Quantitative analysis of myocardial fibrosis in normals, hypertensive hearts, and hypertrophic cardiomyopathy

The distribution of fibrosis was studied quantitatively in the entire left ventricular wall of a transverse slice of the heart from 10 necropsy cases of hypertrophic cardiomyopathy, 10 cases of hypertensive heart disease, and 20 normal adults. The percentage area (mean (SD)) of fibrosis in the left ventricular wall in hypertrophic cardiomyopathy (10.5 (4.3)%) was significantly greater than that in hypertensive heart disease (2.6 (1.5)%) or in normal hearts (1.1 (0.5)%). In hypertrophic cardiomyopathy the percentage area of fibrosis was greater (13.1 (4.8)%) in the ventricular septum than in the left ventricular free wall (7.7 (4.2)%) whereas in hypertensive heart disease and normal hearts values in these two areas were similar. The percentage area of fibrosis in the left ventricular free wall (where myocardial fibre disarray was not extensive even in hypertrophic cardiomyopathy) was greater in hypertrophic cardiomyopathy than in hypertensive heart disease. The percentage area of fibrosis correlated with heart weight in hypertensive heart disease, but not in hypertrophic cardiomyopathy. These results suggest that widespread fibrosis in hypertrophic cardiomyopathy cannot be explained by cardiac hypertrophy alone, and that disarray and other factors are also important in pathogenesis. The increase in the percentage area of fibrosis from the outer to the inner third of the left ventricular free wall in hypertrophic cardiomyopathy and in hypertension probably reflected transmural gradients of wall stress and myocardial fibre diameter. Although fibrosis is not specific to hypertrophic cardiomyopathy, its quantification and analysis of its regional distribution provide information that is useful in investigating the pathophysiology of the disorder.     

Pathological features of hypertrophic cardiomyopathy without asymmetrical septal hypertrophy

In a heart with hypertrophic cardiomyopathy without asymmetrical septal hypertrophy the number of transmural myocytes, the mean size of myocytes, and the percentage area of interstitial space were similar in the ventricular septum and left ventricular posterior wall, whereas in a reported series of 14 hearts with hypertrophic cardiomyopathy with asymmetrical septal hypertrophy the number of transmural myocytes was greater in the ventricular septum than in the left ventricular posterior wall. In hearts with hypertrophic cardiomyopathy without asymmetrical septal hypertrophy the mean size of myocytes was significantly greater than that of normal hearts, but the number of transmural myocytes was not increased. The extent and distribution pattern of myocardial fibre disarray and fibrosis in the left ventricle were similar in hearts with hypertrophic myopathy whether or not asymmetrical septal hypertrophy was present.     

Pathological features of hypertrophic cardiomyopathy without asymmetrical septal hypertrophy.

In a heart with hypertrophic cardiomyopathy without asymmetrical septal hypertrophy the number of transmural myocytes, the mean size of myocytes, and the percentage area of interstitial space were similar in the ventricular septum and left ventricular posterior wall, whereas in a reported series of 14 hearts with hypertrophic cardiomyopathy with asymmetrical septal hypertrophy the number of transmural myocytes was greater in the ventricular septum than in the left ventricular posterior wall. In hearts with hypertrophic cardiomyopathy without asymmetrical septal hypertrophy the mean size of myocytes was significantly greater than that of normal hearts, but the number of transmural myocytes was not increased. The extent and distribution pattern of myocardial fibre disarray and fibrosis in the left ventricle were similar in hearts with hypertrophic myopathy whether or not asymmetrical septal hypertrophy was present.     

Histopathological specificity of hypertrophic obstructive cardiomyopathy. Myocardial fibre disarray and myocardial fibrosis.

