Arnold C. G. Wenink

Straddling and overriding atrioventricular valves: morphology and classification.

Abstract Fifty-seven hearts are described in which either the orifice or tension apparatus of an atrioventricular (A-V) valve was related to both sides of a septum in the ventricular mass. In most of the hearts both the orifice overrode the septum and the tension apparatus straddled the septum. In some hearts straddling of the tension apparatus was present in the absence of overriding of the anulus while in two hearts the anulus overrode in the absence of straddling. Hearts were observed in which the chamber receiving all of one valve and the straddling portion of the other valve had either right or left ventricular morphologic features, and in each type the chamber receiving only part of the straddling valve was found either to the right or the left. When the straddling valve was morphologically a tricuspid valve it always straddled the posterior part of a septum that never extended to the crux; when it was morphologically a mitral valve it always straddled the anterior part of a septum that did extend to the crux. This arrangement was found irrespective of the relations of the chambers. Four basic groups were therefore defined: straddling of the mitral and tricuspid valves in the setting of A-V concordance and discordance, respectively. However, the degree of override of the straddling valve was frequently such that the A-V connection present was double inlet ventricle rather than concordance or discordance. Indeed, in each group a series of anomalous hearts was found between the extremes of concordance or discordance and double inlet. In categorizing the A-V connections, these series were divided at their mid points. The hearts with double inlet connections were considered univentricular hearts and their chambers described accordingly. In each series hearts were found with unequally committed common valves that were virtually identical to the hearts with straddling right or left valves. They were therefore included in the study as were two hearts in which both right and left valves straddled. Examination of the conduction tissues in examples of each series showed that the position of the connecting node depended on whether or not the septum extended to the crux, anterior systems being found when it did not and either anterior or regular systems when it did, the latter variation depending on the A-V connection present. The study shows that straddling or overriding valves can be easily catalogued if attention is paid to the A-V connection and the morphologic features and relations of the ventricular chambers.

Development of the papillary muscles of the mitral valve: morphogenetic background of parachute-like asymmetric mitral valves and other mitral valve anomalies

OBJECTIVESnTo understand papillary muscle malformations, such as in parachute mitral valves or parachute-like asymmetric mitral valves, we studied the development of papillary muscles.nnnMETHODSnNormal human hearts at between 5 and 19 weeks of development were studied with immunohistochemistry, three-dimensional reconstructions, and gross inspection. Scanning electron microscopy was used to study human and rat hearts.nnnRESULTSnIn embryonic hearts a prominent horseshoe-shaped myocardial ridge runs from the anterior wall through the apex to the posterior wall of the left ventricle. In the atrioventricular region this ridge is continuous with atrial myocardium and covered with cushion tissue. The anterior and posterior parts of the trabecular ridge enlarge and loosen their connections with the atrial myocardium. Their lateral sides gradually delaminate from the left ventricular wall, and the continuity between the two parts is incorporated in the apical trabecular network. In this way the anterior and posterior parts of the ridge transform into the anterolateral and the posteromedial papillary muscles, respectively. Simultaneously, the cushions remodel into valve leaflets and chordae. Only the chordal part of the cushions remains attached to the developing papillary muscles.nnnCONCLUSIONSnDisturbed delamination of the anterior or posterior part of the trabecular ridge from the ventricular wall, combined with underdevelopment of chordae, seems to be the cause of asymmetric mitral valves. Parachute valves, however, develop when the connection between the posterior and anterior part of the ridge condenses to form one single papillary muscle. Thus parachute valves and parachute-like asymmetric mitral valves originate in different ways.

Development of the atrioventricular valve tension apparatus in the human heart.

Abstractu2002Using various microscopical techniques we studied the development of the atrioventricular valves in human hearts between 5 and 19 weeks of development. Within the atrioventricular cushions two different layers could be recognized that remained present in all ages studied. The atrial layer, being present at the side of the atrioventricular orifice, was positive for laminin while the ventricular layer, that was connected to the myocardium, was positive for fibronectin and collagen III. Fate-mapping of these two layers, morphometrics, and scanning electron microscopy, supplemented with in vivo labeling of cushion tissue in chicken hearts have lead to new insights in the process of valve development. The cushions became freely movable prevalvular leaflets by delamination of ventricular myocardium underneath the cushion tissue. This myocardium gradually retracted towards annulus and papillary muscles and finally disappeared, resulting in fibrous, non-myocardial valves. The atrial layer of the cushions remained present as a jelly-like surface on the valve leaflets while the ventricular layer of the cushions became the compact fibrous tissue of the leaflets and the chords. Chordal development was first visible at 10 weeks of development when gaps were formed in the ventricular layer of the cushions on top of the papillary muscles. These gaps enlarged into the interchordal spaces while the cushion tissue in between the gaps lengthened to form the chords. We conclude that the leaflets as well as the chords of the atrioventricular valves are derived from atrioventricular cushion tissue. Myocardium is only important for loosening of the leaflets while keeping connection with the developing papillary muscles. Errors in delamination or retraction of myocardium or remodeling of cushion tissue into chords form the basis for various congenital valve anomalies.

