Although displacement of blood is its primary function, each and every beat of this unique muscular pump is initiated and finely regulated by electrical impulses that originate in the heart itself. Electrical currents, not in the form of electrons like those that course through the wires of our house, but in the form of ions, flow across the membrane of each cell causing voltage surges that set the heart in motion. Sodium ions rush into the cells, to be followed by potassium and chloride ions making a quick exit. The resulting voltage spike or action potential regulates the influx of calcium ions that mediate the sliding motion of filaments within each cell causing their shortening or contraction.

This process, repeated in each adjoining cell of the heart, causes the orderly spread of electrical activity and the synchronous contraction of the myocardium (heart muscle). Like other "excitable" tissues, the cells of the heart are electrically connected through low resistance pathways. These pathways facilitate the spread of the electrical impulse, ensuring efficient activation and pumping motion. Without electrical activity, the heart lies motionless and serves no useful purpose. Disorderly electrical activity also known as arrhythmias may also render the heart inefficient or totally useless as a pump. Extreme disorganization of the electrical activity within the heart can lead to sudden death, the single most prevalent mechanism of death in the United States, taking the lives of over 350,000 Americans each year. Nearly every minute of every day someone in this country dies of sudden cardiac death, very often the result of an arrhythmia known as ventricular fibrillation.

Arrhythmias are not always life-threatening. Some, including extrasystoles or "extra beats" may be quite innocuous. Others. like AV nodal tachycardia, although not lethal, may be incapacitating. Still others. like atrial fibrillation may be less crippling, but a nuisance nevertheless.

Through research scientists have identified a number of mechanisms by which cardiac arrhythmias arise. Prevention, diagnosis and treatment have advanced at a steady pace offering a better quality of life for some and a new lease on life for many sufferers of heart disease. Many of these advance are directly attributable to research done at the Masonic Medical Research Laboratory (MMRL), a leading center for the study of cardiac arrhythmias for over 35 years.

The tradition of excellence continues at the MMRL thanks to the generosity of concerned individuals, including NYS Masons. It is only through such generous and considerate gifts that our scientist are able to wage a vigorous fight against the diseases that plaque humankind, Also among those contributing importantly to the research in this area are the Brethren of the Most Worshipful Grand Lodge of Florida. Our Florida Brothers raised over $55,000 in recent months, all devoted to life-saving medical research at the MMRL. A better gift to humanity is hard to conceive.

Seventy times a minute, 100,000 times each day, it beats effortlessly, indefatigability. Your heart is an organ like none other, charged with moving 4,300 gallons of blood each day through the intricate vascular network of our body. Although displacement of blood is its primary function, each and every beat of this unique muscular pump is initiated and finely regulated by electrical impulses that originate in the heart itself. Electrical currents, not in the form of electrons like those that course through the wires of our house, but in the form of ions, flow across the membrane of each cell causing voltage surges that set the heart in motion. Sodium ions rush into the cells, to be followed by potassium and chloride ions making a quick exit. The resulting voltage spike or action potential regulates the influx of calcium ions that mediate the sliding motion of filaments within each cell causing their shortening or contraction.

This process, repeated in each adjoining cell of the heart, causes the orderly spread of electrical activity and the synchronous contraction of the myocardium (heart muscle). Like other "excitable" tissues, the cells of the heart are electrically connected through low resistance pathways. These pathways facilitate the spread of the electrical impulse, ensuring efficient activation and pumping motion. Without electrical activity, the heart lies motionless and serves no useful purpose. Disorderly electrical activity also known as arrhythmias may also render the heart inefficient or totally useless as a pump. Extreme disorganization of the electrical activity within the heart can lead to sudden death, the single most prevalent mechanism of death in the United States, taking the lives of over 350,000 Americans each year. Nearly every minute of every day someone in this country dies of sudden cardiac death, very often the result of an arrhythmia known as ventricular fibrillation.

Arrhythmias are not always life-threatening. Some, including extrasystoles or "extra beats" may be quite innocuous. Others. like AV nodal tachycardia, although not lethal, may be incapacitating. Still others. like atrial fibrillation may be less crippling, but a nuisance nevertheless.

Through research scientists have identified a number of mechanisms by which cardiac arrhythmias arise. Prevention, diagnosis and treatment have advanced at a steady pace offering a better quality of life for some and a new lease on life for many sufferers of heart disease. Many of these advance are directly attributable to research done at the Masonic Medical Research Laboratory (MMRL), a leading center for the study of cardiac arrhythmias for over 35 years.

