Rupture of bacterial intracranial aneurysms following replacement of cardiac valves.
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We have examined the tensile viscoelastic properties of fresh and glycerol-preserved human dura mater, and correlated the results with structural information from the scanning electron microscope. The interwoven laminar structure of dura produces rather high flexural stiffness, while the crossed-fibrillar laminae produce planar mechanical isotropy. Glycerol storage shifts the stress-strain curve to lower strain, reduces stress relaxation and creep, and lowers the ultimate tensile strength and strain at fracture. These changes may be due to glyceraldehyde crosslinking, or to increased interfibrillar friction. The latter hypothesis suggests that glycerol storage may reduce the fatigue lifetime of the tissue.
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OBJECTIVES: We studied the rate of thromboembolism in patients undergoing bioprosthetic replacement of the aortic or mitral valve, or both, at serial intervals after operation and the effects of anticoagulant or antiplatelet treatment and risk factors. BACKGROUND: Thromboembolism appears to occur early after operation, but the incidence, timing and risk factors for thromboembolism and the role, timing, adequacy, effectiveness, duration and risk of anticoagulation and antiplatelet agents are uncertain. METHODS: The rate of thromboembolism was studied at three time intervals after operation (1 to 10, 11 to 90 and > 90 days) in 816 patients who underwent bioprosthetic replacement of the aortic or mitral valve, or both, at the Mayo Clinic from January 1975 to December 1982. The effect of antithrombotic therapy (warfarin, aspirin or dipyridamole, alone or in combination) was evaluated. RESULTS: Median follow-up of surviving patients was 8.6 years. The rate of thromboembolism (%/year) decreased significantly (p < 0.01) at each time interval after operation (1 to 10, 11 to 90 and > 90 days) for mitral valve replacement (55%, 10% and 2.4%/year, respectively) and over the first time interval for aortic valve replacement (41%, 3.6% and 1.9%/year, respectively). During the first 10 days, 52% to 70% of prothrombin time ratios were low (< 1.5 x control). Patients with mitral valve replacement who received anticoagulation had a lower rate of thromboembolism for the entire follow-up period (2.5%/year with vs. 3.9%/year without anticoagulation, p = 0.05). Of 112 patients with a first thromboembolic episode, permanent disability occurred in 38% and death in 4%. Risk factors for emboli were lack of anticoagulation, mitral valve location, history of thromboembolism and increasing age. Only 10% of aortic, 44% of mitral and 17% of double valve recipients had anticoagulation at the time of an event. Patients with bleeding episodes (2.3%/year) were older and usually underwent anticoagulation. Blood transfusions were required in 60 of 111 patients (1.2%/year), and 13 patients (0.3%/year) died. CONCLUSIONS: Thromboembolic risk was especially high for aortic and mitral valve replacement for 90 days after operation, and overall was increased with lack of anticoagulation, mitral valve location, previous thromboembolism and increasing age. Anticoagulation reduced thromboemboli and appears to be indicated in all patients as early as possible for 3 months and thereafter in those with risk factors, but needs prospective testing.
