What The Heck Is Hypertrophic Cardiomyopathy – HCM

Man taking medication in bathroom

Hypertrophic cardiomyopathy (HCM) is a relatively common genetic disorder of the heart (affecting almost 1 in 500 people), that can cause several problems, including heart failure and sudden death. However, the severity of HCM is quite variable from person to person, and many people with HCM can lead virtually normal lives.

What Causes HCM?
HCM is caused by one or another of several genetic mutations that produce a disorder in the growth of the heart muscle fibers.
HCM is passed on as an “autosomal dominant” trait, which means that if the abnormal gene is inherited from a single parent, the child will have the disease.

However, in almost half the patients with HCM, the genetic disorder is not inherited at all, but occurs as a spontaneous gene mutation – in which case, the parents and siblings of the patient will not be at elevated risk for HCM. However, this “new” mutation can be passed on to the next generation.

What Cardiac Problems Are Caused By HCM?
In HCM, the muscular walls of the ventricles (the lower chambers of the heart) become abnormally thickened – a condition called “hypertrophy.” This thickening causes the heart muscle to function abnormally, to at least some extent. If severe, the hypertrophy can lead to heart failure and cardiac arrhythmias.

In addition, if it becomes extreme the hypertrophy can cause a distortion in the ventricles, which can interfere with the function of the aortic valve and the mitral valve, disrupting the flow of blood through the heart.

Read about the heart’s chambers and valves.
HCM can cause at least five kinds of serious cardiac problems:

1) HCM can cause diastolic dysfunction. “Diastolic dysfunction” refers to an abnormal “stiffness” of the ventricular muscle, which makes it more difficult for the ventricles to fill with blood in between each heart beat.
In HCM, the hypertrophy itself produces at least some diastolic dysfunction. If severe enough, this diastolic dysfunction can lead to diastolic heart failure, and severe symptoms of dyspnea (shortness of breath) and fatigue. Even relatively mild diastolic dysfunction makes it more difficult for patients with HCM to tolerate cardiac arrhythmias, especially atrial fibrillation.

Read about diastolic dysfunction and diastolic heart failure.
2) HCM can cause “left ventricular outflow obstruction. (LVOT).” In LVOT, there is a partial obstruction making it difficult for the left ventricle to eject its blood with each heart beat. This problem also occurs with aortic valve stenosis, in which the aortic valve becomes thickened and fails to open normally. However, while aortic stenosis is caused by disease in the heart valve itself, the LVOT with HCM is caused by a thickening of the heart muscle just below the aortic valve. This condition is referred to as “subvalvular stenosis. “ Just as with aortic stenosis, the LVOT caused by HCM can lead to heart failure.
3) HCM can cause mitral regurgitation. In mitral regurgitation, the mitral valve fails to close normally when the left ventricle beats, allowing blood to flow backwards (“regurgitate”) into the left atrium. The mitral regurgitation seen with HCM is not caused by an intrinsic heart valve problem, but rather, is produced by a distortion in the way the ventricle contracts, caused by the thickening of the ventricular muscle. Mitral regurgitation is yet another mechanism by which people with HCM can develop heart failure.

4) HCM can cause ischemia of the heart muscle. Ischemia – oxygen deprivation – is most typically seen in patients with coronary artery disease (CAD), in which a blockage in a coronary artery limits blood flow to a portion of heart muscle. With HCM, the heart muscle can become so thickened that some portions of the muscle simply do not receive enough blood flow, even when the coronary arteries themselves are completely normal. When this happens, angina can occur (especially with exertion), and a myocardial infarction (death of heart muscle) is even possible.

5) HCM can cause sudden death. Sudden death in HCM is usually due to ventricular tachycardia or ventricular fibrillation, and is typically related to extreme exertion. It is likely that ischemia of the heart muscle produces many if not most of the arrhythmias that lead to sudden death in patients with HCM. For this reason, most patients with HCM need to restrict their exercise.

