Ileana L. Piña, MD, MPH; James K. Kirklin, MD


December 19, 2011

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Ileana L. Pina, MD, MPH: I'm Ileana Pina from Albert Einstein College of Medicine and Montefiore Medical Center in the Bronx, in New York, and this is my blog. I really have the pleasure today of having James Kirklin with me. He is the Director of Cardiothoracic Surgery at the University of Alabama in Birmingham. I have known Jim for a long time with his terrific work in the field of mechanical assist devices in transplant, and, in the last few years, leading the way with INTERMACS, the database or registry of the National Institutes of Health (NIH) for mechanical assist devices.

I thought that this would be a really good time to talk to my primary care audience about left ventricular assist devices (LVADs), mechanical assist devices, which can very often save lives. In fact, you may have patients who fit some of these criteria. I will keep the conversation as informative as possible. Hopefully, you will find this useful for your own patients. When you see a patient with bad heart failure, end-stage heart disease you may at least give it a thought.

Jim, welcome and thank you. We're at sessions, and it's a very busy time.

James K. Kirklin, MD: It's my pleasure.

Mechanical Assistance: A Brief History and Overview

Dr. Pina: Thank you. Tell our audience a little bit about the concept of mechanical assistance, which has been around now for quite a few years. How are we progressing through the field?

Dr. Kirklin: Well, mechanical circulatory support really had its origins in patients who were on the waiting list, dying before they could get a heart transplant, in the late 1970s and early 1980s. Those companies that were really putting in the venture capital were interested in very long-term support.

In the mid to late 1990s, and eventually, in the first part of this decade, mechanical support was approved for long-term therapy for patients who had no alternative. For example, those who were not eligible for cardiac transplantation and who were slowly dying. It is for that subset of patients that mechanical support, as an entity, offers us the greatest promise.

Eligibility for Long-Term Therapy With Mechanical Support

Dr. Pina: What would make a patient eligible for the long-term, or destination, therapy, as opposed to transplantation?

Dr. Kirklin: Currently, the most important criteria are that they have had a serious attempt at medical management of their heart failure. When that fails -- and there are many criteria to judge failure -- these patients are considered for other options, such as heart transplantation.

For a number of specific reasons, they may not be eligible. Those reasons, commonly, are things like advanced age. We know that patients who are over about age 70 have a much greater likelihood of having complications after transplantation, which might be fatal, so that's one group that is considered for mechanical support. Patients who have morbid obesity are known to be at higher risk. Patients who have other important organ system dysfunction, such as very [severe] renal disease or some of the advanced sequelae of diabetes or atherosclerosis, also might be appropriately treated with mechanical support, as opposed to cardiac transplantation.

New Devices: Going Smaller and Smaller

Dr. Pina: Through the years, I have seen the change in the devices, and now they're considerably smaller. How small can we go?

Dr. Kirklin: Probably quite small. To put it into perspective for your audience, for the initial pump, called an XVE, which was made by Thoratec and was a big pulsatile pump, we had to create spaces actually within the abdominal cavity to allow the pump to sit. That pump was prone to having problems with infections and failures.

Dr. Pina: For small women, it might not fit.

Dr. Kirklin: It was impossible. It was just not an option for small women.

Throughout the last 2 decades, there was increasing interest in what are called continuous flow or rotary pumps. These are pumps that do not themselves generate a pulse. The first iteration of these that was approved was called the HeartMate II, and that was quite a small pump. It required a little bit of a pocket below the level of the diaphragm.

Dr. Pina: It's still abdominal, though?

Dr. Kirklin: It is in the thoracic space. It is not in the abdomen. It is outside the abdomen, but you have to dissect a little bit over the diaphragm to make a little bit of space for it.

Current iterations [include] a new device called the HeartWare® device. That is the first device in the United States that sits totally within the space around the heart -- the pericardial space. It's very circular, elliptical. It's like a very thick coin. It sits right at the apex of the heart right against the diaphragm.

There's no other dissection required. The chest is easily closed, and the in-flow and out-flow components of the graft sit right next to the heart, so these can be put in very small patients.

Dr. Pina: Is it pulsatile or is it continuous?

Dr. Kirklin: It is not pulsatile. It is a continuous-flow pump. For example, we have recently implanted such a pump in a 9-year-old girl.

Dr. Pina: Oh, my goodness.

Dr. Kirklin: So these pumps have the promise for being implanted, at least, in teenagers and older children. There is a whole new series of devices that are being explored and experimented with, which are potentially applicable to small infants, and potentially, to newborn children.

Dealing With the Pulseless Patients

Dr. Pina: Do you get a blood pressure when you take a blood pressure reading on these patients?

Dr. Kirklin: Many of these patients are absolutely pulseless, and so there has to be special education for all of the medical personnel who are caring for them, whether it be in their local community or in hospitals that are not so used to continuous-flow pumps. There are special Doppler techniques to measure blood flow at some component, like in the wrist, to make sure that patients have some appropriate blood pressure.

Dr. Pina: Especially when the patient is still talking to you and is awake and alert, and you don't get a blood pressure.

