Risk Factors for Development of Atrial Fibrillation on Tyrosine Kinase Inhibitor Therapy

Interview With Muhammad Fazal, MD, MS

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Interview by Jodie Elrod

Watch as Muhammad Fazal, MD, MS, with Stanford University, discusses his winning abstract at Western AFib 2025.

Please introduce yourself and your focus of work. 

My name is Muhammad Fazal, and I am a third-year cardiology fellow at Stanford, and I'll be staying there for my EP fellowship starting in about 4 months as well. I've been working with tyrosine kinase inhibitors for about 5 years now and studying the effects on arrhythmias in patient populations at Stanford. My current research in fellowship is funded by the American Heart Association to study this specific topic as well. I've been working specifically with Dr Tina Baykaner on this topic.  

To give you a brief introduction, tyrosine kinase inhibitors are small molecules. They were first developed in 2001, with Gleevec (imatinib) being the first one, which was approved for treatment in 2001. They treat a bunch of different solid organ and hematologic malignancies. Since their use has increased over the past 20+ years, we've noticed more cardiac side effects such as hypertension and arrhythmias. Our job is to try to identify patients who would be at higher risk for cardiac arrhythmias when treated with these medications, which can allow us to better optimize their monitoring and treatment, because the time off therapy that they have because of these arrhythmias can lead to worse outcomes for these cancer patients. 

Congratulations on winning the David E. Haines EP Fellows Research Competition! Tell us more about your research. 

Thank you so much. I was deeply honored for the opportunity to present and also be awarded the prize for the Fellows Competition, so I completely appreciate that from the Western AFib Symposium. In terms of my research, so like every research question, this came out of a patient. We had a patient with chronic lymphocytic leukemia (CLL) who was being treated with a tyrosine kinase inhibitor and unfortunately developed atrial fibrillation (AFib) while on therapy. They had to go off therapy because of the AFib and was referred to us for management. At the time, this was about 5 years ago, there were no treatment guidelines for these patients. There was no specific guideline therapy. So, we decided to perform AFib ablation on this patient, and after the procedure, the patient did not have any recurrent AFib and was able to go back on therapy. They did miss about 6 to 8 months of their medical cancer medication, which could in the long run, lead to worse overall survival for this patient. So, the question that came out of that was that we know these treatments cause medical problems and cardiac arrhythmias in these patients, so how do we go about identifying these patients before they develop the cardiac arrhythmia so that we can either try an alternate treatment or monitor them closely before they present to the hospital in extremis eventually? That being said, our project, the risk factors for development of AFib on tyrosine kinase inhibitor therapy, is a project that we've started at Stanford University where we've taken about 10,000+ patients that have been treated with these drugs over the past 16 years and tried to see which of these patients develop AFib and see which factors seem to be the most highly correlated with the development of AFib. We've compared this to existing risk prediction models that have been in the field. Unfortunately, a lot of these models are not made on patients receiving this therapy. They're made either in the general population or in patients who just have cancer but are not specifically on this therapy. So, they haven't been as good as we'd like. Thankfully, our model outperformed both of those models and had an 80% prediction of AFib. 

What are the take-home messages you would like viewers to leave with? 

Regarding take-home points, the first thing would be to identify that these medications can cause significant cardiac arrhythmias. The complications arising from them are not just due to the cardiac arrhythmias, but because of the fact that the cancer therapy itself has to be held in order for these patients to be treated, which can lead to worse cancer outcomes as well. That would be the first thing I would want everyone to take home is the medication itself can cause these problems.

Second, I think if we can identify a mechanism to identify these patients earlier than when they develop these cardiac arrhythmias, we can monitor them more closely. We can also provide them with medications or other treatment strategies that would eliminate the arrhythmia and eliminate the need for them to hold the medication that's treating their very important cancer. 

Lastly, we want to improve our own model as well by incorporating new technologies such as electrocardiogram and artificial intelligence to help us improve the performance on our model and try to predict this in a better fashion so that we can then implement it in the electronic medical record for our oncologist to be able to see when they're prescribing this medication that this patient may have a high risk of developing a cardiac arrhythmia. Maybe consider an alternate treatment regimen or refer them to a cardiologist early so we can monitor them early since they're a high-risk patient. 

The transcripts have been edited for clarity and length.