- Clinical science
Hypertrophic cardiomyopathy (HCM) is a genetic condition characterized by left ventricular hypertrophy that is not caused by other cardiac or causative systemic diseases. Patients can be asymptomatic or have chest pain, dyspnea, dizziness, or syncope. Sudden cardiac death may occur. The diagnosis can be established with a resting ECG and echocardiography. Management for all patients involves lifestyle changes and possibly AICD placement, and for symptomatic patients, medical or surgical therapy is indicated. The goals of therapy are to decrease the heart rate to allow for improved left ventricular filling and to reduce LV outflow tract obstruction.
- Second most common cardiomyopathy
- Two types are distinguished: 
- Alongside myocarditis, HCM is one of the most frequent causes of sudden cardiac death in young patients, especially young athletes.
Epidemiological data refers to the US, unless otherwise specified.
HCM is a genetic condition characterized by otherwise unexplained left ventricular hypertrophy. 
- Most common hereditary heart disease
- Autosomal dominant inheritance with varying penetrance
- Most commonly caused by mutations of the sarcomeric protein genes (e.g., myosin heavy chain, myosing binding protein C) → disorganization of myocyte architecture characterized by myofibrillar disarray and fibrosis
- Less commonly due to a mutation in cardiac sarcomeric proteins such as troponin and tropomyosin
- Other conditions that are associated with left-ventricular hypertrophy include the following:
HCM is characterized by hypertrophy of the left ventricle; ; most commonly occurs with asymmetrical septal involvement, which leads to (impaired left ventricular relaxation and filling) → reduced systolic output volume → reduced peripheral and myocardial perfusion. → cardiac arrhythmia and/or heart failure and increased risk of 
Nonobstructive and obstructive HCM 
- Typical features include:
- Increased LV wall thickness with septal predominance , no dilation of left ventricle
- Myofibrillar disarray, interstitial fibrosis, and myocyte hypertrophy
Concentric hypertrophy: a form of cardiac remodeling characterized by parallel duplication of sarcomeres that leads to thickening of the ventricular wall
- In HOCM, concentric hypertrophy is caused by genetic mutations (see “Etiology”).
Concentric hypertrophy can also occur secondary to the following diseases, then potentially mimicking HCM:
- Hypertension and aortic valve stenosis (due to chronic pressure and volume overload); : Chronic hypertension → increased afterload → increased myocardial wall tension → changes in myocardial gene expression → sarcomeres laid down in parallel → increased left ventricular thickness → decreased left ventricular size → diastolic dysfunction
- Storage disorders (e.g., , ) and hereditary syndromes; (e.g., Friedreich ataxia, Noonan syndrome)
- Pathomechanism: increased →LV systolic pressure → prolongation of ventricular relaxation → increased LV diastolic pressure → exacerbation of HCM with further reduction of cardiac output
Mechanisms of obstruction
Systolic anterior motion (SAM) of the mitral valve, results in mitral-septal contact during mid-to-late systole ; caused by either or both:
- Venturi effect: accelerated blood flow through ventricular outflow tract creates negative pressure that pulls the mitral valve towards the septum → increased outflow tract obstruction
- Ejection against an elongated and distorted mitral valve causes leaflets to get pulled into the outflow tract → potential secondary mitral regurgitation
- Muscular obstruction
- Systolic anterior motion (SAM) of the mitral valve, results in mitral-septal contact during mid-to-late systole ; caused by either or both:
- LVOT obstruction is dynamic
- Symptoms: worsen with exercise, dehydration, and use of certain drugs (e.g., diuretics, hydralazine, ACEIs/ARBs, digoxin) 
Physical examination 
- Systolic ejection murmur (crescendo-decrescendo)
- Possible holosystolic murmur from mitral regurgitation
- Sustained apex beat
- S4 gallop
- Paradoxical split of S2
- Pulsus bisferiens: LV outflow obstruction causes a sudden quick rise of the pulse followed by a slower longer rise (biphasic pulse).
Echocardiography is the best initial and confirmatory test. Other investigations (e.g., ECG, CXR, cardiac MRI, exercise testing, and screening for coronary artery disease or genetic diseases) can be done on a case-by-case basis.
Diagnostic criteria 
Both of following are required to make the diagnosis:
Transthoracic echocardiography with Doppler 
- Initial assessment of patients with suspected HCM
- Repeat testing in patients with a new cardiovascular event or change in clinical status
Findings in patients with HCM
- Wall thickness
- Asymmetrically thickened left ventricular wall, (≥ 15 mm); , typically involving the septum 
- LV wall thickness ≥ 30 mm is associated with a high risk of sudden death. 
