Hypertrophic Cardiomyopathy
Disease Details
Family Health Simplified
- Description
- Hypertrophic cardiomyopathy is a condition characterized by abnormal thickening of the heart muscle, which can obstruct blood flow and impair the heart's ability to function properly.
- Type
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Hypertrophic cardiomyopathy (HCM) is a genetic cardiovascular disorder characterized by the thickening of the heart muscle, often primarily affecting the interventricular septum.
Type of genetic transmission: HCM is typically inherited in an autosomal dominant pattern. This means that a person needs only one copy of the mutated gene from one parent to potentially develop the condition. - Signs And Symptoms
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Many people are asymptomatic or mildly symptomatic, and many of those carrying disease genes for HCM do not have clinically detectable disease. The symptoms of HCM include shortness of breath due to stiffening and decreased blood filling of the ventricles, exertional chest pain (sometimes known as angina) due to reduced blood flow to the coronary arteries, uncomfortable awareness of the heart beat (palpitations), as well as disruption of the electrical system running through the abnormal heart muscle, lightheadedness, weakness, fainting and sudden cardiac death.Shortness of breath is largely due to increased thickness of the left ventricle (LV), which impairs filling of the ventricles, but also leads to elevated pressure in the left ventricle and left atrium as a result of increased thickness involving the inter ventricular septum obstructing the left ventricular outflow, causing back pressure and interstitial congestion in the lungs. Symptoms are not closely related to the presence or severity of an outflow tract gradient. Often, symptoms mimic those of congestive heart failure (esp. activity intolerance and dyspnea), but treatment of each is different. Beta blockers are used in both cases, but treatment with diuretics, a mainstay of CHF treatment, will exacerbate symptoms in hypertrophic obstructive cardiomyopathy by decreasing ventricular preload volume and thereby increasing outflow resistance (less blood to push aside the thickened obstructing tissue).Major risk factors for sudden death in individuals with HCM include prior history of cardiac arrest or ventricular fibrillation, spontaneous sustained ventricular tachycardia, abnormal exercise blood pressure and non-sustained ventricular tachycardia, unexplained syncope, family history of premature sudden death, and LVW thickness greater than 15 mm to 30 mm, on echocardiogram.
HCM also presents with a systolic ejection murmur that increases in intensity with decreased preload (as in the Valsalva maneuver or standing), or with decreased afterload (as in vasodilator administration). On the other hand, the murmur decreases in intensity with increased preload (as in squatting) or increased afterload (as in the handgrip maneuver). "Spike and dome" pulse and "triple ripple apical impulse" are two other signs that can be discovered in physical examination.Pulsus bisferiens may occasional be found during examination. - Prognosis
- A systematic review from 2002 concluded that: "Overall, HCM confers an annual mortality rate of about 1%... HCM may be associated with important symptoms and premature death but more frequently with no or relatively mild disability and normal life expectancy."
- Onset
- Hypertrophic cardiomyopathy (HCM) typically presents symptoms during adolescence or early adulthood, though it can occur at any age. Some individuals may remain asymptomatic throughout their life. Diagnosis often follows the appearance of symptoms such as shortness of breath, chest pain, or fainting spells, particularly during physical exertion.
- Prevalence
- Hypertrophic cardiomyopathy (HCM) has a prevalence of approximately 1 in 500 individuals in the general population. It is a common genetic cardiovascular disease characterized by thickening of the heart muscle, particularly the ventricles.
- Epidemiology
- The prevalence of HCM in the general population around the world is 0.2% (1 in 500 adults), as determined from echocardiographic studies. HCM is more common in males than in females. The most common presentation of HCM is in the third decade of life, though it can present at any age, from newborns to the elderly.
- Intractability
- Hypertrophic cardiomyopathy (HCM) is not considered strictly intractable. There are various management and treatment options available, including medications such as beta-blockers and calcium channel blockers, lifestyle changes, and surgical procedures like septal myectomy or alcohol septal ablation. However, while the condition can be managed, it often requires long-term care and monitoring, and the underlying genetic cause cannot be cured.
- Disease Severity
- Hypertrophic cardiomyopathy (HCM) disease severity can vary significantly among individuals. It ranges from no symptoms to severe heart-related issues. Some people may live a normal life with minimal or no symptoms, while others may experience severe symptoms such as breathlessness, chest pain, fainting, or life-threatening arrhythmias. HCM can sometimes lead to sudden cardiac death, particularly in young athletes. Regular monitoring and appropriate management are essential for those diagnosed with the condition.
