Taming the No.1 Killer

By Anastasia Toufexis

Doctors attack heart disease with new techniques and potent drugs

Charles Weiner, 45, was trudging through Boston's snowy streets one night when he suddenly felt a gripping pain in his chest. In the previous eight years he had had two similar experiences, but after thorough physicals, including blood tests and electrocardiograms, doctors could find nothing wrong with his heart and attributed the pains to a mild gall bladder attack or chest muscle strain. This time, though, Weiner was given a new diagnostic test. Doctors injected a radioactive substance into his bloodstream, then took pictures of his heart with a special camera that detects radioactivity. The pictures revealed that his heart was not getting an adequate supply of blood, and further tests showed that the coronary arteries were blocked in several places. Weiner underwent bypass surgery, which eased his discomfort and may have prolonged his life.

Dana Wilson, 41, a lumber company manager in Mehama, Ore., had been taking drugs to control the occasional irregular beating of his heart following a massive heart attack. But the treatment proved unsuccessful; one day several months after the attack, his heart began to race, reaching 250 beats per minute before returning to normal. Doctors turned to an innovative method of studying arrhythmias. They threaded electrodes into his heart and electrically stimulated the tissue to induce the erratic beating. Trying different drugs, they learned that none would be helpful in treating Wilson's condition. But by moving the electrodes around, doctors located the areas of heart tissue that seemed to be generating the faulty rhythms. Last April surgeons operated and removed the suspect tissue.

David Clendenen, 58, an electrical contractor in Sacramento, had never had any indication of heart trouble. But one morning last March, he suddenly felt "like there was an elephant sitting on my chest." Realizing he was having a heart attack, he called for help and was rushed to the hospital by ambulance. Emergency room physicians stabilized his condition and transferred him to a special laboratory for a delicate experimental procedure. A long, thin plastic tube was inserted into an artery in his leg and gently pushed through the blood vessels all the way up into the aorta to the coronary arteries. A radiopaque substance was injected into the coronary vessels, and X-ray pictures were taken, revealing a blood clot. Doctors infused an anticlotting drug through the tube. Within an hour, the clot had dissolved, blood flow was reestablished, and Clendenen was spared extensive heart damage.

A decade or so ago, these techniques were unknown. Today they are just a few of the dramatic new weapons being used to fight the scourge of the 20th century, cardiovascular disease. Disorders involving the heart and blood vessels take many forms; among the most common are high blood pressure, clogged coronary arteries, abnormal heart rhythms, strokes, rheumatic heart disease and congenital defects. Today these ailments represent the leading health problem in the industrialized world, and one that is fast assuming major importance in underdeveloped countries as well. In the U.S. alone, cardiovascular illness claims nearly 1 million lives each year. That makes it the nation's No. 1 killer, accounting for half of all deaths recorded annually. Cancer, though more feared, claims only a third as many victims.

More than two-thirds of the deaths result from heart attacks or strokes. Heart attacks, which take about 550,000 lives each year, occur when the coronary arteries that supply blood to the heart muscle become obstructed. Without oxygen and other nutrients carried in the blood, heart tissue dies or is damaged. If too much tissue is affected, the heart is so weakened that it cannot pump. But even mild damage can kill by disrupting the electrical impulses that govern the heart's rhythmic beating. Stroke claims another 170,000 lives, and is also caused by impeded blood flow, this time to the brain.

A treacherous assassin, cardiovascular illness can go unnoticed for decades and kill without warning. Says Cardiologist Joseph Messer of Chicago's Rush-Presbyterian-St. Luke's Medical Center: "Heart disease is often an iceberg, and the way it breaks the water is likely to mean death or irreparable damage."

Until the 20th century, cardiovascular disease was not considered a serious health problem, in part because it often went unrecognized. Heart attacks, for example, masquerade as acute indigestion and other ailments. About 1940 the incidence of heart disease began to surge, probably because people smoked more, ate fatty foods and exercised infrequently. The price of luxury has proved higher than anyone expected. Heart ailments cost the U.S. $50 billion a year. About half of that amount is the cost of medical care, the rest is lost wages and productivity. Nearly a quarter of fatal heart attack victims are below age 65.

