Mitral and tricuspid lesions associated with polypoid atrial tumors, including myxoma

The related atrioventricular valves in 11 instances of polypoid atrial tumors were examined grossly and histologically. Nine of the tumors involved the left atrium and, of these, seven were myxomas. The two right atrial tumors were myxomas.

Histologically evident lesions of the mitral valve were present in seven of the nine left atrial tumors. The most common change consisted of fibrous thickening of the endocardium in the angle between the left atrium and posterior mitral leaflet and fibrous thickening of the atrial surfaces of the leaflet. Less common changes were a fibrous thickening of the chordae and of the left ventricular mural endocardium in relation to chordae inserting into the posterior leaflet. The changes described were also evident at gross examination in two of the nine cases with left atrial tumors.

In the two cases of right atrial myxoma, both showed fibrous thickening of the atrial surfaces of the tricuspid leaflets; one also exhibited fibrous thickening of the right ventricular endocardium beneath the septal leaflet of the tricuspid valve.

The lesions described are considered responses to the effects of friction by the tumor upon the surfaces involved. It is significant that grossly evident lesions may evolve from this rubbing action.     

Lineage and morphogenetic analysis of the cardiac valves

We used a genetic lineage-labeling system to establish the material contributions of the progeny of 3 specific cell types to the cardiac valves. Thus, we labeled irreversibly the myocardial (alphaMHC-Cre+), endocardial (Tie2-Cre+), and neural crest (Wnt1-Cre+) cells during development and assessed their eventual contribution to the definitive valvar complexes. The leaflets and tendinous cords of the mitral and tricuspid valves, the atrioventricular fibrous continuity, and the leaflets of the outflow tract valves were all found to be generated from mesenchyme derived from the endocardium, with no substantial contribution from cells of the myocardial and neural crest lineages. Analysis of chicken-quail chimeras revealed absence of any substantial contribution from proepicardially derived cells. Molecular and morphogenetic analysis revealed several new aspects of atrioventricular valvar formation. Marked similarities are seen during the formation of the mural leaflets of the mitral and tricuspid valves. These leaflets form by protrusion and growth of a sheet of atrioventricular myocardium into the ventricular lumen, with subsequent formation of valvar mesenchyme on its surface rather than by delamination of lateral cushions from the ventricular myocardial wall. The myocardial layer is subsequently removed by the process of apoptosis. In contrast, the aortic leaflet of the mitral valve, the septal leaflet of the tricuspid valve, and the atrioventricular fibrous continuity between these valves develop from the mesenchyme of the inferior and superior atrioventricular cushions. The tricuspid septal leaflet then delaminates from the muscular ventricular septum late in development.     

Echodetection of disseminated endocardial vegetations in a patient with active IV drug abuse

Infective endocarditis is a known complication of intravenous (IV) drug abuse and typically involves cardiac valves, sparing the myocardial endocardium. We present the case of a young IV drug using patient who developed sepsis. Although cardiac symptoms and signs were minimal, an echocardiogram was done as patient had a history of IV drug abuse and was in sepsis. Echocardiogram demonstrated disseminated vegetations involving the left ventricular and right ventricular endocardium while sparing the valves. Although diagnosis of infective endocarditis was made on two-dimensional transthoracic echocardiogram, two-dimensional and three-dimensional transesophageal echocardiograms demonstrated the pattern of endocarditis with clarity. This patient had severe sepsis and bacteremia with Methicillin sensitive Staphylococcus aureus.     

Contracted form of primary endocardial fibroelastosis in a young adult without congestive heart failure

A case of a 24-year-old man with the contracted form of primary endocardial fibroelastosis diagnosed by left ventricular endomyocardial biopsy showing a markedly thickened endocardium with fibroelastic proliferation is reported. He had no evident symptoms of congestive heart failure except for shortness of breath on moderate exertion. Echocardiogram showed thickened and dense echoes from the left side of the septum and from the posterior left ventricular endocardium. Hemodynamic and angiographic studies revealed marked elevation of right and left ventricular end-diastolic pressures with dip and plateau pressure contours, moderate pulmonary hypertension, left atrial enlargement and mild mitral regurgitation. Further elevation of right and left ventricular diastolic pressures and pulmonary artery pressure was observed at the second evaluation after 5 years. Our patient suggests that primary endocardial fibroelastosis should be included in the differential diagnosis of adult patients with obscure types of cardiac disease.     

