By Kelly Rae Chi

Atrial fibrillation (AFib) is the most common heart arrhythmia. It’s also among the most challenging to control -- first-line therapies don’t work for up to half of patients, raising their risk of heart failure and stroke.

By pinpointing the often-mysterious origins of AFib, fine-tuning drug strategies, and pushing the boundaries of catheter ablation, physicians in Duke’s new Center for Atrial Fibrillation are now restoring healthy heartbeats in more than 90 percent of patients -- and counting.

The heart’s beat begins with an impulse. The sinoatrial node -- our natural pacemaker -- generates electrical signals that travel through the atria and into the ventricles.

These signals set off synchronized contractions in each chamber of the heart, creating the comforting lub-dub sound of the heart’s pumping as it trades spent blood for a freshly oxygenated supply.

Atrial fibrillation (AFib) is the most common disruption of this powerful rhythm, affecting around 2.2 million Americans. It can stem from coronary artery disease, high blood pressure, structural heart defects, or even arise seemingly out of the blue.

Whatever the cause, abnormalities in the heart’s electrical system make the atrial chambers contract too quickly -- up to 350 times per minute. This quivering in the atria causes chaos in the ventricles, which react with a flurry of rapid, irregular beats. The lub-dub becomes more like a pitterpat -- one that is disconcerting at best, life-threatening at worst.

For some patients, AFib is barely noticeable: they have mild symptoms, such as fatigue, or no symptoms at all.

Others feel their hearts racing or experience frightening episodes of heart palpitations. These individuals often live in dread of such events: they don’t want to travel or go to work or school. Others give up exercise and other activities that could trigger the irregular beats.

"AFib symptoms and the anticipation of the episodes are so dramatic for some patients that it almost turns their lives upside down," says James Daubert, MD, the new director of the Duke Heart Center’s electrophysiology (EP) program.

Even worse than unpleasant symptoms, says Daubert, the irregular rhythm can contribute to heart failure, while ineffective pumping allows blood to pool in the ventricles and atria -- turning the chambers of the heart into a breeding ground for blood clots.

In fact, atrial fibrillation is responsible for about 15 percent of strokes.

Managing these symptoms and sequelae has long been a hit-or-miss proposition. The usual front lines of defense -- drug therapy to alleviate the arrhythmia and prevent stroke -- are often ineffective or fraught with complications.

But recent advances in understanding the physiology of AFib are leading to new treatment strategies, including safer, more effective medical management and sophisticated catheter ablation techniques that are providing a new alternative to drug treatment.

At Duke, electrophysiologists, cardiologists, cardiovascular surgeons, and other specialists on the forefront of these efforts are banding together to mount a new attack on AFib -- the Duke Center for Atrial Fibrillation (DCAF).

"The spectrum of therapies necessary to treat AFib today falls under different specialties, and we created the DCAF to draw on our depth of resources," says the center’s director, electrophysiologist Tristram Bahnson, MD.

"As treatment for AFib becomes more precise and personalized, we are bringing together a convergence of specialists to formulate how best to care for each individual patient."

A New Aproach to AFib

Treatment of AFib usually begins with a constellation of drugs, each selected to slow the heart rate, restore the heart’s normal rhythm, or prevent stroke. But medical management of AFib can be problematic.

More than half of patients treated with antiarrhythmic drugs report recurrences of atrial fibrillation within a year of the start of treatment, according to several nationwide studies. And when not used carefully, these drugs can actually trigger dangerous heart rhythms or other serious side effects.

For example, one of the most effective antiarrhythmics, amiodarone, can produce side effects such as skin discoloration, photosensitivity, thyroid imbalance, liver inflammation, or decreased lung function in as many as 30 percent of patients who take the drug for long periods. It also can interfere with the action of anticoagulant drugs, which most AFib patients should take to help prevent stroke.

And while antiarrhythmic drugs may improve symptoms, they do not improve mortality rates compared with those of AFib patients treated with rate-control drugs such as beta-blockers.

Catheter ablation, which cauterizes and neutralizes small spots of heart tissue that generate abnormal electrical patterns, is gaining ground as a strategy to help AFib patients who don’t respond to antiarrhythmic medication. According to a collective review of six smaller studies published in 2003 and 2004, roughly 80 percent of patients in their 50s and 60s who received the minimally invasive procedure were free from recurrent episodes.

"In the past, people who could not get good control of their AFib with medication just had to suffer the symptoms as best they could or perhaps undergo major surgery," says Bahnson.

