The Heart Healers (49 page)
Authors: James Forrester
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BUT WHAT ABOUT
the other central feature of CAD, the inflammation response that creates vulnerable plaques? Recall that the key features of vulnerable plaques are its feverish temperature, its profusion of inflammatory cells, and its thin cap poised to rupture. Since unstable angina and heart attacks are caused by the rupture of vulnerable plaques, shouldn’t we target the inflammatory process as well? We know that by reducing cholesterol accumulation, statins have an anti-inflammatory effect, but what would happen if we supplemented that with an anti-inflammatory drug?
Last year, an intriguing anti-inflammatory candidate emerged from Australia. Colchicine is an old, very familiar drug for the treatment of gout. Investigators Drs. Stephan Nidorff and his boss Peter Thompson noted something very strange: their patients taking colchicine for gout and other inflammatory conditions seemed to have a markedly reduced frequency of heart attacks. So they initiated a clinical trial of low dose colchicine in 532 stable CAD patients already being treated with a statin, memorably christening the trial LoDoCo. Their results, published in the prestigious
Journal of the American College of Cardiology,
astonished the cardiologic world. The fall in unstable angina, heart attack, sudden death, and stroke between the treated and untreated groups was an unprecedented 67%: over three years it fell from 16% to just 5%. In comparison, statin trials find about 30% reduction in events.
LoDoCo is a small trial, but it is already the harbinger of several much larger ongoing anti-inflammatory drug trials. Take a moment to imagine the impact on our society if these results are validated. As I said in my accompanying editorial written with Dr. Robert Vogel, LoDoCo “suggests a new concept: the lipid effects of statins may predominantly inhibit atherogenesis, whereas specific anti-inflammatory agents, such as colchicine, may work synergistically with statins to inhibit plaque rupture. If the results can be confirmed, this study may one day stand as the seminal trial in the use of anti-inflammatory therapy to cool off hot hearts.”
Taken together with lifestyle modification, the PCSK9 and new anti-inflammatory drugs are quite simply a potential knockout blow to CAD. When I entered cardiology those many years ago, Bobby Dylan rasped, “the answer my friend, is blowing in the wind.” Who could then imagine then that one of the greatest would be an answer to the scourge of the twentieth century? But today I can.
For masterpieces are not single and solitary births; they are the outcome of many years of thinking in common, of thinking by the body of the people, so that the experience of the mass is behind the single voice.
—VIRGINIA WOOLF, ENGLISH AUTHOR
LET’S END OUR
story where we started—with Willie the Phillie. As Willy Loman’s wife laments in
Death of a Salesman,
“Willy Loman never made a lot of money. His name was never in the paper. He’s not the finest character that ever lived. But he’s a human being … So attention must be paid. He’s not to be allowed to fall into his grave like an old dog. Attention, attention must finally be paid to such a person.”
Our story began when a vulnerable plaque in the wall of Willie’s coronary artery ruptures as he sleeps at home. Cholesterol gruel within the inflamed atheroma erupts like molten lava into his flowing bloodstream. A clot begins to form over the torn shards of the blood vessel surface. How big will the clot become? As the clot builds in Willie’s artery, blood flow around it slows. A contracting segment of heart muscle, deprived of sufficient oxygen, sends an urgent message to his brain: “I’m choking to death.” Willie experiences chest pain. He takes a nitroglycerin to dilate the coronary artery but the drug has no effect, because the cause of the pain is no longer a stable atheroma; it is a blood clot. Over the next half hour, the clotting stabilizes, and Willie’s chest pain resolves. The clot was not large enough to completely block the vessel. Willie has just experienced an episode of unstable angina. Although his symptoms have disappeared, the sinister clot remains. Willie has more episodes of chest pain over the next few days.
