Heart Diseases

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Heart diseases

Heart diseases (cardiovascular disease ) is any abnormal organic condition of the heart or the heart and circulation. A number of conditions can lead to the development of heart disease, including angina, atherosclerosis, cardiac arrhythmia, cardiomyopathy, chronic venous insufficiency, diabetes, heart attack, high cholesterol , high homocysteine, high triglycerides , hypertension , insulin resistance syndrome , mitral valve prolapse, and stroke .

Coronary artery disease (CAD), which involves atherosclerosis (hardening of the arteries ) that supply the heart with blood is the most common cause of heart attacks and is a leading killer in the United States. The primary risk factors for CAD are diabetes, male gender, family history of coronary disease at an early age, smoking, elevated blood pressure (hypertension), high LDL cholesterol, and low HDL cholesterol. The control of diabetes and blood pressure has resulted in a small benefit in preventing heart attacks. Proper ranges of cholesterol are effective in the prevention of heart attack or stroke. Total blood cholesterol above 200 mg/dl, LDL cholesterol above 130 mg/dl, HDL cholesterol below 35 mg/dl; and lipoprotein(a) level greater than 30 mg/dl are indicators of problematic cholesterol. Cholesterol is not actually a damage mechanism but is more an indicator of compromised liver function, and increased risk of heart attack. These factors mentioned above, however, do not fully account for all of the risks for heart disease since some patients without any of the above risk factors can develop heart attacks.

Throughout history, diseases of the heart have captured the concern and interest of investigators. Ancient Greek and Roman physicians observed the serious and often fatal consequences of heart disease. But effective treatment for heart disease was limited to rest and painkillers until the eighteenth-century discovery of the therapeutic properties of the foxglove plant , whose dried leaf is still used to make the medicine digitalis .

While the heart was once considered a part of the body that could never be improved surgically, the twentieth century has seen a revolution in surgical treatment for heart disease. Blocked coronary arteries can be bypassed using new tissue and failing hearts can be transplanted. Yet heart disease remains the primary cause of death in the United States. Preventive health measures, such as improved diet and regular exercise , have become fundamental tools in the battle against heart disease.


Early knowledge

Early man knew that the heart was important and powerful. As early as 1550 b.c., a passage in the socalled Ebers Papyrus of the ancient Egyptians reported that evidence of pains in the arm and the breast on the side of the heart suggested that death was approaching. Suggested treatment for such problems included beer taken with herbs.

Evidence of heart disease is also present in mummies. A. R. Long described in 1931 the condition of the fragile heart he found in a mummy dating from approximately 1,000 b.c. Further research found evidence of scarring of the heart muscle and of endocarditis, an inflammation , on the mitral valve.

Observational knowledge about the heart increased with the flowering of ancient Greece. According to P. E. Baldry, the earliest description of the circulatory system was developed in 500 b.c. by Alcmaeon, a pupil of the mathematician and scientist Pythagoras. Alcmaeon wrote that the breath, or the spirit, was sent around the body by blood vessels. Hippocrates (460-375 b.c.) and his students made many important observations about the heart. They noted that sharp pains irradiating towards the breast bone and the back were fatal; that those who were fat were more likely to die than those who were thin; and that those in pain should rest immediately. In the second century a.d., another Greek author, Aretaeus, described various ways to treat heart pain while it was occurring, including the offering of wine, the bleeding of the patient, and the encouragement of the physician.

Greek knowledge of the heart was limited by the general prohibition on human dissection. The dissection of humans was allowed in the ancient culture in Alexandria, however, where it enabled such advances as a detailed study of the way the blood vessels worked and the rate of the arterial pulse, conducted by Herophilus in 300 b.c. But the practice of human dissection was prohibited by the ancient Romans and throughout the medieval era in Europe .

The heart held special fascination for Galen (a.d. 130-200), a Greek who practiced medicine in Rome. Galen's extensive writing about the way the heart worked was respected throughout the Middle Ages. Through clinical practice with humans and careful observation of dissected animals, Galen observed that lungs were responsible for expelling waste material and that the heart was responsible for the pulse. He was known for the observation that a young woman's pulse quickened when the name of the man she loved was spoken.

