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Lipid extraction attenuates the calcific degeneration of bovine pericardium used in cardiac valve bioprostheses.

Bovine pericardial bioprostheses frequently fail due to dystrophic calcification. Since (a) recent studies indicate that membrane-associated complexed acidic phospholipids play an important role in the process of both physiologic and pathologic calcification, and (b) cytoplasmic organelles and plasma membrane of interstitial cells seem to serve as initial sites of calcific degeneration of bioprosthetic bovine pericardial tissue, this investigation was undertaken to evaluate whether, and if so, to what extent, the mineralization of valve tissue could be attenuated by previous lipid extraction. Pretreatment of glutaraldehyde-preserved bovine pericardium with acidified sulphuric ether (pH 3.0-4.0) attenuated calcification significantly: 28 days after subcutaneous implantation in young rats the degree of mineral deposition was approximately equal to typical 7 days implants in this model. The mechanism of this beneficial effect is suggested to be due to partial extraction of tissue phospholipids, as demonstrated by electron microscopy, thus reducing the number of available sites for deposition of hydroxyapatite crystals. In addition, and importantly, the present results indicate that any attempt to reduce cardiac valve bioprosthesis mineralization will have to take into account the role of lipids and, particularly, the membranous phospholipids in the calcification mechanism.

Animals↗

Vasculitis of the aortic arch and cardiac valves as the cause of relapsing fever of unknown origin in an elderly, white man.

Here, we report the case of fever of unknown origin (FUO) in a 77-year-old white man. The patient presented with a 3-week history of fever (between 38.5 and 39 degrees C) and general malaise. These symptoms had occurred about five to seven times during the past 30 years, and despite repeated hospitalizations, no diagnosis was made. Physical examination did not reveal any specific signs of infection nor did the patient fulfill the criteria for any rheumatic disease including vasculitides. Blood chemistry showed a greatly elevated C-reactive protein (CRP; 158.2 mg/l) and an erythrocyte sedimentation rate >100 mm, indicating an active inflammatory process, and leukocytes were significantly elevated (20,000/mul). Rheumatological parameters showed only nonspecific changes. Finally, a 2-[(18)F]-fluoro-2-deoxy-D: -glucose-positron emission tomography was performed, revealing a markedly enhanced glucose uptake in the ascending aorta and the cardiac valves, indicating vasculitis as the cause of FUO in this patient. Based on this finding, treatment was started with corticosteroids, and 2 days after the initiation of treatment, the patient had normal body temperature, and after 5 days, CRP values had returned to normal. After tapering and final complete removal of steroid treatment, the patient was still free of symptoms, hence no disease-modifying antirheumatic drug therapy was necessary.

Aged↗

Quantitative evaluation of endothelial progenitors and cardiac valve endothelial cells: proliferation and differentiation on poly-glycolic acid/poly-4-hydroxybutyrate scaffold in response to vascular endothelial growth factor and transforming growth factor beta1.

Three-dimensional scaffolds made of bioabsorbable polymeric constituents are currently being tested for use in tissue engineering of various tissues. A composite scaffold of poly-glycolic acid (PGA) non-woven mesh dip-coated in a 1% solution of poly-4-hydroxybutyrate (P4HB) was shown to be suitable as a scaffold for creation of tissue-engineered trileaflet pulmonic valve replacements in sheep [Hoerstrup, S.P., et al., Circulation 102(Suppl. 3), III44, 2000]. However, little is known about how cells seeded on PGA/P4HB respond in vitro to soluble factors supplied in the culture medium. To optimize tissue development in vitro, before implantation, we set out to develop quantitative biochemical assays to measure how cells seeded on PGA/P4HB respond to growth and differentiation factors. Herein we show that ovine aortic valvular endothelial cells and circulating endothelial progenitor cells (EPCs) seeded onto PGA/P4HB proliferate in response to vascular endothelial growth factor and transdifferentiate to a mesenchymal phenotype in response to transforming growth factor beta(1). Transdifferentiation from an endothelial to mesenchymal phenotype is a critical step during embryonic development of cardiac valves. Our results demonstrate that valvular endothelial cells and EPCs isolated from peripheral blood can recapitulate critical developmental steps on PGA/P4HB. These results demonstrate that PGA/P4HB provides a conducive environment for cellular proliferation, differentiation, and tissue development.

Cell Differentiation↗

[Clinical reasoning and decision-making in practice. A 76 year old woman with gastric carcinoma and cardiac valve disease].

A 76-year-old woman with combined aortic and mitral valve disease presented with anaemia due to a gastric carcinoma. Further staging revealed no evidence for metastatic disease. Approval for surgery for the carcinoma was obtained after a cardiologist and anaesthesiologist were consulted. On the day of surgery, however, the attending anaesthesiologist estimated the operative risk to be unacceptable. The patient reversed her decision and decided not to have the oncological operation, as she felt well at the moment and considered the limited additional survival time not worth the anxiety. The expert opinion of an anaesthesiologist, a cardiologist and an oncologist not primarily involved in this case show that they differ as to the question who is responsible for the decision-making process in patients such as this one. The evidence on estimating operative risk in patients with cardiac valve disease undergoing noncardiac surgery is not unequivocal. Furthermore, there is a shared responsibility when more physicians are involved in the process of decision-making. Agreement on operative risk between physicians is necessary in order to prevent transfer of conflicting information to the patient.

