Rebecca Levit
For the last few years, cardiologist and assistant professor at Emory School of Medicine, Rebecca Levit, has been engrossed in creating a device that more safely delivers a key medicine for patients with atrial fibrillation, a disorder seen in many patients hospitalized with heart problems. She recently received a grant from the National Institutes of Health (NIH) to begin a second set of pre-clinical trials.
Atrial fibrillation — or Afib as it’s also typically called — is an unsteady or irregular heartbeat (arrythmia) that can lead to blood clots, stroke, heart failure and death.
Levit, whose research lab is also funded by the American Heart Association, will begin testing her device on animal models this month. An excerpt of our conversation with her is below.
What is Afib and how common is it?
The heart on average beats close to 100,000 times a day. For some, this rhythm becomes unreliable, leading to less forceful contraction, less efficient blood circulation and an uneven pulse. The heart may race from a normal resting rate of 60 to 90 beats per minute (bpm) to 200 bpm, then slow down after a few moments. This irregularity may persist or come and go over time. Patients often say they feel like their heart is about to jump out their chest. The rapid misfiring can result in mild to severe symptoms, from shortness of breath to dizziness to palpitation to chest pain.
At least 2 million Americans are living with Afib and the Centers for Disease Control and Prevention (CDC) estimates that number will surge to 12 million by the end of the decade. In 2019, Afib was mentioned on 183,000 death certificates.
What causes Afib and what damage can it cause?
Afib has a lot of causes so there’s not just one thing you can fix. People tend to develop the disorder as adults and then live with it for a long time — the risk does increase with age. Those with high blood pressure, prior heart disease, diabetes and sleep apnea are at higher risk for Afib. Excessive alcohol and smoking are some of the behavioral factors associated with the disease.
The risk of stroke is about five times greater in patients with Afib. It’s estimated that more than a third of patients with Afib will have a stroke.
You invented a treatment device for treating Afib?
Nearly 80% of patients admitted to the hospital with heart problems suffer from Afib. One of the most effective therapies, especially for surgical patients, is a drug called amiodarone but less than one percent of this drug goes to the heart when infused or given as a pill. Instead, it builds up at toxic levels in the liver, lungs and thyroid, increasing the risk of poor outcomes and death.
A few years ago, my team along with colleagues from Emory and the Georgia Institute of Technology developed a unique catheter design that allows us to place hydrogels containing amiodarone directly in the pericardial space of the heart ensuring efficient delivery and minimizing any harmful effects to surrounding organs. The procedure is minimally invasive, can be done in a catheterization lab and only takes about 30 minutes.
The study showed that delivered this way, much less amiodarone needs to be given to achieve the same results, and importantly, it helps prevent these off-target organs from developing the toxicities that we now see among Afib patients who get this drug.
What is special about this device?
Our hydrogel delivery device is the first to be specially designed for localization of gels in the heart. While our first application is the medication, amiodarone, many other therapies could be delivered to the heart more efficiently using this device.
What’s next?
We are launching another pre-clinical trial with the NIH grant. This time, we are going to use a surgical prototype that will deliver amiodarone during open heart surgery in animal models. This is the sort of study we need to gather safety data before we can go to the U.S. Food and Drug Administration (FDA) to ask for permission to conduct a small Phase 1 clinical trial among surgical patients.
We are scheduled to begin the trial at the end of February. We think this could be an important use for this device as between 25% to 40% of surgical heart patients develop Afib after the operation. They then must endure longer stays in intensive care, incur more expense and possibly suffer worse outcomes in the longer term.
Your study showed that the device appeared to be both safe and effective in an outpatient setting. Do you plan to launch a clinical trial for that usage?
Yes, once we get the data from the study and funding from investors.
If this next round of pre-clinical trial is successful, we think we can move quickly to understand what the FDA requirements are to launch a clinical trial. Given that there are a lot of patients who are undergoing open heart surgery or at risk for heart failure, we hope to test this among real patients within a year, assuming we get the green light from the agency. We hope the safety information needed for a Phase 1 clinical trial is one that we can easily show.
Can this device be used for other diseases?
Absolutely, and that is the plan. While we are currently focused on Afib to show proof of concept, we think we can use the device to deliver all types of medicines for both surgical and non-surgical patients with other conditions in the future.
Some studies have indicated that COVID-19 affects the heart. Are you looking at that?
We are studying how the immune system influences how well the heart functions. While it appears that SARS-CoV-2 causes indirect damage to the heart, we are following up to look at neutrophils in tissue from patients who died from COVID-19. Neutrophils are the most common circulating white blood cell in the body. We found some evidence that neutrophils trigger inflammation and clotting in COVID-19 patients and that was published in Cell last year. We saw that the higher the neutrophil levels, the more severe the disease. We are investigating further.
We are also investigating the cardiac impact of long COVID by looking at echocardiograms of those who got an ultrasound prior to getting COVID and then comparing their heart pre and post infection. We are not looking at their cardiac activity during COVID but instead, the ECHO is done at least a month later, well after the infection has ended.
What excites you about new advances in treatments for cardiac issues?
I think solutions like the device we are testing that allows us to deliver medicines, biologics or gene therapy to patients can help lead to more effective therapies overall.
Are women still slightly less likely to get heart failure than men?
Yes, but there is much we don’t know about sex and its impact. For instance, we see a heart condition that affects mostly women, and largely perimenopausal women, called coronary micro vascular dysfunction. This was a mystery illness until recently; women would go to see their doctors complaining of chest pain but the cardiac scans would show the coronary arteries to be normal and they would be told that it was just anxiety. Now we are seeing that the disease affects the small arteries and capillaries — which don’t get captured in the scans — and that constricts the blood flow to the heart. So, here you have a very common disease that mainly affects women and is very debilitating and yet we don't really understand it or know anything about why it happens, and until some years ago, wasn’t even characterized as a heart problem. I am excited to be partnering with my cardiologist colleague, Puja Mehta, who is an expert on this condition to start to understand the biological processes driving this disabling disease.
You co-founded a company to raise funding for your hydrogel device. What is one lesson from your startup journey that you want to share with other physician-innovators?
One lesson that I learned about the early stages of device development is that you are the biggest champion and driver of your technology. There are lots of resources at Emory, Georgia Research Alliance and NIH, but preparing applications, meeting with funders and obtaining entrepreneurship training takes time. Anything you can do to align these efforts with your research, academic and clinical tasks will make the process smoother and more likely to succeed.