Cardiologist at Aurora Denver Cardiology Associates, Richard Jantz, MD talks about an implantable device that is keeping failing hearts beating.
Interview conducted by Ivanhoe Broadcast News in 2023.
A statistic I shared with Ivanhoe team was that more than six million Americans live with heart failure, which seems remarkable to me. And there’s a percentage of those I read for the BaroStim team with reduced ejection fraction. What is heart failure and what is reduced ejection?
Jantz: Heart failure is basically inadequate heart output to supply your organs with adequate perfusion. And so there’s two types, a shades of gray, I guess is the better way to look at it. And there are people that have markedly diminished heart muscle function in terms of their contractility, and those people have heart failure with reduced ejection fraction, and then there are people that have mediumly reduced ejection fracture and then normal ejection fraction. And so probably half the people have normal ejection fraction, but they have still inadequate critic output, and it’s because of the fact that their heart doesn’t relax normally or accept blood normally. It’s called diastolic dysfunction. And the other ones who have a weak heart muscle have systolic heart dysfunction and sometimes a combination of both. And so in either case, they tend to retain fluid, and get congested and short of breath and get swelling, can’t lie down flat, sometimes have cough, and both can present in a very similar fashion, and the treatments are slightly different. But nevertheless the patient that we’re speaking about has significant systolic dysfunction weak heart muscle.
You talked a little bit about this, but what is day to day life like for these people? And is it generally older adults? Who does this target?
Jantz: Well, there are a whole litany of causes and it depends on the cause. But in general, it’s more often older people. Because one of the more common causes of systolic heart dysfunction or heart muscle dysfunction, is coronary blockages, and that’s what we’re speaking of has, but there are other causes, including high blood pressure and viral syndromes. Large percentage of patients actually have a genetic predisposition. There are patients who have rapid heart rates, like atrial fibrillation, and toxins like chemotherapy and alcohol, again, it can attack even young people. And so you can see people with ”non ischemic cardiomyopathies” that aren’t due to blockages, who present quite young, and certainly it’s more common in the older people, and then the diastolic dysfunction patients tend to be older frequently, even in octogenarians, very common in older people. But that one also can occur in younger people as well. It can be from infiltrated cardiomyopathies, for instance with amyloid or sarcoid, and sometimes there’s no obvious cause that you can identify. But nevertheless, it tends to be older people but it can be anybody.
How is it typically treated?
Jantz: Well, it turns out that the systolic dysfunction patients, the ones who have weak heart muscles, we now have what we call four pillars of therapy. Only recently we added the fourth pillar, but historically, we block what I call the evil humors, which are neurohmones or cytokines that are activated when the heart muscle is weak. If those are not addressed or blocked, then the heart muscle progressively gets worse until you die. And if you successfully get them treated with those medications, you can block those evil humors. I tell the patients are evil humors because they don’t know what neurohormones are. Neither do, I guess. But nevertheless, there are a whole litany of neurohormones that can be blocked. And some of them, it doesn’t matter if you block but the ones that you do, that do have a benefit, we block with what are called renin angiotensin aldosterone system blockade, which is drugs like enalapril and losartan, and then the most recent one is, which you hear about all the time. We also use the MRAs that are called mineral receptor antagonists, or MRAs, aldosterone antagonists. Those include sperontone and a more recent one, Speninonen. We use Beta blockers and there are three proven Beta blockers and they include carvel, metoproxosinate. And most recently we use SLT-2 antagonists which were originally developed for heart, for diabetes. And lo and behold, they seem to help kidney disease, heart disease, vascular disease, and so now they have an indication in heart failure and we use them early on in systolic heart failure, but they also happen to be good in diastolic heart failure. The entericus has some benefit in diastolic heart failure as well. Controlling the blood pressure and diastolic heart failure is helpful. They’re slightly different. All of them get treated with diuretics varying degrees, and we try to use the least amount of diuretics possible to allow them to tolerate the other medicines which actually improve their heart muscle function. There are people who still have symptoms in spite of that. And unfortunately some people who we call reverse remodel, if they have heart muscle is function and their rejection fracture gets better, contractility improves, and those people we call heart failure in remission now, we used to call that improved rejection refraction. We now call, I guess our latest terminology is heart failure remission as an analogy to cancer. Because the fact is, if you have heart failure remission or heart failure that’s improved from medicines and you stop the medicines, most often, it gets worse again. And frequently, the second time you try to resurrect the heart with those medicines, that doesn’t work as well. So we try to convince people they should keep taking the medicines if they’ve shown improvement, and then those patients who still have symptoms, in spite of being those four pillars of medical therapy, and also the ones for diastolic heart dysfunction, which there are a few of actually. But nevertheless, aldosterone