- Outflow tract abnormalities
- Other findings
- Wall thickness
- Findings more specific to HOCM
- Indication: all patients with suspected HCM
- Classic findings: commonly seen in obstructive HCM
- Other supportive findings
- Associated dysrhythmias: , , or atrial flutter
A normal ECG should prompt further evaluation, as it is only seen in 5–10% of cases. 
- Indication: considered for patients presenting with dyspnea or chest pain of unknown etiology
- Suggestive findings
Exercise testing 
Provocation tests (e.g., exercise testing) are obligatory if no obstruction is discernible at rest.
Exercise echocardiography 
- Indications: to confirm and quantify dynamic LVOT obstruction in patients with inconclusive TTE 
- Findings: LVOT obstruction and/or mitral regurgitation
Treadmill exercise testing 
Cardiac MRI (cMRI)
- Evaluation of ventricular morphology if echocardiographic findings are inconclusive
- Patients with known HCM if additional findings in MRI may require a change in management approach
- Consider in patients with inconclusive risk stratification for sudden cardiac death.
- Evaluation of alternative diagnoses
Genetic testing and family screening: All patients should be assessed for familial inheritance and receive genetic counseling. 
- Indications for genetic testing 
- Considered reasonable in index patients to identify first-degree family members who may be at risk of HCM
- Index patients with an atypical presentation or for whom another genetic cause is suspected
- First-degree relatives: Screen by clinical assessment (with or without genetic testing).
- Patients who undergo genetic testing should receive genetic counseling from someone who is knowledgeable about genetic cardiovascular diseases. 
- Indications for genetic testing 
Assessment for coronary artery disease
- Indicated for patients with chest discomfort for whom a diagnosis of CAD would impact HCM management 
- Includes coronary angiography with levocardiography
- Gold standard for identifying epicardial coronary stenoses
- Used to measure LVOT gradient and hemodynamics
- Considered in patients with an intermediate or high likelihood of CAD
Ambulatory ECG monitor: e.g., 24-hour Holter monitor, 48-hour Holter monitor, or event recorder. 
- All patients
- Asymptomatic patients: No pharmacological or invasive treatment is needed. 
- Symptomatic patients
All patients 
- Avoidance of dehydration
- Maintaining a healthy body weight
- Avoidance of excessive alcohol intake
- Avoidance of strenuous exercise and situations that will likely cause vasodilation (e.g., environmental factors such as high temperatures)
- Absolute indication: known prior history of ventricular fibrillation, sustained ventricular tachycardia, or cardiac arrest
- Relative indications
- Risk stratification: for sudden cardiac death (e.g., documented NSVT)
Symptomatic patients 
The goal of treatment is to alleviate the symptoms of HCM by slowing the heart rate.
Recommended pharmacotherapy 
Initial therapy: for all symptomatic patients with obstructive or nonobstructive HCM
First-line: (e.g., propranolol OR atenolol OR nadolol ) 
- Titrate to goal resting heart rate < 60–65/minute
- Second-line: Nondihydropyridine CCBs
- First-line: (e.g., propranolol OR atenolol OR nadolol ) 
- Additional therapy: to consider adding to beta-blocker or CCB if symptoms are persistent
These medications should be used with caution due to their potential for provoking dysrhythmias (e.g, AV block, QT prolongation) and worsening LVOT obstruction in specific situations (e.g., hypovolemia). Cardiology consultation is advised.
Pharmacotherapy to avoid
- Medications to be avoided in LVOT obstruction
- Medication to be avoided in nonobstructive HCM
These are generally indicated for symptoms that are refractory to medical therapy.
Septal reduction therapy
- Indication: severe symptoms (e.g., dyspnea or chest pain, often NYHA III or IV, exertional syncope or presyncope) due to LVOT obstruction (LVOT gradient ≥ 50 mm Hg) 
- Dual-chamber pacemaker: Consider for patients who are poor candidates for septal reduction therapy.
- Heart transplant: Consider in end-stage nonobstructive HCM when LVEF ≤ 50%.
The following complications can be very challenging to manage and required a specialized approach. Cardiology consultation is advised.
Hypotension: ICU and cardiology consultation required
- Management typically involves fluids and vasopressors with purely vasoconstricting effects and no inotropic effects, e.g., phenylephrine. 
- In patients with severe LVOTO who have cardiogenic shock with pulmonary edema, vasoconstrictors may need to be combined with beta-blockers, e.g., esmolol. 
- Heart failure
- Atrial fibrillation 
- Ventricular dysrhythmias 
We list the most important complications. The selection is not exhaustive.