We did a systematic search of Medline and identified 11 370 relevant articles published in the English language from 1960 to July, 2012, which we selected to create a comprehensive balanced appraisal of hypertrophic cardiomyopathy. Most studies were observational and retrospective, but we gave greater weight to publications from the past 10 years that included large cohorts and were evidence-based, statistically powered, and of a controlled investigational design.
SeminarHypertrophic cardiomyopathy
Introduction
Hypertrophic cardiomyopathy is a heterogeneous monogenic heart disease studied for more than 50 years and recognised to be an important cause of arrhythmic sudden death, heart failure, and atrial fibrillation (with embolic stroke).1, 2, 3, 4, 5, 6, 7, 8 In view of the growing complexity of clinical practice, international differences in strategic approaches, and advances in genetic diseases5, 8, 9, 10, 11, 12, 13 and cardiac imaging,14, 15, 16, 17 not surprisingly the diagnosis, natural history, and management of hypertrophic cardiomyopathy have become sources of uncertainty, misunderstanding,18 and debate.9, 11, 12, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28 In this Seminar, we aim to put into current context the rapidly changing and diverse clinical landscape of hypertrophic cardiomyopathy to enhance our understanding of this complex genetic disease.
Section snippets
Epidemiology
Hypertrophic cardiomyopathy is a truly global disease, with cases reported in more than 50 countries on all continents3 and affecting people of both sexes29 and of various ethnic and racial origins, yet with similar causal mutations, clinical course, and phenotypic expression.3, 28, 29, 30, 31, 32, 33, 34, 35 Hypertrophic cardiomyopathy is either under-recognised or clinical diagnosis is delayed, more frequently in women29 and people of African-American origin.30
In diverse regions, including
Nomenclature
Historically, an obstacle to understanding the clinical diversity of hypertrophic cardiomyopathy has been the many names (n=75) given to this disease entity.18 Idiopathic hypertrophic subaortic stenosis or hypertrophic obstructive cardiomyopathy (popular in the UK) misleadingly infer that obstruction to left-ventricular outflow is invariable. Dynamic subaortic gradients are a highly visible feature of hypertrophic cardiomyopathy. About 70% of a hospital-based cohort will have outflow
Basic principles
Findings of genetic studies show that hypertrophic cardiomyopathy is caused by dominant mutations in 11 or more genes encoding thick and thin contractile myofilament protein components of the sarcomere or the adjacent Z-disc (figure 1).5, 9, 10, 11, 12, 13, 36 Of patients who have been genotyped successfully, about 70% have mutations in two genes, β-myosin heavy chain (MYH7) and myosin-binding protein C (MYBPC3). Troponin T (TNNT2) and several other genes each account for 5% or less of cases.5,
Imaging
Suspicion of hypertrophic cardiomyopathy usually follows the onset of symptoms or a cardiac event but can also arise from recognition of a heart murmur or abnormal 12-lead electrocardiogram (ECG) during routine or preparticipation sports examinations, or in pedigree studies.55, 56 Clinical diagnosis is confirmed conventionally by imaging the hypertrophic cardiomyopathy phenotype with two-dimensional (2D) echocardiography,7, 32, 33, 41, 47 cardiovascular MRI (figure 2),14, 15, 16, 57 or both.
