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Biomedical subjects

G Thiene

Publications and source records attributed to G Thiene.

At least 19 recordsLinked to original sources

Long-term echocardiographic Doppler monitoring of Hancock bioprostheses in the mitral valve position.

Echocardiographic and Doppler studies were performed in 134 patients with a Hancock bioprosthesis in the mitral valve position during a follow-up period of 1 to 216 months. Among the xenografts, 57% were clinically normal and 43% had severe dysfunction. Among the normal bioprostheses, 35% had echocardiographically thickened mitral cusps (> or = 3 mm) with normal hemodynamic function; by setting the lower 95% confidence limit of valve area at 1.7 cm2 these patients had a significantly (p < 0.01) smaller valve area than that of normal control subjects. Evaluation of all thickened normal mitral valves showed the highest incidence of thickening at 9 years after implantation. Valve replacement surgery was subsequently performed in 33 patients with dysfunctioning bioprosthetic and echocardiographic diagnosis was confirmed in 91% of explanted valves (bioprosthetic stenosis 21%, incompetence 46%, and combined stenosis and regurgitation 33%). In 2 valves that were found to be stenotic on echocardiographic examination, a calcium-related commissural tear was also observed at reoperation, and in another, a paravalvular leak was found. Dystrophic calcification, isolated (64%) or occasionally associated with fibrous tissue overgrowth (21%), was the main cause of failure. Pannus was present in prostheses with longer satisfactory function (168 +/- 31 vs 124 +/- 21 months; p < 0.001). Long-term performance was evaluated by the Kaplan-Meier method for up to 18 years of follow-up. Freedom from structural valvular disfunction after mitral replacement was 89% at 6 years, 77% at 8 years, 56% at 10 years, 31% at 12 years, 16% at 15 years, and 15% at 18 years.

Actuarial Analysis

A casual spontaneous mutation as possible cause of the familial form of arrhythmogenic right ventricular cardiomyopathy (arrhythmogenic right ventricular dysplasia).

In a family affected by arrhythmogenic right ventricular cardiomyopathy (ARVC) the familial occurrence was investigated. All 14 members of two generations were investigated carefully, and only 2 (father and one son) members were affected. Both subjects had a massive form of the disease with relevant ventricular arrhythmias. Apart from the limitations of having investigated few subjects, this behavior suggests a genetic mutation appearing in the father and transmitted via an autosomal dominant trait.

Adolescent

The Meadox-Gabbay pericardial xenograft: failure of the unicusp principle.

Durability of a new bioprosthesis, the Meadox-Gabbay unileaflet pericardial xenograft, was evaluated by reviewing a series of 12 patients who received this device in the mitral position from 1983 to 1985. Bioprosthetic failure necessitated reoperation in 5 patients 21, 22, 53, 66, and 81 months after placement. Three patients died of cardiac failure after 31, 52, and 70 months; no postmortem examinations were done. In 2 of the 3 patients, an echocardiographic study had shown signs of valvular dysfunction. Pathological examination of five available explants revealed the presence of redundancy and stretching of the single pericardial leaflet in all of them; in one, this lesion alone caused severe prosthetic incompetence. Other pathological findings included cusp and commissural calcification and commissural tears with or without calcification. Histologic examination and electron microscopy showed intrinsic calcification involving both collagen bundles and cellular debris and various degrees of collagen disruption. In this limited series of patients, the Meadox-Gabbay pericardial xenograft demonstrated various modes of failure that markedly impair its durability and render it unsuitable as a cardiac valve substitute.

Adult

Phenotypic and functional characterization of cytotoxic cells derived from endomyocardial biopsies in human cardiac allografts.