Today, with catheter ablation as a proven alternative for patients who have failed drug therapy, the Duke team is able to control symptoms in more than 90 percent of people seeking treatment, he says. The DCAF currently performs the highest volume of AFib catheter ablations in North Carolina, and Bahnson expects the procedure’s popularity to grow.

Although it’s just coming into its own as a treatment for AFib, ablation to treat other abnormal heart rhythms has been around for several decades. In fact, cutting or removing pieces of heart tissue to cure arrhythmia was pioneered at Duke.

In 1968, a Duke team performed the first successful ablation surgery to treat abnormal heartbeats in a 32-year-old fisherman who had Wolff-Parkinson-White syndrome -- a disorder that causes AFib or other fast heart rhythms.

In 1987, James Cox, MD, a cardiothoracic surgeon at Barnes-Jewish Hospital in St. Louis who had trained at Duke, showed that he could cure AFib by making and then suturing multiple incisions in a grid-like pattern of lines through the atrial chamber walls -- a technique known as the Cox maze procedure, or simply "maze."

The idea was that the incisions would leave lines of scar tissue that could act as barricades, blocking impulse propagation in the heart chamber and preventing AFib from being sustained. Maze surgery is still performed to treat AFib, but usually in conjunction with other major open-heart surgery.

The maze surgery was complex and daunting to imitate with a catheter, says Daubert, who was in training at Duke around that time. When Cox introduced the surgery, many assumed that the electrical source of atrial fibrillations originated within the atria itself.

That idea was challenged as other doctors tried maze and discovered that the pulmonary veins were usually "the money spot" for the origin of the abnormal heartbeat.

"The discovery that it was coming from the pulmonary veins made catheter-based treatment a more feasible target," Daubert says.

Other strategies were also being tested, such as the use of implantable cardioverter defibrillators, or ICDs, to shock the heart and restore normal rhythms. For patients with ventricular arrhythmias, which are sometimes accompanied by atrial fibrillation, ICDs are commonly used, and the devices have been shown to reduce the incidence of sudden cardiac death in patients with heart failure.

In the late 1990s, researchers tried ICDs as a therapy for atrial fibrillation. While the devices worked to shock the heart back into normal rhythm and to reduce the frequency of AF episodes, the shocks were painful and were needed too often to make the treatment practical, Daubert says.

In the late 1990s, Daubert and others did their first catheter ablations to treat atrial fibrillation. It was slow going in this early stage of the technique: they would put the catheters in the heart and wait for the first signs of abnormal activity. Was it coming from the left pulmonary vein, or the right? The doctors would leave the catheters in different regions of the heart, sometimes for hours.

They tried to speed the process along by artificially pacing the heart into AFib and then restoring normal rhythm with a shock, hoping to stir up the sites that led to a recurrence of AFib.

"The problem was that sometimes [the fibrillation] wouldn’t happen during that procedure," Daubert says. "Sometimes, it would come from one vein and we’d ablate there, but another day it would come from a different vein and we hadn’t ablated there."

Over the next few years, it became clear that electrophysiologists needed to ablate around all four pulmonary veins, regardless of where initiating arrhythmias were observed. By then the potential benefits of the treatment began to crystallize.

Better Ablation

Bahnson is also encouraged by the rapid development of ablation and the potential for the technique to improve lives. In fact, the results are so promising that they raise the question of whether ablation could become a first-line therapy for atrial fibrillation.

However, Bahnson cautions, a few important unknowns remain about the procedure’s long-term effectiveness. Bahnson is one of the principal investigators of a large, multi-site investigation coordinated by the Duke Clinical Research Institute that will compare catheter ablation with drug therapies for initial treatment of atrial fibrillation.

"This study will likely be a definitive one to determine whether mortality or stroke rates in AFib patients are improved by catheter ablation as compared to treatment with medications only," says Bahnson.

Meanwhile, Daubert is beginning research that will look at outcomes of ablation treatment in older patients.

"Most patients with AFib are in their 70s or even 80s," he says. "We don't have a lot of data as to whether the ablation is as safe or effective in this group as it is in younger patients."

Catheter ablation does come with risks and challenges. For example, in rare cases, the ablation procedure itself can cause blood clots and subsequent stroke. In other rare instances, parts of the body, such as the esophagus, can be injured during the procedure.

Researchers in the DCAF are investigating a range of novel technologies to make catheter ablation safer and more effective. For example, Duke recently began working with a new system, Hansen Medical’s Sensei X Robotic Catheter System, which allows catheters to be manipulated with greater control and precision within the heart. Outcomes research is under way to establish the value of this system and develop it further.