What Are the Symptoms of HCM?
The symptoms experienced by people with HCM are quite variable. It is common for patients with mild disease not to have any symptoms at all. However, if any of the heart problems just mentioned are present, at least some symptoms are likely. The most common symptoms experienced by patients with HCM are dyspnea with exercise, orthopnea, paroxysmal nocturnal dyspnea, palpitations, episodes of lightheadedness, chest pain, fatigue or swelling of the ankles. Syncope (loss of consciousness) in anyone with HCM, especially if it is associated with exercise, is a very serious matter, and may indicate a very high risk of sudden death. Any episode of syncope needs to be evaluated right away by a doctor.

How Is HCM Diagnosed?
In general, the echocardiogram is the best method of diagnosing HCM. The echocardiogram allows accurate measurement of the thickness of the ventricular walls, and can detect LVOT and mitral regurgitation as well.

The electrocardiogram (ECG) can reveal left ventricular hypertrophy, and has been used as a screening tool to look for HCM in young athletes.

Both an ECG and echocardiogram should be performed in close relatives of anyone diagnosed with HCM, and an echocardiogram should be performed in any person in whom the ECG or the physical examination suggests ventricular hypertrophy.

How Is HCM Treated?
HCM cannot be cured, but in most cases medical management can control symptoms and improve clinical outcomes. However, the management of HCM can become quite complex, and anyone who has symptoms due to HCM should be followed by a cardiologist.

Beta blockers and calcium blockers can help reduce the “stiffness” in the thickened heart muscle. Avoiding dehydration is important in patients with HCM in reducing symptoms related to LVOT. In some patients surgery to remove portions of the thickened heart muscle is necessary to relieve LVOT.

Atrial fibrillation, if it occurs, often causes severe symptoms and needs to be managed more aggressively in patients with HCM than in the general population.

Read about treating atrial fibrillation.
Preventing Sudden Death
HCM is the most common cause of sudden death in young athletes While sudden death is always a devastating problem, it is particularly so when it occurs in young people. For this reason, extreme exertion and competitive exercise should be restricted in patients with HCM.Many methods have been tried for reducing the risk of sudden death in patients with HCM – including using beta blockers and calcium blockers, and antiarrhythmic drugs. However, these methods have not proven sufficiently effective. It now seems clear that, in patients with HCM whose risk of sudden death appears high, an implantable defibrillator should be strongly considered.



10 steps to protect against hypertrophic cardiomyopathy


As if it were yesterday, I recall the death of 18-year-old Ben Breedlove, who suffered from hypertrophic cardiomyopathy (HCM), an ailment in which I specialize as a pediatric cardiologist.

I have seen it rob too many young people unnecessarily of a long and fulfilling life.

Here are 10 steps to protect your children, family members and anyone you love against the ravages of hypertrophic cardiomyopathy:

1. Remember that statistically if one member of your family has been diagnosed with HCM, then one-half of your family members are at risk for developing this disease. Evaluation of first-degree relatives on a regular, repetitive basis can go a long way towards correct diagnosis and effective treatment. It is imperative to extend this medical information to as many relatives as possible. Try to make the effort to contact others, even if you are estranged from them. Remember to breed love.

2. Always remember that hypertrophic cardiomyopathy is a sneaky disease: It is many times missed or misdiagnosed. Common diseases that are confused with HCM are asthma, mitral valve prolapse, anxiety, coronary artery disease and an athletic heart.

3. Be aware of symptoms that require prompt medical attention:
• Chest pain with exercise or simple activities such as walking.
• Passing out is a very important symptom that requires prompt medical attention.
• Shortness of breath, lightheadedness, and extreme tiredness are other symptoms of HCM.

4. Avoid circumstances that increase your risk:
• Avoid hot weather and dehydration.
• Be aware of the need for vigorous fluid resuscitation during infections or gastroenteritis or exercise.
• Avoid burst of activity.
• Avoid isometric activity.

