Overview of the disease
Asymmetric hypertrophy of the ventricles combined with left ventricular outflow tract obstruction is an autosomal dominant disease that can be asymptomatic for a long period of time. The most common symptoms are exertional dyspnea, chest pain, etc. The disease is mainly caused by genetic factors and is mainly treated with medication, but surgery is the preferred option for those who fail to receive medication.
Definition
Hypertrophic obstructive cardiomyopathy is an autosomal dominant disease characterized by asymmetric hypertrophy of the ventricles combined with left ventricular outflow tract obstruction.
Hypertrophic cardiomyopathy is defined as hypertrophic obstructive cardiomyopathy if the difference between the left ventricular outflow tract and peak aortic pressure gradient (LVOTG) is ≥30 mmHg at rest, as measured by echocardiography.
Pathogenesis
Accurate epidemiologic data on hypertrophic obstructive cardiomyopathy are not available.
The prevalence of hypertrophic cardiomyopathy is reported to be 200/100,000 in foreign countries, while the prevalence of hypertrophic cardiomyopathy in China is about 80/100,000 after correcting for age and gender.
Causes
Causes
The majority of the disease is autosomal dominant, and 18 genes have been identified as being associated with the disease, most of which are genes encoding myocardial tubulin.
In addition, 5% to 10% of the cases are caused by mutations in other genes or non-genetic diseases, including inborn metabolic disorders (e.g., glycogen storage disease, carnitine metabolism disease, lysosomal storage disease), neuromuscular disorders (e.g., Friedreich ataxia), mitochondrial disorders, systemic amyloidosis, and others.
In addition, 25% to 30% of cases are of unknown etiology.
Pathogenesis
Abnormalities in myonodal contractile and/or regulatory function due to genetic mutations may be the main cause of pathogenesis.
Myocardial hypertrophy and ventricular diastolic dysfunction occur compensatorily due to the increased number of transverse bridges in cardiomyocytes and impaired contractile function of myofibers as a result of gene mutations.
Gene mutations may result in abnormal myocardial Ca2+ dynamics, which in turn increases the intracellular Ca2+ concentration in cardiomyocytes and may ultimately lead to cardiomyocyte disorders, myocardial fibrosis, and myocardial hypertrophy.
Symptoms
Main Symptoms
Some patients are asymptomatic for a long period of time, while a small number of patients will have sudden death as the first clinical manifestation.
The most frequent symptoms are exertional dyspnea, chest pain, fatigue, and palpitations.
Complications
Atrial fibrillation
The disease can lead to left ventricular diastolic insufficiency, which in turn causes excessive atrial pressure and can induce atrial fibrillation.
Patients may experience symptoms of palpitations and chest tightness.
Heart Failure
With the long-term development of this disease, some patients may progress to heart failure, which is characterized by heart enlargement, thinning of the heart muscle, and poor clinical results.
Patients may experience symptoms such as dyspnea and edema.
Sudden death
The presence of outflow tract obstruction in this disease carries a risk of sudden death and is the most common cause of sudden death in adolescents and athletes.
Patients may experience sudden syncope, loss of consciousness, respiratory and cardiac arrest.
Where to see a doctor
Department of Medicine
Cardiovascular Medicine
If you have exertional dyspnea, chest pain, or if a first-degree family member has been diagnosed with this disease, or if the electrocardiogram reveals left ventricular hypertrophy with strain and T-wave inversion, we recommend that you consult the Department of Cardiovascular Medicine in a timely manner.
Cardiovascular surgery
If the diagnosis of hypertrophic obstructive cardiomyopathy has been confirmed, and the pressure difference between the left ventricular outflow tracts is greater than 50mmHg under medication, septal septectomy may be considered, and it is recommended to consult with the Department of Cardiovascular Surgery in a timely manner.
Emergency Department
In case of sudden syncope, severe chest pain, dyspnea, palpitations, etc., it is recommended to consult the Emergency Department promptly.
Preparation
Consultation: Registration, Preparation of Information, Frequently Asked Questions
Tips for seeking medical treatment
If you have fainted, suddenly collapsed, or have sudden onset of numbness or speech impediment, it is recommended that you go to the hospital immediately, or call the emergency number 120.
During the process of calling emergency, you need to accurately describe the location, the current state of the patient and other key information, and listen to the instructions of the emergency personnel.
Medical Preparation Checklist
Symptom Checklist
Especially focus on the time of onset of symptoms, special manifestations, etc.
Are there any symptoms of dyspnea or chest pain? When do they usually occur? How long does it last?
Is it aggravated by exercise or exertion?
Do you experience palpitations and panic attacks? What is the frequency?
Medical History Checklist
Is there any relative in the family with hypertrophic cardiomyopathy?
