As the name implies, heart failure (HF) is a condition where the heart fails in its duties of circulating blood through the lungs and back out to the tissues. Approximately 4.8 million Americans are currently thought to suffer from heart failure. The incidence of HF more than doubles with each decade of age after 45, and approximately 400,000 new cases are diagnosed each year in the U.S. As the U.S. population continues to age, the prevalence of HF is anticipated to climb. Although HF is more common in older people, it is not an inevitable consequence of aging. Unfortunately, it can also be a disease of the young.
HF results when the heart loses its ability to contract as vigorously as it normally should. Since the heart consists of muscle cells, either death of the cells or other (as yet poorly understood) disorders that cause the living cells to weaken result in loss of contractile vigor. The most common cause of HF in the U.S. is coronary artery disease, wherein cell death results from inadequate blood supply to areas of heart muscle. The inability of heart muscle cells to divide and reproduce themselves limits the hearts capacity to adapt to disease processes that involve cell death. Since the heart is unable to generate replacement tissue, it responds to damage in two ways. First, when myocardial (heart muscle) cells die, scar tissue-fibrous tissue similar to that encountered in the healing of any wound-replaces the dead cells. Scar tissue lacks the ability to contract but does allow the heart to maintain its shape. Second, since the remaining heart has fewer working cells but the same amount of work, surviving muscle cells undergo hypertrophy to compensate for the cell deficit. With hypertrophy, the cells grow extra contractile elements and enlarge. Hypertrophied cells can provide extra working elements to a damaged heart, but they are never able to compensate fully for the damage that has occurred.
Contractile weakness of heart cells is responsible when most cardiomyopathies cause HF. The vast majority of cardiomyopathies have no known cause. Although viral infection and autoimmune processes have long been suspected as causative factors, the mechanism by which otherwise viable cells might weaken by either disease process is still not understood. Some (up to 25%) are transmitted genetically in families, but most occur at random.
To understand what happens when HF becomes manifest requires some knowledge of the hearts functional capacity and how it interacts with the rest of the circulatory system. Interactions with the circulatory system explain why the heart is able to act as more than a simple pump that can only increase its output by increasing its rate. These interactions also help explain the symptoms of HF and the therapeutic approaches to it later in this essay.
The heart interacts with the arteries and veins that make up the circulatory system by a network of nerves that make up the autonomic nervous system. The autonomic nervous system receives and processes information from body sensors in multiple sites and organs and relays this information to the brain. The brain decides what to do and sends signals to the heart, arteries, and veins automatically. Two major branches make up the autonomic nervous system. The parasympthetic nervous system is responsible for rest activities such as the digestion of food and the slowing of the heart rate with relaxation. The sympathetic nervous system is responsible for gearing the body up for exertion or "fight or flight" types of activity. The sympathetic nervous system plays an important role in HF.
Cardiac performance is measured in several different ways, but the most widely used objective indicator of how well the heart works is the left ventricular ejection fraction (LVEF). The LVEF is the percentage of its volume that the left ventricle (the main pumping chamber) pumps out with each beat. Because of its shape, the heart cannot completely empty itself each time it beats. Under normal circumstances, the LVEF is approximately 60%. When stimulated by signals from the sympathetic nervous system, however, the normal heart can increase its LVEF so that the amount of blood pumped with each beat increases.
The increase in cardiac output with exertion is mediated by activation of the sympathetic nervous system. At rest, the body requires approximately 2.5 liters of blood flow each minute for each square meter of body surface area; a 510" man who weighs 150lb would have a cardiac output at rest of approximately 5 liters per minute. During exertion, cardiac output may double or even triple. The sympathetic nervous system sends signals to the heart to beat faster and more forcefully. If the demand for blood flow exceeds the extra amounts provided by these mechanisms, the body is forced to conserve blood flow by redirecting blood away from vital organs that are less involved in exercise. The sympathetic nervous system then sends signals to arteries in the digestive organs, the kidneys, and the skin that cause the arteries to constrict so that less blood flow goes to these organs and can instead be sent to the exercising muscles. The sympathetic nervous system also activates the adrenal glands to release epinephrine into the bloodstream. The kidneys are stimulated to produce a substance called renin, which results in the production of a substance called angiotensin II, which also causes blood vessel constriction. Renin also causes the production of a hormone called aldosterone, which instructs the kidneys not to discard fluid. When the period of exertion comes to an end, the sympathetic nervous system stops sending out signals, and the body returns to its resting state.
