Talking Tall Rounds®: Heart Failure with FMR

Podcast Transcript

Announcer:

Welcome to the Talking Tall Rounds series, brought to you by the Sydell and Arnold Miller Family Heart, Vascular and Thoracic Institute at Cleveland Clinic.

Amar Krishnaswamy, MD:

Good morning, everyone, and thanks for joining us both in person and virtually. So the management of patients with functional mitral regurgitation, like most things we do, really calls for the effort of so many different people involved in a multidisciplinary way. And hopefully we'll highlight that with the talks this morning. And I think, importantly, and one thing that I'd really like to highlight from this session is that we all, in every area of cardiology, take care of patients with functional MR. And I think that often these patients are not in fact referred to sort of the further specialty care that they may benefit from. So hopefully, the talks this morning will put this idea into everyone's mind, and we'll see more of these patients a bit more often. So we'll start out with one of our heart failure fellows, Vanessa Blumer to present the case.

Vanessa Blumer, MD:

I will be starting the morning with a case presentation of management of heart failure patient with functional MR, and hopefully this will set the stage for what I am sure will be a very nice discussion. So this is a 73-year-old gentleman with hypertension, hyperlipidemia, AFib, which I'll tell you a little bit more about, but underwent several ablations, finally was successful, coronary artery disease status post-CABG and CKD stage 3B, who presented to our Heart Failure Clinic for further management of ischemic cardiomyopathy, has heart failure with reduced ejection fraction. The most recent EF was 25%, has moderate-severe MR and currently New York Heart Class III symptoms, stage C. The patient has had several hospital admissions over the past 12 months for acutely decompensated heart failure despite optimal guideline-directed medical therapy. So patients that we see pretty frequently in clinic in our Heart Failure Clinic.

Vanessa Blumer, MD:

So going into a little bit more detail in the timeline presentation of this patient. So the patient, originally, the cardiac history started in 1995 when the patient had CABG times three with LIMA to the LAD and venous grafts to the RCA and OM1. At the time, the patient was fairly stable with an EF of 35, 40% in New York Heart Class II symptoms, and he was started on a beta blocker and ACE inhibitors. Over the pass of the decade, after 1995, he really didn't undergo major hospitalizations and remained as an outpatient following his PCP and his cardiologist at an outside hospital with no major events. Starting in 2015, he started having some issues with AFib and AFib with RVR that warranted some in-hospital admissions. At the time, his EF started to decline somewhat. It was attributed to AFib, eventually underwent two ablations, the last one was successful.

Vanessa Blumer, MD:

Then he had an episode of VT cardiac arrest that warranted an admission. At that time, he had an ICD that was placed for secondary prevention of sudden cardiac arrest, and that led to him being seen in our Heart Failure Clinic. So at that time, he had worsening heart failure symptoms. On interrogation of his symptoms, he had New York Heart Class III symptoms at the time, and an echo that he came with showed a dilated LV with an EF that was now 25% and 3-plus MR. So, obviously, GDMT was optimized. He was now started on co-reg 6.25 BID. His lisinopril was changed to ENTRESTO 24/26 BID, and he was started on an MRA. However, in spite of this, he had several hospitalizations. One of this, he had a new left heart cath that showed patent grafts and no significant CAD of his native vessels.

Vanessa Blumer, MD:

Other hospitalizations were just mostly for volume management. He had IV fluids, and then eventually his GDMT was further uptitrated. He did have a left bundle, and he had underwent a CRT-D upgrade. On physical exam, he had borderline blood pressure that really limited further uptitration of GDMT. Heart rate was 94, and then furthermore, really he was just volume up with evidence of JVD, and physical exam showed a holosystolic murmur typical of MR with bibasilar crackles and hepatojugular reflux. Overall, he was well perfused and no either physical exam findings or biochemical findings of hypoperfusion. I did want to point out that his creatinine was 2.4, and he did stay around CKD stage three every time that he was followed.

