“I’m not aware of any good evidence for alternative therapies for heart failure,” I stammered.
How did I know this without reading up on the current research? he demanded. I felt like a first-year fellow again, unprepared to argue my point. It didn’t matter to Jack that I was the doctor or that I had made it through most of a cardiology fellowship or that I was, in fact, planning on specializing in the treatment of congestive heart failure. Like me, he wanted evidence. He was using my own paradigm against me.
Chastened by his criticism, I offered an apology, which he accepted. Then he told me that besides milk thistle and taurine, he had been taking more than a dozen other unproven off-the-shelf supplements: carnitine, glutathione, goldenseal, corn silk, dandelion, black cohosh, dimethylglycine, coenzyme Q, thiamine, alpha-lipoic acid, stinging nettles, oil of oregano, echinacea, magnesium, selenium, and copper. None were recorded in the chart.
Once the genie was out, he could hardly hold back. He removed the soles of his shoes, embedded with tiny neodymium magnets that he had purchased for forty-five cents apiece at a thrift store. He handed me his glasses; two round magnets were attached to the frames. (That’s what those were!) A few years back, he said, he had had a serious lung infection, requiring treatment with several antibiotics for almost a year. He wasn’t using magnets at the time. He was never going to make that mistake again.
Could it just be random, I asked, this association between magnets and health? Knowing that Jack was well versed in philosophy, I brought up Karl Popper’s theory of science and the requirement of falsifiability. Suggest an ailment we can test, I said excitedly. We could conduct a small trial, on and off magnet therapy. He shrugged, unfazed. “I try to keep myself from analyzing it too much or talking myself out of the placebo effect,” he said.
When he got up to leave, he handed me a tiny magnet as a gift. “Keep it away from your wallet,” he advised. “It’ll erase your MetroCard.”
* * *
It was on Wednesdays that Jack would come to see me at the Bellevue cardiology clinic. Like many of my patients, he was a clinic veteran who had been through several cycles of fellows. “I know I’m getting older when the doctors are getting younger,” he quipped. The clinic was always packed. You’d get ten or twelve minutes per visit, max. You listened to the heart and lungs, went through the problem list, wrote a progress note, maybe wrote a prescription, and then it was off to see the next patient. No surprise, then, that Jack—and many other patients, I suspected—had adopted alternative medicine. I figured Dr. Null spent more time with Jack, listened to him, and showed that he cared. But did his natural remedies work? I took it as a challenge to prove to Jack that my way, informed by science, was better.
At a clinic visit a few weeks after Jack showed me his magnets, I spoke with him about his treatment options. “You have a weak heart,” I said, slowly moving my outstretched fingers, as if palming a basketball, to illustrate. I brought up the option of an implantable defibrillator. The beeper-sized device would be inserted in Jack’s chest to monitor his heartbeat and apply an electrical shock if the rhythm degenerated into something dangerous. It was like the paddles in the ER, but it would always be inside him. A special “biventricular” defibrillator would help to coordinate the contractions of Jack’s failing heart. It might relieve his breathlessness and decrease the frequency of hospitalizations. It might even prolong his life.
Biventricular defibrillators then cost about $40,000 each. In the United States, where more than six million patients have heart failure and half a million new cases are diagnosed each year, if even a small fraction of patients like Jack received the device, the costs could reach billions. But apart from the money, a bigger question in my mind was whether the device was even right for Jack. He was probably going to live at least a year, but certainly no more than five. How did he want to die when his time came? Patients with heart failure mostly die in two ways: either by a sudden, “lights out” arrhythmia, in which the heart abruptly stops, or by progressive pump failure, in which the heart weakens to the point that it cannot deliver adequate blood and oxygen to the tissues. Pump failure is a horrible way to die. The symptoms it creates—nausea, fatigue, and unremitting shortness of breath—are some of the most torturous and feared in the human experience. Wasn’t a sudden arrhythmia a better way for Jack to go than struggling for breath as his lungs filled with fluid from congestive heart failure? Sure, a defibrillator would prevent sudden death. But it would also take away the sudden-death option, potentially directing the dying process down painful, winding paths. Of course, when Jack’s condition inevitably spiraled downward, he could always deactivate the device and prevent it from delivering a painful shock. However, in my experience, few patients ever did. Doctors rarely informed them of this option, and families, struggling to cope with the impending death of a loved one, were often reluctant to make that choice.
