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PubMed2004

Essential role of Sox9 in the pathway that controls formation of cardiac valves and septa.

Epithelial-mesenchymal transformation is a critical developmental process reiterated in multiple organs throughout embryogenesis. Formation of endocardial cushions, primordia of valves and septa, is a classic example of epithelial-mesenchymal transformation. Several gene mutations are known to affect cardiac valve formation. Sox9 is activated when endocardial endothelial cells undergo mesenchymal transformation and migrate into an extracellular matrix, called cardiac jelly, to form endocardial cushions. In Sox9-null mutants, endocardial cushions are markedly hypoplastic. In these mutants, Nfatc1 is ectopically expressed and no longer restricted to endothelial cells. Further, Sox9-deficient endocardial mesenchymal cells fail to express ErbB3, which is required for endocardial cushion cell differentiation and proliferation. Our results reveal a succession of molecular steps in the pathway of endocardial cushion development. We propose that loss of Sox9 inhibits epithelial-mesenchymal transformation after delamination and initial migration, but before definitive mesenchymal transformation.

Animals↗
PubMed2002

Processing of ovine cardiac valve allografts: 3. Implantation following antimicrobial treatment and preservation.

It is known that a satisfactory clinical outcome can follow the implantation of cardiac valve allografts in spite of the loss of living cells in the tissue. If viable cells are not required for long term graft function, then effective disinfection of the tissue might become possible. In an earlier paper in this series we reported that peracetic acid (PAA) is an effective antimicrobial agent for the treatment of valve allografts; it was lethal to the cells but at a concentration of 0.21% had little effect on the mechanical properties or extracellular morphology of the valve leaflets. It was also found that PAA-treatment could be combined with storage in 85% glycerol at 4 degrees C, or cryopreservation with 10% Me(2)SO, without substantial further impairment of microscopic structure or mechanical properties. In this paper we describe the implantation of processed ovine aortic valves in the descending thoracic aorta of sheep. The experimental groups included control untreated valves and valves that had been treated with antibiotics or PAA and either cryopreserved, or stored in 85% glycerol. The recipient sheep showed good clinical appearances until the experiment was terminated at six months. The explanted grafts were examined by standard morphological and mechanical testing methods. The PAA-treated valves were clearly recognisable as valves: the leaflets had fair to medium morphology in both the unpreserved and the cryopreserved groups. All leaflets had a superficial overgrowth of cells. Microsatellite analysis for allelic differences were performed on samples of donor and recipient tissues using three markers of tissue source. Only one valve, which had been treated with PAA, revealed allelic differences between donor and recipient. It is suggested that DNA-fragments may have remained after the destruction of donor cells and six months of implantation: the overgrowing cells were almost certainly of recipient origin. We conclude that our experiments, in which PAA-treatment was combined with preservation, are sufficiently encouraging to justify further studies to refine the technique, but in our opinion they are not sufficient to justify a clinical trial at this time.

Journal Article↗
PubMed1993

Bioprosthetic cardiac valve degeneration: role of inflammatory and immune reactions.

Inflammatory and immune reactions are thought to mediate both calcification and biodegradation of bioprosthetic cardiac valve implants. To investigate the mechanisms of implant degeneration, we evaluated the role of inflammatory and immune reactions and the effects of tissue preservative treatment in three series of experiments. In the first experiment, three kinds of implants, i.e. glutaraldehyde-treated autograft Sprague-Dawley (SD) rat skin, xenograft Swiss-Webster (SW) mouse skin, and saline-treated autograft (control) were subcutaneously implanted in ten weanling SD rats, and retrieved after 70 days. There was no significant difference in the level of calcification in the autograft (113.13 +/- 27.09 micrograms/mg dry weight) and xenograft (78.27 +/- 31.53 micrograms/mg dry weight) (p > 0.05), but both differed significantly from the control specimens (1.55 +/- 0.87 micrograms/mg dry weight). In the second experiment, the immunological response to glutaraldehyde-treated bovine pericardium (glut tBP) and glycerol treated bovine pericardium (glyc tBP) implants were tested in vivo and in vitro. A Gore-Tex implant was used as a control. Sections of these materials were implanted to the abdominal muscle wall of Lewis rats, with each group composed of twelve animals. Lymphocytes and sera from the animals were isolated, and histological examination was performed at two or four weeks post-implantation. Collagen type 1 (calf skin) was used as antigen. Tritiated thymidine incorporation was used to measure lymphocyte response to antigen collagen type 1 (calf skin), and an Enzyme Linked Immunosorbent Assay (ELISA) was used to test antibodies. The results showed that lymphocytes from both the glut tBP and the glyc tBP groups responded to collagen type 1. The ELISA results showed that the glyc tBP group produced more antibodies than did the glut tBP group, with the difference being significant at a level of p < 0.02. Histology revealed that the glyc tBP had greater inflammatory changes and collagen degeneration than did the glut tBP. In the third experiment, sections of glut tBP and glyc tBP were implanted subcutaneously in two groups of ten weanling SD rats, and retrieved after 70 days. The results showed that glut tBP caused more calcification (197.04 +/- 83.56 micrograms/mg dry weight) than did the glyc tBP (6.74 +/- 0.55 microgram/mg dry weight), with the difference being significant at a level of p < 0.05. From these investigations it is concluded that tissue treatment prior to implantation was very important in determining the tendency of tissue to calcify, and that there was no obvious relationship between bioprosthetic calcification and immunogenicity.