Gloomy as these statistics are, heart specialists are optimistic these days, and for good reason. In the past decade, the U.S. death rate from strokes has plummeted 37% and from heart attacks 25%. Experts offer a variety of possible explanations: better emergency treatment, including the training of 15 million Americans in cardiopulmonary resuscitation; improved coronary care in hospitals; the stress on the dangers of cigarettes and the benefits of exercise and "prudent" diet.

Perhaps most important has been the aggressive campaign waged by the National Heart, Lung and Blood Institute and the American Heart Association to detect and treat hypertension, a risk factor in heart attacks and strokes. "Decades ago, there were two schools of thought," says Dr. Robert Levy, director of the N.H.L.B.I. "One said that high blood pressure should be lowered, and the other said that it can be protective [that is, needed to supply more blood to organs like the brain]. Now we know that it's very important that we treat it." Nearly 35 million Americans, one of every four adults (more in blacks), have chronically elevated blood pressure, but most are not aware of it. Hypertension often has no characteristic symptoms, hence its tag "the silent killer." But it can be diagnosed easily enough by taking multiple blood pressure readings. Normal is usually around 120/80, though the figure may vary widely, depending on the individual. The higher number is called systolic pressure and refers to the force exerted by blood pushing against artery walls as the heart contracts and pumps blood; the lower figure, the diastolic pressure, is the force between beats, when the heart is at rest. Persistent measurements over 140/90 are needed to establish that a person has hypertension.

What causes the condition is often unclear. Once diagnosed, however, it can be controlled, though not cured. Losing weight or restricting salt suffices for some patients. More intractable cases can be treated with medication.

Among the most widely prescribed is a group of drugs known collectively as beta blockers. By preventing nerve impulses from reaching special sites (beta receptors) in the heart and blood vessels, these drugs reduce both the rate at which the heart beats and the force of its contractions. Beta blockers were introduced in the U.S. in the 1970s and have caused much excitement. In addition to lowering blood pressure, they are used extensively to control angina and are commonly prescribed for irregular heart rhythms as well. They are now being studied to see if they can prevent death in people who have survived a heart attack. About 10% of survivors die in the year following an attack.

Recent advances in diagnosis and treatment will make damaged hearts easier to mend in the decade ahead. Sophisticated new machines allow doctors to "see" a patient's heart without surgery. Major strides have been made in understanding how the heart works and why disease occurs. These in turn have led to breakthroughs in the operating theater and the drug research laboratory. Says Cardiologist Eugene Braunwald of Brigham and Women's Hospital and Beth Israel in Boston: "There's been more done in cardiology research in the past ten years than in its entire previous history." Roman DeSanctis of Massachusetts General Hospital terms it "one succession of miracles after another."

The most familiar advance dates from 1967, when surgeons performed the first bypass operation on a patient with a coronary artery blockage. In the procedure, a vein taken from the patient's leg is grafted to the aorta and to the unobstructed portion of the coronary artery, thus detouring blood around the blocked area.

The operation usually relieves angina, the severe chest pain that develops when the heart muscle is not getting enough blood. Bypass proponents also feel that the operation reduces the chance of death from heart attack in many patients. From 1975 to 1980, some 540,000 bypasses were performed in the U.S., too many according to some critics, who feel that drug therapy is safer, cheaper (a bypass costs about $15,000) and as effective in many cases. Says Surgeon John Kirklin of the University of Alabama Hospitals in Birmingham, who performs an average of six bypasses a week: "Bypass grafting can make a person absolutely well who has been totally disabled. But you don't want to use such a powerful weapon until you have to. You want to keep your powder dry."

The best way to do that is to detect the disease before it has grown desperate. Today physicians are refining their diagnostic techniques at a remarkable pace. A decade ago, they checked for heart disease by taking a patient's history, doing a physical examination and ordering chest X rays, electrocardiograms and angiograms. X-ray films and EKGs give general information about the heart's structure and electrical activity, respectively. Angiograms, special X-ray pictures made by injecting a radiopaque substance through a thin tube inserted into the heart or coronary arteries, provide more accurate information about constrictions in the coronary arteries. But the technique is costly (about $2,000) and usually requires a two-night stay in the hospital. It carries a slight risk: one of every 1,000 patients dies from the procedure.