I did not go into these details with Jack, however. It was hard enough to fit any sort of discussion, let alone a drawn-out, morbid one, into a ten-minute office visit. I recommended he get a defibrillator. I wasn’t sure it was the right decision, but the device, I figured, would at least help him in the short run. But none of this mattered anyway, because Jack quickly waved off my recommendation. He didn’t want a defibrillator. With time, he was convinced, his magnets were going to work.
* * *
The heart is fundamentally an electrical organ. Without electricity, there would be no heartbeat. Electrical impulses stimulate special proteins in heart cells, causing them to draw together, resulting in contraction of the entire organ. Derangements in the rhythm of these impulses impair the heart’s ability to pump blood. By the early part of the twentieth century, this was understood, and the heart’s wires had been mapped. For example, physiologists knew that nearly every one of the three billion heartbeats that occur during a typical human lifetime begins with the spontaneous activation of cells in a region high up in the right atrium called the sinoatrial node, the heart’s natural pacemaker. Through the flow of charged ions, the voltage of these cells periodically arrives at a threshold; this happens about once a second in a normal person at rest. That induces an electrical wave—an action potential—that spreads through the atria and travels down specialized conductive tissue—wires, really—into the ventricles, stimulating heart cells along the way. (Think of the pulse generated when you jerk the end of a rope up and down.) Just before the wave enters the ventricles, it passes through a narrow, relatively inert disk of tissue called the atrioventricular node. Here, the electrical impulse slows to a crawl for about a fifth of a second, giving the atria time to finish squeezing and filling the ventricles with blood. The wave then passes into the ventricles through thick bundles of tissue that rapidly and finely split into conductive filaments that extend through the ventricles like the roots of a tree. In this way, an impulse originating in one part of the heart quickly conducts through the entire organ, causing the right and left ventricles to contract almost simultaneously, ejecting blood into the lungs and the main body, respectively.
After a cardiac cell is stimulated, it enters a “refractory” period in which the cell becomes essentially quiescent; no electrical stimulus, no matter how intense, will elicit another response. This is a protective mechanism, preventing cardiac tissue from being rapidly and repeatedly activated. If the heart beats too fast, circulation can cease and the person will die.
There are several other layers of protection that ensure the stability of the human heartbeat. For example, if the sinoatrial node, the heart’s natural pacemaker, becomes dysfunctional, any number of backup pacesetters in the heart can take over. These regions normally have different electrical properties and activate more slowly than the sinoatrial node, so their activity is ordinarily suppressed (their cells are in a refractory state) when the sinoatrial node is firing normally. But if one of these regions speeds up because of damage or disease or adrenaline release, it can usurp the sinoatrial node’s pacemaking funct
ion.
The heart’s conduction system: SAN, sinoatrial node; AVN, atrioventricular node; RA, right atrium; LA, left atrium; RV, right ventricle; LV, left ventricle. Dashed lines represent atrial activation; solid lines represent pathways for ventricular activation. (Courtesy of R. E. Klabunde, www.cvphysiology.com, 2017)
By the turn of the century, this paradigm had largely been laid out. Scientists understood that the heartbeat is powered by electricity generated in the right atrium and conducted southward, stimulating billions of electrically coupled cells along the way. What took longer to appreciate is that when the heart stops beating, that is usually because of electricity, too.