5. With hypertrophic cardiomyopathy in humans, the lining of the blood vessels in the heart tends to be affected. Unfortunately, this is not just limited to the heart, but also involves the blood vessels networked to other organs throughout the body:
• Foods that improve the lining of your blood vessel include nuts, seeds, dark chocolate, fruits and vegetables.
• Prolonged periods of walking help revitalize the lining of your blood vessels.
• Foods that decrease the function of the lining of blood vessels include sugary drinks (soda), high salt, high fat, high sugar, high fructose corn syrup, and even high protein. Life is about balance and a balanced diet.

6. Beware of diseases or circumstances that can worsen hypertrophic cardiomyopathy, or cause it to progress faster:
• Sleep apnea, diabetes, obesity, hypertension, rapid weight gain and hypercholesterolemia.
• Steroids, including drugs like prednisone, anabolic steroids, and testosterone can aggravate the condition. The use of growth hormones or supplements that increase growth hormone or testosterone levels may also accelerate HCM.

7. Avoid drugs that can increase your risk of having a bad event:
• Avoid stimulants and decongestants.
• Avoid alcohol consumption as its diuretic effect can lead to decreased blood volume.
• If you are on a blood-thinner (e.g., Coumadin), remember to have your blood checked monthly.

• For any abrupt new onset of neurologic symptoms, such as muscle weakness, severe headache, or change in vision, seek prompt, urgent medical attention.

8. Once diagnosed with HCM, you are restricted from competitive sports and extremes of exercise, such as avoiding heavy lifting.

9. If you are on a beta blocker for HCM, it is imperative that it is taken daily. Missing a dose results in a rebound effect that can make your heart rate increase and put you at an increased risk.

10. Enjoy life, keep active and eat healthy. Most people with HCM have a normal life expectancy.


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New stem-cell model of heart tissue unravels mechanisms linked to hypertrophic cardiomyopathy

Using advanced stem cell technology, scientists from the Icahn School of Medicine at Mount Sinai have created a model of a heart condition called hypertrophic cardiomyopathy (HCM) — an excessive thickening of the heart that is associated with a number of rare and common illnesses, some of which have a strong genetic component. The stem cell lines scientists created in the lab, which are believed to closely resemble human heart tissue, have already yielded insights into unexpected disease mechanisms, including the involvement of cells that have never before been linked to pathogenesis in a human stem-cell model of HCM. The research was published in the journal Stem Cell Reports.

Image result for New stem-cell model of heart tissue unravels mechanisms linked to hypertrophic cardiomyopathy

The genetic disorder discussed in the new study is called cardiofaciocutaneous syndrome (CFC), which is caused by a mutation in a gene called BRAF. The condition is rare and affects fewer than 300 people worldwide, according to the National Institutes of Health. It causes abnormalities of the head, face, skin, and major muscles, including the heart.

To learn more about HCM associated with various genetic diseases, Mount Sinai scientists took skin cells from three CFC patients and turned them into highly versatile stem cells, which were then converted into cells responsible for the beating of the heart. This model has relevance for research on several related and more common genetic disorders, including Noonan syndrome, which is characterized by unusual facial features, short stature, heart defects, and skeletal malformations.

“At present, there is no curative option for HCM in patients with these related genetic conditions,” said Bruce D. Gelb, MD, Director of The Mindich Child Health and Development Institute and Professor in the Departments of Pediatrics, Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai. “If our findings are correct, they suggest we might be able to treat HCM by blocking specific cell signals—which is something we know how to do.”

Dr. Gelb says that about 40 percent of patients with CFC suffer from HCM (two of the three study participants had HCM). This suggests a pathogenic connection, though the link has never been fully explored or explained. The primary goal of the current research was to understand the role of a cell-signaling pathway called RAS/MAPK in the cascade of events leading to HCM in patients with CFCs — and by association, with Noonan syndrome, Costello syndrome, and other similar illnesses.