The angiogram is still the most important diagnostic tool, but now doctors also have an array of safe, "noninvasive" tests at their disposal. Among them:

Ultrasound Imaging. Also known as echocardiography, this is probably the most widely used noninvasive test. By bouncing high-frequency sound waves off the heart in much the same way that surface ships search for submarines, physicians can get a picture of the heart's interior, its chambers and valves.

Nuclear Scanning. Using this technique, doctors can examine the heart's pumping performance and check for evidence of obstruction in the coronary arteries. Radioactive isotopes with affinities for certain tissues are injected into the bloodstream. A special imaging device, called a scintillation camera, picks up the gamma rays emitted by the isotopes, and a computer translates the information into pictures. For example, by using thallium 201, an isotope that lodges in healthy heart muscle, doctors can tell if tissue has died as a result of a heart attack and whether blood is flowing freely through the coronary arteries. The test is usually performed first while the patient is exercising on a treadmill or bicycle and then while resting. Similarly, physicians can radioactively label components of the blood, like red cells, to see how efficiently the organ is pumping.

Positron Emission Tomography. Here the heart is labeled with isotopes that emit charged particles called positrons. A special machine takes simultaneous cross-section views of the heart from different angles; a computer reconstructs the images to give a three-dimensional picture of the heart. "It isn't in clinical use yet, but it's a valuable tool for sophisticated research," says Jeffrey Borer, a cardiologist at New York Hospital.

Balloon Angioplasty. Treatment, like testing, has improved apace. This method has been used on some patients to unclog coronary arteries laden with cholesterol plaque. A catheter is inserted into an artery in the arm or leg and guided to the blocked artery. Then a smaller tube with a tiny, uninflated balloon at its tip is threaded through the larger tube and centered in the plaque-narrowed area. The balloon is inflated for several seconds, flattening the plaque against the artery walls and opening the passage. Dr. Andreas Grvintzig at Emory University, who developed the experimental technique, says it unblocks arteries in 90% of attempts. If the vessel narrows later, as has happened 10% to 15% of the time, the procedure can be done again. Researchers estimate that 5% of those who are candidates for bypass operations might be treated just as effectively--and more quickly and cheaply --by balloon angioplasty.

Clot-Dissolving Streptokinase. Cardiologists are excited about an experimental technique that may be able to stop a blood clot-caused heart attack right in its tracks, and perhaps minimize damage to heart tissue. Says Garrett Lee of the University of California, Davis Medical Center: "Ten years ago, a patient admitted to the hospital would have been taken to the coronary care unit and continued to be monitored. It would be bed rest, oxygen and drugs to prevent such complications as arrhythmias and heart failure--but the heart attack would run its course." With this new technique doctors try to interrupt the attack by feeding a narrow tube through an artery in the groin into the blocked coronary vessel and injecting a drug called Streptokinase, which can dissolve the clot within an hour. Says Lee:

"The main problem with this technique is that patients just don't get into the hospital in time. In the first two to three hours, 50% of the heart muscle that's destined to die will die, then the amount of tissue jeopardized tapers off." Because blood clots tend to form where plaque clogs the artery, researchers are considering following streptokinase therapy with balloon angioplasty. The aim is to prevent extensive-tissue damage and a second attack.

Diagnosing Arrhythmias. A large percentage of the heart disease deaths in the U.S. each year are due to arrhythmias, irreguLar heartbeats that occur when the organ's electrical impulses are disrupted. Normally, the millions of heart cells contract in specific sequence as an electric current flows from one part of the heart to another. Irregular rhythms are associated with coronary artery disease, faulty valves and heart muscle damage resulting from hypertension, heart attacks or excessive drinking. When the system shortcircuits, the heart develops abnormal rhythms, which can lead in extreme situations to fibrillation, a disorganized twitching of the heart muscle. The victim may suddenly feel faint or dizzy or fall unconscious; death can occur within minutes.