This study was undertaken to characterize the phenotype and function of lymphocytes derived from endomyocardial biopsies in heart transplant patients. To this aim, tissue infiltrating lymphocytes were derived from seven heart transplant patients and were analyzed for the expression of a panel of markers, including CD3, CD4, CD8, CD16, CD56, CD45RA, CD45RO, alpha/beta and gamma/delta T cell receptor, and for their ability to lyse a series of targets, including NK-sensitive K-562 targets, NK-resistant Raji targets, donor related, and unrelated normal splenocytes. Our data show that the majority of cultured lymphocytes expressed the CD3+ phenotype and the alpha/beta T cell receptor. The CD4 and CD8 molecules were heterogeneously expressed among T cell lines tested. Concerning cytotoxic related markers, a significant percentage of cells were CD56+. The evaluation of CD45 isoforms showed that both "naive" and "memory" cells were present among heart TIL. Cytotoxic in vitro studies demonstrated that all our T cell lines showed an efficient cytotoxic machinery when tested against NK-sensitive targets. A marked lysis of donor-related splenocytes was demonstrated in all patients tested. To investigate the role of CD3 and HLA class I molecules in the cytotoxic mechanisms taking place in human heart allograft rejection mechanisms, TIL were assessed for their lytic activity against different targets in the presence of anti-CD3 and anti-HLA class I monoclonal antibodies (mAbs). Although donor-specific cytotoxicity was considerably inhibited by the anti-CD3 mAb, no inhibitory effect was displayed by this antibody on TIL-mediated cytotoxicity against donor-unrelated splenocytes. Anti-HLA class I mAb was able to inhibit both allospecific and nonallospecific cytotoxicity. These data suggest that different types of cytotoxic cells may be propagated from biopsy specimens of heart transplant patients.

Adult

Bicuspid aortic and pulmonary valves in the Syrian hamster.

We studied the conditions of the aortic and pulmonary valves of 153 Syrian hamsters belonging to a single family subjected to high endogamous pressure. Semilunar valves of 143 specimens were examined using a stereomicroscope, and in 5 of these cases a histologic study was also performed. The remaining 10 specimens were studied by means of scanning electron microscopy. In 77 specimens both semilunar valves were normal. The aortic valve was bicuspid and the pulmonary valve was normal in 46 animals, while a normal aortic valve and a bicuspid pulmonary valve occurred in 24. In the remaining 6 specimens both semilunar valves were bicuspid. All bicuspid semilunar valves detected herein showed the same morphotype, namely with the leaflets oriented ventrodorsally. The incidence of these anomalous valves did not significantly differ between sexes. Results of a chi 2-test substantiate that conditions of both outflow tract semilunar valves are independent traits. Thus, concurrence of a bicuspid aortic valve and a bicuspid pulmonary valve in an individual is a random event. The present findings support the assumption that bicuspid aortic and pulmonary valves have different morphogenetic origin, although factors producing a bicuspid aortic valve and those leading to a bicuspid pulmonary valve are not mutually exclusive.

Animals

Clinical profile of concealed form of arrhythmogenic right ventricular cardiomyopathy presenting with apparently idiopathic ventricular arrhythmias.

In 24 subjects presenting with apparently idiopathic ventricular arrhythmias, a final diagnosis of arrhythmogenic right ventricular cardiomyopathy was formulated following global evaluation of the clinical, cross-sectional echocardiography and angiographic findings, and the observation of myocardial atrophy with fibrous-fatty substitution in right ventricular endomyocardial biopsy. All patients had good effort tolerance, and a normal cardiac silhouette. Ventricular arrhythmias with a left bundle branch block pattern were present in 23 cases (sustained ventricular tachycardia, nonsustained ventricular tachycardia, ventricular couplets, and ventricular premature complexes); 1 patient experienced an episode of ventricular fibrillation. A nearly constant electrocardiographic feature was T wave negativity in the right precordial leads. Cross-sectional echocardiography and hemodynamic studies showed that right ventricular impairment consisted only of localized structural and dynamic abnormalities; in a few cases the left ventricle was segmentally involved. Familial occurrence was present in 29% of the cases. No case of sudden death was observed during follow-up. These findings confirm that the concealed form of arrhythmogenic right ventricular cardiomyopathy is a cause of so-called "idiopathic" ventricular arrhythmias in subjects with apparently "normal hearts". Echocardiographic and angiographic investigations may lead to the correct diagnosis.

Adolescent

Enhanced A-V nodal conduction (Lown-Ganong-Levine syndrome) by congenitally hypoplastic A-V node.

The basic anatomical substrate of enhanced A-V nodal conduction, manifesting or not as Lown-Ganong-Levine syndrome, is still a controversial issue. We describe the case of a 34-year-old man who presented episodes of ventricular fibrillation. Electrophysiological studies showed that the AH interval was 55 ms, and increased by only 20 ms at paced cycle lengths of 300 ms; atrial pacing induced atrial fibrillation, with a shortest RR interval of 240 ms. Despite verapamil therapy, this patient died suddenly at home. Histological study disclosed a severe A-V node hypoplasia that was evidently congenital in nature; the rest of the conduction system was normal, and no accessory A-V pathways were present. We suggest that enhanced A-V nodal conduction in this patient was due to the developmental defect in the A-V node; this abnormality caused a loss of specific impulse-delaying function, and thus allowed rapid, unfiltered atrial impulses to reach the lower A-V junction and ventricles.