When the heart is damaged, it is unable to eject as much blood with each beat as it normally would-its LVEF is diminished. If the bodys sensors do not detect adequate blood flow, any or all of the same compensatory mechanisms described above to increase blood flow with exertion become activated with lesser degrees of exertion or even at rest. The heart rate increases, the part of the heart that is able to contract hypertrophies (grows more contractile elements in the existing cells in order to increase its contractile force), and the heart enlarges to accept more blood. Signals from the sympathetic nervous system and angiotensin II instruct the arteries and veins to constrict. The kidneys conserve fluid in response to aldosterone and to decreased blood flow. This conservation of fluid results in overflow from the circulatory system into the tissues of the legs, the lungs and abdomen. The free space in the abdominal cavity can fill with fluid like a reservoir. As these tissues swell, they stiffen and malfunction.
When faced with chronic exposure to the chemical mediators the body pours out to accommodate the malfunctioning heart, the heart itself may be adversely affected. Epinephrine and norepinephrine make the heart more electrically irritable and prone to arrhythmias. Other chemical mediators such as tumor necrosis factor may cause the myocardial cells to malfunction or even die. As fluid accumulates in the venous system, the blood pressure inside the heart rises and the blood flow to the heart muscle itself may decrease, especially if there are coronary blockages. Since the heart is forced to beat faster but only receives nourishing blood flow when it is relaxing between beats, the faster heart rate allows less time for the heart to be "fed" even though its for fuel has increased. The longer the process continues, the more likely it is to perpetuate itself.
Although it may seem logical to assume that HF symptoms and their severity correlate well with the degree of damage the heart has suffered, this is frequently not true. People with LVEF of 25% may be able to do their own housework or yard work without difficulty, while those with LVEF of 40% may be breathless at rest. Likewise, deterioration in symptoms does not necessarily mean that the heart has deteriorated. The response to the compensatory mechanisms is frequently the deciding factor in how severe the symptoms of HF are. Symptoms of heart failure usually begin to appear when the ejection fraction falls below 40%.
Constriction of the arteries and veins coupled with fluid conservation by the kidneys results in collection of fluid in tissues. The legs (or whatever part of the body is lowest) will often swell, and the abdomen (another site where the pressure is low) will often accumulate fluid, leading to a sense of bloating. The liver, which has an extensive venous system, will often swell, resulting in loss of appetite, nausea, and mild jaundice. The intestines swell, resulting in constipation and poor absorption of medications. The lungs, as they accumulate fluid, first become stiff, so that breathing deeply becomes more difficult. As fluid continues to accumulate in the lungs, it spills into the air spaces and interferes with oxygen and carbon dioxide transfer. Decreases in blood flow to the kidneys result in decreases in waste filtration and changes in drug metabolism. Blood flow to the skin decreases, resulting in pallor and cold intolerance. As blood flow continues to fall, memory problems and confusion can result.
Virtually any heart disease that causes heart damage can result in HF. Although HF symptoms usually become apparent only when the left ventricular ejection fraction drops below 40%, many people with left ventricular ejection fraction below 40% remain asymptomatic until a second illness such as an infection places extra demands for blood flow on the heart.
In the U.S. adult population, coronary artery disease and myocardial infarction are the most common causes of HF, accounting for about 65% of all cases of HF. Cocaine and drug use have been associated with coronary artery spasm and myocardial infarction. Although myocardial infarctions are usually characterized as painful events, as many as 30-40% of myocardial infarctions are not accompanied by symptoms. Unexplained weakness of the heart muscle has been increasingly recognized as a cause of HF. Cardiomyopathies, diseases in which the heart muscle loses contractile strength but is not replaced by scar tissue, account for approximately 30% of cases of HF. Most cardiomyopathies have no known cause, although long-term heavy alcohol use has been recognized as one cause of cardiomyopathy. It has been estimated that approximately 25% of cardiomyopathies are familial, although most are not accompanied by currently recognized genetically-transmitted diseases. Inflammatory processes attacking the heart muscle called myocarditis can result in cardiomyopathy, and the root cause of the inflammation often cannot be identified. If identified early enough and controlled, myocarditis may not result in enough heart damage to cause HF; oftentimes, however, HF is the first recognizable symptom of myocarditis. Other potential causes include unknown toxic substances and viral infections.