antagonists and the SLT-2 antagonists seem to beneficial along with diuretics and blood pressure control and heart rate control But nevertheless, if you still have symptoms, then there are these actually two implanable devices now. And the one we were talking about in our patient today is Barostim which is a novel approach to modulate the autonomic nervous system or the automatic nervous system. Basically it has the beauty of being a fairly simple procedure, that’s outpatient procedure, that involves making a pocket under the skin and putting a device that has a battery. It stimulates the carotid sinus. Has a little wires put up to the carotid sinus, and then it stimulates the carotid sinus, and it tends to modulate the adrenaline levels, and the vagal tone it’s called the sympathetic or the fight or flight in the relaxation parts of the autonomic nervous system. And that seems to improve function. And so that particular device, called the Barostim therapy, has been demonstrated to reduce hospitalizations and improve quality of life, and improve functional capacity. Just recently they reviewed their, I think it was median follow up 3.7 years as I recall, and nevertheless they were hoping to see a survival benefit, and they missed their primary end point because there wasn’t a clear cut survival benefit. However, if they excluded the patients in the control group who had a heart transplant or a ventricular assist device, there was a significant improvement survival benefit. So point of that of the way we interpret it is, it improves your quality of life and your functional capacity, reduce risk for hospitalization, but it also improves the likelihood that you would not require a heart transplant or a ventricular assist device. But when you actually look at the data, the way the study was done, there was not a statistically significant survival benefit if you don’t exclude the people who had a heart transponder or ventricular assist device. So anyway, it seems to be a useful device. And it turns out that it’s indicated in people who have weak heart muscles, ejection fraction is less than 35%, and there’s really no bottom number. However, from a physician’s perspective, at least my perspective, it’s actually more useful in people who are so symptomatic but not severely ill. And so there’s a sweet spot in order to prescribe it, and to really get the best benefit. We’ve actually and the patient we talked about and actually we have another patient who is also quite ill and both of them have had a response. They have better functional capacity and certainly seem to feel better and have better six minute walk times and that thing. So I think in general I can be used in almost anybody with weak heart muscle but the people who respond the best are not quite as sick and so they have a better response.
And the alternative would be open heart surgery, right?
Jantz: Well the alternatives at this point would be well there’s a drug called vericiguat which doesn’t have a survival but it’s a oral ionotrope which improves contractility and cardiac output. That one is indicated in people who have decompensated heart failure. In spite of adequate medical therapy. And really the other alternatives are ventricular assist devices which are implantable devices and heart cardiac transplantation. If you still have symptoms that are bad enough that you think that the risk of dying without one of those procedures is higher than the risk with the procedure because neither one of them are riskless. There are no riskless options.
Where is it implanted? You mentioned under the skin and is that minimally invasive?
Jantz: It’s usually in the pectoral region. And it is a incision that involves a small incision and making a pocket under the skin. And then the wire that stimulates the crowded sinuses can be surgically tunneled up to that area. There is actually an investigational approach that doesn’t require any incision in the neck and that one when I say it’s investigational has not been approved by the FDA. But actually my partner Dr. Porterfield who’s an electrophysiologist who installs these devices is going to be involved in that trial. And so It’s a ingenious gizmo that has a curve on it and it comes out through the skin and then you managed to get the wire stuck to it. It’s very ingenious actually. And you can do it without an incision in the neck. So that has some advantages I guess. But nevertheless either way it can be done. It’s done with general anesthesia because you want to hold very still but once the general anesthesia is done and it wears off and the wound is stable you can go home typically the same day. And then that device is titrated up so the energy levels are titrated up over time and the majority of the benefit is usually down the road a few weeks two months. The other device, called CCM therapy or impulse modulation therapy has a different mechanism and people have tried to use quantum mechanics of all things to explain how it works. And presumably has benefits in a molecular level in the heart cells may have conformational changes in the certain enzymes but nevertheless it stimulates the heart between beats and so in what’s called the refractory period the relative refractory period. And it doesn’t pace the heart but it actually it requires at this 0.2 wires inside the right ventricle. So the advantage in the Barostim it’s all extra vascular. It’s under the skin and under this- and then outside the vessels. This particular one is like another pacemaker but it doesn’t actually pace the heart in terms of making it beat. It stimulates it between beats for seven hours a day. And that one you also sorely titrate up. That one has a pretty immediate benefit. It can actually improve the ejection fraction. You can see some improvement in ejection fraction with Barostim as well. And it also has improvement in quality of life and reduction hospitalizations. And that one we’ve also used an we’ve had our most dramatic