Endomyocardial biopsy as risk factor in the development of tricuspid insufficiency after heart transplantation.

OBJECTIVE: Endomyocardial biopsy (EMB), which is used to monitor for rejection, may cause tricuspid regurgitation (TR) after orthotopic heart transplantation (OHT). The purpose of this investigation was to examine the occurrence of tricuspid valve tissue in myocardial specimens obtained by routine EMB performed after OHT. PATIENTS AND METHODS: From January 2000 to July 2008, 125 of the patients who underwent OHT survived more than 1 month. Their follow-up varied from 1 month to 8.5 years (mean, 5.1 +/- 3.7 years). EMB was the gold standard examination and myocardial scintigraphy with gallium served as a screen to routinely monitor rejection. RESULTS: Each of 428 EMB including 4 to 7 fragments, totaling 1715 fragments, were reviewed for this study. The number of EMB per patient varied from 3 to 8 (mean, 4.6 +/- 3.5). Histopathological analysis of these fragments showed tricuspid tissue in 4 patients (3.2%), among whom only 1 showed aggravation of TR. CONCLUSIONS: EMB remains the standard method to diagnose rejection after OLT. It can be performed with low risk. Reducing the number of EMB using gallium myocardial scintigraphy or other alternative methods as well as adoption of special care during the biopsy can significantly minimize trauma to the tricuspid valve.

Bioeffects of albumin-encapsulated microbubbles and real-time myocardial contrast echocardiography in an experimental canine model.

Myocardial contrast echocardiography has been used for assessing myocardial perfusion. Some concerns regarding its safety still remain, mainly regarding the induction of microvascular alterations. We sought to determine the bioeffects of microbubbles and real-time myocardial contrast echocardiography (RTMCE) in a closed-chest canine model. Eighteen mongrel dogs were randomly assigned to two groups. Nine were submitted to continuous intravenous infusion of perfluorocarbon-exposed sonicated dextrose albumin (PESDA) plus continuous imaging using power pulse inversion RTMCE for 180 min, associated with manually deflagrated high-mechanical index impulses. The control group consisted of 3 dogs submitted to continuous imaging using RTMCE without PESDA, 3 dogs received PESDA alone, and 3 dogs were sham-operated. Hemodynamics and cardiac rhythm were monitored continuously. Histological analysis was performed on cardiac and pulmonary tissues. No hemodynamic changes or cardiac arrhythmias were observed in any group. Normal left ventricular ejection fraction and myocardial perfusion were maintained throughout the protocol. Frequency of mild and focal microhemorrhage areas in myocardial and pulmonary tissue was similar in PESDA plus RTMCE and control groups. The percentages of positive microscopical fields in the myocardium were 0.4 and 0.7% (P = NS) in the PESDA plus RTMCE and control groups, respectively, and in the lungs they were 2.1 and 1.1%, respectively (P = NS). In this canine model, myocardial perfusion imaging obtained with PESDA and RTMCE was safe, with no alteration in cardiac rhythm or left ventricular function. Mild and focal myocardial and pulmonary microhemorrhages were observed in both groups, and may be attributed to surgical tissue manipulation.

Abnormal multimeric and oligomeric composition is associated with enhanced endothelial expression of von Willebrand factor in pulmonary hypertension.

Abnormalities in endothelial von Willebrand factor (vWF) structure have been reported in pulmonary hypertension. These include loss of high molecular weight plasma multimers, resulting in decreased biologic activity. If endothelial processing of vWF is altered in this disorder, abnormalities in oligomeric composition may also be expected. We examined this possibility in ten adult patients with primary pulmonary hypertension. Enhanced endothelial vWF expression in these patients was indicated by increased plasma levels of vWF antigen (vWF:Ag) (214 +/- 91 vs 99 +/- 51 percent activity in controls, p < 0.001) and intense immunoperoxidase stain of pulmonary arterial endothelium for vWF (autopsy, 1 patient). Plasma from these patients also had a decreased capacity of inducing platelet aggregation in the presence of ristocetin, relative to vWF:Ag levels (57 +/- 20 percent activity). In addition to mild loss of the largest multimers, changes in oligomeric composition of plasma vWF were observed in most patients using both agarose and polyacrylamide gel electrophoresis. These included decreased concentration of dimeric (470 kDa) vWF in most patients, variable concentration of the 860-kDa fraction, and a relative decrease in subunit (223 kDa) density in subjects with elevated vWF:Ag. These findings provide additional information on the mechanisms responsible for endothelial production of dysfunctional vWF in patients with pulmonary hypertension.