Adult

Glutaraldehyde-fixed bovine iliac veins used as bioprosthetic conduits: an experimental animal study.

The ideal prosthetic conduit for surgical repair of complex congenital heart disease has yet to be found. Twenty conduits were implanted between the right ventricle and pulmonary artery in growing sheep as follows: four Dacron porcine valve conduits (mean time in place, 142 days); four avalved glutaraldehyde-fixed bovine iliac veins (mean 132 days); and 12 glutaraldehyde-fixed bovine iliac veins containing a porcine valve (mean 180 days). Fifteen conduits were left in place from 167 to 244 days (mean 204 days), and five were explanted earlier (mean 54 days). Pathological study included gross, x-ray, histological, and ultrastructural investigation. Five conduits failed because of infective endocarditis. The valved Dacron conduits showed significant tissue ingrowth and calcification of the valve graft. The valved bovine iliac veins presented calcification at the valve level and vein wall, as well as a valvelike calcific fibrous ridge at the proximal anastomosis with the right ventricle. The avalved bovine iliac veins also presented calcific deposits along the wall and a valvelike calcific ridge at the ventricular anastomosis. Histological and ultrastructural studies of the vein tunica media revealed the phenomena of inflammatory rejection and foreign body reaction with loss of smooth muscle cells (medionecrosis) and fibrotic replacement. In conclusion, bovine iliac veins undergo inflammation with medionecrosis indicating that smooth muscle cell antigenicity is not attenuated by glutaraldehyde fixation.

Animals

Non-atherosclerotic coronary artery disease and sudden death in the young.

OBJECTIVE: To assess prevalence and type of non-atherosclerotic coronary artery disease in young people (< or = 35 years) who died suddenly. DESIGN: A necropsy study of 150 consecutive cases of sudden death (that is, within 6 h of the onset of symptoms). RESULTS: Death was attributed to coronary artery disease in 48 cases: in 16 (33%) of them the disease was non-atherosclerotic. Twelve subjects (eight males and four females, age range 2-35 years, mean 24.2) had congenital anomalies: a deep intramyocardial course in six, origin from the wrong sinus in three, and ostial obstructions in three. Sudden death was the first manifestation of disease in six cases. The other six had a history of palpitation or syncope or both. An electrocardiogram was available in five cases and showed ventricular arrhythmias in four; none had angina pectoris. Stress testing was available in two cases: neither showed any effort-dependent ST-T abnormalities. In six cases sudden death was related to physical exercise. Acquired non-atherosclerotic coronary artery disease was found in four cases: spontaneous coronary dissection in three previously symptom free patients and Kawasaki coronary arteritis in one child who had had acute myocardial infarction. CONCLUSION: One third of the cases of fatal coronary artery disease were non-atherosclerotic with coronary artery anomalies being the most frequent form. Coronary artery anomalies should be suspected in young patients who have symptoms of ventricular arrhythmias without any overt signs and symptoms of ischaemia.

Adolescent

[Controversies in the selection of donors in heart transplants].

The shortage of ideal donor hearts has led to an increasing number of would-be heart transplant recipients who die while on the waiting list: an extension of the classical donor criteria seems necessary to expand the donor pool. In this paper, the major controversies on donor selection are presented, along with the clinical results obtained in cardiac transplantation with donor grafts not complying with standard criteria. The extension of donor age over 35 years is supported by the decreased incidence of coronary artery disease (CAD) in the Western world. In our experience, the number of donors over 40 years has increased steadily, without concomitant significant increase in postoperative short- and medium-term mortality after cardiac transplantation. The relative importance of CAD risk factors in the older heart donor is to be weighed out on a case-by-case basis. The performance of coronary angiography in 90% of the donor grafts over 50 years has led to more accurate selection. ECG minor alterations and ECHO diagnosed dyskynesias are of uncertain significance. Localized infection, transitory hypotension, brief cardiac arrest and thoracic trauma do not necessarily contraindicate heart donation. The importance of donor/recipient weight mismatch over 20% is critical only in face of high pulmonary vascular resistance. Prolonged dopamine infusion above 10 micrograms/kg/min may predict poorer function outcome. From our data, severe donor dysionemia may be very hazardous. In conclusion, our experience demonstrates that extended donor criteria do not compromise short- and medium-term clinical results of cardiac transplantation. Nevertheless, several controversial aspects of donor graft selection remain open.

