Hypertrophic Cardiomyopathy


Histopathological Changes and Clinical Implications in Patients with Hypertrophic Cardiomyopathy


Vibeke Marie Almaas and Jan Peder Amlie Division of Cardiovascular and Pulmonary Diseases, and Division of Specialised Medicine and Surgery, Oslo University Hospital, Rikshospitalet, University of Oslo


Abstract


Hypertrophic cardiomyopathy (HCM) is a familial disease with a wide clinical spectrum. Many patients have normal life expectancy, some die suddenly – often as adolescents or young adults – whereas only a few develop end-stage heart failure. In the total HCM population, only 25% develop significant left ventricular outflow tract obstruction. The histopathological hallmarks of HCM are general myocyte hypertrophy, regions of myocyte disarray, different types of fibrosis and small-vessel disease. To better understand the disease development and the aetiology of the electrical instability leading to serious arrhythmias and sudden cardiac death (SCD) in these patients, it is important to explore the relationship between histopathological features and clinical findings and outcome in patients with HCM. This article provides a brief overview of this theme.


Keywords Hypertrophic cardiomyopathy, histopathology, disarray, fibrosis, ischaemia, small-vessel disease, sudden cardiac death, heart failure, outcome


Disclosure: The authors have no conflicts of interest to declare. Acknowledgements: The authors thank Erik Heyerdahl Strøm from the Department of Pathology, Oslo University Hospital, for contributing the microscopic photographs. Received: 29 April 2010 Accepted: 24 May 2010 Citation: European Cardiology, 2010;6(2):88–90 Correspondence: Jan Peder Amlie, Oslo University Hospital, Rikshospitalet, Postbox 4950, Nydalen, 0424 Oslo, Norway. E: janaml@medisin.uio.no


Hypertrophic cardiomyopathy (HCM) is a familial disease with a disease-causing mutation in the genes encoding structural components of the cardiac muscle sarcomere in about 60% of cases.1 In a general population of healthy young adults, the prevalence is 1:500.2


clinical spectrum.1


The penetrance is incomplete and age-related with a wide Many patients have normal life expectancy, some


die suddenly – often as adolescents or young adults – whereas only a few develop end-stage heart failure. In the total HCM population, only 25% develop significant left ventricular outflow tract obstruction.3


HCM was first described in 1958 by Teare.4 In the beginning, HCM was


In large reported cohorts of HCM patients, end-diastolic septal thickness averages approximately 20–22mm; however, it may exceed 30mm, can rarely measure up to 50mm and in some patients carrying an HCM disease-causing mutation the septal thickness is in a normal dimension (pre-clinical HCM).1


described as asymmetrical septal hypertrophy of the left ventricle, but it is now clear that practically any patterns of wall thickening may be observed.5,6


The histopathological hallmarks of HCM with general myocyte hypertrophy, i.e. regions of myocyte disarray,7 and small-vessel disease,9


different types of fibrosis8 originate from several autopsy and transplant


studies from HCM patients who suffered sudden cardiac death (SCD) or progression to end-stage heart failure. There are considerably fewer studies from living HCM patients with histopathological evaluation of surgical myectomy specimens or studies of endomyocardial biopsies from the right side of the interventricular septum. In this brief article, the relationship between histopathological features and clinical findings and outcome in patients with HCM will be discussed.


88


Myocyte Disarray


Myocyte disarray is characterised by regions of architectural disorganisation of hypertrophied myocytes and distinct nuclear changes. Adjacent myocytes are arranged obliquely or perpendicularly to each other around foci of interstitial collagen (plexiform fibrosis) in a pinwheel or herringbone pattern. Myocyte disarray is not specific for HCM. This architectural disorganisation of the myocytes has been found, although to a lesser extent, in patients with dilated CM, alcoholic CM, various congenital heart diseases and cardiovascular diseases (systemic hypertension, coronary artery disease and cor pulmonale) and in normal hearts.10


In the majority of cases, myocyte disarray is extensive and >20% of the myocardium will exhibit disarray in at least two tissue blocks.12


This


There is no consensus about the amount of myocyte disarray required to fulfil the criteria for the diagnosis of HCM. Early studies have suggested that 5–10% of ventricular septal myocardium should show disarray.11


In regions with myocyte disarray, Sepp et al. have shown in HCM patients that the intercellular junctions responsible for electromechanical coupling are dispersed over the surface of the myocytes instead of being confined to intercalated discs.13


disorganisation of the intercellular junctions may serve as a substrate for ventricular arrhythmias. Varnava et al.14


concluded that myocyte


disarray is probably a direct response to functional or structural abnormalities of the mutated sarcomeric protein (see Figure 1).


Myocyte Disarray and Clinical Findings In another report from 2001 the same group correlated the pathological findings with cause of death and risk profile in 75


© TOUCH BRIEFINGS 2010


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