Animals↗
PubMed1997

XTT-colorimetric assay as a marker of viability in cryoprocessed cardiac valve.

This study sought to evaluate the use of tetrazolium salt XTT reduction as an indicator of valvular viability in a cryoprocessed porcine cardiac homograft model. The XTT tetrazolium assays was based on the metabolic reduction of Sodium 3'-[1-(phenylamino-carbonyl)-3,4-Tetrazolium]-bis(4-methoxy-6-nitro) benzene sulfonic acid hydrate. The relationship between XTT reduction and: (1) leaflet tissue with various weight (n = 24); (2) morphometric evaluation (n = 30); (3) cadaveric ischemic intervals (n = 30); (4) freeze-thawing (n = 30) has been studied. The measurement of XTT reduction were significantly correlated with the weight of cardiac leaflets, in the range of 30 to 180mg (y=0.015x-0.063; r=0.99). Compared to morphometry of valvular damage, the reduction of mitochondrial enzymatic activity in cardiac leaflets was correlated with matrix cells without irreversible damage (r=0.89, P<0.005). The depletion of XTT reduction occurred dependent of ischemic time intervals. In general, freeze-thawing reduced more than 20% activity of mitochondrial dehydrogenase. We concluded that XTT tetrazolium assay is highly sensitive to determine valvular injury. The study demonstrated its potential for testing of cryopreserved cardiac valve.

Animals↗
PubMed1997

Variability in anticoagulation control predicts thromboembolism after mechanical cardiac valve replacement: a 23-year population-based study.

OBJECTIVE: To assess optimal control of blood anticoagulation to maximize antithrombotic protection after mechanical cardiac valve replacement. DESIGN: A population-based study of 96 patients with a mean follow-up of 7.7 years (range, 1 month to 23 years) was performed in Olmsted County, Minnesota, and 10,301 prothrombin time (PT) ratios were determined after mechanical heart valve replacement. MATERIAL AND METHODS: PT ratios were analyzed in a new time-dependent Cox proportional-hazards model by defining an algorithm for comparing variability in PT ratios at each month of follow-up and relating these to thromboembolic events. The new method was compared with several conventional time-independent definitions. RESULTS: During 740 person-years of follow-up, 19 of 96 patients (20%) had 27 thromboembolic events. Of these 19 patients, 8 (42%) had events within 3 months after valve replacement. Freedom from any thromboembolic event was 72% at 15 years. The event rate was high (7.5% per year) during high variability and low (0.9% per year) during low variability in the PT ratio. This relationship was lost when time dependence was removed. More PT ratios were less than 1.5 during high (27%) than during low (19%) variability. Several conventional definitions of adequacy of anticoagulation that averaged PT ratios before a thromboembolic event or throughout follow-up or that compared the proportion of PT ratios above or below a fixed ratio did not define or only partially defined different thromboembolic risks. CONCLUSION: Periods of high and low variability of PT ratios define high and low risk of thromboembolism, respectively.

Adult↗
PubMed1981

[Decompensated cardiac valve disease associated with tight aortic stenosis. Surgical cure in one stage (author's transl)].

The authors report on 2 cases of severe cardiac valve disease associated with tight stenosis of the aortic isthmus for which the standard techniques could not be safely applied owing to patients' poor condition. Inserting by the median route a dacron tube between the ascending aorta and the subdiaphragmatic descending aorta immediately after heart valve replacement under extracorporeal circulation in our experience proved a simple and safe technique.

Angiocardiography↗
PubMed2004

Lineage and morphogenetic analysis of the cardiac valves.

