Ventricular Assist Devices Demystified

An Interview With Dr Valluvan Jeevanandam

Ileana L. Piña, MD, MPH


February 18, 2016

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Editor's Note:
Ileana L. Piña, MD, MPH, interviews Valluvan Jeevanandam, MD, a professor of surgery and chief of cardiothoracic surgery at the University of Chicago Medicine. Dr Jeevanandam is an expert in the field of ventricular assist devices.

Dr Piña: Hello. I'm Ileana Piña, from Albert Einstein College of Medicine and the Montefiore Medical Center in the Bronx, New York. As a heart-failure transplant doc, I am quite intrigued by the world of devices that we see, particularly the pumps.

With me today is a good friend and former colleague, Dr Valluvan Jeevanandam, who is at the University of Chicago. He is the chief of cardiac and thoracic surgery, and someone with whom I have worked very closely. I've asked him here today to talk to us about ventricular assist devices (VADs) and their future. I am hoping that those of you who are watching are thinking about patients whom you could refer. Often, patients are referred way too late—when they are very, very sick—and there's little that we can offer them. Val, welcome.

Dr Valluvan Jeevanandam: Thank you very much, Ileana. It is great to be here.

Dr Piña: We've been doing this for a while.

Dr Jeevanandam: Over 25 years. That makes us feel old.

Dr Piña: Yes. I remember our first electric VAD, when the patient walked outside and looked at the sun and said, "Wow."

Dr Jeevanandam: That was an amazing time. That was the seventh electric VAD implant in the world at that time.

Dr Piña: Isn't that something? We've come a long way. Now, our heart failure service at Montefiore uses left ventricular assist devices (LVADs) often. But things aren't perfect, and we are seeing a fair amount of bleeding. We've been concerned about thrombosis. Where do you think we are right now in the world of VADs?

Dr Jeevanandam: If we take a step back, we've been doing continuous full LVADs for about 9 years. Really, it's in its infancy. As you recall, it's not like you can go to a book and learn how to take care of a low-pulsatile system, and our species has had a pulse forever.

Dr Piña: Evolution got us this way for some reason.

Dr Jeevanandam: Exactly. So, I think these pumps are great. They're quiet. They're powerful. They're efficient. They certainly save lives, but we do have high-maintenance issues. I think it's going to be an evolution. In the beginning, there were surgical issues. We understand those better.

Dr Piña: [Cardiovascular surgeons] have gotten much better at the surgical issues.

Dr Jeevanandam: A lot of it is cannula positioning. You have to get it off the septum. You have to put the outflow cannula in a certain way. You have to be meticulous about bleeding. There's the surgical aspect. We're not perfect, but we're getting there.

Then, I think there's a huge component of the medical aspect: How do you manage anticoagulation? How do you measure blood pressure? How do you manage the RPMs [rates per minute]? Do you have the ventricle full? Do you have it half empty?

Dr Piña: When do you image? That's even a question.

Dr Jeevanandam: Absolutely.

Dr Piña: Let's back up a minute [to discuss] anticoagulation. There are lots of ways of doing it. Some centers have gone exclusively to aspirin, whereas others have gone exclusively to warfarin. Yet, the recommendation is both. I've seen patients bleed on one but not on the other. What are your thoughts about the anticoagulation scheme?

Dr Jeevanandam: As you know, with rotary pumps, almost all of the patients have abnormal von Willebrand factor (vWF). Aspirin could worsen that because you are going to decrease platelet function. On the other hand, there are some anti-inflammatory aspects of aspirin as well.

At the University of Chicago of Medicine, we generally put them on low-dose aspirin, and then we put them on warfarin. If they have bleeding, we'll take them off the aspirin first. If they continue to bleed, then we'll consider lowering the warfarin dose.

Dr Piña: What's your INR [international normalized ratio] target?

Dr Jeevanandam: It's different for different VADs. For the HeartMate II® (Thoratec; Pleasanton, California), we target about 2. For the HVAD® [System] from HeartWare (Framingham, Massachusetts), we target about 2.5, and for the ReliantHeart HeartAssist 5® device (Houston, Texas), we target in the middle: someplace between 2 and 2.5.

