Dr. Amin Yehya discusses updates in heart failure therapies and clinical trial results from the 2026 European Society of Cardiology.
Good morning everyone and thanks for joining us and sorry for the technical difficulties and I'll talk about uh latest updates from uh European side of cardiology, some of the clinical trials we're doing here at Centera as well. So much closure. So this is we're gonna start, uh, the ESC was, uh, last month in Munich and uh I was there and it was a big, uh, made a big headlines knowing that, uh, the newest, uh, updates in the guidelines, European guidelines, um, these are the classifications of heart failure. We have still stage A, B, C, and D. Um, the newest thing is that we're not having any more heart failure with mildly reduced ejection fraction. So what we're having is preserved and reduced ejection fraction. If ejection fractions less than 50%, they are reduced ejection fraction. If it's more than 50%, it is preserved ejection fraction. So we're not having this mid mildly reduced or mid-range ejection fraction anymore. And stage B is technically for those in the room and outside is that patients who have either structural abnormalities or elevated antipro BMP, but they have no symptoms of heart failure. Stage D patients with end-stage heart failure and stage A patients at risk. And this is uh also the newest uh nomenclature changes for uh heart failure according to the European Society of Cardiology. So now we don't have what we call GDMT. Instead of GDMT we have what we call foundational medical therapy, and this is the pyramid that we're gonna talk about today a little bit. So the foundational medical therapy is what constitutes the four pillars, which include SGLT2 inhibitors, MRAs, ARB-RNE, and beta blockers. And everything in green is class 1 indication. Uh, in yellow, it is class 2A, which is the class 1 is the highest recommendation based upon, uh, randomized clinical trials. And class 2A basically has, um, it's favorable and, um, To use. So, again, as you can see here, we have foundational medical therapy, we have additional medical therapy, we're gonna talk about in a few, and then we have guideline directed interventional therapy. So they added, uh, basically, um, the MTers, uh, TAVRs and whatnot to be part of the guidelines, and you're gonna see where do they stand. This is a diagnostic approach for outpatient heart failure assessment. So if somebody comes in with signs or symptoms of heart failure, We start with the usual ECG, laboratory testing, a chest x-ray, and then we check the natriuretic peptides, and accordingly, based upon the age now, certification based on age, we can define whether patients have positive antipyro BMP or not. So the older we get, the higher level of antipyro BMP is expected, as you can see here. If the antiprobiate MP is elevated, then the patients, then you can do echocardiograms. So it's all of that is trying to minimize use of imaging and um basically prioritizing the resources in Europe. So you don't get echocardiogram directly. Here you know if the anti-proMP is elevated, then you can get an echocardiogram referred to a specialist. If the anti-proMP is low, but the clinical suspicion is still high, then you can get an echo. If the anti-proMP is low and suspicion is low, heart failure is unlikely. And as I mentioned, when you confirm heart failure, you go through reduced and preserved ejection fraction. We don't have mildly reduced. These are the main contributing factors for patients with reduced ejection fraction. We see many now more patients with delta cardiomyopathy. In the past, ischemic cardiomyopathy was the main leading cause of heart failure. Now we're seeing more non-ischemic cardiomyopathy. Heart disease, we see a lot of these in our patient community here infiltrative disease, familial cardiomyopathies, conduction abnormalities, dysrhythmias, toxic, which could be chemotherapy induced or drug abuse or alcohol abuse. So these are basically. The main causes of reduced ejection fraction. What about preserve ejection fraction? We're living in a day and time where there's obesity, sleep apnea, hypertension, and multiple other risk factors that will lead to the rise in the incidence of preserve ejection fraction. In the past it was mainly reduced. Now it's like more than actually half is preserved ejection fraction. Because we're having more and more patients are, you know, having the risk factors and living longer, so we're seeing more patients in this category. Again, main risk factors for that include, um, obesity, sleep apnea, diabetes, hypertension, uh, atrial fibrillation, um, among others. And kidney disease as well. So how do you approach, uh, assessment of the etiology of heart failure going back to the basics history exam, ECG, laboratory, and echocardiogram, uh, but the European side of cardiology, um, not everybody gets, uh, left heart catheterization. Uh, if somebody has pretest probability of, um, having