Differentiation of cardiac amyloidosis and hypertrophic cardiomyopathy. A comparison of familial amyloidosis with polyneuropathy and hypertrophic cardiomyopathy by electrocardiography and echocardiography

The clinical and echocardiographic features of cardiac amyloidosis may closely resemble those of hypertrophic cardiomyopathy, and the disorders may thus be mixed up. The present study was undertaken in an attempt to identify features separating the two conditions by analysis of electro- and echocardiographic findings in patients with familial amyloid polyneuropathy and hypertrophic cardiomyopathy. Twenty-nine patients with familial amyloidosis and 22 with hypertrophic cardiomyopathy were studied. Particular attention was given to the sum of the S wave in V1 and R wave in V5 or V6, the echocardiographic left ventricular mass and cross-sectional area, the presence or absence of asymmetrical septal thickening, granular and sparkling myocardial appearance, thickened heart valves, systolic anterior motion of the mitral valve, and pericardial effusion. A granular and sparkling appearance of the myocardium and thickened heart valves were found to be the best predictors of cardiac amyloidosis, while low QRS amplitudes in relation to echocardiographic left ventricular mass and a pericardial effusion seemed less important. The presence of systolic anterior movement of the mitral valve, a large left ventricular mass and a sum of S in V1 and R in V5 or V6 greater than 35 mm indicated hypertrophic cardiomyopathy. When the four strongest predictors (left ventricular mass, thickened heart valves, a granular sparkling myocardial appearance, and systolic anterior movement of the mitral valve) were used to reclassify the present patients, 28 of 29 amyloidosis patients and 21 of 22 patients with hypertrophic cardiomyopathy were correctly categorized. Noninvasive methods may thus be useful for detecting the myocardial infiltrative process, and cardiac amyloidosis may be confidently diagnosed by typical noninvasive findings together with histopathological documentation of amyloid in an organ other than the heart.     

Familial hypertrophic cardiomyopathy

Two genetically associated observations of the familial cardiomyopathy in a 34-year-old father and 2-day-old son are described. Verification of the lesions is performed by means of macro-and microscopic analysis including the post-mortem contrast cardioventriculography and histotopographic investigation. Specific changes in the interventricular septum and left ventricle are found in both cases as well as asymmetric hypertrophy and elimination of the cavity of the left ventricle in both father and son.     

Progression from hypertrophic cardiomyopathy to dilated cardiomyopathy

The incidence of hypertrophic cardiomyopathy progressing to dilated cardiomyopathy is rare. A patient diagnosed at age 22 and followed for 24 years who progressed to a dilated cardiomyopathy with severe congestive heart failure is reported. Left ventricular dilatation in hypertrophic cardiomyopathy may be due to a complication of surgery, beta-blocker therapy, or myocardial infarction. It may also represent the natural history in a subset of patients with hypertrophic cardiomyopathy.     

Pathological analysis of hypertrophic cardiomyopathy simulating dilated cardiomyopathy

The pathomorphologic features of hypertrophic cardiomyopathy simulating dilated cardiomyopathy in the late stage (HCM-DCM) were compared with those of ordinary hypertrophic cardiomyopathy (HCM). Seven autopsied hearts with HCM-DCM and 11 with HCM were assessed quantitatively using an image analyzer. Unlike HCM, significant left ventricular enlargement and wall thinning were observed in HCM-DCM, and the percentage areas of massive fibrosis and disarray were significantly greater. In HCM-DCM, the disarray was distributed diffusely, whereas massive fibrosis was distributed more intensively in the ventricular septum and anterior wall than in the lateral and posterior wall. Narrowing of intramyocardial small arteries was observed more frequently in HCM-DCM, especially in the ventricular septum and anterior wall, than in HCM. These results suggest that the enlargement and wall thinning of the left ventricle in HCM-DCM are attributable to non-uniform progression of massive fibrosis, which is closely related to small-arterial lesions.     

Posterolateral hypertrophic cardiomyopathy: a rare,but clinically significant variant of hypertrophic cardiomyopathy

Posterolateral hypertrophic cardiomyopathy (HCM) is a rare variant of HCM. Segmental HCM is seen in 12% of cases of HCM. Among the patterns of segmental HCM, posterolateral HCM is the least common type. Our case of an 18-year old male documents this unusual type of cardiomyopathy. In this form of HCM, left ventricular thickness and the extent of hypertrophy might be underestimated by 2-dimensional echocardiography. This case illustrates the echocardiographic and pathologic features of posterolateral HCM.     

Phenotypic diversity in hypertrophic cardiomyopathy

In recent years, the main focus of human genetic studies on hypertrophic cardiomyopathy (HCM) switched from discovering novel genes and defining disease-causing mutations to studies of mutation distribution in disease populations. Eventually these studies will define genotype-phenotype relationships, which may provide clues to understanding the disease process and help to select the most appropriate treatment strategy. Animal models engineered to recapitulate human disease provide a unique tool to investigate the pathogenic mechanisms and evaluate potential therapies. In this review, we present the spectrum of clinical HCM in the context of the genetic heterogeneity of this common human disease. Recent progress made in understanding molecular pathways that result in cardiac hypertrophy and the factors that modify these processes are discussed.     

Genetics of feline hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is characterized by an abnormal increase in myocardial mass that affects cardiac structure and function. HCM is the most common inherited cardiovascular disease in humans (0.2%) and the most common cardiovascular disease in cats (14.7%). Feline HCM phenotype is very similar to the phenotype found in humans, but the time frame for the development of the disease is significantly shorter. Similar therapeutic agents are used in its treatment and it has the same complications, such as heart failure, thromboembolism and sudden cardiac death. In contrast to humans, in whom thousands of genetic variants have been identified, genetic studies in cats have been limited to fragment analysis of two sarcomeric genes identifying two variants in MYBPC3 and one in MYH7. Two of these variants have also been associated with human disease. The high prevalence of the reported variants in non-affected cats hinders the assumption of their pathogenicity in heterozygotes. An in-depth review of the literature about genetic studies on feline HCM in comparison with the same disease in humans is presented here. The close similarity in the phenotype and genotype between cats and humans makes the cat an excellent model for the pathophysiological study of the disease and future therapeutic agents.     

肥厚型心肌病分子遗传学研究进展

肥厚型心肌病(hypertrophic cardiomyopathy,HCM)是一种以常染色体显性遗传为特征的具有遗传异质性的心脏疾病,它是年轻人心源性猝死的首要病因。已发现至少有18种基因的突变可导致家族性肥厚型心肌病,加深对其分子遗传学的认识有利于促进该病的诊断和治疗。现就家族性肥厚型心肌病近期分子遗传学的研究进行了总结。     

The pathology of hypertrophic cardiomyopathy

Sudden cardiac death (SCD) is devastating at any age, but even more so when the individual affected is young and asymptomatic, and the death is entirely unexpected. SCD is a catastrophic complication of hypertrophic cardiomyopathy (HCM) and may be the first manifestation of this disease. HCM is an inherited intrinsic disease of the myocardium characterized by left ventricular hypertrophy without chamber dilatation, in the absence of either a systemic or other cardiac disease, which may cause a similar magnitude of hypertrophy. HCM may be a clinically silent disease. Indeed, the pathologist may be the first to encounter a case of HCM at autopsy. HCM has wide-ranging implications for affected families, who will require cardiac screening and genetic counselling even if mutations are not known. Therefore, prompt and accurate diagnosis of HCM is vital. This review article will focus on the pathological diagnosis of HCM, recent advances in the genetics of this disease, and common pitfalls which may arise, leading to diagnostic uncertainty.