Percutaneous therapies for valvular heart disease.

Balloon valvuloplasty has been in clinical use for over 20 years, but the prospect of repairing and replacing cardiac valves via catheter-based techniques represents a truly recent development. This review introduces evolving technologies and their relevance to cardiovascular pathologists.     

Pathology of inflammatory native valvular heart disease.

Rheumatic disease is an important cause of inflammatory native heart valve disease. However, with increased understanding of the pathoetiology of valve disease and valve injury, it is evident that inflammation may play a role in many valve disorders. We are only beginning to understand these complex processes. With increasing knowledge that many of these processes are active, there may be opportunity for intervention or even prevention.     

Cronic non-rheumatic valvular heart disease. An autopsy study.

The frequency of chronic non-rheumatic valvular heart disease in Iceland was investigated via autoposies performed from November 1965 through December 1974. During this period, about 12.400 Icelanders died at the age of 16 years and older and 28.8 per cent of these were included in the study. At autopsy, males outnumbered females by 2:1. The frequency of calcific aortic stenosis was found to be 3.63 per cent and the prevalence was calculated to be 3.17 per cent among males and 4.50 per cent among females. Calcific aortic stenosis in tricuspid valves was more frequent in females and calcific aortic stenosis in bicuspid valves was more frequent in males. Among the hearts with calcific aortic stenosis, 70.8 per cent were found to have normally tricuspid valves, 25.4 per cent bicuspid valves and 3.8 per cent tricuspid valves with an unicommissural fusion. In 0.59 per cent of the hearts the aortic valve was either bicuspid or had an uncommissural fusion without the features of calcific stenosis. However, a functional stenosis was suggested by the increased weight of most of these hearts. The frequency of bicuspid aortic valves was 1.2 per cent with a prevalence in males of 1.54 per cent and in females 0.50 per cent. A calcified mitral annulus was found in 1.98 per cent of the hearts and in most, it was either associated with calcific aortic stenosis in a tricuspid valve, or it was a single valvular disease. Rheumatic valvular disease was found in 1.08 per cent of the heart examined.     

Chronic rheumatic valvular heart disease. An autopsy study.

The incidence of chronic rheumatic valvular heart disease in Iceland was investigated via autopsies performed from November 1965 through December 1974. During this period, approximately 12.400 Icelanders died at the age of 16 years and older and 28.8 per cent of these are included in the study. At autopsy, males were found to outnumber females by 2:1. Rheumatic valvular heart disease was found in 38 subjects, i.e. in 1.08 per cent of the cases, the sex distribution being 0.67 per cent males and 1.83 per cent females. As regards the hearts with chronically deformed valves, the deformity was of rheumatic origin only in 20 per cent of the cases; the majority, or 69 per cent, presented calcified aortic stenosis. Hospital records applying to most of the subjects were available and according to these, only 18 per cent disclosed a history of rheumatic fever. The diagnosis of rheumatic valvular disease was first established at autopsy in 71 per cent of the cases. An evaluation of the functional derangements of the diseased valves was not attempted, but there is reason to believe that many of the lesions were too mild to provoke significant symptoms and signs. Previous doubts about the existence of rheumatic heart disease in Iceland have been settled in this study.     

Oesophageal symptoms and manometry in valvular heart disease

A possible relationship between heart disease, oesophageal dysfunction (OD) and symptomatology was studied in 47 patients with valvular heart disease. They were investigated with oesophageal manometry and oesophageal acid perfusion test. OD was found in 32 percent of the patients. A local pressure increase in the middle part of the oesophagus, probably an effect of cardiac enlargement and compression of the oesophagus, was found at manometry in 38 percent. The incidence of OD and of oesophageal symptoms was the same in patients with and without oesophageal compression. We did not find any indications that valvular disease in itself provokes OD, nor that symptoms of chest pain and cough in patients with valvular heart disease are due to OD.     

Morphologic and pathogenetic aspects of coronary artery atherosclerosis in ischemic heart disease

The surface of coronary arteries is subjected to pronounced changes in all stages of atherogenesis. Structural and functional re-arrangements within the endothelial cell monolayer reflect one or another degree of manifestation of defensive or adaptative reactions in the course of pathogenesis. The formation of crater-like defects and monocyte adhesions is a constant and characteristic feature of initial stages of atherosclerosis. Focal formation of microthrombi can be observed in initial stages of atherogenesis. Endothelium impairment and its regeneration occur at all stages of atherogenesis. Macrophages of monocyte origin play a key role in the formation of foam cells.     

Screening for lupus anticoagulant and anticardiolipin antibodies in women with fetal loss.

Sixty six women with first or second trimester fetal loss were investigated for the presence of lupus anticoagulant by routine coagulation tests and the dilute Russell's viper venom time with a platelet neutralisation procedure, and for raised anticardiolipin antibodies by an enzyme linked immunosorbent assay. Of 35 women with recurrent fetal loss, seven were positive for lupus anticoagulant and six had increased IgG anticardiolipin antibodies, while of 31 women with only one or two episodes of fetal loss, one had lupus anticoagulant and none increased IgG anticardiolipin antibodies. These findings were significantly different. There was no difference in the incidence of increased IgM anticardiolipin antibodies between the two groups (three and two cases, respectively). A further 11 women with intrauterine death in the third trimester were studied and lupus anticoagulant and raised IgM anticardiolipin antibodies were found in one case. No woman was known to have systemic lupus erythematosus. It is concluded that lupus anticoagulant and increased IgG anticardiolipin antibodies are independently associated with recurrent first and second trimester fetal loss and that such cases should be investigated, even in the presence of otherwise good health, by a comprehensive methodological approach.     

