The Impact of Excess Iron on Cardiac Function in MDS

Transcript:James M. Foran, MD, FRCPC: I don’t think we really appreciate the impact of iron overload on cardiac morbidity and cardiac mortality. And congestive heart failure, or dyspnea, or associated symptoms don’t really get worked up or evaluated in as much detail, maybe because we’re so focused on the hematology and we don’t always have the ability to coordinate with a cardiologist, for instance. But I have the impression that cardiac morbidity is high also. Has that been your experience?

Azra Raza, MD: I’d like to illustrate my experience with a little anecdote about a patient. So, I have a patient in his 70s who was diagnosed with regular RARS, and we went through the whole gamut of starting ESAs. And he responded for a while and then stopped responding. We added GCSF. He responded for a while, and then stopped responding. We gave immune modulatory drugs. He didn’t respond. We went to hypomethylating agents. Throughout this time, the patient is getting transfusions. Once his ferritin started climbing over 1,000, I started having a conversation with him, because I am very aggressive about the fact that the only way we are going to be able to sustain a good quality of life for a patient is to give them transfusions safely, which means you transfuse, but try to remove excess iron.

So, I start having this conversation with the patient about how important it is, and he basically keeps not taking me seriously. He was an endocrinologist, and eventually one day, he ended up in the emergency room, James, with a heart rate of 180, in atrial fibrillation—imminent danger of dying. This is how serious it can be. His ferritin level is now 5,000. He has had 70 units of transfusions. This is a true medical emergency. The patient could have died. We kept him in the ICU for 6 weeks, aggressively chelating intravenously, as well as orally; the two together because one was not sufficient. After 6 weeks, we bring him to the floor, another 6 weeks of aggressive chelation. And now 2 years later, we are still aggressively chelating him, subcutaneous pump as well as oral. But he’s still alive, and he’s now fully functional and back to normal. So, the danger can be very acute if we don’t take care of it. And cardiac danger is not appreciated enough times, but thankfully we have colleagues who understand iron overload being a cause for sudden presentation in cardiac failure with atrial fibrillation and all of that.

James M. Foran, MD, FRCPC: Right. I think you know doctors make the worst patients anyway. An anecdote like that is compelling. And even though I share your point of view, I know there are many who would push back and say that we haven’t shown that chelation makes that impact, and maybe it’s just medical management, maybe it’s ACE inhibitors and diuretics that makes that impact. So how would you respond if somebody said we haven’t proved that chelation really got that patient better, for instance?

Azra Raza, MD: I would respond by saying, well, look at the patient’s course. It’s only by adding the iron chelation therapy that has brought the ferritin level down. And besides, we followed the patient with T2* MRI also, and you can see a difference in the rate at which that cardiac muscle is now moving. Once it’s gotten rid of so much iron, the movement is so much faster.

James M. Foran, MD, FRCPC: With the hemoglobinopathies, I think that the T2* gets used and people appreciate this, certainly with thalassemia and to a lesser extent, with sickle cell disease. Maybe that’s because it’s a life-long disorder and people feel it matters more in children or young adults than older adults. But it doesn’t get taken with as much weight in this population, and hopefully we’ll get the data to help support that. Because I agree with you. I’ll be interested to hear Dr. Steensma’s opinion on this as well.

Azra Raza, MD: And you know, the cardiac events from which patients have morbidity and mortality in MDS are much higher, statistically significantly higher for patients who are getting transfusions compared to patients who are not.

James M. Foran, MD, FRCPC: That’s an important point. In your practice, you would appreciate that. I think if you only had a few MDS patients, it’s harder to observe that phenomenon and really connect the dots. So, I think that’s an important point.

Transcript Edited for Clarity