Vanessa Blumer, MD:

On his EKG, he was BiV paced. And then this was the echocardiogram that was obtained in one of his initial visits. As you can see here, he has global LV systolic dysfunction with a severely reduced LV ejection fraction that was estimated to be around 25%. The LV was severely dilated with an LVESD of 5.7 centimeters, and the calculated end diastolic volume was greater than 200 ml. He had moderately to severe holosystolic mitral valve regurgitation due to apical tethering of a normal mitral valve leaflet that was attributed to the LV enlargement that resulted in posteriorlar-directed MR. And the MR effective regurgitant orifice area as determined by PISA was estimated to be 0.44.

Vanessa Blumer, MD:

So to summarize a little bit on the plan and the follow-up, so this is a 73-year-old gentleman that has some degree of comorbidity burden, has ischemic cardiomyopathy, HFrEF with an EF of 25%, moderate to severe functional MR, class three symptoms, stage C, that now has multiple hospital admissions over the past 12 months for acutely decompensated heart failure, despite optimal guideline directed medical therapy. So obviously a lot went into the discussion of what to do with this patient moving forward, but ultimately the patient underwent successful percutaneous mitral valve repair with grasping of A2P2. And here I'm going to play the images after the MitraClip for you guys to see. And then the patient was seen in follow-up in our Heart Failure Clinic and pretty good clinic clinical result. The patient's symptoms improved to now class two symptoms and back to pretty much what he was doing a decade ago with a reduction in his mitral valve regurgitation from plus four to plus one.

Amar Krishnaswamy, MD:

I'd like to continue with what are some of the options that we have for the percutaneous repair of functional mitral valve regurgitation, really covering a little bit on contemporary edge-to-edge repair and then moving on a bit to indirect annuloplasty, which is a bit newer. So we've already seen, of course, a number of different cases, and this is similarly representative, a 70-year-old gentleman with prior myocardial infarction and multivessel coronary stenting, who despite optimization of guideline-directed medical therapies, remains with significant and symptomatic functional MR. Importantly, and what I'd like to just focus on in this, is that in the bottom right, in the 3D image, you see it's a relatively focal jet of FMR, similar to patients that Rhonda and Vanessa have both shown. And what you can see here with the NPR imaging that Rhonda has demonstrated, we have a very easy way, frankly, to address this exact and focal pathology.

Amar Krishnaswamy, MD:

And of course our imaging colleagues have been pioneers in demonstrating the utility of this kind of multiplanar reconstruction imaging. And the patient ultimately ended up with a trivial residual mitral regurgitation. And as Mangeet has shown, we know that the co-op trial provides a benefit or that MitraClip provides a benefit in these outcomes, both mortality and heart failure in patients with FMR. There's a similar but slightly different device called a PASCAL device from Edwards and still in trial, this is the class one trial showing treatment of patients with functional mitral regurgitation with this device that includes not only these two paddles, similar to the MitraClip arms, but a spacer in between to allow the device to function a bit differently. But similar to the data supporting MitraClip, you see that almost all patients, or all patients I should say, out at one year had less than mild to moderate MR. We are currently enrolling patients in a trial called Class II F that's randomizing patients between this device and the MitraClip.

Amar Krishnaswamy, MD:

But importantly, we know that even after... while so many people do well with edge-to-edge repair, if we leave them with residual significant MR, they don't do as well. And so this is why it's important that we have numerous options in this regard. And so I'd like to spend the next few minutes just demonstrating the benefits of indirect annuloplasty. So indirect annuloplasty, just to forecast, utilizes or leverages the relationship between the coronary sinus and the posterior mitral valve annulus. So you can see here this patient, as opposed to our prior one, if you look at the bottom right frame, has a pretty diffuse functional mitral valve regurgitation extending along the coaptation line. Now, this is the indirect annuloplasty device, the Carillon. You can see here it's a band with two anchors. And the idea is that once we gain access via the internal jugular vein, we take a coronary sinus venogram. This is of course quite familiar to our electrophysiology colleagues. And what we do is we place this band distally, and then we cinch the band and deploy the proximal anchor. And what you see here is that this coronary sinus that we started with becomes this. And this then placates the mitral valve anmulus. As you can see for that patient that I presented initially, has a pretty substantial reduction in mitral valve regurgitation with the treatment. Now, thus far, the device has been trialed in a number of European studies, though in overall relatively small numbers, though all of these trials do show the same direction of treatment benefit with regard to improvements in regurgitant volume and left ventricular volumes, demonstrating the benefits to remodeling. Now, importantly, we currently have the EMPOWER study, which is the National PI is Samir Kapadia, my colleague, and on the steering committee includes Dr. Starling and Dr. Gillinov in heart failure and cardiac surgery respectively.