Observing the disease progression in these heart cells, called cardiomyocytes, Dr. Gelb and his team found that some of the changes were caused by interactions with cells that resemble fibroblasts — the same kinds of cells that produce collagen and other proteins. Fibroblasts make up a significant portion of total heart tissue, although it is the cardiomyocytes that are primarily responsible for pumping blood. “These fibroblast-like cells seem to be producing an excess of a protein growth factor called TGF-beta, which, in turn, caused the cardiomyocytes to hypertrophy, or grow larger,” Dr. Gelb said. “We believe this is the first time the phenomenon has been observed using a human induced pluripotent stem cell model of the disease.”

Prior to this observation, Dr. Gelb and his team assumed hypertrophy was “cell autonomous,” meaning intrinsic to the cardiomyocytes themselves. “Based on our cell culture model, we saw that fibroblasts are playing a key role in giving the heart cells the signal that causes them to get big,” Dr. Gelb said. “That was quite unexpected.”

The therapeutic implications may also be profound. “We were able to block TGF-beta in vitro using antibodies that bind to the protein. When we did that, the cardiomyocytes no longer hypertrophy,” Dr. Gelb said. It’s not certain the same effect would be seen in the many clinical cases of HCM that are not influenced by BRAF or the RAS pathway—essentially a chain of cellular proteins that help transmit signals from surface receptors on the cell to DNA in the nucleus -but researchers believe this could be the case.

The bigger surprise, said Dr. Gelb, “is that we may be talking about a signaling circle” in which fibroblasts trigger the release of a growth factor, which causes cardiomyocytes to hypertrophy, which in turn, prompts fibroblasts to release more of the growth factor.” Dr. Gelb didn’t witness this last part of the circle in his stem cell culture, but evidence of fibroblast stimulation has been reported in mouse models that don’t express the RAS mutation. If the circle theory is validated, Dr. Gelb said, there could be new and broad therapeutic interventions for HCM in both RAS and non-RAS contexts. “In theory, at least, a therapy could be useful for both,” he said.


Mount Sinai Health System


Implantable cardioverter-defibrillators can reduce sudden death in young patients with hypertrophic cardiomyopathy

A multicenter registry has demonstrated that the use of implantable cardioverter-defibrillators (ICDs) to combat sudden cardiac death in high-risk pediatric patients suffering from hypertrophic cardiomyopathy (HCM). The study is being presented Nov. 5 at the 2012 Scientific Sessions of the American Heart Association (AHA) in Los Angeles.

While the study found that the rate of possible device complications adds a level of complexity to this age group, it also demonstrated that life-saving ICD interventions were common in younger patients when terminating irregular heart rhythms, called ventricular tachyarrhythmias or fibrillation.

“While HCM is the most common cause of sudden death in the young,existing research has shown that the use of ICDs in adult patients with HCM have been very effective,” said the study’s lead author Barry J. Maron, MD, director of the Hypertrophic Cardiomyopathy Center at the Minneapolis Heart Institute Foundation in Minneapolis. “This registry is continuing to reveal important implications for younger patients suffering from this disease .”

For the study, the researchers evaluated an international registry of ICDs, implanted from 1987 to 2011, and found 224 patients with HCM judged at high risk for sudden death who received ICDs. They found that 188 patients received ICDs for primary prevention and 36 for secondary prevention after undergoing evaluation at 22 referral and non-referral institutions in U.S., Europe and Australia.

ICDs terminated ventricular tachycardia/fibrillation in 19 percent of patients over 4.3 years, according to the study authors. Also, primary prevention discharge rate terminating ventricular tachycardia/fibrillation was the same in patients implanted for one, two, three or more risk factors.

Extreme LV hypertrophywas most frequently associated with appropriate interventions in patients experiencing primary prevention interventions (65 percent). Also, ICD-related complications, particularly inappropriate shocks and lead malfunction, occurred in 41 percent of the patients at 17 years.

ICDs are a potential life-saving device in children with HCM, the most common cause of sudden death in the young.