Age Factors

Durability of glutaraldehyde-fixed pericardial valve prostheses: clinical and animal experimental studies.

Bovine pericardium has been widely employed as a xenograft tissue for the manufacture of bioprosthetic valve substitutes. Early three-leaflet valve models showed poor tissue preservation and shortcomings in valve design, which accounted for tissue wear and prosthesis failure due to cuspal tear. Reducing the number of cusps in the unicusp pericardial valve has proved unsuccessful due to stretching of the single pericardial leaflet with consequent valvular incompetence. The new generation of pericardial xenografts present basic changes in valve design and optimal tissue preservation after industrial processing, with no evidence of leaflet tear at medium term follow up. However, clinical experience is limited and, similarly to porcine xenografts, dystrophic calcification still appears to be a major problem.

Adult

Original expectations of the Hancock valve and 20 years of clinical reality.

The standard (glutaraldehyde-preserved) Hancock porcine bioprosthesis was introduced into clinical practice in order to provide surgeons with a cardiac valve substitute which would be nonthrombogenic and therefore would not require anticoagulation, and would be durable, anatomically suitable, and noiseless. In the present report we have reviewed our long-term experience with Hancock porcine valve recipients in order to verify the original expectations of this bioprosthesis have been met.

Adolescent

Heart valve bioprosthesis durability: a challenge to the new generation of porcine valves.

Long-term experience with first generation porcine valve xenografts enabled identification of the major limitations to their durability: (1) prosthetic-ventricular mismatch due to the high profile of the stent in patients with mitral stenosis and a small left ventricle; (2) high-pressure fixation with loss of natural collagen crimping in the fibrosa, and wash-out of proteoglycans in the spongiosa; (3) xenograft tissue autolysis, due to the long interval between animal slaughter and aortic valve removal fixation; (4) muscle shelf in the right coronary cusp, which created a gradient and could undergo accelerated calcification and/or spontaneous perforation with time; (5) a flexible polypropylene stent, which could creep or even fracture with consequent inward bending of the stent; (6) progressive time-related dystrophic calcification; (7) host fibrous tissue ingrowth. An awareness of these limitations stimulated technical modifications, which frequently brought about distinct improvements: (1) the reduction of the stent profile eliminated the problem of mismatch, but resulted in a higher tendency towards cusp prolapse and earlier commissural tearing; (2) natural collagen waviness, proteoglycans and cusp extensibility were preserved by employing low or even zero pressure during the fixation process; (3) earlier valve fixation enabled preservation of cell integrity; (4) a new orifice for small valves was designed by replacing the right muscular cusp, thus achieving less gradient and avoiding muscle-shelf-related complications; (5) polypropylene was replaced by Delrin as stent material; (6) calcium-retarding agents like T6 and toluidine blue were applied during commercial processing and storage in order to mitigate tissue mineralization.(ABSTRACT TRUNCATED AT 250 WORDS)

Bioprosthesis

Heart valve replacement with the Sorin tilting-disc prosthesis. A 10-year experience.

