WHAT IS HYPERTROPHIC CARDIOMYOPATHY?

Cardiomyopathy is a condition in which the muscle of the heart is abnormal in the absence of an apparent cause. This terminology is purely descriptive and is based on the Latin derivation. There are four types of cardiomyopathy: Hypertrophic (HCM), Dilated (DCM), Restrictive (RCM) and Arrhythmogenic Right Ventricular (ARVC). The main feature of Hypertrophic Cardiomyopathy is an excessive thickening of the heart muscle (hypertrophy literally means to thicken). Heart muscle may thicken in normal individuals as a result of high blood pressure or prolonged athletic training. In Hypertrophic Cardiomyopathy, however, the muscle thickening occurs without an obvious cause. In addition, microscopic examination of the heart muscle in Hypertrophic Cardiomyopathy shows that it is abnormal. The normal alignment of muscle cells is absent and this abnormality is called myocardial disarray (See Figure 1).

 

FIGURE I

Myocardial Disarray

These diagrams contrast the regular, parallel alignment of muscle cells in a normal heart with the irregular, disorganised alignment of muscle cells or myocardial disarray found in some parts of the heart in Hypertrophic Cardiomyopathy.

 

HISTORY AND OTHER NAMES

Hypertrophic Cardiomyopathy was first recognised in the late 1950s. The condition has been known by a number of names including Hypertrophic Obstructive Cardiomyopathy (HOCM), Idiopathic Hypertrophic Sub-aortic Stenosis (IHSS) and Muscular Sub-aortic Stenosis. The general term Hypertrophic Cardiomyopathy (HCM) is now most widely used.

 

HOW COMMON IS HYPERTROPHIC CARDIOMYOPATHY?

Recent studies in the USA have suggested that Hypertrophic Cardiomyopathy is more common than previously reported. It is now estimated that approximately l in every 500 of the UK population suffers from the disease. An important objective of the Cardiomyopathy Association is to establish exactly how many people are affected in the UK.

WHAT IS THE CAUSE OF HYPERTROPHIC CARDIOMYOPATHY?

The cause of Hypertrophic Cardiomyopathy is not yet known. In the majority of cases the condition is inherited. In others there is either no evidence of inheritance or there is insufficient information about the individual's family to assess inheritance. In affected families the condition usually passes from one generation to the next and generations are not skipped. This pattern of inheritance is called dominant see Figure 2, and the condition may be passed on from affected males and females.

 

FIGURE 2

A Family Tree

This family tree shows four generations affected by Hypertrophic Cardiomyopathy. The condition is transmitted from one generation to the next without skipping a generation. This is called dominant inheritance. Each child of an affected person has a 50:50 chance of inheriting the condition.

 

NEW DISCOVERIES

Recently research has identified abnormalities in at least 6 related genes that are important in the development of heart muscle cells. The abnormality is known as a mutation and may be likened to a spelling mistake in the genetic code make up of DNA. In approximately 50-60% of families, affected individuals are found to have a mutation in the gene for myosin, troponin T, alpha tropomyosin, cardiac myosin binding protein-C, or the essential and regulatory light chains. These are important proteins for the contraction of the heart.

Our bodies are made of millions of cells   Each cell has a nucleus   Each nucleus has 46 chromosomes   Each chromosome is made up of a long spiral of DNA   The DNA spiral is divided into genes   FIGURE 3

 

From Chromosome to Protein Look at this book case! We are searching for a specific word with a spelling mistake!

The cell nucleus contains 22 pairs of chromosomes
plus one pair of sex chromosomes
A chromosome can be likened to a volume of an encyclopedia.
Each person has two copies of the same
volume, one copy from each parent

FIGURE 4

 

-------- D N A --------

DNA is a very long molecule composed of four different types of units.

The units are called nucleotides, and they are Adenine, Thymine Guanine and Cytosine.

The nucleotides pair specifically to each other, in the manner A to T and C to G. This bonding keeps the two DNA strands together.

