Podcast appearances and mentions of stefan anker

Mamas Mamas, Stefan Anker, and Volker Rudolph talk about their studies of MitraClip for functional MR in patients with heart failure.

#295 – Autotelefon-Autorätsel: Welches "tolle" kleines Auto mag das wohl sein? Es wurde als Limousine, Kombi, Coupé und Fastback gebaut, verkaufte sich in acht Jahren rund 2,7 Mio. mal und war das erste Auto von Stefan Anker. – Ja, heute zählt die gesuchte Marke zum Stellantis-Konzern und über die dortige Unruhe müssen wir natürlich sprechen. Ebenso im Programm: Das in Miami enthüllte Konzeptauto Type 00 von Jaguar und der Ineos Grenadier vor der eigenen Haustür. // Autotelefon – Der Podcast über Autos. // Jetzt abonnieren! Wir freuen uns über Bewertungen und Rezensionen! Besucht gerne unsere neue Website https://autotelefon-podcast.de

With Jozine ter Maaten, University Medical Center Groningen - The Netherlands, Antonio Cannata, King's College London - UK, Mateusz Sokolski, Wroclaw Medical University - Poland, Henrike Arfsten, Medical University of Vienna - Austria, Stefan Anker, Charité University Hospital Berlin - Germany, Muthiuh Vaduganathan, Brigham and Women's hospital, Harvard Medical School Boston - USA, and Kengo Kusano, National Cerebral and Cardiovascular Center Hospital, Osaka, Japan. In this multivoice podcast from the ESC Congress 2024, the main results of three randomized controlled clinical trials (FINEARTS-HF, RESHAPE-HF2, and CRABL-HF) are discussed.  Links to the papers:  FINEARTS-HF RESHAPE-HF2    This 2024 HFA CardioTalk podcast serie is supported by Novartis in the form of an educational grant. The discussion has not been influenced in any way by its sponsor. 

CME credits: 0.25 Valid until: 01-12-2024 Claim your CME credit at https://reachmd.com/programs/cme/addressing-issues-of-cv-mortality-in-clinical-trials-with-iv-iron-are-we-still-getting-a-medical-benefit/15333/ Iron deficiency is a common heart failure comorbidity with a negative impact on patients' quality of life and mortality. Recent world events may have influenced clinical trial outcomes with IV iron in heart failure, and secondary analysis has become commonplace. Are the findings still clinically relevant, and are we still getting a clinical benefit? Join Drs. Stefan Anker, Piotr Ponikowski, and John Cleland as they differentiate the design of IV iron trials and break down the relevance of key clinical endpoints. Are we still asking the right questions? =

CME credits: 0.25 Valid until: 03-11-2024 Claim your CME credit at https://reachmd.com/programs/cme/clinical-implications-of-the-evidence-from-iv-iron-trials-in-heart-failure/15334/ Iron deficiency is an independent predictor of decreased functional capacity and reduced survival in our patients with heart failure. Multiple clinical trials have addressed the issue, but we continue to struggle with the clinical implications of the data. Join Drs. Stefan Anker, Robert Mentz, and Piotr Ponikowski as they discuss the evidence from IV iron trials in heart failure, past and present, and what the results mean for your practice and patients. =

CME credits: 0.50 Valid until: 20-12-2023 Claim your CME credit at https://reachmd.com/programs/cme/treating-iron-deficiency-in-patients-with-hfref-a-review-of-the-recent-data-for-iv-iron-replacement-therapy/13508/ Symptoms from iron deficiency can greatly affect the overall quality of life of our patients with heart failure. Recent clinical evidence from the IRONMAN trial explores the use of IV iron replacement in patients with chronic heart failure. Join Drs. Javed Butler, Stefan Anker, Piotr Ponikowski, and Robert Mentz as they discuss the clinical trial design and outcomes from IRONMAN compared to the current body of evidence for managing iron deficiency in this setting.

