Cardio-Oncology, From an Electrophysiologist’s Perspective

In the next episode of The EP Edit podcast, we speak with electrophysiologist Dr. Michael Fradley about the emergence, development and future of cardio-oncology. Dr. Fradley is the Director of the joint USF-Moffitt Cancer Center Cardio-Oncology Program and Associate Professor of Medicine at the University of South Florida, Morsani College of Medicine in Tampa, Florida. Enclosed here are the edited transcripts of the podcast.

Tell me about your medical background.

I completed medical school at Johns Hopkins, and then stayed there and did my internal medicine residency at the Johns Hopkins Hospital.

After that, I moved to Boston and completed my cardiology fellowship and electrophysiology fellowship at Massachusetts General Hospital/Harvard Medical School.

As director of the joint USF-Moffitt Cancer Center Cardio-Oncology Program, what interested you about and how did you become involved in the field of cardio-oncology?

That’s a great question. Obviously, it’s a little bit of an unusual career path, especially for someone who trained in electrophysiology, but when I did my training in Boston, I was starting to see quite a few consults from the oncology services related to arrhythmias. So from an intellectual standpoint, that really started to spark my interest about why there were so many arrhythmias in this patient population. Beyond that, I have a personal connection to both cancer and cardiovascular disease, and I wanted to figure out a way to put those two passions together.

What is the role of the cardio-oncologist? When do patients need to see a cardio-oncologist?

Cardio-oncology is a multidisciplinary specialty aimed at the prevention and management of cardiovascular disease in cancer patients and survivors. I think there is a role for cardio-oncology evaluation before starting high-risk therapy, certainly during therapy, and also in cancer survivors, because as we know, certain treatments have delayed effects and require long-term follow-up by a cardio-oncologist.

Tell me more about that — what are the risk factors for developing cardiac side effects from treatment?

It’s obviously quite variable depending on the treatment itself. For example, the field is really borne out of anthracyclines and trastuzumab, which are associated with left ventricular function dysfunction and heart failure. But there has been a paradigm shift in the approach to cancer treatment, focusing on targeted and immunotherapies. As such, we are now recognizing a broad array of cardiotoxicities, ranging from arrhythmias to vascular diseases to myocarditis.

Risk factors associated with the development of cardiotoxicity varies on the specific agents, but there are some risk factors that are quite generalizable. Certainly anyone that comes into their cancer diagnosis with baseline cardiovascular risk factors or disease is going to be at higher risk for developing cardiovascular complications, because everything is additive. If a person has hypertension, hyperlipidemia, and underlying atherosclerotic vascular disease, he or she is already at higher risk for developing future problems. If you then add chemotherapy or radiation therapy, this is going to be a particularly vulnerable subset of patients. We also know that age extremes tend to be more susceptible for developing cardiovascular dysfunction, as is the female gender.

How is a multidisciplinary approach important in the care of these patients?

Multidisciplinary approaches are essential for the optimal care of these patients. Traditionally in medicine, we tend to practice in silos — cardiologists take care of the heart and that is all they’re focused on, the oncologists are thinking about cancer, and the pulmonologists are thinking about the lungs. Cardio-oncology is really the overlap between cardiovascular disease and cancer. So the cardiologist has to work closely with the oncologist to develop a treatment plan that will minimize cardiovascular toxicity while still allowing them to receive optimal cancer treatment. It requires a lot of conversation and a lot of treatment planning, working together as a group. I think it can really be the model for the future of medicine.

Tell me about the relationship between atrial fibrillation and cancer. What is the incidence and prognosis of atrial fibrillation in patients with cancer?

Atrial fibrillation is actually quite common in cancer patients. The incidence varies quite a bit, but on average, more than 5% of patients are going to experience atrial fibrillation during the course of their cancer therapy. For patients undergoing stem cell transplantation, rates of atrial fibrillation are higher, around 10-12%. If they are receiving ibrutinib, an oral medication for B-cell malignancies that they may take every day for many years, the incidence of atrial fibrillation is more like 14-15%. There are a lot of management challenges in cancer patients, especially as it relates to rhythm control strategies and anticoagulation.

What fundamental questions still remain about how to best manage cardio-oncology patients?

The field is quite young and many questions still exist. We are still identifying risk factors and ways to predict those individuals most likely to develop the toxicities from these drugs as well as ways to mitigate those risks. The core of cardio-oncology is risk factor modification and prevention. For example, how do you prevent and manage atrial fibrillation in a cancer patient? The CHA₂DS₂-VASc score has been repeatedly shown to be a relatively poor predictor of thromboembolic events in the cancer patient population as opposed to the general population. It’s currently our only tool, but we have to recognize that it’s quite limited in this population. So, there is a lot of opportunity for future research and investigation.

When was the Moffitt Cancer Center’s Cardio-Oncology Program established?

We started in 2014, and it was a collaborative effort between the University of South Florida and Moffitt Cancer Center. It has continued to grow and develop over the last 5+ years.

Are you seeing an increase in cardio-oncology programs in the U.S.?

Absolutely. As the field has become more recognized and as the patient population has grown, we have seen more and more of these programs develop. Right now, it is estimated that there are about 14 million cancer survivors living in the United States. That number is expected to increase tremendously over the next decade. Patients with cancer are living longer, and in many cases, surviving their diseases. The last thing that we want is for cardiovascular disease to become a barrier for them to receive effective therapy or for the patient who survived the cancer to be left with a lifelong debilitating cardiovascular problem. So for that reason, we’re starting to see programs everywhere. I would say they exist at the overwhelming majority of academic centers. We’re also starting to see them in the community setting as well.

What do you believe were some of the key take-home messages from the recent Global Cardio-Oncology Summit?

It was another fantastic meeting this year in São Paulo, Brazil. I actually was the chair of the meeting last year when it was in Tampa, so it was nice to be on the other side of the table this year and just participate, as opposed to having to organize and execute it. I think the key take-home messages from this year’s meeting were first, the need for enhanced collaboration between cardiologists and oncologists, both locally as well as internationally. Additionally, there is a need to understand mechanistically why these cardiovascular toxicities are occurring. We’ve described them quite well, but understanding them at the molecular level needs to be a focus, because it will help determine how to best manage and treat these individuals.

Finally, what are some of the future directions in the field of cardio-oncology?

I think the future is limitless in cardio-oncology. But right now, I think the two areas of greatest focus in oncology are targeted therapies as well as immunotherapies. Immunotherapy has become the new frontier for oncology, and we are still learning all of the effects of the activated immune system on the heart and vasculature. 

Disclosure: Dr. Fradley has no conflicts of interest to report regarding the content herein. Outside the submitted work, he reports grants from Medtronic and personal fees from Novartis.