Aged↗

Clinical and hemodynamic results with the St. Jude Medical cardiac valve prosthesis. A three-year experience.

Two hundred thirty-two consecutive patients (October 3, 1977, through December, 31, 1980) underwent aortic (AVR), mitral (MVR), or double (DVR) valve replacement with the St. Jude Medical (SJM) prosthesis. Operative mortality for the entire group was 7.3%. There was 100% follow-up. Warfarin (Coumadin) anticoagulation was recommended for all patients. There were no cases of mechanical failure. The incidence of thromboembolism was 0.6/1,000 patient-months for those with AVR, 3/1,000 patient-months for those with MVR, and 0% for those with DVR. Thrombosis of a prosthesis occurred in two patients with DVR. Clinically significant hemolysis occurred in three patients with paravalvar leaks following MVR. Late postoperative prosthetic infection has not occurred. Postoperative catheterization studies in 33 patients revealed no transvalvular gradient at rest in 21 patients. The remainder of the patients catheterizd had low transvalvular gradients. There was a minimal increase in transvalvular gradient with exercise. The SJM cardiac valve is a viable alternative in the surgical therapy of valvular heart disease.

Adolescent↗

Variability of Doppler microembolic signal counts in patients with prosthetic cardiac valves.

BACKGROUND AND PURPOSE: The purpose of this study was the evaluation of intraobserver, interobserver, and intrasubject variability in the Doppler detection of microembolic signals in patients with mechanical prosthetic valves. Simultaneously, the feasibility of automated embolus detection by means of a neuronal network was investigated. METHODS: From 25 patients with mechanical prosthetic heart valves, single transcranial Doppler monitoring sessions of 30 minutes' duration were recorded on videotape, randomized, and subsequently analyzed by eight independent trained observers from three centers. Three observers evaluated these tapes on three separate occasions, blinded to their previous results. An additional 48 patients with prosthetic heart valves were repetitively monitored with transcranial Doppler ultrasonography for 30 minutes three times within 1 year to examine the long-term variability in the occurrence of microembolic signals. Finally, in an effort to assess the short-term intrasubject variability, 20 patients were examined for 90 minutes, and the results of the three 30-minute periods were compared. The interobserver, intraobserver, and intrasubject (both short- and long-term) variability was evaluated. RESULTS: No significant differences in microembolic signal counts were found among the different observers, between the human observers and the neuronal network, or among the three separate evaluations of stored data by the same observer. The same was true for repeat examinations of the same patient (P > .05, Student's two-paired t test and Friedman's test). CONCLUSIONS: The detection of microembolic signals in patients with prosthetic cardiac valves is a reproducible technique. The reliable performance of the neuronal network argues for a broader use of this device. The intrasubject stability of the microembolic rate over 1 year supports the concept that the underlying emboligenic process is associated with intrinsic mechanical properties of the valve implant and not due to a thromboembolic process in the heart.

Cerebral Arteries↗

Cavitation versus degassing: in vitro study of the microbubble phenomenon observed during echocardiography in patients with mechanical prosthetic cardiac valves.

BACKGROUND: With the advent of second harmonic imaging in echocardiography, microbubbles have been observed during opening and closure of mechanical prosthetic valves. The single phenomenon of cavitation, an extremely short event described in the literature, cannot explain the persistence of microbubbles during several hundred milliseconds. Therefore, in vitro we reproduced two distinct phenomena created by a local depression occurring during the closure and/or opening of prosthetic valves: Cavitation and degassing. METHODS: We used a water circuit system enriched with CO(2) that passes through a Venturi tube in order to create variable pressure gradients. Three types of observations were performed: (1). the dimensions of the bubbles as a function of pressure, (2). calibration of the echocardiograph, and (3). comparison and illustrations of the difference between bubble formation by cavitation (vaporization) and degassing (liberation of CO(2)). RESULTS: According to the different pressures exerted, the dimensions of the bubbles only vary by several microns, not measurable in practice. Second, the calibration of the echocardiograph reveals that the dimensions of the bubbles measured by ultrasound are greater by a factor of 1.75. Finally, the observed cavitation is a short phenomenon (several milliseconds) and happens under a great local pressure gradient. The degassing produces microbubbles lasting up to as long as > 1 second under much lower pressure. CONCLUSION: This in vitro study suggests that microbubbles observed during several hundred milliseconds after the opening of prosthetic cardiac valves are the result of degassing of CO(2) in blood rather than a cavitation phenomenon as suggested in the literature.

Biophysical Phenomena↗

Age does not limit quality of life improvement in cardiac valve surgery.

