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.     

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.     

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.

     

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.     

Myocardial fascicle and fiber disarray in 25 mu-thick sections

We compared the histologic picture of myocardial fiber disarray in thin (4 mu) and thick (25 mu) sections of tissues obtained at autopsy from 18 adults and eight infants with clinically normal hearts, from 10 hearts with concentric hypertrophy (hypertensive patients), nine with myocardial infarction and four with hypertrophic cardiomyopathy (HCM). In the thick sections, so-called bizarre myocardial fiber disarray in thin sections was seen as a bizarre fascicle disarray. Therefore, the usual fiber disarray reported in cases of HCM is actually a fascicle disarray with a three-dimensional complex network. There was no marked difference in distribution and frequency of fascicle disarray among normal adult and infant hearts, and diseased hearts with hypertension and myocardial infarction. In the four hearts with HCM, diffuse bizarre fascicle disarray in the thick section was detected in the septum and anterior and posterior walls of the left ventricles in all cases, and in the lateral walls in one case. In the portions without the diffuse fascicle disarray, the distribution of disarray was the same as that in hearts with no HCM. Such fascicle disarray, including that of HCM, is probably congenital.     

Myocardial contrast echocardiography. A review of clinical studies

A review is presented of to date published studies devoted to contrast echocardiography of the myocardium and covering a total of 169 patients. No complications occurred during investigations; slight transient ECG and haemodynamic changes of less than 30 s duration were not as pronounced as during coronary arteriography. Intracoronary administration of a 3-4 ml solution containing microbubles close to erythrocyte size leads to opacification of the perfused part of the myocardium in echocardiographic image, whereas the echogenity of nonperfused parts remains unchanged. With the use of this method it might be possible to evaluate the significance of coronary stenosis, to diagnose the "disease of small arteries", to assess the collateral circulation, myocardial infarction size, and to quantify the blood flow in various parts of the myocardium in real time. The method is promising for the assessment of myocardial microcirculation as a complement of coronary arteriography.     

Myocardial perfusion scintigraphy in asymptomatic diabetic patients: a critical review

The increasing prevalence of diabetes mellitus and the associated high cardiovascular risk has made the non‐invasive identification of silent coronary heart disease in diabetic individuals an important issue. This strategy could identify higher risk asymptomatic patients with diabetes mellitus in whom coronary revascularization may improve the outcome beyond that achieved by currently recommended medical management. Stress myocardial perfusion imaging has been shown to be effective in detecting coronary heart disease and predicting adverse cardiac events in asymptomatic diabetic patients. However, the clinical utility of myocardial perfusion scintigraphy is debated intensively due to the paucity of prospective and outcome based evidence. The controversy stems from several observational studies, epidemiologic data and cost‐effectiveness analyses. Thus, although several authors and professional organizations advocate the use of stress imaging for screening higher risk asymptomatic diabetic patients, others are cautious in recommending any kind of stress testing in that population. This review is based on a broad survey of the literature and discusses the potential role of stress myocardial perfusion scintigraphy in screening asymptomatic diabetic subjects for coronary heart disease in the current era and in relation with other non‐invasive screening tools. Copyright © 2010 John Wiley & Sons, Ltd.     

Exogenous factors in Crohn's disease. A critical review.

The etiology of Crohn's disease remains elusive. Though there may be a genetic predisposition to the disease, epidemiologic evidence suggests that environmental factors are important. The role of dietary components and enhanced intestinal permeability deserve more attention. From this review of past studies, this investigator believes that ingested compounds may play an important role in the pathogenesis of Crohn's disease. Silica and various silicates provide models of how dietary factors might cause the disease and explain some of its features.     

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.     

Myocardial Bridge: a clinical review.

Human coronary arteries occasionally course intramyocardially--a condition termed Myocardial Bridge. We review the anatomic and pathophysiological basis of the Myocardial Bridge and discuss clinical presentations, prognoses and the current treatment options for this interesting coronary angiographic variant.