obstructive coronary artery disease not high, it could be low or medium. You have to start with a CTA CT angio before going to the uh left heart catheterization. Also, if you have clinical suspicion of sarcoidosis, uh, you can do FTG PET, um, if you know somebody is worried about infiltrative diseases such as amyloid, among others, you can do cardiac MRI, um, also you can do uh PYP scan. Um, and, uh, biopsy, for example, somebody with myocarditis, and somebody with acute, uh, heart rate exacerbation. And I'm gonna also, since I mentioned acute, they're not using anymore the term acute heart failure exacerbation, they're using decompensated because patients where they think heart failure has been going on for a minute before they present, so it's not acute technically, it is decompensated heart failure. So we have a chronic heart failure and decompensated heart failure. There's no acute heart failure according to the newest guidelines. So what about the ischemic etiology as I mentioned, not everybody got that you have to have a, uh, because again going back to resources, risks and benefit of doing procedures, um, so if you're suspecting somebody with ischemic cardiomyopathy, sometimes, you know, uh. Uh, shortness of breath and dyspnea on exertion could be ischemia evaluate like an ischemia mimic. Uh, so think about it. You look at the risk factors for having obstructive disease, be it hypertension, diabetes, dyslipidemia, uh, whether you had peripheral arterial disease or not, and then you can order the diagnostic testing if you get an echocardiogram and they have motion abnormalities or evidence of some. Um, you know, some, uh, abnormalities on the echocardiogram, you can, you need to assess their, uh, coronary anatomy. Um, then you'd figure out if the obstruction in the, in the coronary artery disease is the etiology of the heart failure, or it could be just a bystander, because we have a lot of patients who have some CAD, but the degree of their heart failure is out of proportion of the um artery that is affected. So it could be a mixed ischemic and non-ischemic heart disease. Um, so I'm gonna share some of the recommendations, uh, for the, uh, European side of cardiology. Now it is class one. it's a new recommendation to counseling everybody on healthy life choices, weight reduction, um, smoking, alcohol. We do that on a daily basis, but it's a part of the guidelines now. Tell them don't do cocaine and amphetamines, um, so it's important to highlight. Uh, this is the new, which is I think it's important for us, uh, in the states, and I think it's gonna come over is that the GLP-1 receptor agonists are now class 2A. It's part of the guidelines. GLP-1s are, uh, people know them as kind of weight reducing, uh, medications, so they are part of the guidelines in Europe it's class 2A, um, for everybody who, um, have type 2 diabetes and additional risk factors, it is important to consider them. Um, also ACE ARBs and Arneys, uh, mainly ACE and ARB here in Europe, um, recommended for stage B heart failure with EF less than 40%, beta blocker if EF less than 50% with, uh, to reduce risk of heart failure, hospitalization of cardiovascular death. Epilione is recommended over spironolactone based on EFFIS trial, uh, for patients with an MI with EF less than 40%. Or history of heart or diabetes. Uh, also, part of the new recommendation, the foundational medical therapy should be initiated, ideally in the hospital. The four, pillars, and it has to be up titrated every 1 to 2 weeks. I don't know, and during the, uh, meeting, How, um, convenient or how possible it is to, uh, titrate, uh, therapy every two weeks is not, uh, because, uh, the challenges of getting patients to be seen and evaluated and getting their blood pressure checks and, uh, And laboratory testing, but what they recommend is having a titration of therapy every 1 to 2 weeks, checking their vital signs and also monitoring some of their blood testing. Um, the max tolerated doses recommended. What's new here is that in some patient populations, uh, if their ejection fraction is normalizes and it remains normal with normalization of their biomarkers and, and organ dysfunction, if it resolves, there is some class 2B recommendation that you can consider potentially, uh, taking them off the medications. Cause one thing is, uh, our patients always ask, when can I get off the medicine, get off the medicine? Uh, it's class 2B now made it to the guidelines in Europe. But it's for, for like I would not recommend doing it much, especially if our patients were sick before. There are multiple trials that have shown if patients with improved ejection fraction, take them off their medication, around 40, 50 to 60% of these patients, their ejection fraction were sensitive before. Um, again, um, ACE-ARB RNE are class 2B and preserved ejection fraction. And what I can talk with the CRT later on. Also, the revised, this is a new, uh, in the States, uh, MRAs