Nobuhisa Baba

Cardiac pathology of transvenous pacemakers

Abstract The cardiac pathology of the nine case with transvenous pacemakers was reviewed. Thrombosis which developed along the wire of the pacemakers was organized into a tight fibrous sheath adherent to the tricuspid valve or chordae tendineae, which may hinder replacement of the pacemakers. After inflammation subsided around the tip of the electrode, gradual fibrous thickening of the underlying endocardium occurred that may result in increased pacemaker threshold. Initial inflammation and thrombosis was noted in the SA node area which may be of no clinical significance. Complications of pulmonary embolism and perforation of the apex were also observed.

Evolution of a hereditary cardiac conduction and muscle disorder: a study involving a family with six generations affected.

This study describes six generations of a family with autosomal dominant cardiac conduction system and myocardial disease with recognizable clinical stages. A 20 year follow-up of nine family members, a medical questionnaire of 196, electrocardiographic screening of 91, noninvasive testing of 20, and catheterization with endomyocardial biopsy of six are the basis of this report. The clinical stages are as follows: Stage I occurs in the second and third decades of life and is characterized by an absence of symptoms, normal heart size, sinus bradycardia, and premature atrial contractions. Stage II is marked by first-degree atrioventricular block in the third and fourth decades. Stage III occurs in the fourth and fifth decades and is accompanied by chest pain, fatigue, lightheadedness, and advanced atrioventricular block followed by the development of atrial fibrillation or flutter. Stage IV, in the fifth and sixth decades of life, is characterized by congestive heart failure and recurrent ventricular arrhythmias. Light microscopy of right ventricular endomyocardial biopsy specimens from patients in stage II revealed very mild fibrosis; electron microscopy of the specimens demonstrated mild dilatation of tubules, mitochondrial swelling, and minimal myofibrillar loss. Biopsy specimens from patients with stage III disease were similar to those from patients with stage II disease except for an increase of myofibrillar loss. The stage IV specimens had diffuse fibrosis and more severe tubular dilatation, mitochondrial cristolysis, and myofibrillar loss. At autopsy in the proband, the atrial changes were more severe than the ventricular and were especially marked in the sinoatrial and atrial myocardium. Early recognition of the disease and use of pacemakers and antiarrhythmic agents have proved beneficial for affected family members. Thorough family studies of patients with conduction system disease and/or dilated cardiomyopathy are necessary to better understand the hereditary basis and natural course of this category of disease.

Myxomatous mitral valves: collagen dissolution as the primary defect.

We studied the morphologic and histologic characteristics of redundant prolapsing (“myxomatous”) mitral valves from 12 symptomatic patients with severe mitral regurgitation who required mitral valve replacement and compared our findings with those in 13 control valves. The mean surface area of the “myxomatous” mitral valves (MMVs) was 1990 mm and of the control mitral valves (CMVs) was 760 mm2 (p < 0.001). The mean longest diameter of MMVs was 56.4 mm and of the CMVs was 36.8 mm (p < 0.001); the mean shortest diameter of MMVs was 44.8 mm and of CMVs was 22.7 mm (p < 0.001). The mean commissural diameter for MMVs was 50.4 mm and for CMVs was 30.0 mm (p < 0.001). The mean coapting line distance of MMVs was 34.1 mm and of CMVs 22.5 mm (p < 0.001). The mean surface area of the anterior cusp of MMVs was 910 mm2 and of CMVs was 560 mm2 (p < 0.01). The mean surface area of posterior leaflet was 927 mm2 in MMVs and 534 mm2 in CMVs (p < 0.02). CMV densities were nearly uniform (1.07 g/cm3), while the mean density of MMVs was 0.687 g/cm3 (p < 0.01). Dissolution of elastin was only slightly more frequent in MMVs than in CMVs. Myxomatous degeneration, noted in one‐half of CMVs, was found in chordae and pars fibrosa only in MMVs (p < 0.05). Mucopolysaccharide infiltration was more severe in all sites except the annulus in MMVs than in CMVs (p < 0.05). Fragmentation of collagen was severe in either the pars fibrosa or chorda of all MMVs, but was not seen in any CMV in these areas (p < 0.05). Gross morphology (increased surface area, increased diameter and decreased density) and histologic characteristics (collagen dissolution with myxomatous degeneration) allowed clear separation between CMVs and MMVs that produced severe mitral regurgitation. Collagen dissolution in the pars fibrosa and chordae was present only in MMVs, which suggests the primacy of collagen dissolution in mitral valves of patients with severe mitral regurgitation complicating the mitral valve prolapse syndrome. We therefore consider this process to be a disorder of collagen synthesis, content or organization (i.e., a dyscollagenosis).

