A Broken Heart

By LANCE MORROW

It was August 1976. The Reagan people in the balcony would not shut up. Roberts' Rules of Order could go to hell. The Californians on one side of the hall screamed, "!Viva!" and those on the other side howled back, "!Ole!" The convention nominated Gerald Ford anyway. Reagan would have to wait four years. I smoked three or four packs that day and, in the bluish cigarette haze of a room in the Muehlbach, wrote TIME's cover story: dreary convention, dismal story; hot, clear Kansas City summer outside. At least that's what I remember of it now.

As I finished writing the last paragraph, a sensation like poisoned gas began to wraith around inside my chest--a sick green glow, the lightly radioactive foretaste of something awful. Then a vise beneath my breastbone tightened...and tightened...and tightened, a slow-motion black implosion of the body's core. I had a heart attack. Quite a surprise. I was 36.

Thus, 22 years ago, began my cardiac education, which--with another heart attack in 1993 and with the reappearance last spring of the radioactive symptoms--is well along in its postgraduate phase. I share this with you (as they say in group) because the history of my heart's misadventures happens, luckily for me, to parallel the story of the late 20th century's medical advances in the treatment of heart disease. And because at the American Heart Association's meeting last week in Dallas, still more remarkable new treatments were auditioned. I have enjoyed, so far, an existential scissors graph: my heart gets worse; medicine gets better. (How long will this happy pattern last?)

I have managed to get this far--bodysurfing on each new wave of knowledge--with the help of two multiple coronary bypasses (1976, 1993), an angioplasty with stents (successful just the other day; a couple of efforts to unblock other coronary tunnels by angioplasty failed painfully), and a supporting cast of ACE inhibitors, beta blockers, cholesterol thwarters, diuretics, aspirin to make the platelets slippery, nitroglycerine, blood-pressure suppressants, vitamin E, folic acid, a rowing machine, a stoic personality and the diet of a desert mystic. It goes without saying that a heart attack is also a good way to quit smoking. I was instantly cured of nicotine addiction that night in Kansas City.

Heart disease has a way of upping the ante: the future always needs tending. After two bypasses my heart will not take a third--too dangerous for a surgeon to work with all the rubbery scar tissue on the heart, like so much plastic in his hands. With an ejection fraction of 31% (the ejection fraction is the percentage of blood expelled, with each heartbeat, from the left ventricle; normal is 50% or more), with venous grafts to the left anterior descending artery and with the right coronary artery totally occluded, I have pretty much exhausted the surgical techniques available until now.

From here on the going gets dicier and, in terms of the future of heart treatment, more interesting. On the horizon, and closing fast, are experimental techniques--most immediately gene and laser therapies--that have the potential to make yesterday's miracles (bypasses and angioplasties) seem like rudimentary plumbing repairs. Remember: potential.

So, with the guidance of my cardiologist, Dr. Robert Ascheim, I am shopping in the experimental boutiques.

The other day I talked at New York Presbyterian Hospital with Dr. Todd Rosengart, a young (38) cardiothoracic surgeon who is among the first to perform angiogenesis gene therapy--the injection into the heart of the gene coding for a protein (vascular endothelial growth factor, or VEGF) that encourages new blood vessels to sprout from existing ones. If you are lucky, in other words, the body performs its own coronary bypass--or many bypasses. And these new vessels are less inclined to silt up again.

I had expected the operation would require the full trauma of the open chest used in bypasses--you are unconscious for the bypass, of course, but somehow remember feeling like a butterflied rack of lamb. (After Henry Kissinger had a multiple-bypass operation some years ago, he reported to a colleague of his--my father--"Oh, Hughie, diss vass a bitch!")

Rosengart explained that he needs to make only a 2-in. incision and inject the VEGF between two ribs, directly into the area of the heart that most needs improved blood flow--in my case, the front wall. It is likely that within a year or two surgeons will have perfected the even less invasive technique of making the injection by way of a catheter fed to the heart through the femoral artery in the groin.

Gene therapy was the big news at the American Heart Association's meeting. The procedure was greeted with both enthusiasm and wariness. Work in gene therapy, like the efforts to trigger blood-vessel growth using lasers (more on this later), has not yet yielded definitive results. Both techniques are still too new to have produced an accurate picture either of side effects or the prospects of long-term success. The best that can be said--and it is a lot--is that both procedures hold immense promise and that so far the worst of the feared side effects have not materialized.

Seven years ago, at St. Elizabeth's Medical Center in Boston, Dr. Jeffrey Isner began testing the effectiveness of gene therapy in encouraging angiogenesis--the formation of new blood vessels--in animal limbs. He started with rabbits, tying off arteries in their legs and, using a catheter and small balloon, applying the genes directly onto the smooth-muscle cells lining the artery. Within three to 10 days, new blood vessels began to sprout and find their way around the blockage. Isner then moved to humans. In December 1994 he tried the therapy on a patient with ulcers in his leg; circulation in the leg was so bad that if angiogenesis had not worked, the only other option would have been amputation. Using the same catheter technique to deliver trillions of copies of the gene directly to the area on the diseased artery, Isner performed the first human gene therapy for a blood-vessel disorder.

In Dallas last week Isner reported on the progress made by five heart patients whom he and his team have treated with gene therapy. One of them, Floyd Stokes, 58, a peanut and cotton farmer in Seminole, Texas, had approached Isner earlier this year suffering from chest pains and a dilemma somewhat like mine--another bypass was impossible. It hurt Stokes to breathe; getting on and off his tractor was a project. "The only way I ever felt good was lying down in bed," he says, "and I didn't feel real good then." Isner performed the gene therapy in May. "When I came to," says Stokes, "I had no pain." He went home in five days, and in another five he planted 600 acres of peanuts. Twenty days after the procedure, "I woke up, and I told my wife, 'I can breathe today.' I hadn't felt so good in 15 years."

