Hypertrophic Cardiomyopathy

What is Hypertrophic Cardiomyopathy?

Hypertrophic cardiomyopathy, or HCM, is a type of heart disease that can be passed down through families. It’s caused by changes in parts of genes related to the heart’s muscle structure and function. This disease can lead to a thicker heart muscle wall on the left side of the heart, blockages in the blood flow out of the heart, problems with the heart filling with blood, lack of oxygen to the heart muscle, irregular heart rhythms, issues with the heart’s natural racing and slowing functions and leakage from the mitral valve, which is the heart valve that controls the flow of blood in the left part of the heart. HCM was once referred to as idiopathic hypertrophic subaortic stenosis. It is the most frequently found cause of sudden heart-related death in healthy people under 35 in the United States, including well-trained athletes.

While some 60% of people with HCM have a known gene mutation impacting the heart or related parts, it’s critical to gather a thorough family health history to determine a patient’s risk level. A comprehensive patient history combined with a complete physical exam can also help identify those at risk of a harmful irregular heart rhythm. Symptoms of these heart structure and function abnormalities can include fatigue, shortness of breath, chest pain, abnormal heartbeats, and fainting. Early treatment that may include medication, the placement of a device to control irregular heart rhythms, and surgery when needed, has significantly increased the survival rates of people with HCM in the last few decades.

What Causes Hypertrophic Cardiomyopathy?

In about 60% of cases, Hypertrophic Cardiomyopathy (HCM) – an inherited heart condition where the heart muscle becomes abnormally thick – is passed down in families. This is called ‘familial’ HCM and it’s passed down in what’s known as a ‘dominant’ way, meaning you only need to get the faulty gene from one parent to develop the condition. Yet, this genetic disorder can present itself unpredictably, even among members of the same family.

For those diagnosed with HCM and have a known harmful gene variant, the two most commonly detected genes are β-myosin heavy chain 7 (MYH7) and myosin-binding protein C3 (MYBPC3). These genes are found in about 75% of patients who are known to have a variant. There are also less common genetic variants that mainly involve proteins involved in muscle contraction. However, these mutations are found less often, accounting for about 1% to 5% of patients.

Overall, over 1500 variations causing HCM have been identified, and most of these are unique to each family. However, it’s important to note that there isn’t a clear link between the prognosis (how the disease will likely progress) and specific gene mutations.

Interestingly, a significant number of people diagnosed with HCM do not have a known genetic reason for their condition. This includes some patients who don’t have any family members with the disease – this is known as “nonfamilial” HCM. These observations imply that there might be other unknown processes contributing to this condition. There’s also recent studies linking abnormal calcium behavior in heart muscle cells to the thickening of heart muscle and specific features of HCM, especially in patients with abnormal heart relaxation.

Risk Factors and Frequency for Hypertrophic Cardiomyopathy

It’s estimated that hypertrophic cardiomyopathy (HCM) affect about 0.2% of the worldwide population, the equivalent of 1 in 500 adults. This estimation is based from echocardiography, which is a type of heart scan. Some interesting facts about this condition are:

• About 25% of close family members of people with HCM also show signs of the condition.
• HCM tends to be more common in males, despite any person, regardless of their gender, can inherit it.
• Evindence suggests women generally get diagnosed later than men and might have more serious outcomes, hinting that we might need to revisit how we diagnose the condition.
• The most usual time for people to be diagnosed with HCM is in their 30s, however, it can appear at any age, even in newborns or older people.

Signs and Symptoms of Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is a condition that can be present without symptoms, or only mild ones, in up to 50% of diagnosed individuals—especially those without left ventricular obstruction (LVOTO). When exploring a patient’s history, it’s important to consider both their own experiences and their family’s health history.

• Family history of HCM, sudden cardiac death, unexplained fainting
• Personal history of chest pain, fainting, unexplained dizziness, palpitations, shortness of breath

Shortness of breath and chest discomfort are often a result of diastolic dysfunction and LVOTO. Chest pain can feel like typical or atypical chest tightness related to heart disease. Those with LVOTO may have more severe symptoms after a heavy meal. Dizziness and fainting can occur at rest or during physical activity, with irregular heartbeat patterns or dynamic LVOTO often being the causes. Palpitations are also common and could point to underlying episodes of atrial fibrillation or ventricular arrhythmia. Sudden cardiac death is the most severe symptom.

Physical examinations usually reveal characteristics like a “jerky” pulse with rapid upstroke and downstroke, a normal first heart sound and split second heart sound, an additional heart sound due to decompensated heart failure, a strong “a wave” of jugular venous pressure, a laterally displaced apical impulse, and a double carotid pulse. A fourth heart sound is also common with left ventricular hypertrophy (LVH).

A distinct mid-systolic ejection murmur at the left border of the sternum can have its intensity affected in different ways:

• Decreased intensity with increased preload (squatting) or afterload (handgrip)
• Increased intensity with a decrease in preload (Valsalva maneuver, standing) or with any reduction in afterload (vasodilator administration)

Exercise will also increase the murmur. If mitral regurgitation is present, there may be a continuous, blowing murmur that is loudest at the apex of the heart.

