Dr. J. Thomas Heywood presents data on newly approved treatments for heart failure patients with preserved and reduced ejection fraction.
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Good morning and welcome everybody back to the second day of our eighth annual clinical advances in heart failure and arrhythmia is conference. We're so grateful that you're here and um appreciate you being here yesterday and hope that you got a lot out of yesterday's sessions. We have two great sessions today as well with a number of excellent faculty um that I think you're going to enjoy very much. Thank you for attending and we'll go ahead and jump right into session three. Our first session of the morning, our first speaker is Dr Tom Haywood. Dr Heywood finished. It was fellowship trained in uh cardiovascular disease and specializes in treating patients with congestive heart failure and those with advanced heart failure. DR Heywood joined Scripts clinic in 2000 and five to serve as the director of the heart failure recovery and research program and the division of cardiology here at scripts. In addition to his clinical practice, he conducts research on heart failure, including renal dysfunction and heart failure, implanted heart failure monitors and efforts to improve outcomes for patients. In 2012 he became the medical director of the L VAD program, which implants small pumps in those with in stage heart failure. He supervises the delivery of heart failure services for all five scripts hospitals. In addition, he's co director for the pulmonary hypertension clinic. As most of you know, tom is internationally recognized, an internationally recognized expert in heart failure and has authored more than 80 publications and lectured throughout the world on state of the Art cardiomyopathy treatment. In 2011 he published a book with john Burnett of the Mayo Clinic entitled the cardio renal syndrome. And from prior to joining scripts from 1992 to 2005, Dr Heywood directed the prestigious cardiomyopathy and cardiac transplant services at the Loma linda International Heart Institute in Loma linda, California. Please join me in welcoming dr Heywood who is going to be speaking to us about the whirlwind changes in heart failure and what you need to know for your patients. Dr Heywood, thanks john very much for your kind introduction. Well, this is gonna be a whirlwind. So let's get started. Uh These are my disclosures. Um but really, I I want to just give my conclusion now. This is really a golden age for our heart failure patients. We have new therapies that are making huge differences. I really can't overestimate or overstate how important these changes are and all of us have to be aware of them. So our patients with reduced ef The drug of choice is now so Cupertino val sardine or in Sesto, an SDLT two inhibitor. We are using human dynamic monitors and L VADs for selected patients. For patients with Hef path, preserve the f. We used to have not much therapy but we can use the cooper trove. I'll start in selected patients. I'll talk about that. The S. G. LT two inhibitors work there and we're recognizing that amyloid heart disease is more of an issue With these patients as well. So lots going on to talk about in our 20 minutes. So uh now seven years ago the paradigm trial came out. This was this combination of al certain and so cooper trill cooper till is a never listen inhibitor. What knepper listen does is a block an enzyme box knepper listen, which breaks down BMP. And when you block the enzyme then you get more visibility ation so it lowers after load, lowers blood pressure, reduces sympathetic tone and causes a natural resources. Diaries Is what you need to know as a clinician. Is that a limiting factor with these agents is blood pressure. So one major reason I think patients can take this drug is because of low blood pressure. Because of that. We did a trial with half dose c cooper trove al sardine and showed that that works to in selected patients. Obviously it's not the preferred dose, but if you can only use half dose that appears to work as well. And then there's our old friend val Certain which blocks uh angiotensin two receptor and lowers blood pressure as well. So that's why you have this kind of double whammy. But you have to have val certain with this because if you didn't um angiotensin two levels would go up if you just use uh cooper Trow by itself. So the study met its primary endpoint reduced heart failure, hospitalizations and death by uh CVS cv death by 20%. But it was also a clinical trial, home run. Something that rarely happens where all cause mortality was reduced by 16%. So patients often don't care why they die of that, what they die of, they just don't want to die. And so reducing all cause mortality is really quite rare and really very important. There are cases where you would not use the Cupertino val sergeant. These would be any pregnancy where you can't use any wrasse blocker. Very important, any history of anti oedema, you can't use it. So if they've ever had enjoyed um at all, you can't use it current Ace does. So if you wouldn't