The Heart Healers (47 page)

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THE FUTURE OF
heart muscle disease is regeneration through stem cells. The potential impact of unlocking stem cell therapy for regenerating heart muscle is so tantalizing that about eight years ago, my former fellow Dr. Raj Makkar (he calls me Papa Jim) and I initiated studies of bone marrow stem cell therapy in animals with acute myocardial infarction. Other labs had some impressive results suggesting successful regeneration of heart muscle following delivery of stem cells.

To test the effectiveness of stem cell strategy in already existing heart failure, we delayed the injection of the stem cells until one month after inducing a myocardial infarction (heart attack) in a pig. The heart’s function stabilized compared to untreated animals.

We used these results to convince the National Institutes of Health to allow us to initiate the first study of stem cell therapy in patients with a heart attack in the United States. We proved the safety of infusing bone marrow cells in patients with heart attack, but the number of patients was too small to prove effectiveness. Soon thereafter our Medical Center succeeded in recruiting Dr. Eduardo Marbán, one of the world leaders in cardiac stem cell therapy as director of our Heart Institute.

Dr. Marbán has advanced the field by developing a method for extracting stem cells from the heart itself, then multiplying them in culture, and delivering them back to the injured heart. From animal studies he concluded that these cardiac stem cells reduce scarring after myocardial infarction, increase the mass of living heart muscle, and boost cardiac function. Now amply funded by the California Institute for Regenerative Medicine, the next step was to use a biopsy of our patients’ own heart muscle to grow many millions of cardiac stem cells in culture dishes, and then reinject the cells back into each patient’s own arteries. So as the plaque in Edward Sukyas’s coronary artery ruptured, our staff was preparing to open a new chapter in the treatment of heart attack.

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EDWARD PAUSED ON
his walk, staggered by the sudden onset of pain in his chest and back. He phoned his wife Kathy for help. When she arrived minutes later, Edward already knew. “I think I’m having a heart attack,” he gasped. He was right. But for Edward there was an element of astounding good fortune in the midst of tragedy. Within an hour of the onset of pain, he had been whisked through the Cedars-Sinai emergency department to our sixth-floor cath lab where cath lab director Dr. Raj Makkar stood ready. With consummate skill and speed, Dr. Makkar placed three stents in Edward’s obstructed coronary arteries. As Edward says in our hospital journal, “It was over in half an hour.” But having arrived at this point in our chronicle, you and I realize nothing is further from the truth. Edward’s life had been saved, but he had sustained extensive death of heart muscle, and now faced the risk of heart failure.

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THE FIRST RANDOMIZED
study to test the safety of Dr. Marbán’s cardiac stem cells in patients with heart failure following heart attack was now in progress. Edward was twice lucky. Only one more patient remained to be entered in the trial. Our staff described both the uncertainty and the promise of cardiac stem cell therapy. For a former carpet maker, restaurateur, and commodity broker, it was an easy decision: “You have to accept a certain dose of risk in life,” Edward said, and he became the study’s last recruit. A few weeks after his heart attack he returned to the cath lab where Raj Makkar infused millions of Edward’s own cardiac stem cells into his coronary artery.

Edward resumed his walks six weeks after his heart attack, and then returned for a battery of tests over the next year. His test of lung function (called oxygen consumption) improved from 1.9 liters before treatment to 2.5 liters at six months and 3.2 liters at one year. “I almost didn’t need those results to know how I was doing,” Edward recalls. “Before my heart attack, I had shortness of breath when I was under effort, such as exercising or climbing stairs … I don’t experience that anymore.”

Dr. Makkar published the results of our Heart Institute’s trial in 2013. Edward’s results fit with the other treated patients. He has a smaller heart muscle scar, and the heart muscle in the area of his heart attack functions better, compared to the patients who were randomized to receive standard care. Dr. Marbán calculates that the stem cell recipients grew the equivalent of 600 million new heart cells, or about 60% of the billion cells lost in a typical heart attack. As Marbán likes to say, “We are recruiting nature’s own healing process and just amplifying it.”