Some of Galen's statements about the heart were wrong. He erroneously believed that some vessels could be used for blood flowing in two directions, and, while he knew there were chambers in the heart, he believed there were invisible pores in the tissue separating the right and left ventricles through which blood could flow. Galen wrote that these pores enabled blood to mix with air in the left ventricle. Due to the popularity of his work, these errors were passed down for centuries.


The Middle Ages

The emphasis in medieval Europe on suffering as an experience of spiritual growth did not bode well for research concerning the heart. However, advances were made by Arab scholars, whose culture encouraged scholarly research. The medical writing of Ibn Sina, known as Avicenna (980-1037), included a rich sampling of astute observations about heart disease. This book was translated widely in the East and West and was highly influential for centuries. Although he repeated some of Galen's errors about the heart, Avicenna also distinguished between many types of heart disease, including those caused by a wound or abscess , those caused by collapse of the heart, and those caused by an obstruction in the heart. In the thirteenth century, Ibn Nafis challenged some of Galen and Avicenna's incorrect assumptions about the heart, particularly Galen's belief that invisible pores allowed blood to pass between the left and right ventricles. Nafis correctly believed that blood was mixed with air in the lungs.

Medieval healers and magicians had many cures for heart pain, deriving from scholarship and folk medicine as well as quackery. One popular cure called for serving the individual a radish with salt while he sat in a vapor bath. While folk remedies may not have been effective by current standards, they may have provided patients with a sense of calm and well-being, still considered to be of value in the battle against heart disease.


The artful heart

As the prohibition against human dissection was abandoned in the Renaissance era, knowledge of anatomy and the heart grew significantly. Fascination with the heart led the artist and inventor Leonardo da Vinci (1452-1519) to create models and numerous finely detailed drawings of the organ . Da Vinci was one of many Renaissance artists who used dissection of the dead as a tool in the understanding of human life. His drawings clearly show the way the heart works as a pump and document the changes of aging blood vessels. But Da Vinci's drawings had little influence on contemporary medicine because they were held privately and were not seen by many physicians.

Andreas Vesalius (1514-1564) was far more influential among healers. His classic physiology text featured the first accurate descriptions and drawings of the heart to be publicized. Vesalius also challenged Galen's "hidden passage" idea, arguing that this was not possible given the physiology of the heart. His description of autopsy
reports revealed increasing understanding of the diversity of heart problems. One report described a huge mass of flesh in the left ventricle of a man's heart that weighed almost two pounds. Such an obstruction is known by contemporary physicians as a thrombus, a mass of blood tissue which can block blood vessels.

Another great influence in the development of knowledge about the heart was William Harvey (1578-1657), a physician whose findings about the blood and the circulatory system changed medicine profoundly. He was the first to show that blood traveled in a circle through the body. Harvey also understood the rhythmic nature of the heart's work. His work described the way blood was expelled from the heart with each contraction and entered the heart with every relaxation.

Though Harvey revealed the principles of blood circulation, he and his contemporaries did not understand the purpose of the lungs in the circulatory system. True understanding about the functioning of the lungs did not occur until the nineteenth century, when knowledge of chemistry advanced and researchers gained knowledge about the lungs' role in oxygenating blood for the tissues of the body.


Explosion of knowledge

Researchers in the eighteenth and nineteenth centuries developed effective treatment for some types of heart disease and greatly expanded their diagnostic knowledge. One important finding was the discovery that the purple foxglove plant contained a substance that was an effective medicine for some types of heart disease.

In 1775, William Withering (1741-1799), a British physician and botanist, was called to evaluate a folk remedy for dropsy, a serious condition involving an accumulation of fluid in the body that can affect the heart, the liver, and other organs. The remedy had 20 or more herbs, and Withering determined that foxglove was the active ingredient. Using his poor patients to test the remedy, Withering found the drug to be helpful in dropsy and in heart disease.

Contemporary physicians use foxglove, now called digitalis, to boost the strength of heart contractions and to lower the heart rate. It is often used in cases of congestive heart failure but can be used for other types of heart disease as well. Withering realized the potential danger in using too much foxglove and warned in 1785 that too much of the medicine could cause illness and death. Nevertheless, the medicine was used in excessive quantities by his contemporaries, leading to the death of patients and the eventual shunning of the medication. By the end of the eighteenth century, foxglove was no longer used widely for heart disease. The medication was reintroduced at the end of the nineteenth century, when its therapeutic properties were reassessed.