Altered collagen composition in a prolapsing mitral valve with ruptured chordae tendineae.

A patient presented with mitral valve prolapse, ruptured chordae tendineae, severe mitral regurgitation and congestive heart failure. Pathologic studies demonstrated myxomatous changes of both mitral leaflets. Collagen analysis of the valve and of the chordae tendineae revealed the presence of type I collagen in normal quantities and a striking absence of type III and AB collagens. The altered collagen in this patients mitral valve probably contributed to the development of his mitral valve disorder.

The pattern of myocardial degeneration in nonischemic congestive cardiomyopathy

The histopathologic features of nonischemic congestive cardiomyopathy (CCM) include diffuse and focal fibrosis, vacuolar degeneration, and myofiber hypertrophy. Eleven patients with CCM and five controls were studied. Fibrosis and degree of vacuolization were quantified by means of stereologic techniques; myocardial cell diameter was measured with an ocular micrometer. Five levels of the left ventricular free wall were examined. Area I was immediately subepicardial, and area 5 was immediately subendocardial. In all areas, fibrosis, vacuolization, and fiber diameter were significantly greater in the experimental group than in the control group (P less than 0.05). In addition, fibrosis and vacuolization had an umbrella distribution, which peaked in area 4, the area adjacent to the subendocardium (P less than 0.01). The distributions of fibrosis and vacuolar degeneration suggest compromised blood flow to the inner myocardial layers, with relative sparing of the immediate subendocardial region owing to its proximity to the left ventricular cavity.

Histochemistry of creatine phosphokinase.

Abstract In a preliminary experiment, brief formaldehyde fixation of rat myocardium permitted preservation of creatine phosphokinase (CPK) activity and fine structure. Electrophoresis of the homogenate of the fresh and fixed myocardium demonstrated mitochondrial and three non-mitochondrial CPK isoenzymes. An osmiophilic tetrazolium salt and ferricyanide were used for the electron microscopic demonstration of CPK. With tetrazolium, the reaction products were localized near the inner mitochondrial membrane in the intermembranous space of mitochondria, but the reaction was noted on the matrix side of the membranes with ferricyanide. Reaction was also present in the sarcoplasmic reticulum (SR) of the skeletal muscle. Both heart and skeletal muscle showed diffuse background cytoplasmic reaction. The heat-sensitive brain-type isoenzyme of CPK was present in the extramitochondrial sarcoplasm of the heart muscle. CPK activity was demonstrated in isolated heart mitochondria and skeletal muscle SR. Myocardial degeneration was produced in the rat myocardium by injection of isoproterenol. Two to 4 h after the injection there was an extensive histochemical reduction of CPK activity in the myocardium. Twelve to 24 h after injection, most of the areas with initially reduced CPK reaction recovered the enzyme activity and only the subendocardial layer underwent necrosis without recovery of the CPK activity. The maximal rate of increase in serum CPK activity coincided with the most extensive depletion of the myocardium CPK. Mitochondrial isoenzyme did contribute to elevation of serum CPK and appeared to remain in the injured myocardial cells.

The prognostic significance of lymphocytic infiltration in malignant melanoma of the choroid.