give this with lights in april, there would be no reason to do that. But you need to stop aces for 36 hours before you stop start. This drug hypertension is a major reason. So we don't use it when the blood pressure is typically below 90. Although sometimes I'll push that a little bit in selected patients and then patients with severe hepatic impairment. You can't use it in dialysis patients either. So what about patients with acute heart failure patients that come into the hospital isn't useful there. And that was the pioneer trial that was published several years ago now. And the key findings for that trial was that if you started C cooper Travel Sergeant in patients with low ejection fractions in the hospital, you reduced Readmissions by eight weeks by about 40%. You reduce them from about 13.8 to 8%. So if you want to reduce readmissions for heart failure in the hospital you'll put patients on C. Cooper Travel Sergeant. Now It's important that patients may come in with an a. So you have to stop the ace for 36 hours before you would start this. And the hospital is a prime place to start the drug because patients are fluid overloaded and patients tolerate this drug better when their volume overloaded rather than their dry. And then finally uh last year, uh or two years ago now we did the trial looking at patients with normal ejection fraction and it didn't quite make statistically significant. So heart failure. Hospitalization was reduced by 15% but it didn't meet its primary endpoint. Unfortunately, I think the power the trial was slightly underpowered. If seven more people had had an endpoint in the SaCU Patrol group, it would have been positive, but be that as it may, it didn't quite meet statistical significance. But there were important subgroups, for example, in women, the drug was highly effective. So and also patients with E. S. That were somewhat reduced but not, but not absolutely normal. So people with CFS less than 57% really benefited. Also, patients with new onset heart failure tended tended to benefit. So because of this and looking at data from the other trial, the FDA actually voted to approve c cooper travel certain for half pep in selected patients. So there was this 22% reduction in uh with an Ef less than 50 57%. 27% reduction in women Were expressed have started within 30 days. So we're using this agent in people with e. s. uh so called mid range reduced for mid ref where the F. Is say 45 50 for those patients, 55% not the patients with the f 80% or so, especially if they have higher blood pressures, especially if they're women, especially if they've been recently hospitalized. So this this drug does have a role some role in selected patients now. And and the guidelines recommend that it be the drug of choice in lo E. F. That even if patients are quote stable on an ace inhibitor an A. R. B. We should consider changing them. In fact, in our Heart failure order set for the hospital we've made. So Cooper 12 al certain are preferred agent because we think it's so important that people leave the hospital on it to try to avoid readmissions if we can. The other class of drugs that have been very important. And you heard about these yesterday with Dr Einhorn is the S. G. L. T. Two inhibitors and these work, glucose is such a small molecule, it's filtered in the glamorous realists and gets into the tube you'll and if it wasn't re absorbed you'd spill all your glucose and you you know, you'd starve to death. But this agent blocks some of that glucose reabsorption. And so you spilled locus in your urine. And patients can lose Uh as much as 300 calories a day from this and also they lose volume. It's an osmotic diuretic may also have other effects that we're not aware of. But it does have these volume uh yeah affecting results. So what were the outcomes this our cardiovascular outcome? This is this is actually from the Emperor Greg trial. You can see that it met its end point and again it reduced debt by any cause in patients these are patients with um cardiovascular disease and diabetes. And significantly it really reduced heart failure hospitalizations which was an unexpected finding. So these drugs have been evaluated for heart failure and looking at real outcomes in heart failure. You can see when you add the drug, G. F. R. Goes down a little bit but over time it actually improves so that these agents, remarkably In patients with heart failure reduce the need for dialysis, renal transplant or profound drop in G. fr by 50%. So one of the major problems that heart failure patients have is worsening renal function over time. And if we can prevent that decline. Uh this is very important in keeping people alive. So this is a real benefit to patients long term. And again we're using these agents now in patients without diabetes and we're finding that they're an okay drug for diabetes but they're really an important is drug and cardiovascular disease. Third agent that we're using or device is called the cardio mum's. This is a small chip, it's about the size of a paper clip that we put in the pulmonary artery and it measures the pressure