case I think that we’ve had actually was off label. And a woman that had been taken off the kidney transplant list because her ejection fraction dropped. And we couldn’t get her on our standard medicines because she was on dialysis and her pressures wouldn’t tolerate it. And so in not having other options we decided well we’ll try impulse dilation therapy and lo and behold, she came one day without her daughters and I said where are your daughters? And she says well they don’t visit me anymore. I said why not? They say you’re not sick anymore. She says I’m not sick anymore. And her ejection fraction got better and she ended up getting a kidney transplant. So that one was pretty much of a home run and sometimes we’ve done it in other people that I think it’s a similar story to Barostim. It’s better to do it when people aren’t circling the drain and they’re little better. And if you wait too late and too long it doesn’t have as much benefit. But as a matter of fact that one if the ejection fraction is below 25% is not indicative. We have a new trial going on with that one though that I think is quite exciting because it turns out a lot of people who have heart failure end up getting what’s called a primary prevention defibrillator. Because when you have weak heart muscle you can either die because of progressive heart muscle dysfunction or because of a sudden death or rhythm disturbance. So those people get what we call a primary prevention defibrillator which doesn’t make you feel any better except that it there’s an insurance policy in case you need to get shocked. Well now they have developed a device that not only is a primary prevention defibrillator but also has a CCM impulse modulation technology. And so because of that if you have a patient on optimal medical therapy who still has some symptoms and needs a primary prevention device instead of having two devices you can have one device that does both things insurance and also impulse migration therapy. And so there’s a trial that’s going to start next month or two that includes that as an option so that people that need a primary prevention defibrillator who might also benefit from impulse migration therapy will be able to get with one device. And so that’s actually appealing to me in particular because once again it’s hard to recommend for instance if somebody already has the defiblator and they’re doing okay but not great which is just the person who needs the device. It’s still hard to recommend a device and a lot of people say well I don’t feel that bad I’m not going to have another device. And but if you could do it all at one fell swoop and it works out that seems like that would be an ideal option. So that might become an option depending on what the trial shows obviously which hasn’t been done.
Well I think you describe nicely who a good candidate is. Who’s not a good candidate?
Jantz: Well basically some of the people we’ve given it to. So for instance there’s a test we do that looks at congestion called the BNP test or the proBNP tests. And so the optimal person at least in the trial for Barostim for instance had a BNP of less than 1,600. A normal depending on your kidney function and your age and whatever is less than 300. So It’s pretty high but not extremely high. And we’ve been known to try to put it in people that have a proBNP of 20,000 which is a lot more than 1,600 .So those people may not respond as well. Although we have a person who did respond pretty well in that scenario. And then certainly people who have ejection fractions that are really low don’t respond too well to the impulse modulation therapy. But the CCM the Barostim does seem to respond better. But once again it’s the people that have little better ejection fraction are. Do better with, I suppose, both of them, but for instance the Barostim is better if you’re not as sick, and the same is true for CCM therapy. If you wait until people are really very end stage, it’s not as helpful. We’ve tried that and it didn’t help.
You’re giving the heart a little help. Does the heart get stronger?
Jantz: Yes, it can. As a matter of fact, one of the things that we do in our heart clinic that I think is not commonly done, maybe, is that we actually use heart muscle function as a determinant for how aggressively we pursue the medicines. So unfortunately, frequently in the world of medicine in general and cardiology as well, there’s a big emphasis on seeing lots of people quickly. And so everybody gets started on some medicine, but it’s never titrated to optimal doses. And so what we do is we keep monitoring the function, and we keep pushing the doses and we add more medicine if we need to. There are other drugs that aren’t in our four pillars that we can sometimes use Hydrazine and nitrates. And that’s why I told you about and any rate. So if one does carefully modify the medicines, get back on the diuretics, get to optimal doses, we expect at least half of our patients to show significant improvement. Now the problem being that it may not be durable. They might do well for a few years and then start slipping again. And then that’s where these other- for instance, I saw a man today who I’ve been wanting to put a Barostim in because I’ve known him for a number of years. And he got better then he’s been slowly getting worse. And so I thought he was a great candidate and right now we’ve been having trouble with his insurance, but if it finally gets approved, I think he’s a great candidate. Because he’s- actually his BNP is now down to 1,300. It’s a sweet spot. He’s been out, he has breathlessness and exercise intolerance, but he’s been out. He’s selling his farm. He’s got all kinds of stuff that he’s got to get rid of. He’s been hauling it in. So he’s actually the kind of person that actually would- it’s right at the right time, not too late and not too early. And I think that’s- and that’s actually, I think one of the keys to try to figure out when to use these therapies.