OBJECTIVES: We sought to determine the association of age with the change in quality of life (QOL) after valve surgery. BACKGROUND: Improvement in QOL is one of the principal goals of valve surgery. These procedures are being done with increasing frequency for older patients. METHODS: We prospectively studied 148 patients with aortic valve procedures and 72 patients with mitral valve procedures. Patients' QOL was measured at baseline and at 18 months using the Medical Outcomes Trust Short Form 36-Item (SF-36) Health Survey (response rate 90%). The association of age with change in QOL was measured by multiple regression analysis and based on two meta-scores of the SF-36: the Mental Component Summary (MCS) and the Physical Component Summary (PCS). RESULTS: Overall improvement in most domains of the SF-36, including the MCS and the PCS scores, was substantial. Improvement in the MCS score was not influenced by age in either aortic (0.09 score point improvement per 10-year age increments; p = 0.9) or mitral (0.90 score point improvement per 10-year age increments; p = 0.3) patients. Similarly, improvement in the PCS score did not vary by age in aortic patients (-1.00 score points per 10-year age increments; p = 0.2) and only slightly varied by age in mitral patients (-1.90 score points per 10-year age increments, p = 0.02). In the latter, despite statistical significance, the association was not substantial or clinically important. CONCLUSIONS: Among patients referred for cardiac valve surgery, age does not appear to limit the QOL benefits of surgery.

Aged↗

Estimation of the rotational undamped natural frequency of bileaflet cardiac valve prostheses.

The angular momentum balance is solved numerically for a size 29 mm CarboMedics prosthetic heart valve. The lift force is estimated from potential flow theory, while the drag force is estimated from the lift force and a blunt body empiricism. Buoyancy and gravitational effects are calculated based on the assumption of homogeneous leaflets. Other assumptions include uniform flow, negligible friction at the pivot axis, negligible viscous damping and fluid inertance, and a symmetry flow condition. Oscillations are predicted in the opening dynamics in the range of 2-25 Hz, for flow rates through one-half of the orifice in the range of 0.1-10.0 l/min. The frequency of these oscillations is dependent upon the orientation of the leaflet in relation to the gravitational field and the magnitude of the flow rate. In vivo and in vitro measurements by other investigators demonstrate similar effects of gravity and flow rate, with flutter frequencies of the order of 10-100 Hz. Excitation frequencies, based on vortex shedding, are estimated to be of the order 2-200 Hz, for the range of flow rates of the theoretical model. These results suggest that the natural frequency of this rotational second order system may, in theory, be a contributing factor to the flutter observed in bileaflet cardiac valve prostheses. The clinical significance of this finding is yet to be established.

Blood Flow Velocity↗

Immunofluorescence studies of cardiac valves in infective endocarditis.

Mitral and aortic valves removed at emergency cardiac surgery from a patient with infective endocarditis caused by Streptococcus viridans were studied by immunofluorescence to ascertain the extent and pattern of various immune reactants within the large valvular vegetations. Heavy intravalvular deposits of IgG as well as bacterial antigen were present. Much more focal interstitial IgM and C3 deposits were noted within vegetations and valve substance. Diffuse endocardial and subendocardial deposition of C5b-C9 and C9 complement neoantigens was present. Direct staining of valvular tissues and vegetations for rheumatoid factor showed extensive interstitial tissue deposition. These findings emphasize the large amounts of immune reactants and constituents of immune complexes present in valves and vegetations of patients with infective endocarditis.

Adult↗

Cost-effectiveness of leucocyte-depleted erythrocyte transfusion in cardiac valve surgery.

Cost-effectiveness of leucodepleted erythrocytes (LD) over buffy-coat-depleted packed cells (PC) is estimated from the primary dataset of a recently reported randomized clinical trial involving valve surgery (+/-CABG) patients. Data on the patient level of 474 adult patients who were randomized double-blind to LD or PC were used in order to calculate the healthcare costs and longevity per patient. The incremental cost-effectiveness ratio (ICER) in net costs per life-year gained was established from the healthcare perspective. Bootstrapping and cost-effectiveness acceptability curves were used in order to determine the confidence interval (CI) of the ICER. The longevity of patients in the PC and LD group was 10.6 and 11.4 years, respectively. Relative to PC, LD yielded an estimated 0.8 (95% CI = -0.27 to 1.84) life-year in the baseline. Adjusted for age and sex differences, health gains for LD are 0.4 life-year gained (95% CI = -0.67 to 1.44). Healthcare costs per patient averaged 10163 US dollars per patient in the PC group and 9949 US dollars in the LD group. Average cost-savings were 214 US dollars (95% CI = -1536 to 1964) per patient. Acceptability curves constructed from bootstrap simulations showed a probability of being cost-saving of 59% for universal leucodepletion from the healthcare perspective. The probability of adopting leucodepletion regardless of the costs reaches 92.7%. LD in patients receiving four or more transfusions showed the highest cost-savings and health gains. Leucodepletion of erythrocytes is a cost-saving strategy in cardiac valve (+/-CABG) patients. However, probablistic analysis failed to show a significant difference with buffy-coat-depleted PC.

Aged↗