Corinn Cross, MD (Host): Welcome to HeartSpeak Consult brought to you by Baylor, Scott & White Heart & Vascular Hospital, Dallas, Fort Worth, and Waxahachie, joint ownership with physicians.

I'm your host, Dr. Cori Cross. Today, we'll be discussing guideline directed medical therapy for heart failure patients who have reduced ejection fraction.

Guideline directed medical therapy, or GDMT, is the cornerstone of pharmacological therapy for patients with heart failure, but it is underutilized despite the multiple random trials demonstrating improved clinical outcomes. For this discussion, we are honored to be joined by Dr. Shelley Hall. She is Chief of the Transplant Cardiology, Mechanical Circulatory Support and Heart Failure at Bell University Medical Center and a Cardiologist on the medical staff at Baylor Scott & White Heart & Vascular Hospital. Dr. Hall is the Bradley Family Endowed Chair of Cardiovascular Medicine at Baylor Scott & White Heart & Vascular Hospital. She is the immediate past president and was the first woman to hold the role as president of the Texas chapter of the American College of Cardiology. Dr. Hall, thank you so much for joining us today.

Shelley Hall, MD, FACC, FHFSA, FAST: Good pleasure.

Host: So let's start with a broad overview for those of us who might be a little less familiar with guideline directed medical therapy. Can you explain to us what GDMT is?

Shelley Hall, MD, FACC, FHFSA, FAST: Certainly. GDMT, as you mentioned, guideline directed medical therapy, some are now saying goal directed medical therapy, is really a terminology that's utilized to explain the appropriate medications that a heart failure patient should be on based upon all of the various trials that are out there. And there are four basic pillars to that regimen.

And we throw a lot of acronyms around in cardiology, but I'll try and remember to explain all of them. The first family of medicines that was discovered in this guideline directed medical therapy were the ACE inhibitors, angiotensin converting enzyme inhibitors. And these have now evolved to several other types of medicine, ARBs or angiotensin receptor blockers, and now ARNI's angiotensin receptor blockers-neprilysin inhibitors.

Lots and lots of words, which is why we always condense them down to these letters. And they all form one family of really a vasodilator category. There's a lot of other pharmacology that's involved, but for simplicity's sake, these medicines tend to lower blood pressure and so we remember them that way and that was really the first family that was discovered.

Starting with ACE inhibitors, then moving to the ARBs and then ultimately the ARNIs; ARNIs are now considered the first choice and there's only one medication available in that family currently, named Entresto, but there are some patients who can't tolerate that so we still have the other medicines to be utilized behind that if they can't either afford it, can't get it, or they don't tolerate it.

The second pillar of medication is the beta blockers, and there are several medications in that. That was the second big breakthrough in heart failure medicine. Believe it or not, I, did this research as a resident, and back then, beta blockers weren't even considered appropriate for heart failure.

And when I told friends and peers that I was doing research with beta blockers and heart failure, they're like, why are you going to do that? That's not going to do anything for your career. And it turned out I ended up with the first publication to show that it actually helped heart failure and is now referenced in board review courses.

So trainees never know what their potential research work could lead to. And that was a really big discovery because we did think that it was contraindicated for so long. And then we kind of had a dry spell for many years.

And those were the two pillars that we utilized. And then, ultimately, the next big discovery was actually a very old medication, spironolactone. And this is part of the family called mineralocorticoid antagonists.

Again, why we use letters, MRA, it's easier. And that was the third pillar that was discovered that benefited heart failure. And then the most recent, fourth pillar, are the SGLT2s. These are the medications that were first being studied in diabetes and incidentally found that heart failure patients who were in the trial actually did better from a heart failure perspective.

And now this medication is probably prescribed just as much for heart failure as it is for diabetes. And there are several medicines in that family. And that's where we are today with GDMT. These four categories of medicines are what we call the four pillars.

Host: That makes sense. So is one group of medicine or one of these four pillars more important than another?

Shelley Hall, MD, FACC, FHFSA, FAST: That is a very common question that we get because telling somebody we're going to need to put you on four pills minimum is intimidating. People don't want to take pills, especially if the pills have side effects when you're starting them on. So often it depends upon how far advanced the disease is and what other medical problems the patient has and what limitations there might be.

All four are important and our objective is to get a patient on all four, but they each have different side effects. And so often if we are struggling with getting everything on at once, we determine what is a side effect that the patient may not be able to tolerate. So for example, the MRA, these medications have minimal to no effect on blood pressure.

They can cause the potassium to rise a little bit in the blood. And usually that's benign, but if somebody is having a kidney issue where their potassium already runs high, this may be a more difficult medicine to utilize. On the flip side, if their blood pressure is low and we know that the other medications lower blood pressure and this one doesn't, then it may be a very easy medicine to put on the patient.

Ideally, we try to get all four started on the patient at low dose and then based upon patient tolerance, we will advance them as tolerated. Only the first two pillars really have titration involved. So the MRA medications and the SGLT2 medications, pillars three and four that came along just in the order of discovery; those don't have any titration.