From 1978 to 1988, 697 patients with a mean age of 48 +/- 11 years (range 5 to 75 years) received a Sorin tilting-disc prosthesis; 358 had had aortic valve replacement, 247 mitral valve replacement, and 92 mitral and aortic valve replacement. Operative mortality rates were 7.8%, 11.3%, and 10.8%, respectively, in the three groups. Cumulative duration of follow-up is 1650 patient-years for aortic valve replacement (maximum follow-up 11.4 years), 963 patient-years for mitral valve replacement (maximum follow-up 9.9 years) and 328 patient-years for mitral and aortic valve replacement (maximum follow-up 9.4 years). Actuarial survival at 9 years is 72% +/- 4% after mitral valve replacement, 70% +/- 3% after aortic valve replacement, and 50% +/- 12% after mitral and aortic valve replacement, and actuarial freedom from valve-related deaths is 97% +/- 2% after mitral valve replacement, 92% +/- 2% after aortic valve replacement, and 62% +/- 15% after mitral and aortic valve replacement. Thromboembolic events occurred in 21 patients with aortic valve replacement (1.3% +/- 0.2%/pt-yr), in 12 with mitral valve replacement (1.2% +/- 0.3% pt-yr), and in seven with mitral and aortic valve replacement (2.1% +/- 0.8%), with one case of prosthetic thrombosis in each group; actuarial freedom from thromboembolism at 9 years is 92% +/- 3% after mitral valve replacement, 91% +/- 3% after aortic valve replacement, and 74% +/- 16% after mitral and aortic valve replacement. Anticoagulant-related hemorrhage was observed in 15 patients after aortic valve replacement (0.9% +/- 0.2%/pt-yr), in 9 after mitral valve replacement (0.9% +/- 0.3%/pt-yr), and in 6 with mitral and aortic valve replacement (0.9% +/- 0.5%/pt-yr); actuarial freedom from this complication at 9 years is 94% +/- 2% after aortic valve replacement, 91% +/- 4% after mitral valve replacement, and 68% +/- 16% after mitral and aortic valve replacement. Actuarial freedom from reoperation at 9 years is 97% +/- 2% after mitral and aortic valve replacement, 92% +/- 4% after mitral valve replacement, and 89% +/- 3% after aortic valve replacement, with no cases of mechanical fracture. The Sorin valve has shown a satisfactory long-term overall performance, comparable with other mechanical prostheses, and an excellent durability that renders it a reliable heart valve substitute for the mitral and aortic positions.

Actuarial Analysis

Failure of Hancock pericardial xenografts: is prophylactic bioprosthetic replacement justified?

The incidence of major valve-related complications was evaluated in a series of patients in whom the Hancock pericardial xenograft was used for aortic (AVR; n = 84), mitral (MVR; n = 17) and mitral-aortic (MAVR; n = 13) valve replacement. At 7 years actuarial survival is 66% +/- 8% after AVR, 64% +/- 13% after MVR, and 41% +/- 15% after MAVR, whereas actuarial freedom from valve-related death is 79% +/- 7% after AVR, 78% +/- 13% after MVR, and 81% +/- 12% after MAVR. Actuarial freedom from thromboemboli and anticoagulant-related hemorrhage at 7 years is 93% +/- 4% and 98% +/- 2% after AVR and 83% +/- 10% and 88% +/- 11% after MVR; no such complications occurred after MAVR. Structural valve deterioration determined at reoperation, at autopsy, or by clinical investigation was observed in 34 patients with AVR (10.0 +/- 0.2%/patient-year), in 10 with MVR (10.6 +/- 3.3%/patient-year), and in 9 with MAVR (16.6 +/- 5.5%/patient-year). After AVR, 19 patients underwent reoperation and 2 died before reoperation; 4 patients with MVR underwent reoperation, and 7 patients with MAVR underwent reoperation and 1 died before reoperation. Seventy-eight percent of the current survivors (13 patients with AVR, 7 with MVR, and 1 with MAVR) have clinical evidence of valve failure. At 7 years actuarial freedom from structural deterioration of the Hancock pericardial xenograft is 25% +/- 7% after AVR, 29% +/- 14% after MVR, and 0% after MAVR.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Cardiomyopathy: a necessary revision of the WHO classification.

The classification of myocardial disease proposed by the WHO/ISFC task force in 1980 distinguishes specific heart muscle diseases from myocardial diseases of unknown origin, termed cardiomyopathies, and differentiated into the dilated, hypertrophic and restrictive forms. This last group includes endomyocardiofibrosis and fibroblastic parietal endocarditis. In more recent years, two new forms of heart muscle disease have been recognized: so-called "primary" restrictive cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy. Primary restrictive cardiomyopathy is characterized anatomically by normally sized, non-hypertrophic ventricles with dilated atria, and functionally by impaired diastolic compliance due to myocardial stiffness. The clinical picture is that of chronic congestive heart failure; histology shows interstitial fibrosis and myocardial disarray, but not hypereosinophilia. In arrhythmogenic right ventricular cardiomyopathy, the myocardium of the right ventricular free wall is substituted by fibrous and/or adipose tissue, which results in regional dynamic alterations and ominous ventricular arrhythmias. The left ventricle is usually spared. Both forms should be classified as heart muscle diseases of unknown origin, and kept clearly distinct from the other cardiomyopathies listed in the WHO classification.

Arrhythmias, Cardiac