The above post is reprinted from materials provided by Minneapolis Heart Institute Foundation

dna double helix in abstract background

Genetic tests may be misdiagnosing hypertrophic cardiomyopathy in black Americans

We believe that what we’re seeing in the case of hypertrophic cardiomyopathy may be the tip of the iceberg of a larger problem that transcends a single genetic disease,” Arjun Manrai, PhD, a research fellow in the department of biomedical informatics at Harvard Medical School, said in a press release. “We hope our study motivates a systematic review of this issue across other genetic conditions.”

Manrai and colleagues discovered through their analysis of more than 8,000 DNA samples from the NIH’s Mendelian Exome Sequencing Project, the 1,000 Genomes Project and the Human Genome Diversity Project that the false-positive diagnoses are the result of clinical studies in which the majority of the control groups consisted of white participants who tend to have fewer benign variants than black participants.

Benign variants

Between 2.9% and 27% of black Americans have one or more of the five high-frequency benign genetic variants associated with hypertrophic cardiomyopathy compared with the 0.02% to 2.9% of white Americans (P < .001), according to the researchers.

In addition, after examining the health records of more than 2,000 patients and their family members at the Laboratory for Molecular Medicine, Partners Healthcare, Boston, between 2004 and 2014, the researchers observed that seven patients who received notification that they had a pathogenic mutation (TNN13 P82S or MYBPC3 G278E) were reclassified as benign. Of those seven patients, five were black and two were of unknown ancestry. The need for more reclassification is expected in the next decade, according to the researchers.

Manrai and colleagues also found that the five original genetic studies on hypertrophic cardiomyopathy did not include black participants in the control groups.

“Our study powerfully illustrates the importance of racial and ethnic diversity in research,” Isaac S. Kohane, MD, PhD, chair of the department of biomedical informatics, Harvard Medical School, said in the release. “Racial and ethnical inclusiveness improves the validity and accuracy of clinical trials and, in doing so, can better guide clinical decision making and choice of optimal therapy. This is the essence of precision medicine.”

‘Moral imperative’

The researchers also illustrated using statistical simulations that even small studies can be racially diverse. They gave an example of a sample of 200 people that included 20 black participants. This sample would only have a 50% chance of a correct diagnosis, but if one-third of the population or half the population were black, then accuracy would improve to 80% and 90%, respectively, Manrai and colleagues wrote.

“Ensuring that genomic medicine benefits all people and all populations equally is nothing short of a moral imperative, not only for scientists and clinicians but for political and health policy powers that be,” Kohane said in the release. – by Tracey Romero

Genetic tests for potentially fatal heart anomaly can misdiagnose condition in black Americans

  • Studies in which DNA mutations are being sought as a cause for a disease such as familial hypertrophic cardiomyopathy are vulnerable with respect to African Americans. The DNA of Africans and African Americans has been modified much more than the other races since they stayed in Africa. The DNA of all other races are derived from individuals that left Africa about 100,000 years ago. The sequencing of the human genome, which until recently was Caucasians and not Africans, has been used as the standard for comparison of potential disease-causing mutations.

    It is well-recognized that mutations that are disease-producing in groups such as Caucasians or Asians or Chinese may not necessarily be disease-causing in Africans or African Americans. One good example is the recent discovery of 9p21, a genetic risk variant for CAD, which is not a risk factor in Africans or African Americans but is a risk factor for all the others who left Africa 100,000 years ago. Another example is that Africans have a mutation that bestows resistance to malaria, and when they come to cooler climates, the same mutation induces sickle cell anemia. Other races, including Caucasians, have lost that mutation. Thus, if one is identifying a disease-causing mutation solely on the basis of a DNA sequence, it may become necessary to compare the DNA sequence of an African or African American to an African or African-American reference sequence.

