Atrial fibrillation is a heart disorder that causes the upper chambers of the heart to spasm instead of beating regularly. While that sounds dangerous, the lack of a regular heartbeat itself isn't dangerous. Instead, a-fib causes lots of indirect problems that can be debilitating or fatal. We're making progress in understanding the disease, as evidenced by two new papers that identify a total of 18 genes that predispose people to a-fib.

That should be exciting news. And it should be especially exciting to me, since I could have easily contributed to that studyas one of its subjects. I have a-fib, which I seem to have inherited from my mother.

Getting a better understanding of a disease can open all sorts of possibilities for better treatments, even ones tailored to your own particular genetics. But that's not really the case with a-fib, and it provides a great example of how science can sometimes run up against limits even as it successfully increases our knowledge.

Your heart has four chambers, two smaller ones on top called atria, and two much larger ones called ventricles. The rhythmic beat of your heart is the product of the regular contractions of these sets of chambers, first the atria, and then the ventricles. These contractions are organized by the unique properties of the heart muscle cells. These cells are driven to contract by a small electrical jolt delivered by a neighboring cell. In addition to contracting, this jolt causes these cells to release ions from storage areas, creating a small electrical jolt that they forward to their neighbors.

Some of their neighbors have already contracted, and so can't respond to this electrical signal immediately. The rest contract and forward it on further. This creates a wave of contractions that can only travel in one direction: away from the source of the signal at the top of the atria (or top of the ventricles), towards cells that haven't yet been triggered to contract. This organized wave of contraction, combined with a system of valves, drives the flow of blood in one direction.

In a-fib, all of this goes wrong. Multiple signals start, and take confused routes through the heart. Rather than a directional wave of contraction, the atria twitch and spasm. Rather than being driven in to the ventricles, the blood gets pulled in irregularly as they expand.

This might sound catastrophic, but the main force driving your blood through your body is the contraction of the larger ventricles. Some people remain completely unaware that they've developed a-fib until it's picked up during routine screening. Others, however, experience a variety of symptoms: pounding or irregular heart beats, changes in blood pressure, light headedness, and more. (My a-fib announced itself by a racing, pounding heartbeat that woke me from sleep at two in the morning.)

But none of those symptoms makes a-fib a serious health threat. Instead, the problems are invisible and insidious. Without the ordered contractions that drive blood out of the atria, it tends to pool up in the quieter corners, sometimes forming small clots. These eventually travel throughout the body until they lodge in small blood vessels, cutting off the blood supply to a small piece of tissue. Over time, this damage piles upin the heart, in the brain. A-fib is a major risk factor for strokes, heart failure, and early-onset dementia.

It's a terrible disease for those who suffer from these debilitating consequences, and they place a large burden on our healthcare system. Obviously, understanding more about why it happens would be a positive development.

Some cases of a-fib are rare events, brought on by things like hormone imbalances or even a bout of heavy drinking (ER doctors apparently refer to it as "Friday night heart"). But for many people, once it starts, it's there to stay. And it tends to run in some families like mine, suggesting that genes can help contribute to the risk of developing the disorder.

That fact would seem to provide a lot of hope for people suffering from it. After all, if we could understand the gene involved, we might be able to identify the environmental factors that convert that risk into actual symptoms. Or we could design drugs that specifically target the defective proteins that are causing the problem. Or even, in the not too distant future, we could intervene at the genetic level itself, editing or replacing the troublemaking stretch of DNA.

Genetics, as these new papers drive home, isn't being quite so cooperative. There is not a single, or even a handful of genes involved in raising the risk of a-fib; the new papers bring the total up to the neighborhood of 30, with the potential for even more to come. Some risk factors appear for the moment to be specific to different ethnic groups, for reasons we don't understand yet.

