution protocol. Valves exposed to 10% DMSO were subjected to 4-, 2- or 1-step dilution to remove the DMSO. Experiment 2-Warming rate. The rate of warming was increased by reducing the volume of cryoprotectant medium in which the valves were frozen. Valves were exposed to 10% DMSO, frozen in different volumes (100, 50, 25 or 0 ml) of cryoprotectant medium, and warmed in a 37 degrees C water bath. The DMSO was removed by 4-step dilution. Experiment 3-Standard vs. Modified protocol. Valves were either frozen in 100 ml 10% DMSO, thawed, and subjected to 4-step dilution (Standard) or frozen in 50 ml 10% DMSO, thawed, and the DMSO removed by single-step dilution (Modified). RESULTS: Neither the rate of warming nor the rate of dilution of DMSO had any influence on the subsequent outgrowth of valve leaflet fibroblasts. There were no differences in the outgrowth of cells from valve leaflets cryopreserved by the Standard or Modified protocols. CONCLUSION: The time taken for thawing and dilution of heart valves could be reduced from >20 min to <10 min without detriment to the viability of the leaflet fibroblasts. This should have a positive impact on valve replacement surgery as the thawing and dilution of valves are typically carried out while the patients are on cardiopulmonary bypass.

Animals↗
PubMed2004

[Anticoagulation in chinese patients with carbomedics mechanical prosthetic heart valves].

OBJECTIVE: To provide some references for defining the Chinese optimal intensity of anticoagulation after mechanical heart valve prostheses replacement. METHODS: For the 178 patients with carbomedics mechanical prosthetic heart valves, the means of INR were compared between the patients with complications and those without complications at the standard of INR1. 4 - 2.0. Also, the variations of INR were compared among different follow-ups. RESULTS: During the follow-up, 22 hemorrhagic and 1 thromboembolic complication occurred. The total linearized rate of anticoagulation-related hemorrhage was 5.83% pty. The total linearized rate thromboembolism was 0.26% pty. The late mortality was 0.79% pty (3 cases ). The final mean INR was 1.68 +/- 0.38. The final mean oral warfarin dose was 2.34 +/- 0.80 mg. The differences of variations of INR in five periods were significant (F = 5.072, P < 0.05). The mean INR in the first month of follow-up was 1.75 +/- 0.27. CONCLUSION: For Chinese patients with mechanical prosthetic heart valve, hemorrhage is the principal complication, the ratio of which is much higher than that of thromboembolism. The low-dose anticoagulation (INR1. 4-2.0) could remarkably decrease hemorrhagic events as effectively as prevent the thrombolic events. Moreover the INR is the most unstable in the first month of follow-up, so re-examination for the patients in the first month after the operation is vitally important.

Adolescent↗
PubMed1998

The dilemma of discontinuation of anticoagulation therapy for patients with intracranial hemorrhage and mechanical heart valves.

BACKGROUND: Anticoagulant-related hemorrhage occurs with an incidence of approximately 1%/patient-year in mechanical heart valve recipients. Intracranial hemorrhage poses a difficult clinical choice; continuing anticoagulation therapy may enlarge the volume of the hemorrhage, early reinstitution of anticoagulation therapy may predispose patients to recurrence, and reversal of anticoagulation therapy may place patients at risk for systemic embolization involving the brain. The risk of embolization may also be greater for patients with atrial fibrillation, cage-ball valves in the mitral position, and reduced ventricular function. This dilemma exists because of a lack of data for a large series of patients. METHODS: We reviewed the medical records and neuroimaging studies for a consecutive group of patients admitted with intracranial hemorrhage and mechanical heart valves. We reviewed neurological presenting data, cardiac risk factors for systemic embolization (atrial fibrillation, enlarged atrial chambers, reduced ventricular function, and the type and location of the metallic valve), and hospital management. RESULTS: We studied 39 patients with intracranial hemorrhage and mechanical heart valves (median age, 69 yr). Four patients had experienced previous transient ischemic attacks or minor strokes. The time from valve replacement to intracranial hemorrhage ranged from 2 months to 19 years (median, 6 yr). The type of intracranial hemorrhage was acute subdural hematoma (n = 20), lobar hematoma (n = 10), subarachnoid hemorrhage (n = 4), cerebellar hematoma (n = 3), or basal ganglionic hematoma (n = 2). Thirteen patients died within 2 days of admission. All 26 surviving patients received fresh frozen plasma and vitamin K. Fifteen patients underwent evacuation of acute subdural hematoma, and in one patient an anterior communicating aneurysm was clipped. The duration of discontinuation of anticoagulation therapy varied from 2 days to 3 months (median, 8 d). None of the patients developed transient ischemic attacks, ischemic strokes, valve thrombosis, or systemic embolization. No recurrence of intracranial hemorrhaging was observed during hospitalization and reinstitution of anticoagulation or antiplatelet agent administration. CONCLUSION: Temporary interruption of anticoagulation therapy seems safe for patients with intracranial hemorrhage and mechanical heart valves but without previous evidence of systemic embolization. For most patients, discontinuation for 1 to 2 weeks should be sufficient to observe the evolution of a parenchymal hematoma, to clip or coil a ruptured aneurysm, or to evacuate an acute subdural hematoma.