The topography and specificity of fibre disarray and fibrosis in hypertrophic obstructive cardiomyopathy were determined in a histological study comprising 40 necropsy hearts--10 with hypertrophic cardiomyopathy, 10 with congestive cardiomyopathy, 10 with aortic valve stenosis, and 10 normal hearts. Seven standard regional sections were sampled from each heart and graded "double-blind" (tissue location and disease entity) for severity and extent of fibre dissarray and four distinct types of myocardial fibrosis. Statistical comparison of the severity and distribution of indices of fibre disarray and fibrosis within each group and between the normal and the disease groups showed that fibre disarray and fibrosis were qualitatively non-specific for hypertrophic cardiomyopathy. However, when fibre disarray was quantified (1) it was significantly increased in hypertrophic cardiomyopathy and allowed separation of hearts with hypertrophic cardiomyopathy from normal hearts and from those with congestive cardiomyopathy and aortic stenosis, (2) it did not vary significantly among sections of the left ventricle (that is, between the septum and the free wall) in hypertrophic cardiomyopathy, (3) it was closely associated with plexiform fibrosis, and (4) it varied independently of wall and septal thickness. Though the histogenesis of fibre disarray is unknown, it probably represents an exaggeration of a non-specific common pathway for many diverse pathophysiological processes.     

Extensive myocardial fiber disarray in aortic and pulmonary atresia. Relevance to hypertrophic cardiomyopathy

Myocardial fiber disarray is a distinctive histopathologic finding seen in asymmetric hypertrophic cardiomyopathy. We studied 14 hearts with aortic atresia and intact interventricular septum, six hearts with pulmonic atresia and intact interventricular septum, eight normal infant hearts matched for age of the study hearts, and one nonadult heart with hypertrophic cardiomyopathy and asymmetric hypertrophy and quantitatively analyzed tissue sections through both ventricles and the septum. Normal hearts had an average overall fiber disarray of 8.7% (range 3.8-17%) of the left ventricle including septum. Hearts with pulmonary atresia had an overall disarray of 70.4% (range 13-97%) of the entire right ventricle, and those with aortic atresia 62.1% (range 26-97%) of the left ventricle. The one infant heart with hypertrophic cardiomyopathy showed 15.5% disorder of the left ventricular free wall, 75% disorder of the septum and 47% overall myocardial fiber disarray. Thus, while quantitative criterion distinguished normal from abnormal hearts, they did not distinguish among the various pathologic states. Although extensive myocardial fiber disarray is not exclusive to, or pathognomonic of, hypertrophic cardiomyopathy, it is a useful finding taken in the context of the overall disease. The sensitivity and specificity of this isolated morphologic observation as an indication of hypertrophic cardiomyopathy may be misleading.     

Quantitative analysis of narrowings of intramyocardial small arteries in normal hearts, hypertensive hearts, and hearts with hypertrophic cardiomyopathy

To clarify the pathophysiologic role of intramyocardial small artery (IMSA) diseases in hypertrophied hearts, narrowings of the IMSA were quantitatively evaluated in 39 autopsied hearts, 10 from patients with typical hypertrophic cardiomyopathy (HCM), four from patients with HCM showing features mimicking dilated cardiomyopathy (DCM-like HCM), 10 from patients with hypertension, and 15 from normal adults. The relations of narrowings of the IMSA to myocytic hypertrophy, myocardial fiber disarray, and fibrosis were also examined. The external caliber and the ratio of the luminal area to the total vascular area (percent luminal area, % lumen) were calculated by an image analyzer in 85 to 203 IMSAs from each patient. The external calibers of the IMSAs were similar among groups of hearts with HCM, hypertensive hearts, and normal hearts but were greater in those with DCM-like HCM. The mean % lumen of the IMSAs was similarly reduced in the hearts with HCM (29 +/- 5% in the ventricular septum and 31 +/- 5% in the left ventricular free wall) and in hypertensive hearts (30 +/- 8% and 31 +/- 7%) compared with that in normal hearts (40 +/- 5% and 38 +/- 5%) and was the lowest in the ventricular septum of hearts with DCM-like HCM (17 +/- 3%). The mean % lumen of the IMSA was inversely correlated with heart weight (r = -.59), the mean size of myocytes (r = -.66 in the ventricular septum, r = -.63 in the free wall), and percent fibrotic area in the septum (r = -.68). The mean % lumen values of the IMSAs in the tissues with and without disarray in the hearts with HCM were similar. Thus IMSA disease is of pathophysiologic importance in patients with HCM, DCM-like HCM in particular, or with hypertension.     