Dr Piña: What do you think is the etiology of the bleeding? We've heard a lot about the vWF, but we've also heard about arteriovenous malformations (AVMs) that remind us of aortic stenosis, where the patients develop AVMs in the colon.

Dr Jeevanandam: That's Heyde syndrome, where it is thought that the low pulsatility caused congestion of submucosal blood, leading to AVMs. I think that's exactly what we're seeing here. You have low pulsatility in the central system, which then gets exaggerated in the peripheral system in the submucosa. You have a little bit of congestion. You get a little bit of trauma. You'll have bleeding. I think it's multifactorial. There's a degradation of vWF, and there's the loss of pulsatility that hurts. There's also activation of different enzymes that actually promote angiogenesis that we're [investigating] at the University of Chicago. So, multiple effects occur.

When you have low pulsatility, you do a lot of things to the endothelium. In a sense, the endothelium is the largest organ that we have.

Dr Piña: It's a protective organ.

Dr Jeevanandam: It has such a large surface area. I think we're just scratching the surface on how the endothelial effects are leading to systemic effects.

Dr Piña: Do you think that in the future, we should do some pulsatility and some nonpulsatility? How should that work?

Dr Jeevanandam: It's interesting. Different pumps are trying to accomplish that. For instance, the HeartMate II has a mode where for a couple of seconds, the speed decreases and then goes back up, then it comes back to baseline. This is repeated in a pattern of 30 times per minute. I don't think that creates enough of a pulse to effect the endothelium, but what it does do is create a better washout and perhaps decrease the chance of thrombosis within the pump.

Dr Piña: It cleans the pump, literally.

Dr Jeevanandam: It's interesting that in the old days, when you and I were taking care of pulsatile patients, we never saw gastrointestinal (GI) bleeding. As a matter of fact, those patients were rarely on anticoagulation.

Dr Piña: That's exactly right. A very occasional thrombus, a very occasional stroke, but not the majority of the patients.

Dr Jeevanandam: That combination of different effects on the endothelium is what we're seeing. There are some solutions. I don't think we'll ever get a pulse with the continuous flow devices, but perhaps we can identify a block or an angiogenesis. I know thalidomide is now being used in some of these GI bleeders. Medicine has a way to go.

Then, there's pump design. For instance, the newer pumps, such as the HeartMate 3—and it's completely magnetically levitated so it can run at very low RPMs and not have a problem with the bearings—have larger gaps, so hopefully we'll have less blood trauma. It's a very powerful pump.

HeartWare has the miniature VAD (MVAD), which is a smaller pump. [Newer pumps may have] better design. [But] we won't know how the design is going to affect the biological specimen until we actually do the trials.

Dr Piña: Some European centers, such as Charité in Berlin, are doing INRs in the home. Warfarin, you know, is fraught with all sorts of problems. The INR may be one thing now, and the next day it's something else, and the patient bleeds. The ability to do on-site testing may help keep that INR as stable as possible.

What do you think of the new oral anticoagulants (NOACs) for the pumps?

Dr Jeevanandam: I think the NOACs are great; because you don't have to do the testing and it's one pill a day, the compliance is much better. I was looking at a study on Coumadin®: Only 50% of the time are patients in the therapeutic range.

So, the NOACs make them more therapeutic. I'm trying to find the first center that's going to have the cojones to go ahead and put somebody on a NOAC, and maybe that's the right thing to do.

Dr Piña: We don't have a reversal agent yet. There's one that's just been approved (idarucizumab [Praxbind®]). I think that's the fear of all of us: If the bleeding begins, you're in trouble. You've got to correct it, and you don't have the perfect antidote.

Take me into other pumps. Let's tell the audience about other ways to help.

Dr Jeevanandam: If you think about heart failure, it's when there isn't enough energy in the circulation. So, these mechanical pumps eject energy into the circulation. Basically, you can do it in two ways. You have direct-blood pumps, such as the HeartMate II, the HeartMate 3, the HVAD, and the ReliantHeart device. The other way is counterpulsation. We don't pay as much attention to counterpulsation, although the most used device in the world is the intra-artery balloon pump.