On the final day, as I begin my examination, the clot finally completely occludes his coronary artery. Unrelenting chest pain, more severe than any of his prior episodes, begins anew. As Willie the Phillie collapses, gasping, pleading for help, I realize that I have no tools to save him. Because a large muscle segment is deprived of oxygen, his heart contracts ineffectively. I see this as I monitor the progressive fall in his blood pressure. Next, an electrical impulse arriving to stimulate the oxygen starved muscle segment is rerouted, causing the ventricle to contract at triple speed. I detect this as I palpate his pulse, feeling the sudden increase in heart rate. The badly injured ventricle cannot sustain this rate for more than a minute or two, and the ventricle fibrillates. Now with no effective cardiac contraction, Willie has no blood flow to his brain. His eyes roll back as he loses consciousness five seconds later. My resuscitation of Willie is a shambles. I am slow to initiate chest compressions after Willie loses consciousness. I politely allow a minute to pass with no chest compression as the anesthesiologist inserts his tube. The defibrillator is not readily available and arrives far too late to save him.
But now, let’s raise Willie from his bed, and ask him to stroll with us through the ensuing decades of what might have been, what came to be in the years that followed. In the mid-1960s during my Los Angeles medical residency, hospitals created programs to train doctors and nurses in the ABCs of cardiac resuscitation. Just a year or two after Willie died, I would not have stumbled through the procedure as I did. Willie would have had a modest chance of being resuscitated in his ward bed.
By the time I arrive in Boston in the late 1960s, Willie would have been admitted directly to a coronary care unit from the emergency room. With our bedside monitors we detect disordered cardiac rhythms long before his final episode and place him on preventive therapy. If he breaks through our preventive therapy into ventricular fibrillation, a specially trained nurse delivers a shock less than a minute after its onset. His chances of leaving the hospital would be good.
In those same Boston years when Willie first sees me for chest pain, I am able to perform a coronary angiogram, where I discover a single atheroma in the proximal portion of his left anterior descending artery. I refer Willie for bypass surgery, which completely relieves his angina, and protects him when the atheroma ruptures in his coronary artery.
As the 1970s open I return to Los Angeles to direct the Myocardial Infarction Research Unit. We resuscitate Willie, then monitor his heart function, which allows us to give him a spectrum of new drugs to sustain him through the crisis. His heart is badly damaged, but he survives.
As we enter the 1980s, the sudden onset of the ECG manifestation of a heart attack on the monitor beside Willie’s bed triggers an immediate intravenous infusion of the clot busting drug, t-PA. Half an hour after we begin the infusion, the clot in his coronary artery dissolves. Having the good fortune to have his heart attack in a hospital, Willie’s heart is only minimally damaged by the brief half hour of complete coronary occlusion.
A few years later, now mentoring younger doctors, instead of clot-dissolving therapy I counsel referrals for immediate coronary angioplasty. Willie is wheeled into the cath lab located adjacent to the CCU, where an interventionalist opens the clot-clogged vessel within a few minutes. Fully opened, the vessel does not reocclude, and Willie leaves the hospital with minimal heart damage.
Skip again to the early 1990s when I stop by to see Willie as chief of cardiology in that long-forgotten outpatient clinic of yesteryear. I suggest we order a blood lipid panel. His LDL cholesterol is 190 mg/dl. I “drape the crepe” with Willie about his risk for heart attack. Willie buys into my plan. I refer him to both a nutritionist and a smoking clinic. Since his bad cholesterol is far outside the normal range, I prescribe a statin. His angina episodes diminish in frequency within a few weeks. By year-end he is angina-free. Willie becomes one of those patients you see every year.
It’s the present and today is his annual visit. Willie now follows a prudent diet and he walks a brisk mile almost every day. With thirty less pounds he no longer reminds me of Babe Ruth. In the years I have been seeing him several of the statins have gone off patent. I have put him on the most potent one, which has lowered his LDL cholesterol to 70 mg/dl with no side effects. I turn the conversation to the Phillies finally winning the World Series in 2008, but he cuts the conversation short. “Gotta go, Doc, it’s my grandson’s high school graduation,” he says. We both know that the atheroma is still there, but now it’s fast asleep, and together we’ll keep it that way. But the final victory lies in an imagined future, when from his youth Willie embraces all the tenets of a healthy lifestyle. Atheromas do not form in his coronary arteries, and so he never appears in my office.
