The electrocardiogram inspires this “sizzling” depiction of the relationship between heart and brain health. (Image credit: ©PASIEKA/PHOTO RESEARCHERS, INC.)
Thursday, February 28, 2008

Your Brain and Heart Surgery

By: Guy McKhann, M.D., and Brenda Patoine

Some heart surgery patients have cognitive problems afterward, but the idea that the surgery causes these problems is misleading. Guy McKhann and Brenda Patoine reveal how brain health before surgery appears to be the key influence on brain health afterward; recent findings suggest that the same problems affecting the arteries of the heart, pre-surgery, are also affecting the blood vessels feeding the brain. These findings have important implications for treatment options and how doctors inform patients of risks. Last but not least, they reinforce the idea that what’s good for the heart is good for the brain, too.

Since the earliest days of cardiac surgery—unquestionably one of the great medical triumphs of the late 20th century—post-surgery memory problems and mental fogginess have been observed in patients. Heart doctors even had a nickname for it: “pump head.” The slang referred to the heart-lung bypass machine that made the surgeries possible but was presumed to be the cause of the problem.

Fortunately, such short-term cognitive problems usually resolve within a few weeks; by a year post-surgery, most people are back to normal. It is also not at all clear that the “pump” itself is the culprit, since cognitive problems are also associated with newer “off-pump” procedures.

But the biggest controversy surrounding heart disease and the brain is the question of longer-term cognitive problems. It has become conventional wisdom that after bypass surgery, some people have cognitive dysfunction. In practice, this message often gets oversimplified, leaving the impression that bypass surgery in fact causes cognitive decline. Indeed, the perceived cognitive risks of this surgery influence treatment decisions all the time.

As it turns out, this line of thinking not only oversimplifies a complex problem; it may in fact be downright misleading.

My research group’s most recent data suggest something quite different. We found that over the long term, people with documented coronary artery disease have essentially the same rate of cognitive problems whether they have bypass surgery or some less invasive procedure. Although people who have cardiac surgery to remedy their heart disease do generally experience modest cognitive decline over time, the rate of decline is not significantly different for them than for people whose heart disease is treated with stents, for example. In fact, the best predictor of whether a person will suffer latent cognitive decline is not whether they have bypass surgery but how healthy their brain was before any intervention.

Taken together, these findings suggest to us that cognitive decline occurs in these patients—all of whom clearly have heart disease—because the same disease processes that have gradually closed their heart arteries have also affected blood vessels feeding their brains. Our working hypothesis is that surgical patients who go on to suffer cognitively started out with some level of cerebrovascular disease to begin with—it just may not have been far enough along to produce noticeable clinical symptoms. Several lines of evidence support this hypothesis.

The implications of this concept, should it prove true, are important. We may need to carefully rethink how we screen people for surgery, how we talk to people about the risks of surgery, and what needs to be done to lower risk factors that are modifiable. In addition, this hypothesis would affect the contentious debate raging right now about the comparative risks and benefits of bypass surgery versus “non-surgical” interventions such as stenting, in which a catheter embedded with a mechanical device is threaded through an artery in the groin to fix problem arteries in the heart. The risk of latent cognitive decline with surgery has entered into this debate and is often cited by proponents of non-surgical techniques as one more reason their approach is better.

There are public health implications as well. Despite decades of health messages urging otherwise, Americans are notorious for lifestyles that increase the risk of heart disease, such as eating too much fat and not getting enough exercise. Perhaps we will pay more attention if we understand that a heart-healthy lifestyle also might help save our brains.

I don’t know of anyone who desires to spend their golden years in the fog of cognitive dysfunction or dementia, and baby boomers seem to be particularly inclined to take steps to protect their mental health. Such protection could go a long way toward improving public health and controlling health-care costs, given the dire predictions about the looming impact of age-related brain diseases as boomers grow old. The message is clear: do your heart good and you do good for your brain as well.

Five Decades Fixing the Heart

When it was introduced in the 1950s, the cardiopulmonary bypass machine, or “heart-lung machine,” changed cardiology forever. Pioneered by John Gibbon in collaboration with his wife, Mary, and engineers from IBM, it was first used successfully in 1953 on 18-year-old Cecilia Bavolek to close a hole between the upper chambers of her heart. Refinements continued rapidly as surgeons embraced the technique, and the era of cardiovascular surgery was born.

The bypass machine acts as a temporary stand-in for both heart and lungs, pumping blood and oxygen through the patient’s body even while the heart is stopped. This makes it possible to operate directly on heart valves, chambers or the aorta, the major vessel that routes blood out of the heart. Temporarily stopping the heart from beating also stills it so delicate surgical procedures can be performed more precisely.

In bypass surgery—technically called coronary artery bypass grafting (CABG)—the surgeon literally sews in a grafted vein, usually from the patient’s leg, to bypass blockage in one or more of the arteries that supply the heart. The evidence is clear that CABG can be remarkably effective in relieving chest pain (angina), a common symptom among people with heart vessel diseases.