Dr. Kirklin: Correct. But it also gets really strange especially if they were ill, and for example, if a patient was in a coma. You can imagine what might happen when [medical staff] can't feel a blood pressure and are starting to do resuscitations, when actually, if they hooked [the patient] up to the appropriate console and measured the flows, they would see this patient has a normal cardiac output, but no blood pressure.

Where Physicians Can Learn About Mechanical Devices

Dr. Pina: Along with this, for our primary care audience, education is very, very critical. Can they go on the Web anywhere to learn more about mechanical assistance?

Dr. Kirklin: Yes, there are a number of Websites. They can, for example, look for information on HeartMate HeartMate or HeartWare. Those would be very educational Websites, and then, of course, there is a host of information on the INTERMACS Website.

INTERMACS: Lifelong Tracking of Patients on Mechanical Support

Dr. Pina: Tell us about INTERMACS, because that was really, to me so groundbreaking, and, part of the background is [that] many years ago, we didn't have a huge number of patients in any one site for any one site to have an enormous database. So we had to pool our resources. For many years, you and your team at University of Alabama at Birmingham did that for us, and gave us tremendous amounts of information about transplant patients and things that we're using today. However, INTERMACS was different, so tell our primary care audience about that.

Dr. Kirklin: Back in about 1980 -- a long time ago -- there was a group that was put together by the National Heart, Lung and Blood Institute (NHLBI) and the Institute of Medicine (IOM) to look at the total artificial heart and what we might see in the future. In their report, they very prophetically stated that these complex patients supported by these devices should be followed for the rest of their lives by very careful data collection from experienced medical groups.

Dr. Pina: Very prophetic.

Dr. Kirklin: When mechanical support was approved for so-called destination therapy, which means permanent therapy for a patient with end-stage heart disease, there was increasing interest from the NHLBI in having a repository for data collection that would actually do a number of things. It would help facilitate the introduction of new devices in the field. It would gather information from a number of centers -- since any one center may not have enough patients to get meaningful data -- so to generate truths as closely as we can approximate, and to help decide which devices would be most suitable for which patients.

An interesting experiment was put forth, which was a collaborative effort between Centers for Medicare & Medicaid Services (CMS), the US Food and Drug Administration (FDA), and NIH to form this database called INTERMACS, which stands for Interagency Registry for Mechanically Assisted Circulatory Support. This was approved in 2006. We began data collection in July of that year, and we recently have renewed for another 5 years of data

Dr. Pina: Congratulations on that. That's terrific.

Dr. Kirklin: Thank you very much.

Dr. Pina: That's a good one. How many patients are in there now?

Dr. Kirklin: There are over 4000 patients entered into INTERMACS at this time. The success of the continuous flow pumps, which really have only been approved for 3 years now, constituted 95% of device applications. So of all of the potentially durable devices that are implanted, 95% of them are continuous flow pumps. For now, these bigger, bulky pulsatile pumps are really a relic of history.

The Infection Rate With Devices: Has It Decreased?

Dr. Pina: I know you collect a lot of events. How are we doing with infections, because that was always such an issue with the bigger pumps and the drivelines? Have you seen a change in infection rate?

Dr. Kirklin: The infection rate has dramatically decreased with continuous flow pumps, compared with the old pulsatile pumps. One of the reasons is that the drivelines themselves are much smaller. In addition, the fact that you don't have to create a large pocket [means that] you get rid of a lot of dead space that promotes infection.

Dr. Pina: Sure, abscess formation and everything else.

Dr. Kirklin: With these big pumps, they are such a large foreign body, and the surface of them does not have any way to combat bacteria themselves, so that if there was any contamination of the pump with this big dead space, then that tends to get infected. The drivelines also are prone to infection in the older pumps because they were very large.

An interesting finding has been that most of these drivelines were coated by a velour coating, which was thought to promote tissue ingrowth. But in recent years, it's increasingly believed that the actual velour, because of its complex interstices, can actually attract and maintain bacteria, so that it does get a lot of tissue ingrowth. But if the driveline moves at all, which is very common in daily living, they tend to become infected, so the more current devices are actually burying all of the velour below the skin line. When you see a driveline now, the part that extends out from the skin is very smooth. We have not proven it yet, but there is very suggestive evidence that driveline infections are importantly reduced with the smaller continuous flow pumps.

Dr. Pina: That's terrific. You can see the progression, and obviously, the database will capture that change.

The Longest Destination Time

Dr. Pina: How long is the longest destination therapy that you know of?

Dr. Kirklin: The Jarvik would probably be the longest, certainly, in excess of 5 years, but it may be 7 or 8 for isolated patients.

Dr. Pina: So this is really a difference when we did REMATCH.[1] The patients were dying, if not at the [first] year, at the second year for sure.

Dr. Kirklin: For those in your audience who may not be so familiar with it, REMATCH was the pivotal trial that really allowed destination therapy to be approved, which was with this very big, bulky pulsatile pump. At 2 years, only 30% or 40% of those patients were alive, even with the pumps. It just turns out that the [mortality rates] in patients treated medically were terrible. They were all dying.