in the pulmonary artery. This is really a clever device in that it doesn't need a battery. We send a radio wave through the body on a special device that the patient lays on and it sends back there pulmonary artery pressures to us that we can follow over time. And we're able to manage their medications with this device. So you can see that this is the champion trial where we put this device in during the 1st 50 days of putting this. Our first six months of putting this in half of the patients had their pressures monitored and the other half didn't. And then after six months, everyone did. In the first six months, we were able to reduce heart failure, hospitalizations by 30% which was very significant. After six months everybody was monitored and we were able to reduce um Heart failure admissions by 38 number needed to treat only four. So currently this is approved for people who have New York Heart Association Class three Heart failure and have been hospitalist within the last year. But right now we're doing the guide trial and uh, this is the largest team of dynamic trial that was ever done. Mortality is its endpoint. It's the most inclusive trial where you were studying all ejection fractions and it doesn't require hospitalization if the BNP is elevated. So, uh right now we finished the randomized portion of this trial. We have um, We've enrolled 1000 patients and we're waiting and we will probably hear this month what the result of that was. We're continuing this trial in patients who are class three, either were hospitalized or had a BNP elevated. And what we want to learn from that portion of the trial is, is an elevated BNP sufficient to put in a cardio memes. In other words, if somebody has a high BNP, we know they have increased mortality. So what, that would be good to put a cardio in before they were ever hospitalized. The reason I'm so excited about this trial is we've never had this model where we used thermodynamics to guide therapy when patients are in the hospital. We use human dynamics all the time with the swan Ganz catheter, but we don't use them for outpatients and we guess about what their volume status is. We might see them every two or three months. We tell them to weigh themselves and we know that patients don't always weigh themselves. And even when they weigh themselves, they don't call us when their weight goes up. But with the cardio memes device in, we can, we can follow their volume status very closely. We can look at their um Pressures and lower their pulmonary artery pressures. Over time we see many patients totally normalized. We just completed a study of 1200 patients. And in that study over two years, 59 of the patients were never admitted to the hospital again with congestive heart failure. So this works very well. If the if the guide studies positive then will mean that many more patients will get this device and it will become a standard of therapy for treating heart failure. And we should know that very shortly. So we have this new paradigm for heart failure management. In just six short years ago, the paradigm was for low ef we'd use an ace or an A. R. B. A. Beta blocker, diuretic spironolactone. And we could use cardamom pods in half to half. It was basically diuretics control blood pressure and cardamom is to try to lower heart failure, hospitalizations. But we didn't really have any therapy that reduced mortality for half bath 2021. Things are very different for reduced DF heart failure. So cooper val certain is preferred. We can still use aces ray RBS but cooper Travel Certain is preferred. We continue to use beta blockers. We use S. G. LT two inhibitors as much as we can in patients and patients with profound renal dysfunction. We can't use them. But if we want to prevent profound renal function this function then you should use these agents and they can be used with or without diabetes. We use diuretics but we're using diuretics much less often in this disease because patients don't need them because both see cooper Travel certain and S. GLT two inhibitors tend to uh cause volume loss. In fact volume loss can be so significant that I tell people to drink more water and often go off their low sodium diet, which they really love. We continue to use spironolactone and we use cardio memes. We're going to find out if cardio memes reduces mortality. If it does then it will go up further in this list and more and more people will get cardio members monitoring big changes in half path. We're using c cooper to val certain and selected patients. Mhm. Most patients would would be candidates for an SDLT two inhibitor. We use diuretics to maintain volume spironolactone. We use instead of potassium supplementation as we can patients with acceptable renal function. In one trial, in the United States there was an improvement was thrown lactose so we tend to use this and then cardio memes as well. Finally, I'm going to end on amyloid. This is treatment that's changing very quickly. Emily Lloyd heart disease is really much more common than we thought and is usually not recognized. We suspect it when we see a very thick