Inherited cardiac conditions (ICCs)

What are Inherited Cardiac Conditions?

ICCs are conditions that affect around 1 in 250 people worldwide​ - around 260,000 people in the UK. Inherited heart diseases can cause the heart to stop suddenly or cause progressive heart failure in young people. Every week in the UK, 12 people under the age of 35 die of an undiagnosed heart condition, very often caused by one of these inherited heart diseases. Around half of all heart transplants are needed because of a heart muscle disease (also known as genetic cardiomyopathies) and current treatments do not prevent the condition from progressing. Importantly, those affected by genetic cardiomyopathies, have a 50:50 risk that they will pass their faulty genes on to each of their children. In many cases, multiple members of the same family will develop heart failure, need a heart transplant, or are lost to sudden cardiac death at a young age.

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There are two main types of inherited cardiac conditions: cardiomyopathies and channelopathies. There are also inherited diseases of the aorta (aortopathies) and metabolic inherited conditions. 

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Cardiomyopathies

Cardiomyopathies are a group of conditions that can affect the heart muscle. Different cardiomyopathies can cause the heart muscle to thicken, weaken, or develop fatty tissue and scarring. These conditions can ultimately affect the ability of the heart to pump blood around the body and they can also cause abnormal rhythms.

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Examples of cardiomyopathies include:

• Hypertrophic cardiomyopathy (HCM) - when the heart muscle becomes thick and stiff

• Dilated cardiomyopathy (DCM) - when the heart muscle becomes thin and weak

• Arrhythmogenic right/left ventricular cardiomyopathy (ARVC/ALVC) or arrhythmogenic cardiomyopathy (ACM) -
  caused when the heart muscle becomes weakened, and the muscle is replaced with fat and scar tissue

• Restrictive cardiomyopathy (RCM) - when the heart becomes stiff

• Left ventricular non-compaction (LVNC) - occurs when the heart muscle tissue becomes thick and spongy.

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Channelopathies

Channelopathies are a group of conditions that affect the electrical system of the heart, more specifically the ion channels in heart muscle cells.

These control the electrical messages that allow the heart to pump. This condition can cause irregular heart rhythms (arrhythmias). Those affected may experience palpitations, and dizziness or blackouts.

Examples of channelopathies include (links go to British Heart Foundation):

• Long and short QT syndrome (LQTS, SQTS)
  when there is a delay in the electrical system that causes the heart to beat, which can put you at risk of abnormal rhythms

• Brugada syndrome (BrS)
  when there is a problem with the way that electrical signals pass through the heart, which can put you at risk of abnormal rhythms

• Catecholaminergic polymorphic ventricular tachycardia (CPVT)
  when the heart responds abnormally to exercise or emotional stress, which can put you at risk of abnormal rhythms.

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Vascular Disorders (aortopathies) 

Aortopathy means any disease of the aorta, which is the main artery of the body. It supplies oxygenated blood to the circulatory system and passes over the heart from the left ventricle and runs down in front of the backbone.

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Types of aortopathy disease: There are two main types of aortopathy disease -  either thoracic aortic enlargement progressing to acute aortic dissection or thoracic aortic dissection in the absence of aortic enlargement. Aortic involvement can be part of a collection of physical signs and symptoms, which is known as a syndrome. Examples of these conditions comprise: Marfan, Loeys Deitz, Ehlers-Danlos syndromes. 

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Inflammatory heart conditions (eg. myocarditis)

The heart muscle can become inflamed. The cause of the inflammation is most commonly a virus or bacteria. Other conditions (eg. sarcoidosis) can also cause the heart muscle to become inflamed.

• Myocarditis - Myocarditis is inflammation of the heart muscle. It can affect the function of the heart and the normal electrical signalling of the heart. Myocarditis can cause dilated cardiomyopathy (DCM) in some people.

• Cardiac sarcoidosis - is a rare condition that is challenging to diagnose due to its non-specific symptoms. However, if discovered too late, it can lead to potentially life-threatening arrhythmias, heart block and heart failure. Although there is no definitive cure, there are treatments which can significantly improve a patient’s prognosis and quality of life. The cause of the disease is unknown, but research suggests it may be linked to an over-reaction of the immune system to infectious and environmental agents. Genetics can play a part, with family members of those with sarcoidosis having a five-fold increased risk of being affected. Also, people of African/Caribbean or Northern European (Scandinavian) descent have a higher incidence of the disease, suggesting a genetic predisposition in these ethnic groups. Clinically overt cardiac sarcoidosis is identified in approximately 5-10 per cent of all sarcoidosis patients. However, recent research suggests that this may be as high as 30 per cent, with most cases being undiagnosed. Cardiac involvement is responsible for up to 75 per cent of deaths from sarcoidosis, which is why it is an important condition not to miss. Diagnosing cardiac sarcoidosis can be challenging, particularly as symptoms do not appear until structural changes or rhythm abnormalities have occurred, by which time a patient’s prognosis may have already been affected. 

• Systemic and autoimmune disease and the heart

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Sudden Arrhythmic Death Syndrome (SADS)

SADS is usually identified when a person dies suddenly and other reasons for their passing are ruled out. It usually means there was an undiagnosed genetic issue causing abnormal and dangerous heart rhythms in that person.