The Development of the Cardiac Specialized Tissue

It is a reasonable premise that knowledge of the development of any system provides a sound basis for the comprehension of both its normal and abnormal structure. It can also be argued that awareness of the morphogenetic nature of components of any system can provide some evidence relative to its function. In our opinion, all of these statements hold good for the cardiac specialized or conducting tissue. However, there is considerable divergence of opinion regarding the precise origin of certain parts of the conducting system, in particular the atrioventricular junctional area, while controversy continues to rage concerning the extent of specialized structures within the atrial tissues. Review of the relevant literature shows that in many cases these disagreements relate more to differences in interpretation than to variation in observations, while other arguments relate more to definitions and semantics. In this review we will present our own observations relative to the development of the cardiac specialized tissue. These have been based on histologic study of human embryos and specimens of congenitally malformed human hearts, together with combined morphologic and electrophysiologic studies of human fetal hearts. Where any topic is contentious we shall refer to the results of previous investigators. However, we shall not attempt to provide an exhaustive review of prior studies of development of the cardiac specialized tissue. Rather we will attempt to provide an outline of embryogenesis which we hope will facilitate interpretation and aid comprehension of the subsequent contributions to this book.

The parachute-like asymmetric mitral valve and its two papillary muscles ☆ ☆☆ ★ ★★

OBJECTIVESnThe morphologic features of parachute-like asymmetric mitral valves are described to discriminate this anomaly from parachute mitral valves.nnnBACKGROUNDnMitral valves with unifocal attachment of chords have been called parachute valves, independent of the number of papillary muscles. Therefore the anomaly involving two papillary muscles has not received separate attention.nnnMETHODSnThe gross anatomy of 29 mitral valves with focalized attachment of chords was studied.nnnRESULTSnIn 28 of the autopsy specimens asymmetric mitral valves with two papillary muscles were present, and one of the muscles was elongated, located higher in the left ventricle with its tip reaching to the anulus, and attached at both its base and lateral side to the left ventricular wall. The valve leaflets could be directly attached to this abnormal muscle that received few chords or, in three hearts, no chords at all, resulting in an oblique and eccentric orifice. Because of the focalized attachment of chords to one of the two papillary muscles, we call this malformation parachute-like asymmetric mitral valve, We found only one true parachute mitral valve, that is, one having a single papillary muscle that received all chords.nnnCONCLUSIONSnThe morphologic features of asymmetric mitral valves are essentially different from those of true parachute valves. A distinction between these two anomalies will contribute to recognition by the pediatric cardiologist and surgeon.

Chronic right ventricular pressure overload results in a hyperplastic rather than a hypertrophic myocardial response

Myocardial hyperplasia is generally considered to occur only during fetal development. However, recent evidence suggests that this type of response may also be triggered by cardiac overload after birth. In congenital heart disease, loading conditions are frequently abnormal, thereby affecting ventricular function. We hypothesized that chronic right ventricular pressure overload imposed on neonatal hearts initiates a hyperplastic response in the right ventricular myocardium. To test this, young lambs (aged 2–3 weeks) underwent adjustable pulmonary artery banding to obtain peak right ventricular pressures equal to left ventricular pressures for 8 weeks. Transmural cardiac tissue samples from the right and left ventricles of five banded and five age‐matched control animals were studied. We found that chronic right ventricular pressure overload resulted in a twofold increase in right‐to‐left ventricle wall thickness ratio. Morphometric right ventricular myocardial tissue analysis revealed no changes in tissue composition between the two groups; nor were right ventricular myocyte dimensions, relative number of binucleated myocytes, or myocardial DNA concentration significantly different from control values. In chronic pressure overloaded right ventricular myocardium, significantly (P < 0.01) more myocyte nuclei were positive for the proliferation marker proliferating cellular nuclear antigen than in control right ventricular myocardium. Chronic right ventricular pressure overload applied in neonatal sheep hearts results in a significant increase in right ventricular free wall thickness which is primarily the result of a hyperplastic myocardial response.