Other eighteenth century findings found more immediate acceptance, such as the discovery by Austrian Joseph Leopold Auenbrugger (1722-1809) that one could detect heart disease by tapping the chest in different places. A skilled examiner can use this technique (called percussion) to detect areas in the heart or lungs which have too much fluid.

Another advance which changed medicine was the invention of the stethoscope by René-Théophile-Hyacinthe Laënnec (1781-1826). Earlier physicians, such as Harvey, described the sounds of the heart. In 1816, Laënnec realized he could amplify those sounds. He first created a paper cylinder and then began using a wooden instrument. Laënnec used the stethoscope to expand knowledge about the heart, diagnosing narrowed valves and heart murmurs. The stethoscope enabled physicians to diagnose heart disease earlier in its course. The device also showed physicians that heart disease was not invariably fatal.

During the first half of the nineteenth century, physicians learned to distinguish between different types of heart murmur and the different types of valve damage they suggested. British physician James Hope conducted extensive experiments in which he used the poison curare to conduct surgery to examine the heart and other organs in animals. This experimentation led Hope to draw and describe, in 1839, two widely seen problems of the mitral valve, which is located between the left atrium and the left ventricle. Mitral valve incompetence occurs when the valve does not fit tightly, while mitral valve stenosis takes place when the valves do not open properly.

Another important finding about the heart was made in 1838, when Italian physicist Carlo Matteucci discovered that the heart muscle generates electricity . This electrical force enables the healthy heart to beat steadily and regulate its own activity. This finding cleared the way for electronic measurement of the heart, a technological advance which remains central to contemporary diagnosis of heart problems. The electrocardiogram was developed by William Einthoven (1860-1927), a German professor of physiology. Einthoven's electrocardiogram, which he first described in 1903, documented contraction and relaxation of different parts of the heart.

The death from heart disease of a young woman in labor motivated physician James Mackenzie (1835-1925) to begin an exhaustive study of heart disease early in his career. Mackenzie monitored the hearts of pregnant women and others using a polygraph he developed to detect and document the pulse in the neck. Through careful observation of patients over many years, Mackenzie realized that patients with certain types of irregular, extra heart beats were normal and could live normal lives. This contradicted contemporary wisdom, which advised the confinement of children and adults with abnormal heart beats. Mackenzie's 1908 textbook on heart disease also described auricular fibrillation (now known as atrial fibrillation), a type of irregular heart beat characterized by the ineffectual movement of the auricles, or atrial heart muscles, which can result in heart failure.


The critical arteries

Mackenzie's observations about coronary arteries reflected growing interest in the blood vessels leading to and from the heart. It had long before been observed by Da Vinci and others that a hardening occurred in blood vessels in some people. But the first well-documented report of coronary artery disease was presented by William Heberden, a British physician, in 1772. He named the condition angina pectoris, drawing the term from the Greek agkhone for strangling. He said that the condition tended to get worse and that patients often experienced it when walking. Heberden noted that when patients with this condition died, their aortas resembled bone or a bony-like substance. Contemporary researchers have found that coronary artery disease cuts down blood flow to the heart, causing pain. This pain can be triggered by emotional strain.

Another risk to individuals with thickened coronary arteries is coronary thrombosis , the most common cause of heart attack. This occurs when a blood clot forms, preventing blood flow and potentially causing death. This condition was identified by Dr. Adam Hammer, a German-born American, in 1878. Hammer suspected that the heart of one of his patients had been stopped by an obstruction and found upon autopsy that the heart was clogged by a jelly-like plug.

The nineteenth and twentieth centuries also saw advancing knowledge in the diagnosis of congenital heart disease. Currently, about eight per 1,000 infants are born with some sort of heart abnormality, including many that do not need to be treated. While most instances of congenital disorder occur for unknown reasons, congenital heart disease can also be caused by genetic disorders , such as Down's syndrome, or through maternal exposure to disease.

Cogenital heart disease, the atrial septal defect, was first described in 1900 by George Gibson of Edinburgh. This problem, which occurs when there is an opening in the wall (or septum) between two atria, can cause the right ventricle to be overwhelmed with blood, a condition that eventually leads to heart failure. In some cases, however, the holes are small and do not cause problems. For years, there was little physicians could do to help children with the problem. The development of successful surgical procedures to repair atrial septal defects was one of a multitude of dramatic modern advances in heart surgery.