The greatest threat of arrhythmias is that the first episode can be fatal. In emergencies the heart can be electrically shocked to restore a healthy beat. But many people do not get help in time and are not resuscitated. One device that doctors now use to diagnose a patient's irregular rhythms is the 24-hour EKG recording. A person wears a tape recorder-size monitor that has electrodes leading from it to his chest as he pursues his normal daily routine. The machine automatically records his heart's rhythm over the day, during which time he keeps a diary of his activities and symptoms. Doctors then analyze both sets of data. If previously unsuspected and potentially dangerous rhythms are detected they can then be treated with either drugs or pacemakers. Introduced in the late 1950s, pacemakers regulate the heartbeat through a steady stream of electrical impulses. Nearly a million people now rely on implanted devices, which last from six to twelve years.

Electrophysiology. At the University of Pennsylvania and several other institutions, cardiac electrophysiologists are investigating the heart's electrical conduction system to learn where abnormal beats originate and to develop appropriate treatment. They do this by inserting several narrow tubes containing electrodes to induce a faulty rhythm in the heart. Says Penn's Mark Josephson: "Using electrical stimulation of the heart and mapping, we can decide whether to use drugs, a pacemaker or surgery."

Implantable Defibrillators. To help some patients with severe rhythm disruption, scientists at Johns Hopkins University and Sinai Hospital of Baltimore developed a small device called an automatic implantable defibrillator. This is placed in the abdomen and has electrodes that are connected to the heart's right atrium and to the ventricles' pointed tip. It is powered by lithium batteries good for three years or 100 shocks. Says Hopkins Cardiologist Myron Weisfeldt: "When the patient has an arrhythmia persisting for at least ten seconds, the machine waits another five seconds and then discharges an electric shock, which usually stops the arrhythmia."

Treating Atherosclerosis. This condition refers to the narrowing of the arteries by a buildup of fatty deposits. Today many heart specialists theorize that atherosclerosis is a complex process that starts with a minor injury to the smooth single layer of cells that line the arteries in a cobblestone pattern. Researchers speculate that the damage may result from cigarette smoking, high blood pressure or virus infection.

To restore the pathway, the body musters its repair troops, led by the platelets, tiny disc-shaped particles in the blood that help stop bleeding by promoting clotting. These "little plates" produce a chemical, thromboxane, that constricts blood vessels and signals other platelets to gather round. The platelets also manufacture a chemical that induces the artery's exposed underlying muscle cells to multiply. "If the injury is short-lived," says Russell Ross of the University of Washington School of Medicine in Seattle, "the proliferation process is reversible. But if the injury is chronic and repeated in the same sites in an artery wall, then you have a buildup." Cholesterol and debris collect around the muscle cells, an atherosclerotic plaque develops and the artery narrows. Platelets continue to congregate and may eventually help create a clot that completely blocks blood flow. Says DeWitt Goodman of the Columbia University College of Physicians and Surgeons: "There is good reason to think if you interfere with platelet function you might reduce the chance of heart attack or stroke, but it is not 100% proved."

One drug being studied as a platelet fighter is that old standby, aspirin. Results so far have been equivocal, but, says Goodman, "many doctors, including myself, tell patients with a very high risk of heart disease to take half an aspirin a day." A drug for possible future use is a synthetic version of prostacyclin, a chemical related to thromboxane but produced by the cells lining the artery and having exactly the opposite effect: it relaxes blood vessels and prevents platelets from clumping.

Calcium Blockers. Researchers have also discovered that calcium plays a crucial role in the heart's workings. The electrical stimulation and subsequent contraction of the heart muscle are both partially governed by the flow of calcium ions into the muscle cells. Because of this, drugs that inhibit the flow of calcium ions have attracted intense interest. Declares Boston's Braunwald: "Calcium blockers are not just another class of drugs that has come along. They lower blood pressure, they raise cardiac output in heart failure, they are effective in arrhythmias. They are also useful for angina. They're almost too good to be true."

The calcium blockers, which have been mainstays of therapy in Europe and Japan for some years but are just now being introduced in the U.S., also promise to deal beneficially with coronary artery spasm, a phenomenon whose importance is becoming more widely recognized. These sudden clampdowns can close arteries that are clear of plaque, leaving no trace, after the vessels relax, that the spasm ever occurred.