Lung beta-adrenoceptors in pulmonary hypertension. A study of biopsy specimens in children with congenital heart disease.

Characteristics of beta-adrenoceptors were analyzed using radioligand-binding techniques with 3H-dihydroalprenolol in lung specimens from 11 children with pulmonary hypertension (median age, three years) undergoing surgical repair of congenital heart defects and four pediatric control subjects (median age, five years) undergoing thoracotomy for removal of neoplasms or cysts. Scatchard analysis of 3H-DHA binding to lung membranes showed similar values of the dissociation constant in both groups (Kd = 0.72 +/- 0.22 nM in patients vs 1.22 +/- 0.22 nM in controls; p = NS). The receptor density was significantly increased in patients in comparison with controls, with respective values of 164 +/- 19 and 95 +/- 13 fmol/mg of protein (p less than 0.025), and correlated directly with mean pulmonary arterial pressure (r = 0.82; p less than 0.0005). No significant relationship was observed between receptor number and pulmonary arterial medial thickness. Thus, the increase in receptor density in these patients may be related to adaptative changes in cells other than vascular smooth muscle.

Reversible pulmonary trunk banding with a balloon catheter: assessment of rapid pulmonary ventricular hypertrophy.

OBJECTIVE: We sought to assess the rapid hypertrophy of the right ventricle of young goats submitted to progressive pressure load by a balloon catheter. METHODS: The hearts of 6 young goats were assessed by means of echocardiography and cell morphology during and after right ventricular hypertrophy had been produced by a balloon catheter. Myocardial samples of the right ventricular outflow tract were harvested for microscopic studies. The external diameter of longitudinally sectioned myocytes was measured at the nucleus level. The volume density of mitochondria was also determined. A balloon catheter was then placed through the right ventricular outflow tract in the pulmonary trunk and progressively inflated every 2 days. Postoperative serial echocardiography was performed at intervals of 1 to 2 days. The animals were killed after 2 to 3 weeks of right ventricular training for morphologic analysis. RESULTS: Under optical microscopy, there was a 20.5% increase in the mean diameter of the myocyte of the trained right ventricle. However, under electron microscopy, there was no significant change in the mean volume density of mitochondria from the trained right ventricle. Serial echocardiography showed equalization of the ventricular thickness over a short interval of 6 to 10 days of progressive balloon inflation. CONCLUSIONS: The balloon catheter permits the manipulation of the pressure load over the right ventricle, causing rapid hypertrophy in a 6- to 10-day period. This study suggests that nonsurgical preparation of the "pulmonary ventricle" in patients with transposition of great arteries with intact ventricular septum beyond the neonatal period could probably be accomplished within a very few days.

Myocardial ANP expression in Pompe's disease: An immunohistochemical study.

The expression of atrial natriuretic peptide (ANP) was analyzed in the atrial and ventricular myocardium in three cases of Pompe's disease (glycogen storage disease of the myocardium), using an immunoperoxidase technique. The cytoplasm of almost all atrial myocytes and some subendocardial myocytes from the right and left ventricles were ANP-positive, excluding the typical central vacuole, which was occupied by glycogen. Ventricular ANP expression was usually more prominent in left ventricular samples, and its distribution was similar to that described in dilated, hypertrophic, restrictive, or ischemic heart disease; however, the enlargement of the myocytes in Pompe's disease is not caused by hypertrophy. We conclude that the atrial myocytes in Pompe's disease maintain ANP expression, despite severe cytoplasmic vacuolization. These results suggest that ventricular ANP expression may be related to mechanical stimuli, such as the increase in wall stress, and not directly related to myocyte hypertrophy.

Adventitial layer enlargement correlates with the percentage of medial thickness in peripheral pulmonary arteries from patients with congenital heart defects.

Arterial walls undergo modifications during the course of pulmonary hypertension, particularly in the medial and intimal layers, leading to progressive occlusion of the lumen. Adventitial layer enlargement has been described as being present in the experimental hypoxic model and in the persistent pulmonary hypertension of the newborn. It was suggested that this enlargement may be related to stimulating factors derived from the medial smooth muscle cells. This study was designed to verify if different degrees of medial hypertrophy are correlated to the volume density of the adventitial layer in pulmonary hypertension secondary to congenital heart defects. Reviewing 21 lung biopsies from patients with congenital heart defects, we concluded that there is a statistically significant positive linear correlation between the mean percentage of medial arterial thickness and the volume density of the adventitial layer in the biopsies showing isolated medial hypertrophy. On the other hand, in biopsies showing frequent intimal proliferative lesions and irregular medial layer hypertrophy the correlation coefficient was lower. These findings suggest that the adventitial layer participates in the arterial remodeling process in secondary pulmonary hypertension, and that its enlargement depends on the qualitative degree of pulmonary vaso-occlusive disease.

