Part 1 of this series (vol. 6, no. 2) addressed cardiomyopathy, the degeneration of heart muscle that often occurs in many neuromuscular diseases. In this part, we'll address electrical problems that can occur in the heart as an effect of neuromuscular diseases, including Duchenne, Becker, Emery-Dreifuss and myotonic muscular dystrophies; a type of limb-girdle muscular dystrophy; Friedreich's ataxia; hyperkalemic and hypokalemic periodic paralysis; and some metabolic and mitochondrial disorders. We'll explore some of the results of these problems and some available treatments.

 Q    HOW DO NEUROMUSCULAR DISORDERS CAUSE PROBLEMS IN THE HEART?

 A   Some neuromuscular diseases, such as Duchenne and Becker muscular dystrophies, frequently lead to cardiomyopathy, a problem with the muscle layer of the heart. Part 1 of this series explored cardiomyopathy in depth.

Another type of heart problem that occurs in neuromuscular disorders is cardiac arrhythmias, abnormalities in the heart's electrical pacing system, or a heartbeat or pulse rate that's too fast, too slow or irregular. Electrical heart problems can be common and serious in myotonic (MMD) and Emery-Dreifuss (EDMD) muscular dystrophies and in some other neuromuscular disorders. These conditions may involve direct damage to the cells of the cardiac conduction system.

Everyone with a neuromuscular disease should be aware that heart rhythm problems can also occur as a result of cardiomyopathy or respiratory problems. The good news is that arrhythmias, whatever the cause, can be treated. It's important to be alert to signs of arrhythmias so you can get early treatment.

 Q    WHAT IS THE HEART'S 'ELECTRICAL SYSTEM'?

 A   It may sound funny to talk about the electrical properties of the heart, but electricity is a form of energy that results from the flow of charged particles, whether they're in a biological or manufactured system. In the heart, it's the electrical system -- usually called the conduction system -- that regulates the heartbeat. Abnormalities in the heartbeat's rate or rhythm are called arrhythmias or dysrhythmias.

In the heart, as in other muscles and in nerves, electrical signals are produced by a flow of charged particles known as ions that move in and out of cells across membranes. The key ions in this process are particles of sodium, calcium and potassium. Their flow is regulated in large part by the actions of ion channels, submicroscopic pores in the cell membrane that open and close and allow ions to travel through the membrane at very high speeds. Most medications used to treat cardiac arrhythmias act on these ion channels (see Medications chart).

The heartbeat is produced by an electrical current that starts in the right atrium, then goes to the left atrium and then to the ventricles. When the current is interrupted or impulses don't form in the usual way, an abnormal heartbeat, or arrhythmia, is the likely result. This occurs in some types of neuromuscular disease. Arrhythmias can also be a byproduct of cardiomyopathy (a problem in the muscle layer of the heart), which is common in some other neuromuscular disorders.

 Q    WHAT IS THE HEART'S CONDUCTION SYSTEM?

 A   About 99 percent of the heart's muscle layer (myocardium) consists of muscle cells that contract in response to electrochemical signals (see "The Heart Is a Muscle, Too," vol. 6, no. 2). About 1 percent of the muscle layer is made up of specialized cells known as the conduction system, similar to the wiring in a mechanical device. These "wiring" cells control the rate and rhythm of the heartbeat by controlling the rate and direction of electrical impulses as they go through the heart (see illustration).

The heart's "master pacemaker" is the sinoatrial (SA) node, which sits high in the right atrium, one of the two upper chambers of the heart. The SA node is a little like a car's battery. Without a functioning battery, the car's engine won't start, even if it's in fine condition. Without a working SA node, the heart won't beat at a normal rate, even if it's otherwise healthy. But unlike a car, which has only one battery, the heart has auxiliary pacemaker sites that can take over for a dead SA node. The problem is that they usually set a pace that's considerably slower than the master pacemaker.

From the SA node, electrical impulses quickly spread through the right and left atria via muscle cells in the myocardium. Experts disagree about whether there are also specialized conduction pathways in the atria.