Electrophysiological responses of canine atrial endocardium and epicardium to acetylcholine and 4-aminopyridine.

OBJECTIVES: Prior studies demonstrated marked electrophysiological and pharmacological differences between canine ventricular epicardium and endocardium. For atrium, however, it has been assumed that, because of the thin wall, electrical properties of epicardium and endocardium are similar. The aim of the present study was to compare the action potential (AP) characteristics in epicardial and endocardial atrial cells before and following addition of acetylcholine (ACh) and 4-aminopyridine (4-AP). METHODS AND RESULTS: Microelectrode techniques were used to study the effects of ACh (10(-7)-10(-5) M) and 4-AP (0.5 mM) on epicardial and endocardial AP of canine right atrial free wall at cycle lengths (CL) of 250 to 2000 ms. ACh hyperpolarized epicardial and endocardial cells (by 5-8 mV at 10(-5) M). In control, AP duration to 90% repolarization (APD90) was longer in endocardium at all CL. ACh shortened APD90 in either tissue with more prominent effect in endocardium (at 10(-5) M and CL = 2000 ms, from 179 +/- 10 to 90 +/- 11 ms in epicardium and from 209 +/- 10 to 65 +/- 6 ms in endocardium, P < 0.05). As a result, at 10(-5) M, APD90 in endocardium was shorter than in epicardium at all CL 4-AP effects on AP duration were similar in both tissue types. No effects of 4-AP was seen at CL = 250 ms and at long CL, the compound shortened APD90 and prolonged AP duration to 50% repolarization. CONCLUSIONS: (1) ACh exerts direct effects on atrial epicardial and endocardial AP; (2) 4-AP-sensitive transient outward current (Itol) is expressed both in canine atrial epicardial and endocardial cells; (3) differential response of epicardial and endocardial APD to ACh may alter the gradient of repolarization across the atrial wall and contribute to vagally induced atrial flutter and fibrillation.     

Uhl's disease: An uncommon presentation of a rare disease

Uhl's disease, also known as Uhl anomaly, is a rare disease secondary to selective but uncontrolled apoptosis of right ventricular myocytes during the perinatal period, after complete cardiac development, leading to the absence of right ventricular myocardium and the direct apposition of endocardium to epicardium without a myocardial layer in between, resulting in right ventricular failure.The present paper describes a case of Uhl's disease with an uncommon presentation. A 28-year-old man was admitted with dyspnea and cyanosis. Transthoracic echocardiography showed severe dilation of the right chambers, impaired right ventricular systolic function and a large ostium secundum atrial septal defect (ASD). Cardiac catheterization revealed pulmonary hypertension, with increased pulmonary capillary wedge pressure (mean 19 mmHg) and Qp:QS 0.88:1. At this point, the authors considered that a main diagnosis of ASD could not explain the clinical features and hemodynamic data. A primary disease of the right ventricle was the most likely hypothesis and cardiac magnetic resonance imaging was performed, which demonstrated an extremely thin-walled right ventricle, with almost complete absence of right ventricular free wall myocardium, compatible with Uhl's disease.     

Morphological changes in endocardium subjected to global ischaemia

Summary To provide insight into the effects of severe ischaemia on endocardium, the sequence of morphological changes which develop in the endocardium of the isolated rat heart subjected to 0–12 hours of global ischaemia at 37°C was examined. A progression of changes occurred. Following one or more hours of ischaemia crater-like depressions and blebs appeared on the luminal surfaces of ventricular endothelial cells, with margination and clumping of nuclear chromatin, loss of glycogen granules, swelling of mitochondria, and the development of subendothelial membrane-bound dilatations of myocytes. Following two or more hours of ischaemia there was progressive separation of endothelial cells along their intercellular boundaries and desquamation of an increasing proportion of these cells. In regions of desquamation the surface was initially smooth due to persistence of the lamina densa of the basal lamina, but after longer periods of ischaemia the surface became rough with exposure first of the subendothelial connective tissue fibres (4 hours) and eventually of cardiac muscle cells (12 hours).     

