Heart Disease

Although most heart damage in the adult population of the United States occurs as a result of coronary artery disease and myocardial infarction, a significant number of people are discovered to have no demonstrable evidence of coronary artery disease when they develop arrhythmias or heart failure. Cardiomyopathy (Greek: cardio=heart; myo=muscle; pathy=disease) refers to a family of diseases which accounts for an important cause of structural heart disease that seldom comes to the attention of the general public.

Cardiomyopathy refers to abnormal heart muscle function not caused by coronary artery disease, congenital heart disease, hypertension, or valvular disease. In the heart affected by cardiomyopathy, each and every heart muscle cell is damaged so that it contracts poorly. The hearts overall systolic (pumping) function is therefore impaired. In an attempt to compensate for its reduced ability to pump, the heart muscle hypertrophies (thickens) and the hearts chambers enlarge. In association with the process of hypertrophy, scar tissue proliferates and infiltrates the heart muscle so that arrhythmias may develop.

Three general types of cardiomyopathy have been described. The most common of the three is dilated cardiomyopathy, in which the ventricles enlarge and the hearts pumping function is often severely depressed. The second most common type is hypertrophic cardiomyopathy, in which genetically-transmitted abnormalities of the contractile proteins predispose the heart to massive hypertrophy. Because the heart muscle grows so much, it may actually take up space in the ventricles, causing the chamber sizes to be abnormally small and outflow of blood from the heart to be impeded. The third most common type is restrictive cardiomyopathy, which is characterized by stiffness of the ventricular myocardium and normal ventricular size. Restrictive cardiomyopathy is rare and will not be discussed further in this section.

Dilated cardiomyopathy is so called because the earliest (and often most prominent) feature is enlargement of the left ventricle due to decreased force of contraction. Other cardiac chambers may also enlarge, but usually not to the degree that the LV enlarges. LV contraction is usually moderately to severely impaired so that the first symptoms the patient notices are often those of fatigue and congestive heart failure. In fact, many patients remain asymptomatic for several years before heart failure symptoms or the development of arrhythmias brings the disease to their attention.

How and when dilated cardiomyopathy comes about is, for the most part, poorly understood. The pathologic findings associated with dilated cardiomyopathy appear to be caused by most or all of the disease processes that cause dilated cardiomyopathy. At least 75 diseases are known to produce dilated cardiomyopathy, but many cases remain idiopathic. Approximately 20% of cases are transmitted genetically as familial diseases, sometimes associated with other genetic syndromes and sometimes not. The exact genetic mechanisms resulting in the development of dilated cardiomyopathy remain unknown. Toxins such as alcohol, cocaine, and doxorubicin (a cancer chemotherapeutic drug) have long been known to damage the heart, but, for unclear reasons, only certain individuals who consume alcohol or cocaine or receive doxorubicin sustain severe heart damage. Viral infections have also been implicated in causing dilated cardiomyopathy, but it is not known whether the infection itself damages the heart or whether it is the immune response to the infection that causes the damage. It has also been observed that viruses cause genetic changes in the cells that in turn may cause the cells to malfunction. The role of the immune system in the development of cardiomyopathy has long been suspected, since myocarditis (inflammation involving the heart muscle) is sometimes identified as a precursor to cardiomyopathy. When, how, and why the immune system attacks the heart remain obscure.

Dilated cardiomyopathy has no clearly defined natural history, probably due to the fact that it is a mixture of so many different diseases. Since many patients are asymptomatic for unclear periods of time, there may be long periods of symptom-free survival. Spontaneous remissions are not uncommon in dilated cardiomyopathy; patients may recover a significant degree of heart function for long periods before relapsing, and some never relapse. For example, patients with cardiomyopathy due to alcohol consumption may improve dramatically and remain in remission simply by abstaining from alcohol. Overall survival correlates with the degree of left ventricular dysfunction, and the appearance of heart failure symptoms suggests a relatively poor prognosis. Severely impaired left ventricular function correlates with 30% one-year mortality. Mortality rates for patients referred to tertiary care medical facilities are approximately 25 to 30% at one year and 50% at five years, although these patients are probably the sickest of those with dilated cardiomyopathy. Studies including less symptomatic patients suggest that the five-year mortality may be more like 20%. Angiotensin-converting enzyme inhibitors and beta blockers have been used to treat heart failure associated with dilated cardiomyopathy and have been shown to reduce mortality rates. Since the mortality rates referenced above predate the widespread use of these medications, mortality rates may have improved significantly in recent years.

Ventricular arrhythmias, including PVC and nonsustained VT, are very common findings in patients with dilated cardiomyopathy. Sudden cardiac death is estimated to occur in approximately 30% of patients, with the remainder succumbing to progressive heart failure or other medical problems. PVC are observed in virtually all patients, and nonsustained VT is seen in approximately 40% of patients. Bradyarrhythmias (slow heart rates) probably account for some deaths, but how many is not clear.

