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Hypertrophic cardiomyopathy (HCM) is a type of cardiomyopathy defined by left ventricular hypertrophy, that cannot be only explained by abnormal loading conditions another cardiac, metabolic or systemic disease. It is the leading cause of sudden cardiac death (from arrhythmias) in infants, teenagers, and young adults.
Although hypertrophic cardiomyopathy can generally describe a hypertrophied and non-dilated left ventricle due to any cause, this article focuses on hypertrophic cardiomyopathy in the absence of another systemic or cardiac disease.
There is a slight male prevalence and is present in 1 out of 500 in the general population, probably remaining undiagnosed and asymptomatic in the majority of affected individuals 15.
LVOT obstruction is present in 70% of cases 12, it is defined as a gradient >30 mmHg
- a gradient >50 mm Hg is often considered the threshold of hemodynamic significance 13
- often 'obstructive hypertrophic cardiomyopathy' is used when LVOT obstruction is present
- most commonly occurs at the basal interventricular septum
- with systolic anterior motion (SAM) of the chordal apparatus, the dynamic obstruction may occur deeper within the left ventricle
- hypertrophic papillary muscles may cause obstruction in the mid-cavity
- can be associated with systolic anterior motion (SAM) of the anterior mitral leaflet, which can increase LVOT obstruction and decreased coronary and systemic outflow
- systolic anterior motion of the posterior leaflet, less commonly, may also occur
- other secondary signs include:
- leaflet accessory tissue and elongation may also be observed
- left auricle dilation
- papillary muscle abnormalities
- direct insertion to anterior leaflet of mitral valve
- antero-internal displacement
- mitral regurgitation
The clinical diagnosis can be made by imaging modalities such as echocardiography or cardiac MRI by the demonstration of a maximal left ventricular wall thickness of ≥15 mm in the absence of any other causes of left ventricular hypertrophy 17.
Patients present with symptoms and signs of left-predominant congestive heart failure. Patients with a left ventricular outflow tract (LVOT) obstruction may have additional signs such as an ejection systolic murmur that is classically louder with the Valsalva manoeuver.
The electrocardiogram is abnormal in over 95% of cases; the most common abnormalities include high precordial QRS voltages, secondary repolarization abnormalities (ST-segment depression, T wave inversion), left axis deviation, and deep, narrow so-called "needle-like" q waves, typically in leads I, L, V5 and V6.
Hypertrophic cardiomyopathy is characterized by left ventricular hypertrophy (wall thickness >12-15 mm; normal wall thickness is 12 mm or less, measured during diastole) without obvious etiology. Associated right ventricular hypertrophy may be seen in 15-17% of cases.
Hypertrophic cardiomyopathy is an autosomal dominant genetic disorder with incomplete penetrance involving the cardiac sarcomere. Mutations in a group of related genes that make up the cardiac sarcomere are found in up to 60% of individuals with a family history of HCM and 30% of those without a family history. Commonly affected genes include 12:
- MYBPC3 (myosin binding protein): 30%-40%, chromosome 11
- MYH7 (myosin heavy chain): 20%-30%, chromosome 14
- TNNT2 (cardiac muscle troponin): ~10%, chromosome 1
- TNNI3 (troponin I type 3): ~7%, chromosome 19
- MYL2 (myosin light chain 2): ~4%, chromosome 12
- MYL3 (myosin light chain 3): ~2%, chromosome 3
- TPM1 (tropomyosin 1): ~1%, chromosome 15
Morphologically there are several recognized subtypes or phenotypes of hypertrophic cardiomyopathy. It may be classified as 4,12:
asymmetric hypertrophic cardiomyopathy
- most common morphologic variant (accounts for up to 60-70% of cases)
- disproportionately enlarged ventricular septum, with the anteroseptal myocardium, most commonly involved
- septal hypertrophy can be limited to the subaortic, midventricular, or apical regions
- in adults, septal wall thickness is ≥15 mm or when the ratio of the septal thickness to the thickness of the inferior wall at the midventricular level is greater than 1.5
- in children, septal wall thickness is greater than or equal to two standard deviations above the mean for age, sex, or body size (z score ≥2)
- symmetrical or concentric hypertrophic cardiomyopathy
- second most common
- characterized by diffuse left ventricular wall thickening with an associated decrease in left ventricular cavity size
- diagnosis should be made in the absence of a secondary cause like hypertension, aortic stenosis, or the patient being an endurance athlete
apical hypertrophic cardiomyopathy (Yamaguchi syndrome)
- left ventricular wall thickening is predominantly confined to the apex giving a characteristic 'ace of spades' appearance
- apical thickness ≥15 mm
- ratio of apical wall thicknesses to basal wall thicknesses of 1.3-1.5
midventricular hypertrophic cardiomyopathy
- characterized by left ventricular hypertrophy predominantly localized in the mid-myocardial segment
- gives a characteristic hourglass or dumbbell shape to the left ventricle at cardiac CT and MRI
- can lead to mid-cavity obstruction
mass-like hypertrophic cardiomyopathy 4,12/tumefactive hypertrophic cardiomyopathy 8
- there is an exuberant focal thickening of a segment of the left ventricular wall, simulating a cardiac mass
- cardiac CT and MRI play a crucial role in differentiating this form of hypertrophic cardiomyopathy from a cardiac tumor. The following features of mass-like hypertrophic cardiomyopathy can be useful in differentiation from a suspected cardiac mass:
- presence of contractility
- isointense to myocardium on T1- and T2-weighted images
- first-pass enhancement
- patchy and midventricular type of delayed enhancement
- absence of calcification on CT
burned-out phase: end-stage
- characterized by systolic dysfunction (LV-EF < 50%)
Another method is a four-pattern model 10:
- septal hypertrophy alone ~45%
- septal and other segments hypertrophy but sparing the apex ~ 16%
- apical segments along with any other segment hypertrophy ~ 27%
- apical hypertrophy alone ~ 13%
Chest radiographic findings can vary from normal to an enlarged heart. Chest radiographs are more useful in identifying complications of cardiomyopathy, such as pulmonary edema.