Until a few years ago, CABG surgery was one of the most common procedures done in many hospitals in the United States; it was not unusual for major medical centers to do 1,000 to 2,000 a year. In its heyday, roughly 800,000 CABG surgeries were done annually, but that number is now down to about 250,000, largely because of the increased use of stents.

Stents are small tubes that are placed inside blood vessels to keep them open. Modern stents are often impregnated with drugs or chemicals designed to keep them functioning longer once they are implanted. While stents have not yet displaced CABG, they have become the treatment of choice for many physicians when coronary artery disease is limited to one or two blood vessels.

Some surgeons have also turned to off-pump surgery, in which the bypass pump is not used and surgery is done on the beating heart as an alternative to CABG. They hoped that this approach would have fewer brain complications, but the results have been mixed: Off-pump surgery is associated with fewer strokes but does not appear to offer much benefit in terms of reducing longer-term cognitive deficits.

Paradoxically, as a result of the rise of stents and off-pump surgery, the people who are treated with CABG today tend to be the same ones who are at greater risk for latent cognitive problems: they are typically older and have more risk factors for vascular disease.

My colleagues at Johns Hopkins University Medical School and I first became interested more than 15 years ago in finding out what happens to the brains of people who have had CABG procedures. In our experience, cognitive difficulties arise shortly after surgery in about 30 percent of patients. The underlying biological mechanisms are not entirely clear, but many factors are likely to be involved. Older people and those who have symptoms of brain swelling (“encephalopathy”) as a result of surgery are more likely to have short-term problems, and surgery patients should expect their doctors to discuss the possibility of short-term changes in cognition with them, as well as with their family members and friends. The good news is that people get better, many within three months of surgery and most within a year.

Thus we have turned our attention to problems over the longer term.

Rethinking Latent Decline

During the past several years, considerable controversy has arisen over whether a person who undergoes CABG is more likely in succeeding years to have progressive decline in cognitive function or heightened risk for Alzheimer’s disease or other types of dementia. Several studies have reported long-term cognitive changes after CABG, including an oft-cited 2001 report in the New England Journal of Medicine by Mark Newman and colleagues, who found significant cognitive decline in more than 40 percent of CABG patients five years post-surgery.

This and other studies have fueled a widespread belief in the “CABG-equals-cognitive decline” mantra. The problem is that the studies on which this belief is based did not include any control groups to which surgical patients were compared. For us, this begs the question “Cognitive decline compared with whom?”

My colleagues and I have recently completed a long-term prospective study in which we have tracked for six years people who had coronary bypass grafting. We compared them with people who have proven coronary artery disease but did not have surgery (a group we call “non-surgical controls,” most of whom had stent procedures) and with a group of people we call “heart-healthy controls” because they have no known risk factors for coronary artery disease.

We performed a battery of cognitive tests on everyone at the study’s start, before any interventions were performed, and then at time points of one, three and six years afterward. The “baseline” analysis at the study’s start proved very interesting in and of itself.

It turns out that the people in our study who had existing coronary artery disease, whether or not they went on to have surgery, were quite different as a group at baseline than the heart-healthy controls. They performed more poorly on various tests of cognitive function, particularly on tests that gauge executive function, which encompasses abilities related to planning, making decisions and controlling impulses. Memory function, in contrast, was quite similar among the groups at the beginning of the study.

After one year, all three groups showed some improvement in the cognitive testing, most likely because of a practice effect (i.e., they got better at taking the test each time they took it). But the two groups with coronary artery disease didn’t improve as much as those in the healthy control group. In other words, their cognitive scores were comparable to one another but not on a par with those of the heart-healthy controls. At six years, we do see a moderate decline in cognitive function, but it is essentially the same in both groups with coronary artery disease. There is no long-term decline specific to those who had surgery. A logical explanation for this is that blood vessels throughout the body and brain, not only the heart, had already been damaged by arterial disease. It was this ongoing disease process—not the surgery per se—that set these people up for later cognitive decline.

Predicting Stroke and Other Risks

Although CABG surgery seems not to be the cause of cognitive decline in cardiac patients, extra care may be necessary in patients who are at risk for stroke and other problems. Stroke occurs when an area of the brain does not get enough blood. Blood supplies oxygen, and the brain needs oxygen to function. Strokes can be caused by either a hemorrhage in the brain or the blockage of a brain blood vessel. Think of the analogy of a sprinkler system on a lawn: if one of the pipes in the system becomes clogged, that area of the lawn does not get water and eventually dries up and dies. A similar process occurs in the brain if a blood vessel becomes clogged and blood flow to a region of the brain is restricted.