Currently, 70% of the patients who receive primary implants of continuous flow pumps are alive at 1 year, and, out to 2 years; it's just below 70%, so the progress has been really dramatic. In some institutions, with proper selection of patients and so on, the 1-year survival exceeds 80%. My belief is that within a few years, when we better match the patient to the device, we may be getting survivals of 80%-85% at 1 and 2 years with the devices, which will then be, interestingly, competitive with heart transplantation.

Dr. Pina: That's amazing to think that clinicians can think of an alternative for their patients who physiologically may still not be too bad, but have all those risk factors that you've mentioned.

The Cost of Mechanical Assistance

Dr. Pina: Tell the audience a little bit about the cost.

Dr. Kirklin: These pumps are expensive. Typically, a pump costs about $75,000. These are generally covered by insurance carriers. The cost of hospitalization on the average for a VAD implant is about $130,000, which is more than a heart transplant, but the interesting studies, which remain to be done, are the comparisons over a 5-year or a 2-year period, in which the upfront cost of the device is substantial. It will be interesting to see if the actual costs are less with the device, compared with, for example, transplantation with all the expensive immunosuppressive therapies required.

Dr. Pina: And the returning hospitalizations that happen.

Dr. Kirklin: Correct. And compared with advanced heart failure patients with their repeat hospitalizations. That is one of the very important areas of investigation that's ongoing, comparing the costs of these devices, as well as the quality of life of patients with these various therapies.

The Quality of Life of the Patient on Devices

Dr. Pina: We have a lot of work still ahead and a lot of research that still needs to be done. I know some of our colleagues are working on quality of life assessments because, obviously, the quality of life aspects of a person on a VAD are very different from the instruments that we currently have, and we badly need to quantitate how the patients truly feel.

Dr. Kirklin: Yes. An important part of INTERMACS is encouraging centers to enter data about quality of life, to collect it routinely, as well as patients' functional outcome, because one of the very important aspects of devices is safely applying them to patients who are not really at the end stages of heart failure. Clearly, we want to make sure that we're not putting a device in too soon for somebody who could be taken care of well with medical therapy or a heart transplant, but yet, putting them in early enough, so that they have the best chance of achieving a long-term good result with a good quality of life.

Dr. Pina: It's finding that little place in the curve before the curve goes the wrong way.

Dr. Kirklin: Correct. There is a trial called REVIVE-IT, which is supported, in part, by the NHLBI, which is examining HeartWare, this smaller pump that sits totally within the pericardial space against medical therapy, for patients who have New York Heart Association class IIIB, who are not quite class IV patients. This study will begin enrolling patients soon and will be a pivotal point for gathering information about the safe extension of these devices.

Defining Heart Failure for Best Treatment

Dr. Pina: To me, as a clinician, one of the big aspects of INTERMACS [is the] much more accurate description of the patients in different levels. Because, you think of a "III", well, I can line up 5 "IIIs" and they're all different, and a "IV" certainly looks different than a "III", but maybe overnight, they become a "III." The descriptors that we have -- the crash-and-burn, or on inotrope, not on inotrope -- have really allowed us to hone in and try to define that population, which has also been a big contribution, so INTERMACS has not just been a registry to collect data, but we're also learning a lot.

Dr. Kirklin: What we've done is to divide New York Heart Association class IV into 5 INTERMACS levels. As you indicated, if there was a crash-and-burn -- those patients are really who are in impending cardiogenic shock -- it's important for your audience to understand that those patients, who are in the act of dying from really profound cardiogenic shock, should probably be supported with a more temporary device. There are a number of those out there. The most basic form of that is extracorporeal membrane oxygenation (ECMO) support, but then, if they can be stabilized on those devices, then they can be moved to a more durable pump.

As we examine the medical groups that are potentially candidates for mechanical support, there is a very important area of INTERMACS, which I know you personally are interested in, the so-called MEDAMACS, which is a very, interesting NHLBI initiative to gather a growing medical cohort of patients in the lower portions of the INTERMACS categorization -- that is early class IV or class IIIB. A large number of those patients will be followed, some of whom will eventually get devices, some not, so that we'll have a chance to do good, clinical, scientific investigations to compare outcomes.

Dr. Pina: Almost the natural history of the patient journey into that area.

Dr. Kirklin: Correct. And [we can] then get better information as to which patients would be better suited for device therapy, as they move along in the natural history of heart failure and those that might not be.

Dr. Pina: We've shared incredible, good information today, and I want to really thank you for coming and sharing this with us. I couldn't think of anybody better to give us a little bit of this history. I think for our primary care audience, if you have patients that even could potentially look like this, the best advice is early referral to a heart failure program that has the capabilities of doing mechanical assist devices, with or without transplantation, and who have the experts who can really help shepherd the patient through the process and make decisions, whether in fact, these patients are eligible or not.

I want to thank you for being with us today, and I hope this is helpful for your practice. From the American Heart Association Sessions in Orlando, I bid you a good day.


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