Notch signaling in cardiac development

The Notch signaling pathway has been demonstrated to play a critical role during mammalian cardiac development based on recent findings from gene-targeted mice. In addition, mutations in the Notch signaling pathway have been associated with human congenital heart defects such as Alagille syndrome, bicuspid aortic valve disease, calcification of the heart valves, and ventricular septal defects. Recently, it was demonstrated that Notch activation in the endocardium regulates ventricular myocardial development and that the Notch downstream target genes Hey1 and Hey2 are required for the establishment of the atrioventricular canal myocardial boundary. The Notch pathway has previously been implicated in regulating endothelial-to-mesenchymal transition during development of the heart valves, and recent reports further dissect the role of individual Notch downstream target genes during this process. In addition, a role for the Notch pathway during cardiac neural crest cell development has been identified, which provides a potential mechanism for the findings seen in Alagille syndrome. This review focuses on recently reported findings that elucidate mechanisms regulated by the Notch pathway during ventricular, atrioventricular canal, and outflow tract development.     

Unusual location of mural thrombi in the right atrium caused by pathological changes in the sinoatrial node

We present a post-mortem examination of two hearts in which we found organized mural thrombi attached to the right atrial endocardium in the recess called antrum atrii dextri. This region is a place where the sinus node is situated very close to the endocardium of right atrium. Any pathological process involving the node (inflammation, degeneration) may reach this part of endocardium by continuity, this in turn creates convenient conditions for mural thrombi formation. The first case--a 52-year old man who died of severe congestive heart failure caused by rheumatic disease with mitral and aortic stenosis. Atrial fibrillation had developed several years before his death. Apart from typical changes of mitral and aortic valves a post-mortem examination revealed an organized, globular thrombus in antrum atrii dextri. In the microscopical findings of the sino-atrial region the fatty degeneration of the sinus node with multiple mononuclear cell infiltration was the most striking feature. The sinus node artery was narrowed due to fibro-muscular dysplasia of its wall. The second case--a 74-years old man who suffered from arterial hypertension and chronic pyelonephritis with a history of heart infarct in the past. The ECG recording showed multifocal atrial rythm with variable P wave morphology and P-Q distance. At necropsy the whole heart was significantly enlarged with no scars or any other signs of healed infarct. The microscopical findings revealed the heart muscle to be infiltrated by amyloid deposits particularly apparent in the sinus node. Similar thrombus of 1.5 cm in diameter was found in antrum of the right atrium.(ABSTRACT TRUNCATED AT 250 WORDS)     

Distribution of the neural cell adhesion molecule (NCAM) during heart development

The neural cell adhesion molecule, NCAM, was localized in the embryonic chick heart from Hamburger-Hamilton stage 14 up to hatching and in the adult heart. A monoclonal antibody directed to NCAM was used with the indirect antibody technique to stain frozen sections with immunoperoxidase. The myocardium showed immunoreactivity at stages 15 and 21, with little to no staining of epicardium, endocardium or atrioventricular endocardial cushion tissue. At stage 22, additional immunoreactivity was found in the endocardium of both the atrial septum and the atrial and ventricular surfaces of the atrioventricular cushions. Endocardial-derived mesenchymal cells within the cushions were also immunostained for NCAM. A gradient of NCAM staining was evident in the ventricular wall by stage 16. The staining intensity in the myocardium subjacent to the epicardium was less than found near the ventricular lumen. Biochemical analyses revealed that the embryonic heart expresses polysialylated NCAM. Upon desialylation with the endoneuraminidase Endo-N, the predominant heart NCAM has an apparent molecular weight of 155 to 160 kDa, which is distinct in size from the predominant forms found in embryonic chick nervous system (180, 140 and 120 kDa). NCAM expression is regionally regulated in the heart. The pattern of its expression is consistent with our hypothesis that it is involved in (1) differentiation of the atrial and ventricular walls, (2) fusion of the atrial septum with the endocardial cushions, (3) fusion of the endocardial cushions, and (4) formation and remodeling of ventricular trabeculae.     

