CRT in HFrEF Management: Updates Plus 'What's Next?'

Eugene S. Chung, MD, FACC, FHSFA; Ankit K. Bhatia, MD, FACC


December 08, 2022

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This transcript has been edited for clarity.

Eugene S. Chung, MD, FACC, FHFSA: Hello. My name is Eugene Chung. I'm a heart failure cardiologist here at The Christ Hospital in Cincinnati and medical director of the Center for Innovation. It's a pleasure to talk a little bit about cardiac resynchronization therapy (CRT) with one of our cardiologists, Ankit Bhatia, who will introduce himself in a minute.

Just to set the background, CRT, or biventricular (BiV) pacing, was introduced as a part of routine therapies for patients with heart failure almost 20 years ago with the initiation of the MIRACLE and MIRACLE ICD trials, followed by COMPANION. Initially, these patients had low ejection fraction, QRS duration > 120 or 130 msec, and New York Heart Association (NYHA) functional class III [or IV].

Over the subsequent decades, there have been refinements to these indications. For me, this has always been a very important part of heart failure treatment for those who do not always respond to the standard medical therapies that we might give them.

I wanted to introduce Dr Bhatia to bring us up to date on some of the evolution of indications, how and where these therapies fit in the scheme of things today for patients with low ejection fraction or heart failure with reduced ejection fraction (HFrEF). Ankit, please introduce yourself and then we can go over a couple of scenarios.

Ankit K. Bhatia, MD, FACC: My name is Ankit Bhatia. I am an advanced heart failure and transplant cardiologist here at The Christ Hospital in Cincinnati, Ohio. I look forward to going over some cases with you, Gene.

CRT and The Updated Guideline for HF Management

Chung: Let's say you have a patient — and we all have these patients — whose ejection fraction is 30%. They have symptoms, but they're going about their lives, with NYHA class II to III disease, let's say. Their QRS duration is prolonged.

They're on good medicines — the three or four medicines that most people would think about for patients with HFrEF — yet not much has changed. The ejection fraction still remains low, they're symptomatic, and the QRS has widened. You're considering a defibrillator therapy for someone like this. Tell me about how you approach someone like this for possible CRT.

Bhatia: That's a great question, and one that we run into every day. First, as we all know, there have been many new additions when it comes to medical therapy for heart failure. I first want to ensure that that patient is someone who is on the classic quad therapy, or the four medications that we know of that improve survival and symptom profile in HFrEF. Those are beta-blockers, angiotensin receptor-neprilysin inhibitors (ARNIs), mineralocorticoid receptor antagonists (MRAs), and now sodium-glucose cotransporter 2 (SGLT2) inhibitors.

After ensuring that, I usually give the patient an interval, whether that be 3-6 months, even sometimes longer in patients who have minimal symptoms, and then reassess their ejection fraction to see if there's any improvement. In folks who remain with an ejection fraction < 35%, and as you mentioned, have a wide QRS, those are the folks I consider for CRT.

One of the trials I really look at here to help guide me is the RAFT trial. This was the next iteration of CRT trials after MIRACLE, as Gene had pointed out. This was a trial of about 1800 patients with HFrEF < 30%. They all had QRS durations > 120 msec as well. They were randomized in a 1:1 ratio to receive implantable cardioverter–defibrillator (ICD) alone for primary prevention vs ICD plus CRT.

Among these patients, what was found for the composite endpoint of heart failure hospitalizations and mortality was that participants who had CRT in that population did better. What was great about that trial is the fact that you could actually stratify, based on substudies, to see who benefited the most. Looking at the subpopulations, what we found was exactly what you mentioned.

Folks with QRS durations specifically > 150 msec; people with wide QRS durations, especially in a left bundle branch formation; and, finally, women and patients with ischemic and nonischemic causes of heart failure were the groups that benefited the most.

When I think about it then, I think about just that, and that's what the guidelines line up as. There's a class 1 indication for NYHA class II-IV patients with a QRS duration > 150 msec and a left bundle branch block. I look at that, and I look at some of the other factors in the trial, and from there, I guide who would benefit from CRT.