The order and length of the nucleotides determines which protein will be produced from the DNA sequence.

 

FIGURE 5

 

FIGURE 6

A gene is a  sequence of  "letters"; the length and order of the characters define the nature of the protein it produces

A mutation occurs where the sequence varies from the norm.  That difference could be as minute as a single "letter" mismatch.

The discovery of these gene abnormalities is a major step towards understanding the cause of Hypertrophic Cardiomyopathy.  Ultimately this should allow diagnosis from a blood or saliva test which will be particularly useful in children and adolescents.

Ongoing research aims to identify the other gene(s) which cause Hypertrophic Cardiomyopathy and to understand how these gene abnormalities result in the heart abnormalities which we recognise.

Such work is taking place worldwide, and in the UK, predominately at St George's Hospital Medical School in London, alongside research aimed at discovering other genes which may modify the disease and hence explain how people within the same family can have very different forms of Hypertrophic Cardiomyopathy.

 

HOW DOES HYPERTROPHIC CARDIOMYOPATHY AFFECT THE HEART?

The Normal Heart

It is helpful to be familiar with the structure and function of the normal heart in order to understand the abnormalities in Hypertrophic Cardiomyopathy. Figure 7 shows a normal heart and indicates the heart chambers, valves and the direction of blood flow. The walls of the heart are composed of specialised muscle known as the myocardium. It is this part of the heart which is abnormal in Hypertrophic Cardiomyopathy.

Normal Heart FIGURE 7

The Normal Heart Structure and Function

This is a diagrammatic representation of the internal structure of a normal heart. The four chambers and four one-way valves are indicated. The arrows show the direction of blood flow through the heart: the right atrium receives blood from the body, transfers it to the right ventricle which pumps it into the lungs to receive oxygen. Blood returns from the lungs to the left atrium. It is transferred to the left ventricle which pumps it around the body for another cycle.

Figure 8 shows a normal heart and in this diagram the electrical activity of the heart is shown. Every heartbeat results from an electrical signal starting at the top and passing down through the heart. The contraction of the heart follows the same course. The abnormality of the heart muscle in Hypertrophic Cardiomyopathy can sometimes interfere with this normal electrical activity. In abnormal segments of the heart the electrical signal may become unstable as it crosses the areas of fibrosis (scarring) and disarrayed cells. This in turn can lead to disorganised electrical impulses that generate fast or erratic heart rhythms.

Normal Electrical Signal in the Heart FIGURE 8

The Normal Electrical Impulse in the Heart

The normal electrical impulse starts in the right atrium as shown by the arrows.  It travels by special conducting tissue down through the heart and into the muscle to start a contraction.

 

THE HEART IN HYPERTROPHIC CARDIOMYOPATHY

The major abnormality of the heart in Hypertrophic Cardiomyopathy is an excessive thickening of the muscle. The distribution of muscle thickening or hypertrophy is variable. The left ventricle is almost always affected and in some patients the muscle of the right ventricle also thickens.

Asymmetric Septal Hypertrophy

Figure 9 shows the commonest form of Hypertrophic Cardiomyopathy where the muscle thickening occurs predominantly in the septum or dividing wall between the right and left sides of the heart.

Hypertrophic Cardiomyopathy Asymmetric septal hypertrophy without obstruction FIGURE 9

Hypertrophic Cardiomyopathy: Asymmetric Septal Hypertrophy without Obstruction

This diagram shows the commonest form of Hypertrophic Cardiomyopathy where the muscle thickening occurs mainly in the upper part of the septum.  Note that the mitral valve maintains a normal position.