And, perhaps most significantly, they show that, on a biological level, a-fib isn't a single disorder. It's four or more. Many of the genes encode channels that let ions move within and between cells, an activity that helps create the tiny electrical jolts that trigger contractions. Others seem to be involved in the structure of cardiac muscle itself. Yet another class appears to help control the development of the heart, and may cause the disorder by creating structural defects. A possibly related class helps the nervous system form connections; failure of that process could also lead to structural defects.

Then there are the oddballs that we don't understand at all yet, like the genethat is involved in a-fib and "has been shown to be important in determining the invasiveness of cancer cells and has been suggested to mediate the neurotoxic effect of -amyloid in Alzheimer disease."

It's easiest to see why these results are pretty unhelpful by going through different points where you could intervene with a-fib. For most people, a-fib doesn't develop until later in life (mine started in my 40s), suggesting that it might involve some combination of genetic predisposition and environmental factors. But the complicated genetics suggest that, if environmental factorsexist, there may be lots of them, some specific to different classes of genes. It's a recipe for incredibly slow progress; teasing out any one of these could potentially take an entire career, and numerous (and expensive) human cohort studies.

Another option for intervention, and one used now, is to minimize the consequences of a-fib. The worst of these are caused by blood clots, so people with the disorder are often given anti-coagulants. (The recent development of a more effective anticoagulant has even led to an a-fib-specific pharmaceutical ad blitz.) Here, the underlying genetics are irrelevant. Regardless of what's causing the disease, limiting the risk of blood clots will be effective at cutting down on consequences.

For some of the genes, however, there is some cause for optimism when it comes to other treatments. Standard therapiesfor a-fib include trying a set of drugs that tone down the action of ion channels, making the heart a bit less reactive to electrical signals. This can reduce or eliminate periods of a-fib for some people, but finding the right drug and dose is a matter of trial and errorone that doesn't always end in success. If we know that a specific ion channel is the problem in a patient, it's possible that we could direct this process with some intelligence, identifying those who a drug is likely to work for and which drugs are likely to work.

But for people with structural defects put in place early in development, the only option would seem to be to redo the architecture of the heart. And, perhaps surprisingly, this is an option. But it doesn't depend on knowing anything about the heart's architectural problems.

The standard surgical intervention for a-fib relies on a somewhat odd finding. Medical researchers noted that cardiac muscle cells don't stay restricted to the heart. A few of them will migrate up into the blood vessels that connect the atria to the lungs. There, they end up outside the flow of electrical signals that organizecontractions across the heart. But, if they happen to contract spontaneouslysomething heart muscle cells will do even if you're growing them in culture dishthey can send electrical signals back in to the heart. These signals can interfere with the heart's normal rhythm, setting off a-fib.

The surgical treatment involves sending a probe through arteries and into the heart. There, doctors use an intense burst of radio waves to heat and kill small groups of cardiac cells, burning rings around the blood vessels that lead to the lung. These rings are repaired by scar tissue, which doesn't conduct electrical signals. Thisworks in the majority, but not all casessome people need try it multiple times before their a-fib is calmed. If the procedure is successful, though, the cells in the blood vessels can send all thesignals they want towards the atria;they never get there. Freed of the interference, the heart beats normally.

Perhaps the most striking thing about this procedure is that it seems to work for nearly everyone, regardless of what type of genetic predisposition they might have. For people who end up opting for this treatment, their genetic status is irrelevant. It seems to work if the problem is the heart's architecture, or if it's in the muscle cells themselves. Even if the problem is an ion channel that's found throughout the heart, silencing this one source of noise seems to be enough to quiet the problem.

Unfortunately, these sorts of results are not unusual in biology. People who follow biomedical research superficially can be forgiven if they get the impression that there are constant promises of progress that largely remain unfulfilled. But these new findings represent real progress, even if they don't tell me, a geneticist, anything useful about a genetic disease I have. They don't help us much when it comes to treatments at the moment, and it's hard to see how they will in the immediate future.

But the knowledge won't go away, and there may well be a time where this lays the foundation for a more refined treatment than burning scar tissue into the heart.

More here:
Why understanding the genetics of my heart disease isn't much help - Ars Technica