are class 2B for heart failure and preserve ejection fraction. Now they are class 1 recommendation. For all heart failure, be it preserved or reduced. In the States, uh, we use the non-steroidal MRAs for heart failure and preserve ejection fraction based upon the Fine Art study which showed that using phenerone compared to placebo, there is significant improvement in cardiovascular outcomes and reduction in heart failure hospitalizations. But in Europe, uh, they added non-steroidal and non-steroidal MRAs, which are steroidal MRAs include eplerenone and spironolactone. And independent of what they are, everybody technically with heart failure, it's a class one indication to be on MRAs. Um, also, uh, you cannot get rid of, uh, digoxin. Digoxin resurfaced again, part of the guidelines. Now it went from Class 2B to Class 2A. So everybody with EF less than 40% here in the states we put patients in, uh, low EF with, uh, AFib, but now independent of atrial fibrillation, it is a class 2A, which is the highest level of evidence that digoxin has, uh, achieved in any of the guidelines. EF less than 40%. And symptomatic heart failure, uh, these patients could be placed on digoxin to reduce risk of heart failure hospitalization, and that's in addition to the foundational medical management. Verigua, which is Vercuvo based upon Victoria trial, it remains class 2B. And um CRT uh rather than RV pacing uh should be considered in patients with uh reduced ejection fraction regardless of their NYHA classification or QRS width who have indication for V pacing. For high degree AV block, it reduces risk of heart failure, hospitalization, or death. Again, um, part also updating the guidelines, uh, remote hemodynamics such as Cardiomems. We implant Cardiomems here and we use it to manage patients with heart failure to risk of heart, to reduce the risk of heart failure hospitalization. Now it went from Class 2B to Class 2A, which is the highest level of evidence it, uh, it has. Uh, Cardiomems have shown based upon, um, the CHAMPIN trial and multiple other trials and guide HF to reduce risk of heart failure hospitalizations. In patients who have been hospitalized in a year or elevated antipro BMP and symptomatic from heart failure. Uh, as I mentioned, semaglutide or trazipetide, uh, have should be considered in patients with preserved ejection fraction, EF more than 45%, and BMI greater than equal to 30% regardless of their diabetes to reduce the body weight and improve exercise capacity and quality of life. And this is based upon multiple trials, HF and other trials and select trials as well. So again, um. Semaglutide and trilipetide, they are now class 2A for our patients with obesity. So it's not just, uh, for weight loss, but again, they have cardiovascular benefits. And I'm doing, we're doing, uh, clinical trials here at Center. I'm going to share with you one of our trials. In Europe, again, it's class 2A. In the States, it, it does not make it to the guidelines yet. Uh, bariatric surgery, uh, is now also part of the guideline, it's class 2B. It has not been the guidelines before, which means if patients, uh, BMI of more than 35%, 35, uh, in spite being on medications for weight loss, patients, uh, BMI remains more than 35, these patients should be considered for bariatric surgery as well. And also new to the guidelines as well, we're looking at obstructive sleep apnea using ASV now to be considered. In the past they found that CPAP and ASV did not improve outcomes, actually can worsen outcomes in patients with heart failure. But in Europe they found they added ASV, which is adaptive seroventilation, to be part of the guidelines of Class 2B. Also important to assess anxiety, depression, frailty should be part of our evaluation as well. Um, also, part of the recommendation, cardiac rehab should be offered to all patients with heart failure. Uh, nowadays, I mean, one of the challenges in the states would be payment, uh, know if we can pay for preserved ejection fraction. Uh, the main, you know, just refresher for people, like cardiac rehab is approved for patients post MI, CABG, valvular disease, transplant, or heart for hospitalization. Uh, but it's not approved for patients with preserved ejection fractions, so now it's part of the guidelines in Europe, class one indication, and also the after cardiac rehab, the maintenance program is also recommended for patients with heart failure, class one. Um, also in patients with durable support. Uh, long term plan as well as recommended. Uh, it's always important to, um, counsel women in, you know, in their, um, their, um, fertility, like, you know, preconception about some medications, about the importance of contraception, especially if they have heart failure, do they, due to the increased risk of peripartum cardiomyopathy. Also, genetic testing is recommended because also it can help with counseling and, and determining the risk for the fetus if they're gonna have, um, the