It can be seen from Figure 9 that the hypertrophy is usually greatest in the upper septum, in the area where blood flows out of the heart into the aorta or outflow tract. The muscle thickening in this region may be sufficient to narrow the outflow tract, Figure 10. In such cases during the ejection of the blood flow from the heart, the mitral valve touches the septum (there should normally be a considerable gap between these structures, (Figure 9). This narrowing of the outflow tract interferes with the normal ejection of blood. It causes turbulent blood flow and sometimes obstruction to flow. The turbulent flow produces a murmur which is audible with a stethoscope. In such patients, the abnormal position of the mitral valve may cause it to leak. This is called mitral regurgitation and may also cause a murmur (Figure 10).

Hypertrophic Cardiomyopathy

Asymmetric septal hypertrophy with obstruction FIGURE 10

 

Hypertrophic Cardiomyopathy: Asymmetric Septal Hypertrophy with Obstruction

In some cases of asymmetric septal hypertrophy obstruction to the outflow of blood from the heart may occur as shown here. Note that the mitral valve now touches the septum, blocking the outflow tract (Systolic Anterior Motion of the Mitral Valve or SAM). Some blood is leaking back through the mitral valve (mitral regurgitation).

Other patterns of muscle thickening

In approximately 2O-25% of patients the muscle thickening is evenly distributed throughout the ventricle. This is known as symmetric or concentric left ventricular hypertrophy (Figure 11). In a small proportion of patients (approximately 10%), myocardial thickening is predominantly at the tip or apex of the heart, (Figure 12). This appears to be a more common pattern of hypertrophy in Japan than in the West. Patients with Concentric and Apical Hypertrophic Cardiomyopathy usually do not have a murmur.

Function of the heart in Hypertrophic Cardiomyopathy

The thickened muscle usually contracts well and ejects most of the blood from the heart. However the muscle in Hypertrophic Cardiomyopathy is often stiff and relaxes poorly, requiring higher pressures than normal to expand with the inflow of blood. The amount of blood which the heart can hold is therefore reduced and this in turn will limit the amount of blood which can be ejected with the next contraction.

Occasionally patients present with minimal or no hypertrophy, but severe restriction to the normal inflow of blood into the ventricles. The differentiation from Restrictive Cardiomyopathy may be difficult and accurate diagnosis relies on the presence of other features of the two conditions.

Muscle cells under the microscope

Examination of the heart muscle in Hypertrophic Cardiomyopathy under a microscope shows that the normal parallel alignment of muscle cells has been lost. The cells appear disorganised. This abnormality is called myocardial disarray (Figure 1). It is probable that myocardial disarray interferes with normal electrical transmission and predisposes to irregularities of the heart beat.

Normal parts of the heart in Hypertrophic Cardiomyopathy

Finally, it is important to note that parts of the heart commonly affected in other conditions e.g. the heart valves and the main coronary arteries (blood vessels that supply the heart) are normal in Hypertrophic Cardiomyopathy.

Hypertrophic Cardiomyopathy Symmetric hypertrophy FIGURE 11

Hypertrophic Cardiomyopathy: Symmetric Hypertrophy

In this case the muscle thickening is of equal severity throughout the whole left ventricle.

Hypertrophic Cardiomyopathy A typical hypertrophy FIGURE 12

Hypertrophic Cardiomyopathy: Apical Hypertrophy

In this form of Hypertrophic Cardiomyopathy the muscle thickening occurs predominantly at the tip (apex of the left ventricle) Only a small slit-like cavity remains.

WHEN DOES HYPERTROPHIC CARDIOMYOPATHY DEVELOP?

Although hypertrophy may be present at birth or in childhood, it is much more common for the heart to appear normal at this time. Occasionally, Hypertrophic Cardiomyopathy is the cause of a stillbirth. The condition can also develop during infancy, and if this is present with congestive heart failure it may be fatal. However, hypertrophy more commonly develops in association with growth and is usually apparent by the late teens or early twenties. After this time it appears that there is no significant change in muscle thickness in the years of adult life.

Children and adolescents with the condition are usually identified when family screening is performed after an adult in the family is found to be affected. Of these adults approximately 50% will have experienced symptoms. In the remainder the diagnosis is made during family screening or following the detection of a murmur or an abnormality on routine electrocardiogram (ECG) and echocardiogram (ECHO).