Elevated collagen content in volume overload induced cardiac hypertrophy

This investigation was designed to determine if chronic volume overload is associated with altered collagen content of five regions of the myocardium. Five adult cats were subjected to a 6-week period of chronic volume overload induced by atrial septotomy and five untreated animals served as controls. Significant (P < 0.05) right ventricular hypertrophy was present as indicated by the right ventricular body weight ratio. For control animals this ratio was 0.68 ± 0.04 g/kg; for volume overloaded animals it was 0.83 ± 0.05 g/kg.) The collagen content was assessed by measuring the hydroxyproline content of the dried cardiac muscle. Right ventricular endocardium hydroxyproline in volume overloaded animals was significantly elevated above that in control animals (in the latter it was 5.30 ± 0.36 μg/mg; in the former it was 6.33 ± 0.18 μg/mg) while the epicardial collagen content was unchanged. Similarly, the amount of collagen found in the left ventricle was significantly increased in the endocardium and normal in the epicardium. Septal collagen concentration was unaltered in volume overloaded animals. This study demonstrated that alterations in cardiac muscle collagen concentration are associated with volume overload and that these cellular changes are nonuniform.     

Expression of HLA-DR antigen and smooth muscle cell differentiation markers by valvular fibroblasts in degenerative aortic stenosis

Objectives. This study was designed to analyze the functional characteristics of fibroblasts present in aortic valves with degenerative stenosis.Background. Morphologic analysis of degenerative stenosis of tricuspid aortic valves has revealed an extensive interstitial fibrosis.Methods. Stenotic aortic valves collected during aortic valve replacement and control valves collected at autopsy were fixed in formaldehyde, cryosectioned and stained with antibodies against leukocyte markers, HLA-DR and intracellular filaments. Fibroblasts isolated from stenotic valve and skin explants were grown in cell culture, and their proliferative activity was analyzed by cell ocunting and uptake of tritiated thymidine.Results. In the stenotic valves nearly all interstitial cells expressed vimentin, and ~60% of the cells also expressed alpha-actin and desmin. HLA-DR was present on inflammatory cells as well as on one-third of the fibroblast-like cells in the interstitium. Macrophages were found in the interstitium and T lymphocytes close to calcium deposits and in subendothelial areas. In control valves, fibroblasts expressed vimentin but not alpha-actin or desmin. Few inflammatory cells were present in these valves, and HLA-DR expression was restricted to the endothelial surface. In culture, stenotic valve fibroblasts had a reduced ability to proliferate in serum and to activate DNA synthesis in response to growth factors compared with skin fibroblasts from the same patient.Conclusions. The observation that fibroblasts present in aortic valves with degenerative stenosis express smooth muscle cell characteristics and HLA-DR antigen and show signs of cellular senescence in vitro suggests that they are in a state of chronic activation similar to that observed in fibromatosis and scleroderma lesions.     

Ultrastructural cytochemistry of atrial muscle cells: IX. Reactivity of specific granules in cultured cardiocytes

A technique for the culture of neonatal (2- to 3-day-old) rat cardiocytes is described. With this technique, ventricular cardiocytes started beating earlier and lived longer, atrial cardiocytes degenerating after 10 days of culture. Specific granules, mostly of the A type, were present in atrial but not ventricular cardiocytes at all time intervals. These specific granules were argentaphobic when stained according to the periodic acid-thiocarbohydrazide-silver proteinate technique of Thiery. The core of these granules was moderately positive after staining fine sections with phosphotungstic acid at low pH. A similar reaction was shown in both atria and ventricle by the cell coat, residual bodies (C-granules) and Z-discs. The Golgi complex was more extensively stained by phosphotungstic acid in atrial than in ventricular cultured cardiocytes or in atrial and ventricular cardiocytes of young (3- and 13-day-old) rats in situ. Multivesicular bodies with a dense core, identical to those already noted in the cells of various endocrine glands, and thought to be crinophagic, were present, as in atrial cardiocytes in situ, in cultured atrial but not ventricular cardiocytes. They were silver negative. Their dense core, as in situ, reacted to phosphotungstic acid but their matrix, contrary to classical multivesicular bodies without a dense core, did not. Numerous, small, phosphotungstic acid-positive vesicles were present in cultured atrial and, to a lesser extent, in cultured ventricular cardiocytes. Vesicles of the same type were rare in either atrial of ventricular cardiocytes of young rats in situ. Glycogen, as revealed by the periodic acid Schiff and Thiery techniques, was equally abundant in cardiocytes in situ and in 1-day-old cultures of cultured cardiocytes from atria and ventricle. These results indicate that specific granules of cultured atrial cardiocytes are probably made up, as in situ, of glycoproteins.     