#208 – Welcher Gebrauchtwagen ist etwas bieder, aber so viel wert, dass man allein für sein Innenleben 60 000 Euro hinblättern müsste? Willkommen in der Welt der unlösbaren Autotelefon-Autorätsel, powered by Stefan Anker. Möglichst viel Power sollten auch die beiden herausnehmbaren Bluetooth-Boxen haben, die Bestandteil der elektrischen Konzeptstudie Citroën OLI (all-ë) sind. Eine klassische Hifi-Anlage gibt es hier nicht. Das Motto des aufsehenerregenden Wägelchens lautet: Weniger ist mehr. Eine gute Idee für die Zukunft, oder? // Autotelefon – Der Podcast über Autos. // Jetzt abonnieren! Wir freuen uns über Bewertungen und Rezensionen! Kontakt zu uns bitte via http://instagram.com/autotelefonpodcast

C. Michael Gibson and Stefan Anker discuss the effects of empagliflozin on CV death and HF hospitalizations in patients with HFpEF, with and without diabetes.

This week, please join authors Mikhail Kosiborod and Christian Schulze and Editorialist Stefan Anker as they discuss the original articles "Effects of Empagliflozin on Symptoms, Physical Limitations and Quality of Life in Patients Hospitalized for Acute Heart Failure: Results From the EMPULSE Trial" and "Effects of Early Empagliflozin Initiation on Diuresis and Kidney Function in Patients With Acute Decompensated Heart Failure (EMPAG-HF)" and the editorial "SGLT2 Inhibitors: From Antihyperglycemic Agents to All-Around Heart Failure Therapy." Dr. Carolyn Lam:             Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. We're your co-hosts. I'm Dr. Carolyn Lam, Associate Editor from the National Heart Center and Duke National University of Singapore. Dr. Greg Hundley:           And I'm Dr. Greg Hundley, associate editor, director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Dr. Carolyn Lam:             I'm so excited about the feature discussion this week. It is a paired feature along with their editorial and it's all focused on SGLT2 inhibitors. The first, results from the EMPULSE trial, Effects of Empagliflozin on Symptoms, Physical Limitations and Quality of Life in Patients Hospitalized for Acute Heart Failure; and the second, the EMPAG-heart failure trial, The Effects of Early Empagliflozin Initiation on Diuresis and Kidney Function in Patients with Acute Heart Failure. Incredibly important topics, incredibly important discussion. Wait up for it. We're just going to tell you a little bit more about two other original papers in today's issue, and I'm going to go first, Greg. Is that okay? Dr. Greg Hundley:           You bet. Dr. Carolyn Lam:             Now, really interesting topic here. We have strong evidence supporting the effective blood pressure and cardiovascular disease risk lowering properties of healthy diet such as the DASH diet, Mediterranean diet, and so on and so on. But what about the diet consumed by a fifth of the entire world's population? The Chinese cuisine. Interestingly, today's paper addresses just that. This is from authors, Dr. Wu, from Peking University Clinical Research Institute and colleagues who performed a multicenter patient and outcome assessor blind randomized feeding trial among 265 participants with baseline systolic blood pressure of 130 to 159 in four major Chinese cuisines. And these are the Shandong, Huaiyang, Cantonese, and Szechuan cuisines, and here's how they did it. After a seven day run in period on a control diet matching the usual local diets, participants were randomized to continue with the control diet or the cuisine based Chinese heart healthy diet for another 28 days. The primary outcome was systolic blood pressure. The study developed the first heart healthy Chinese diet that fits Chinese food culture and emphasizes its palatability by involving master shifts in developing the recipes. Dr. Greg Hundley:           Oh wow. Carolyn, this is really interesting, especially one fifth of the world's population in studying a heart healthy diet. So did it work? I can't wait to hear the results. Dr. Carolyn Lam:             Well, the change in systolic and diastolic blood pressure from baseline to the end of the study in the control group was five millimeters mercury and 2.8 millimeters mercury reduction, respectively. The net difference of change between the two groups in systolic and diastolic blood pressure were a reduction of 10 and almost four millimeters mercury, respectively. The effect size did not differ among cuisines, and so in summary, with a patient and assessor blind randomized feeding trial, this study really demonstrated that the blood pressure lowering effect of the Chinese heart health diet could indeed be substantial, and importantly, be compatible with medications while palatable and affordable in Chinese adults with high blood pressure, and so these results support the idea that food is medicine and will give many patients with high blood pressure the confidence to adopt heart healthy diets in their lifestyle treatment. Dr. Greg Hundley:           Wow, Carolyn, that is really an interesting article. So many of these articles today could all