cardiomyopathy. We should switch away from non-selective beta blockers to metoprolol or bisoprolol, uh, close monitoring of the fetus, ACE-ARBs, RNEs, MRAs, ivabidine, SGLT2 inhibitors are not recommended due to pregnancy. Uh, due to risk of fetotoxicity or to agenicity, so we do not use these medications in pregnant women. And if somebody is gonna wants to get pregnant, you take them off these medications. Uh, indications for CRT now, uh, in Europe, I mean in the States as well, if you check QRS, if the QRS is more than 150 and you have left bundle branch block, it's class 1 indication for CRT non-left bundle branch block class 2A. And if it's QRS between 130 to 150 in a left bundle class 2A for CRT, it's class 2B for non-left bundle branch block, QRS less than 130, it is class 3. Uh, so this is diagnosing decompensated heart failure, um, getting physical exam, history, laboratory testing, and then you have first to rule out cardiogenic shock and pulmonary embolism. If you rule them out, you have clinical suspicion for decompensated heart failure, then you do echocardiogram, uh, and then basically treat accordingly. Again, as you can see here, uh, imagings are not like a, uh, knee jerk reflex. Everybody gets echo or anything. So here they have to go through different, uh, you know, small hoops to get that. Uh, so how do you manage it? Um, we have to rule out things that can kill the patients at the beginning called the CHAMP. It CHAMP is acute coronary syndrome, hypertensive emergency, arrhythmias, mechanical causes, PE infectious of tamponnade, and then patients are categorized into cardiogenic shock, which has, you can treat them with onotropes, vasopressors, or temporary mechanical support. If they have pulmonary edema, accordingly, you can diff TPA or thrombectomy, decompensated left sided heart failure, you can diuretic and GDMT in the right side, you have to optimize their fluid management. So identifying what is the cause of decompensation is important because it determines the clinical management for these patients. And these are the clinical phases that we have to address for patients. The most important thing is we need to assess, uh, stabilize, make them feel better, and then try to work on discharging them by optimizing their volume, status, and guideline directed medical therapy. So how do you assess congestion and decongestion before sending patients home? Multiple trials have shown around 50% of patients who come to the hospital for decompensated heart failure leave the hospital with the same weight. Or maybe even higher, so we don't do enough good job uh in getting volume off. So the, uh, ESC or side of cardiology looked at multiple criteria including clinical, laboratory and imaging. Clinical, there is the, a congestive score looking if they're asking patients if they have shortness of breath, uh, orthopnea PND, they have rails on exam, um, and, uh, if their score is 0, it's perfect, uh, and everyone gets like orthopnea 1, shortness of breath 1, And if they have exam per exam, they have like 1 acceptable 1 to 2, um, goal is to lose weight as well from diuresis and they're looking at their NYA classification laboratory testing, uh, what we're looking at the technically, uh, the delta change in antipro BMP by 30% or greater, or the antipro BMP is less than. 1500, but again we have chronic patients who run usually antiprogram P on a normal basis in 7,000 8000. So in these patient population what we look for, we look at the delta change of 30%, which is important, which is clinically significant uh recently published uh with a lot of colleagues. The nation position statement that's published in JAC Heart Failure on what is clinically meaningful for patients, and we discussed in our paper that antipro BMP again greater than 30% is what is meaningful for outcomes and for patients. Also, we can look at chest X-rays where we can see signs of congestion. The B lines also look at ventricular filling if you have an echocardiogram, IVC, look at the IVC if it's engorged or not, and you can do an ultrasound of the lungs and assess if uh the B lines and whatnot. This is the measure of congestion which I think is important. We were talking yesterday during rounds. So if somebody is diuretic naive, come into the hospital, you start with a 40 mg of IV furosemide, or if they are on a diuretic at home, you double that dose. In the states, uh, we use 2.5. In Europe they said double that dose, and then you have to check if they responded to diuretics through checking the pot urine sodium. At 2 hours should be more than 70 per liter or you can look at the urine output should be more than 100 mL per hour and if that's that's the case perfect keep doing what you're doing they're responding if not you double the diuretic or loop diuretic and or consider adding metolazone or um acetazolamide uh or even can add Diamox and you can check the spots urine uh urine output if they remain. Um, congested, you have