Amar Krishnaswamy, MD:

Now, importantly, this trial is going to randomize patients, 300 total patients, either treatment with a Carillon or control, which is continued GDMT. This is a sham blinded study, so the patients all come for a procedure and then are randomized after the coronary sinus venogram. A very important part of this trial is that after patients are treated with the Carillon or if they're randomized to guideline-directed medical therapies, if they remain symptomatic with significant MR at six months down the road, they're eligible for alternative therapies, whether they cross over to treatment with the MitraClip or further kind of heart failure directive therapy such as LVAD or so forth.

Amar Krishnaswamy, MD:

The other very important part of this trial is that there have been prior analyses led by Dr. Starling and others that demonstrate that, with or without significant MR, patients with heart failure and LV dilation can benefit from coronary sinus annuloplasty. So taking together these two studies, which have both been published last year, demonstrate improvements in NYJ class, quality of life scores, and heart failure hospitalizations, again in patients with LV dilation, not specifically with significant MR associated. And so, importantly, the EMPOWER trial that I just showed you is in fact more focused as an LV dysfunction trial rather than a mitral regurgitation trial. And so in fact, the inclusion, which I've highlighted in red here, is that patients only need to have mild FMR or greater, but importantly need to have LV dilation and dysfunction.

Amar Krishnaswamy, MD:

So if we look at sort of the algorithmic approach that we have here in the patient with isolated native FMR, it's really important, again, I think this entire session has demonstrated the importance of the multidisciplinary aspect of this care, we first want to make sure that their heart failure guideline-directed medical therapies or appropriately titrated. We need to see whether they have options for revascularization, as up to a third of patients after revascularization will improve their FMR. We didn't address the specific rhythm disturbances here, but whether the patients a candidate for CRT or AFib management, as a number of my colleagues have already shown here, this is also very important before we start taking next steps toward device-based therapies. If after all of these things there is a reduction in the FMR to moderate or less, these are patients really who might benefit from consideration of annuloplasty, indirect annuloplasty, I should say with the Carillon device as I demonstrated.

And in patients with continued severe FMR, this is where we then take the aid of our imaging colleagues to understand what is the best option for that patient anatomically. Is it a MitraClip? Is it an annuloplasty? Or as Dr. Kapadia will discuss, is it a percutaneous mitral valve replacement?

Amar Krishnaswamy, MD:

I will just mention parenthetically, in the patient who has combined FMR and tricuspid valve regurgitation, at the current time, we do try our best to treat them with a MitraClip because that gives us the option of treating their tricuspid valve at the same time.

Amar Krishnaswamy, MD:

Conclude, functional MR treatment, as we've all demonstrated, I think, is multidisciplinary treatment of the valve disease, in many ways as the last step after rhythm management, GDMT, optimization, et cetera. Edge-to-edge repair using either the MitraClip or the PASCAL, which is still in trial, can be very effective for patients with a focal regurgitant orifice. More diffuse FMR may be better suited to annular therapies or valve replacement, as you'll hear. And even patients with mild regurgitation may benefit from annuloplasty when a left ventricular dilation is present. So thanks very much.

Amar Krishnaswamy, MD:

I have a number of questions as always. I quickly just want to put Dr. Saliba on the spot because I see him in the audience, and we didn't include a portion on rhythm management in this session, but I think rhythm management is as important as anything else. And so Dr. Saliba, if you can just give us a perspective. I think the old wisdom was you can have rate control, you can have rhythm control, don't worry about it. But I think in the more recent times, just from a... we're much more aggressive on a rhythm management standpoint, and I think we're also understanding how that impacts, keeping people in sinus impacts subsequent complications like heart failure and functional mitral regurgitation with atrial dilation. So if you can just speak a moment on what your thoughts are about contemporary AFib management and how this can affect these patients.