be features in and of themselves. That was just outstanding. Well, my next paper comes to us from the world of preclinical science, and it's from Dr. Sean Wu from Stanford University School of Medicine. So Carolyn, immune checkpoint inhibitors are monoclonal antibodies that are used to activate the immune system against tumor cells. Now, despite their therapeutic benefits, immune checkpoint inhibitors have the potential to cause immune mediated adverse events such as myocarditis, a rare but serious side effect with up to 50% mortality in affected patients. Now histologically, patients with immune checkpoint inhibitor of myocarditis have lymphocytic infiltrates in the heart implicating T-cell mediated mechanisms. However, the precise pathologic immune subsets and molecular changes in immune checkpoint inhibitor myocarditis are unknown. Dr. Carolyn Lam:             Wow. So insights into the etiology of these immune checkpoint associated myocarditis cases must be very important. So what did they find? Dr. Greg Hundley:           Right, Carolyn? So clonal cytotoxic, TEMRA CD8+ cells were found to be significantly increased in the blood of patients with immune checkpoint inhibitor myocarditis corresponding with an analogous increase in effector cytotoxic CD8+ cells in the blood and hearts of PD-1 deficient mice with myocarditis. These expanded effector CD8+ cells had unique transcriptional changes, including upregulation of the chemokines CCL5, CCL4, and CCL4L2, and they may serve as attractive diagnostic therapeutic targets for reducing life threatening cardiac immune related adverse events in immune checkpoint inhibitor treated cancer patients, and Carolyn, just like so many of our articles, there's a very nice accompanying editorial by Professor Gianluigi Condorelli that also offers an update on current research pertaining to non-systemic steroid therapy to treat immune mediated myocarditis. Well, Carolyn, how about we jump to some of the other articles in the issue? Dr. Carolyn Lam:             Oh, you bet, Greg. There's an exchange of letters between Drs. Madias and Knops regarding the article “Efficacy and Safety of Appropriate Shocks and Antitachycardia Pacing in Transvenous and Subcutaneous Implantable Defibrillators: The Analysis of All Appropriate Therapy in the PRAETORIAN Trial.” Dr. Greg Hundley:           And also in the mail bag, Professor Mark has a Research Letter entitled “Effect of Empagliflozin on Kidney Biochemical and Imaging Outcomes in Patients with Type 2 Diabetes, or Prediabetes, and Heart Failure with Reduced Ejection Fraction, The SUGAR-DM-HF Study,” and our own Tracy Hampton has several synopses from articles published elsewhere in our piece on cardiovascular news. Well, how about we get onto that feature forum discussion, two papers, two editorialists. I can't wait. Dr. Carolyn Lam:             Me too. Let's go, Greg. Dr. Greg Hundley:           Welcome, listeners to this July 26th feature forum discussion. So remember, listeners, for forum discussions, we have several manuscripts that focus on a singular topic and we bring together the authors, our associate editors, and also an editorialist, and today, I want to introduce, we have with us Dr. Mikhail Kosiborod from Mid America Heart Institute in Kansas City, Missouri, Dr. Christian Shults from University Hospital Jena in Germany, Stefan Anker from Charité in Berlin, Germany, and our Associate Editors, Brendan Everett from Brigham and Women's Hospital in Boston, Massachusetts, and Justin Grodin from University of Texas Southwestern Medical Center in Dallas, Texas. Welcome, gentleman, and we'll start with you, Mikhail. Could you describe for us the background information that went into the preparation of your study and what was the hypothesis that you wanted to address? Dr. Mikhail Kosiborod:   Well, thanks very much, Greg. The background for the study, which was the secondary analysis of the EMPULSE trial was patients that are hospitalized with acute decompensated heart failure represent a very high risk group. We know that they have high risk of death and hospitalizations, and we also know that they have very poor health status that's very high burden of symptoms, physical limitations, and poor quality of life, and so addressing those treatment goals, trying to reduce the risk of clinical events like death and hospitalizations and improve the symptoms and physical limitations in this patient population are very important treatment goals. Now we previously demonstrated in the main results of the EMPULSE trials that using empagliflozin initiating empagliflozin SGLT2 inhibitor in this patient population as compared with placebo provided a significant total clinical benefit, which was a composite of total death, repeat hospitalizations for heart failure, or a change in a Kansas City cardiomyopathy questionnaire, which is a kind of a gold standard measure of patient's health status. What we tried to do in a much more granular fashion in this study is to understand the effects of empagliflozin as compared