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CHAPTER SUMMARY AND CENTRAL ILLUSTRATION

Chapter Summary

This chapter discusses the epidemiology, pathophysiology, diagnosis, and management of hypertrophic cardiomyopathy (HCM), a common inherited condition. In ~50% of cases, HCM is due to a pathogenic variant in a sarcomere protein gene (see Fuster and Hurst’s Central Illustration) and is inherited as an autosomal dominant trait with incomplete penetrance. Phenocopies should be actively ruled out during diagnostic work-up. The pathophysiology is complex and consists of multiple interrelated factors, including myocardial ischemia, diastolic (and rarely systolic) dysfunction, left ventricular outflow tract (and/or midcavity) obstruction (LVOTO), mitral regurgitation, and atrial fibrillation. Symptoms related to LVOTO are managed medically in the first instance but may require invasive treatment with surgical septal myectomy or alcohol septal ablation. Heart failure is an important cause of death and is treated according to the current standard recommendations. Atrial fibrillation carries a high thromboembolic risk and mandates anticoagulation. Defibrillators are the only effective protection from sudden death in high-risk patients.

eFig 42-01 Chapter 42: Hypertrophic Cardiomyopathy

DEFINITION AND EPIDEMIOLOGY

Hypertrophic cardiomyopathy (HCM) is defined as left ventricular (LV) hypertrophy in the absence of abnormal loading conditions, such as severe hypertension or valve disease, sufficient to cause the observed phenotype.1,2 Echocardiographic studies in healthy young adults suggest a prevalence of around 1:500, with no significant differences across ethnicities or geographical location. Extrapolation based on the autosomal genetic basis of disease has led to speculation that this may be an underestimate.3 Conversely, studies based on electronic health records indicate that the clinically evident prevalence may be closer to 1:2500.4 Large cohorts have a male predominance of 60% to 65%. Ventricular hypertrophy most frequently develops during periods of rapid somatic growth, but can appear de novo at any time from infancy to old age.5,6

The term hypertrophic cardiomyopathy does not indicate a single condition, but rather describes a phenotype that is shared by a range of disorders that can be grouped into familial/genetic and nonfamilial/nongenetic subtypes.7,8 In 50% to 60% of adolescents and adults, HCM is inherited as an autosomal dominant trait caused by mutations in cardiac sarcomere protein genes. Overall, 5% to 10% of HCM cases are caused by phenocopies (disorders with the same phenotype but different etiology) that include metabolic or storage disorders (eg, Anderson–Fabry, glycogen storage diseases), mitochondrial disorders, cardiac amyloidosis, neuromuscular disorders, chromosome abnormalities, and genetic syndromes such as cardio-facial-cutaneous syndromes, RASopathies, and LEOPARD syndrome.9 The prevalence of individual phenocopies varies with age,10,11 and many have a very different natural history from sarcomeric HCM and a correct diagnosis is of paramount importance for patient management, risk stratification, and in some cases (eg, cardiac amyloidosis and Anderson–Fabry disease) to initiate specific treatment.12 The remaining 25% to 30% of HCM cases, that are ...

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