We used a genetic lineage-labeling system to establish the material contributions of the progeny of 3 specific cell types to the cardiac valves. Thus, we labeled irreversibly the myocardial (alphaMHC-Cre+), endocardial (Tie2-Cre+), and neural crest (Wnt1-Cre+) cells during development and assessed their eventual contribution to the definitive valvar complexes. The leaflets and tendinous cords of the mitral and tricuspid valves, the atrioventricular fibrous continuity, and the leaflets of the outflow tract valves were all found to be generated from mesenchyme derived from the endocardium, with no substantial contribution from cells of the myocardial and neural crest lineages. Analysis of chicken-quail chimeras revealed absence of any substantial contribution from proepicardially derived cells. Molecular and morphogenetic analysis revealed several new aspects of atrioventricular valvar formation. Marked similarities are seen during the formation of the mural leaflets of the mitral and tricuspid valves. These leaflets form by protrusion and growth of a sheet of atrioventricular myocardium into the ventricular lumen, with subsequent formation of valvar mesenchyme on its surface rather than by delamination of lateral cushions from the ventricular myocardial wall. The myocardial layer is subsequently removed by the process of apoptosis. In contrast, the aortic leaflet of the mitral valve, the septal leaflet of the tricuspid valve, and the atrioventricular fibrous continuity between these valves develop from the mesenchyme of the inferior and superior atrioventricular cushions. The tricuspid septal leaflet then delaminates from the muscular ventricular septum late in development.

Animals↗
PubMed1998

Autologous pericardial patch harvesting site for cardiac valve repair: anatomic and morphometric considerations.

BACKGROUND AND AIMS OF THE STUDY: Short-term glutaraldehyde-fixed autologous pericardium is widely used in cardiac valve repair or in autologous pericardial bioprosthesis construction. The thinner the tissue, the better the fixation. The aim of this study was to determine thickness and useful surface area of pericardium in relation to harvesting site using a digital thickness counter (0.01 mm precision). METHODS: Parietal pericardium fragments were obtained from the pericardial sac of six fresh cadavers (group I). In the other groups, pericardial strips (80 x 30 mm) were obtained from patients undergoing surgery: group II patients (n = 5 females) and group III (n = 10 males) were non-cardiomegalic (cardiothoracic ratio (CTR)<0.5), while group IV patients (n = 5) were all cardiomegalic (CTR >0.5). RESULTS: Results were reported on a coloric scale according to measurement position. In group I, mean surface area was 93+/-18 cm2, and thickness gradually increased from 0.1 to 0.6 mm, maximally on the diaphragm, along the left heart side. In other groups, a gradual increase in thickness was identified towards the diaphragmatic zone. Significant differences in tissue thickness appear as a result of cardiomegaly, but are not related to the sex of the patients. CONCLUSIONS: Pericardium taken from the right anterior aspect of the pericardial sac in patients without cardiomegaly is the most appropriate tissue for valve reconstructive surgery, due to its thin nature and hence better fixation properties.

Cadaver↗
PubMed2005

Rheumatic involvement of all four cardiac valves.

Rheumatic involvement of all four heart valves is rare. A 35 year old woman presented with gradually progressive exertional dyspnoea for the preceding 10 years. On evaluation she was in atrial fibrillation with congestive heart failure. Clinical examination found evidence of stenosis of the mitral aortic and tricuspid valves with a history of rheumatic fever in childhood. Transthoracic echocardiography showed the involvement of all four cardiac valves. Few reports are available in the literature describing rheumatic quadrivalvar damage. Operator awareness of possible rheumatic involvement of all four valves is essential for appropriate diagnosis.

Adult↗
PubMed1989

[Anticoagulant management of patients with cardiac valve prostheses].

This article reports the methods and results of anticoagulant management in 653 patients with China-made Björk-Shiley mode Tilting Disc Cardiac Valve Prostheses. The total incidence of thromboembolic complications and valve thrombosis is 0.98 per 100 patient-years during the anticoagulation. The incidence of anticoagulant-related hemorrhage is 1.86 per 100 patient-years. In the anticoagulant period, 61 surgical operations were performed on 58 patients. The results showed that anticoagulant can be maintained in minor, superficial operations where blood ooze can be arrested by compression, temporarily discontinued in elective operations, and reversed abruptly by injecting Vitamin K1 in urgent operations. In addition we handled the contradictions between anticoagulant therapy and menses, contraceptive, pregnancy or delivery (29 patients) for 303 female patients favorably. We conclude that our methods gave excellent results, and were reasonable and practicable.