Walid Saliba, MD:

Okay. Thank you very much, actually, for the opportunity. As I was listening to the presentations, a lot of questions came to mind, and it's amazing that we live on the same floor, yet we don't communicate as much as we should communicate on those patients that we have. So there's no question about it that whenever we see a patient in the clinic who has atrial fibrillation coming in, referred from outside for an ablation, and that patient, we get an echocardiogram and there is two plus or moderate to severe mitral regurgitation on the echo. I think that we should put in a little bit more thought process in terms of what is the next thing that we should do for this patient. It's always a dilemma. Do we have to do something about the mitral valve? Or do we put the patient in normal rhythm and see what happens to the mitral regurgitation? Or the presence of the mitral regurgitation, how much is it going to affect the outcome of an ablation procedure?

Walid Saliba, MD:

And that's always a back and forth thing, and we never get, really, a good answer. And then listening to what I'm listening to here and better characterizing the mechanism of the mitral regurgitation and maybe giving the patient one attempt at normal rhythm and see what happens to the mitral regurgitation, I think that there is a lot of opportunity to combining... I'm not going to say combining procedures as much as I'm going to say combining efforts to improve the outcome of that patient's symptom speed from mitral regurgitation or atrial fibrillation. I think it goes a long way to be able to do that, because clearly, if we do an ablation and the patient still have mitral regurgitation, I can tell that patient that you're going to have AFib definitely within the next year and it's going to be difficult to maintain normal rhythm even with antirrhythmic medication. But if we can do something about the mitral regurgitation in addition to the atrial fibrillation, I think that... And this is something that we can do research about, I think that we can improve the outcome of these patients.

Samir Kapadia, MD:

No, I think just to the point that we are having a mitral valve multidisciplinary meeting for all the patients, including the EP, imaging, cardiac surgery. So this is a great opportunity, as you say, to understand that if you combine the two procedures, we are always in a sequential mode to say that let us try the EP or mitral valve therapy first and see what happens. I think the atrial MR is a new entity, newer entity, not super new, but new enough. And I think we are trying to learn that how we can handle it, and that's why the Carillon device is of a great interest to us. So I think we are looking forward to doing some more research in this particular area of atrial mitral regurgitation, which happens along with ventricular mitral regurgitation. So many people used to think that there's only atrial mitral regurgitation, but most of the patients with ventricular mitral regurgitation has atrial component of mitral regurgitation.

Walid Saliba, MD:

Definitely. So whenever we look at an echo and we see moderate to severe mitral regurgitation.

Samir Kapadia, MD:

Please refer to us.

Walid Saliba, MD:

For me, I mean, it just goes over my head. I want to have more granularity in terms of what is causing the mitral regurgitation? What is the mechanism? Is there a way that we can improve the mitral regurgitation beyond just an AFib ablation or treating their Afib? Is it functional MR? Is it ventricular? Is it atrial? Is it ischemic? And is it annular dilation? Because that goes a long way in terms of actually making the outcome of procedures better. And-

Samir Kapadia, MD:

We love that. So we will work, and Dr. Starling and I, we want to enroll patients with moderate MR in this because this is now an opportunity to enroll the patients as Amar also pointed out in the Carillon trial. So this is a very important part that we want to include these patients in.

Amar Krishnaswamy, MD:

So, Dr. Griffin.

Brian Griffin, MD:

Yes, lovely, this was a lovely session, very informative. Is there an opportunity to use two devices in one patient? I mean, when the surgeons do a repair, they often will do an annuloplasty and do something to the valve, and we have patients where it seems like just doing a clip may not be enough. Is there a possibility to put in a Carillon device if the clip fails or vice versa?

Amar Krishnaswamy, MD:

So it's a great question. In the current time, this is one of the benefits we think of the Carillon trial. So if we have patients who have more annular dilation, more diffuse MR, the trial allows you to put them first for a Carillon, and if the MR continues to be significant and symptomatic, then you can come back at six months and then add a MitraClip. So the hope in this trial is that in some patients we'll be able to have that understanding, but otherwise we don't currently have anything commercially available outside of the MitraClip in the United States, so combination therapy isn't readily feasible.