Natural history and clinical course
Hypertrophic cardiomyopathy is perhaps unique among cardiovascular diseases, with presentation at any age from infancy to old age.2, 4, 7, 28, 29, 30, 34, 44, 79, 80, 81, 82 A growing number of children with sarcomeric hypertrophic cardiomyopathy are being identified with phenotypic expression at a young age (<10 years, including in infancy) and adults are surviving to advanced ages (>80 years).80, 81 Many patients with hypertrophic cardiomyopathy achieve normal life expectancy with little or
Epidemiology and pathophysiology
Sudden death is the most visible, devastating, and unpredictable consequence of hypertrophic cardiomyopathy,1, 2, 4, 6, 7, 25, 34, 61, 88, 92, 93, 94, 95, 96 although it is relatively infrequent within the vast disease spectrum (about 5% in hospital-based populations).24, 34, 92 Nevertheless, hypertrophic cardiomyopathy is the most common cause of sudden death in young people, with particular predilection for children and young adults (age <30 years),6, 7, 34, 79, 83, 84, 92, 93 although risk
Presentation
Symptoms related to heart failure, which are associated with preserved left-ventricular systolic function (ie, exertional dyspnoea), can arise at virtually any age, but most frequently in middle-aged adults.2, 4, 7, 29, 47, 86, 88, 116 Evolution to severe progressive heart failure disability (ie, New York Heart Association [NYHA] functional classes III or IV) represents a relatively small but important subset of patients, comprising 10–20% of an unselected hospital-based cohort.2, 4, 7, 29, 47,
Atrial fibrillation
Atrial fibrillation is the most common sustained arrhythmia in hypertrophic cardiomyopathy, occurring in about 20% of patients, four times the proportion expected in the general population. Atrial fibrillation affects patients with hypertrophic cardiomyopathy by increasing the risk of heart-failure progression or embolic stroke (prevalence 6%, incidence 0·8% per year),90, 91 which is most substantial in patients with left-ventricular outflow obstruction.
Susceptibility to atrial fibrillation is
Search strategy and selection criteria
References (146)
Hypertrophic cardiomyopathy: an important global disease
Am J Med
(2004)- et al.
A report of the American College of Cardiology Foundation Task Force on clinical expert consensus documents and the European Society of Cardiology committee for practice guidelines
J Am Coll Cardiol
(2003) - et al.
Prevalence and age-dependence of malignant mutations in the beta-myosin heavy chain and troponin T genes in hypertrophic cardiomyopathy: a comprehensive outpatient perspective
J Am Coll Cardiol
(2002) - et al.
Hypertrophic cardiomyopathy phenotype revisited after 50 years with cardiovascular magnetic resonance
J Am Coll Cardiol
(2009) - et al.
Comparison of surgical septal myectomy and alcohol septal ablation with cardiac magnetic resonance imaging in patients with hypertrophic obstructive cardiomyopathy
J Am Coll Cardiol
(2007) - et al.
Surgical myectomy versus alcohol septal ablation for obstructive hypertrophic cardiomyopathy: will there ever be a randomized trial?
J Am Coll Cardiol
(2007) - et al.
The 50-year history, controversy, and clinical implications of left ventricular outflow tract obstruction in hypertrophic cardiomyopathy: from idiopathic hypertrophic subaortic stenosis to hypertrophic cardiomyopathy
J Am Coll Cardiol
(2009) - et al.
Updated meta-analysis of septal alcohol ablation versus myectomy for hypertrophic cardiomyopathy
J Am Coll Cardiol
(2010) - et al.
Relation between severity of left-ventricular hypertrophy and prognosis in patients with hypertrophic cardiomyopathy
Lancet
(2001) - et al.
