BASICS
DESCRIPTION
- Hypertrophic cardiomyopathy (HCM) is a form of primary myocardial hypertrophy, with or without presence of left ventricular outflow tract (LVOT) obstruction; it is characterized by four cardinal features:
- Idiopathic LV hypertrophy (LVH) in absence of other cardiac or systemic disease causing hypertrophy of such magnitude
- Cardiac myocyte and myofibrillar disarray
- Familial occurrence
- Associated sudden cardiac death (SCD)
- System(s) affected: cardiovascular
- Synonym(s): hypertrophic obstructive cardiomyopathy (HOCM); muscular subaortic stenosis (MSS), idiopathic hypertrophic subaortic stenosis (IHSS)
EPIDEMIOLOGY
- The disorder may present at any age.
- It is seen in equal frequency in both sexes, although it is often underrecognized in females and African Americans.
- Apical HCM is a variant seen more often in China and Japan (Yamaguchi apical variant).
Incidence
~1% of patients with HCM die annually, but this is no different from the overall population.
Prevalence
Prevalence of HCM (positive phenotype or gene carrier) in the adult general population is 1:200 (1).
ETIOLOGY AND PATHOPHYSIOLOGY
- LVH
- ≥1 region of LV wall are thickened: classically at the basal anterior septum but may involve posterior septum or LV free wall and apex
- Hypertrophy develops usually in adolescence, with an average 100% increase in LV mass.
- Systolic anterior motion (SAM) of the mitral valve
- Mitral valve abnormalities are primary manifestations of HCM: One or both leaflets may be elongated.
- SAM is the abrupt motion of the MV leaflet toward the septum, which creates dynamic LVOT obstruction in contact with the septum.
- Caused by drag effect of the high-velocity jet caused by ejection through a narrowed LVOT and/or a Venturi phenomenon
- Disorganized myocardial architecture
- Myocytes and myofilaments are laid down in disorganized pattern, with increased matrix components causing myocyte disarray.
- Microvascular disease leads to ischemia and replacement fibrosis.
- Diastolic dysfunction
- Result of reduced ventricular compliance; contributes predominantly to the symptoms of heart failure, such as dyspnea
Genetics
- Inherited as a Mendelian autosomal dominant trait with >50% penetrance and variable expressivity
- 11 sarcomeric gene mutations are known, including, among others, β-myosin heavy chain, myosin-binding protein C, and troponins I and T.
RISK FACTORS
Risk factors for SCD in patients with IHSS include the following (2):
- A prior history of cardiac arrest or spontaneous sustained ventricular tachycardia (VT)
- Family history of premature SCD (especially in first-degree relative(s)
- Unexplained syncope
- Extreme LVH measuring >30 mm
- Hypotensive response to exercise: inability to increase by at least 20 mm Hg or a drop of at least 20 mm Hg
- Nonsustained VT during Holter monitoring
- Other factors that may indicate increased risk are LVOT obstruction (resting gradient >30 mm Hg), LV apical aneurysm, high-risk mutation, delayed enhancement on cardiac MRI
- A predicted risk ≥6% using a novel risk prediction model is classified as high risk by European Society of Cardiology (3).
GENERAL PREVENTION
- Avoid strenuous exercise (particularly involving burst exertion) and heavy lifting (induces Valsalva maneuver).
- Maintain hydration to avoid volume depletion.
- Avoid alcohol.
- Certain drugs, such as nitrates, digoxin, β-agonists, vasodilators, and diuretics, are best avoided, particularly in the presence of increased LVOT gradient.
- Implantable cardioverter defibrillator (ICD) is recommended for patients at high risk for SCD (3)[B],(4)[C].
DIAGNOSIS
HISTORY
- Symptoms of heart failure: dyspnea, paroxysmal nocturnal dyspnea, fatigue
- Angina pectoris
- Palpitations
- Exertional syncope or presyncope
- Symptoms may be worsened by anemia, hot and humid weather, a large meal, alcohol, or fever.
- Clinical symptoms correlate poorly with the severity of LVOT obstruction.
- 50% of these patients have positive family history for HCM (and 50% are sporadic).
PHYSICAL EXAM
- A systolic crescendo/decrescendo murmur from LVOT obstruction is best heard at the left lower sternal border.
- Intensity of murmur is dynamic and changes with maneuvers that affect the degree of obstruction.
- Maneuvers that decrease venous return (e.g., Valsalva, standing position, amyl nitrite) increase intensity of the murmur.
- Maneuvers that increase LV afterload (e.g., handgrip) will soften the murmur.