Asymmetric septal hypertrophy in a 41-year-old woman with Noonan's syndrome

A 41-year-old woman had Noonan's syndrome. Her heart was complicated by asymmetric septal hypertrophy, hypertrophy of the left ventricular free wall, severe pulmonary stenosis, and right ventricular hypertension. On autopsy, a quantitative histologic analysis of the heart revealed that the area of disarray was limited both to the ventricular septum and the left ventricular free wall as in a normal heart. This is not typical of hypertrophic cardiomyopathy because the extent of disarray is high in most cases of hypertrophic cardiomyopathy. Some form of hypertrophic cardiomyopathy, however, seemed to be present in this patient because right ventricular pressure overload did not affect the left ventricular free wall. To clarify the relation between hypertrophic cardiomyopathy and Noonan's syndrome, quantitative histologic analysis is necessary.     

Hypertrophic cardiomyopathy: the interrelation of disarray, fibrosis, and small vessel disease

OBJECTIVE—To make a quantitative assessment of the relation between disarray, fibrosis, and small vessel disease in hypertrophic cardiomyopathy.
DESIGN—Detailed macroscopic and histological examination at 19 segments of the left and right ventricle and the left atrial free wall.
PATIENTS—72 patients with hypertrophic cardiomyopathy who had suffered sudden death or progression to end stage cardiac failure (resulting in death or heart transplantation).
MAIN OUTCOME MEASURES—The presence of scarring, atrial dilatation, and a mitral valve impact lesion were noted, and heart weight, wall thickness, per cent disarray, per cent fibrosis, and per cent small vessel disease quantitated for each heart.
RESULTS—Within an individual heart the magnitude of hypertrophy correlated with the severity of fibrosis (p = 0.006) and disarray (p = 0.0002). Overall, however, total heart weight related weakly but significantly to fibrosis (r = 0.4, p = 0.0001) and small vessel disease (r = 0.3, p = 0.03), but not to disarray. Disarray was greater in hearts with mild left ventricular hypertrophy (maximum wall thickness < 20 mm) and preserved systolic function (60.9 (26)% v 43 (20.4)% respectively, p = 0.02) and hearts without a mitral valve impact lesion (26.3% v 18.9%, p = 0.04), but was uninfluenced by sex. Fibrosis was influenced by sex (7% in male patients and 4% in female, p = 0.04), but not by the presence of an impact lesion. No relation was found between disarray, fibrosis, and small vessel disease.
CONCLUSIONS—Myocyte disarray is probably a direct response to functional or structural abnormalities of the mutated sarcomeric protein, while fibrosis and small vessel disease are secondary phenomena unrelated to disarray, but modified by factors such as left ventricular mass, sex, and perhaps local autocrine factors.


Keywords: hypertrophic cardiomyopathy; histopathology; small vessel disease     

Expression and distribution of atrial natriuretic peptide in human hypertrophic ventricle of hypertensive hearts and hearts with hypertrophic cardiomyopathy.