George Mines, circa 1914 (Courtesy of Physiological Laboratory, Cambridge University, England. Reprinted with permission)
The key figure to explain this connection was the Englishman George Mines, a product of the famed Cambridge School of Physiology. As a young man, Mines was a piano prodigy and briefly considered a career as a musician. This predilection for rhythms stayed with him. He received his PhD from Cambridge in 1912, when he was twenty-six. An avid photographer, Mines introduced the moving-image camera to cardiac physiology, recording the contractions of a pithed frog’s heart by photographing it at fifteen frames per second on bromide paper, using a method pioneered by a close acquaintance, the cinematographer Lucien Bull. After he graduated from Cambridge, Mines did postdoctoral sabbaticals in England, Italy, and France before accepting a professorship in physiology at McGill University in Montreal. Mines’s two most important discoveries—perhaps the most fundamental in the history of cardiac electrophysiology—were made during this period, in experiments he conducted on tortoises, fish, and frogs.
The first discovery was that small electrical channels can exist outside the normal conduction pathway in the heart. Normally, these extraneous circuits are excited uniformly and do not alter the heartbeat. But if one side of such a circuit—call it side A—has a longer refractory period than side B, because of illness or electrolyte disturbance or injury from a heart attack, for example, it may be in a refractory state when a premature impulse arrives and will therefore not conduct. The impulse will travel only down side B, which has recovered excitability because of its shorter refractory period. Mines’s great insight was that if side A recovers excitability before the impulse reaches the bottom of the circuit, the impulse may conduct back up side A and then again down side B (which quickly recovers excitability because of its shorter refractory period), repeating this pattern over and over. Theoretically, the impulse could circulate indefinitely, without any further external stimulation. With every rotation, a portion of the circulating wave can leak out of the circuit and activate surrounding heart tissue, like a lighthouse beacon sending its signal to faraway ships. In this way, the circulating wave could usurp the activity of the sinoatrial node and become the dominant pacesetter in the heart.
Mines called this phenomenon “reentry,” and he was able to visualize the circulating current in experiments on rings of jellyfish. He published a classic figure still in use (akin to the one shown below) that illustrates “circus movement” in these myocardial circuits and how such movement can initiate rapid arrhythmias. He also showed that cutting the circuit will instantly terminate the circulating wave, an observation that is the basis for surgical treatment of many arrhythmias today.
Cardiac reentry (Created by Liam Eisenberg, Koyo Designs)
The modern depiction of reentry preserves Mines’s essential insight. In this scheme, a circulating (or spiral) wave is set up in the presence of nonconductive tissue, such as a scar formed after a heart attack. If the scar is small compared with the wavelength of the impulse, the waves hardly notice it—as when water waves pass over a tiny pebble unperturbed.
But if the obstacle is large, the wave can break, the edges lagging behind as the rest of the wave moves ahead, thus causing the segments to begin to curl (as when flowing water encounters a large rock and forms an eddy current downstream). Far enough out, the wave edges become the center of circular (or spiral) waves.
The circular pattern reflects the need for refractory heart tissue to return to an excitable state in order for the wave to propagate and not die out. The simplest pattern to do this is a spiral, that iconic image of psychedelia, that anchors at one point, circulates, and slowly moves outward. As Mines discovered in his experiments on jellyfish, these spiral waves are self-sustaining: they can constantly reenter tissue that has recovered its excitability and persist indefinitely.
Wave hitting a small obstruction
Wave hitting a large obstruction
Spiral wave in a computer model of cardiac tissue (Courtesy of Alan Garfinkel)
Spiral waves are ubiquitous in nature. They are created when smoke flows through cold air (see the picture on page 146) or when water flows across pebbles. They occur in superconductors and multicellular aggregates of amoebas, and in many chemical reactions, too. Even the visible mass in the universe is organized into spiral galaxies. With so many natural manifestations, it is no surprise that this pattern is seen in the heart as well.
Though Mines observed reentry only in lower animals, mostly fish, the phenomenon was soon confirmed in human hearts in 1924. It is now widely accepted that spiral wave reentry underlies most abnormally fast heart rhythms, including ventricular fibrillation, the most common cause of cardiovascular death in the Western world.
