Heart doi:10.1136/heartjnl-2012-301995
  • Education in Heart
  • Myocardial disease

New approaches to the clinical diagnosis of inherited heart muscle disease

  1. Perry Mark Elliott
  1. UCL Institute of Cardiovascular Science, The Heart Hospital, London, UK
  1. Correspondence to Professor Perry M Elliott, UCL Institute of Cardiovascular Science, The Heart Hospital, 16-18 Westmoreland Street, London W1G 8PH, UK; perry.elliott{at}

Cardiomyopathies are defined as disorders of heart muscle unexplained by coronary artery disease, hypertension, valvular disease or congenital heart disease.1 They are classified by morphological and functional phenotype into hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), restrictive cardiomyopathy (RCM), and arrhythmogenic right ventricular cardiomyopathy (ARVC) subtypes.1 Table 1 shows the European Society of Cardiology working group classification of cardiomyopathies.

View this table:
Table 1

European Society of Cardiology classification of cardiomyopathies

All forms of cardiomyopathy can be caused by genetic and non-genetic mechanisms. The first genetic locus associated with HCM was discovered by linkage analysis2 in 1989 and the responsible gene, β-myosin heavy chain (MYH7), was identified in the subsequent year.w1 Since then, extraordinary progress has been made in the understanding of the molecular genetic background of all inherited heart muscle disorders.3w2 Most genetic forms of cardiomyopathy are inherited as autosomal dominant Mendelian diseases and are characterised by locus and allelic genetic heterogeneity, highly variable intra- and interfamilial expressivity, and incomplete clinical penetrance.1 ,4 This very high level of genotype–phenotype plasticity may result from the influence of modifier genes, epigenetic effects, post-transcriptional and post-translational modifications, and environmental effects.5 ,6

The genetic and phenotypic heterogeneity that characterises all cardiomyopathies pose major clinical challenges. In this article, we focus on the task of diagnosis, exploring how a systematic clinical approach can be used to identify specific disorders and guide the selection of further diagnostic tests, including molecular genetic analysis. The basic premise is that a cardiomyopathy focused approach to history and examination combined with conventional and emerging diagnostic tests can be used to identify clues or ‘red flags’ that suggest particular genetic and non-genetic sub-phenotypes (figure 1).

Figure 1

Step-by-step approach for the diagnosis of inherited heart disease. CK, creatine phosphokinase; LVH, left ventricular hypertrophy.

Family history

While a brief enquiry …