- Bisferiens pulse
- Double or triple apical impulse
- Prominent S4
- Holosystolic murmur of mitral regurgitation may be heard at the apex.
DIFFERENTIAL DIAGNOSIS
- Valvular aortic stenosis
- Hypertensive heart disease, especially in elderly
- Athlete's heart: differentiated by normal/enlarged LV cavity, regression of LVH on deconditioning, normal diastolic parameters
- Cardiac amyloidosis
- Noonan syndrome, mitochondrial myopathy, and metabolic storage disorders (e.g., Anderson Fabry disease and Friedrich ataxia)
DIAGNOSTIC TESTS & INTERPRETATION
- ECG: common findings (50-90%):
- Nonspecific ST-T wave abnormalities
- LVH: Pediatric-specific criterion of RaVL+SV2 >23 mm may have superiority for screening (5).
- ECG: less common findings (<50%):
- Prominent and abnormal Q waves in anterior precordial and lateral limbs lead
- Left atrial enlargement
- Diffuse, marked, symmetric giant negative T waves in lateral precordial leads seen in patients with apical HCM
- Holter monitoring is recommended (3,4), and findings may include supraventricular tachycardia (SVT), premature ventricular contractions (PVCs), nonsustained VT, and atrial fibrillation.
- Chest x-ray may show cardiomegaly and left atrial enlargement.
- Echocardiogram helps establish the diagnosis most easily and reliably. Typical echocardiogram findings:
- Asymmetric septal hypertrophy with septal-to-free-wall ratio >1.3:1 classically
- LVH (especially LV wall thickness in diastole >15 mm)
- Small LV chamber
- In patients with apical HCM, LV cavity has a spade-like shape.
- Abnormal SAM of mitral valve leaflet
- Continuous-wave Doppler best measures significant dynamic outflow obstruction.
- Evidence of diastolic dysfunction
- Provocative measures, such as inhalation of amyl nitrate/Valsalva/dobutamine/exercise, may be necessary to elicit significant LVOT gradients during echocardiography.
- Stress testing may be used to assess BP response with exercise or to assess for exercise provoked LVOT gradient in symptomatic patients with no significant LVOT obstruction on resting/Valsalva echocardiogram (3,4).
- Cardiac MRI is useful if echo images are suboptimal or LV segmental hypertrophy is seen in an unusual location; delayed gadolinium enhancement is increasingly being considered as an independent risk factor for mortality (3,4).
TREATMENT
- These patients must be counseled against competitive athletics, irrespective of LVOT obstruction, presence of ICD, previous septal reduction therapy, and associated symptoms (3,4).
- Adequate hydration should be maintained.
- Not a high-risk condition for endocarditis prophylaxis
- Genetic counseling may be appropriate.
- Only symptomatic patients will benefit from drug therapy.
MEDICATION
First Line
- β-Blockers
- First-line drugs for patients with provocable gradient
- Indicated for treatment of symptoms (angina/dyspnea) in adults with HCM (obstructive or nonobstructive) (3,4)
- 1/3 to 2/3 of patients experience symptomatic improvement.
- Disopyramide
- Used as an adjunct with β-blockers or calcium channel blockers only because it may accelerate atrioventricular (AV) conduction (3,4)[B]
- Verapamil
- Treatment of those who do not tolerate/respond to β-blockers
- Caution in patients with high gradients/advanced heart failure, given the systemic vasodilatory effects (4).
- Dihydropyridine calcium channel blockers are potentially harmful in HCM patients with resting or provocable obstruction (4)[C].
Second Line
- Atrial fibrillation is common and should be controlled.
- Maintenance of sinus rhythm should be strongly considered (3)[C].
- Amiodarone is most effective for sinus rhythm maintenance in IHSS-associated atrial fibrillation; disopyramide with concomitant β-blockers or verapamil is an alternative option.
- Anticoagulation is recommended in all HCM patients who develop atrial fibrillation irrespective of CHADS2-VASc score (3)[B].
ADDITIONAL THERAPIES
Pregnant patients with HCM:
- Patients who wish to become pregnant should be counseled prenatally regarding its autosomal dominant inheritance.
- In women with HCM who are asymptomatic or whose symptoms are controlled on β-blockers (3,4)[C]:
- Pregnancy is reasonable.
- β-Blockers should be continued, but increased fetal surveillance is warranted for bradycardia or related complications.
- Expert maternal/fetal medical specialist care, including cardiovascular and prenatal monitoring, is recommended.
