We recently concluded our annual Heart Rhythm Society professional meetings in Boston. The Heart Rhythm Society is the largest group in the world focused on the electrical system of the heart. In the meetings, researchers present the latest studies that guide the practices of heart rhythm specialists throughout the world. Occasionally, a research study is presented that changes the way I think about a certain disease and gives me optimism that better therapies are on the horizon.
This year I listened to one of these presentations that involved atrial fibrillation after heart bypass surgery and, of all things, Botox (botulinum toxin type A).
Botox is an injectable therapy to improve the appearance of deep frown lines or age-related lines in their face. It is also used for other conditions, such as overactive bladder problems, migraines, severe underarm sweating, and muscle spasticity.
And research presented at the meeting shows it may also have a role in heart disease, as I will explain.
Botox: From Dangerous Bacterium to Useful Drug
Botox is made from the toxin of bacteria called Clostridium botulinum. This same toxin that is used to help many medical conditions in small controlled doses can also cause a life-threatening food poisoning called botulism.
I have only encountered botulism once, in a young child who consumed honey from a local farm. In addition to honey, botulism can come from incompletely preserved home-canned foods. The little boy came to the hospital with trouble swallowing, was severely weak, and had difficulty breathing. He was in the intensive care unit for many weeks before he recovered. Botulism treatment often involves giving an antitoxin in addition to intensive care support.
The Clostridium botulinum toxin affects our nerves by inhibiting the release of a chemical called acetylcholine. Acetylcholine is a neurotransmitter that is released at synapses, the sites where nerve cells communicate with one another and other tissues. When these neurotransmitters are blocked, nerve communication is lost and paralysis develops. When applied locally in small areas, Botox takes away facial muscle tension on the skin and the appearance of facial lines improves. But when the toxin is spread throughout the body, then the life-threatening disorder known as botulism develops.
Atrial Fibrillation and Your Nerves
The most common abnormal heart rhythm cardiologists see in their practices, atrial fibrillation(afib) is an abnormal heart rhythm of the upper heart chambers. It can cause symptoms of a racing heart, palpitations, chest discomfort, shortness of breath, swelling in your legs, loss of energy, dizziness, and loss in exercise capacity. It can also cause stroke, heart failure, heart attacks, and dementia, and increase your risk of death. You have a 10 percent to 20 percent lifetime risk of developing afib if you live in a developed country. At the time of cardiac surgery for other heart disorders, such as abnormal heart valve function or multiple narrowings of the coronary arteries, atrial fibrillation risk goes up to 50 percent.
In fact, treatment for afib is one of the most common reasons people who undergo heart surgery stay longer than expected in the hospital. You can take steps yourself to help treat atrial fibrillation, like getting enough sleep, treating sleep apnea if you have it, losing weight, eating a whole food, plant-based diet, and exercising. But you may need treatment, and you may be surprised to learn that the treatment targets your nerves.
The Heart’s ‘Brain’ and Botox Injection
Our hearts respond quickly to our brains. Just the thought of something stressful such as exercising, giving a speech or presentation, or solving a complex equation will raise our heart rates. Similarly, thinking about a good meal or sleep will often slow the heart rate. However, the heart has its own “brain”: There are numerous small nerve cells called neurons in the heart, with a command center of neurons called a ganglion plexus. These command centers make careful, rapid adjustments to the heart that are critical to keeping our blood pressure and heart function normal.
For example, just to stand up from a seated position requires numerous complex signaling processes for the body to respond immediately and elevate your blood pressure, slightly stiffen your arteries, and raise your heart rate. The multiple small command centers are constantly responding to our environments, so for the most part we think very little about the job our heart is doing. But these same nerves and nerve command centers could also potentially be blocked by Botox.
Not all of the nerve cells in the heart do the same thing. Some slow the heart down and others speed it up. When some areas of the heart are being stimulated to speed up and other are simultaneously being stimulated to slow down, abnormal heart rhythms develop.
Atrial fibrillation is most often a consequence of the pulmonary veins that drain blood from the lungs to the heart being sped up electrically. These rapid abnormal impulses go into the top heart chambers, which may be, at the same time, being stimulated to speed up or slow down. The abnormal electrical impulses collide, and the electrical rhythm becomes unstable and chaotic.
Altering the Heart’s Nervous System
The most-used atrial fibrillation treatment is a drug that slows the rapid electrical signals of the pulmonary veins. When the drug fails, or is not tolerated because of side effects, we perform a catheter ablation procedure. Ablation creates small scar boundaries around the pulmonary veins to block electrical signals from the vein from getting out into the heart.
Doctors often try to find the ganglion plexi (the nerve command centers) and injure them as well, to control their rapid electrical triggering of the veins. Surgeons also do this when they perform amini-Maze procedure for atrial fibrillation, or when they do an ablation at the time of a heart surgery.
But long-term success rates for keeping patients free of atrial fibrillation are between 70 percent and 80 percent, even at the best centers.
Where Botox Comes Into the Picture
Evgeny Pokushalov, MD, PhD, from the State Research Institute of Circulation Pathology in Novosibirsk, Russia, reported on his study of 60 patients who had a history of atrial fibrillation and underwent coronary artery bypass surgery. Typically, 30 percent to 40 percent of these patients would develop atrial fibrillation immediately after surgery.
Investigators randomized these patients to get injections of Botox in the ganglion plexi or throughout the upper heart chambers, or to get placebo (salt water injections). To accurately measure all atrial fibrillation episodes immediately after the surgery and over the next year, each patient had a small cardiac monitor placed just under the skin.
The findings immediately after surgery were extraordinary:
7 percent of the patients who got the Botox experienced atrial fibrillation.
30 percent of the patients who got the placebo experienced atrial fibrillation.
Although this was a relatively small study, this research finding suggests that inhibiting the heart’s nerve centers can almost completely block the significant surgical stresses that cause atrial fibrillation: the effects of physically manipulating the heart and increasing the inflammation of the heart and the heart sack (pericardium).
Botox Effects on the Heart: 30 Days Later
The story doesn’t end there, which makes the study even more interesting. All these patients were then followed for one year. Each time they were seen in follow-up, the measurements made by the implanted cardiac monitor were studied.
No patients who got Botox developed atrial fibrillation.
27 percent of those who got the placebo therapy did develop atrial fibrillation.
The local paralysis of Botox typically only lasts for two to three months. That is why people who use Botox for wrinkles often go back several times a year for more injections. In this study, despite the anticipation that the effect of Botox would only protect these patients in the surgical healing period, after which they would require other therapies for atrial fibrillation, the benefit persisted.
The Botox benefit was much better than for ablation, when surgeons burn or destroy the ganglion plexus structure in a mini-Maze procedure, and perform additional ablation to electrically separate the pulmonary veins.
This finding tells us that small alterations to the nerve centers are very important, more so than simply trying to destroy the ganglion to prevent its bad influence.
When I heard this study at the Heart Rhythm Scientific Sessions meeting, I immediately thought that as physicians, we need to be more precise in how we target these ganglia. Perhaps looking at ways to reset them and restore normal function will be more valuable than simply removing or separating them from the heart through aggressive ablation. In doing so, success rates of these procedures may start to reach 90 percent to 100 percent, similar to what was seen by this team of Russian scientists.
Clearly, this is only one study, and it is relatively small, but the findings represent a new discovery that may help us develop better therapies and approaches to atrial fibrillation.
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