Testing for Hypertrophic Cardiomyopathy

If you have a family history of Hypertrophic Cardiomyopathy (HCM) – a disease that makes the heart muscle excessively thick -, have experienced heart-related issues or have had abnormal results from a routine heart health checkup, your doctor may suggest further evaluations. This usually includes gathering comprehensive information about your health and your immediate family’s heart health history. Your physical examination could include specific tests that provoke a reaction from your heart. Your doctor will also probably want to get an electrocardiogram (ECG), a test that checks the heart’s electrical activity, and do some imaging to check for enlarged heart muscles.

Your doctor may order some blood tests to further understand your condition. These might include tests to measure Troponin I and T, proteins that elevate with heart muscle damage, and hormonal tests to check for stress and damage on the heart muscles and the entire heart’s function.

An ECG can show abnormalities even if there’s no obstruction in the left ventricle outflow tract (LVOTO), a part of your heart. Certain changes in the ECG reports may indicate the thickening of the septal wall of the heart, a characteristic sign of HCM.

An echocardiogram, which is an ultrasound of your heart, can show changes typically seen in HCM, such as thickening of heart walls. This test can also provide other vital information regarding your heart’s function and structure. In cases where an echocardiogram does not provide clear images, the doctor might use a specific contrast material or opt for a cardiac magnetic resonance imaging scan (cardiac MRI).

A cardiac MRI provides more detailed images of the heart’s structure, can detect fibrous tissues in the heart, and, with the use of a contrast agent, can also detect a characteristic sign of heart muscle damage termed late gadolinium enhancement. This technique is increasingly being used to evaluate HCM.

Your doctor could also order a 24- to 48-hours heart rhythm monitoring using Holter monitor and an exercise stress test, especially for assessing your risk of severe heart rhythm problems and sudden death associated with HCM.

In some situations, your doctor may advise additional testing including cardiac catheterization, a test to understand your heart’s function, and electrophysiological studies to determine the cause of abnormal heart rhythms.

Unfortunately, HCM is a major cause of sudden cardiac deaths in young athletes. Hence, if you are a young athlete with fainting episodes or a family history of fainting or sudden cardiac death, you may require an ECG, echocardiogram or possibly an MRI for early detection of HCM. Also, guidelines currently recommend against competitive sports and strenuous exercise for most people with HCM due to the associated risk of sudden deaths. However, the final decision regarding the level of physical activity should be a result of a detailed discussion with your doctor regarding possible risks and benefits.

Treatment Options for Hypertrophic Cardiomyopathy

Treatment strategies for Hypertrophic Cardiomyopathy (HCM) – a condition where parts of the heart muscle become thickened – are usually based on observed data and doctors’ experiences because large clinical trials have not been done. The first choice of treatment usually revolves around medication. This can include drugs called negative inotropic agents like beta blockers or calcium channel blockers, both of which make the heart contract less forcefully and more slowly, or disopyramide.

A new medication approved in 2022 by the Food and Drug Administration (FDA), called mavacamten, specifically treats a form of obstructive HCM. Essentially, it works by temporarily blocking the interaction between proteins in the heart muscle cells, which in turn makes the heart pump less forcefully. This helps relieve the blockage in the heart’s left ventricle, or the left lower chamber, which improves blood flow and eases symptoms. Mavacamten is currently used for adults who have symptoms of heart failure due to obstructive HCM. However, it can cause side effects such as dizziness, fainting, and shortness of breath, and may cause heart failure if not monitored and adjusted properly.

Beta-blockers are usually the primary treatment for most people with HCM as they can help reduce the symptoms. However, different individuals may require different dosages. Calcium channel blockers, such as diltiazem and verapamil, are often used to help ease symptoms in individuals with obstructive HCM, but their use may be limited due to potential side effects. Disopyramide, another type of medication, might also be used in some instances to reduce blockages and symptoms in HCM, even though it is not its primary use. Depending on the person’s condition, diuretics, drugs that help remove excess fluid, could also be given. However, some medications could potentially worsen symptoms.

Healthcare providers also consider other interventions, such as the use of an Implantable Cardiac-Defibrillator (ICD). These devices are implanted into the chest or abdomen to help regulate abnormal heart rhythms and have been noted to lower mortality rates for HCM over the last couple of decades. They are particularly considered for individuals who have risk factors for sudden cardiac death.

If a patient doesn’t respond well to medication, surgical intervention may be considered. This might include left ventricular septal myectomy, a type of open heart surgery that removes part of the thickened heart muscle, to relieve the obstruction in the heart’s left lower chamber. Alternatively, alcohol septal ablation may be performed, a procedure that involves injecting alcohol into the heart to kill the cells causing the blockage. Atrial fibrillation, a type of irregular heart rhythm, is commonly related to HCM. If required, a surgery called a Maze procedure can also be performed to resolve or reduce this issue.

Radiofrequency ablation – a technique that uses heat to destroy part of the heart muscle that’s causing the abnormal heart rhythm – is another newer technique being explored for left ventricular septal reduction. But more studies are needed to fully understand the benefits and potential risks, such as fluid build up around the heart that needs to be drained. As a last resort, a heart transplant may be recommended in cases where all other treatments have failed.