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For more information please visit: SADS Foundation

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Other conditions: ​

• Mitochondrial disease

• Storage disorders (eg. Fabry disease, cardiac amyloidosis)

• RASopathies (e.g. Noonan syndrome, Leopard syndrome)

• Familial hypercholesterolaemia (FH)

• Neuromuscular diseases (e.g. Muscular dystrophies)

• Metabolic inherited diseases 

• Premature atrial fibrillation 

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What causes inherited cardiac conditions? 

ICCs is often caused by a fault or change in a specific gene. Genes control the production of proteins that have specific functions in the body, and how the body grows and develops. If a genetic change disrupts a protein which is important in the heart, this can lead to an inherited cardiac condition developing. We know that there are many genes associated with inherited heart conditions - a change in any one of those genes may be sufficient to cause the condition. 

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How are ICCs inherited?

Inherited cardiac conditions are usually caused by a change in a single gene (‘monogenic’), which is enough on its own to cause the disorder. This is different to more common forms of heart disease such as coronary artery disease, which are caused by many different genes and are influenced by environmental factors such as diet and lifestyle.

 

Familial cardiomyopathies and arrhythmias are usually inherited from a parent, but can arise for the first time in an individual. When this happens there is no family history of the disorder, but the person in whom the disorder first occurs can pass it onto their children.

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The pattern of inheritance for most cardiomyopathies and arrhythmias is autosomal dominant, which means that one copy of the gene fault, inherited from either parent, is enough to cause the condition. An unaffected person cannot pass the condition onto their children. 

 

Other patterns of inheritance can account for cardiomyopathies and arrhythmias but this is much less common.  More information about genetics can be found on our education page which sign posts to a number of locations including www.geneticseducation.nhs.uk.

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Information for patients:

At an appointment patients can expect to have an ECG, which measures the electrical rhythm of the heart. They may also require an echocardiogram, which looks at the pumping function of the heart. During the appointment the family history will be ascertained. A discussion about further treatment will then be had to decide upon an appropriate care plan and upon any necessary follow-up care including whether further tests are needed, or any treatment options are available.

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If tests confirm an inherited cardiac condition, other family members may also be at risk of developing the same condition. We may therefore recommend that other family members are referred for checks on their hearts (particularly an ECG and echocardiogram).

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It may be discussed whether genetic testing may be helpful for the patient and their family. This can help clarify whether there is a 'spelling mistake' in the DNA that has caused an inherited cardiac condition in the family, or indeed may help to confirm whether the patient carries the 'spelling mistake' already known to be causing heart issues in their family (a predictive test or, if asymptomatic, a pre-symptomatic test). This genetic testing requires a discussion to decide whether the patient may wish to go ahead with the testing (which requires their consent and a blood or saliva sample). Results of genetic testing can take up to 3-4 months to be analysed and shared with them. 

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Tests that a patient (or their first-degree relatives) may require comprise: 

• Electrocardiogram (ECG) and/or Holter monitor: An ECG measures the electrical activity of your heart. A Holter monitor is an ECG that you wear over a period of 24 hours to one week. Electrocardiogram (ECG) - NHS website

• Echocardiogram or 'echo':  An echocardiogram is an ultrasound test that looks at the structure of your heart to see if blood is being pumped around the body normally. Echocardiogram - NHS website

• Genetic testing: Genetic testing can determine whether you carry a gene change that might be causing heart problems in you and/or your family. It consists of a blood test (or for children a saliva sample), which is then sent to our lab to be analysed. Genetic and genomic testing - NHS website. 

• What does genetic testing mean for relatives? If the laboratory finds a genetic cause for the inherited heart disease in one person in a family, relatives can be offered a blood test to look for the same gene change. This applies to close blood relatives. This kind of test is called a ‘pre-symptomatic genetic test’, and will tell us whether a relative is at risk of developing the inherited heart condition, even if they have no symptoms. It is important to realise that pre-symptomatic testing cannot tell whether a person will develop the inherited heart condition, or when. Relatives who have inherited the same gene change should then see a cardiologist who will look at heart structure and function by, for example, echocardiogram and ECG. Relatives who don’t inherit the gene change don’t need to see a cardiologist. A genetic test for inherited heart disease does not always find a cause - this does not mean the condition is not inherited. Close blood relatives should be screened by echocardiogram and ECG, to see whether there are signs of the condition in their heart.

• Exercise tolerance / stress test / cardiopulmonary exercise test / exercise echocardiogram: This test measures how your heart responds when you do exercise. This usually happens on a bike or treadmill, and your heart rhythms will be monitored for any changes. What is a stress test? - bhf.org.uk

• Blood tests

• Cardiac MRI scan (CMR): A cardiac MRI is a type of scan that takes very detailed pictures of your heart, and usually takes around an hour.  Having a Cardiac MRI Scan (pdf)

• Computed tomography coronary angiogram or invasive coronary angiogram: These tests may be performed to ensure that the blood supply to your heart is normal. Coronary angiogram - bhf.org.uk

• PET scan: A PET scan is used to identify active inflammation within your heart. It requires a strict dietary preparation protocol to be followed before the scan is performed. PET scan - NHS website

• Cardiac biopsy

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Referrals to UK wide ICC Services:

The AICC has created a Nationwide Directory of Services to facilitate the referral of patients their families to the local designated ICC service. Please see 'The Directory of Services' for more information.  

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Links

• British Heart Foundation

• Cardiomyopathy UK

• Cardiac Risk in the Young

• Sudden Arrhythmic Death Syndrome UK

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