Since the study was very small, Dr. Makkar does not claim his patients’ clinical outcomes are different with cardiac stem cell therapy. Consequently, we cannot say we have yet achieved what we set out to do with stem cell therapy, which is to reverse heart failure. That will require larger trials with longer follow-up. Once again we have glimpsed an incandescent light behind a partially open door. Regenerative medicine is that light. When we finally succeed, we will have achieved a breakthrough as important as any in this chronicle.

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WHEN EDWARD SPEAKS
of his experience today, he captures the ineffable spiritual bond, the shared exhilaration between patient and doctor I have so often experienced in risk-taking, ground-breaking clinical research. “These doctors are at the frontier of something big, a major advance in medicine … In my own infinitesimal way, it’s like I planted a flag.”

And the Rest of the Story? Edward’s French cheese omelets, chocolate éclairs, and sauce Béarnaise have receded into poignant memory. “When you come from the Mediterranean, food isn’t just food,” he laments. “It’s what ties you to your social environment.” Today he gets by with gourmet ways to prepare salmon and chicken and sea bass. And well, no one’s perfect: a slice of roast beef every two weeks. Edward’s brisk walks continue, but nowadays a new metaphor looms when he pauses on the south side of Third Street to inhale those delicious Italian aromas of Locanda Veneta. It’s his metaphor of survival, regeneration, and longevity. And it’s on the north side of the street.

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HE HEART’S ELECTRICAL SYSTEM: LIVING IN A WIRELESS WORLD

TREATMENT OF DISORDERS
of the heart’s electrical system is also poised to undergo a revolution. Paraphrasing my friend Dr. Michael Gold, director of cardiology at the University of South Carolina and an expert in such disorders, “The future is wireless.” Here’s why. Today, pacemaker hardware consists of a battery and computer algorithms that control delivery of electrical impulses to the heart. This hardware, about the size of a matchbook, is placed in a surgically created pocket under the skin in the chest wall. The pacing impulse is then connected to wires that we thread through blood vessels back into the heart. And therein lies the rub. The wires, being flexed sixty times a minute by the heartbeat, can be a problem. Some get infected; others break. Broken wires, often locked in place by layers of scar tissue, can be very difficult and even dangerous to remove when they become nonfunctional.

We are now beginning to test clever ways of eliminating the wires. Imagine an electrode the size of a grain of rice, which we can implant directly in the heart muscle. It is a passive receiver whose power comes from an ultrasonic generator inserted in a small skin pocket in the chest wall. The receiver converts the generator’s acoustic energy into an electric pulse. Voilà. No more wires. The first generation of such new devices has been implanted in over one hundred European patients. In the near future we will have wireless systems capable of both pacing and defibrillating the heart.

An alternate version of a wireless pacemaker is a device a tenth of the size of conventional pacemakers, which are about the size of a triple A battery. It is implanted directly in the heart, having been inserted through a leg vein in the catheterization laboratory. In a European study thirty-two patients are now being followed to establish the pacemaker’s longevity, and ease of replacement. And this is just the beginning. The small company that developed the device was recently bought by the giant medical device company St. Jude.

When perfected, these devices will alter the lives of millions of people: around the world 4 million people currently have implanted devices, and 700,000 new devices are implanted each year.

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WORRIED ABOUT THAT
disturbing feeling in your chest? How about recording and displaying your ECG on your cell phone, and instantly sending it to your doctor? I have one attached to my iPhone, and I read the ECG myself. My iPhone app stores any duration of the ECG recording on my phone, and operates for 100 hours on a 3.0V coin cell battery.

Right now we are seeing a mad scramble among innovators to create the most user-friendly and medically useful device. The one that currently draws gasps, even from cardiologists, has a casing with two electrodes that inconspicuously attaches to your cell phone. Grip the two electrodes with your two thumbs, and in seconds, your ECG appears on the face of phone. Send it to me from the ninth hole after that hole in one, and continue on with your friends. I will text you back if it looks like more than indigestion. Oh, yes, and with different sensors you can send me your blood glucose if you are a diabetic. In the future, most of the measurements we make in cardiology will be transmittable from a remote location by a patient with a cell phone. Yes, the digital and wireless revolutions have arrived in cardiology.

H
EART VALVES: REPLACING VALVES WITHOUT SURGERY

THE MOST STUNNING
advances in cardiology, however, are now occurring in the treatment of valve disease. Let’s look at two of them.