Why are strokes associated with CABG and other forms of heart surgery? The most likely explanation is that during surgery, small bits of material, usually blood clots or bits of tissue associated with arteriosclerosis (so-called “hardening of the arteries”), break off and are carried through the bloodstream to the brain. There, they lodge inside blood vessels and eventually block blood flow to the brain. Stroke can also occur when blood pressure falls too low to pump enough blood to the brain. For these reasons, blood pressure is carefully monitored during surgery. In most people who suffer a stroke as a result of heart surgery, bits of material and low blood pressure seem to be working together to cause damage.

By studying the characteristics of people who have had a stroke associated with CABG, it has been possible to develop a paradigm to estimate an individual’s chance of having a stroke based on identified risk factors. Age is one important factor. A history of hypertension or diabetes is another, because these conditions are associated with vascular disease. A previous stroke or narrowing of blood vessels in the neck or the legs also indicates heightened risk. For those at higher risk for stroke, we advocate a preoperative magnetic resonance imaging study. However, the information we would most like to have, the status of the small blood vessels of the brain, is not obtainable by present imaging methods.

Also sometimes associated with cardiac surgery is encephalopathy, a pathological process involving large areas of the brain. People with encephalopathy are generally slow to wake up from the anesthesia used during surgery and are often quite confused—even delirious—when they do wake up. They may be combative and have problems with memory, in some cases not even recognizing family members. Postoperative management for these patients can be challenging.

We consider stroke and encephalopathy to be part of a continuum with common underlying mechanisms—namely, lack of blood flow to the brain because of low pressure (“hypo-perfusion”) and/or multiple small strokes. The same kind of predictive modeling that is used for stroke can be used to estimate an individual’s risk for encephalopathy. Both stroke and encephalopathy are associated with poor recovery and increased risk of death.

Reducing Surgical Risks to the Brain

In a perfect world, all surgical candidates would undergo testing that would determine the extent of damage and disease within their neurovascular systems. In that world, we would also have medications that could be used prior to surgery to protect the brain from injury. Preventing injuries would be very difficult, but changing the brain’s reaction to the injury—so-called “neuroprotection”—is a realistic goal.

There have been many attempts to develop neuroprotective drugs, but despite promising results in experimental animals, very little has been transferred to the human. Large-scale clinical trials have failed, without exception. But cardiac surgery patients are an excellent group in which to evaluate neuroprotective drugs because we can take baseline measurements before surgery, carefully control what happens during surgery, and track patients over time to determine if there is a protective effect and how it might be maximized. That is clearly a next step in research related to this surgery.

If a person is deemed to be at high risk for stroke or encephalopathy, several steps should be taken. The first is to reevaluate how badly he or she needs the surgery and to consider all other alternatives, such as unblocking the artery with a stent. The second is to alter the surgical procedure, which might involve placing filters in the bypass system to prevent clots from reaching the brain. Alternatively, some surgeons have attempted off-pump surgery. However, the evidence that this approach is markedly better than conventional CABG is not conclusive.

Finally, people at high risk for complications require careful evaluation prior to surgery to determine, as best we can, the status of the blood vessels that supply the brain and those within the brain itself. New techniques for evaluating what we call brain perfusion—how much blood is being pumped to various parts of the brain—hold promise for providing necessary information about the status of someone’s brain before or after surgery.

In the meantime, there are things that can be done to reduce the risk of cognitive complications, not just from surgery but in general. And guess what? They are the same things we should be doing to improve the blood vessels of the heart. Perhaps you’ve heard the line: What’s good for the heart is good for the brain. This is a fundamental tenet that modern neuroscience has taught us. Stopping smoking, increasing your level of physical exercise, and keeping your weight under control are essential components of a “brain-healthy” lifestyle, as is proper management of risk factors such as hypertension, diabetes and high cholesterol. This sounds obvious, but many patients who have surgery go back to the very lifestyle that got them into trouble in the first place.

CABG is clearly a very valuable procedure, and an important treatment option for people with serious heart disease. We now know that it is possible to predict who is likely to sail through the procedure without much trouble and who is at risk for having cognitive complications in the aftermath of surgery or much later. Anyone in one of these now well-defined high-risk categories who is facing heart surgery should have a serious discussion with his or her cardiologist and surgeon to explore possible alternatives and determine how to lower the risk as much as possible.



About Cerebrum

 
Bill Glovin, editor
Carolyn Asbury, Ph.D., consultant

Scientific Advisory Board
Joseph T. Coyle, M.D., Harvard Medical School
Kay Redfield Jamison, Ph.D., The Johns Hopkins University School of Medicine
Pierre J. Magistretti, M.D., Ph.D., University of Lausanne Medical School and Hospital
Robert Malenka, M.D., Ph.D., Stanford University School of Medicine
Bruce S. McEwen, Ph.D., The Rockefeller University
Donald Price, M.D., The Johns Hopkins University School of Medicine

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