The next stop for the electrical impulses is the atrioventricular (AV) node, low in the right atrium. Here, impulses are delayed for about a 10th of a second, just long enough to allow the atria to contract and add blood to the heart's lower chambers -- the ventricles -- before the ventricles get the signal to contract. (The ventricles have mostly filled with blood before the atria contract, but atrial contraction adds more.) It's the ventricles that are the most crucial part of the working myocardium, responsible for pumping blood to the lungs and to the rest of the body.

The impulses then pass into the ventricles, where they first meet the common bundle, also known as the bundle of His. The common bundle is like a telephone cable and transmits impulses from the AV node to the rest of the ventricles. It divides into two thinner "cables," known as the left and right bundle branches.

The bundle branches divide into still thinner cables called Purkinje fibers, which transmit impulses to all parts of the ventricles. After leaving the Purkinje fibers, impulses travel from muscle cell to muscle cell to all cells of the ventricular muscle layer. The cells in the lower part of each ventricle contract slightly earlier than the cells in the upper parts, which helps eject blood from the ventricles, in the same way that toothpaste is emptied from the tube from the bottom up.

The whole process normally takes a fraction of a second, with all cells contracting nearly simultaneously.

The process can be assessed with an electrocardiogram (EKG), a test in which electrodes applied to the skin indirectly measure the path of impulses as they travel through the heart.

 Q    WHAT HAPPENS WHEN THE CONDUCTION SYSTEM MALFUNCTIONS?

 A   The cardiac conduction system can malfunction in several ways. Electrical impulses might never get started -- a "dead battery" scenario. Or they might not be conducted all the way through the normal pathway -- a "short circuit" scenario. Or they might take the wrong route: An impulse could start from somewhere outside the normal pathway or circle back when it should move in only one direction. Or, impulses could be conducted too quickly or too slowly through the heart.

All these abnormalities of both impulse formation and impulse conduction can occur. In general, the fast arrhythmias (when the heart beats too fast) and the ones that involve "off the beaten path" circuits or "off the path" beats (which usually make the heartbeat too fast or irregular) are secondary to factors such as cardiomyopathy, respiratory impairment or medications -- any of which can occur in a neuromuscular disease. In contrast, the slow arrhythmias (when the heart beats too slowly), which are also seen in some neuromuscular diseases, are generally due to the direct effects of the disease on the cells of the cardiac conduction system. Some arrhythmias need no treatment, while others need immediate treatment. Good treatments are available for most arrhythmias.

 Q    HOW CAN CARDIOMYOPATHY AND OTHER FACTORS AFFECT CONDUCTION?

 A   The SA node can set a pace for the heart without any input from the rest of the body. But, under normal conditions, the SA node receives and heeds chemical signals from the body via hormones from the blood and chemical neurotransmitters from nerve endings. These signals tell the SA node to speed up under conditions of stress, such as exercise, anxiety or a sudden increase in the need for oxygen for any reason (such as a change in altitude or a breathing problem).

The SA node would set a pace of about 100 beats a minute without any outside input. With normal input from the nervous system and other feedback systems, the SA node's pacing rate is usually between 60 and 100 beats a minute. It can be much higher under special conditions, such as strenuous exercise.

Because the SA node responds to signals from elsewhere in the body reporting on everything from blood oxygen and carbon dioxide levels to anxiety, it's easy to see how problems anywhere in the cardiovascular or respiratory system could affect the SA node's behavior and, thus, the heart rate.

Nearly everyone with heart muscle damage -- cardiomyopathy -- is prone to cardiac arrhythmias, usually fast ones, which are called tachyarrhythmias. These probably occur because of signals to the SA node and perhaps other parts of the heart as well. So, neuromuscular diseases that cause cardiomyopathy can also lead to tachyarrhythmias.

Likewise, people with failing respiratory muscles, also a common problem in neuromuscular disease, are susceptible to arrhythmias as their blood oxygen levels fall.

So, sometimes in neuromuscular disease, the cardiac arrhythmias are secondary to another, primary problem, such as cardiac or respiratory muscle damage. These arrhythmias may resolve when the primary problem is treated; or they may not, in which case the arrhythmia needs separate treatment.