 

WHAT SYMPTOMS DOES HYPERTROPHIC CARDIOMYOPATHY CAUSE?

There is no particular symptom or complaint which is unique to Hypertrophic Cardiomyopathy. The reason for the onset of symptoms is often not clear although they may occur at any stage in a person's life, even though the condition may have been present for some time. Symptoms may include:

Shortness of breath

Exercise capacity may be limited by breathlessness and fatigue. Most individuals experience only mild exercise limitation, but occasionally limitation is severe and a minority may have shortness of breath at rest.

Chest pain

Chest pain (sometimes called angina) is a common symptom. It is usually brought on by exertion and relieved by rest, but pain may occur at rest or during sleep and may persist. The cause of the pain is thought to be insufficient oxygen supply to the myocardium. In Hypertrophic Cardiomyopathy, the main coronary arteries are usually normal, but the greatly thickened muscle demands an increased oxygen supply which cannot be met in some circumstances.

Palpitation

People may occasionally feel an extra beat or a skipped beat but this is usually normal. Sometimes, however, an awareness of the heart beating does suggest an irregular heart rhythm. In this case, palpitation may start suddenly, appear to be very fast and may be associated with sweating or light-headedness. The cause of such episodes should be determined and treated.

Light-headedness and blackouts

Persons with the condition may experience light-headedness, dizziness and, more seriously, blackouts. Episodes may occur in association with exercise, with palpitation, or without any apparent provocation. The reasons for these episodes are not always clear. They may be due to an irregularity of the heart beat, or a fall in blood pressure. Episodes of light-headedness and certainly a blackout should be reported to one's doctor and investigated.

 

PHYSICAL EXAMINATION

In the majority of patients with Hypertrophic Cardiomyopathy, the physical examination is unremarkable and the abnormalities detected may be subtle. Most patients have a forceful or jerky pulse and a forceful heart beat, which can be felt on the left side of the chest. Both of these reflect the thickened, strongly contracting heart. However the most obvious abnormality on physical examination is a heart murmur, which is present in 30-40% of patients.

 

HOW IS HYPERTROPHIC CARDIOMYOPATHY DIAGNOSED?

Hypertrophic Cardiomyopathy may be suspected because of symptoms, a murmur or an abnormal ECG. An individual with the condition may present with any of the symptoms described above but because such symptoms could be caused by a large number of other conditions, further tests are necessary.

Electrocardiogram or ECG

An ECG records the electrical signal from the heart and is performed by placing electrodes on the chest, wrists and ankles (Figure 13). In Hypertrophic Cardiomyopathy the ECG usually shows an abnormal electrical signal due to muscle thickening and disorganization of the muscle structure. In a minority of patients (5-10%) the ECG may be normal or show only minor changes. ECG abnormalities are also not specific to Hypertrophic Cardiomyopathy and may be found in other heart conditions.

 

FIGURE 13

Echocardiogram or ECHO

Nowadays the diagnosis of Hypertrophic Cardiomyopathy is made by an ultrasound scan of the heart called an echocardiogram or ECHO for short. Like the ECG this is an entirely safe test and produces a picture of the heart similar to those in Figures 9-12, where excessive thickness of the muscle can be easily measured.

Additional equipment called Doppler ultrasound can produce a colour image of blood flow within the heart and measure the heart's contraction and filling. Turbulent flow can be detected. Therefore ECHO provides a very thorough assessment of Hypertrophic Cardiomyopathy.

 

FIGURE 14

OTHER INVESTIGATIONS WHICH MAY BE NECESSARY

Additional investigations may be required to assess symptoms, to assess the risk of complications, particularly sudden death, and to select the best treatment.