Determining which patients will suffer arrhythmic death is not possible using current technology. Some studies have suggested that electrophysiologic study may be helpful in separating out patients at highest risk of arrhythmic death, but other studies have shown no clear benefit to electrophysiology study. Suppression of PVC and nonsustained VT using antiarrhythmic medications has not been proven to improve survival. The only antiarrhythmic therapy proven to improve survival is implantation of a defibrillator. However, while defibrillator implantation has improved survival from arrhythmias, its impact on total survival (given the fact that 70% of patients with dilated cardiomyopathy will die of non-arrhythmia related causes) is still under investigation. The Sudden Cardiac Death Heart Failure Trial, sponsored by the U.S. National Institutes of Health and ongoing at the Texas Arrhythmia Institute, will compare treatment strategies of medications versus defibrillator implantation for patients with heart failure of all causes to see whether defibrillator implantation in patients who have not had serious ventricular arrhythmias will prolong survival.

Hypertrophic cardiomyopathy (HCM) refers to a family of diseases in which the heart muscle grows in abnormal patterns to produce abnormally thick chamber walls and, in some circumstances, abnormal narrowing of the main pumping chambers. Whereas hypertension and other heart diseases can also result in thickening of the heart walls, the cells in HCM contain abnormal proteins that result in unusual cell shapes, arrangement of the cells in disorganized patterns, and the appearance of fibrous tissue mixed in with the muscle tissue. Mutations in the contractile proteins cause the individual cells to contract less vigorously than normal cells. Nevertheless, the hypertrophy of the heart muscle allows the overall pumping function of the heart to be normal or even unusually vigorous in contrast to the poor left ventricular pumping function seen with most cardiomyopathies. The coronary arteries are frequently imbedded in the muscle tissue. Overgrowth of muscle tissue and vigorous contraction can lead to problems maintaining adequate blood flow to the muscle and a propensity in some patients to develop arrhythmias.

HCM, like all cardiomyopathies, is a disease caused by problems within individual heart muscle cells that lead to abnormalities in the hearts architecture. Before echocardiography became available as a quick and easy way to define cardiac anatomy, HCM was difficult to detect and to characterize. As a result, many of the features of HCM described in old studies were based upon only the most severely affected and symptomatic of patients. A recent study in Olmsted County, Minnesota reviewed anatomic and clinical findings of all of the people in the county who carried the diagnosis of HCM and compared the findings with those of patients with cardiac hypertrophy associated with hypertension. The HCM patients were more likely to exhibit localized areas of hypertrophy within the heart as opposed to generalized hypertrophy seen with hypertension. The interventricular septum was the site most likely to be involved by localized hypertrophy, but 38% of the HCM patients had generalized cardiac hypertrophy. In some patients, the thickening of the interventricular septum causes the left ventricular outflow tract (which leads to the aorta) to be partially obstructed when the heart contracts. When obstruction occurs, a higher pressure is necessary inside the heart to generate any given blood pressure. The higher the interior pressure in the LV, the more energy is required and the lower the blood flow in the coronary arteries. In the past, septal hypertrophy was thought to result in obstruction to blood flow out of the left ventricle in the majority of patients. More recent studies have noted a much lower frequency of LV outflow tract obstruction, and only approximately 5% of patients require aggressive therapy for management of LV outflow obstruction.

Genetic studies have identified mutations in genes for proteins that make up the muscle elements in each individual cell in HCM. These mutations result in the production of structurally abnormal contractile proteins. More than 50 different mutations that result in HCM have been identified so far, and the mutations appear to be transmitted in an autosomal dominant fashion. It is estimated that one in 500 people actually has some form of HCM, making HCM the most common genetic malformation of the heart. Some of these genetic studies have led to the identification of HCM in asymptomatic family members who would not otherwise have been discovered to have HCM. This genetic diversity explains why HCM behaves so differently among different patients.

Beside symptoms from LV outflow obstruction, the other major concern with regard to HCM is arrhythmias. The abnormally thick heart walls are prone to inadequate blood flow during tachycardias, and very fast rhythms (whether supraventricular or ventricular) can cause the heart muscle to starve. When the muscle receives inadequate blood flow, it pumps less vigorously and relaxes poorly such that an initial decrease in blood flow can initiate a vicious cycle of starvation and malfunction. This is especially true if LV outflow obstruction is present. If the cycle is not interrupted, ventricular fibrillation and sudden cardiac death can ensue.

Atrial fibrillation is seen in many HCM patients. The hypertrophied heart can cause the atria to dilate so that atrial fibrillation becomes easy to initiate. People with HCM also are more prone to have accessory AV pathways, which may allow signals from the atria to be transmitted to the ventricles at a very fast rate. However, unless there is poor control of the ventricular rate or a high degree of LV outflow obstruction, atrial fibrillation is no different for HCM patients than it is for patients with other heart conditions.