The tradition of excellence continues at the MMRL thanks to the generosity of concerned individuals, including NYS Masons. It is only through such generous and considerate gifts that our scientist are able to wage a vigorous fight against the diseases that plaque humankind, Also among those contributing importantly to the research in this area are the Brethren of the Most Worshipful Grand Lodge of Florida. Our Florida Brothers raised over $55,000 in recent months, all devoted to life-saving medical research at the MMRL. A better gift to humanity is hard to conceive.

Like a metronome, our heart maintains a steady beat helping us to keep time with the musical interludes of life. But that faithful pace can be interrupted, slowed or accelerated disrupting the harmony of our lives. As discussed in part II of this series, cardiac arrhythmias can take many forms ranging from single extra beats sensed as occasional palpitations to totally uncoordinated contractions known as fibrillation. Fibrillation of the upper chambers of the heart (atria) usually leads to a fast somewhat irregular heart rate, accompanied by fatigue, chest discomfort and, in people with coronary disease, anginal pain. Fibrillation of the main pumping chambers (ventricles) is a bit more serious in that it leads to death unless reversed in a timely manner. Between these two extremes exist a wide variety of irregular rhythms that impact on the quality of our lives and in some cases are life-threatening.

Detection of an arrhythmia, the most important first step in dealing with the problem, is at times easier said than done. Physicians have a number of tools in their armamentarium to tackle this problem. The most important is the electrocardiogram or ECG. This wonderful device records the electrical activity generated by the heart at the body surface. You may recall from our discussion in Part I of this series, that although the heart is a muscular pump, each of its beats is initiated and finely regulated by electrical activity generated by the flow of ions across the cardiac cell. The humps and bumps recorded by the ECG provide your doctor a wealth of information about the condition of your heart. It can tell him whether your heart is functioning normally or alternatively whether your heart is beating too fast, too slow or unevenly. If it is beating too slow, the ECG will reveal whether this is due to a problem with your primary pacemaker, the sinus node, or the "gatekeeper" that controls the flow of impulses from the atria to the ventricle known as the atrioventricular (AV) node. If it is beating too fast, the ECG will indicate whether this is due to rapid generation of electrical impulses in the atria or ventricles and provide the physician some clue as to the mechanism of the tachycardia (fast rate), flutter (very fast rate) or fibrillation (ultrafast rate due to disorganization of the electrical impulse leading to uncoordinated contractions). The ECG will also reveal whether a patient may have suffered a heart attack recently or at some time in the past and whether a congenital heart defect should be suspected. Electrocardiograms can even predict whether a drug like erythromycin, a widely prescribed antibiotic, may be life-threatening to individual people. Although medical science and ECG interpretation have advanced considerably in recent years, our understanding of the ECG remains incomplete and is one of the areas of study at the MMRL.

One of the principal difficulties in dealing with arrhythmias is the ability to catch up with them, for they are often elusive, appearing for short periods of time and then subsiding for hours, days, weeks or even months. Although infrequent, they may be troublesome causing occasional dizzy spells as in the case of paroxysmal tachycardia and may even be deadly as in the case of ventricular fibrillation (sudden death) or Torsade de Pointes. The physician has additional tools at his disposal to detect these isolated events and when necessary to provoke them. The first of these is non-invasive and involves the attachment of several stick-on electrodes to the chest wall which are then connected to a Holter monitor. This device is a miniaturized portable ECG recorder generally worn for a period of 24 or 48 hours. Data are recorded on small cassette tapes which are analyzed at the doctor’s office or clinic. Holter monitors detect arrhythmias that are intermittent but frequent, but are unlikely to detect those that appear once a week or once a month. This limitation is circumvented by devices called event recorders which are miniaturized ECG recorders worn for much longer periods and activated by the patient when symptoms occur. These units not only record the ECG but are capable of transmitting it to the physician over the telephone.

When these methodologies fail to detect suspected arrhythmias, the physician may resort to an electrophysiological (EP) study. This procedure is usually recommended for patients who have previously experienced life-threatening events. An EP study involves the insertion of a cathode electrode into the heart through either an artery or vein in the groin, arm or neck. Electrical impulses are introduced through the electrode to stimulate the heart and provoke the arrhythmia. Recordings of local activity within the heart may be obtained with the same or different electrode to localize the region of troublesome activity. Drugs may be tested during the EP study to assess their ability to prevent the induction of the arrhythmia. Alternatively, a special catheter may be introduced into the heart to destroy the tissue that is giving rise to the erratic electrical activity by using radiofrequency energy to heat the tip of the electrode. Known as catheter ablation, this procedure has gained considerable popularity as the procedure of choice in the treatment of a variety arrhythmias, including AV nodal tachycardia and the Wolf-Parkinson-White syndrome.