And would you ever take one out if someone over a decade later they’re doing so well, would you remove it?
Jantz: Well, I think you could turn both of them off.
Turn them off?
Jantz: You could turn them off, I guess you could remove them as well. Although typically, probably just as well just turn it off, I think.
That’s what I’m wondering. And you’ve absolutely seen patients improve with this device. And what do you like most about it?
Jantz: Well, I think it’s because it’s another option. The obviously, for instance, ventricular cyst devices are implantable devices that actually show benefit, but it’s a subcutaneous device and you put intake from the core of the ventricle. So we have to core out the ventricle, put in, take in, and it has a battery, you got to carry it around and it has a drive line. So although it has clearly been beneficial effects. And actually at one year approaches heart transplantation in some stories. But the cost of it is that there’s a higher risk of bleeding, a higher risk of infection, a higher risk of stroke. So it’s not a free lunch. There’s no perfect solution. Heart transplantation is dramatic, its just- truly can’t be, when we had our heart transplant program we saw- I just saw one of our final remaining people from already 30 years ago who I just saw him, he lives in Wyoming. He’s down here the other day. And I have another person who’s in S Park, he’s 30, some years out. There are people who have dramatic responses. And then obviously, the majority of the patients we transpired back in the ’80s and ’90s have not survived. And usually because of infection or cancer, because immunosuppression has its issues, kidney failure, some of the medications and pair healing and so on. So it’s not a perfect solution either, although, of the treatments for severe heart failure, it’s the most dramatic because we give you a new heart. And interestingly enough of all the bad things about Fentanyl, the number of donors now has gone up because of Fentanyl. And so we don’t do transplants here, but probably a year ago, maybe even six or eight months ago already, if you were on the list for a heart transplant at the university, you would not get one unless you got admitted to the hospital and you were really sick. And you would be on the list for a long time and it took a long time to get. And recently I had a patient I was thinking about Barostim actually because he didn’t want heart transplant and I thought he need heart transplant. And to make the long story short, he ended up at the university for another reason. And I said, well, he’s in your hospital, go see him. And they went and saw him and they thought he was in bad shape. And they ended up- he ended up getting a heart transplant in a couple of weeks. It was amazing. And they transplanted almost their entire list. And it’s primarily because of these patients who overdose on Fentanyl. And interestingly, it’s not because they’re brain dead, but they’re not functional. And so they do this new technique called DCD, where they take them off support and wait for a period of time, and there’s a specific protocol. And then if they succumb to not being on support, then they immediately harvest the organs for whatever they can.
In all the stories I have done, I have not heard that described like that.
Jantz: Well, yes, about Barostim, obviously, I remember one of my patients when I was doing heart transplantation was an artist. And he had a cartoon he made which showed a highway and a stick of tree hanging out over the highway with a vulture on it. And that’s the way he felt. He felt like he was a vulture waiting for an automobile accident because somebody has to die for you to get heart transplant. So it is sad that people die from Fentanyl, but the only good thing about it is they become a source of donors that actually helps people that couldn’t previously get heart transplant.
That’s amazing. What am I missing? What else would you say about be Barostim or CCM?
Jantz: And that’s the one that stimulates the carotid sinus, and then the CCM is the one that stimulates the heart. So the- the only thing about- so when one tries to decide between the two, it’s hard because there’s no head trial. So I don’t know which one is better really, but they have each one that has her spot. And so the- the CCM probably is better in a little higher ejection fractions and they’re actually studying it in diastolic dysfunction, but it requires it to be charged once a month- once a week. It’s more hardware inside your vessels across the tricuspid valve. And so that’s, I guess, it’s disadvantage. The Barostim has the advantage of being no low end on the ejection fraction, extravascular and doesn’t need to be restart- it doesn’t need to be recharged. And so you set it in and forget it. There’s some commercial that says that about something.
END OF INTERVIEW
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