Adult↗
PubMed2006

Isolation and characterization of Streptococcus mutans in heart valve and dental plaque specimens from a patient with infective endocarditis.

Streptococcus mutans, known to be an aetiologic agent of dental caries, also causes infective endocarditis (IE), although a comparison of isolates from the oral cavity and infected heart valve of the same patient has not been reported. In the present study, infected heart valve and dental plaque samples from a patient with IE were analysed. Broad-range PCR with DNA sequencing revealed that 50 clones from the dental plaque isolates were composed of oral streptococci and periodontopathic bacteria, whereas only Streptococcus mutans was detected in 50 clones from the heart valve. Eighteen strains of Streptococcus mutans were isolated from dental plaque and seven from the heart valve, and the biochemical properties of each were in accordance with those of Streptococcus mutans. DNA fingerprinting analysis revealed that all the oral isolates of Streptococcus mutans had similar patterns, which were different from those of the isolates from the infected heart valve. Western blotting using glucosyltransferase (GTF)-specific antiserum showed that the seven strains from the heart valve lacked the three types of intact GTF. In addition, the sucrose-dependent adhesion rates of these isolates were significantly lower than those of the oral isolates (P<0.001). Furthermore, the isolates from the heart valve were less susceptible to erythromycin and kanamycin. These results indicate that the properties of the Streptococcus mutans strains isolated from the infected valve were different from those of typical oral strains, which may be related to the effects of IE.

Anti-Bacterial Agents↗
PubMed2003

[A xenogeneic acellularized matrix for heart valve tissue engineering: in vivo study in a sheep model].

BACKGROUND: The ideal scaffold material for tissue engineered heart valves is discussed controversially. We evaluated acellularized xenogenic matrix constructs with and without seeding with autologous vascular cells in the pulmonary circulation in a sheep model. METHODS: Porcine pulmonary valve conduits (n=16) were acellularized by trypsin/ EDTA incubation. Autologous myofibroblasts and endothelial cells were harvested from carotid arteries; xenogenic valve conduits (n=10) were repopulated with these autologous cells resulting in uniform cellular restitution of the pulmonary valve conduit surface. Using this method, we implanted autologous cell/xenogenic matrix constructs (XB) in ten animals. In six control animals acellularized/xenogenic matrix constructs (XA) were implanted. In each animal, cardiopulmonary bypass was used to resect the pulmonary valve and replace it with the xenogenic pulmonary valve conduits. The animals were killed after 6, 9 or 12 months. The explanted valves were examined histologically and biochemically. RESULTS: After explantation XB showed severe cusp degeneration, which resulted in severe valvular regurgitation. In comparison, XA appeared macroscopically normal with preserved valvular function. The surface of XB were covered with an incomplete endothelial multilayer. The extracellular matrix (ECM) of XB showed pathological amounts of collagenous and elastic fibers as well as proteoglycan content combined with an increase cellularity. The XA were completely repopulated by an endothelial cell monolayer; the ECM was repopulated with a myofibroblast population comparable to native ovine heart valve tissue. CONCLUSIONS: Approaches to heart valve engineering based on acellularized/xenogenic matrices provide promising results and will hopefully led to the "ideal" valve substitute in clinical heart valve replacement.