Recurrent sustained ventricular tachycardia: structure and ultrastructure of subendocardial regions in which tachycardia originates

Surgical resection of the endocardium and subendocardium often abolishes chronic recurrent sustained ventricular tachycardia in patients with healed myocardial infarcts or ventricular aneurysms, presumably by interrupting the reentrant pathway. To define the morphologic characteristics of cells in the reentrant pathway, we studied the histology and ultrastructure of the endocardial resections of 23 patients who underwent this procedure. Bundles of apparently viable myocardial fibers embedded in dense fibrous tissue were identified throughout the endocardial resections from all patients. These bundles of cells were separated from one another by fibrous tissue but extended uninterrupted to the margins of the surgical resection. In 14 patients Purkinje fibers were identified beneath the thickened endocardium whereas the remaining bundles were composed of ventricular muscle. The Purkinje fibers appeared to have normal ultrastructure and ventricular cells with both normal and abnormal ultrastructures were present. The abnormal muscle cells were characterized by loss of contractile elements, aggregates of dilated sarcoplasmic reticulum, and osmiophilic dense bodies. The sarcolemma was intact and the nuclear chromatin was evenly dispersed suggesting that these cells were still viable. The abnormal structure and arrangement of the surviving cardiac fibers in the endocardium may cause the abnormal electrophysiologic function that results in ventricular tachycardia.     

Pacemaker-induced cardiovascular failure. Hemodynamic and angiographic observations

A 71 year old woman underwent permanent transvenous right ventricular pacemaker implantation for prolonged syncope and atrioventricular conduction defects. Each time the patient's heart rate spontaneously decreased to less than 70 beats/min, cardiovascular collapse with hypotension and reduced cardiac output occurred. Left ventricular cineangiography performed during both sinus rhythm and right ventricular pacing demonstrated reduced left ventricular end-diastolic volume, secondary to a loss of atrial contribution to left ventricular filling, and severe, acute mitral regurgitation with significantly decreased effective stroke volume and cardiac output. Pacing from the left ventricular endocardium had the same effect. The detrimental effects of cardiac pacing necessitated removal of the right ventricular pacemaker.     

Atrioventricular valve abnormalities in infancy: two-dimensional echocardiographic and angiocardiographic comparison

The results of two-dimensional echocardiography and biplane angiocardiography from 47 infants with congenital atrioventricular (AV) valve abnormalities were compared. Eleven patients had atresia of the right AV valve, 10 had atresia of the left AV valve, 4 had hypoplasia of the right AV valve and 5 had hypoplasia of the left AV valve. Twelve patients had endocardial cushion defect, three had single ventricle and two had straddling of the left AV valve. There was agreement between the two techniques as to the number of AV valves present in each patient. The echocardiographic estimate of valve anular diameter was below normal in seven of the eight patients thought to have a hypoplastic anulus by angiocardiography. In 10 of the 12 patients with endocardial cushion defect, there was agreement between the two techniques as to the presence or absence of atrial and ventricular septal defect. The chordal attachments of straddling valves were better visualized by echocardiography; flow patterns and effective orifice size were better demonstrated by angiocardiography. The subcostal four chamber echocardiographic views and cranially angulated oblique angiocardiographic views were comparable and provided the best images for determination of the size and number of AV valves and their relation to the atrial and ventricular septa.     