Dr Piña: The balloon pump, yes.

Dr Jeevanandam: How many times have you had a patient who comes in with decompensated heart failure? The first thing you rush to is the balloon pump. They stabilize, and then you're kind of stuck with the balloon.

There are two companies that are trying to address that problem. Sunshine Heart (Eden Prairie, Minnesota) has a counterpulsation device that wraps around the aorta. It's about a 20-mL displacement pump. There's a company called NuPulse (Boston, Massachusetts) that has actually developed an ambulatory, outpatient (at-home) design: a 50-mL displacement descending aorta pump. That will start clinical trials hopefully early next year.

Sunshine Heart is already enrolling. They will probably solve some of the problems with endothelial function, because there's certainly a pulse. So, you don't have the nonpulsatility issues.

Dr Piña: Maybe the bleeding?

Dr Jeevanandam: I think they're going to be advantageous in terms of bleeding [and] stroke. And also, these pumps are nonobligatory, in that if you stop them, it is not catastrophic for the patient. A patient doesn't have to spend [his or her] entire life focused on a pump running. If it stops, it's okay.

Dr Piña: Which is how it is now with the VADs. Their whole lives revolve around the pump.

Dr Jeevanandam: They have the chance to have them on and off. So, there's potential for that class.

When I look at heart failure as a spectrum, you have class III, class IV, and then you have the INTERMACS[1] subdivisions, right? We have really good devices now for the INTERMACS 1, 2, and 3 patients.

Then you have cardiac resynchronization therapy (CRT) that gets into the class III patient. There's this huge gap between class III and the walking class IV [patients]. We need some devices for that. Maybe the counterpulsation devices are the devices for that group. With heart failure, you keep resetting heart failure. With medicine, you reset for 5 years. Then you put in a CRT [device], you reset. Then maybe those devices can reset, and then when they really get further along, then they'll go in with the continuous-flow LVADs.

Dr Piña: So, you're buying some time.

Dr Jeevanandam: In heart failure, Ileana, we always try to buy time.

Dr Piña: The other interesting thing is that we've always [tried to identify] whether a patient is a bridge-to-transplant or for destination therapy—in other words, not a transplant candidate. How often do you get someone whom you really don't know? They're very sick. You haven't had an opportunity to do a good evaluation. I remember you and me and our team on the phone in the middle of the night, trying to figure out whether this was a transplantation or not. I think the bridge to decision is very innovative and more compatible with reality when we meet those patients.

Dr Jeevanandam: You're absolutely right. The bridge-to-transplant and destination therapy [categorizations] were artificially created for trial design.

Dr Piña: That's right, because you have to have some entry criteria.

Dr Jeevanandam: Right. The original trials that we were involved in were bridge-to-transplant, and the FDA [US Food and Drug Administration] wanted to get the devices back. They could explant the devices and could see how they're evolving. They became kind of a 6-month device. Then we got destination therapy. Now you got stuck with two entities that didn't make clinical sense, right?

The MOMENTUM 3 trial, comparing the HeartMate 3 vs the HeartMate II, tries to solve that problem by having short-term and long-term endpoints.[2] There's no distinction between bridge and destination. It actually becomes how you and I would take care of a patient: You put it in, and if they are transplant candidates, they get transplanted. If they are not transplant candidates, then it's their permanent device.

It takes away that designation. If anything happened in the last year that's revolutionary, it's getting rid of the bridge and destination categorization, which is very important.

Dr Piña: To remind our audience, sometimes a destination therapy candidate may turn around and become a good bridge-to-transplant candidate. Their pulmonary hypertension may resolve, or if they have had a malignancy, the time of staying disease-free has passed, and now you're willing to take the risk. It's a moving target, and an exciting time. Everybody's trying to do the next best thing.

I'm counting on you for providing a lot of these answers. Thank you, Val, for being with us.

Dr Jeevanandam: It was great being here, Ileana.

Dr Piña: I want to thank our audience for joining us. This is Ileana Pina. Have a great day.

Disclosures: Valluvan Jeevanandam, MD, has disclosed the following relevant financial relationships:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Thoratec Corporation; HeartWare, Inc; ReliantHeart


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