Other DCAF research is testing arrhythmia-mapping techniques to identify areas that should be targeted for ablation and to determine when enough ablation energy has been delivered at any given site within the heart.

"A big question in the catheter-ablation arena is how do you know when you’ve created a lesion in the heart that’s sufficient?" says Bahnson.

The DCAF group is now assessing catheter-created lesions in real time, working with Duke bioengineers on intracardiac ultrasound techniques that image the heart from within.

Various types of catheters in development might also make ablation safer and easier. Duke physicians are working on one new type that freezes heart tissue instead of cauterizing it, as with radiofrequency ablation. Daubert says the technique, called cryoablation, may make ablation safer than with traditional methods.

"If we’re ablating too close to the pulmonary vein, we could cause it to scar or narrow," Daubert says. "With the cryoablation, that problem is almost completely eliminated."

Another new type, an irrigated catheter, has six pin-sized holes at the tip that can be flushed with saline to prevent the catheter tip from overheating, thereby reducing the risk of blood clots. Both new catheter types, Daubert says, may help minimize the risk of stroke.

New techniques may also make catheter ablation for AFib more efficient. Daubert is currently experimenting with inflating a balloon at the opening of the pulmonary vein, which allows physicians to ablate all the way around the vein using radiofrequency energy or freezing techniques, rather than having to make small lesions, point by point, sometimes over the course of several treatments.

Personalized Rhythms

Despite the impressive advances in catheter ablation, the procedure may not be necessary or appropriate for all patients.

"There are so many players that act in the development and continuation of AFib," says Patrick Hranitzky, MD, director of the EP fellowship program at Duke, who is leading research to better understand the condition.

"It’s very difficult to decipher what all the contributors are," which can make it tough for physicians to select the best treatment.

For example, Hranitzky says, "There’s a clear difference in the mechanism of AFib in a 30-year-old marathon runner as opposed to an 80-year-old with a long-standing history of hypertension -- these differences involve not only what sustains it but what initiates it."

In the marathoner, extreme physical stress can cause changes in electrical properties within the heart, triggering episodes of AFib in athletes predisposed to the condition.

In contrast, an elderly person might develop AFib because of age-related structural changes in the heart muscle. The heart becomes less flexible, and can develop tiny scars or fibrosis that can worsen with time, especially if high blood pressure is not controlled. This fibrosis can cause atrial fibrillation.

For the marathoner, doctors aim to prevent the triggering of the arrhythmia, Hranitzky says. If the triggers can be identified -- usually they are found near the junction of the pulmonary veins and the left atrium of the heart -- the arrhythmia can often be effectively treated with antiarrhythmic medications that abate the triggers, or cured with catheter ablation.

The elderly person, however, has a more complex situation. His heart cells have undergone a process of “remodeling,” and merely eliminating the triggers does not suffice.

"We must also alter the remodeled substrate," Hranitzky says, using either drugs or ablation to target the affected heart tissue.

The researchers are now probing deeper into what makes AFib different in each person.

"Clearly there are people who have genetic predispositions to AFib," says Hranitsky, but "it’s not going to be a single gene that determines whether someone will have AFib or not."

To help untangle the complex causes of the condition, Hranitzky and his colleagues began assembling a biorepository and clinical database for arrhythmia research in 2006 -- collecting DNA, messenger RNA, and protein from consenting patients in the electrophysiology lab.

By identifying alterations in these molecules, the researchers hope to find new clues about the underlying mechanisms of atrial fibrillation. They plan to look for genetic or molecular predispositions based on gender, age, and race differences, as well as for differences in the way individuals respond to treatment. The findings could lead to better prevention strategies and more targeted treatments. Researchers at other institutions are working on these same types of studies.

"In reality it’s going to take a collaborative effort among many centers," Hranitzky says. "We’re not going to have all the answers, but personalized treatment for arrhythmias is something that we’re moving toward."

Daubert, who created and led the University of Rochester’s heart rhythm program until he returned to Duke this summer, says the range of new AFib treatment techniques and technologies introduced over the course of his career is heartening -- just a decade ago, for his patients with AFib that didn’t respond to medical therapy, he could do little more than watch their hearts quiver. He says he’s pleased to be back at his alma mater to tackle the next frontiers in atrial fibrillation.

"Coming back to head up the program that pioneered some of these ideas that have brought us this far is really an awesome opportunity. This is a team with the expertise and drive to truly make a difference in people’s lives."

This article was first published in the Fall 2009 edition of DukeMed Magazine.