to up titrate the loop diuretic and then eventually can consider aquaphoresis. Um, it's important also to, uh, uh, to trash patients for advanced heart failure, especially those patients with an OHA Class 3 and 4, despite being on GDMT and, uh, or foundational medical therapy in Europe now, and additional medical therapy and guideline, um, therapies. So, um, refer them to discuss advanced surgical options and RHA Class 2. Keep treating them and look at, I need help, uh, I need help, uh, it's kind of like a mnemonic for either and isotropes, sodium is low, ejection fraction is low, and organs function, um, hospitalizations for heart failure, liver enzymes elevated, hyponatremia among others. Uh, again, uh, if they have limited life expectancy and you don't think they're gonna do well after transplant, just consider palliative care and, um, treat them medically. This is a refresher for Intermax. What is Intermax, which is a way where we can assess the patient's. Um, clinical, uh, conditions and clinical status at the time of being evaluated. We have intermex 7s, from 1 to 71 is crash and burn. Patients had a cardiogenic shock, class intermex 2 patients sliding on inotropes, 3 stable on inotropes, 4 symptomatic at rest, not on inotropes, more than like 5 and 6 and 7, symptomatic heart failure. For, uh, intermex 1 and 2, these patients should need temporary mechanical circuitory support as a bridge either for transplant, durable VAD. Or palliative care. If the end organ did not improve, um, you can consider withdrawal of MCS and palliative care. And if the end organ got better but the heart function is still low, uh, these patients should go to transplant or a durable vet if they want. If the heart function and uh got better and then we're going to get better, these patients can wean MCS off. Uh, again, shock team is instrumental. So we have a shock team here. Um, they get calls from throughout the system and outside where we have, uh, uh, cardio heart failure cardiologist, uh, pulmonary critical paramedicine, and, uh, uh, surgeon, as well as bed tower and everybody, they come together, discuss the case and see if the patients would be qualified technically for temporary support or, um, in our facility. Uh, temporary mechanical support is now Class 2A. It is part of the guidelines now, uh, in Europe for patients with cardiogenic shock and STEMI with LV dysfunction with no hypoxic brain injury. Sometimes we get patients who had like rested for a long period of time. They had a lot of downtime, so we don't know their neuro status. Uh, so these patients with unknown neuro status, we do not usually recommend, uh, temporary mechanical circuitory support. Um, early consultation of CHF is important, but also in cryogenic shock patients, discontinuation of beta blockers or irabidine should be considered in select patients, and when the patients go into that or transplant, take, uh, look at the pathology of the heart. Uh, continuous ionotropes went from class 2B to class 2A. Now they are, you know, it's, we can put patients on continuous ionotropes as a bridge to decision or a bridge to transplant or palliative care. And durable MCS is class one. So what about management of uh coronary artery disease in patients with heart failure? It is new in the guidelines. Here, as you can see, if ejection fraction is reduced, which is less than 50%. If the patients have multi-vessel disease with EF of less than 35%, they should be referred to a multidisciplinary team to be evaluated for coronary artery bypass graft for CABG. If they have multi-vessel disease with EF less than 35%, these patients are definitely at higher risk. If their EF is, um, if they're not having multi-vessel. Disease and their EF is preserved. You do foundational medical therapy which is instrumental for both. You have to optimize patients on medical management with mainly beta blocker, make sure they're on good beta blocker. If the patients with preserved ejection fraction despite optimization of therapy. Continue to have angina, then you have to up titrate antianginal drugs, and these patients don't have multi vessel disease. Again, as you can see here, not everybody goes into surgery, not everybody goes to PCIs. They are very much prioritizing medical management. Go up on the antianginal, go up on medical therapy. If the, um, angina is, um, is still there despite optimization of therapy, then you consider heart team and consider for CABG or PCI. If, uh, the angina is gone, basically, you can still, um, you have to consider it, but you have to understand the increased risk in this patient population. What about measurement of mitral regurgitation? It is now class one, to have severe MR being treated, um, but you have to go as foundational medical management first, optimization if they need CRT, and if they remain symptomatic, despite all of that, you consider trans catheter edge to edge repair. Um, and if the patients with low ejection fraction and