To investigate the ventricular expression of atrial natriuretic peptide (ANP) in human hypertrophic hearts, we conducted an immunohistochemical study of 130 endomyocardial biopsy specimens obtained from the right side of the ventricular septum (RVB), left ventricular free wall (LVB), or both from a total of 80 patients: 44 patients with hypertrophic cardiomyopathy (HCM), 14 with apical hypertrophic cardiomyopathy (APH), 13 with hypertensive hearts (HHD), and nine without hypertrophy (controls). No patients had apparent congestive heart failure. ANP was not seen in ventricular myocytes in controls but was identified in biopsy specimens of hypertrophic hearts, and its distribution was characteristic in each hypertrophic group: 15 RVB (37%) and two LVB (7%) of the HCM group, one RVB (7%) and two LVB (18%) of the APH group, and zero RVB (0%) and five LVB (46%) of the HHD group. Clinical data (including echocardiographic, hemodynamic, and angiographic data) were not directly related to ventricular ANP expression in HCM, APH, or HHD with one exception. In HHD patients, LVB specimens with ANP showed greater ventricular wall thickness than LVB specimens without ANP. According to histological data, however, the ANP-present RVB specimens of HCM or ANP-present LVB specimens of HHD had greater myocyte size than did the ANP-absent specimens. In addition, in HCM patients, the ANP-present RVB specimens showed more severe fibrosis and myofiber disarray than did the ANP-absent specimens. We conclude that a failing state and hemodynamic overload are not likely to be indispensable for ANP expression in human hypertrophic ventricles and that ventricular ANP expression occurs as a response to disease-specific changes: hemodynamic overload in HHD and histological changes such as myocardial fiber disarray, hypertrophy of myocytes, and fibrosis in HCM, which may reflect the characteristic distribution of intraventricular ANP.     

Myocardial fiber diameter and regional distribution in the ventricular wall of normal adult hearts, hypertensive hearts and hearts with hypertrophic cardiomyopathy

Myocardial fiber diameters were measured to determine their distribution throughout the ventricular wall in normal adult hearts, hypertensive hearts and hearts with hypertrophic cardiomyopathy (HCM). In normal adult hearts and hypertensive hearts, the diameter decreased from the inner to the outer third of the left ventricular free wall and from the left ventricular side to the right ventricular side of the septum. In HCM, these regional differences were preserved in the left ventricular free wall, but not in the septum. The diameter was greatest in the middle third of the septum, where myocardial fiber disarray was widely distributed. The diameters of the fibers in the right ventricular side of the septum were significantly larger than those of the fibers in the left ventricular side of the septum in HCM. This finding, in contrast to that in normal adult hearts or hypertensive hearts, was considered to be related to the inward convex curvature of the left ventricular chamber. Although there was no significant difference in the diameter of myocardial fibers in the left ventricular free wall between hypertensive hearts and hearts with HCM, the diameters of those in the right ventricular free wall, in the right ventricular side of the septum and in the middle third of the septum were significantly larger in HCM than in hypertensive hearts. We conclude that there is a transmural variation of myocardial fiber diameter in the left ventricular free wall and the ventricular septum, and such transmural variation in HCM is clearly different from that in hypertensive hearts.     

Myocardial disarray in Noonan syndrome.

OBJECTIVE--To characterise the histopathology of the left ventricular hypertrophy commonly associated with Noonan syndrome by assessing the extent of myocyte disarray and therefore to define one aspect of the relation between this disease and idiopathic hypertrophic cardiomyopathy. DESIGN--Blinded histological analysis. SETTING--Hospital medical school. PATIENTS--Six hearts of children with the Noonan phenotype and isolated ventricular hypertrophy were compared with age and sex matched controls. METHODS--Histological analysis was performed with an image analyser under light microscopy. Representative sections from the entire left ventricular free wall were examined. Results were expressed as the percentage of fields showing disarray related to the number of fields evaluated: 100 fields were examined for each patient. RESULTS--In the patients with Noonan syndrome myocardial disarray was present in the ventricular septum in 24 (5.7)% (mean (SD)) of fields and in the free wall in 22.2 (6.8)%. In the controls disarray was present in the septum in 3.8 (2.3)% of fields and in the free wall in 2.4 (2.8)%. In both regions the extent of disarray was significantly greater in patients with Noonan syndrome (p < 0.0005; 95% confidence interval 14 to 26.3 for the septum: p < 0.005, 95% confidence interval 11.4 to 28.2 for the free wall). CONCLUSIONS--The ventricular hypertrophy associated with Noonan syndrome is histologically similar to hypertrophic cardiomyopathy but whether the two diseases are the expression of the same genetic defect remains to be determined.     