Lymphocytic and plasmocytic infiltration surrounding a malignant tumor probably represents an immunologic response of the host directed against the neoplasm. It has been documented that lymphocytic infiltration has a favorable effect on prognosis in a number of human tumor systems, including cutaneous melanoma. In the present study, 309 consecutive cases of choroidal melanoma were examined for cellular infiltration, and these data were correlated with other histologic parameters and with prognosis. An intense cellular infiltration was found in 15 tumors (4.9%) and a moderate infiltration in 37 (12.0%). Tumors with cellular infiltration were significantly larger and more vascularized than the remaining tumors, which may be related to the accessibility of the immune system to the tumor. There was a higher percentage of poorly differentiated tumors among the tumors with cellular infiltration. However, it does not appear that cellular infiltration favorably influences the prognosis of choroidal melanoma. The 5‐year survival rates of patients with like cell types did not depend upon the degree of cellular infiltration demonstrated by the primary tumor. Although choroidal melanomas are capable of inciting an immune response, this response is apparently ineffective in preventing metastatic spread.

Biochemical and histologic correlates of ventricular end-diastolic pressure☆

The associations of elevated left ventricular (LV) and right ventricular (RV) end-diastolic pressure (EDP) were evaluated in 28 patients with non-ischemic congestive cardiomyopathy. Right-sided endomyocardial biopsies from each patient were evaluated for ATP content, percent fibrosis and myocardial fiber diameter. The resting RVEDP and LVEDP and the post-angiographic LVEDP were correlated with the results from the biopsies. There was a correlation of the LVEDP with the RVEDP (r = 0.67, P less than 0.001) by a linear plot. There was no correlation of any EDP measurement with the percent fibrosis. There was, however, a rough correlation of the myocardial fiber diameter with RVEDP (r = 0.40, P less than 0.05). Myocardial ATP content correlated with the RVEDP (r = -0.53, P less than 0.005), the LVEDP (r = -0.65, P less than 0.001) and the post-angiographic LVEDP (r = -0.72, P less than 0.001). These data demonstrate that an elevated ventricular EDP correlates most closely with depressed levels of myocardial ATP. The myocardial cell diameter correlated less well and there was no correlation of EDP with fibrosis. Metabolic factors may be more important than histologic parameters in the elevated ventricular EDP of non-ischemic congestive cardiomyopathy.

Thrombotic Calcific Mitral Stenosis: Morphology of the Calcific Mitral Valve

We compared the morphology of the calcific stenotic mitral valve (CSMV) with noncalcific stenotic mitral valves (NCSMV) removed at surgery; control valves were obtained at autopsy. X-rays of the excised valves permitted localization and quantitation of calcification. A classification of CSMV applicable to noninvasive techniques based on this methodology is presented. Moderate to heavily CSMV had greater weight, volume, specific gravity, weight per area, with smaller orifice size when compared with NCSMV and controls. Leaflet mobility was obliterated in moderate to heavily CSMV, while most NCSMV had some degree of leaflet mobility.Surface morphology was strikingly different in CSMV with 1) surface ulceration, due to eruption of the underlying calcific focus through valvular endothelium, 2) thrombosis in the areas of ulceration ( associated with symptomatic arterial embolization in four patients), 3) whisker formation, filamentous stalks along the line of valve closure.Calcification in the CSMV is viewed as an active, progressive process resulting in altered physical characteristics of the valve, progressive leaflet immobility and orifice narrowing, and eruptive surface changes with thrombus formation and arterial embolization arising from the CSMV itself. Clinical implications and a rationale for more precise classification of mitral stenosis on the basis of valvular calcification are presented.

Observations on the heart in a case of combined Ehlers-Danlos and Marfan syndromes

Abstract Postmortem cardiac findings in a patient with severe valvular heart disease afflicted with both the Ehlers-Danlos and the Marfan syndromes are presented. Excluding the pathologic features of the heart, the clinical features of the Ehlers-Danlos syndrome included hyperelasticity of the skin, fine scar tissue and marked joint hyperextensibility, while the patients body habitus, kyphoscoliosis and myopia reflected characteristics of the Marfan syndrome. Gross and microscopic cardiac observations correlated well with a connective tissue defect. Comments are made on the present state of knowledge concerning the basic defect in each of these heritable disorders of connective tissue.