These diagnostic procedures and therapeutic modalities are available today because of many years of painstaking research conducted at medical research laboratories worldwide. Among the laboratories that have contributed fundamentally to our present day knowledge of cardiac electrophysiology and arrhythmias is the Masonic Medical Research Laboratory. For nearly forty years, scientists at the MMRL have worked to define the function of the heart in both health and disease. On-going research continues to focus on the mechanisms of arrhythmias, how they can be prevented and controlled; how drugs like erythromycin can produce them and what the various waves in the ECG are trying to tell us. In coming segments of this series, I hope to expand on specific arrhythmias, their causes,treatments and, in some cases, cures.

Like the beating of distant drums, your heart modulates its pace, adjusting to environmental and physical demands by slowing down and speeding up. Occasionally, it goes into a frenzy, beating out of control, racing against time for no good reason. As discussed in part III of this series, this type of cardiac arrhythmia is referred to as a ventricular tachycardia (VT). It is most frequently observed after a heart attack, in otherwise diseased or scarred hearts, and occasionally in apparently normal and healthy hearts. In most cases, VT is due to a short-circuiting of electrical activity within the ventricles of the heart, thus giving rise to a circular movement of the electrical wave. This mechanism, known as reentry, continuously re-excites the heart, causing it to beat at rapid rates. In some individuals, VT is caused via a "focal" mechanism involving a rapid and repeated firing of a small group of abnormal "pacemaker" cells within the ventricles of the heart. In the latter case, the arr hythmias are often very sensitive to the sympathetic nervous system activity and to various stimulants.

Ventricular tachycardia, when relatively slow and regular, may occur without symptoms. At more rapid and/or irregular rates, VT usually produces symptoms in the form of palpitations, pre-syncope (dizziness) and syncope (fainting spells). The dizziness and fainting spells occur because the pumping chambers do not have sufficient time to fill with blood and as a consequence are inefficient in pumping blood to the brain and other organs of the body. The ECG will alert your physician as to how dangerous the arrhythmia may be. If the ECG signals attending each beat of the tachycardia are similar in size and shape, the tachycardia is said to be monomorphic. In contrast, when the signals are of varying amplitude and shape, the arrhythmia is said to be polymorphic. Generally speaking, the latter is more likely to be life-threatening. The danger of a rapid polymorphic tachycardia is that it can degenerate into ventricular fibrillation (VF), which is the principal cause of sudden death. Although a heart in VF beats at an extremely rapid rate, it is useless as a pump because the contractions are uncoordinated.

Treatment of VT depends on the cause. When secondary to a focal or discrete reentry mechanism, ablation therapy may be able to prevent the arrhythmia, using radiofrequency energy to burn the abnormal pacemaker or the troublesome tissue that allows reentry to develop. In some cases, antiarrhythmic drugs, such as amiodarone, beta-adrenergic blockers (propranolol), potassium and sodium channel blockers, may be helpful. In the case of life-threatening arrhythmias, the first line treatment is an Implantable Cardioverter Defibrillator (ICD). This is a device that senses when the heart goes into ventricular fibrillation and automatically delivers a shock to restore normal rhythm. These marvelous devices have dramatically changed the treatment of arrhythmias over the past decade and have extended the lives of hundreds of thousands of people. In some cases, an ICD may be used in conjunction with antiarrhythmic drugs to limit the number of times that the device is activated.

VT/VF occurring in apparently normal hearts has been the subject of intense study over the past 5 years. These studies have demonstrated the existence of primary electrical disease caused by defects in specific ion channels. The heart is otherwise normal in structure and function. One form of this type of disease is called the long QT syndrome (LQTS), because the QT interval in the ECG is prolonged in patients afflicted with this problem. It is hereditary and has now been linked to a genetic defect in one of four different ion channel genes that contain the genetic message for three different ion channels (potassium and sodium channels). The ion channel defects give rise to the development of a polymorphic tachycardia which can degenerate to ventricular fibrillation. The syndrome tragically takes the lives of teenagers and young adults. Children and young adults experiencing one or more syncope events, are usually fully evaluated to rule out LQTS. The genetic definition of the disease has made possible the development of gene-specific therapy. While many patients are protected by use of beta-blockers, others require ICDs. Studies currently underway are examining the therapeutic value of sodium channel blockers like mexiletine in the three genetic forms of the diseases, based on recent reports from the Masonic Medical Research Labortory.