They're just a simple starting dose and occasionally you can go up once on them, but there's not really a target for those. Whereas the first two pillars, your vasodilator medicines and your beta blockers, those are titrated up over time to the maximally tolerated doses. And it depends upon which medication is chosen, as to what that dose may be, and also the frequency per day of what they're taking.

Some of the medicines are once a day, some are twice a day. We try and keep things as simple as possible for the patient, but we also want to put them on the best medicines that have the strongest data first and only compromise that to what we call the second or third choice if they're intolerant of our first choice.

 So it is a lot of speaking and just to really get to the question, ultimately, no single medicine is the most important. It is the combination of all of them that provides the additive survival benefit and symptom management control.

Host: So let's talk a little bit about what you were talking about, the titration. So for the ACE and the ARBs, how quickly can these medications be up titrated and do you titrate it up and then wait and plateau a little bit? And then also can you speak to are there ever instances where a patient is tolerating it and then for whatever reason stops tolerating it?

Shelley Hall, MD, FACC, FHFSA, FAST: Absolutely. So the titration process, we used to be very conservative, and that is part of the problem with the low penetration of getting these heart failure patients on all four of these medications. And I guess I should state, this is only for the heart failure patients with reduced ejection fraction, meaning their heart is weak and it doesn't squeeze well.

There are other types of heart failure that have different categories of medicines. But when we talk about GDMT, we're predominantly talking about the weakened heart. And we used to be very, very slow. So back in my day, when the first beta blocker came out, we literally had the patient come to our office, we would give them the pill. We would take their vitals every 15 minutes for an hour, make sure they were doing okay. We would send them home with two weeks of the medicine, they had to come back in two weeks and sit in the office and repeat the whole process again with the next dose. That is how frightened we were of the medications back then.

Nowadays, it's much easier, much simpler, and we've learned a lot. We do this often by telephone or by written instructions to the patient to up titrate themselves, usually every one to two weeks based upon if they have side effects or not. And, it has been shown in the hospital that you can get all four of these pillars started before they go home and even up titrate them over a matter of days to a couple of weeks to target dosing.

So what we're learning as a heart failure community that the more rapidly we can up titrate these medications, the better, the sooner you're going to have the beneficial effects. And if they don't tolerate it, that is starting to identify the patients who may be more advanced and may need more advanced therapies.

Now the second question you asked is what about the patient who was doing fine, and then now you're having to back off. So they're on medicines. They've been doing great for X number of months, years, hopefully decades. And now they're getting symptomatic. And the most common things that will happen there is either they're getting dizzy. Their blood pressure's getting lower and they're not tolerating it as well anymore. Or their blood work is showing that their kidney function is starting to deteriorate. Those are the two most common things we will identify as intolerance that makes us back off of medicines. And that is actually a very strong indicator that the disease process is advancing and it's time to start looking at other things beyond the four pillars of medicine, whether it be ancillary medicines that are out there, whether it be devices, or the final stage of heart failure for advanced therapies would be transplant or a left ventricular assist device.

Host: I think you've made a very good point as to why the four pillars are the gold standard. For physicians who might be listening, how would a physician get a patient onto a program with GDMT?

Shelley Hall, MD, FACC, FHFSA, FAST: There's no doubt this takes work. And today's modern medical office is overwhelmed. They don't have enough time to spend with their patients and certainly talking about all the side effects and addressing those side effects if they happen; it really hinders our ability to get the patients on properly.

So empowering patients with written titration instructions to take home, having a nurse or nurse practitioner or other staff that can do this by telephone, to me is the future. This is, virtually being able to talk with the patients, see how they're doing and giving them the encouragement and freedom to go up on the next dose of the various medicines, is going to be the key. Because the in person offices are overwhelmed and really need to deal with far more complicated issues. And it can be very challenging for patients to drive. Some of these patients, especially in a big rural state like Texas, can drive three, four, five hours to see a cardiologist only to be told everything looks good, go up on your pill, come back in three months.

That's a lot of wasted work time, family time to get people to change their medicine. And so personally, I feel like the future of this is going to be virtual titration programs, and we have just launched one in our Dallas site and, plan to spread that across the entire Baylor Scott & White healthcare system.

Host: What a wonderful take home message. And I think that is a great point that medicine is changing and we really can provide more to our patients without making them work harder for it. Dr. Hall, this has been so educational. Thank you so much for taking the time to discuss such an important topic with us today.

Shelley Hall, MD, FACC, FHFSA, FAST: Of course. Thanks for having me.

Host: For more information about GDMT or the Baylor Scott & White Advanced Heart Failure Clinic Dallas, please call 214-820-6856, or search for the clinic on our website, BSWHealth.com. That's BSWHealth.com. That concludes this episode of HeartSpeak Consult, brought to you by Baylor Scott & White Heart & Vascular Hospital.

If you've enjoyed this episode, please remember to subscribe, rate, and review this podcast, and check out other episodes of HeartSpeak Consult. I'm your host, Dr. Cori Cross. Thanks for listening to HeartSpeak Consult.

Corinn Cross, MD (Host): Baylor, Scott & White Heart & Vascular Hospital, Dallas, Fort Worth, and Waxahachie, joint ownership with physicians.