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The osmotic swelling characteristics of cardiac valve prostheses.

Several types of mechanical cardiac prostheses have been constructed with Delrin occluders, a material that is subject to osmotic swelling. The leaftets are designed to expand to specific tolerances when immersed in blood. The synthetic blood analogs commonly used in vitro contain hydrophilic compounds that can alter the osmotic expansion of the Delrin occluders. A static leak test chamber was employed to illustrate the effects of various test fluids on the sustained regurgitation phase of Delrin valves.

Equipment Failure Analysis↗

Cardiac valve replacement in patients over 75 years of age.

Elderly patients with symptomatic cardiac valvular malfunction have a grave prognosis if managed medically but can be offered a reasonable chance for long-term survival and a good chance for improvement by replacement of the malfunctioning valve. A series of patients 75 years of age and older who underwent aortic valve replacement (31 patients) mitral valve replacement (9 patients), or combined valve replacement (on patient) has been reviewed. The overall operative mortality for aortic valve replacement was 23% (17% over the past 5 years) and the 5-year actuarial survival was 54 +/- 11%. The operative mortality for mitral replacement was 11% and the 5-year actuarial survival was 55 +/- 21%. The average hospital stay for survivors was 19 days after aortic valve replacement. Four patients have had embolic events since valve replacement, 3 after aortic and one after mitral valve replacement. The addition of coronary artery bypass surgery to the valve replacement procedure is becoming more frequent and may have contributed to improved operative survival. A literature review of reported clinical experience shows that the advancement of cardiac surgery has permitted a redefining of the group thought as "elderly", and that this group has an improved operative survival with the improvements in cardiac valve surgery.

Age Factors↗

The transcription factor NF-ATc is essential for cardiac valve formation.

Nuclear factor of activated T cells (NF-AT) is the name of a family of four related transcription factors that may be needed for cytokine gene expression in activated lymphocytes. Here we report that mice with a targeted disruption of the NF-ATc gene show an unexpected and dramatic defect in cardiac morphogenesis, with selective absence of the aortic and pulmonary valves, leading to death in utero from congestive heart failure at days 13.5-17.5 of gestation. In contrast, tricuspid and mitral valve morphogenesis is normal. NF-ATc is the first transcription factor known to be expressed only in the endothelial cells of the heart. As in T cells, nuclear translocation of NF-ATc in cardiac endothelial cells is controlled by the calcium-regulated phosphatase calcineurin: NF-ATc remains cytoplasmic in normal embryos cultured with cyclosporin A, an inhibitor of calcineurin. Abnormal development of the cardiac valves and septae is the most frequent form of birth defect, yet few molecular regulators of valve formation are known. Our results indicate that NF-ATc may play a critical role in signal-transduction processes required for normal cardiac valve formation.

Animals↗

Comparative method for actuarial analysis of cardiac valve replacements.

The use of survival analysis in cardiac surgical reports has been widely accepted in order to characterise and compare performances of different valve prostheses. However, the analyses that have been described elsewhere may be improved in several respects. The original method proposed for prosthetic valve evalation examined follow-up related to patients rather than the valves themselves and therefore neglected the possibility of factors other than the valve itself which could affect the fate of cardiac patients. Furthermore, there has not yet been any application of life table methods to compare two different sets of data, or to estimate the average time before an event occurs. The present work defines valve function and malfunction and separates patient survival from valve performance. We define statistical indices, namely the median remaining lifetime and the instantaneous decrement rate. Both indices can be useful; the former measures the average survival time and the latter focuses attention on the intensity of risk changes. Using established statistical theory we calculate the significance level of difference between two independent survival rates. We qualify the presentation of probabilities with a statement of the associated standard errors.

Actuarial Analysis↗

Changes in patterns of left ventricular hypertrophy after aortic valve replacement for aortic stenosis and regurgitation with St. Jude Medical cardiac valves.