Association of an increase in CD8+ T cells with the presence of Trypanosoma cruzi antigens in chronic, human, chagasic myocarditis.

The role of Trypanosoma cruzi in the pathogenesis of myocarditis in the chronic phase of Chagas' disease is still controversial, with autoimmune mechanisms frequently being proposed. In the present work, we demonstrate that higher numbers of CD8+ T cells are correlated with the presence of parasite antigens, suggesting an important role for the parasite in the development of myocardial inflammation. Quantification of the mean numbers of CD8+ and CD4+ T cells per 400x microscopic field was performed in myocardial specimens from 33 chronic chagasic patients with heart failures (nine biopsies and 24 necropsies), using an immunoperoxidase technique. The cases were grouped according to a semiquantitative score of the relative amounts of T. cruzi antigens: group 1 = absent (14 cases); group 2 = scarce extracellular or intramacrophagic antigens (12 cases); group 3 = many extracellular or intramacrophagic antigens plus T. cruzi intramyocytic pseudocysts (seven cases). The mean numbers of CD8+ and CD4+ T cells in groups 1,2, and 3 were 6.94 and 3.79, 13.89 and 6.24, and 17.91 and 5.97, respectively. The numbers of CD8+ T cells in groups 2 and 3 were significantly higher compared with group 1 (no T. cruzi antigens), but were not different from each other. Scarce, extramyocytic T. cruzi antigens were associated with an intense inflammatory infiltrate, suggesting that delayed-type hypersensitivity immune mechanism is induced by the parasite; intact myocardiocytes containing parasites did not show an inflammatory reaction around them. A poor inflammatory response was frequently associated with many extramyocytic antigens and myocardial parasite pseudocysts, suggesting that active proliferation and dissemination of the parasites occur when the immunologic response is diminished. The number of CD4+ T cells did not vary significantly among the three groups. We conclude that the CD8+ T cell is the main cell type responsible for immune activation in chronic, human, chagasic myocarditis and is probably activated by the presence of T. cruzi antigens associated with internal myocytic host antigens. The absence of a significant member of CD4+ T cells in the presence of T. cruzi antigens suggests inhibition of CD4+ T cell activation or the lack of a class II major histocompatibility complex molecule presentation mechanism.

Cryosurgical ablation of fetal atrioventricular node: new model to treat fetal malignant tachyarrhythmias.

BACKGROUND: Sustained tachyarrhythmia resulting in fetal hydrops is often refractory to medical therapy. Fetal atrioventricular node ablation associated with epicardial fetal pacing has the potential to be an effective procedure for this morbid association. METHODS: To assess the feasibility of therapeutic fetal heart block, we developed a technique of intrauterine cryosurgical ablation of fetal atrioventricular node without the need for cardiac bypass in 8 fetal lambs. Complete heart block was obtained by applying the cryoprobe over the coronary sinus. Fetal pacing was then performed to allow fetal survival. RESULTS: Complete heart block was achieved in 100% of the fetal lambs. Postoperative evaluation revealed persistent atrioventricular block. The hearts were studied at different postoperative times. Morphologic evaluation of the area containing the cryosurgical lesion revealed varied extension of necrosis of the atrioventricular node and hemorrhage, with involvement of the His bundle and proximal right bundle branch. CONCLUSIONS: This procedure is technically feasible and offers an alternative approach to the treatment of drug-resistant, life-threatening fetal supraventricular tachyarrhythmias associated with hydrops fetalis.

Coexistence of divided left atrium (cor triatriatum) and tetralogy of Fallot.

The association of a partitioned left atrium (cor triatriatum) and tetralogy of Fallot has been reported a few times in the literature. In all of these cases, there was no clinical evidence of an obstructive lesion in the left heart, raising difficulties in establishing the proper diagnosis. We call attention to this rare combination of anomalies and to the particular morphological presentation of the dividing atrial shelf, which was partially formed by the wall of the left superior caval vein.

Common arterial trunk associated with absence of right atrioventricular connexion.

Common arterial trunk is a rare congenital anomaly, usually found in the setting of a concordant atrioventricular connexion. The association of a common arterial trunk with absence of the right atrioventricular connexion is very rare, having, as far as we know, been reported only twice in the literature. In the case reported here the pulmonary arteries originated separately from the posterior wall of the arterial trunk, and the trunk overrode the septum between the dominant left- and the right-sided rudimentary right ventricle. We discuss the electrocardiographic features which can help in the diagnosis of this malformation.