Adolescent↗
PubMed1993

Copper deficiency alters collagen types and covalent cross-linking in swine myocardium and cardiac valves.

Dietary copper deficiency induces alterations of connective tissue metabolism that are associated with lesions in cardiovascular and other organ systems. To determine the impact of copper deficiency on characteristics of collagen in porcine myocardium and cardiac valves, weaned pigs were fed diets with adequate or deficient levels of copper. Although dietary copper did not affect the concentration of collagen in either myocardium or bicuspid valves, the degree of collagen cross-linking, as assessed by the level of hydroxylysylpyridinoline, was lower in both tissues of copper-deficient pigs. Proportions of type III collagen were increased in the left ventricle and bicuspid valves of copper-deficient pigs. Copper deficiency induced extensive remodeling, however, of the collagen fraction of cardiac interstitium. Reduction in left ventricular collagen cross-linking may provide the stimulus for the development of cardiac hypertrophy, which characterizes severe copper deficiency, by increasing the compliance of the ventricular wall. The shift in the phenotypic profile of collagen that is associated with this cardiac hypertrophy indicates synthesis of new collagen, which could affect collagen cross-linking irrespective of copper status.

Animals↗
PubMed1990

The central axis prosthetic cardiac valve: an in vitro study of pressure drop assessment under steady-state flow conditions.

In this work, a new mechanical prosthetic heart valve, the central axis valve, is presented. This new prosthesis has been tested in vitro, and compared with four other common prosthetic cardiac valves (Starr-Edwards 6120, Bjork-Shiley monostrut, Medtronic-Hall, and St Jude Medical valves). All valves studied have the same orifice diameter of 22 mm. The prostheses were installed inside a transparent mitral test chamber, which enables pressure drop measurement to be made under steady-state flow conditions using a blood analogue fluid. Pressure drop loss is one important factor affecting the overall performance of a prosthetic heart valve. Steady-state flow tests are essential to predict certain flow characteristics and pressure gradient loss before more complicated, expensive, and difficult-to-interpret pulsatile flow tests are conducted. All experiments were performed in vitro and at steady volumetric flow rates of 10 to 30 l/min. The Starr-Edwards SE 6120 showed the highest values for pressure drop. The St Jude Medical valve offers the minimum resistance to flow. The central axis valve comes second to the Starr Edwards valve for this type of measurement. The new valve is promising. A complete valve evaluation programme, covering initial conceptional design through to clinical use, is in progress. Materials for the fabrication of the new valve are also under consideration.

Biocompatible Materials↗
PubMed1996

Failure of adjusted doses of subcutaneous heparin to prevent thromboembolic phenomena in pregnant patients with mechanical cardiac valve prostheses.

OBJECTIVES: This report describes our experience with the use of an anticoagulant regimen of adjusted doses of subcutaneous heparin during pregnancy in women with cardiac valve prostheses. BACKGROUND: Gravid patients with prosthetic heart valves require long-term anticoagulant therapy. To avoid the increased incidence of fetal morbidity and mortality associated with the use of coumarin agents in such patients during pregnancy, anticoagulation with subcutaneous heparin has been suggested. Controversy exists concerning the appropriate treatment of these patients. METHODS: Forty pregnancies in 37 women with prosthetic heart valves were prospectively followed up. Subcutaneous heparin was administered from the 6th until the end of the 12th week and in the last 2 weeks of gestation. Heparin was given every 8 h in the first 36 cases and every 6 h in the last 4 cases, and the dose adjusted to maintain the activated partial thromboplastin time at 1.5 to 2.5 times the control level. Acenocoumarol was used at other times. RESULTS: The incidence rate of spontaneous abortions was 37.5%; there was one neonatal death (2.5%) due to cerebral hemorrhage. No signs of coumarin-induced embryopathy were found in any of the 16 live-born infants studied by the geneticist. One mother died of gastrointestinal bleeding while receiving oral anticoagulant agents. There were two cases of fatal massive thrombosis of a mitral tilting-disk prosthesis during heparin therapy. The study was interrupted after the last of these two cases. CONCLUSIONS: The regimen of adjusted doses of subcutaneous heparin used in this study is not effective to prevent thrombosis of mechanical valve prostheses during pregnancy. The use of heparin from the 6th to the 12th week of gestation does not decrease the high incidence of fetal wastage associated with anticoagulant therapy. Coumarin agents provide adequate protection against thromboembolism during pregnancy in patients with mechanical valve prostheses.