Echocardiographic observations in malfunctioning heart valves due to thrombosis (author's transl)]

The study includes two patients with obstruction of prosthetic heart valves by thrombosis. In the first patient, a thrombus attached to the ventricular side of the cage of a Smeloff-Cutter mitral prosthesis caused incomplete excursion of the ball in most cardiac cycles, which was detected by echocardiography. In the second patient a thrombosis of the atrial and ventricular side of a Lillehei-Kaster mitral prosthesis delayed opening of the disc. The initial part of the opening movement was "rounded", the excursion of the disk diminished. The cases presented indicate that in patients whose condition deteriorates after prosthetic valve replacement, echocardiography can help identify the cause. In particular, the technique makes it possible to differentiate between valvular dysfunction and muscular insufficiency of the left ventricle. Comparison with recordings obtained in the early postoperative period facilitate the detection of a malfunctioning prosthesis.     

Cardiac papillary fibroelastoma originating from pulmonary vein--a case report

Cardiac papillary fibroelastoma is a primary cardiac neoplasm that typically affects the cardiac valves, mainly the aortic and mitral valves, and very rarely the endocardium of cardiac chambers. Cardiac papillary fibroelastoma is rarely diagnosed during life, as the majority are incidental findings at autopsy, but with the advent of echocardiography, it is being increasingly recognized. Although the tumor is usually small and histologically benign, it may have a malignant propensity for life-threatening complications, such as a cerebrovascular accident, myocardial ischemia or infarction, or sudden death. The patient reported here presented with an embolic stroke from a thrombus on the surface of a left atrial papillary fibroelastoma. The papillary fibroelastoma was originating from the lower portion of the left inferior pulmonary vein and was protruding into the left atrial cavity. Papillary fibroelastoma originating from the pulmonary veins has not been reported before. The tumor was successfully removed by intraoperative transesophageal echocardiography-guided cardiac surgery. Grossly, the surface of the tumor was smooth and translucent. The gelatinous membrane on the surface tore easily, and soft papillary tumor with multiple fronds was visible. Histology confirmed the mass was a papillary fibroelastoma. Postoperative recovery was uneventful. Follow-up transthoracic echocardiogram revealed no residual or recurrence of tumor. The patient was in excellent health at 2-year follow-up. The case is described and the clinical characteristics of cardiac papillary fibroelastoma are reviewed.     

Regulation of cardiac development by receptor tyrosine kinases

The development of a functional heart depends on the coordinated growth, differentiation, migration, and apoptosis of cell populations of diverse embryological origins. These processes are regulated in part by soluble polypeptide growth factors that exert their effects via binding to cell surface receptors with intrinsic tyrosine kinase activity. In particular, members of this class of receptors and their ligands have been shown to regulate the development of distinctive regions of the heart, such as the mesodermally derived cardiac myocyte, the endocardium, and outflow tract and septa, which depend on cardiac neural crest. The hepatocyte growth factor receptor, c-met the fibroblast growth factor receptors; and the neuregulin receptors have been shown to influence cardiomyocyte proliferation and/or differentiation. Receptors binding to vascular endothelial cell growth factor or angiopoietin have been implicated in the development of the endocardium. Finally, gene-targeting experiments in the mouse have demonstrated functional roles for neurotrophins and their cognate trk receptor tyrosine kinases in the development of outflow tract, septa, and valves that are structures derived from cardiac neural crest.     

Surface cables of cardiac myocytes

Heart muscle cells prepared by mechanical disaggregation were seen by transmission electron microscopy (TEM) to possess an intact glycocalyx. Scanning electron microscopy (SEM) studies of the surface of these cells revealed longitudinally oriented cables, 10 to 12 nm thick. Each surface cable appeared to be less than one sarcomere long, extending longitudinally from the glycocalyx close to one M-line to the glycocalyx close to an adjacent M-line. Cables having similar orientation, distribution, thickness, and attachment positions were present in SEM preparations of mechanically disaggregated myocytes from hamster, rat, and dog. Unbanded tubular fibrils, similar to the surface cables in size and location, were demonstrable by TEM. Tubular fibrils indistinguishable from those in contact with the glycocalyx were seen in the interstitial space at a distance from the cell surface. Similar fibrils were also seen in association with interstitial elastin that occasionally remained attached to the isolated myocytes. It is postulated that the tubular filaments and the surface cables are the same structure, and may be an important determinant of the mechanical properties of myocardium.