Hypertrophic cardiomyopathy simulating an infiltrative myocardial disease

Congestive heart failure developed in a patient with low electrocardiographic QRS voltages, diffuse thickening of the septum and free cardiac wall, and a reduction in left ventricular internal diameter, which suggested an infiltrative heart muscle disease. Histological examination at necropsy showed hypertrophic cardiomyopathy with symmetrical left ventricular hypertrophy. Myocardial disarray of type 1A disorganisation was extensive and equally distributed in the ventricular septum and the left anterior and left posterior ventricular free walls. Severe fibrosis (40%) was also present and may have been a possible cause of the electrocardiographic abnormalities as well as of the lack of ventricular dilatation.     

Hypertrophic cardiomyopathy simulating an infiltrative myocardial disease.

Congestive heart failure developed in a patient with low electrocardiographic QRS voltages, diffuse thickening of the septum and free cardiac wall, and a reduction in left ventricular internal diameter, which suggested an infiltrative heart muscle disease. Histological examination at necropsy showed hypertrophic cardiomyopathy with symmetrical left ventricular hypertrophy. Myocardial disarray of type 1A disorganisation was extensive and equally distributed in the ventricular septum and the left anterior and left posterior ventricular free walls. Severe fibrosis (40%) was also present and may have been a possible cause of the electrocardiographic abnormalities as well as of the lack of ventricular dilatation.     

Familial hypertrophic cardiomyopathy mimicing typical dilated cardiomyopathy

An autopsied patient who showed typical dilated cardiomyopathy (DCM)-like features and was pathologically diagnosed with hypertrophic cardiomyopathy (HCM) is presented. The patient, a 60-year-old male at the time of death, died of intractable congestive heart failure. At autopsy the heart weighed 570g and showed marked left ventricular (LV) dilatation with a thin wall (ventricular septum/free wall of the LV = 7 mm/8 mm). There was no evidence of significant stenosis in the extramural coronary arteries. Massive fibrosis was found in the middle and outer thirds of the ventricular septum and anterior wall of the LV (48% in the ventricular septum and 9% in the free wall of the LV). As myocytes were not present in the area with massive fibrosis, percent area of disarray was calculated excluding the area of massive fibrosis and found to be 30% in the ventricular septum. Based on the marked increase in the percent area of disarray, this case was diagnosed as HCM. The patient's 37-year-old son showed asymmetric septal hypertrophy on echocardiography (ventricular septum/posterior wall of the LV = 15 mm/11 mm), marked LV hypertrophy on electrocardiography, and diffuse and marked disarray by endomyocardial biopsy. There were also LV dilatation (LV diastolic dimension = 51 mm) and hypokinesis of the LV; as a result, a diagnosis of HCM with features of DCM was made.     

Myocardial disarray at junction of ventricular septum and left and right ventricular free walls in hypertrophic cardiomyopathy.