- Healthcare Professionals
- Disease Ontology ID - DOID:11984
- Pathophysiology
- Ventricular hypertrophy causes a dynamic pressure gradient across the left ventricular outflow tract (LVOT), which is associated with further narrowing of the outflow during systole. Pulling of the mitral valve leaflets towards the septum contributes to the outflow obstruction. This pulling is thought to occur by several proposed mechanisms, including that flow of blood through the narrowed outflow tract results in it having a higher velocity, and less pressure through the Venturi effect. This low pressure then causes the anterior leaflet of the mitral valve to be pulled into the outflow tract, resulting in further obstruction.
- Carrier Status
- Hypertrophic cardiomyopathy (HCM) is typically inherited in an autosomal dominant manner. This means that a single copy of the altered gene in each cell is sufficient to cause the disorder. Consequently, carrier status is not generally applicable in the same way it is for recessive conditions, where a person can carry the gene without showing symptoms. Individuals with a mutated gene for HCM often exhibit some form of the disease. However, expressivity can vary, meaning the severity and presence of symptoms can differ greatly among individuals with the same genetic mutation.
- Mechanism
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Hypertrophic cardiomyopathy (HCM) is a genetic heart disorder characterized by the thickening of the heart muscle, particularly the ventricles.
**Mechanism:**
The primary mechanism in HCM involves the thickening of the myocardium (heart muscle), which can lead to obstruction of blood flow out of the left ventricle. This thickening is often asymmetric and predominantly affects the interventricular septum. As a result, the heart's ability to pump blood effectively is compromised, and it may lead to symptoms such as shortness of breath, chest pain, and palpitations. In severe cases, HCM can cause arrhythmias and sudden cardiac death.
**Molecular Mechanisms:**
1. **Genetic Mutations:** HCM is most commonly caused by mutations in genes coding for sarcomeric proteins, which are essential for muscle contraction. The most frequently implicated genes include:
- MYH7 (beta-myosin heavy chain)
- MYBPC3 (myosin-binding protein C)
- TNNT2 (cardiac troponin T)
- TNNI3 (cardiac troponin I)
- MYL2 and MYL3 (myosin light chains)
2. **Sarcomere Dysfunction:** Mutations in these genes lead to dysfunctional sarcomeres (the basic units of muscle contraction), which result in abnormal thickening of the heart muscle fibers. The exact mutations can vary, impacting the protein structure and function, thus leading to varied clinical presentations and severity.
3. **Energy Deficiency:** Mutations may also cause inefficient energy utilization within the cardiomyocytes (heart muscle cells), leading to an energy deficit that further exacerbates hypertrophy.
4. **Cell Signaling Pathways:** Dysregulation of signaling pathways such as the MAPK, PI3K/Akt, and PKC pathways also contributes to pathological muscle growth and fibrosis (scarring).
5. **Calcium Handling:** Abnormal calcium handling within the cardiomyocytes, due to defective sarcomeric proteins, can affect muscle contraction and relaxation, contributing to the overall pathophysiology of HCM.
Understanding these mechanisms aids in diagnosing and developing targeted treatments for HCM, which may range from lifestyle modifications and medications to surgical interventions like septal myectomy or implantable cardioverter-defibrillators (ICDs). - Treatment
- Treatment for hypertrophic cardiomyopathy (HCM) typically includes medications, lifestyle changes, and sometimes surgical interventions. Medications such as beta-blockers, calcium channel blockers, and antiarrhythmic drugs are used to improve symptoms and reduce the risk of complications. Lifestyle changes might involve avoiding intense physical activity and managing other health conditions like hypertension. In some cases, surgical procedures such as septal myectomy or alcohol septal ablation are performed to reduce the thickness of the heart muscle. Implanted devices like implantable cardioverter-defibrillators (ICDs) may also be used to prevent sudden cardiac death.
- Compassionate Use Treatment
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Compassionate use treatment and off-label or experimental treatments for hypertrophic cardiomyopathy (HCM) typically are pursued under specific circumstances when standard therapies are ineffective or unsuitable. Some of these potential treatments include:
1. **Mavacamten (Camzyos)**:
- Initially available through clinical trials, this myosin inhibitor has shown promise in reducing left ventricular outflow tract obstruction and improving symptoms.
2. **Alcohol Septal Ablation**:
- Used as an alternative to surgical myectomy for patients who are not candidates for surgery. This procedure involves injecting alcohol into a small branch of the coronary artery to reduce the thickened heart muscle.
3. **Disopyramide**:
- Although primarily an anti-arrhythmic, it is sometimes used off-label to manage symptoms of HCM due to its ability to reduce the contractility of the heart muscle.
4. **Investigational Gene Therapies**:
- There are ongoing research efforts examining gene therapy to target the underlying genetic causes of HCM, although these treatments are still largely experimental and not widely available.
5. **Beta-blockers and Calcium Channel Blockers**:
- These are often the first line of treatment, but in scenarios where typical beta-blockers (like metoprolol) or calcium channel blockers (like verapamil) are not effective, alternative dosing or combinations may be considered.