In ventricular fibrillation, the heartbeat is so rapid and irregular that effective pumping of blood ceases to the brain, lungs, and other vital organs, resulting in a precipitous drop in blood pressure and the almost immediate onset of cell death. Though the heart is still quivering, blood flow has essentially stopped.1 “Sudden cardiac failure does not usually take the form of a simple ventricular standstill,” the Scottish physiologist John Alexander MacWilliam wrote in 1889. “It assumes, on the contrary, the form of violent, though irregular and uncoordinated, manifestations of ventricular energy.” Every hour in the United States, forty people suffer an out-of-hospital cardiac arrest, mostly because of ventricular fibrillation. Fewer than one in ten survive. Ninety percent don’t even make it to the hospital alive. Ethnic minorities and lower socioeconomic communities fare the worst, perhaps because of a lack of access to external defibrillators and a lack of education in bystander CPR. Survival after in-hospital cardiac arrest isn’t much higher, about 25 percent. During the past several decades, mortality has decreased because of the proliferation of cardiac care units, community-based emergency rescue programs, and developments in cardiac electrophysiology. Yet ventricular fibrillation remains a death sentence for millions worldwide. An American dies of cardiovascular disease (including stroke and heart failure) every thirty-three seconds, accounting for about one in four deaths nationwide, and the terminal event in most of those deaths is ventricular fibrillation. Purveyor of life, the heart is also its Grim Reaper.
Ventricular fibrillation most often occurs in diseased hearts, where damaged cells and disrupted electrical signaling create the conditions for reentry. However—and this should come as a shock—fibrillation can occur in normal hearts, too. In what was perhaps his most important discovery, Mines experimentally determined that there is a narrow period in the cardiac cycle—a “vulnerable period,” he called it, about ten milliseconds in duration—during which a stimulus—an electrical shock or even a punch to the chest, in which mechanical energy is converted to electrical energy—can cause a perfectly normal heart to fibrillate and stop. To show this, Mines developed an apparatus to deliver single electrical shocks via taps of a Morse key to platinum electrodes placed on the ventricles of a rabbit’s heart. In a number of instances, he found that “a single tap of the Morse key if properly timed would start fibrillation.” The timing was crucial. “The stimulus employed would never cause fibrillation unless it was set in at a certain critical instant,” Mines wrote. A stimulus delivered before the vulnerable period would do nothing; after the vulnerable period, the stimulus would merely initia
te an extra heartbeat. But a stimulus applied within the vulnerable period could excite tissue just recovering from the last beat and precipitate fibrillation. In his 1913 report “On Dynamic Equilibrium in the Heart,” Mines wrote that his findings “suggest an explanation of the important and interesting condition of delirium cordis,” or madness of the heart.
The vulnerable period is crucial to understanding why normal hearts can self-electrocute. For example, when a healthy young athlete drops dead after getting a blow to the chest from a baseball or hockey puck, it is because the heart was hit during its vulnerable period. Scientists have confirmed the presence of the vulnerable period in mammals by slamming a baseball mounted at the end of an aluminum shaft into the chests of eight- to twelve-week-old anesthetized piglets at various times in the cardiac cycle. They found that when the impact occurs within a narrow window 10 milliseconds long and approximately 350 milliseconds after the previous heartbeat, it can induce cardiac arrest.
The explanation behind ventricular fibrillation in normal hearts is often also reentry. In a diseased heart with scar tissue, the mechanism is obvious: as we have seen, a wave breaks by interacting with inert scar tissue, forming spirals out of its edges. But reentry can occur even when there is no scar. In this case, a wave breaks by interacting with another wave, spinning around the refractory tissue formed in the other wave’s wake as if a scar were present. This is known as “functional” reentry (as opposed to the “anatomic” reentry) and is just as deadly. The impulse that induces the spiral wave must occur at exactly the right time and place to collide with the wake of a previous wave. This is precisely the vulnerable period that Mines discovered in his rabbit experiments.
The first experimental observation of cardiac spiral waves was made by José Jalife and his colleagues at Syracuse University in 1992 and published in the journal Nature. Using a special camera to detect fluorescence from canine heart tissue injected with specific chemicals, they produced an image with the shape of a counter-rotating spiral with a size of about two centimeters. Jalife’s group found that these spirals often anchor at scars or other inhomogeneities and can theoretically circulate indefinitely, each turn bringing the signal back to full strength, as Mines first showed.
Heart--A History Page 14