Abnormalities, Drug-Induced↗
PubMed1997

Doppler microembolic signals in children with prosthetic cardiac valves.

BACKGROUND AND PURPOSE: The aim of this study was the evaluation of the prevalence and counts of Doppler microembolic signals (MES) in children with prosthetic cardiac valves and their comparison to those obtained in corresponding adult patients. PATIENTS AND METHODS: Nine children and 43 adults with ATS valves implanted in the aortic position were monitored over both middle cerebral arteries with transcranial Doppler ultrasound. MES were identified on-line according to standard criteria. Heart rate and rhythm, valve type, size and duration, patients' height, International Normalized Ratio, and prevalence of neurological complications were obtained from all study participants. RESULTS: MES prevalence and counts were significantly higher in children compared with adult patients (100% versus 25.5% and 58 [18.5 to 115.5] versus 55 [2 to 10.5], median, 95% CI, respectively). No corresponding differences in valve duration of valve implant were evident, but children has heart rates and were significantly smaller compared with adults. A positive correlation between patients' size, heart rate, and MES counts was noted. CONCLUSIONS: MES counts in children with mechanical prosthetic valves are significantly higher compared with those in corresponding adults. We hypothesize that this is due to (1) the shorter distance between aortic valve and middle cerebral artery, since cavitation bubbles have a short life span and are bound to dissolve with time, and (2) the faster heart rate in children, resulting in a higher number of valve closures per minute.

Adolescent↗
PubMed2006

Endothelium-derived microparticles inhibit human cardiac valve endothelial cell function.

Elevated numbers of endothelium-derived microparticles (EMPs) in the circulation are found in a variety of critical illnesses. EMPs have been associated with vascular dysfunction, including thrombotic complications and loss of normal vascular reactivity, common responses associated with cardiac valve injury. However, the exact mechanisms of this dysfunction and the potential impact on cardiac endothelium are unknown. We hypothesize that pathologic levels of circulating EMPs negatively regulate proliferation and migration of valvular endothelial cells (ECs), leading to downstream endothelial dysfunction. EMPs were generated from plasminogen activation inhibitor 1-stimulated human umbilical vein endothelial cells (HUVECs). Human mitral valve endothelial cells (HMVECs) were isolated and characterized by platelet endothelial cell-derived adhesion molecule-1 (PECAM-1, or CD31) and von Willebrand factor immunocytochemistry. HMVECs were treated with increasing EMP doses, and then, the effects of EMPs on growth factor-induced proliferation and migration were tested. Proliferation was assessed by H-thymidine incorporation. EC migration was assayed by photographing microtubules of HMVECs and HUVECs in fibrin gel incubated with EMPs +/- growth factors for 48 h. The EMP effects on non-valve HUVECs were tested in parallel. EMPs inhibited HMVEC proliferation at high doses but stimulated HUVEC proliferation at all doses. In HMVECs, EMPs inhibited basic fibroblast growth factor- and vascular endothelial growth factor-induced proliferation and migration. Taken together, these data suggest EMPs regulate valvular EC proliferation in a dose-dependent manner and, furthermore, modulate growth factor signaling in ECs. These results implicate EMPs as a possible source of downstream EC dysfunction in disease states. EMPs may play a role in valvular leaflet injury in human disease by inhibiting normal growth and repair of endothelium.

Cell Movement↗
PubMed1995

Cardiac valve involvement in systemic lupus erythematosus and primary antiphospholipid syndrome: lack of correlation with antiphospholipid antibodies.

The aim of this study was to determine the prevalence of cardiac valve disease in systemic lupus erythematosus or in patients with primary antiphospholipid syndrome and to assess the role of the antiphospholipid antibodies as risk factor for endocardial lesions. We studied 39 consecutive patients with systemic lupus erythematosus (mean age 34 +/- 12 years, 38 female and one male), 20 women with primary antiphospholipid syndrome (mean age 32 +/- 4 years) and 20 normal subjects (mean age 35 +/- 8 years, 15 female and five male). All patients with primary antiphospholipid syndrome had increased levels of serum anticardiolipin antibodies and recurrent fetal abortions; some of them also had arterial and/or venous thrombosis and/or thrombocytopenia. M-mode, two-dimensional and Doppler echocardiography were performed in all patients. IgG anticardiolipin antibodies were measured by an enzyme-linked immunosorbent assay. Valvular lesions were observed in 15 patients (38%) with systemic lupus erythematosus. These abnormalities included: mitral valve thickening or vegetation, mitral valve prolapse and aortic valve vegetation; mitral, aortic and tricuspid regurgitation; mitral stenosis. None of the patients with primary antiphospholipid syndrome and of the normal subjects was found to have valvular abnormalities. In systemic lupus erythematosus, high levels of anticardiolipin antibodies were detected in 73% of the patients with valvular lesions and in 67% of the patients without valvular lesions (P > 0.05). We conclude that valvular involvement is frequent in patients with systemic lupus erythematosus but it is apparently unrelated to antiphospholipid autoimmunization.