    In the past, we would have determined if hypertrophic cardiomyopathy is due to a mutation by doing linkage analysis, which requires 7 to 10 affected individuals from at least two generations. In linkage analysis, we can show by segregation that the mutation is indeed causal of the disease. However, since it is often impossible to have two-generation families with an adequate number of individuals affected with hypertrophic cardiomyopathy, we frequently today turn to sequencing. In the case of the Africans or African Americans, this has further problems, for the reasons I stated earlier.

    • Robert Roberts, MD, MACC, FRSC, FRCPC, LLD (Hon.)
    • Cardiology Today Editorial Board Member
      Professor of Medicine
      College of Medicine – Phoenix
      University of Arizona. 


Anterior cross section view of heart with cardiomyopathy
SOURCE: 1) Mayo Clinic (2006). "Examples of Hypertrophic Cardiomyopathy." retrieved at: http://www.mayoclinic.org/hypertrophic-cardiomyopathy/examples.html 
2)Medline Plus (2004). "Hypertrophic cardiomyopathy." retrieved at: http://www.nlm.nih.gov/medlineplus/ency/imagepages/18141.htm

When Your Child Has Hypertrophic Cardiomyopathy-drug rehab

Hypertrophic cardiomyopathy is a problem with the heart muscle. It may not cause symptoms that bother your child. But it can lead to serious problems over time. The good news is that it can usually be managed. Your child’s doctor will discuss treatment options with you. This sheet tells you more about this problem and how it is treated.

Cross section of heart showing blood flow through atria and ventricles. Cross section of heart with hypertrophic cardiomyopathy.

The Normal Heart

The heart is divided into 4 chambers that hold blood as it moves through the heart. The 2 upper chambers are called atria. The 2 lower chambers are called ventricles. The heart also contains 4 valves between the chambers. The valves open and close to keep blood flowing forward through the heart.

What Is Hypertrophic Cardiomyopathy?

With this condition, the heart muscle thickens. A too-thick heart muscle can’t pump blood normally. It may affect the entire left ventricle. Or, it may just affect the wall that separates the ventricles (ventricular septum).

Why Is Hypertrophic Cardiomyopathy a Problem?

A thickened heart muscle can:

  • Block blood flow leaving the heart. This forces the heart to work harder than normal to pump blood. If the heart no longer pumps blood well, a condition called congestive heart failure (CHF) can develop.
  • Damage heart valves. The mitral valve is most likely to be affected. This valve is found between the left atrium and the left ventricle. Blood may leak backward through the valve. This is called valve insufficiency.
  • Damage electrical cells in the heart. These cells control the beating of the heart. Damage to these cells can cause abnormal heart rhythms (arrhythmias). In rare cases, a severe arrhythmia can lead to sudden death.

What Causes Hypertrophic Cardiomyopathy?

This condition can occur in your child by chance. It can also be passed from parent to child in some families. If you or your child has this condition, each close family member should be tested for it.

What Are the Symptoms of Hypertrophic Cardiomyopathy?

Most children with this condition have no symptoms. If they do occur, they often show up when children are active. Symptoms may include:

  • Lightheadedness, dizzy spells, or fainting
  • Rapid, pounding heartbeat
  • Shortness of breath or tiredness
  • Tightness or pressure in the chest

How Is Hypertrophic Cardiomyopathy Diagnosed?

Heart problems in children are managed by a pediatric cardiologist. The doctor will do a physical exam. This is to check for heart problems. Several tests may be done. They can help confirm a diagnosis or tell more about the heart problem. These tests may include:

  • Echocardiogram (echo). Sound waves (ultrasound) are used to create a picture of the heart. This helps find problems with heart structure or function.
  • Electrocardiogram (ECG or EKG). This test records the electrical activity of the heart. It helps find arrhythmias or some problems with heart size or structure.
  • Holter or event monitor. This test records the electrical activity of the heart over time. A special monitor is used. It can help detect problems with the heart rhythm.
  • Exercise stress test. This records the electrical activity of the heart while your child exercises. It helps detect problems with the heart rhythm when the heart beats faster.

How Is Hypertrophic Cardiomyopathy Treated?