Ebstein's malformation of the tricuspid and mitral valves associated with hypoplasia of the ascending aorta.

The clinical and morphological features of Ebstein's malformation were well defined many years ago. This report analyses the clinical and morphological aspects of an unusual case which presented Ebstein's malformation of both the tricuspid and mitral valves in association with hypoplasia of the ascending aorta.

Rupture of posteromedial papillary muscle as a mechanism of death in dilated cardiomyopathy.

The pathogenesis of mitral regurgitation in dilated cardiomyopathy is ascribed to several mechanisms. The authors describe the case of an adult male with idiopathic dilated cardiomyopathy who developed myocardial infarction in the absence of coronary atherosclerosis and died from acute lung edema following rupture of a papillary muscle of the left ventricle. The possibility of coronary embolism could not be ruled out.

Atresia of the left atrioventricular valve with patency of the aorta: anatomico-functional analysis of 23 patients.

We analyzed the findings in 23 patients with atresia of the left atrioventricular valve and a patent aorta seen in the period from January 1980 to July 1989. Having divided the cases according to the anatomical findings, we made a subsequent analysis of the clinical and surgical results with the aim of establishing the management most likely to diminish risks, still high, in treatment of this complex anomaly. From the anatomical viewpoint, three variants were observed. In the first, made up of 15 cases, there was absence of the left atrioventricular connexion. The characteristic finding in the second group, with five cases, was an imperforate left atrioventricular valve in the setting of concordant atrioventricular connexions. The third group, of these cases, was dominated by the presence of isomerism of the atrial appendages, both appendages being of left morphology in one case, and of right morphology in the other two. Further anatomical variation was then found in each group. Nine of the 15 with absence of the left atrioventricular connexion had the right atrium connected to a dominant left ventricle in presence of a rudimentary and incomplete right ventricle associated with discordant ventriculo-arterial connexions, all of them being in usual atrial arrangement and three with pulmonary stenosis. The remaining six in this first variant had the right atrium connected to a dominant right ventricle. In the five patients with imperforate left atrioventricular valves, two had discordant and three had concordant ventriculo-arterial connexions. In the three cases with isomerism, two had absence of the left atrioventricular connexion, with a dominant right ventricle. The last patient had an imperforate left atrioventricular valve and a discordant ventriculo-arterial connexion. From the functional viewpoint, there were 14 patients (10 with absence of an atrioventricular connexion, four with imperforate atrioventricular valve) with congestive heart failure and nine patients (five from the first, one from second, and three from the third variant) with hypoxia. Long-term follow-up (median 16.4 months--varying from 1 to 41 months--in the group with congestion and 27.7 months--varying from 12 to 57 months--in those with hypoxia) showed favorable clinical evolution in 11 (91%). We conclude that an anatomico-functional division can point towards the most appropriate management in this complex anomaly.

Detection of Mycoplasma pneumoniae and Chlamydia pneumoniae in ruptured atherosclerotic plaques.

This paper reports what is apparently the first observation of Mycoplasma pneumoniae in association with Chlamydia pneumoniae in thrombosed ruptured atheromas. We performed electron microscopy and in situ hybridization in specimens from three patients who died of acute myocardial infarction. These patients had typical symptoms of acute ischemic syndrome. Mycoplasmas were present mainly in the lipid core of the ruptured thrombosed plaque. Vulnerable atheromas are rich in cholesterol and may favor the growth of mycoplasmas, the only microorganisms that require cholesterol for survival. We suggest that the association of Mycoplasma pneumoniae and Chlamydia pneumoniae may increase the virulence of these microorganisms, favoring proliferation, plaque inflammation and possibly plaque rupture.

Immunohistochemical expression of atrial natriuretic peptide (ANP) in the conducting system and internodal atrial myocardium of human hearts.

Expression and distribution of atrial natriuretic peptide (ANP) were studied immunohistochemically in the conducting system and internodal atrial myocardium of 5 adult human hearts. Myocytes from the sinus node and compact atrioventricular node were usually ANP-negative; only a very few cells exhibited ANP immunoreactivity. These ANP-positive myocytes were small and did not appear to be trapped working atrial myocytes which are larger than nodal cells. The transitional cell zones of the sinus node and the atrioventricular node were composed of bundles of ANP-positive myocytes, intermingled with non-reactive myocytes. The internodal atrial myocardium exhibited a comparable intensity of myocyte staining in each case examined. Thus, morphologically distinct connecting pathways between the sinus node and the atrioventricular node with regard to myocyte ANP immunoreactivity could not be demonstrated, reinforcing the notion that they actually do not exist. The penetrating bundle, branching bundle and bundle branches were usually composed of ANP-negative myocytes although some ANP-positive myocytes were observed in the branching bundle and bundle branches in 4 cases. Myocytes from the ventricular conducting tissue presenting ANP immunoreactivity have been designated Purkinje fibers and have been found in several mammalian species.