Cardiac Catheterisation

Patients with breathlessness, which does not respond to therapy may require cardiac catheterisation. In this test a fine tube is passed from a blood vessel (usually in the groin) to the heart using x-ray guidance. Pressures inside the heart are then measured and an angiography (x-ray) of the heart is taken to assess mitral regurgitation and overall function.

Coronary angiography

Patients who experience chest pain which does not respond to therapy, may require coronary angiography. This is an x-ray of the coronary arteries to determine if they are diseased and is performed during cardiac catheterisation.

Electrophysiological Studies (EPS)

These are a specialised form of catheterisation performed to define the risk of electrical instability which may predispose to sudden death. Electrophysiological studies involve the passage of fine wires from the veins in the groin, arm or shoulder to the heart under x-ray guidance. These wires are then used to apply electrical stimuli to record the response of the electrical system of the heart.

Exercise testing

The severity of exercise limitation and the effect of therapy can be assessed with bicycle or treadmill exercise testing. Exercise testing also provides an objective measurement of improvement, stability or deterioration over time.

Holter monitor

This test is a continuous ambulatory recording of the heart beat over 24 to 48 hours, see Figure 15. A Holter monitor is a simple and safe test which will detect irregularity of the heart beat (otherwise known as arrhythmia).

Radionuclide Studies

In these tests, substances producing very tiny (safe) amounts of radioactivity are given by injection. These tests may be used to assess the contraction, filling, structure and function of the heart and also to estimate its blood supply at rest and on exercise.

 

FIGURE 15

 

WHAT IS THE OUTLOOK FOR AFFECTED PERSONS?

The severity of symptoms and risk of complications varies greatly between patients but it should be emphasised that many people never have any serious problems related to their condition. Each person, however, must be assessed and advised individually and this website can only give a broad overview of the outlook for affected persons.

Pattern of Symptoms

In general, symptoms, whether mild or considerable, tend to be stable throughout adult life. Some people experience a worsening of symptoms in later life and this may be due to a progressive stiffening of the heart muscle or, in rare cases, to a reduction in the force of contraction.

 

COMPLICATIONS OF HYPERTROPHIC CARDIOMYOPATHY

In a minority of cases a number of specific complications can occur and may include:

Arrhythmias

Arrhythmias, irregularities of the heart beat, are a common complication. Symptoms such as palpitation may occur but not often. Exercise testing or Holter monitoring may detect them. The arrhythmias called ventricular tachycardia (arising from the ventricles) or atrial fibrillation are particularly important and may require treatment.

Atrial fibrillation

The normal regular rhythm of the heart beat is lost and replaced by an irregular rhythm which may be episodic (paroxysmal atrial fibrillation) or persistent. The loss of normal atrial contraction produces a risk of clot formation in the atria. Anticoagulation and drugs to slow the heart rate are required. Sometimes Electrical Cardioversion may be used to shock the heart back into normal rhythm. If this procedure is necessary, it is carried out under general anaesthesia.

Endocarditis

This is an infection of the heart which occurs rarely in Hypertrophic Cardiomyopathy. Bacteria in the bloodstream can stick to the inside of the heart where it has been roughened by turbulent blood flow.

Heart Block

The normal electrical signal may travel down to the ventricles slowly or may even be completely blocked, heart block. This is uncommon, but if this occurs, a pacemaker is implanted (see other forms of therapy).

Sudden Death

A small number of patients with Hypertrophic Cardiomyopathy have an increased risk of premature death, which may occur with little or no warning. Systematic evaluation can identify the majority of patients at particular risk, with potential for targeted therapy i.e. drugs, pacemaker, ICD or surgery as appropriate.

 

IS THERE A CURE AVAILABLE?

At present there is no cure for Hypertrophic Cardiomyopathy although there is a slight possibility that some drugs may decrease the degree of muscle thickening. Regrettably, no treatment has yet been shown to return the heart to normal but research is continuing in this area. Developments are most likely to come from the early detection of persons carrying the gene for Hypertrophic Cardiomyopathy and from treating them to prevent the development of hypertrophy.