Treatment reduces symptoms. It helps prevent CHF. It can also reduce the risk of severe arrhythmia and sudden death. Your child’s treatment plan may include:

  • Medications. Beta-blockers and calcium channel blockers may be prescribed. These medications can lower blood pressure and slow heart rate. They help to prevent arrhythmias. They may also improve the heart’s pumping action.
  • Surgery. This is done in severe cases. Surgery removes a portion of the heart muscle. This improves blood flow from the heart to the body.
  • Implantable cardioverter defibrillator (ICD). An ICD is a device that is placed in the chest. It tracks the heart rate. When needed, it delivers an electric shock to the heart. This stops a life-threatening heart rhythm.
  • Heart transplantation. In rare cases, heart transplantation may be needed. Your child’s cardiologist will discuss this with you.

What Are the Long-term Concerns?

  • With treatment, most children with this condition can be active. But they may have to limit certain sports or physical activities. Talk to the doctor about activities that are safe for your child.
  • Your child needs to have regular visits with the cardiologist for the rest of his or her life. This is to check that the heart is working properly. If an ICD is placed, this needs regular checks.
  • Your child may need to take medications for the rest of his or her life.

Call the Doctor

Contact your doctor if your child has any of the following:

  • Fainting or dizzy spells
  • Trouble breathing
  • Tightness or pain in the chest
  • Irregular, rapid heartbeats (palpitations)



Hypertrophic cardiomyopathy: Who has an inherited risk?

Genetic testing can help doctors guide care for families with a history of heart disease.

Having a family member with heart disease—especially when it shows up at a young age—is a warning sign that you too may be at risk. The more common maladies such as high blood pressure and coronary artery disease are influenced by an array of different genes and compounded by lifestyle choices and environmental factors. However, certain relatively rare conditions stem from only one or a few faulty genes with powerful disease-causing effects. The most common of these inherited heart conditions is hypertrophic cardiomyopathy (HCM), which affects up to one in every 500 people.

What is HCM?

Best known for cutting down young athletes in their prime, HCM causes an abnormal thickening of the heart wall. In rare cases, the first inkling of disease may be fainting or sudden death due to an abnormal heart rhythm. More often, symptoms such as shortness of breath or chest pain with exercise develop over time.

The key feature of inherited HCM is that the thickening of the heart muscle is unexplained, says Dr. Carolyn Y. Ho, medical director of the cardiovascular genetics center at Harvard-affiliated Brigham and Women’s Hospital. “We wouldn’t leap to the diagnosis of HCM if we saw these changes in an older person with a history of high blood pressure. But if it occurs early in life without the presence of other triggering factors, we would think about HCM and look for a familial pattern,” she says.

The detective work

The genetic risk for HCM is passed from one generation to the next by way of dominant-acting mutations in genes governing the structure of the heart muscle. That means that first-degree relatives (parents, siblings, and children) of an affected person have a 50% chance of having inherited the same mutation. Before genetic testing became widely available, doctors had only this information to help guide families. Now, it’s possible to determine if a family member is at risk for developing HCM even before the disease can be clinically diagnosed.

“When you decide do genetic testing, the implications go beyond just the individual being tested,” says Dr. Ho. The most efficient approach is first to do comprehensive gene sequencing on the person with the most serious manifestation of disease. This gives the best chance of uncovering the most important disease-causing mutations. If an HCM mutation is found, other family members can undergo more limited—and less costly—screening to look for that specific mutation.

Decision making in the family

In that scenario, if you have a negative result showing that you do not carry the problem mutation, you can feel relatively reassured that you are not at increased risk for developing the disease. Nor do you need to worry about passing the trait to your offspring. However, Dr. Ho cautions, anyone with a strong family history of HCM should get checked out by a cardiologist, regardless of the results of a genetic screening, if a heart murmur or other unexplained heart symptom develops.