Another type of primary electrical disease, recently discovered, is known as the Brugada Syndrome. Like LQTS, the Brugada syndrome has been linked to a defect in the sodium channel gene. A very rapid polymorphic tachycardia develops in these patients, causing them to pass out. In some cases sudden death is the first symptom. This too is an hereditary disease whose incidence is highest in individuals of Southeast Asian origin. For reasons that physicians and scientists do not as yet understand, the disease often lies dormant for three to four decades before emerging to rear its ugly head. The average age of death of Brugada patients is 39. ICDs are indicated in patients who have previously experienced syncope or who have been resuscitated from sudden death. Recent work from the Masonic Medical Research Laboratory has suggested a new pharmacological approach to therapy using "transient outward current" blockers. This pharmacologic alternative may be critically important in many parts of the world where ICDs are not affordable.

The knowledge that has made these diagnostic procedures and therapeutic measures available emanated from decades of painstaking research conducted at medical research laboratories throughout the world. Among the laboratories contributing fundamentally to our present day knowledge of cardiac electrophysiology and cardiac arrhythmias is the Masonic Medical Research Laboratory. For forty years, scientists at the MMRL have contributed to our understanding of the function of the heart in both health and disease. On-going research continues to focus on cardiac arrhythmias, the single most prevalent mechanism of death of Americans. In coming segments of this series, I will expand on other arrhythmias, their causes, treatments and cures.

Seventy times a minute, 100,000 times each day, it beats effortlessly, indefatigability. Your heart is an organ like none other, charged with moving 4,300 gallons of blood each day through the intricate vascular network of our body. Although displacement of blood is its primary function, each and every beat of this unique muscular pump is initiated and finely regulated by electrical impulses that originate in the heart itself Electrical currents, not in the form of electrons like those that course through the wires of our house, but in the form of ions, flow across the membrane of each cell causing voltage surges that set the heart in motion. Sodium ions rush into the cells, to be followed by potassium and chloride ions making a quick exit. The resulting voltage spike or action potential regulates the influx of calcium ions that mediate the sliding motion of filaments within each cell causing their shortening or contraction.

This process, repeated in each adjoining cell of the heart, causes the orderly spread of electrical activity and the synchronous contraction of the myocardium (heart muscle). Like other "excitable" tissues, the cells of the heart are electrically connected through low resistance pathways. These pathways facilitate the spread of the electrical impulse, ensuring efficient activation and pumping motion. Without electrical activity, the heart lies motionless and serves no useful purpose. Disorderly electrical activity also known as arrhythmias may also render the heart inefficient or totally useless as a pump. Extreme disorganization of the electrical activity within the heart can lead to sudden death, the single most prevalent mechanism of death in the United States, taking the lives of over 350,000 Americans each year. Nearly every minute of every day someone in this country dies of sudden cardiac death, very often the result of an arrhythmia known as ventricular fibrillation.

Arrhythmias are not always life-threatening. Some, including extrasystoles or "extra beats" may be quite innocuous. Others, like AV nodal tachycardia, although not lethal, may be incapacitating. Still others, like atrial fibrillation, may be less crippling, but a nuisance nevertheless.

Ventricular tachycardia, when relatively slow and regular, may occur without symptoms. At more rapid and/or irregular rates, VT usually produces symptoms in the form of palpitations, presyncope (dizziness) and syncope (fainting spells). The dizziness and fainting spells occur because the pumping chambers do not have sufficient time to fill with blood and as a consequence are inefficient in pumping blood to the brain and other organs of the body. The ECG alerts your physician as to how dangerous the arrhythmia may be. If the ECG signals attending each beat of the tachycardia are similar in size and shape, the tachycardia is said to be monomorphic. In contrast, when the signals are of varying amplitude and shape, the arrhythmia is said to be polymorphic. Generally speaking, the latter is more likely to be life-threatening. The danger of a rapid polymorphic tachycardia is that it can degenerate into ventricular fibrillation (VF), which is the principal cause of sudden death. Although a heart in VF beats at an extremely rapid rate, it is useless as a pump because the contractions are uncoordinated.