Echocardiography is the initial and most common imaging modality used in the evaluation of hypertrophic cardiomyopathy due to its practical utility, availability, and high temporal resolution 12. It is used for the evaluation of LVOT gradients and obstruction abnormalities, especially during physiologic provocation.
Using pulsed-wave Doppler from an apical 5 chamber view and advancing the gate from an apical to basal position the location of the obstruction may be noted, yielding a characteristic dagger-shaped flow envelope.
ECG-gated cardiac CT is not routinely performed for hypertrophic cardiomyopathy. It does not provide information on fibrosis and flow dynamics. However, cardiac CT offers excellent spatial resolution and serves as an alternative modality in patients in whom MRI is contraindicated 12.
Cardiac MRI, with its capabilities in evaluating cardiac morphology and function, has emerged as a technique particularly well-suited to hypertrophic cardiomyopathy diagnosis and phenotypic characterization. It is superior to echocardiography in identifying areas of segmental hypertrophy not reliably visualized or underestimated by echocardiography (i.e. anterolateral and apical segments). MRI is useful in evaluating hypertrophic cardiomyopathy patients with thin-walled scarred left ventricular apical aneurysms, end-stage systolic dysfunction, massive left ventricular wall hypertrophy, associated thickening of the right ventricular wall as well as substantial morphologic diversity with regard to papillary muscles and mitral valve.
MRI can also demonstrate systolic anterior motion (SAM) of the mitral valve, which along with basal septal hypertrophy, results in LVOT obstruction. Mitral regurgitation may also be noted.
Cardiac MRI plays a key role in risk stratification 12. Negative prognostic indicators in high-risk patients include:
- left ventricular wall thickness ≥30 mm
- gradient across LVOT ≥30 mmHg
- delayed wall enhancement which represents fibrosis
- decreased ejection fraction to <50% (burned-out phase)
- presence of left ventricular apical aneurysms
Cardiac MRI has a role in asymptomatic HCM mutation carriers by identifying phenotypic markers of HCM in the absence of left ventricular hypertrophy including:
- myocardial crypts 12
- elongated mitral valve leaflets
late gadolinium enhancement
- patchy/streaky intramyocardial patterns at the right ventricular insertion sites within the hypertrophied myocardium suggest fibrosis
- prognostic value with increased risk of sudden cardiac death (SCD)
Treatment and prognosis
Treatment depends on the severity of the disease. The goal is to relieve symptoms and prevent sudden cardiac death in high-risk patients. The base of treatment is to control heart rate by avoiding extreme physical efforts and by giving medications (e.g. beta-blockers). Other treatment options include septal myomectomy, septal ablation (alcohol arterial embolization), and placement of an implantable cardioverter-defibrillator device.
History and etymology
Hypertrophic cardiomyopathy was first described and originally termed idiopathic hypertrophic subaortic stenosis (IHSS) by Brent et al. in 1960 11,12. The term hypertrophic cardiomyopathy (HCM) came into common use in the latter half of the 1980s replacing IHSS, which was considered an inappropriate characterization.
systemic hypertension: the commonest secondary cause of concentric LV hypertrophy
athlete's heart: maximal wall thickness usually 13-15 mm, normal diastolic function, detraining can regress the hypertrophy
aortic stenosis: MRI demonstrates restricted aortic leaflet excursion with elevated transvalvular gradients
Danon disease: genetic cause of massive concentric hypertrophic cardiomyopathy, associated with skeletal myopathy and mild intellectual disability
infiltrative cardiomyopathy: can cause systolic and diastolic dysfunction. Fabry disease, hemochromatosis (abnormal T2*), amyloidosis, and glycogen storage diseases
- dynamic left ventricular outflow tract obstruction (LVOTO) is not specific to hypertrophic cardiomyopathy, nor is the systolic anterior motion of the mitral valve
- hypovolemia, myocardial infarctions, and sigmoid septal hypertrophy are three recognized causes 14
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