have advanced heart failure, these patients should be evaluated for advanced surgical options rather than just going to get into empty ears. Um, also, they talked about amyloidosis in the past. In the guidelines, they only had teemitus as a class one, for patients with amyloidosis. Now, teemitus and acromedis, which are stabilizers of the tetramer, which is the amyloid, uh, molecule. The, and are in class one indication. And, uh, we have the silencer, which is votisuran, um, uh, which is Ambutra is also class one indications for patients with amyloidosis. And this is the algorithm for diagnosing amyloid is to have suspicion of amyloidosis, you have to check, uh, the serum urine and urine, uh, immunofixation and light chains as well. If they were, uh, abnormal, then you think probably they have amyloidosis, you refer them to hematology. Uh, and if they're negative, uh, but you have suspicion of I'm lowered, you can get a PYP scan and look, uh, upon, uh, the PYP scan results and treat accordingly. So this is kind of a summary of uh what is the guidelines look like. Uh, and again, green is class 1, yellow class 2A, and I don't know, orange is class 2B. We have foundational medical therapy, uh, based upon the ejection fractions. Then you go to additional medical therapies. Again, um, diuretic class one, treat the iron, ivabidine class two. A, I, I can see based upon the ejection fractions, uh, varicegla class two B. As I mentioned, the new thing they added is a guideline directed interventional therapy, uh, ICDCRT, the SAVR or TAVI tier transplant valve. Ablation is class two. A in Europe for patients with heart failure and. A, And again sleep breathing disorders, uh, ASV. Additional management cardiac rehab is class one. So clinical trials that were also key uh late breaking trials in Europe, I wanna share with you, uh, one of them is uh for hypertrophic cardiomyopathy, Eficamptan used for non-obstructive HCM. Uh, HCM basically, um, hypertrophic cardiomyopathy, uh, patients. We treat patients with mevicamptin, which is myosin inhibitor, only if they're, um, obstructive. So non-obstructive CAD, uh, non-obstructive, I'm sorry, HCM, they looked at, uh, an Acacia trial. They randomized patients, uh, to efficamptin versus, uh, standard of care, and standard of care was just beta blocker, and they wanted to look at, uh, basically, um, quality of life, KCCQ, basically, and CPET and peak VO2. What they found with Efficampton, which is, um, in the Acacia trial, um, have, is the only drug that has shown, uh, improvement in quality of life and outcomes in, uh, this patient population. Again, there was no medications approved for this patient population other than beta blockers, but Efficampton in the Acacia trial have shown that, uh, in symptomatic patients with non-obstructive hypertrophic cardiomyopathy, uh, compared to placebo, uh, Efficampton was superior. Uh, it improved exercise capacity, health outcomes, symptoms, and antipro BMP as well. So it was well tolerated and majority of patients, uh, you know, because one of the side effects of these medications can lower the ejection fraction because it's a myosin inhibitors. Um, if EF dropped less than 50%, and most of these patients tolerated the highest dose, uh, the reduction less than 50% simply managed by down titration of medication. So everybody tolerated the medicines, and this is very promising because. Uh, it will get, uh, approval for this medications to be used in this, uh, patient population. Again, it's a great option for our patients. Uh, another trial, which also late breaking trial for amyloidosis patient, uh, which is, uh, eplotersin, uh, which is, uh, Guynuva, Uh, it, it's the cardio TTR transform phase 3 trial, which is the largest amyloidosis trial, uh, ever, uh, that's been used, uh, that's been done. I'm sorry, and they randomized patient 1 to 1, uh, to lonarcin, which is Wainua versus placebo, and these patients with TTR, uh, amyloidosis, um, again, these patients Wainua is, uh. Silencer silencers prevent the production of the tetramer, the molecule of the amyloidosis that we know of that can be, you know, deposited when it goes from tetramer to uh to single unit to oligomer. To monomers, I'm sorry. And then, um, so, so silencer prevent the production, stabilizers such as uh tefematis and rematis can stabilize this tetramer. So when they looked at preventing production of this molecule versus the standard of care, uh, showed any difference in outcomes, uh, the primary outcome was cardiovascular death and heart failure hospitalizations, and secondary outcome were change in 6 minute walk, KCCQ, cardiovascular events, and all cause of mortality. Basically, uh, it's kind of was watched this trial in the sense that there was no difference in outcomes, as you can see here, there's a cross of the line of unity here, um, the confidence interval. Uh, across, so there is no difference in cardiovascular death or recurrent cardiovascular events