Samir Kapadia, MD:

Dr. Starling has a comment.

Randall Starling, MD, MPH:

Dr. Griffin was looking into the future, as he usually does. So we have actually done two cases at the Cleveland Clinic. We had to get FDA compassionate use approval, but these are two patients that failed MitraClip that subsequently had the Carillon device put in. In Germany, there's quite an extensive experience now with doing both procedures at the same time. That, of course, is not part of the EMPOWER clinical trial, but, as has been emphasized, the clipping in a patient who progressed with the annuloplasty is certainly an endpoint. I just wanted to mention, I don't want to digress from this great topic, but this whole issue of atrial myopathy and MR, I personally think the real money in that is related to tricuspid regurgitation, which is a topic for another day.

Amar Krishnaswamy, MD:

I'm going to have you keep the microphone for a minute, Dr. Starling. So Vanessa, in her clinical presentation, demonstrated the care of a patient who's clearly been followed in the heart failure section for a while. So she very easily said, and obviously the GDMT was optimized, which is going to happen in a heart failure clinic. But we all take care of patients, non-heart failure specialists that we are, with functional MR. And so in your mind, should all of these patients be seeing a heart failure specialist? And if so, where is that... How is the heart failure specialist going to help? I'm obviously biased. I think they all should. But if you can provide a more eloquent answer than that.

Randall Starling, MD, MPH:

Dr. Krishnaswamy, don't set me up to make enemies, but I will give my opinion, of course. So we all know that every cardiologist is more than competent to provide guideline-directed medical therapy. However, we would advocate for a low threshold to refer a patient that is either challenging to implement guideline-directed medical therapy or appears to be doing poorly with guideline-directed medical therapy. Because there are many nuances that a non-heart failure specialist may not be comfortable with managing. Certainly, in a Valve Center like this, the entry point for secondary mitral regurgitation in this setting of ventricular dysfunction that's advanced and that has, quote/unquote, failed guideline-directed medical therapy, there are a smaller percentage of patients that we can rescue, so to speak, or provide alternative therapies. But hopefully that addressed your question.

Samir Kapadia, MD:

And I think one thing to just add to that is that with Tre Martyn and with Jerry and your help, we have a standardized system to automatically consult heart failure for X, Y, and Z criteria. And this is a very important step forward, and I know that in HFSA, you are also trying to implement similar initiative. So this is heart failure, this mitral regurgitation is a heart failure subspecialty. It is not an interventional or clinical subspecialty. And so go ahead.

Miram Jacob, MD:

I mean, I think co-op taught us a lot. When Dr. Starling and I and Dr. Taylor had to bring these patients to a committee and we heard a lot of things, it was really rigorous about getting people on GDMT and how often you found people were not there, even within a clinical trial. And I think we also have to reflect on the fact a lot of these patients are too sick, so I think that referral at least once is so helpful because sometimes we catch the person who really needs to be referred for VAD or transplant in coap. I think another thing to address, Amar, is just when is it too late? I think you see these patients a lot and then you have a lot of say in saying this is too much. I think we all want to get a clip into somebody, but... Can you address that part, the people who are just too sick?

Amar Krishnaswamy, MD:

I think there's a lot of nuance that goes into the conversation about someone being... it's too late or saying someone it's too late, and it's also not something that we like to say, right, to any of our patients. And so I would just close to echo what both you and Dr. Starling and others have said, which is if this is not what you do day in and day out, don't tell the patient it's too late. Say let's see if there are other options. Because the moment that they get referred into our Mitral Valve Center, they're going to see a heart failure specialist, an imaging specialist, an interventionalist, a cardiac surgeon to all understand, can we provide something to that patient? Maybe for some, unfortunately, it's going to be too late, but we often have an opportunity to do something, whether it's medical, interventional, surgical, for most people.

Amar Krishnaswamy, MD:

So thanks everyone for this wonderful session and sorry to put some audience members into the hot seat, but thank you for your valuable insights.

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