Mitral valve dysfunction, where cardiac surgery all began, is now being treated in the catheterization lab. In Western countries, following the conquering of rheumatic heart disease by antibiotic therapy, the only patients I see with mitral stenosis are immigrants from third world countries. On the other hand I see many patients with mitral valve insufficiency: when the left ventricle contracts, the two leaflets of the one-way mitral valve, which separates the left ventricle from the atrium, fail to come fully together. Blood jets backward from ventricle to atrium, then into the lungs, causing congestion and shortness of breath.

About a decade ago California cardiologist Dr. Frederick St. Goar devised a clip that could be passed into the heart in the catheterization lab. The clip grasps the two leaflets of the mitral valve and brings them together, creating a narrower, double-barrel valve opening.

My mentee Dr. Saibal Kar now has the nation’s largest experience with this device. Compared to surgery, patients have strikingly improved heart function and quality of life at one year. Positive outcomes are somewhat greater with surgery; safety outcomes favor the clip. The role of the clip will become more clearly defined as long-term follow-up becomes available. Even now, however, for frail and elderly patients who are poor candidates for surgery the mitral clip represents a lifesaving advance.

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IN THE COMING
decade many heart valves will be replaced without surgery. When I see my mentee Dr. Raj Makkar perform the procedure, I feel it is the single most jaw-dropping, mind-boggling event in my career in cardiology. I can only marvel, how in the world did that doctor put that valve inside that patient’s heart without opening the chest?

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LEON SALIBA IS
the son of immigrants, born in the hills of Beirut, Lebanon, who came to the United States in the early 1900s. Leon was born in tiny Campbell, Missouri, in 1911, but grew up in Los Angeles. Leon is now 102 years old. As the son of a poor dry goods merchant, Leon realized early in life that he would have to make his own way. He would have to be independent. In the summers he labored for a big construction company, which was paving Wilshire Boulevard, then still a dirt road. The company was required to provide a huge surety bond, which would reimburse the city if they failed to perform on time. Since Leon was bright, exceptional at math, and articulate in English, his foreign-born employers designated him as their representative to negotiate with the bond company. Leon learned a quick lesson in life when he was paid four times as much in his bond commission as he had earned in construction labor. During that summer he was admitted to the prestigious California Institute of Technology. Unable to pay the tuition, Leon did the next best thing: he formed his own bond company. It was 1928.

The next year the stock market crashed, but somehow Leon, principled, professional, unpretentious, and self-taught, survived with his fledgling company intact. As his company became successful, Leon’s clients became leaders in the developing city. When one client, the Van Nuys family (after whom the Los Angeles suburb is named) built a new office building on Wilshire Boulevard they offered him space, where he stayed for the next quarter century. Leon Saliba became a leader in the Lebanese community of Los Angeles and in his Orthodox Christian Church (in Lebanese,
salib
means cross, and
saliba
means follower of the cross). He and his wife had six children and sent them to college and graduate school. In the 1970s a New York Stock Exchange insurance company offered to acquire his company. Independent at age sixty, Leon retired to pursue his passion for golf from his house adjacent to the tenth hole of his country club.

Leon’s wife of fifty-five years passed away when he was eighty-three. When she died, Leon had a choice. He could live out his years in an assisted living facility, or he could take care of himself at home. Leon chose independence. As Leon approached 100 he began to have the symptoms and signs of severe aortic stenosis (aortic valve narrowing). Referred to our center, we had to give Leon some further bad news. In addition to severe aortic stenosis, he had severe stenosis in his left anterior descending coronary artery (the one known as “the widow maker”). Although otherwise healthy, Leon had reached the end of the line. He would be lucky to survive another six months. But in the past year or two, my former fellow, Dr. Raj Makkar, had become a world leader in a new research therapy. Raj agreed to replace Leon’s aortic valve without surgery, but first he would have to protect the heart with a stent across the stenosis in his LAD. After Leon recovered from the coronary angioplasty, if he was still alive with his aortic stenosis, Raj would replace the valve. Leon recovered from the stent placement without a hitch. The time had come to replace his aortic valve.