[Growth factors in the myocardium of patients with chronic chagasic cardiomyopathy]. / Factores de crescimento presentes no miocárdio de pacientes com cardiopatia chagásica crônica.

In this work we quantified various growth factors in the myocardium of 19 patients with chronic chagasic cardiomyopathy and heart failure, through the immunoperoxidase technique. We looked for T. cruzi antigens, growth factors (GM-CSF, TGF-beta1, PDGF-A and PDGF-B) and inflammatory cells (CD4+, CD8+, CD20+ and CD68+). The mean ratio of CD4+/CD8+ T lymphocytes was 0.6 +/- 0.3. The mean number of positive interstitial cells was 5.9 +/- 3.1 for CD68+ (macrophages); 7.5 +/- 4.3 for PDGF-A+; 2.9 +/- 2.7 for PDGF-B+, 2.2 +/- 1.9 for TGF-beta1+ and 2.3 +/- 1.9 for GM-CSF+. The immunoreaction for PDGF-A was intense, occurring also in the endothelium, smooth muscle cells and the sarcolemma; there was no correlation between the number of positive interstitial cells and the semiquantitation of the same growth factors in the other cells. TGF-beta1 presented low expression in 100% of the cases. In conclusion, PDGF-A and B are probably the growth factors most related to the proliferative lesions and fibrosis present in chronic chagasic cardiomyopathy. GM-CSF and TGF-beta1 are present in low levels. There was no statistical correlation between growth factors and the quantity of the parasitic antigens.

Double-outlet right ventricle associated with discordant atrioventricular connection and dextrocardia in a cat.

The prevalence of congenital cardiac disease in cats varies from 0.2 to 1 per cent, with males being more affected than females. This is probably an underestimate due to the fact that not all affected kittens are presented. Discordant atrioventricular connection (where the morphological right atrium connects to the morphological left ventricle, and the morphological left atrium connects to the morphological right ventricle) is an uncommon condition in humans and, to the authors' knowledge, has not to date been described in animals. The association between this anomaly and the double-outlet right ventricle (where both great arteries arise entirely or partially from the morphological right ventricle) is extremely rare in children. This report describes a case of a cat which presented with this association of cardiac defects.

[Tetralogy of Fallot: considerations about morphologic features of a well described entity]. / Tetralogia de Fallot. considerações sobre aspectos morfológicos de uma entidade descrita com perfeição.

PURPOSE: To analyze some morphological aspects of the tetralogy of Fallot which have been raising controversies in the literature, due to the different approach to the nomenclature of congenital heart defects by different authors regarding the definition of double outlet right ventricle and its concomitance with tetralogy. METHODS: We reviewed the original description of the anomaly, and also analyzed the morphology of 22 anatomical specimens, describing the degree of aortic overriding, the type of ventricular septal defect, the degree of sub-pulmonary stenosis, etc. RESULTS: Regarding the degree of aortic overriding, there was only one case where that vessel connected predominantly to the left ventricle. In the remaining hearts, the degree of overriding was between 50% and 75% in 10 cases and greater than 75% in 11. The intensity of infundibular stenosis was evaluated as mild in half the available hearts, and the pulmonary valve was bicuspid in 11 cases. Right aortic arch was present in 40% of the available hearts and the ventricular septal defect had muscular borders in just one case (5%). CONCLUSION: We could conclude that if double outlet is only a type of ventricle-arterial connexion, and so, depending on the degree of overriding of the aorta over the trabecular septum, we may have the malformation coexisting with the tetralogy.

[Absence of right atrioventricular connection. Morphological and clinical presentation when the dominant ventricle is morphologically right]. / Ausência de conexão atrioventricular à direita. Apresentação morfológica e clínica quando o ventrículo principal é morfologicamente direito.

Absent right atrioventricular connection, with the left atrium connected to a dominant left-sided morphologically right ventricle is a rare situation. We report five cases with these anatomical features, with emphasis on the morphological and clinical aspects. Although this combination of lesions is very uncommon, the sequential segmental analysis can easily provide an accurate description of the anomaly.