Polymorphic ventricular tachycardias commonly occur in patients with an hereditary syndrome, known as the long QT syndrome. Children born with this syndrome, usually lead a normal childhood, but begin to experience dizzy spells in their teenage years or early adulthood. The dizzy spells are due to an atypical polymorphic ventricular tachycardia known as Torsade de Pointes. If not properly diagnosed and treated, one of the dizzy spells can result in sudden death. It has long been appreciated that the sympathetic (adrenergic fight or flight) nervous system plays a key role in precipitating attacks leading to sudden death in these children. In some individuals, the attack occurs during or soon after strenuous exercise, in others it occurs after a sudden startle such as an alarm clock going off, and in still others it occurs during sleep. The mechanism for this has escaped the grasp of scientists for over 30 years. Antzelevitch, and coworkers recently developed experimental models of three genetic forms of the long QT syndrome and demonstrated that sympathetic activity can cause the deadly arrhythmia by different mechanisms in each of the three hereditary variants of the disease, Moreover, they showed that in one form of the disease, sympathetic activity was protective, thus challenging the common practice of prescribing ? adrenergic blockers to all patients with this disease. Investigations by the same group recently showed that a class of drugs known as sodium channel blockers may also be of therapeutic value in all three genetic variants of the disease.

Antzelevitch and his Experimental Cardiology team are world renowned for their work related to these hereditary diseases and other forms of sudden cardiac death. Studies by this group were the first to demonstrate that the ventricles of the heart are comprised of at least three electrically distinct myocardial cell types: epicardium, endocardium and a unique cell type discovered at the Masonic Medical Research Laboratory, called the M cell. The three cell types respond differently to a variety of drugs and disease states and thus can contribute to the development of a variety of cardiac arrhythmias, including Torsade de Pointes associated with the long QT syndrome. Members of the group have been selected for four international distinctions in the form of young investigator awards over the past 2 years.

The mechanisms uncovered by these investigations have suggested new approaches to therapy of the long QT syndrome. These are currently undergoing clinical trials at medical centers worldwide. One day soon, the families of individuals born with these syndromes may be able to rest easy knowing that their loved ones are protected from what could otherwise be a catastrophic outcome.

Racing faster and faster, the electrical impulses twist and turn tortuously through the upper chambers of the heart causing a fluttering sensation and an irregular heart rhythm. In some this arrhythmia goes unnoticed, in others it may cause dizziness, lightheadedness or even fainting spells. In many, it leads to fatigue, a tightness in the chest and/or shortness of breath. The culprit is an arrhythmia known as atrial fibrillation (AF).

AF is the most common symptomatic abnormal heart rhythm. Over 2.2 million Americans are afflicted with the disease and its incidence is increasing, in part, related to increasing age of the population. AF is a particularly common in older individuals. At age 70, the incidence of atrial fibrillation is 5% (1 in 20). At 80 years of age 1 in 10 (10%) will develop AF.

The most important fact that you need to know about atrial fibrillation is that one third of all debilitating strokes in the United States are caused by untreated AF. For this reason, if you suspect AF, due to a fast and irregular heart rhythm, you should seek medical help without delay.

AF is caused by abnormal, rapid and irregular electrical activation of the upper chambers (atria) of the heart. Although the atria are activated hundreds of times per minute, many of the impulses generated are blocked at the level of the atrioventricular (AV) node, the safety valve of the heart, and are not transmitted to the ventricles, the main pumping chambers of the heart. The pulses that succeed in making it through the AV node emerge at an uneven pace, causing an irregular rhythm, most commonly at heart rates ranging between 100 to 175 beats per minute. Less commonly, particularly in the presence of drugs, a large fraction of the impulses may be blocked within the AV node, causing abnormally slow heart rates. Although both abnormally slow and rapid rates can be problematic, AF is usually not life-threatening, so long as both patient and doctor are vigilant about proper anticoagulation.

AF can develop both in the presence and absence structural heart disease or systemic disease. Some cases of AF have no identifiable cause. Others are linked to dysfunction of the sinus node (the "natural pacemaker" of the heart) and a number of heart and lung disorders including coronary artery disease, rheumatic heart disease, mitral valve disorders, and pericarditis. It is a common but transient complication of coronary artery bypass graft surgery (CABG). Hypertension (high blood pressure), hyperthyroidism, and recent heavy alcohol use (binge drinking) or surgery of the heart, also predispose to the development of AF. Some forms of AF are inherited, in which case the arrhythmia may appear at a very early age, even in infants. Familial forms of AF are often associated with more deadly syndromes such Brugada, Short QT and Long QT syndromes.

Treatment of AF depends on the cause and on whether the arrhythmia is chronic or of recent onset. There are four distinct issues that are important to consider in patients with AF:

• rate control (control of rate of beating of the ventricles);
• rhythm control via conversion of the atrial fibrillation to sinus rhythm;
• maintenance of sinus rhythm following conversion; and
• prevention of embolic stroke from thrombi that form in the fibrillating atria.