Abortion, Habitual↗
PubMed2006

Human semilunar cardiac valve remodeling by activated cells from fetus to adult: implications for postnatal adaptation, pathology, and tissue engineering.

BACKGROUND: The evolution of cell phenotypes and matrix architecture in cardiac valves during fetal maturation and postnatal adaptation through senescence remains unexplored. METHODS AND RESULTS: We hypothesized that valvular interstitial (VIC) and endothelial cell (VEC) phenotypes, critical for maintaining valve function, change throughout life in response to environmental stimuli. We performed quantitative histological assessment of 91 human semilunar valves obtained from fetuses at 14 to 19 and 20 to 39 weeks' gestation; neonates minutes to 30 days old; children aged 2 to 16 years; and adults. A trilaminar architecture appeared by 36 weeks of gestation but remained rudimentary compared with that of adult valves. VECs expressed an activated phenotype throughout fetal development. VIC density, proliferation, and apoptosis were significantly higher in fetal than adult valves. Pulmonary and aortic fetal VICs showed an activated myofibroblast-like phenotype (alpha-actin expression), abundant embryonic myosin, and matrix metalloproteinase-collagenases, which indicates an immature/activated phenotype engaged in matrix remodeling versus a quiescent fibroblast-like phenotype in adults. At birth, the abrupt change from fetal to neonatal circulation was associated with a greater number of alpha-actin-positive VICs in neonatal aortic versus pulmonary valves. Collagen content increased from early to late fetal stages but was subsequently unchanged, whereas elastin significantly increased postnatally. Collagen fiber color analysis revealed a progressive temporal decrease in thin fibers and a corresponding increase in thick fibers. Additionally, collagen fibers were more aligned in adult than fetal valves. CONCLUSIONS: Fetal valves possess a dynamic/adaptive structure and contain cells with an activated/immature phenotype. During postnatal life, activated cells gradually become quiescent, whereas collagen matures, which suggests a progressive, environmentally mediated adaptation.

Adaptation, Physiological↗
PubMed1998

Prevalence of microbubbles associated with mechanical prosthetic cardiac valves: a prospective transesophageal echocardiography study.

BACKGROUND AND AIM OF THE STUDY: The study aim was to identify the prevalence of microbubbles in different types of mechanical cardiac valve and, if feasible, to associate microbubbles with various clinical conditions, including thrombotic occlusion of the valves. METHODS: A total of 153 mechanical prosthetic valves were studied (58 aortic, 95 mitral) in 140 patients, prospectively. All valves were functioning normally. In addition, eight mitral prosthetic valves were selected without microbubbles and with an obstructive valvular thrombosis that had undergone successful thrombolysis (group 1); a further eight patients with unsuccessful thrombolysis (group 2) were studied by transesophageal echocardiography before and after thrombolytic therapy. RESULTS: Microbubbles were detected in 75% (114/153) of prosthetic valves, 99% (88/89) of bileaflet valves, and 45% (29/64) of monoleaflet valves (p < 0.0001). Only 14% (4/28) of Sorin monoleaflet valves were associated with microbubbles, which is distinctively less than other valves (p < 0.001 for each); 71% and 77% of aortic and mitral prosthetic valves, respectively, were associated with microbubbles (p = NS). Prosthetic valves with an obstructive thrombosis and no microbubbles in group 1 showed new appearance of microbubbles in 88% (7/8) of cases after successful thrombolysis. Absence of microbubbles in group 2 persisted in all eight patients at the second examination. CONCLUSIONS: Microbubbles were detected in a greater proportion of patients than reported previously and were found to be associated more with bileaflet prosthetic heart valves than with monoleaflet valves. Sorin monoleaflet valves were associated with microbubbles dramatically less than all other valves. The new appearance of microbubbles after thrombolytic therapy of mechanical prosthetic heart valves with an obstructive thrombosis may indicate successful thrombolysis.

Adult↗