in this trial, which makes us pause a little bit and, uh, think about other silencers and what's the difference between this silencer and other silencers. So cardio TTR transform was the largest, as I mentioned, trial to date, uh, looking at, uh, eplantercin versus placebo in contemporary management. Um, combining the silencer with the stabilizer was not associated with incremental benefit and as a monotherapy was not only significant, uh, side effect, uh, significant effects on the primary and multiple secondary end points, so it's kind of like a wash. Uh, this is a trial which uh also got a lot of, uh, You know, attention single AF trial, uh, which looking at patients with, uh, atrial fibrillation who have CHADVAS score of 1 for male or 2 for female, and some, uh, physicians here, uh, different practices use, uh, manage differently among, uh, electrophysiologists even within our practice. If their, um, CHADVAS score is 1 or for a male or 2 for female, some of them just tell them take aspirin. But so they looked at it, uh. Um, trial in, uh, Asia basically and they looked at this patient population randomizing patients with CHADVAS one for male and two for female, um, getting oral anticoagulants versus just aspirin and standard of care, um, and they looked if there's any difference in the primary input of stroke, embolism, major bleeding, cardiovascular death. So what it showed actually patients who received DA, uh, where they had these JADVAS scores, they had significantly lower incidence of stroke, systolic systemic embolism, and major bleeding, which is pretty significant. Because this could be, um, you know, practice changing. So, uh, it's the first randomized controlled trial showing that DOAC therapy. Lowers the risk of composite of stroke, systemic embolism, or major bleeding at 24 month. That, rather than no anticoagulation in patients with intermediate risk. So, again, we recommend, uh, based upon that, uh, to these patients to be, um, uh, you know, sorted. And that will be incident. Yes. The one Uh, so the incident 1.5 versus 0.1, 0.5, the absolute difference was 1% changes. Confidence interval is, uh, you know, I can see it here. The hazard ratio is 0.028. Um, so it's closed, I mean, but the benefit is there, uh, definitely that. Benefit is More, but it's not as like it's not prominent as it is. That means to hear from our electrophysiology team as well and anybody here about that too. So final takeaway from this trial is that in single AF, uh, patients with atrial fibrillation, intermediate risk for stroke, DA therapy was better than no anticoagulation. And again, as you, you see here, we're worried about, you know, balancing everything in life. We're balancing the risks and benefit, risk of being on anticoagulation, risk of bleeding, but also the benefit potentially be lower risk of uh stroke. Um, and it seems that when they combined this composite endpoint of bleeding, uh, stroke, and systemic embolization, the benefit was still there. I just wanna talk, uh, last couple of minutes about a couple of clinical trials that they're doing at Centera. Um, I think one of, uh, my colleagues when, when they're gonna give their talks they can talk about their other trials. What they're doing, um, is that, um, these are the trials we're doing now, more, uh, clinical trials, uh, as you all know, the research have, uh, been reorganized and since that now we have directorships. Uh, for heart failure, uh, interventional EP, um, in heart failure, we take pride now, um, doing more and more inclusive studies. We're doing, uh, more amyloidosis and HCM trials, uh, pulmonary hypertension and preserved, uh, doing mainly preserved and, uh, reduced CF and cardio metabolic. Doctor Benza, uh, and Doctor Soy are doing more, uh, preserve, uh, uh, pulmonary hypertension. And Doctor Tusak is doing uh our amyloid and also we're bringing more uh HCM trials. As you can see here, we're doing more trials, which is very important and um we got uh. For one of the trials that is PI on, I got an award by the American Heart Association which, uh, for our site, uh, to be an award for site-based research study for our quality of data and improve and, uh, recruitment and Hermes trial. We are top 3rd highest in enrolling site in, uh, North America. So I'm gonna talk for everybody online, I appreciate you all significant help and recruitment for these trials. uh HF Polaris. So HF Polaris is studying a molecule called xenagemptide, which as you can see here looks like a heel. It is a combined molecule of semaglutide, which you all know as Wagovi or Ozempic, and additional molecule called emylin. And they're combined together by this linker and this acetylation which keeps the molecule stable. So, uh, it is sponsored by Novo Nordisk and and patients with HF Polaris. Uh, these patients have to be male or females more than 18 years old and BMI more than 30 and a New York Heart Association 2 to 4 with ejection fraction more than 40 