They are a greater threat when the arteries are already narrowed. "There are probably some patients with pure atherosclerosis, and some with pure coronary artery spasm," says Braunwald, "but I suspect the majority of patients have both."

The Food and Drug Administration is expected to approve marketing of calcium blockers within months. Excitement over their potential applications is so high that major pharmaceutical companies are bringing out their own brand names, mostly for angina sufferers.

Sadly, many patients are beyond the stage when standard treatments can be of any help. For them, doctors are working on a dramatic last-resort weapon-the replacement of failed hearts. Transplants were all but abandoned in the mid-1970s; only about 20% of the more than a hundred recipients survived a year. Interest is reviving, primarily because of work done at Stanford University. Led by Surgeon Norman Shumway, the Stanford team has performed 209 transplants since 1968 and reports that half of recipients can now be expected to live at least five years. These improved results are largely due to the ability to predict more accurately when the donor heart will be rejected. This allows doctors to use anti-rejection drugs with precision, minimizing undesired side effects.

On March 9 Stanford surgeons performed a heart-lung transplant, only the fourth such operation ever and the first since 1971. The patient was Mary Gohlke, 45, a newspaper executive from Mesa, Ariz. She had been suffering from pulmonary hypertension, a condition in which high blood pressure in the vessels of the lungs impairs breathing and eventually damages the heart. Dr. Bruce Reitz and his Stanford team severed the aorta and trachea and cut through the heart's right atrium to remove the heart and lungs. "The whole thing comes out as a package," explains Reitz. Then they replaced it with healthy organs from a 15-year-old boy killed in a car accident.

Gohlke, who is expected to be released from the hospital within the next two weeks, is doing well--walking and taking short trips outside the hospital in a wheelchair. On May 1 Reitz performed another heart-lung transplant, this one on a former undertaker, Charles Walker, 30, who had a congenital heart defect. He too is doing well.

Even more spectacular is an operation that researchers at the University of Utah hope to do soon: implantation of an artificial heart. The challenge is formidable, since the heart is one of nature's masterpieces. The fist-size organ beats 100,000 times a day, and over a lifetime pumps enough blood through the 60,000-mile circulatory system to fill 13 million bbl. The Utah heart, dubbed the Jarvik 7 for its designer, Robert Jarvik, is made of plastic and aluminum and powered by electricity. The implant operation will be performed by Utah Surgeon William DeVries. He will cut away the heart's lower chambers (the ventricles), leaving the upper ones (the atria) intact. Then he will sew Dacron fittings to the aorta, pulmonary artery and atria. The artificial heart, actually two ventricles, is then snapped into place "like Tupperware," says DeVries. A plastic tube leads from each ventricle through openings made in the patient's abdomen to a breadbox-size console that controls the rate and pressure of air pulsed to the heart. The console in turn is connected to an air compressor. As air flows into each ventricle, it pushes a thin membrane upward, expelling blood that has entered through the atria out through the pulmonary artery and the aorta.

The Utah team expects no mechanical difficulties. A Jarvik 7 pumped water in a test tank from April 1978 until this March. Of more concern is the chance of infection, a problem that has occurred in about half of the implants in animals, often in tissue along the air hose lines. Though calves have lived an average of two to three months with artificial hearts (one, Tennyson, made it to 268 days), the researchers are wary of making predictions for human recipients. Says Jarvik: "It's likely a patient could live a year if he lives a day."

In March the FDA held up permission for implants in humans until the Utah team supplies additional details on how and when the mechanical device would be used. Last month a team of researchers from Temple University Hospital in Philadelphia implanted the Jarvik 7 in a woman who had been declared "brain dead." The device kept the woman's kidneys functioning and maintained blood pressure for two hours before doctors removed it for study.