To date the worst result the surgeons have encountered is no result--no new vessels. It takes two to four weeks to learn the outcome, one way or the other. The sprouting of new vessels, if it occurs, seems to stop after four to six weeks.

Miracles are not guaranteed. In total, Isner's team at St. Elizabeth's has treated 82 patients (for both limb and heart blockages) since 1994; 60 of them showed signs of new vessel growth. In some cases Isner can actually see the new vessels sprouting on an angiogram. But often the vessels are so tiny that scans cannot pick them up. The best proof of success may be indirect--simply the absence of pain.

Isner's report to the AHA was the first proof that the growth factor used alone--not in conjunction with bypass or angioplasty--could revascularize the heart. But Isner is not the only doctor experimenting with genetic revascularization, and his method is not the only way to achieve it.

Isner injects the gene directly into the left ventricle (the pumping chamber) of the heart. By contrast, Rosengart--the doctor I'm talking to at New York Presbyterian Hospital--uses a weakened cold virus as a vehicle to carry the gene. He believes the virus has a better chance of penetrating heart-muscle cells than does the naked DNA of the gene alone. "The virus has had millions of years to evolve and find the best way to get into a cell," says Rosengart. Studies on animals, at least, have been dramatic. In pigs, he reports, "the blood vessels were literally as good as we could accomplish with surgery." Rosengart and his colleagues at New York Presbyterian, led by Dr. Ronald Crystal, have performed the therapy on 21 patients but say it is too early to assess their success rate.

There are 13.9 million Americans like me with heart disease, the nation's leading killer. Every year 1.1 million of us have heart attacks. Every year about half a million people die of heart disease. It is hard for us not to feel a leap of hope when we hear Rosengart assure us that gene therapy "is not a 10% phenomenon, but a dramatic new area of heart-disease treatment." Or hear Isner declare that gene therapy will make open-heart surgery unnecessary for some heart patients, especially among the 7.2 million Americans who live with the pain of angina.

Not all surgeons and cardiologists are convinced. Is gene therapy safe? Does it last? Can it be repeated?

One danger of using a virus, as the New York team does, may be infection. No such problem has arisen so far. Another possibility: you might not be able to repeat the procedure, because the patient's body may have developed an immunity to the virus that was used the first time. Rosengart expects it will be possible in the future to do repeat procedures simply by using a different strain of the virus.

Theoretically, two other problems could arise. The first: tumors in blood vessels. So far, none of the animals tested over seven years has developed abnormal growths. The second: impaired vision, the hypothetical result of too much of the protein, especially in diabetics, promoting excessive blood-vessel growth in the retina. No problem so far.

Gene therapy seems wondrous and, as a new form of intimate intervention in nature's business, vaguely disconcerting. The other major approach to angiogenesis--drilling tiny holes directly into the beating heart muscle with a laser--seems aggressively screwy. But the procedure (called transmyocardial revascularization) seems to work. And as violent as it sounds, it appears to be relatively safe.

In TMR a surgeon makes a small incision in the left side of the chest and exposes the left ventricle, the chamber that forces oxygenated blood into the arteries. While the heart pauses between beats and fills with blood, a laser is used to shoot a minuscule hole through the muscle. (Zapping the heart in synch minimizes potential fibrillation by keeping time with the heartbeats.) The 30 to 45 wounds on the outside of the heart close up almost instantly, with help from pressure by the surgeon's finger. But the channels created inside the muscle remain open--at least for a little while. Patients have reported feeling immediate relief from chest pain, probably because blood seeps up the laser channels and nourishes the oxygen-starved heart muscle.

When lasers were first used for the treatment in the mid-'80s, researchers believed the channels remained open. Apparently not. It is now thought that the drilling provokes new blood-vessel growth where the laser burns a hole. (Others suggest the angina may be eased simply because the laser numbs pain-sensing nerves of the heart.) Scar tissue from the laser holes seems minimal.

Laser therapy costs half as much as a bypass operation, which can run $40,000 or more. Gene therapy has no fixed price yet, although it is expected to cost significantly less than bypass surgery. There's no argument that laser therapy provides short-term relief for severe angina. Some studies suggest longer-term benefits. One found that almost three years after tmr, patients who had the worst form of angina (class IV, the kind that wakes you up at night) could maintain on average class I or II (pain with exertion only).

Everyone with heart disease knows that if you survive a first attack, life becomes a long, complex negotiation with the menace--the killer in black pajamas who has come to live in the basement. You hear him down there. Sometimes he climbs the stairs and beats on the kitchen door. You feed him sublingual pellets of nitro and tell him to settle down.

The negotiation in my case now revolves around the question of whether I have the time to wait for the doctors to learn more about gene therapy and TMR--the time, put bluntly, to let them experiment on other patients, not me. Then, too, I could die waiting. I'm thinking. I'm thinking.

Meantime, one oscillates between extremes of depression and gratitude--gratitude being the only decent thing a patient can feel at medicine's largesse. Of course one slides back and forth through a middle range of buoyancy and irritability. A few weeks ago, I went to the Harvard Club and cleared out the squash locker that I had used twice a week for more than 20 years. An aging yuppie's lament: no more squash. I was depressed until it began to seem funny, as if John O'Hara had written that moment of my life.

--With reporting by Unmesh Kher and Alice Park/New York

With reporting by Unmesh Kher and Alice Park/New York