The abnormality of the myocardium in hearts with hypertrophic cardiomyopathy (HC) was assessed regarding whether the muscle bundle in the mid-wall layer maintains its normal circular and continuous orientation surrounding the left ventricular (LV) cavity. Forty-seven autopsied hearts with HC were examined. The LV wall midway between the base and apex was divided into 6 segments in the transverse plane. Histologically, the circular orientation was destroyed largely or completely due to marked fascicle disarray in 77% of the anterior and posterior junctional segments. In 33% of the middle portion of the ventricular septum and in 34% of the anterior and posterior portions of the LV free wall, the midwall layer showed disarray of muscle fibers or small fascicles. In contrast, the lateral LV free wall was devoid of disarranged fibers in its midwall layer. Myocardial fibrosis usually was predominant in the portion where disarray was marked. There were deep tissue clefts often in the area of junction. In 11 hearts (7 from patients aged > 65 years), the circular unit was intact in almost every segment, as it was in 9 of 10 control hearts. The destruction of the circular unit in the area of septal-free wall junctions in most patients with HC is a previously undescribed morphologic feature of HC. This discontinuity may result from retention of an abnormal fetal myocardial architecture in which the septal latitudinal muscle was continuous with the right ventricular free wall.     

Asymmetric septal hypertrophy and myocardial fiber disarray. Features of normal, developing, and malformed hearts.

The specificity and significance of the asymmetric septal hypertrophy (ASH) and myocardial fiber disarray of idiopathic hypertrophic subaortic stenosis (IHSS) is uncertain. To examine this we studied 215 hearts, including normal embryos, fetuses, children, and adults; and hearts with congenital and acquired disease. Disproportionate septal thickening was present in all embryos and in some abnormal hearts, particularly those with severe right ventricular hypertrophy due to congenital malformations. Some myocardial fiber disarray was present in all hearts at the junctions of interventricular septum and ventricular free wall. In hearts with semilunar valve atresia with intact ventricular septums, and in the infundibulum of some with tetralogy of Fallot, however, extensive fiber disarray was present. Thus, ASH occurs in the normal developing heart and in some malformed hearts with RVH; marked muscle fiber disarray may occur in certain congenital lesions with abnormal systolic contraction. Neither morphologic finding independently or in combination is pathognomonic of idiopathic hypertrophic subaortic stenosis.     

Myocardial disarray. A critical review.

Myocardial disarray or disorganisation is at present a contentious topic, not least because its value as a clinical marker for hypertrophic cardiomyopathy has changed considerably over the years. Initially observed as one of the features of asymmetric septal hypertrophy, disarray has since been promoted as its pathognomonic histological feature, regarded by some observers as the morphological manifestation of a genetically transmitted myocardial defect. Recently, however, it has become evident that myocardial disarray is not limited to hypertrophic cardiomyopathy, but is encountered in hearts with both congenital and acquired conditions, and is also observed in normal hearts. The specificity of disarray for hypertrophic cardiomyopathy is thus seriously questioned. Latterly, it has been suggested that disarray, judged from through-and-through sections of the ventricular midseptum is a highly specific and sensitive marker of hypertrophic cardiomyopathy when considered in quantitative rather than qualitative fashion. The present study sets out to answer the question whether disarray could be the histological expression of the normal but intricate fibre architecture of the heart, a consideration also initiated by debatable definitions of normality and abnormality of myocardial histology. Gross fibre dissections in five normal hearts showed that many sites occurred in which disarray was a natural phenomenon. In five more hearts it was found that the plane of section of a tissue block might profoundly influence the histology. In fact, tissue cubicles sampled from different faces showed a change in histology in the vast majority. Thus the diagnostic significance of myocardial disarray as a marker of hypertrophic cardiomyopathy in the clinical setting almost vanishes; a change in orientation of a tissue section may actually turn "normality" into "disarray".     

Morphological quantification and differentiation of left ventricular hypertrophy in hypertrophic cardiomyopathy and hypertensive heart disease. A two dimensional echocardiographic study