Patients considering compassionate use or experimental treatments should be closely monitored by their healthcare provider and thoroughly discuss potential risks and benefits. - Lifestyle Recommendations
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### Lifestyle Recommendations for Hypertrophic Cardiomyopathy (HCM)
1. **Regular Monitoring:**
- Frequent check-ups with a cardiologist.
- Routine echocardiograms and ECGs to monitor heart function.
2. **Physical Activity:**
- Engage in moderate-intensity activities; avoid high-intensity sports and competitive athletics.
- Consult with a healthcare provider before starting any exercise regimen.
3. **Medication Adherence:**
- Take all prescribed medications as directed to manage symptoms and prevent complications.
- Regularly review medications with your healthcare provider.
4. **Dietary Habits:**
- Maintain a balanced diet low in sodium to manage blood pressure.
- Stay hydrated but avoid excessive fluid intake.
5. **Limit Alcohol and Caffeine:**
- Reduce or eliminate alcohol consumption, as it can trigger arrhythmias.
- Limit caffeine to prevent heart palpitations.
6. **Weight Management:**
- Aim for a healthy weight to reduce the workload on the heart.
7. **Avoid Stimulants:**
- Stay away from decongestants and other over-the-counter medications that can increase heart rate and blood pressure.
8. **Stress Management:**
- Practice relaxation techniques such as yoga, meditation, or deep breathing exercises.
9. **Smoking Cessation:**
- Quit smoking and avoid secondhand smoke.
10. **Emergency Preparedness:**
- Have a plan for handling emergencies, including knowing the signs of heart failure and having emergency contact numbers readily available.
11. **Family Screening:**
- Encourage family members to get screened, as HCM can be hereditary.
12. **Medical Identification:**
- Consider wearing a medical alert bracelet that notes your HCM condition. - Medication
- The primary goal of medications is to relieve symptoms such as chest pain, shortness of breath, and palpitations. Beta blockers are considered first-line agents, as they can slow down the heart rate and decrease the likelihood of ectopic beats. For people who cannot tolerate beta blockers, nondihydropyridine calcium channel blockers such as verapamil can be used, but are potentially harmful in people who also have low blood pressure or severe shortness of breath at rest. These medications also decrease the heart rate, though their use in people with severe outflow obstruction, elevated pulmonary artery wedge pressure, and low blood pressures should be done with caution. Dihydropyridine calcium channel blockers should be avoided in people with evidence of obstruction. For people whose symptoms are not relieved by the above treatments, disopyramide can be considered for further symptom relief. Diuretics can be considered for people with evidence of fluid overload, though cautiously used in those with evidence of obstruction. People who continue to have symptoms despite drug therapy can consider more invasive therapies. Intravenous phenylephrine (or another pure vasoconstricting agent) can be used in the acute setting of low blood pressure in those with obstructive hypertrophic cardiomyopathy who do not respond to fluid administration.Mavacamten was approved for medical use in the United States in April 2022.
- Repurposable Drugs
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Repurposable drugs for hypertrophic cardiomyopathy (HCM) include:
1. **Beta-blockers** (e.g., metoprolol, atenolol) to reduce heart rate and myocardial oxygen demand.
2. **Calcium channel blockers** (e.g., verapamil, diltiazem) to improve diastolic function and reduce myocardial contractility.
3. **Disopyramide** for its negative inotropic effect to reduce left ventricular outflow tract obstruction.
4. **Angiotensin II receptor blockers (ARBs)** (e.g., losartan, valsartan) which may have beneficial effects on myocardial fibrosis.
Research is ongoing to identify additional drugs that could be repurposed for treating HCM. - Metabolites
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For hypertrophic cardiomyopathy (HCM), key metabolites involved include:
1. **Lactate**: Elevated levels can indicate impaired myocardial energetics.
2. **Troponin**: An increase can reflect cardiac muscle damage.
3. **Creatine Kinase-MB (CK-MB)**: May be elevated in conditions affecting cardiac muscle.
These metabolites play a role in diagnosing and understanding the severity of HCM. - Nutraceuticals
- There is currently no strong evidence to support the use of nutraceuticals (food-derived substances with health benefits) specifically for the treatment or management of hypertrophic cardiomyopathy (HCM). Treatment for HCM generally focuses on the use of medications, lifestyle modifications, and sometimes surgical interventions to manage symptoms and prevent complications. Always consult a healthcare professional before starting any new treatment regimen.
- Peptides
- In hypertrophic cardiomyopathy (HCM), peptides and nanoparticles (nanotechnology) are emerging areas of research. Specific peptides, such as those targeting heart muscle contraction proteins (e.g., myosin inhibitors), are being studied for therapeutic potential. Nanotechnology, including nanoparticle-based drug delivery systems, is being explored to improve the targeted delivery of these therapeutic agents, potentially enhancing their effectiveness and reducing side effects.