heart, low voltage on the E. K. G but not always low voltage and the heart can be less thick than you think. But it has a typical appearance. There's two major types. There's al amyloid which is light chain disease and Wild type, which is seen usually in elderly men much more commonly, but it can be seen in women. There's also a familiar form found in african americans. Why this is so important is because the diagnosis and more importantly, there's treatment Now if you suspect amyloid, order Captain Lambda Light chains and protein electrophoresis. If these are normal, then order a technician pyro phosphates can, you know, a bone scan and this is what a positive bone scan looks like an amyloid. You see the heart looks tremendously black and that's it. We don't have to buy a biopsy. These patients most often if the light changes are abnormal, you have to refer them to hematology because they have probably some form of multiple myeloma and this is a very serious disease. But again very treatable in the hands of a human Ecologist. Uh, so most amyloid is Wild Type. They have a positive P. Y. P. Again, Wild Type has a more benign course. Um, and we have treatment now which is to feminists which was actually developed at scripts. And this actually showed all cause mortality was reduced by treating Wild Type. Uh, amyloid with two feminist. So it's very important to make this diagnosis and we make a diagnosis of amyloid literally every week in the cardio myopathy program. Think amyloid often in men, especially if they have a history of carpal tunnel disease or spinal stenosis is a tip off as well. But the echo, it will say, infiltrated disease. So some final notes. Both the cooper val certain and STL T two inhibitors can reduce volume loss, which is often a good thing. If you see the blood pressure go down, you may need to reduce or even eliminate the diuretics as you up titrate the med. The diuretic is the disposable medication in the heart failure management. So you can reduce these. And as I say, I often have patients on no diuretics anymore. And in fact have them drink more water, even actually have them eat a little bit more salt to maintain their blood pressure. You can use up tight super trove. Al certain as you can. But sometimes I just have them on half a pill, twice a day. Blood pressure is often a limiting factor. Eliminate other hypertensive and we've used half dose. So really very exciting times for heart failure. Patients are thriving with these new medications. Uh There is some titillation with the sick over drove al certain but it's really worth it. And the S. G. L. T. Two inhibitors are coming on strong and we'll hear about cardio members of mortality this month. So please come back next year for more exciting news. Thanks very much. Thank you Tom. Um Tom I received a message that we do have some questions and we've got time I've left over in your time slot. Thank you very much for that awesome lecture. I learned a lot and took notes over here so I'm excited about that. So let's go and take our first question. It's a two part question is fluid restricts. Excuse me is fluid restrictions still recommended and be compensated heart failure. And if so does taking an S. G. L. T. Two and drug which generally requires high fluid volumes to prevent dehydration. Play a factor in that recommendation. So we've we've done fluid restriction over the years. It's kind of been right recommended over time. Thought to be a good idea but there's really no evidence that it's valuable. So for most patients I do not fluid restrict them. I do fluid restrict patients who drink excessive amounts of water and we know that because they become hyponatremia. So people are hyponatremia of sodium of below 1 31 below 1 30. I do tend to fluid restrict those patients. But for the most part I don't fluid restrict my patients, you know, there's enough to do in heart failure. As I tell patients I want heart failure to be their hobby and not the, not the center of their life. And so they need to do some things. But if something is not proven, I tend not to push it. So we don't push fluid restriction very, we certainly don't do it for everybody. We certainly almost no fluid restrict nobody. Ah you know, if somebody's massively fluid overloaded and then the hospital, we might do it for a short time. Uh in terms of salt restriction. Again, we don't have good evidence that salt restriction plays a role. Now, we would focus more on salt restriction in the past when we used if I have to use a lot of diuretics and patients and we tend to sodium restrict them. But as with these new agents which which both caused both water and salt excretion as a diuretic goes, goes, goes down. I think the need for sodium restriction goes down as well. Again this is more in my opinion than has been proven. But as I said, there's really very little evidence that sodium restriction makes much difference anyway. So I've actually had patients stop their sodium restrictions because I need their blood pressure to be higher. So I can use the Cupertino val certain and S. G. L. T two inhibitor. And I have