Differentiation between hypertrophic cardiomyopathy and hypertensive heart disease is a diagnostic challenge. M-mode echocardiography only permits assessment of hypertrophy in limited areas of the left ventricular wall. 2-D echocardiography allows visualization of most of the myocardium. To assess the reliability of conventional M-mode echocardiographic and 2-D echocardiographic criteria in patients with hypertrophic cardiomyopathy (HCM) and hypertensive heart disease (HY), 30 patients with hypertrophic cardiomyopathy and 30 patients with hypertension and severe cardiac hypertrophy were examined using M-mode and 2-D echocardiography. Although the M-mode echocardiographic features showed statistically significant differences between the mean values in the two groups, the degree of overlap made the differentiation of the individual patients difficult. The diagnostic sensitivity and specificity of classic echocardiographic features were assessed: ventricular septal thickness greater than or equal to 1.5 cm, 90% and 43% (sensitivity and specificity, respectively); ventricular septal thickness to posterior wall ratio greater than or equal to 1.5, 83% and 56%; cross-sectional area at papillary level greater than 21 cm2m-2, 80% and 73%; septal segment of the myocardial ring at papillary level greater than 6.5 cm2m-2, 80% and 87%; and the combined criteria of cross-sectional area at papillary level greater than 21 cm2m-2 and septal segment greater than 6.5 cm2m-2, 77% and 93%. Quantitative 2-D echocardiography is useful to differentiate patients with hypertrophic cardiomyopathy from those with secondary myocardial hypertrophy due to hypertension. Hypertrophic cardiomyopathy is characterized by a spectrum of different morphological patterns of hypertrophy. Patients with the predominant region of hypertrophy in the anterolateral free wall or the apical region of the left ventricle were not detected with our quantitative method. Patients with this type of hypertrophy are relatively rare in the western population.     

Microvolt T wave alternans in human cardiac hypertrophy: electrical instability and abnormal myocardial arrangement

INTRODUCTION: Although T wave alternans (TWA) is a promising risk marker for myocardial electrical instability, it remains unclear how the presence of TWA is related to myocardial damage. METHODS AND RESULTS: TWA was measured in 28 patients with hypertrophic cardiomyopathy (HCM), 29 patients with hypertensive left ventricular hypertrophy (HLVH), and 15 normal volunteers using a CH2000 system. The amplitude of TWA (Valt) was measured at the lead with the maximum amplitude. Cardiac biopsy was performed in 12 HCM patients, who were divided into two groups (severe and mild) based on histologic findings of myocardial disarray and fibrosis. TWA was positive (Valt > 1.9 microV) in 61% of HCM and 31% of HLVH, despite a nearly identical left ventricular mass index (176 +/- 65 g/m2 vs 175 +/- 39 g/m2). Valt at heart rate = 110 beats/min was significantly greater in HCM with severe disarray and fibrosis than in HCM with mild disarray and in HLVH. CONCLUSION: In HCM patients, a positive TWA test probably is related to abnormal myocardial arrangement (disarray) and/or fibrosis, and it may reflect electrical instability of the myocardium.     

Spontaneously occurring hypertrophic cardiomyopathy in the rat. I. Pathologic features

The gross anatomic and microscopic appearance of the hearts of young and adult WKY/NCrj rats was examined in comparison with that of normotensive Wistar and SHR/NCrj rats. In a substantial number of the WKY rats, the heart weight and thickness of ventricular septum were much greater than those of the Wistar and SHR rats. The ventricular septum to left ventricular free wall thickness ratio was greater than 1.3 in about one sixth of the WKY rats. In most of the hypertrophied WKY hearts, the transverse area of the left ventricular cavity was smaller in relation to the wall area than in the Wistar and SHR rat hearts, although in a few it was greater. Abnormal fiber arrangement, myocyte hypertrophy, and myocardial fibrosis were far more prominent in the hypertrophied myocardium of the WKY rats compared with the Wistar or SHR rats. Intramural arteries with marked wall thickening existed frequently in the hypertrophied and dilated hearts. Electron microscopic examination revealed marked disarrangement of bundles of myofilaments and widened Z-bands in the hypertrophied myocardium. Blood pressure was not elevated in the rats with cardiac hypertrophy. These findings show that a disease of the myocardium with the pathologic features similar to those of hypertrophic cardiomyopathy in man occurs spontaneously in rats.