Twentieth-century advances

In the twentieth century, physicians have acquired the tools to prevent heart disease in some cases and treat it effectively in many others. Major medical advances, such as the development of antibiotic therapy in the 1940s, have dramatically reduced heart disease due to syphilis and rheumatic fever . Developments in surgery, new drugs, diagnostic skill, and increasing knowledge about preventive medicine have also greatly reduced deaths from heart disease. Between 1980 and 1990, the death rate from heart disease dropped 26.7% in the United States, according to the American Heart Association (AHA).


The open heart

For most of medical history, the heart was seen as untouchable, limited by the difficulty of operating on the organ that kept the body alive. An 1896 book about chest surgery by Stephen Paget noted that "surgery of the heart has probably reached the limits set by nature to all surgery." But even as Paget cautioned doctors against trying unproven surgery on the heart, the effort was already being made. In 1882, German physician M. H. Block described his successful suturing of rabbit hearts, and by 1896, German physician Ludwig Rehn successfully repaired a lacerated heart using sutures.

Obstacles to more ambitious heart surgery took some time to overcome. High death rates marked a series of operations performed in the 1920s to correct mitral stenosis, the narrowing of the area where the mitral valve is located. One of the first successful operations was the 1939 operation on a child by Robert Gross of Boston to correct patent ductus arteriosus, an abnormality in which the circulatory pattern used by the fetus is not converted over to the type of circulation necessary for survival outside of the womb.

New types of surgery were made possible with a series of technological advances. In 1934, the American John H. Gibbon developed a machine that allowed the heart to stop beating during surgery while the blood was oxygenated outside the body. Gibbon spent nearly 20 years testing the machine on animals. In 1953, Gibbon became the first surgeon to operate on an open heart when he repaired an 18-year-old girl's atrial septal defect.

With new access to the heart, the treatment of heart disease changed dramatically. The development of the first electric pacemaker in 1950 enabled doctors to correct many arrhythmias and numerous types of heart block. In 1992, a total of 113,000 pacemakers were implanted in the United States, according to the American Heart Association.

A significant change in the treatment of coronary heart disease was the development of coronary bypass surgery in 1967 in the United States. The surgery uses blood vessels taken from elsewhere in the body, often the leg, to pass around diseased tissue. In 1992, about 468,000 coronary artery bypass grafts were performed in the United States, according to the AHA.

Another commonly performed procedure for individuals with coronary heart disease is angioplasty, during which narrowed arteries are stretched to enable blood to flow more easily. The surgery involves threading a tube through the body and stretching the artery by using a plastic balloon that is inflated when the tube is in the coronary artery. A total of 399,000 angioplasty procedures were performed in 1992, according to the AHA.

The most dramatic change in treatment of heart disease was the development of methods to replace the most damaged hearts with healthy human hearts or even animal hearts. The first successful human heart transplant was performed by South African surgeon Christiaan Barnard in 1967. The patient, however, died in 18 days. Though many surgeons tried the operation, success was limited, most patients dying after days or months, until the early 1980s, when effective drugs were developed to fight organ rejection. By 1993, a total of 2,300 heart transplants were performed in the United States, where the one-year survival rate is 81.6%, according to the AHA.


A healthier life

Physician William Osler observed in 1910 that certain types of people were most likely to develop coronary artery disease, particularly individuals who were "keen and ambitious." Contemporary efforts to prevent heart disease focus on identifying types of behavior and activity that increase the risk of heart disease and on encouraging individuals to adopt healthier lifestyles.

The massive body of evidence linking various types of risk factors to heart disease derives from a series of ambitious twentieth-century studies of heart disease in large groups of people over a long period of time. One of the best known of these efforts is the Framingham study, which has traced thousands of residents since 1949. This and other studies have led to findings that individuals are at a greater risk of heart disease if they have high levels of certain types of cholesterol in the blood, if they smoke cigarettes, if they are obese, if they have high blood pressure, and if they are male. Blood cholesterol, a fat-like substance found in all human and animal tissue, is a primary focus of efforts to prevent heart disease. High cholesterol levels are shaped, in part, by diet and can be lowered. Experts suggest limiting consumption of foods high in saturated fats, such as cream, meat, and cheese. Such a diet reduces the risk of high levels of low-density lipoprotein, or LDL, the type of cholesterol which increases the risk of heart disease.