- Women with gradient >50 mm Hg or with uncontrolled symptoms have increased risk with pregnancy and referral to high-risk obstetrician is indicated.
- Pregnancy with HCM and advanced heart failure is associated with excess morbidity/mortality.
- Should be monitored closely in a tertiary care center during labor because peripheral vasodilatation, fluid shift, and epidural analgesia pose a theoretical risk in presence of LVOT obstruction
- Spinal analgesia is contraindicated. Careful administration of epidural analgesia is controversial.
SURGERY/OTHER PROCEDURES
- Ventricular septal myotomy-myectomy (Morrow procedure)
- First-line therapy for drug-refractory symptomatic patients with obstructive IHSS (3,4)[B] and for relief of obstruction with outflow gradient >50 mm Hg at rest/with provocation
- Most (about 70%) patients achieve subjective improvement in symptoms lasting ≥5 years following their surgery.
- Postoperative complications may include left bundle branch block (LBBB), ventricular septal defect (VSD), and aortic regurgitation.
- Percutaneous alcohol septal ablation
- Controlled alcohol-induced septal myocardial infarction resulting in an akinetic septal segment with instantaneous improvement of the outflow obstruction/gradient
- Preferred in patients at high risk from septal myectomy, those who refuse surgical therapy, and those who have failed surgical myectomy
- Medium- to long-term outcomes reported to be similar to myectomy (6).
- Implantable cardiac defibrillators for prevention of SCD in patient at high risk (3,4)[C]
- Heart transplant is advocated for HCM patients not amenable to other treatment modalities (3,4)[B] and children with refractory symptoms due to restrictive physiology not responding to conventional treatment (4)[C].
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
- Annual follow-up is recommended for stable patients.
- Among the first-degree relatives, screening with ECG and echo is recommended every 12 to 18 months between ages 12 and 21 years and every 5 years in adults, particularly if adverse HCM-related events have occurred in the family.
- Genetic testing can be used for index patient and to help screen first-degree relatives (3,4)[B].
PATIENT EDUCATION
Patients with characteristic phenotype of HCM (LVH) are excluded from all competitive sports except those with low static and dynamic intensity (e.g., golf) (3,4)[C].
PROGNOSIS
Annual mortality of 1% is no different from the general U.S. population. Although HCM may be associated with important symptoms and premature SCD, most of these patients have no or relatively mild disability and normal life expectancy.
COMPLICATIONS
- Sudden death (1% per year), usually due to ventricular arrhythmia
- Atrial fibrillation
- Infective mitral endocarditis
- Progressive heart failure
REFERENCES
11 Semsarian C, Ingles J, Maron MS, et al. New perspectives on the prevalence of hypertrophic cardiomyopathy. J Am Coll Cardiol. 2015;65(12):1249-1254.22 Maron BJ. Contemporary insights and strategies for risk stratification and prevention of sudden death in hypertrophic cardiomyopathy. Circulation. 2010;121(3):445-456.33 Elliot PM, Anastasakis A, Borger MA, et al. 2014 ESC guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). Eur Heart J. 2014;35(39):2733-2779.44 Gersh BJ, Maron BJ, Bonow RO, et al. 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2011;124(24):2761-2796.55 Brothers MB, Oster ME, Ehrlich A, et al. Novel electrocardiographic screening criterion for hypertrophic cardiomyopathy in children. Am J Cardiol. 2014;113(7):1246-1249.66 Steggerda RC, Damman K, Balt JC, et al. Periprocedural complications and long-term outcome after alcohol septal ablation versus surgical myectomy in hypertrophic obstructive cardiomyopathy: a single-center experience. JACC Cardiovasc Interv. 2014;7(11):1227-1234.
CODES
ICD10
- I42.2 Other hypertrophic cardiomyopathy
- I42.1 Obstructive hypertrophic cardiomyopathy
ICD9
- 425.18 Other hypertrophic cardiomyopathy
- 425.11 Hypertrophic obstructive cardiomyopathy
SNOMED
- Hypertrophic cardiomyopathy (disorder)
- Hypertrophic obstructive cardiomyopathy (disorder)
- Hypertrophic cardiomyopathy without obstruction
- Primary idiopathic hypertrophic cardiomyopathy
CLINICAL PEARLS
- HCM should be considered in all patients with a history of unexplained SCD. It is the most common cause of SCD in young athletes in the United States.
- Delayed de novo onset of LVH may occur in midlife.
- Intense competitive sports, strenuous exercise, and heavy lifting should be restricted because of high risk of SCD.