Chung: That's interesting. Even in the original studies, even if the indication for enrollment was a QRS duration of 130 msec, on average, these patients had a duration of 160 msec. Most, I believe, had left bundle branch blocks. Most of these patients actually aligned with the guidelines, as they sit today.

How do you approach atrial fibrillation in somebody whom you're considering for CRT?

Bhatia: Atrial fibrillation, I think of in terms of pacing requirement, I think of that as a situation where someone may be dependent on more pacing. Then we can draw more on some other literature that we're going to get into — which is, what do you do with heart failure patients who require chronic pacing?

For this, the trial that I often look at is BLOCK-HF. This was a trial of patients with reduced ejection fraction < 50% who had some form of high-degree atrioventricular (AV) block. These were folks with second- or third-degree AV block or significant first-degree AV block. They randomized these patients to right ventricular pacing vs BiV pacing.

For the composite endpoint of all-cause mortality, heart failure events, and a 15% or more increase in the left ventricular end-systolic volume index, what was found was that the patients who received BiV pacing did substantially better.

This led to a class 2A recommendation for patients who require chronic pacing with HFrEF. Specifically, in the guidelines, it states that for patients who have a left ventricular ejection fraction (LVEF) < 35%, where there's an anticipated requirement for ventricular pacing > 40%, those folks will benefit from CRT up front.

Chung: Even if the ejection fraction is > 45% or 50%, because BLOCK-HF had a requirement for ejection fraction ≤ 50% with high anticipated right ventricular pacing, CRT indication is extended beyond the HFrEF patients in this group — most of the patients in the study had an ejection fraction [> 35%].

Bhatia: That's how I typically apply it. The guidelines have a 35% LVEF cutoff that they use for the class 2A recommendation. That being said, in my practice, I practice just as you say. Anybody with a reduced ejection fraction is someone whom I would consider for CRT if they have a high pacing requirement.

Choosing the Right Patients: Alternative Methods

Chung: Let's touch on a few other things. Since the establishment of CRT as viable therapy in a subgroup of patients with heart failure, there have been many attempts to fine-tune the selection criteria, with many studies using echocardiography to detect the synchrony, different ways to analyze the ECG, scar location, and scar burden by cardiac MRI.

Do you use any of these alternative methods to select patients?

Bhatia: I use those added tools when I need a tiebreaker in a patient where it's ambiguous. Someone who's got a class 2 recommendation, someone who doesn't necessarily have the QRS duration ≥ 150 msec, someone who's somewhere in the middle. Also, I use it to help inform the patient.

When a patient needs a better understanding as to why CRT may benefit them, the use of these added diagnostics may be helpful in that situation. Again, as we mentioned, I heavily consider nonischemic etiology as a group that would benefit as well.

Chung: Once a patient gets CRT for heart failure, how do you follow these patients subsequently? Obviously, you'll see them clinically and see if they're feeling better. Occasionally, you have them do an echocardiogram to see if the ejection fraction improves. Do you do anything other than that, such as optimizing AV timing and interventricular pacing intervals (VV), looking for less dyssynchrony, or anything like that?

Bhatia: The simplistic answer from the humble heart failure cardiologist is that I look at every visit to ensure that there's a high degree of BiV pacing. If there is not, I send a message over to my electrophysiologist colleagues to better determine if there's an avenue to improve BiV pacing.

Chung: I think that's probably the right answer for all of us. I look for someone who's pacing above 96% or 97% of the time. If someone is pacing 80% because of premature ventricular contractions (PVCs) or intermittent atrial fibrillation or the native heart rate, then the electrophysiologist will typically help us address that topic to maximize BiV pacing, if at all possible.

I think there are other quirky things to think about. There are actually fairly strong data that the required duration of QRS to achieve a good clinical response is somewhat dependent on the patient's height. If you're a tall person, your QRS should be pretty long in order to achieve a good response. If you're a short person, you may achieve a similar response with a narrower QRS duration.

Now, that hasn't been adopted into guidelines obviously, but the data that I've seen from that cohort, the Medtronic studies, in particular, are very striking. It's just one more little tiebreaker, if you need something to think about, that I look at periodically.