The mechanical valve produced by Sorin is a modified tilting disc device. Between March 1979 and November 1985, 763 Sorin prostheses were implanted in 710 patients. The study has been restricted to 504 isolated mitral or aortic valves. There were 238 females and 266 males whose ages ranged from 2 to 71 years (mean 43.8). Follow-up is 99.23% and covers 1045 patient-years. No structural failure has been observed. In the aortic position, 282 Sorin prostheses were implanted with the large orifice orientated towards the right coronary sinus. Hospital mortality was 5% (14/282). Actuarial survival at 78 months was 94.68% +/- 1.6% with a linearized mortality rate of 1.7% patient-years. There were 11 late deaths (9 valve-related and 2 non valve-related). The linearized rate of occurrence of embolic events was 0.32 patient-years (2/268). Actuarial survival complication-free at 78 months was 90.88% +/- 2.83%. Preoperatively, 19.8% patients were in NYHA class II, 68.5% in III and 11.7% in IV; postoperatively, 79.3% patients were in NYHA class I, 19.5% in II and 1.2% in III. In the mitral position, 222 Sorin prostheses were implanted with the large orifice orientated anteriorly in 46 patients (group 1) and posteriorly-in 176 patients (group 2). Hospital mortality was 4.5% (10/222). Actuarial survival at 66 months was 93.25% +/- 2.1% with a linearized mortality rate of 2.8 patient-years. There were 12 late deaths (9 valve-related and 3 non valve-related). The 66-month actuarial freedom from embolic events was 95.8% +/- 1.89% with a linearized rate of occurrence of 1.44 patient-years.(ABSTRACT TRUNCATED AT 250 WORDS)
The clinical use of cryopreserved allograft valves is rapidly increasing. Viability of valve leaflet fibroblasts has been proposed to be critical to durability. Harvesting of allograft valves involves variable warm ischemia times, defined as the time from cessation of donor heart beat to initial cooling for transport. This ischemic period has been implicated as one of the more critical periods of injury to leaflet cell, even though adequate characterization of this potentially injurious phase has never been accomplished. The present study was undertaken to characterize the metabolic response to warm ischemia in a porcine valve leaflet model. Valve handling was similar to clinical valve harvest and transport protocols. Injury was assessed by protein (1H) and phosphorus (31P) magnetic resonance spectroscopy of 224 porcine semilunar valves. Leaflets were analyzed over time for lactate accumulation and ATP degradation. A radiolabelled incubation assay (48 valves) was used to measure proline accumulation by fibroblasts. Electron microscopy was performed on 36 valves with varying warm ischemia times. ATP stores were entirely depleted after 2 h hypoxia (p less than 0.05). However, lactate continued to accumulate over 24 h. Although aerobic metabolism ceased after 2 h warm ischemia, anaerobic metabolism continued for up to 24 h, which may represent an extended window for harvesting fresh tissue for allograft valve implantation.
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In the fabrication of a bioprosthetic heart valve from bovine pericardial tissues, the tissues are subjected to suturing. The stress-strain response of sutured as well as unsutured strips of this tissue were examined. The stress-strain response was determined using a tensile-testing machine. It was found that suturing weakens the tissue in that sutured strips are more extensible, exhibit a lower stress at rupture and a lower final elastic modulus. In addition, it was also found that the bigger the suture/needle size used the greater the decrease in tissue strength. In all, tissue strength was observed to decrease by 22 to 59% in this study. The weakening of the tissue is attributed to the puncture holes created by the surgeon's needle which create regions of weakness. This response of bovine pericardial tissue to suturing should be given due consideration in the fabrication of a bioprosthetic heart valve using this tissue.
This review concerns the issues affecting the in vitro evaluation of conduit-mounted prosthetic heart valves at the design development stage, and the question of standardisation of testing at the quality assurance stage. Particular attention is given to areas of conduit valve development and research which have been neglected, ambiguously covered or left to the discretion of the researcher in the current standard for conventional prosthetic valves, ISO 5840.
Although providing an historical overview of the development and clinical applications of conduit-mounted prosthetic heart valves, with elementary explanations of operative techniques, this review concentrates on the impact of design and surgical considerations on their in vivo performance. Areas showing potential for design improvement of mechanical prostheses are highlighted, both in terms of haemodynamic efficiency and haemocompatibility. Comparisons are drawn throughout the paper with conventional valve prostheses, and the key features where they differ significantly are pointed out. It is concluded that there is considerable scope for further worthwhile development.
We summarize herein selected contributions over the past several decades by pathologists and others to the diagnosis, understanding, and management of valvular heart disease, including the structural basis of valve function, the pathology/pathobiology of common naturally occurring and iatrogenic lesions, developments in valve substitution, and novel approaches to valve repair, replacement, and regeneration.