In the young, congenital cardiac abnormalities such as ventricular septal defects and valve or artery stenosis with normal ventricular function have been the usual causes of HF, although CAD has also been seen in many young people in the U.S.
Prolonged tachycardia can decrease the cardiac output and raise the blood pressure in the lungs and veins such that it appears that compensatory mechanisms have been invoked. If the tachycardia continues for a long period of time, a cardiomyopathy can develop. This so-called "tachycardia cardiomyopathy" is an important disease to identify, since restoration of the normal rhythm often allows the heart to recover normal function.
It is also important to realize that the symptoms of HF described above do not necessarily imply that the heart is failing. Swelling, the HF symptom most familiar to most people, can also occur with an otherwise normal heart in several situations. Simple varicose veins or increases in venous pressure due to obstruction of large veins in the legs or abdomen can cause swelling, and the patient may experience shortness of breath when attempting to walk simply because the legs are heavy. Severe hypertension can raise the resistance to blood flow such that the heart must invoke compensatory measures to maintain the circulation. Fluid retention with swelling is common, as is shortness of breath from elevated blood pressures in the lungs. Kidney disease can result in fluid retention so that the swelling and shortness of breath result without compromise of the circulation. Liver diseases such as cirrhosis can also result in massive fluid retention. Inappropriate connections between arteries and veins can result in high venous pressures and low arterial pressures in the absence of heart problems; closing the connection restores normal circulation and relieves HF symptoms. It is therefore vital that a proper diagnosis of HF be based on a careful evaluation of the whole person rather than upon one symptom in isolation.
Death from HF occurs as a result of progressive pump failure in only about one-half of HF patients. The other fifty percent of patients with HF die suddenly without any warning symptoms. Both tachyarrhythmias and bradyarrhythmias have been observed to be responsible for arrhythmic death in HF, but ventricular tachyarrhythmias have been thought responsible for the majority of the deaths. For patients with poorly compensated HF, the prognosis without treatment is poor. Only 50% of patients with New York Heart Association class 3 or 4 HF survive the first 2 years following diagnosis. Long-term survival in HF is based upon the extent to which the pumping elements of the left ventricle are damaged. In general, the lower the left ventricular ejection fraction, the poorer the prognosis for the patient with HF.
Clinical trials in which HF patients have received implantable cardioverter-defibrillators have suggested that sudden death may be preventable in many if not most of these patients. Nonsustained ventricular tachycardia has been observed in a large percentage of patients with HF. Many HF patients who have happened to be wearing electrocardiographic monitors when they died have been observed to have sudden sustained ventricular tachycardia at the time of their deaths. Whether HF patients who have only exhibited nonsustained ventricular tachycardia may benefit from prophylactic ICD implantation is currently not known but under investigation.
Antiarrhythmic drugs, on the other hand, have shown mixed results in preventing death in HF. Quinidine, procainamide, flecainide, and encainide have been shown in good studies to actually worsen survival in patients with HF who are treated with them. Amiodarone and beta blockers have shown some benefit in decreasing death from arrhythmias with some studies suggesting up to a 50% reduction in mortality among HF patients treated with them.
Beside preventing sudden death in the patient with HF, the major issue with HF involves maximizing circulatory function while minimizing workload on the heart. Vasodilator drugs-drugs that relax arteries and veins and thereby lower the blood pressure against which the heart must pump and the volume of blood the heart must move-have been demonstrated to increase survival of HF patients when they are made part of the therapeutic regimen. Survival improvements of 25-30% have been demonstrated in several studies. Interestingly, the vasodilator drugs have principally reduced sudden death in HF patients rather than death from circulatory failure.
Agents to make the heart beat stronger exist and have been in use for many years but carry several drawbacks. All of them must be given by continuous intravenous infusion. In addition, some studies suggest that the drugs may improve HF symptoms but shorten survival. Mechanical devices to assist with pumping have recently become available and continue to undergo development.
Cardiac transplantation remains the one long-term answer to HF at this time. Despite improvements in anti-rejection drugs in recent years, rejection-acute and chronic-remains a serious problem for transplant patients, as do side effects from anti-rejection medications and the development of coronary artery disease in the transplanted heart.
Since many HF related deaths are preventable by controlling arrhythmias, we at the Texas Arrhythmia Institute believe that solutions already exist for at least some of the problems faced by the HF patient. As mechanical heart assist devices improve, we are optimistic that HF will become a more manageable disease in the near future.