Similarly, you can look at baseline LV volumes. Between the volume and height, they can actually help you lean one way or the other when it comes to these things.

The other thing I think about is whether someone has limiting symptomatic heart failure. If a physician tells you that with this treatment — and you've got to get a defibrillator anyway — this additional therapy might give you a 30% chance of improving your quality of life, I think I'd probably take that. Obviously, that's a very personal decision. That's just something to think about in various patients that we encounter.

Bhatia: Gene, you bring up a great point, which is that we talk about these guideline-directed medical therapy medications, but many patients can't tolerate them for a variety of reasons. With folks who do meet criteria for CRT, oftentimes I'm not waiting as long as 3-6 months because I know that they have a significant symptom profile and they're minimally getting improvement from medications. Oftentimes, I move even faster toward approaching an electrophysiologist and discussing evaluation.

Chung: That brings up one more scenario, which is that of a super-responder patient, right? The female nonischemic patient with an ejection fraction of 25, QRS duration of 160 msec, left bundle block, sinus rhythm. This person gets a device. The ejection fraction becomes normal. They feel fine.

Do they really need beta-blockers, ARNIs, and SGLT2s and spironolactone? I don't know that anyone's done that study, but it's a question I ask. I'll sometimes take away some of these medications one at a time.

Do you have a habit of doing that as well?

Bhatia: Drawing from the available evidence and the lack thereof, if they're able to tolerate guideline-directed medical therapy, I keep patients on it. As you know, every patient wants to be on less meds, so it's a shared discussion. Just as you mentioned, the super-responder is someone I'd be more willing to make some adjustments with than I would with others.

Future Directions in CRT Technology

Chung: To close, I think it's important to touch a little bit on what's upcoming in terms of resynchronization. Right now, we simplistically think of BiV pacing as you get a right ventricle endocardial lead, a lead on the left ventricle, and you're synchronizing the timing. There are actually more elegant ways to pace the left bundle, to pace the His bundle, and left ventricular pacing, or left ventricular endocardial pacing.

Without going into every one of those topics, I think it's important to keep in mind that there will be more and more targeted, elegant, evidence-based ways to overcome dyssynchrony. Left bundle branch pacing and His bundle pacing are more about restoring natural conduction, overcoming dyssynchrony. I'll just leave it at that.

Do you have any comments about what might be coming up in terms of new technologies?

Bhatia: Gene, just as you mentioned, I think we touched on CRT nicely here. For these devices, whether they be CRT or ICD, one of the great areas of innovation we've seen is in the heart failure diagnostic space. What we know full well from remote patient monitoring is that this is also a technology that can help to improve symptoms and reduce heart failure events in patients. The jury is still out on how beneficial the ICD- and CRT-related diagnostics are, but there is some promise there.

One trial I pull on is MANAGE-HF. It's using the HeartLogic heart failure diagnostic developed by Boston Scientific. Each one of these device companies has their own algorithm, but most of them are a composite of [heart sounds], intrathoracic impedance, respiratory rate, heart rate, and activity level. What they are doing is providing scores that are baselines for a patient. Then if patients with these devices exceed a critical threshold for high risk for decompensation, clinical teams are alerted.

What we've done in our practice is establish algorithms, whereby if a patient is above a threshold based on these HeartLogic alerts, we then provide them with upfront medical therapy, most often increasing diuretics, presymptomatically with the hope of helping to avoid a heart failure event.

In the MANAGE-HF trial, phase 1 was purely feasibility but did show a reduction of roughly [60%] heart failure remissions in a matched 1-year prior to 1-year prospective approach in 200 patients. Phase 2 is going to include several thousand patients, looking at a composite outcome of mortality and heart failure events. There is more to come in that space for us to see how effective this is as a therapy.

Chung: I'm glad you touched on the possibility of remote monitoring because these are implanted computers with remarkable capabilities. I think that's a very exciting field that's upcoming, and I'm looking forward to taking care of patients with these new technologies.

Thank you very much.

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