The last step in my own odyssey comes when I step down to return to what is my professional passion, mentoring through teaching clinical research and patient care. Today it seems to work well for both parties: in our clinical case conferences, I pontificate and the cardiology fellows act like I still know what I am talking about. When I leave the conference perhaps someone says of the former little boy listening under his father’s mahogany table that the science is gone, and only the compassion remains. That’s OK. For me, the journey itself was the reward. My profession and I began in ignorance; we made our share of blunders in the early years, and ultimately succeeded (mine, modestly) with equal doses of persistence and good fortune. If, from time to time, we lost contact with the essential values of our profession during that passage, we found our way back. If we did not find solutions, we discovered how to ask new questions. Our future remains forever beyond our grasp, but our past gives us hope.
As Willie closes the door, I muse about this brief segment of human history. Where does it stand among the greatest contemporary scientific achievements of its era? The Manhattan Project brought together our most brilliant physicists to create a weapon that ended the war with Japan. Its legacy, however, became the painful deaths of many innocent Japanese and seven decades of unresolved world conflict over nuclear weapons. The Moon Landing achieved a dream of mankind for thousands of years. Its legacy remains relatively small, as the U.S. federal government abandons manned space flight. Discovery of the double helical structure of DNA will surely someday be the last century’s greatest scientific achievement, but its legacy will be defined in this century. I suggest that cardiology’s Golden Age deserves a place on the short list of the last half century’s scientific wonders. We successfully operated on a damaged heart, achieved mankind’s millennia-old dream of restoring life after sudden death, replaced the function of our heart and lungs with a machine, replaced a failing heart with a new one, discovered dramatically effective treatments for heart attacks, and concluded our symphony with the clash of cymbals by transforming the scourge of the twentieth century into a preventable disease.
As I survey this tapestry of ongoing cardiovascular breakthroughs I see an international village, peopled with patients, iconoclasts, risk-takers, persisters, and entrepreneurs standing shoulder to shoulder, proud of their individual emotional, scientific, and technological achievements that together have no parallel in the history of medicine. We were ordinary people caught up in an extraordinary time, an era of courage, daring, resourcefulness, serendipity, and ingenuity. It’s true, friend Willie.
Attention has been paid.
Please note that some of the following links referenced in this work are no longer active.
Prologue
Intuition and induction in science.
In
Pluto’s Republic: Incorporating the Art of the Soluble and Induction and Intuition in Scientific Thought
. New York: Oxford University Press; 1982, British physiologist Dr. Peter Medawar distinguishes induction and intuition in the processes of scientific discovery. Induction is reasoning from specific facts to general principles. In research this approach is also called the Scientific Method, wherein a hypothesis forms the basis of data collection. Intuition, on the other hand, is the ability to understand immediately, without the need for conscious reasoning. Medawar links intuition and induction, observing that a flash of intuition often triggers inductive research.
Life expectancy in the United States since 1950.
Many population and economic data sets are available at
www.data360.org/dataset.aspx?Data_Set_Id=338
.
CAD mortality rate.
Fox KA, Steg PG, Eagle KA, Goodman SG, Anderson FA Jr, Granger CB, et al. Decline in rates of death and heart failure in acute coronary syndromes, 1999–2006.
JAMA
. 2007;297(17):1892–1900.
Global burden of disease.
Lozano R, Naghavi M, Lim SS, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: A systematic analysis for the Global Burden of Disease Study 2010.
Lancet.
2012;380:2095–2128.
Risk factors for diseases.
Lim SS, Vos T, Flaxman AD, et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: A systematic analysis for the Global Burden of Disease Study 2010.
Lancet.
2012;380:2224–2260.