Exercise has also been promoted as a protection against heart disease. Numerous studies have shown that individuals who do not exercise are more likely to develop coronary heart disease. Exercise reduces blood pressure and eases blood flow through the heart. In addition, people who exercise are less likely to be overweight.

Individuals who burn more calories are also more likely to have higher levels of what has been called the "good" cholesterol—high-density lipoprotein, or HDL. This type of cholesterol is believed to reduce the risk of heart disease. Other activities that boost the level of HDL include maintaining average weight and not smoking cigarettes.


New drug and diagnostic therapies

The conventional treatment for cardiovascular disease includes specific therapy for any underlying causes and may also include drugs such as ACE inhibitors (e.g., captopril, enalapril, lisinopril), blood thinners (e.g., aspirin, warfarin), the combination of hydralazine and isosorbide dinitrate, digitalis, nitroglycerin, diuretics, and beta-blockers (e.g., propranolol). The last few decades of the twentieth century have also seen the introduction of numerous drugs which prolong life and activity for individuals with heart disease. Beta blockers are used to treat angina, high blood pressure, and arrhythmia. They are also given to individuals who have had heart attacks. These drugs block the neurohormone norepinephrine from stimulating the organs of the body. This makes the heart beat more slowly and slows the dilation of certain blood vessels.

Another important class of drugs for the treatment of heart disease is the vasodilators, which cause blood vessels to dilate, or increase in diameter. These drugs, including the so-called ACE inhibitors, are used to ease the symptoms of angina by easing the work of the heart, to forestall complete congestive heart failure, and to prolong life in people who have had heart attacks.

A third important type of drug reduces cholesterol in the blood. The process by which these drugs eliminate cholesterol from the blood varies, but several work by preventing the reabsorption of bile salts by the body. Bile salts play a role in digestion, and they contain cholesterol.

Diagnostic advances have also made a difference in the treatment of heart disease. Cardiac catheterization enables doctors to see how the heart works without surgery. The process, which was first explored in humans in 1936, involves sending a tube through an existing blood vessel and filling the tube with a contrast material that can be tracked as it circulates through the heart. In 1992, a total of 1,084,000 of these procedures were performed to diagnose heart problems.


Future challenges

Though knowledge about the treatment and prevention of heart disease has expanded dramatically, heart disease remains an immense threat. A total of 925,000 Americans die each year of cardiovascular disease, a general category which includes heart disease, stroke, and high blood pressure, all of which are linked. The biggest killer is coronary heart disease, which claimed 480,170 U.S. deaths in 1992. Stroke and hypertension together killed about 180,000 and artery diseases killed 40,730.

Many more people suffer than die from heart disease. For example, a total of 5.6 million Americans had angina pectoris in 1992, and 1,290 people died from it, according to the AHA. As many as 11.2 million Americans have a history of heart attack, chest pain, or both. While 39,206 Americans died of heart failure in 1991, more than 800,000 Americans were discharged from the hospital after treatment for the problem in 1992.

Approximately 250,000 Americans die sudden and unexpected deaths due to heart disease each year, the AHA reports. Such findings support the need for educational efforts about heart disease and for the expansion of emergency care for heart attack victims.

Genetic therapy for heart disease is considered a fertile area for progress. In 1994, surgeons performed a procedure on a woman who had a genetic defect that prevented her liver from removing adequate amounts of LDL cholesterol. She had suffered a heart attack at age 16. The procedure, which took place in Michigan, involved the insertion of genetically modified cells in her liver, to enable the organ to remove LDL cholesterol properly. With the new cells, her heart should no longer be threatened by high levels of cholesterol.

Though much is known about risk factors for heart disease, new theories will continue to be tested in the future. For example, various studies have shown that individuals who eat large amounts of fish (especially containing particular oils called omega-3 fatty acids ) or who consume vitamin E have a lower than average rate of coronary heart disease. But more ambitious studies are needed to confirm this information.

Researchers are also looking carefully at women and heart disease, a topic which has been overshadowed by research concerning men and heart disease in the past. Certain estrogen/progestin supplements that were thought to reduce the risk of heart disease in postmenopausal women were found to actually increase the number of heart attacks in a long-term study published in 2002 by the NIH (National Institutes of Health).