with placebo on this very important outcome, the Kansas City cardiomyopathy questionnaire, and we actually evaluate all of the key domains and composite symptoms, physical limitations, as well as quality of life. Dr. Greg Hundley:           Very nice, and Mikhail, can you describe for us what study population specifically, and then what was your study design? Dr. Mikhail Kosiborod:   Well, this was a population of patients that were hospitalized with heart failure and that EMPULSE was unique in its design because first of all, previous SGLT2 inhibitor trials mostly focused on patients with chronic heart failures that were in an outpatient setting, including prior trials of empagliflozin, and EMPULSE really focused on acutely hospitalized patient population, but it included patients regardless of ejection fraction. So as they were hospitalized with decompensated heart failure and reduced or preserved ejection fraction. They were enrolled regardless of if they had type 2 diabetes, they were enrolled essentially, regardless of kidney function, only patients with EGFR of less than 20 were excluded, and also importantly, was this study and a unique feature of the study in particular was that we enrolled patients whether they had acute de novo heart failure. That means that was a new diagnosis of heart failure that was bad enough for them to be hospitalized or worsening chronic heart failure requiring hospitalization. So it was really an all-comer trial for patients acutely hospitalized for heart failure. So we had just over 500 patients and they were randomized in the hospital. After a brief period of stabilization, we use empagliflozin, 10 milligrams daily or placebo and treated for 90 days, and the primary outcome at 90 days was a total clinical benefit that I described that was a composite, hierarchical composite of total death hospitalizations, repeat hospitalizations for heart failure and changing KCCQ. In this study, again, we focused predominantly on KCCQ, trying to understand the effects on health status, again, symptoms, physical limitations, and quality of life. Dr. Greg Hundley:           Excellent. And Mikhail, what were your study results? Dr. Mikhail Kosiborod:   Well, what we observed, a couple of things. One is we first examined the effects of empagliflozin on the primary endpoint across the range of KCCQ and baseline, and what we found was that regardless of the degree of symptomatic impairment and baseline, empagliflozin was consistent in providing them total clinical benefits that I described previously, and then kind of shifting to what I think is the most interesting findings, the effects of empagliflozin versus placebo on KCCQ, what we found was that as you would imagine in this population of patients that were acutely hospitalized with heart failures, that had very poor health status, very low KCCQ at baseline, and within the first 90 days, which was observation period, both groups of patients had substantial improvements in KCCQs. As one would expect after acutely decompensated episode of heart failure and treatment in a hospital, everyone got better. But patients treated with empagliflozin had significantly greater improvement in KCCQs than those that were treated with placebo, and that was first of all, a very substantial difference between the two groups. It was more than five points in favor of empagliflozin already at 15 days and was highly statistically significant, and it was maintained throughout the 90 day treatment period. So the fact that we saw both a clinical meaningful and statistically significant improvement in just 15 days, I think is a very important clinical message, and then finally, I guess what I will mention is these benefits of empagliflozin while main outcome we looked at was KCCQ total symptoms, we're focusing on the symptoms, but it was consistent when we looked at physical limitations as well as quality of life. So really, all key domains of KCCQ were impacted in a similar way. Dr. Greg Hundley:           Very nice. So in acute heart failure, marked symptomatic improvement after the administration of the SGLT2 inhibitor empagliflozin at 10 milligrams per day. Well, now listeners, we're going to turn to our associate editor, Dr. Brendan Everett, and Brendan, again, you have many papers come across your desk. What attracted you to this particular manuscript? Dr. Brendan Everett:      Well, thanks, Greg, and I think this manuscript caught my eye because of the importance of the clinical question, and Mikhail outlined why I think that was really relevant. So we understand that this class of medications or SGLT2 inhibitors have important effects on outcomes like re-hospitalization in patients with heart failure, and what was particularly striking about this paper is that it took patients rather than those with chronic heart failure, but as Mikhail mentioned, enrolled a patient population that was actually in the hospital, and I think this was an important frontier for this particular question about when to start the SGLT2 inhibitor and