What else can Hypertrophic Cardiomyopathy be?

When diagnosing HCM (Hypertrophic Cardiomyopathy), it’s important to rule out other similar health conditions first. These can include:

• Fabry disease: An inherited illness characterized by a deficiency in the α-galactosidase enzyme. Its symptoms often include skin abnormalities called angiokeratomas and peripheral nerve damage.
• LEOPARD syndrome: Affected people typically show a high number of skin spots known as lentigines.
• Amyloidosis: This condition may be the cause of thickening in heart chambers. Symptoms can include wrist pain (carpal tunnel syndrome), kidney issues (nephrotic syndrome), or skin changes. An ECG might show artery blockage and an echocardiogram might display a “sparkling” texture.
• Danon disease: It’s an inherited disease that stores glycogen in cells leading to skeletal muscle weakening, heart conditions, and intellectual disability.
• Friedrich ataxia: This is the most common genetically passed down cause of unsteady movements, speech difficulty, and other motor coordination issues.
• Aortic stenosis or insufficiency/pulmonary hypertension: These illnesses could modify the appearance of the heart and its valves causing LVH (left ventricular hypertrophy), which is similar to HCM. An echocardiogram can help identify these abnormalities.
• Athlete’s heart: A history of athletic activity and strenuous training can differentiate it from HCM. Though, the heart’s contractility reserve or pumping strength is increased, it might not be evident in an echocardiography. A CMR (Cardiovascular Magnetic Resonance) can be helpful in differentiating these conditions.
• Hypertensive heart disease: Broad atherosclerotic changes and a history of chronic high blood pressure should point towards this diagnosis. Though, HCM is also linked with extra forward motion during the heart’s pumping phase, a biased involvement of the heart’s different portions, something not typically seen with hypertensive heart disease.

As a result, physicians must consider these possibilities and conduct appropriate tests to arrive at a precise diagnosis.

What to expect with Hypertrophic Cardiomyopathy

Understanding how hypertrophic cardiomyopathy (HCM – a condition where the heart muscle becomes abnormally thick) may progress is really important for doctors in planning the best care for their patients. Different factors can have a big impact on what happens in the long term. These include: when the condition starts, whether there are genetic mutations involved, how thick the heart muscle becomes, whether there are any symptoms, and any complications that arise.

In the past, the annual death rates for people with HCM were estimated to be between 1% and 4%. Thanks to appropriate treatments, that number is thought to be now closer to 0.5%.

Even though many people with HCM may not experience any symptoms, the condition can sometimes first show itself through sudden death caused by very dangerous irregular heart rhythms. Also, an enlarged left atrium (one of the four chambers of the heart) – more than 48 mm across or more than 118 mL in volume – has been linked to an increased risk of death, heart failure (when your heart doesn’t pump blood as well as it should) and atrial fibrillation (irregular, often rapid, heart rate).

Possible Complications When Diagnosed with Hypertrophic Cardiomyopathy

Hypertrophic Cardiomyopathy (HCM) complications can introduce significant problems in managing the condition and predicting its course. Knowing the variety of complications related to HCM is key for doctors to start the correct preventive actions and treatments to ultimately enhance the patient’s health and quality of life.

These complications cover a range of heart-related events such as:

• Ventricular arrhythmias
• Congestive heart failure
• Infection of the mitral valve, also called infective endocarditis
• Atrial fibrillation or irregular heartbeats
• Embolic phenomena or blood clots
• Sudden death

Preventing Hypertrophic Cardiomyopathy

Preventing and slowing down the progression of HCM, or Hypertrophic Cardiomyopathy (a heart condition where the heart muscle becomes abnormally thick), is crucial in reducing related illness and death. Changes in lifestyle and specific medical interventions can be vital in reducing the impact of HCM. It’s important for doctors to understand these prevention strategies to guide patients with HCM towards improving their long-term heart health.

Patients should be checked and counseled on how to prevent and manage health conditions that can aggravate HCM. These conditions include atherosclerotic cardiovascular disease (heart disease caused by hardening or narrowing of arteries), obesity, high blood pressure, and sleep apnea (a condition where breathing stops and starts while you’re asleep)

If someone has had a family member who died suddenly within the last three generations, they should be checked for HCM. This check often begins with procedures like an ECG (Electrocardiogram, which monitors the heart’s electrical activity), echocardiography (an ultrasound of the heart), or CMR (Cardiovascular Magnetic Resonance, a type of heart imaging), starting from the age of 12 and continuing each year until they are 21. After 21, these checks can take place every 3 to 5 years. Doctors can sometimes identify the gene that causes HCM, and in these cases, genetic testing may be done. However, the Journal of the American College of Cardiology does not always recommend this, because the way this gene affects people can differ greatly and in up to 40% of HCM cases, this gene cannot be identified.

People with abnormal blood pressure during exercise should also be screened for HCM. There is considerable debate about whether individuals with HCM should participate in organized or competitive sports, due to associated risks, particularly the risk of sudden cardiac death. It’s important for doctors to discuss these risks in detail with patients with HCM and their caregivers.