Additionally, scientists are studying the correlation between levels of a protein in the blood known as known as C-reactive protein (CRP) and heart disease. Blood levels of C-reactive protein increase in the presence of systemic (throughout the body) inflammation, and increased CRP levels have been linked to heart attack and stroke. With elevated levels of CRP indicating blood vessel inflammation, the white blood cells are stimulated and may cause fatty cholesterol deposits to break from the vessel walls and clog arteries. Inflamed artery walls may also release greater portions of the weakened plaques, causing stroke. Elevated CRP is considered a predictor of heart disease even in the absence of other risk factors such as obesity , high blood pressure, or smoking, and may indicate heart disease even before symptoms are present. A blood test is becoming widely available to detect CRP levels.

In 1998, the American Heart Association published its third list of what it considers to be the most promising research areas in heart disease. These included: gene therapy which could potentially encourage the growth of new blood vessels to and from the heart, thus bypassing diseases vessels; the discovery of new "super aspirins" which seem to have even greater protective effects for both heart attack and stroke; more data to support the association between inflammation and heart attacks; better techniques for early detection of obstructed vessels in the heart (using magnetic resonance imaging, or MRI); hope that damaged left ventricular muscle can regain better functioning, if a mechanical device called a left ventricular assist device (LVAD) takes over the work of the left ventricle for a time; further evidence that tobacco is a crucial risk factor in the development of heart disease, as evidenced by research which showed that as few as 10 cigarettes a day shortens life; more research supporting the importance of diet and exercise on levels of cholesterol in the blood; efforts to encourage people to seek treatment more quickly when a heart attack is suspected; the association between non-responsiveness to nitric oxide, and the development of high blood pressure.

Over the past century, researchers have made huge advances in the understanding, treatment, and prevention of heart disease. For the first time in history, medicine has acquired the tools to provide many individuals who suffer from heart disease with active, full lives. Being born with a faulty heart is no longer a reason to live a sedentary, shortened life. Yet even as the medical profession has gained skill in healing, preserving, and even replacing the failing heart, this crucial organ remains vulnerable.

See also Angiography; Transplant, surgical.


Resources

books

Bulpitt, C.J. Epidemiology of Hypertension. Series: Handbook of Hypertension. Vol. 20. Amsterdam: Elsevier, 2000.

Crawford, M.H., and J.P. DiMarco, ed. Cardiology. London: Mosby Limited Ltd., 2000.

Grubb, N., and D. Newby. Churchill's Pocketbook of Cardiology. London: Churchill Livingstone, 2000

Grundy, S.M., ed. Cholesterol-Lowering Therapy—Evaluation of Clinical Trial Evidence. New York: Dekker, 2000

Katz, A.M. Physiology of the Heart. 3rd ed. Philadelphia: Lippincott Williams & Wilkins, 2000

periodicals

Avezum Jr., Alvaro, Marcus Flather, and Salim Yusuf. "Recent Advances and Future Directions in Myocardial Infarction." Cardiology 84 (1994): 391-407.

Detjen, Jim. "U.S. Scientists Successfully Treat Patient with Gene Therapy." Knight-Ridder-Tribune News Service (March 31, 1994).

"A Heart Disease Checkup." Tufts University Diet and Nutrition Letter (September 1993): 2.


Patricia Braus

KEY TERMS

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Angina pectoris

—Chest pain that occurs when blood flow to the heart is reduced, causing a shortage of oxygen. The pain is marked by a suffocating feeling.

Auricular fibrillation

—Now known as atrial fibrillation; a condition marked by the irregular contraction of the atrial heart muscle.

Coronary artery disease, or ischemic heart disease

—Common cause of death due to heart attack, which results from narrowing or blockage of the coronary arteries. The disease can also cause angina.

Coronary thrombosis

—A potentially fatal event in which the coronary artery is blocked by a thrombus, a clot of platelets and other blood factors which can prevent the passage of blood.

Electrocardiogram (ECG)

—A picture of the operation of the heart, obtained by measuring the electric potential of the heart muscle.

Heart block

—Impairment of the electrical signal which controls the heart's activity.

Heart failure

—A clinical syndrome which takes place when the heart's activity no longer meets the body's needs. Congestive heart failure is marked by water retention and breathlessness.

Stenosis

—The narrowing of a canal or duct.