Have you ever had a syncope? If so, were there any specific symptoms prior to the syncope?
Checklist
Test results in the last 6 months, which can be brought to the doctor’s office
Electrocardiogram (including routine electrocardiogram and ambulatory electrocardiogram)
Echocardiography
Magnetic Resonance Imaging (MRI) of the heart
Coronary CT or coronary angiography
List of medications
Medication use in the last 3 months, if available in a box or package, bring it with you to the doctor’s office
Beta-blockers: metoprolol, bisoprolol, etc.
Non-dihydropyridine calcium antagonists: verapamil, diltiazem, etc.
Diagnosis
Diagnosis is based on
Medical history
Family history of hypertrophic cardiomyopathy.
History of chest pain or dyspnea, dizziness or syncope.
Clinical manifestations
A coarse jet systolic murmur can be heard in the third and fourth intercostal spaces at the left sternal border, and a systolic murmur can often be heard in the apical region.
Electrocardiogram
Electrocardiogram (ECG) mainly shows left ventricular hypervoltage, T-wave inversion and abnormal Q-waves.
If cardiac function permits, an ECG exercise stress test can be performed to further determine the patient’s cardiac function.
Imaging
Echocardiography
Echocardiography can show the structure and function of the heart.
Early manifestations are characterized by asymmetric ventricular hypertrophy without ventricular chamber enlargement, and the septum can be more than 15 mm thick in diastole. Anterior motion of the anterior mitral leaflet (SAM phenomenon) is seen.
Cardiac Magnetic Resonance Imaging
Examines the structure and function of the heart.
Cardiac magnetic resonance shows myocardial hypertrophy, irregular enhancement of the myocardium on delayed scanning, and the SAM phenomenon.
Coronary Angiography
Coronary angiography is used to identify coronary atherosclerotic heart disease (coronary artery disease).
Chest X-ray
It can show the size, shape, position and contour of the large blood vessels of the heart.
Plain chest X-ray heart images can be normal in size or have an enlarged left ventricle.
Cardiac Catheterization
Cardiac catheterization may show increased end-diastolic pressure in the left ventricle
Ventriculography may show deformation of the ventricles, which may be banana, tongue, or fusiform, giving a “ballerina foot” shape.
Endomyocardial biopsy
Myocardial hypertrophy, disordered arrangement, flaky or diffuse fibrosis can be seen, which is valuable for the exclusion of infiltrative cardiomyopathy.
Genetic testing
Hypertrophic obstructive cardiomyopathy has genetic mutations, and patients suspected of having this disease can undergo genetic testing.
Diagnostic criteria
Combined with medical history and physical examination, hypertrophic cardiomyopathy can be diagnosed when echocardiography suggests a diastolic septal thickness ≥15 mm, or ≥13 mm in those with a positive family history, while excluding other causes of ventricular hypertrophy.
Hypertrophic obstructive cardiomyopathy is diagnosed in patients with hypertrophic cardiomyopathy with a resting or exercise stress echocardiogram suggesting a left ventricular outflow tract pressure step difference ≥30 mmHg.
Grading
Clinicians need to assess the patient’s cardiac function status at the time of treatment, often using the New York Heart Association cardiac function classification.
The New York Heart Association (NYHA) categorizes cardiac function in patients with heart disease into 4 classes based on the patient’s ability to live.
Class I: general physical activity is not limited.
Grade II: mild restriction of general physical activity, palpitations and mild shortness of breath after activity, no symptoms at rest.
Grade III: obvious limitation of general physical activity, no discomfort at rest, discomfort, palpitation, dyspnea with minor daily work, or previous history of heart failure.
Grade IV: severe limitation of general physical activity, inability to perform any physical activity, palpitations, dyspnea and other manifestations of heart failure at rest.
Differential Diagnosis
Many diseases such as hypertension and aortic valve stenosis may lead to myocardial hypertrophy, whose symptoms may be similar to those of hypertrophic cardiomyopathy and difficult to recognize. Relevant imaging tests, genetic testing and myocardial biopsy can clarify the diagnosis.
Treatment
Aim of treatment: to relieve symptoms and slow down disease progression.
Treatment principle: reduce left ventricular outflow tract obstruction, prevent sudden death.
Drug therapy
Drugs to reduce left ventricular outflow tract obstruction
Beta-blockers such as metoprolol and non-dihydropyridine calcium antagonists such as verapamil can improve ventricular diastolic function and reduce left ventricular outflow tract obstruction, among which beta-blockers are preferred.
Novel drugs that act on myofibrils
Mavacamten is a novel small-molecule modulator of cardiac myosin that improves myocardial hypercontractility, and thus myocardial diastolic function and prognosis, in patients with HCM by inhibiting troponin-myosin binding and preventing myocardial bridge formation.