A positive result indicates that the relative has inherited the mutation and is at risk for developing HCM. But, as of now, we cannot predict when, or even if, HCM will develop or how severe it will be, says Dr. Ho. Therefore, relatives who have inherited the mutation are advised to undergo clinical screening on a regular basis to detect the earliest signs of heart muscle changes. This includes having an echocardiogram (heart ultrasound) every year during adolescence and young adulthood, when HCM most commonly develops. Even a person who has remained symptom-free into middle age should be screened occasionally because the disease has been known to crop up later in life.

Although there currently aren’t any therapies to prevent or delay HCM, much can be done to help individuals live comfortably with the disease and treat potential problems as early as possible. That is why Dr. Ho stresses that families at risk should be followed by a team of doctors experienced with HCM. She and others are investigating how gene mutations cause HCM with the goal of discovering ways to delay or prevent the disease.

Hypertrophic cardiomyopathy

Classic signs of HCM include thickening of the muscular wall separating the right and left sides of the heart (septum) and the heart’s main pumping chamber (left ventricle). Instead of neatly lining up, muscle cells are irregular and disorganized. The thickened septum can restrict blood flow out of the left ventricle.



Two essential cardiac disorders improvement in patients with hypertrophic cardiomyopathy

Sudden cardiac death and heart failure are the most serious complications of hypertrophic cardiomyopathy ( HCM ). To prevent these serious complications, 2 essential cardiac disorders in patients with HCM must be corrected. These are left ventricular (LV) hypertrophy and LV diastolic dysfunction. In addition, the prognosis for HCM patients with an LV pressure gradient (hypertrophic obstructive cardiomyopathy, HOCM) is known to be worse in those without an LV pressure gradient (hypertrophic nonobstructive cardiomyopathy, HNCM). Maron and Spirito mentioned in their review that there is no intervention capable of inducing LV hypertrophy regression in patients with HCM without causing a clinically unfavorable end-stage disease. In addition, Harris et al. reported that the interval between identifying end-stage disease and death or transplantation is short.

Fig. 1.

Fig. 1.

Recently, we reported that long-term treatment with cibenzoline improved the LV pressure gradient, LV diastolic dysfunction, and LV hypertrophy in patients with HOCM without causing serious complications. Figure 1 indicates the study results. (A, LV pressure gradient change; B, LV size; C, LV systolic function; D, left atrial size; E and F, extent of LV hypertrophy; G and H, extent of LV diastolic dysfunction). As shown in figure 1, the LV pressure gradient decreased, LV diastolic dimensions increased and were close to normal, LV systolic function remained normal, left atrial size decreased and was close to normal, LV hypertrophy regressed (improved) in both echocardiographic (E) and electrocardiographic (F) assessments, and LV diastolic dysfunction also improved. Figure 2 shows the change in electrocardiogram results, following cibenzoline treatment, in a patient with HOCM. As shown in Figure 2, the voltage in each lead decreased markedly, reflecting LV hypertrophy regression. The fact that the fractional shortening observed in the patients in this study was normal to hyper-dynamic, and remained unchanged during the study, is very important. This finding indicates that LV hypertrophy regression is not the result of the advancement of LV remodeling (deterioration of LV function), but is the result of LV reverse remodeling (recovery to a better condition) associated with cibenzoline therapy. To our knowledge, this is the first report to elucidate LV hypertrophy regression in patients with HOCM undergoing medical treatment. In addition, the patients’ QTc intervals were significantly shortened as a result of the treatment. The QT interval is a surrogate marker for predicting serious adverse drug effects, syncope, or death due to torsade de pointes.

Fig. 2.

Fig. 2.

To avoid the potentially serious complications associated with cibenzoline treatment, patient’s renal function, age, etc. must be considered. We believe that cibenzoline treatment avoids the development of heart failure in patients with LV hypertrophy and LV diastolic dysfunction associated with HCM.

Mareomi Hamada, MD and Shuntaro Ikeda, MD
Division of Cardiology, Uwajima City Hospital, Japan