documented by echo, MRI or CT. Again, they have to be heart failure in the sense mildly reduced or preserved EF, and they have to have one of the following either they have heart failure decompensation within a year, or their GFR is less than 60, or urine creatinine to albumin ratio more than 30, and they have to have elevated antipro BMP, which is not significant much as you can see here, 100 of their BMI more than 35 or 150. So again, these patients um will be randomized 1 to 1 to receiving the molecule which is xenagli xenagamtide versus placebo um and why it's important, uh, just wanna go also a little bit about some excellent criteria is similar to many other studies, uh, what we're looking in this study is that looking at card solid cardiovascular outcomes, which means cardiovascular death and heart failure hospitalization. So, uh, if you're out there, uh, and you have patients with EF more than 40, uh, BMI more than 30, hospitalized in the year, or GFR less than 60, or urine average creatinine ratio more than 30 with elevated, uh, anti-pro BMP. Please, please, please, uh, text me, call me, email me, chat, message me, uh, about trying to enroll these patients in this clinical trial. Again, it's not just about the weight loss that they can get, but it is about the heart failure, uh, benefit, which is cardiovascular death and hospitalization. Uh, the other trial by Novo, it's called Ambience Trial, and this is a very interesting trial for the Gem cards interventional cardiology group and vascular surgery. Why? Because it's gonna recruit different patient population, uh, patients age 45, BMI more than 27, which is. Very, uh, much a large patient population, but these patients to qualify to be in this ambience trial, they should have history of prior MI or peripheral arterial disease or history of stroke. And this MRI should be in the past 2 years, uh, or they could be hospitalized for heart failure in 2 years, or their GFR is less than 60 or have history of Afib. So we have a lot of, uh, all these risk factors inclusion criteria. They, uh, we see it a lot in our patient population. So I ask if you or anyone knows about these patients with BMI more than 27 with prior MI or peripheral artery disease or prior history of stroke. Again, uh, call me, text me, chat, message me. Uh, so, to enroll these patients in this trial were Xena Gemtide, uh, versus placebo. Excluding criteria if they have a stroke MI within 30 days, they have, uh, they need revascularization for carotid disease, MIA class 4, if they are on GLP-1 or GIP and they have pancreatitis in the past, um, 180 days, 6 months, and, Their active or unstable depression, uh, with poorly controlled diabetes or type one diabetics. Other trial I wanna talk to you about is called Redefine HF trial, which is in preserved ejection fraction. If you have somebody with preserved ejection fraction or mildly reduced, you have more than 40% who are not on MRA. These patients, uh, could be, who are hospitalized within 30 days for heart failure. Uh, with elevated antipro BMP, um, who received IV diuretic, we wanna, uh, see if these patients could qualify for a redefined trial, which is randomizing patients to phenerenone, which is, uh, Kinia versus placebo, and we're looking at total cardiovascular, um, outcome, which is hospitalization, urgent visit, or CV death, um, so again, pretty simple rules if they're not on MRA for 7 days, hospitalized for heart failure with preserved ejection fraction. Please, please, please let us know, um, and these are the major exclusion criteria available to you, so. One other uh trial we're doing too, uh, for, um, it's called confirmation trial, and this is also be great benefit for our patients because all of these patients who are who have hospitalized for heart failure be preserved or reduced ejection fraction and they're not on MRA or SGLT2 inhibitors, these patients will be randomized to SGLT2 and placebo versus SGLT2. And phenerone. So why it's important because the patient will get SGLT2 medications for free anyway, uh, so independent, uh, if, you know, if somebody is not able to afford SGLT2 medications, these patients can get SGLT2 independent of, um, what they will be getting placebo or phenerone or Corinia. And again, we're looking at major cardiovascular events, be it heart failure hospitalization. And cardiovascular death and also looking at uh KCCQ, which is um basically Kansas City cardiomyopathy questionnaire about quality of life for these patients. So again, if you have any of these patients with elevated antipro BMP with hospitalization in 30 days, reduced preserved, not on MRA, not on SGLT2, they could be randomized and get SGLT2 for free, and uh they can get benefit from being on phenerone again this is confirmation HF trial. On that, um, I would, uh, this is kinda end of, uh, study, the, the talk today. If you have any questions, please, um, let me know.
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