OBJECTIVES: We studied the diagnostic performance of 64-slice computed tomography coronary angiography (CTCA) to rule out or detect significant coronary stenosis in patients referred for valve surgery. BACKGROUND: Invasive conventional coronary angiography (CCA) is recommended in most patients scheduled for valve surgery. METHODS: During a 6-month period, 145 patients were prospectively identified from a consecutive patient population scheduled for valve surgery. Thirty-five patients were excluded because of CTCA criteria: irregular heart rhythm (n = 26), impaired renal function (n = 5), and known contrast allergy (n = 4). General exclusion criteria were: hospitalization in community hospital (n = 4), no need for CCA (n = 4), previous coronary artery bypass surgery (n = 1), or percutaneous coronary intervention (n = 4). Of the remaining 97 patients, 27 denied written informed consent. Thus, the study population comprised 70 patients (49 male, 21 female; mean age 63 +/- 11 years). RESULTS: Prevalence of significant coronary artery disease, defined as having at least 1 > or =50% stenosis per patient, was 25.7%. Beta-blockers were administered in 71%, and 64% received lorazepam. The mean heart rate dropped from 72.5 +/- 12.4 to 59.5 +/- 7.5 beats/min. The mean scan time was 12.8 +/- 1.3 s. On a per-patient analysis, the sensitivity, specificity, and positive and negative predictive values were: 100% (18 of 18; 95% confidence interval [CI] 78 to 100), 92% (48 of 52; 95% CI 81 to 98), 82% (18 of 22; 95% CI 59 to 94), and 100% (48 of 48; 95% CI 91 to 100), respectively. CONCLUSIONS: The diagnostic accuracy of 64-slice CTCA for ruling out the presence of significant coronary stenoses in patients undergoing valve surgery is excellent and allows CTCA implementation as a gatekeeper for invasive CCA in these patients.
Epithelial-mesenchymal transformation (EMT) occurs during both development and tumorigenesis. Transforming growth factor beta (TGFbeta) ligands signal EMT in the atrioventricular (AV) cushion of the developing heart, a critical step in valve formation. TGFbeta signals through a complex of type I and type II receptors. Several type I receptors exist although activin receptor-like kinase (ALK) 5 mediates the majority of TGFbeta signaling. Here, we demonstrate that ALK2 is sufficient to induce EMT in the heart. Both ALK2 and ALK5 are expressed throughout the heart with ALK2 expressed abundantly in endocardial cells of the outflow tract (OFT), ventricle, and AV cushion. Misexpression of constitutively active (ca) ALK2 in non-transforming ventricular endocardial cells induced EMT, while caALK5 did not, thus demonstrating that ALK2 activity alone is sufficient to stimulate EMT. Smad6, an inhibitor of Smad signaling downstream of ALK2, but not ALK5, inhibited EMT in AV cushion endocardial cells. These data suggest that ALK2 activation may stimulate EMT in the AV cushion and that Smad6 may act downstream of ALK2 to negatively regulate EMT.
Congenital heart defects, the leading cause of deaths from birth defects, are estimated to occur in close to 1% of live newborns. Among these, abnormal septation of the heart and valve anomalies are the most frequent forms. Despite progress defining several genes involved in normal heart development, we still have a limited understanding of the signaling pathways involved in morphogenesis of the outflow tract (OFT) and, to date, very few genes have been identified that are responsible for defects in humans. Bone Morphogenetic Protein (BMP) signaling pathways are emerging as vital regulators of multiple aspects of cardiogenesis, including the septation of the OFT and valve maturation. Genetic and other in vivo evidence is now supporting the role for BMPs as inducers of endocardial cushion epithelial-to-mesenchymal transformation that was suggested by in vitro explant studies as well as by their patterns of expression in the developing heart. Here, we review briefly the in vitro data, and detail the novel mouse models where perturbed BMP signaling pathways result in impaired OFT septation and semilunar valvulogenesis. We propose that growth of the OFT valve cushions is regulated by the level of BMP signaling, under the control of other signaling pathways.
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Some studies describe an increased risk for emboli in infective endocarditis patients with large (>10 mm) and mobile vegetations. Other studies fail to demonstrate the above relation. Most studies have been performed using transthoracic echocardiography or with a monoplane transesophageal approach. The present study examines whether distinctive characteristics of vegetative lesions detected by transthoracic and multiplane transesophageal echocardiography are predictive of embolic risk. We reviewed both transthoracic and transesophageal echocardiograms of 57 patients with diagnosis of acute infective endocarditis and no documented or suspected previous embolic events. We evaluated site, length, width, mobility, and echodensity of vegetations. Twenty-five patients (44%) had embolic events. No statistical differences in age, sex distribution, location of endocarditis, or offending pathogens between embolic (n = 25) and nonembolic (n = 32) patients were found. There were no differences in any of the echo characteristics of vegetations detected by transthoracic and transesophageal approach in embolic and nonembolic groups. Thus, transthoracic and transesophageal characteristics of vegetations are not helpful in defining embolic risk in patients with infective endocarditis.