Syncope has also been observed in HCM patients, and its presence may be ominous since sudden cardiac death is also thought to be more common in HCM. Although syncope can result from a simple fall in blood pressure as it does in patients who do not have HCM, syncope can also result from life-threatening arrhythmias that happen by chance to stop spontaneously. HCM patients may be more prone to episodes of hypotension because of the medications they may take or because of obstruction to LV outflow. Interestingly, of the several established risk factors for sudden cardiac death which have been identified among HCM patients, syncope is not among them. The strongest risk factors include documented sustained ventricular tachycardia or ventricular fibrillation, a family history of sudden cardiac death (especially if two or more family members have died at a young age), and a high risk genetic mutation. Although genetic typing is not routinely performed on HCM patients, recent studies have suggested that certain mutations are associated with reduced survival, even when hypertrophy is not marked. Other risk factors for sudden cardiac death which have been suggested include nonsustained ventricular tachycardia during 24-hour ECG monitoring, marked wall thickening, marked enlargement of the left atrium, substantial LV outflow obstruction, and a drop in blood pressure during exercise; the degree of risk associated with each of these is less clear. ICD implantation has become the standard therapy for ventricular tachycardia or ventricular fibrillation in the HCM patient, and, since the ICD has become relatively simple to implant, erring in the direction of safety for the HCM patient with risk factors has become a very attractive option.

Recent studies of less symptomatic HCM patients have revealed no difference in prognosis between these HCM patients and the general population. Old studies had suggested that the annual mortality rate for patients with markedly symptomatic HCM was approximately 6% (compared to an annual mortality rate of approximately 1% in the general population). The main problem that remains is that asymptomatic people with HCM can still suffer from serious arrhythmias and even sudden cardiac death without any prior warning. Despite the suggestion from statistics that syncope in a HCM patient is a benign phenomenon in the population at large, the risk in the individual patient can only be inferred by careful consideration of each case.

Newer methods for relieving LV outflow obstruction in HCM patients may lead to differences from what has so far been reported regarding the likelihood of arrhythmias and overall prognosis. Nonsurgical septal reduction therapy, now performed as an alternative to open heart surgery with removal of septal tissue, involves the injection of alcohol into a branch of one of the coronary arteries to cause controlled destruction of part of the interventricular septum. The success rates of reducing LV outflow obstruction have been quite high. However, destruction of the septum has also been shown to inflict temporary damage the conduction system in up to 50% of patients and permanent conduction system damage requiring permanent pacemaker implantation in up to 25% of patients. Ventricular fibrillation has been reported several weeks after the procedure, and follow-up has been too brief to determine how frequently the septal scar will later act as a circuit for ventricular tachycardia. Ventricular tachycardia occurring months to years after the procedure may result in an adverse prognosis for those who have undergone nonsurgical septal reduction.

Hypertrophic cardiomyopathies (HCM) are genetically transmitted (autosomal dominant) diseases and important cause of SCD and syncope in young people. HCM is due to the mutations of contractile protein genes, in particular the myosin gene, that renders heart muscle contraction ineffective. To compensate for this inefficiency the heart muscle cells enlarge resulting in thickened walls. In contrast to hypertrophy seen with hypertension, all growth in HCM is disorganized and often associated with growth of fibrous tissue in the heart wall. Systolic function is often normal or even better than normal.

No variables can reliably predict which HCM patient will die suddenly. Characteristics indicating an increased risk of SCD include: family history of SCD (<age 55); onset of symptoms in childhood or adolescents; history of cardiac arrest or syncope; non-sustained ventricular tachycardia with impaired consciousness; myocardial ischemia with hypotension; and possibly specific mutations of the myosin gene.

Arrhythmogenic right ventricular dysplasia (ARVD) is a rare condition with unclear etiology that produces VT. This condition is characterized by replacement of the right ventricular myocardium with fatty and fibrous tissue. Since the pulmonary circulation involves a low pressure, symptoms of right-sided congestive heart failure are seldom seen in the early stages of the disease. What usually brings the disease to the attention of the patient is symptoms of palpitation or syncope. VT is the most common arrhythmia recorded. The natural history of ARVD is unknown since it often causes sudden death as its first symptom, but it is thought that the left ventricle may eventually be involved by the degenerative process. ARVD is most frequently found in young adult males but is seen in both sexes and at any age. Physical examination may be normal, but the ECG often shows right ventricular conduction delay or right bundle branch block.

The incidence of ARVD is unknown, but ARVD is emerging as a cause of sudden death in young otherwise healthy adults. Although there is no known treatment for the degenerative process, the arrhythmias can be managed with drugs or ICD implantation.

Hereditary or familial diseases associated with arrhythmias in the presence of normal heart anatomy (no "structural heart disease") have been called "primary electric diseases" of the heart. Two of these entities are discussed below. It is important to realize, however, that many individuals who suffer episodes of sudden death or ventricular fibrillation will not exhibit either these diseases or structural heart disease of any kind currently recognized. There is still much to learn in this field of primary electrical diseases of the heart.