There are also a few conditions in which the concentration of ions in the fluid around heart cells is abnormal, such as during attacks of hyperkalemic or hypokalemic periodic paralysis. Because the heart cells contract and relax in response to ion flow, these unusual ion concentrations can influence the heartbeat. Specialists say direct involvement of ion channels in cardiac muscle may also occur in some people with periodic paralysis, but this hasn't been well studied.

 Q    WHAT HAPPENS WHEN THE CELLS OF THE CONDUCTION SYSTEM ARE DIRECTLY DAMAGED BY A NEUROMUSCULAR DISORDER?

 A   There are some neuromuscular disorders in which direct damage to the cells of the cardiac conduction system occurs. This type of problem occurs mainly in myotonic muscular dystrophy (MMD), Emery-Dreifuss muscular dystrophy (EDMD), a chromosome 1 form of limb-girdle muscular dystrophy (LGMD type 1B), Friedreich's ataxia (FRDA), and some of the metabolic and mitochondrial disorders that affect muscle, particularly debrancher enzyme deficiency and Kearns-Sayre syndrome.

It can also occur in Duchenne and Becker MD, but in these disorders cardiomyopathy is usually the more serious and common problem. In general, the cardiac problems in neuromuscular disorders develop gradually and increase in severity with age.

When cells in the conduction system are damaged, the usual result is either a cardiac conduction block, which is like a "short circuit," or disordered impulse formation, which is like a battery problem. Another term for conduction block is heart block.

When the SA node fails to pace the heart or when its impulses are blocked, cells lower in the heart that are capable of pace setting usually take over. However, their pacing rate is slower than that of the SA node, and the person develops a slow heart rate, called a bradyarrhythmia. If the heart rate is much below 60, the person won't be able to do much exercise and may feel uncomfortable even at rest. Most people pass out with a heart rate of less than 40 beats a minute.

Blocked conduction from the atria to the ventricles -- AV block -- is one type of conduction disorder. It's often seen in EDMD. Pacemaker cells lower in the heart take over at a very slow rate. These blocks can be partial or complete.

Blocks can also occur in the bundle branches, changing the normal pathway through which impulses travel, and at other places along the cardiac conduction pathway.

Conduction system damage can also affect impulse formation in the SA node so that the SA pacemaker is set at too fast or too slow a rate. It may alternate between rates that are too fast and too slow, a condition known as sick sinus syndrome or tachy-brady syndrome.

Conduction system abnormalities in EDMD are a special case. In addition to conduction block (usually an AV block), people with EDMD get very fast heart rhythms affecting only the atria, or they develop an unusual condition called atrial standstill. These conditions seem to be related to direct damage to the conduction system.

In atrial standstill, the atria are electrically dead and paralyzed, so there's no atrial contraction to add blood to the ventricles. In very fast atrial rhythms, the atria are beating so fast that they have little or no time to fill with blood and they fail to enhance ventricular filling. In atrial flutter, the atria contract about 300 times a minute -- like a hummingbird's wings; in atrial fibrillation, the atria are like a bag of worms, constantly quivering with no effective pumping action.

Very fast atrial rhythms and atrial standstill both cause blood to pool in the atria, which can lead to the formation of clots and increase the risk of stroke. If the atrial problem can't be corrected, a drug is usually prescribed to reduce the blood's clotting ability.

Another unusual factor in EDMD is that female carriers of the X-linked form of the disease can show heart problems. X-linked diseases are carried on the X chromosome and usually affect only males.

NORMAL CONDUCTION AND TWO TYPES OF ARRHYTHMIAS
Abnormal Pacing from Atrium Cells in an atrium take on pacemaker role, overriding the SA node and leading to fast heart rates.	Normal Heart Normal conduction path is from SA node to atria and AV node, then to bundle branches and Purkinje fibers. Heart rate is about 60 to 100 beats per minute.	Atrioventricular Block Pacemaker cells in common bundle can pace heart, but heart rate is too slow.

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