Left ventricular cellular hypertrophy in pressure- and volume-overload valvular heart disease

To determine the dependence of myocyte hypertrophy in chronic valvular heart disease on the site and type of lesion, the myocardium was studied from 11 patients with either pressure-overload hypertrophy (PO; four patients with aortic stenosis and two with mixed aortic stenosis/insufficiency) or pure volume-overload hypertrophy (VO; two patients with mitral regurgitation and three with aortic insufficiency). These patients, all without coronary artery disease, died zero to 34 days after valve replacement surgery. Diameters of 25 longitudinally oriented myocytes in the circular midwall myocardium were measured with a calibrated light microscope eyepiece reticle on each of five transmural, transverse, histologic sections from the apical, anterolateral, posterolateral, anteroseptal, and posteroseptal left ventricle. Statistical analysis by modified two-way analysis of variance (ANOVA) demonstrated that mean myocyte size (based on 125 measurements) varied widely among cases but was not statistically different among sites. The myocyte diameter for PO lesions (25.9 +/- 1.1 micron, mean +/- SEM) was significantly greater (P less than 0.05) than that for pure VO lesions (20.4 +/- 0.7 micron), despite equal relative heart weights (measured/predicted from body weight: 2.5 +/- 0.2 [mean +/- SD] versus 2.5 +/- 0.5). This study suggests that 1) cellular hypertrophy in valvular heart disease occurs uniformly throughout the left ventricular myocardium; and 2) mean myocyte diameters are greater in PO than in VO hypertrophy for equivalent cardiac enlargement.     

The heart in selected congenital malformations. A lesson in pathogenetic relationships

The application of new knowledge on the pathogenesis of congenital heart defects has increased our understanding of associated, non-cardiac malformations seen in certain syndromes. Defects in the proliferation and migration of neural crest cells are thought to contribute to conotruncal defects. These are seen in association with conditions such as DiGeorge syndrome. CHARGE association, hemifacial microsomia, and Shprintzen syndrome. They also form part of the isotretinoin and thalidomide embryopathies. Their association with conotruncal defects suggests that abnormal migration of neural crest cells may play a role in the pathogenesis of these syndromes.     

Etiology of acquired valvular heart disease in adults. A survey of 18,132 autopsies and 100 consecutive valve-replacement operations

The cardiac valve pathology in 18,132 autopsies was analyzed. A total of 1,136 patients (6.3%) had acquired valvular disease. The most commonly diseased cardiac valve was the mitral valve (49%), followed by the aortic valve (42%) and the tricuspid (9%) and pulmonary valves (0.3%). Rheumatic fever accounted for 99.7% of cases of mitral stenosis and 68.4% of mitral incompetence. The autopsy incidence of mitral stenosis remained constant over 30 years (1950 to 1979). Only 44.4% of the cases of acquired aortic stenosis were due to rheumatic fever. Review of 100 consecutive, surgically excised native valves revealed that if the pathologist is given adequate information regarding the macroscopic appearance of the intact valve prior to excision, an accurate etiopathologic diagnosis can be made in 81% of cases compared with only 35% of cases without such information.     

A model for lupus brain disease

Systemic lupus erythematosus is an autoimmune disease characterized by antibodies that bind target autoantigens in multiple organs in the body. In peripheral organs, immune complexes engage the complement cascade, recruiting blood-borne inflammatory cells and initiating tissue inflammation. Immune complex-mediated activation of Fc receptors on infiltrating blood-borne cells and tissue resident cells amplifies an inflammatory cascade with resulting damage to tissue function, ultimately leading to tissue destruction. This pathophysiology appears to explain tissue injury throughout the body, except in the central nervous system. This review addresses a paradigm we have developed for autoantibody-mediated brain damage. This paradigm suggests that antibody-mediated brain disease does not depend on immune complex formation but rather on antibody-mediated alterations in neuronal activation and survival. Moreover, antibodies only access brain tissue when blood-brain barrier integrity is impaired, leading to a lack of concurrence of brain disease and tissue injury in other organs. We discuss the implications of this model for lupus and for identifying other antibodies that may contribute to brain disease.     

Sir A. E. Garrod, congenital heart disease in Down syndrome, and the doctrine of fetal endocarditis.

Archibald Garrod was apparently the first to document congenital heart disease as a component of Down syndrome. This arose from his interest in fetal endocarditis, a theoretical cause of cardiac malformations, in vogue roughly from 1840-1940, that drew its strength from analogies with rheumatic heart disease in adults. Garrod's discovery sheds light not only on nineteenth century ideas about teratology, but also on his methodology, genius, and approaches that, in many ways, foreshadowed the techniques that guided his later work on inborn errors.     

Sir A.E. Garrod,congenital heart disease in Down syndrome,and the doctrine of fetal endocarditis

Archibald Garrod was apparently the first to document congenital heart disease as a component of Down syndrome. This arose from his interest in fetal endocarditis, a theoretical cause of cardiac malformations, in vogue roughly from 1840–1940, that drew its strength from analogies with rheumatic heart disease in adults. Garrod's discovery sheds light not only on nineteenth century ideas about teratology, but also on his methodology, genius, and approaches that, in many ways, foreshadowed the techniques that guided his later work on inborn errors.