hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is a type of cardiomyopathy and is the leading cause of sudden death (from arrhythmias) in infants, teenagers, and young adults.

Terminology

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.

Epidemiology

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 .

Clinical presentation

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.

Pathology

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.

Genetics

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 :

• 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

Subtypes

Morphologically there are several recognized subtypes or phenotypes of hypertrophic cardiomyopathy. It may be classified as :

• 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 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
  • rare
  • 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 / tumefactive hypertrophic cardiomyopathy
  • 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 HCM from a cardiac tumor. The following features of mass-like HCM 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 

Another method is a four-pattern model :

• 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% 

Associations

• LVOT obstruction is present in 70% of cases , it is defined as a gradient >30 mmHg
  • a gradient > 50 mm Hg is often considered the threshold of hemodynamic significance
  • often 'obstructive hypertrophic cardiomyopathy' is used when LVOT obstruction is present
    • most commonly occurs at the basal interventricular septum
    • with 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 SAM (systolic anterior motion) 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: 
  • mitral regurgitation
    • leaflet accessory tissue and elongation may also be observed
  • left auricle dilation
  • papillary muscle abnormalities
    • hypertrophy
    • direct insertion to anterior leaflet of mitral valve
    • antero-internal displacement

Radiographic features

Plain radiograph

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

Echocardiography is the initial and most common imaging modality used in the evaluation of HCM due to its practical utility, availability, and high temporal resolution . It is used for 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.

CT

ECG-gated cardiac CT is not routinely performed for HCM. 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 .

MRI

Cardiac MRI, with its capabilities in evaluating cardiac morphology and function, has emerged as a technique particularly well-suited to HCM 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 HCM 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 . 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
• 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 . The term hypertrophic cardiomyopathy (HCM) came into common use in the latter half of the 1980s replacing IHSS, which was considered an inappropriate characterization.

Differential diagnosis

• 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 HCM, nor is the systolic anterior motion of the mitral valve
  • hypovolemia, myocardial infarctions, and sigmoid septal hypertrophy are three recognized causes