Gender-related differences in the clinical presentation and outcome of hypertrophic cardiomyopathy
J Am Coll Cardiol
(2005)
Relationship of race to sudden cardiac death in competitive athletes with hypertrophic cardiomyopathy
J Am Coll Cardiol
Comparison of prevalence of apical hypertrophic cardiomyopathy in Japan and the United States
Am J Cardiol
Development of left ventricular hypertrophy in adults in hypertrophic cardiomyopathy caused by cardiac myosin-binding protein C gene mutations
J Am Coll Cardiol
Diagnostic, prognostic, and therapeutic implications of genetic testing for hypertrophic cardiomyopathy
J Am Coll Cardiol
The case for myocardial ischemia in hypertrophic cardiomyopathy
J Am Coll Cardiol
Phenotypic spectrum and patterns of left ventricular hypertrophy in hypertrophic cardiomyopathy: morphologic observations and significance as assessed by two-dimensional echocardiography in 600 patients
J Am Coll Cardiol
Onset of apical hypertrophic cardiomyopathy in adulthood
Am J Cardiol
Prevalence, clinical significance, and genetic basis of hypertrophic cardiomyopathy with restrictive phenotype
J Am Coll Cardiol
Determinants for clinical diagnosis of hypertrophic cardiomyopathy
Am J Cardiol
Right ventricular involvement in hypertrophic cardiomyopathy
Am J Cardiol
Management implications of massive left ventricular hypertrophy in hypertrophic cardiomyopathy significantly underestimated by echocardiography but identified by cardiovascular magnetic resonance
Am J Cardiol
Assessment and significance of left ventricular mass by cardiovascular magnetic resonance in hypertrophic cardiomyopathy
J Am Coll Cardiol
Outcome of patients with hypertrophic cardiomyopathy and a normal electrocardiogram
J Am Coll Cardiol
Clinical challenges of genotype positive (+)-phenotype negative (–) family members in hypertrophic cardiomyopathy
Am J Cardiol
CMR with late gadolinium enhancement in genotype positive-phenotype negative hypertrophic cardiomyopathy
JACC Cardiovasc Imaging
Structural abnormalities of the inferoseptal left ventricular wall detected by cardiac magnetic resonance imaging in carriers of hypertrophic cardiomyopathy mutations
J Am Coll Cardiol
Ventricular fibrillation in MYH7-related hypertrophic cardiomyopathy before onset of ventricular hypertrophy
Heart Rhythm
Task Force 4: HCM and other cardiomyopathies, mitral valve prolapse, myocarditis, and Marfan syndrome
J Am Coll Cardiol
Proposal for contemporary screening strategies in families with hypertrophic cardiomyopathy
J Am Coll Cardiol
Risk factors and mode of death in isolated hypertrophic cardiomyopathy in children
J Am Coll Cardiol
Clinical course of hypertrophic cardiomyopathy with survival to advanced age
J Am Coll Cardiol
Hypertrophic cardiomyopathy with longevity to 90 years or older
Am J Cardiol
Ventricular arrhythmia following alcohol septal ablation for obstructive hypertrophic cardiomyopathy
Am J Cardiol
Long-term effects of surgical septal myectomy on survival in patients with obstructive hypertrophic cardiomyopathy
J Am Coll Cardiol
Clinical profile of stroke in 900 patients with hypertrophic cardiomyopathy
J Am Coll Cardiol
Sudden death in hypertrophic cardiomyopathy: identification of high risk patients
J Am Coll Cardiol
Sudden cardiac arrest in hypertrophic cardiomyopathy in the absence of conventional criteria for high risk status
Am J Cardiol
Circadian patterns in the occurrence of malignant ventricular tachyarrhythmias triggering defibrillator interventions in patients with hypertrophic cardiomyopathy
Heart Rhythm
Long-term survival after cardiac arrest in hypertrophic cardiomyopathy
Heart Rhythm
Hypertrophic cardiomyopathy and sudden death in the young: pathologic evidence of myocardial ischemia
Hum Pathol
Idiopathic hypertrophic subaortic stenosis, I: a description of the disease based upon an analysis of 64 patients
Circulation
Hypertrophic cardiomyopathy: clinical spectrum and treatment
Circulation
Hypertrophic cardiomyopathy: a systematic review
JAMA
Genetic basis of hypertrophic cardiomyopathy: from bench to the clinics
J Cardiovasc Electrophysiol
Contemporary insights and strategies for risk stratification and prevention of sudden death in hypertrophic cardiomyopathy
Circulation
Identifying sarcomere gene mutations in hypertrophic cardiomyopathy: a personal history
Circ Res
Mutations in the gene for cardiac myosin-binding protein C and late-onset familial hypertrophic cardiomyopathy
N Engl J Med
Prevalence and severity of “benign” mutations in the beta-myosin heavy chain, cardiac troponin T, and alpha-tropomyosin genes in hypertrophic cardiomyopathy
Circulation
Mutation type is not clinically useful in predicting prognosis in hypertrophic cardiomyopathy
Circulation
Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy
Circulation
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