In this study, we analyzed the extent and pattern of regression of left ventricular (LV) hypertrophy after aortic valve replacement in patients with aortic stenosis (AS) and compared the results with those of another group of patients with aortic regurgitation (AR). Seventy patients who underwent isolated aortic valve replacement were divided into 2 groups. Group 1 was comprised of 29 patients who underwent aortic valve replacement for aortic stenosis, and Group 2 of 41 patients who underwent aortic valve replacement for aortic regurgitation. A third group of 10 healthy subjects served as a healthy control group. Echocardiographic studies were done before the operation and 5 years postoperatively. At follow-up, a significant reduction in the left ventricular mass was found in both groups, but it remained significantly greater than in the healthy control group. The ratio of LV wall thickness to radius (th/r) in Group 1 decreased significantly, and at follow-up it was within the normal value. In Group 2, the th/r ratio increased, and at follow-up it was within the normal value. After aortic valve replacement, the wall thickness remained significantly greater than normal for patients with AS, and the chamber radius remained significantly greater than normal for patients with AR. For these reasons, LV hypertrophy still existed in both groups at postoperative follow-up. The actuarial survival rate was 85.3% at 16 years for Group 1 and 83.4% at 18 years for Group 2. There was no significant difference in the long-term survival rates between the 2 groups. Actuarial freedom from valve-related events was 91.9% at 16 years for Group 1 and 82% at 18 years for Group 2. There was no significant difference in the valve-related event free curves between groups. After 5 years of follow-up, th/r reached normal for both groups, indicating remodeling of the LV geometry after aortic valve replacement.

Adult↗

St. Jude Medical cardiac valve prosthesis in infants and children: early and intermediate experience.

The St. Jude Medical valve prosthesis has been used for valve replacement in 14 children. Ages ranged from 14 months to 17 years (average 8.5 years). Preoperative diagnosis included mitral regurgitation in five patients, aortic stenosis in one patient, aortic regurgitation in one, mitral stenosis in one, combined aortic stenosis and aortic regurgitation in five patients, and other in one patient. Seven patients required mitral valve replacement and seven aortic valve replacement. All patients survived operation and there have been no late deaths. Ten patients have been maintained on warfarin anticoagulation and four on aspirin alone. During a follow-up period of two months to three years (average 20.5 months) there have been no complications related to the valve, no thromboemboli, and no incidence of hemolysis. Three patients have had postoperative cardiac catheterization, and satisfactory pressure and angiographic studies have been recorded. The St. Jude Medical valve prosthesis initially appears to be a satisfactory device for valve replacement in children.

Adolescent↗

Cardiac valve orifice equation independent of valvular flow intervals: application to mitral valve area computation in mitral stenosis and comparison with the Gorlin formula and direct anatomical measurements.

An orifice equation is developed which relates the effective mitral valve area (A), the average mitral valve pressure gradient (dP), the cardiac output (Q) and the heart frequency (f) through considerations of momentum conservation across the mitral valve. The form of the new equation is A = (4.75 X 10(-5)Qf/dP, where A, Q, and dP are expressed in cm2, ml X min-1 and mmHg respectively. Mitral valve areas computed with the new orifice formula are found to correlate with those computed by the Gorlin formula in conditions of equilibrium associated with the resting state at a level of r = 0.95, SE = 0.15 cm2, with autopsy measurements at a level of r = 0.85, SE = 0.18 cm2 and with direct anatomical measurements of excised valves at a level of r = 0.78, SE = 0.41 cm2. The results suggest that the new formula may be considered as an independent orifice equation enjoying a similar domain of validity as the Gorlin formula. The new equation offers the possibility of deriving additional useful haemodynamic relationships when used in combination with established cardiological formulas.

Hemodynamics↗

Detection of osteopontin in calcified human aortic valves.

Cardiac valve calcification often results in obstruction of blood flow, which eventually leads to valve replacement. The molecular mechanisms resulting in valve calcification are unknown. Collagen and specific bone matrix proteins are thought to provide the framework for ectopic tissue calcification. This investigation was performed to determine whether the bone matrix protein osteopontin was present in calcified human aortic valves. Proteins extracted from human aortic valve tissue were subjected to polyacrylamide gel electrophoresis followed by Western blotting, using polyclonal antibodies directed against osteopontin. Fresh frozen tissue sections were also screened for osteopontin and macrophages using immunohistochemical techniques. Osteopontin was present in both heavily and minimally calcified aortic valves and absent in noncalcified purely regurgitant or normal aortic valves by both radioimmunoassay (n = 16) and immunohistochemical techniques (n = 8). Osteopontin colocalized with valvular calcific deposits, and macrophages were identified in the vicinity of osteopontin. These results, in addition to showing that osteopontin is present in calcified human aortic valves, suggest that osteopontin is a regulatory protein in pathological calcification. Identification of the cells producing osteopontin in abnormal cardiac valves and of proximate stimuli for its secretion may lead to novel therapeutic strategies to prevent and/or reverse calcific valve disease.

Adult↗