The U.S. Food and Drug Administration (FDA) has approved mavacamten for the treatment of adult patients with symptomatic hypertrophic obstructive cardiomyopathy in cardiac function NYHA class II to III. In China, the drug is still in the clinical trial stage and is not yet available.
Interventional therapy
Percutaneous septal alcohol ablation
Percutaneous septal alcohol ablation, also known as percutaneous septal myocardial ablation, may be considered for patients with a pressure gradient of ≥50 mm Hg in the left ventricular outflow tract who have failed to respond to pharmacologic therapy.
Injection of anhydrous alcohol through the septal branch of the coronary artery causes necrosis of the ventricular septum in the area of altered blood supply, which can reduce outflow tract obstruction and mitral regurgitation.
It is indicated for patients with the following hypertrophic obstructive cardiomyopathy:
Patients who have been treated with strict pharmacologic therapy for 3 months, whose basal heart rate is controlled at about 60 beats per minute, who still have severe dyspnea or chest pain symptoms at rest or after light activity, who have had poor results or serious adverse effects of previous pharmacologic therapy, and who are suffering from cardiac insufficiency (NYHA cardiac function class III-IV).
Ventricular septum thickness ≥15 mm.
Surgical treatment
Ventricular septal myocardial resection
Septal myocardial resection may be considered in patients with left ventricular outflow tract pressure gradient ≥50 mmHg who have failed drug therapy.
It is indicated for patients with the following hypertrophic obstructive cardiomyopathy:
Poorly treated with medications and still have dyspnea or chest pain (NYHA cardiac function class II-IV) or other symptoms (e.g., syncope, syncope with aura).
For some patients with mild symptoms (NYHA cardiac class I) but with moderate-to-severe mitral valve closure insufficiency, atrial fibrillation, or significant left atrial enlargement.
Heart Transplantation
Heart transplantation may be considered in patients with end-stage heart disease, especially in NYHA class III or IV, who have not responded to all conventional treatments.
Implantation of a permanent pacemaker
A permanent pacemaker may be implanted in patients who have indications for pacemaker implantation, are in sinus rhythm and not responding to medication, are not candidates for percutaneous septal myocardial ablation or surgical septal septal septectomy, or are at high risk for postoperative heart block.
In addition, AV node ablation with permanent pacemaker implantation may be considered when pharmacologic control of ventricular rate is unsatisfactory in the presence of atrial arrhythmias.
Implantable cardioverter-defibrillator (ICD) implantation
ICD implantation is necessary for the prevention of sudden death in patients with risk factors for sudden death and after assessment of the risk of sudden death.
Risk factors for sudden death include:
Previous cardiac arrest.
Sudden death in a first-degree relative.
Severe left ventricular hypertrophy (≥30 mm).
Previous unexplained syncope.
High left ventricular outflow tract hyperpressure step difference.
Prognosis
Cure.
There is no complete cure for this disease; the key to treatment is to reduce left ventricular outflow tract obstruction and prevent sudden death.
Prognostic factors
Early onset of cardiac enlargement and heart failure have a poorer prognosis.
Patients with risk factors for sudden death are at higher risk of sudden death.
Hazards
Delayed progression of the disease can lead to heart enlargement, heart failure, and ultimately to the need for heart transplantation.
Some patients are at risk of sudden death.
Daily
Daily management
Life management
Go to bed early and get up early, avoid staying up late.
Avoid over-exertion, avoid excessive high-intensity exercise, which may induce sudden death, and moderate exercise under the guidance of a physician.
Avoid coffee, strong tea, quit smoking and drinking.
Diet management
Avoid overeating, try to eat small and frequent meals, and try to make the food soft and easy to digest.
Minimize the intake of high salt and high fat foods, such as salted vegetables, fatty meat, fried foods, etc.
Emotion Management
Avoid bad emotions such as tension, anxiety, anger and depression.
Keep a good attitude and face life positively.
Follow-up and review
For those with stabilized condition, it is recommended to have checkups every 12 to 24 months, including 12-lead electrocardiogram, transthoracic echocardiography, and 48-hour ambulatory echocardiography test; exercise load checkups every 2 to 3 years; and cardiac magnetic resonance imaging checkups every 5 years.
For those in sinus rhythm and with a left atrial internal diameter ≥45 mm, 48-hour ambulatory cardiographic testing is recommended every 6 to 12 months.
For patients with progressive disease, 12-lead electrocardiography and transthoracic echocardiography may be performed in a timely manner; exercise stress testing every 2 to 3 years; and cardiac magnetic resonance imaging every 5 years.
Prevention
This disease is mostly hereditary, without effective preventive measures. Those with family history should do relevant examinations in time and genetic testing if necessary for early detection and intervention.