HNK-1 expression patterns in the embryonic rat heart distinguish between sinuatrial tissues and atrial myocardium

HNK-1 expression was studied by immunohistochemistry in serial sections of embryonic and fetal rat hearts from 11.5 to 16.5 embryonic days. Graphic reconstructions were made to obtain detailed 3D information on the localization of immunoreactive tissues. The antibody used appeared to stain most parts of the venous sinus and the sinuatrial transitional zone as well as the atrioventricular transitional zone, but the patterns varied through the different developmental stages. At 11.5 days, positive myocardium was found in the right atrium and on top of the ventricular septal primordium. At 13.5 days, the left venous valve and the posterior atrial wall containing the orifice of the pulmonary vein were immunoreactive, and so were the right venous valve, the septum spurium and the superior, right-lateral and inferior parts of the atrioventricular canal. From the latter, immunoreactivity continued onto the crest of the ventricular septum. At 15.5 days, HNK-1 positivity in the two venous valves had become continuous, whereas the right-lateral part of the atrioventricular canal had lost its positivity, thus making the positive areas in the superior and inferior parts of this canal discontinuous. From the venous valves immunoreaction continued into the venous sinus septum but this area remained discontinuous with the inferior part of the atrioventricular canal. It is concluded that the entirety of venous sinus and sinuatrial transitional zone expresses the HNK-1 antigen and that the orifice of the pulmonary vein belongs to this complex, rather than to the embryonic atrium proper, which is HNK-1 negative. Extrapolation of these data to the adult human atrium leads to the conclusion hat most ’’atrial septal structures’’ are of sinuatrial origin, leaving the flap valve of the oval fossa (atrial septum primum) as the only really atrial structure. It is suggested that the atrioventricular node is derived from the inferior portion of the atrioventricular canal, and that two expansions of sinuatrial tissue form the substrate for anterior and posterior atrionodal inputs which in the literature have been described as internodal tracts.

Flexible electronic feedback using the virtues of progress testing.

The potential richness of the feedback for learners and teachers is one of the educational advantages of progress tests (PTs). Every test administration yields information on a students knowledge level in each sub-domain of the test (cross-sectional information), and it adds a next point to the corresponding knowledge growth curve (longitudinal information). Traditional paper-based feedback has severe limitations and requires considerable effort from the learners to give meaning to the data. We reasoned that the PT data should be flexibly accessible in all pathways and with any available comparison data, according to the personal interest of the learner. For that purpose, a web-based tool (Progress test Feedback, the ProF system) was developed. This article presents the principles and features of the generated feedback and shows how it can be used. In addition to enhancement of the feedback, the ProF database of longitudinal PT-data also provides new opportunities for research on knowledge growth, and these are currently being explored.

Straddling atrioventricular valve with absent atrioventricular connection. Report of 10 cases.

From the Department ofPaediatrics and Surgery, Cardiothoracic Institute, Brompton Hospital, Fulham Road, London; Thoracic Unit, The Hospitalfor Sick Children, London; Freeman Road Hospital, Newcastle-upon-Tyne; Department ofPathology, University ofAmsterdam, Holland; Department ofAnatomy, State University ofLeiden, Holland; Department ofPathology, Grimsby General Hospital, South Humberside; and Institute of Child Health, University of Liverpool

Development of the Cardiac Conduction System in Atrioventricular Septal Defect in Human Trisomy 21

In patients with atrioventricular septal defect (AVSD), the occurrence of nonsurgical AV block has been reported. We have looked for an explanation in the development of the AV conduction system. Human embryos with AVSD and trisomy 21 and normal embryos were examined (age 5–16 wk gestation). Antibodies to human natural killer cell-1 (HNK-1), muscle actin (HHF-35), and collagen VI were used to delineate the conduction system. As in normal hearts, HNK-1 transiently stains the AV conduction system, the sinoatrial node, and parts of the sinus venosus in AVSD. A large distance is present between the superior and inferior node-like part of the right AV ring bundle, comparable to 6-wk-old normal hearts. The definitive inferior AV node remains in dorsal position from 7 wk onward and does not appose to the superior node-like part as seen in normal hearts. Furthermore, in AVSD, a transient third HNK-1–positive “middle bundle” branch that is continuous with the retroaortic root branch and the superior node-like part can be identified, and thus the AV conduction system forms a figure-of-eight loop. At later stages, the AV node remains in dorsal position close to the coronary sinus ostium with a long nonbranching bundle that runs through thin fibrous tissue toward the ventricular septum. The formation of the AV node and the ventricular conduction system in AVSD and Down syndrome differs from normal development, which can be a causative factor in the development of AV conduction disturbances.