what kind of benefits there might be. Furthermore, I think the fact that they did not select the population based on ejection fraction was particularly striking, and of course, I think is remarkable, but now old news, they did not select on the presence or absence of diabetes as well. And so those three components really attracted me to the paper. I also think the outcome is one that really is valuable and worth exploring, and specifically, I'm talking about how patients feel on the medication after a hospitalization for heart failure. Appropriately, we focused on re-hospitalization for heart failure and cardiovascular death in prior trials in this space, and I think we need to embellish those findings or further deepen those findings with a perspective on how patients actually feel when they get the medication, and of course, it goes without saying that what's particularly important here also is that it was a randomized placebo controlled trial, and so the results have some element of internal validity that I think is really important. So those were the things, Greg, that really attracted my attention as I read the paper for the first time. Dr. Greg Hundley:           Thank you so much, Brendan. Well, listeners, we've got a second paper today and we're next going to hear from Dr. Christian Shults, and he also is focusing on really another aspect of the administration of empagliflozin in patients with acute heart failure and that pertains to the renal function of the patients. So Christian, could you describe for us the background pertaining to your study and what was the hypothesis that you were intending to address? Dr. Christian Schulze:     Thanks, Greg. Well, it's great to introduce all study here in this running. So our study impacted those in acute decompensated heart failure. The impact HF trial was a study based on the hypothesis that we wanted to test, whether empagliflozin has effects in acute decompensated heart failure, and we focused on the patient population that was not addressed in EMPULSE, patients that came to the ER and needed to be treated right away, and we wanted to know and this was our main hypothesis, but are the diuretic and [inaudible 00:17:11] effects of the SGLT2 inhibitor on this case, empagliflozin, actually had an impact on diuretic regimens and kidney functions since this is one of the main end points that limits treatment, and also is one of the outcomes of patients with acute decompensated heart failure in the hospital. Dr. Greg Hundley:           Very nice. And so Christian, what study design did you implement and who was included in your study population? Dr. Christian Schulze:     So we also used the randomized two arm study design. We included patients with acute decompensated heart failure independent of left ventricular ejection fraction. Patients needed to have an NT-proBNP of more than 500. The average NT-proBNP in fact was 4,300 in our entire patient population, and we included patients within 12 hours of presentation. So many of these patients have been recruited in the ER, they presented two hour cardiology heart failure service, and then were immediately randomized to the trial in the two arms, and we tested not 10 milligrams of empagliflozin. We actually tested 25 milligrams of empagliflozin based on in-house data that 25 milligrams potentially had a stronger diuretic effect compared to 10 milligrams. Dr. Greg Hundley:           And what did you find? Dr. Christian Schulze:     So we followed patients for five days. It was a relatively short period of time. It was designed to address the in-house phase of patients with acute decompensated heart failure. The mean duration of stay was 6.3 days in the hospital so this was exactly the time that we wanted to test. We had a 30 day endpoint for safety issues, and what we could see is that patients on 25 milligrams on empagliflozin on top of standard diuretic regimens and medical care had 25% higher diuretic outputs compared to patients in the placebo group. We also found no differences in markers of renal injury dysfunction, and could in fact confirm that after 30 days, patients in the empagliflozin group had a better EGFR compared to patients in the placebo group. On top, we saw a more rapid decrease in body weight and also a more profound decrease in NT-proBNT values. Dr. Greg Hundley:           And Christian, just for our listeners to put a little bit of this in perspective, what was the range of serum creatinine for the patients that were enrolled in your study? Dr. Christian Schulze:     So the main EGFR in the entire population was around 60 and the creatinine values were around 107 on average in the entire cohort. So this is a very typical population. We had around 30% of the population with de Novo heart failure, around 20 to 30% of the population was pre-treated for preexisting heart failure. So very typical population of patients with heart failure presenting to the emergency room. Dr. Greg Hundley:           And did you have any kind of lower level EGFR cutoff, I mean, for