some very happy patients who can eat a more normal diet. You can imagine if suddenly after five years you get to have some mexican food again, it's uh can be life changing. Yeah. Okay. And tom the actual second question was um what selection criteria do you employ for making a decision regarding the use of interest? Oh, in Hedgpeth patients. Yeah, that's a great question. So again, the The data seems to indicate that patients with EFF less than 57%. Uh That was the cut off in the in the paragon trial where there was benefits. So uh and also uh women tend to have the genotype where they tend to benefit from uh cooper 12 al certain. Uh Also I have to have enough blood pressure. So The perfect person would be an f of 50 A woman and blood pressure of 120 and 30. That'd be a perfect person, I think to consider for c cooper koval. Certain the person I definitely would not use it in is somebody with an eF of 80%. And there are people with half past that have these hyper dynamic ventricles. They often don't even tolerate an ace inhibitor. And so cooper travel certain would be a disaster for those patients. So I certainly don't have as much experience with uh this agent in the in the heft of patients because um this has this recommendation has just come out but I've certainly used it in in 20 or 30 patients so far and I think too good result. The other thing I would look for is an elevated BNP BNP over 1000 as a marker for bad prognosis. And see cooper travelstart intends to lower that if you get the BNP below 1000 that's an indicator that you're really benefiting the patient. So those are the kind of patients uh that I would start uh trial of super travel started again if the blood pressure is a little marginal or if you're not sure, just start half dose, Half dose and up titrate further. Always check labs after you start the Cooper Jovel started after a week or two because blood pressure can go down And you can have some sometimes some renal dysfunction, mild renal dysfunction shouldn't dissuade you. If the credit goes from 1.2 to 1.4, that's fine. Again, always carefully assess volume status. If you any chance you have to reduce diuretics is probably a good thing. Diuretics were indispensable in the past and they will probably always have a place in heart failure but their role is less than it was. And if we can I think patients complain more about diuretic than any agent that I have to give them an heart failure. You know uh they complain about peeing all the time. I said well you know your fluid overloaded. You need to be a lot and but they really hate it. They feel like it interferes with their life. And again I want I want this disease to be their hobby. I don't want it to be the center of their life. And so if I can do things that mm. You know they take a couple of pills a day and then they go about the day without much problem. That that's that's my preference. Well tom we have about three minutes left. There's one more question just to give you the time frame there. The question is if the pipe is positive but it is just over the threshold for confirmation. Do you treat or confirm with biopsy? And how often do you biopsy? Yeah. So that's a great question. Um if you know if I'm not sure. So this amyloid things continuum. And you know you have mild amyloid, moderate amyloid and severe amyloid and a severe amyloid has a very positive P. Y. P. Scan. And the mild amyloid can be just over. So I look at the scan myself and I get dr Mohan to look at it with me because he's our local expert and we think well that that does look positive and we're not sure. I look at the echo again to see if it has the if the myocardial structure looks like amyloid. I look at the history, remember the history and you know do they have the carpal tunnel and other factors? Uh But I have a low threshold for biopsy thing. Uh And the reason being if they have wild type amyloid Their life is going to be changed by being on two families. Their their life expectancy will go up. Their quality of life goes up. I didn't show those slides but their quality of life goes up almost immediately. And the major principle of amyloid is that the sooner you treat it the better the patient does. Because these drugs tend to stabilize them where they are rather than make them better. So if I'm if they might have amyloid, I will biopsy them. Biopsies are pretty benign in big thick amyloid type hearts I've never had, I'm gonna knock on wood now. I've never heard anyone with the biopsy of or amyloid heart disease. So I do biopsy people. I just don't have to biopsy them as much as I used to. But I don't want to deny them really a life saving therapy if they might have early amyloid and I can keep them at early stage amyloid for the rest of their life. I think it's important to do. These are great, great questions. I'm glad I had a chance to answer them now. Great, well thank you Tom and there are more questions but we can save them for the panel so we can stay on time. I think I really appreciate um all that you taught us and like I said, I've got running notes here. So it helped me a lot. Thank you