According to DeVries, the first implants will be restricted to patients without other options, specifically those who at the finish of heart surgery cannot be weaned from the heart-lung machine that supports their circulation. Since the decision to implant an artificial heart will be made on the spot, the Utah team will have to outline the ramifications to the patient and get his permission before the original heart surgery. The patient will have to reside near Salt Lake City for a while to permit follow-up care. His living quarters will have to be on a single floor, with space available for the bulky support equipment, including an electrically run air compressor and tanks of compressed air for use during power failures. The person with the artificial heart will lead a fairly sedentary, chair-to-bed existence. "But we're not ruling out sex," says DeVries.

Some heart experts suggest that the Utah plans are overly ambitious, if not completely illadvised. They are most disturbed by the practical and psychological consequences of tethering a patient to an air compressor. Jarvik and DeVries point out, however, that life with an artificial heart may actually be an improvement for some patients. "We're not talking about people who are active tennis players or swimmers," says DeVries. "These people are in terrible condition. They often have difficulty breathing, let alone doing anything else." Still, members of the Utah team acknowledge that some recipients may-have difficulty coping. Says Utah's Willem Kolff, who developed the artificial kidney and also worked on a prototype artificial heart that was tested in dogs in 1957: "If someone knew he would otherwise be dead, he might accept that life as a precious gift. But if he decides he doesn't want it, he can take a pair of scissors and cut the air lines. And I'm not going to take away the scissors."

A better alternative, according to some researchers, is a device that could take over temporarily for either of the two main pumping chambers of the heart, particularly the workhorse left ventricle. These assist devices shunt blood from the ventricle to a pump outside the body that sends it directly to the abdominal aorta or femoral artery to continue its natural circulation. The heart is left intact but goes on a sort of holiday, rebuilding its strength so that it can later resume its full work load. Says John C. Norman of the Texas Heart Institute in Houston, who has been working on left ventricular devices since 1965: "If I take your heart out and put in a totally artificial heart, I have burned all bridges. If I put in an auxiliary heart, your own heart is still in and can help support the circulation."

No matter how dazzling, heart transplants and mechanical hearts are last-ditch measures. They will save, at best, a tiny fraction of the lives now claimed by heart disease. Fewer than 50 heart transplants are done each year in the U.S., owing to the difficulty of finding donors, the unsolved problem of tissue rejection and the high cost (averaging $100,000).

Ultimately, a successful artificial heart may be able to help more patients, perhaps a maximum of 50,000 annually. But the expense could be astronomical. Implanting the device will cost upwards of $30,000, and home equipment and maintenance will cost many thousands more. The Government now pays more than $1 billion a year to dialyze more than 50,000 patients with kidney disease. Should it also pick up the tab for artificial heart implants?

Says Alabama's Kirklin: "Healthcare delivery in this country is restrained by dollars available. I wonder what other things would be curtailed if a disproportionate share went to artificial hearts?"

In the long run the most significant advances may come from learning how the cardiovascular system works on a cellular and chemical level. Says Goodman:

"If we can understand more about the disease process, we can do more to retard or prevent it." Cholesterol's role in heart disease should become clearer in 1983 when the first results from a National Heart, Lung and Blood Institute-sponsored study begun in 1976 become available.

Pharmacologist Philip Needleman of Washington University in St. Louis predicts that within five years doctors will begin testing drugs that limit the clogging of blood vessels initiated by platelets. Says he: "This is not a remote dream. This is a strategy that will have important applications quickly."

Cardiologist Thomas James of the University of Alabama in Birmingham anticipates still other strides in basic knowledge. "In the next ten years," he says, "we will understand why artery walls degenerate and why hypertension happens, and develop the means for preventing both." Heredity's complex role in cardiovascular illness will be better understood as well. Says Robert Brandenberg of the Mayo Clinic: "We're probably just on the edge of a whole new series of breakthroughs."

He may be right if recent progress is any measure. Cardiovascular science has come a long way from 30 years ago, when all that could be done for a heart attack patient was to prescribe rest for four to six weeks. If innovations in diagnosis and treatment continue at the same impressive pace, cardiovascular disease may one day yield its claim to being the nation's No. 1 killer. --By Anastasia Toufexis. Reported by Anne Constable/Atlanta and Dick Thompson/San Francisco, with other U.S. bureaus

With reporting by Anne Constable, Dick Thompson

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