Animals↗
PubMed1992

Amino-aciduria and enzymuria in patients with artificial heart valves.

Fifteen patients with artificial heart valves and evidence of chronic intravascular haemolysis were studied for proximal tubular dysfunction. Three patients had haemosiderinuria and haemoglobinuria; 2 had haemoglobinuria alone. Increased urinary amino acid nitrogen occurred in 8, raised fractional beta 2-microglobulin excretion in 2, hypophosphataemia in 4, renal glycosuria in 1 and enhanced fractional urate excretion in 1. Urinary N-acetyl-beta-glucosaminidase (NAG) excretion increased in 7; the mean urinary NAG/creatinine ratio was raised to twice the upper limit of the normal range. Renal haemosiderosis due to chronic intravascular haemolysis could cause tubular injury.

Acetylglucosaminidase↗
PubMed1995

Physicochemical characterization of natural and bioprosthetic heart valve calcific deposits: implications for prevention.

This investigation was performed to provide a comprehensive physicochemical characterization of calcific deposits (CDs) that form on human heart valves under various pathological conditions. We examined and characterized CDs associated with aortic stenosis on congenitally bicuspid valves (n = 10), degenerative aortic stenosis on valves with previously normal anatomy (n = 10), and rheumatic aortic (n = 10) and mitral (n = 10) stenosis. Native and deproteinated CDs underwent chemical analysis and structural characterization, whereas deproteinated CDs were measured for thermodynamic solubility. The CDs in valvular heart disease were microcrystalline apatitic products containing substantial amounts of sodium, magnesium, carbonate, fluoride, and organic fraction. The properties of natural heart valve CDs were compared with those of previously measured CDs that form on or in heart valve bioprostheses. Compared with bioprosthetic valve CDs, natural valve CDs have a higher ratio of calcium to phosphorus, higher crystallinity, and lower solubility. These differences indicate that natural heart valve CDs appear to comprise a more mature biomineral. If the formation of mature CDs proceeds through transient stages involving unstable precursors, then the main strategy for prevention of calcific deterioration of bioprosthetic heart valves would be the development of locally applied long-term inhibitors that both (1) suppress nucleation and growth of more soluble precursors and (2) inhibit subsequent augmentation of less soluble CDs.

Adult↗
PubMed2000

Low-molecular-weight heparin for prosthetic heart valves: treatment failure.

There is no adequate substitute therapy for patients with prosthetic heart valves, in whom anticoagulation with warfarin or unfractionated heparin must be withheld. In the literature there are several reports describing successful treatment with low-molecular-weight heparin in patients with prosthetic heart valves. We report two cases of low-molecular-weight heparin treatment failure resulting in thrombosed prosthetic heart valves with stormy clinical presentations, who underwent successful valve replacements.

Adult↗
PubMed1997

Survival and cause of death after mitral valve replacement in patients aged 80 years and over: collective results from the UK heart valve registry.

OBJECTIVE: Over the last decade there has been an increasing number of patients aged 80 years and over undergoing heart valve replacement. However, literature on the outcome of mitral valve replacement (MVR) in this age group is still limited. METHODS: We conducted the present study by analysing data extracted from the UK Heart Valve Registry. From January 1986 to December 1994, 86 patients underwent isolated MVR and 10 underwent combined MVR with aortic valve replacement (AVR) and were reported to the Registry. RESULTS: The 30 day mortality was 10.4% (9/86) in the MVR group and 10% (1/10) in the MVR and AVR group. The actuarial survival was 79.8, 64.1 and 40.7% at 1, 3 and 5 years, respectively, in the MVR group. Of the 10 early (30 day) deaths, 8 were due to cardiac reasons and 19 of the 28 late deaths were due to non-cardiac reasons. A total of 55 (57.2%) patients received a bioprosthetic valve implant and 41 (42.8%) patients received a mechanical valve implant. There was no difference in survival between the two groups. CONCLUSIONS: The above results suggest that MVR in octogenarians produces a satisfactory early postoperative outcome and moderate medium-term benefit. There is no difference in survival between patients receiving bioprosthetic and patients receiving mechanical valve implants.

Actuarial Analysis↗