enrollment into this study? Dr. Christian Schulze:     So when we designed the trial, we actually still had the sub classification of diabetes or impaired glucose or homeostasis as an inclusion criteria. We dropped it before we started the trial because the data came out that this is actually, in fact, not a critical issue for patients with heart failure. So diabetes was not a subgroup in our trial and the lower limit of EGFR was actually a thoroughly defined protocol. Dr. Greg Hundley:           Very nice. Well, listeners, now we're going to turn to our second associate editor, Dr. Justin Grodin from University of Texas Southwestern Medical Center in Dallas, Texas, and Justin, similar to Brendan, and you see many papers come across your desk and so what attracted you to this particular paper by Christian and his colleagues? Dr. Justin Grodin:            Well, Greg, I think first and foremost, and I think very similar to Brendan, but I think what's always striking is if I may just take a step back, decompensated heart failure in the United States is the number one cause for hospitalization among Medicare beneficiaries. So I think really, the brunt and really the truly public health message of the disease is very important in the applicability, and even though that decompensated heart failures is one of the most common things that we ever encounter when we practice, internists, cardiologists, et cetera, we have very, very little clinical trial guidance that tells us how to decongest individuals when they're hospitalized with swelling and heart failure and a lot of these individuals can be quite ill, and we have some clinical trial data, but largely, we have a lot of negative studies or inconclusive studies in this space. So certainly, what drew me to this trial was definitely that context, and obviously, based on the mechanistic data with SGLT2 inhibitors, I think one of the natural questions, which Christian addresses, is that we know that up front, they do augment natriuresis. So I think it's very compelling to marry those two together because this is what many of us that use these medications regularly have been asking is whether or not they would have some efficacy in that regard, and then another thing that caught my eye and me as a cardiorenal investigator was, just as Christian highlighted, was we have a clinical trial that randomly assigned individuals, really that were ill and many of whom were not stabilized within 12 hours of presentation, and we're talking about patients that are coming into the hospital at all times during the day in and I think that's very remarkable that we have something with standard... We have a study with standardized assessments where we're really trying to ask a very practical, pragmatic question, which is do these therapies lower the sodium balance in individuals with decompensated heart failure, and I think what's important is largely, we've got a lot of medications that supplement loop diuretics, which are the class of drugs that the majority of us use, and we have a lot of other therapies that we use that really have very little data or poor data that guide us such as thiazide diuretics, carbonic and hydrase inhibitors, mineralocorticoid receptor antagonists, and so here, we have a clinical trial that asks a question that's on many people's minds. And then we do have very compelling, at least short term pragmatic and mechanistic data that does tell us that these individuals do have a greater natriuretic effect when empagliflozin is used as an adjunct to standardized loop diuretic therapy. So it's a very practical clinical question, and I think what's very important, and we could debate probably all day about the implications of GFR change and kidney function change while we're decongesting somebody with diuretics, but I think what's reassuring to all the clinicians is we really didn't see an effect on kidney function despite a greater natriuretic effect or enhanced diuretic effect, if you will, with the use of empagliflozin. Dr. Greg Hundley:           Very nice. Well, thank you, Justin. Listeners, now we have an editorialist and as you know, editorialists really help us put the scientific presentation of an original manuscript into the perspective of really the global theme of a topic, and we have Stefan Anker from Berlin, and Stefan, can you describe for us how do we put these two manuscripts and results that we've heard about really in the context now of moving forward with the use of SGLT2 inhibitors in the management of patients with acute decompensated heart failure? Dr. Stefan Anker:            Thank you so much. Really, I think these two papers, on the one hand, enhance our certainty about early use, and on the other hand, possibly show us that there might be even more to achieve by, on the one hand, moving even earlier with the application of SGLT2 inhibitors or possibly consider the higher dose. Now let's take one step back. These drugs were developed in type two diabetes and the first successful trial was the [inaudible 00:25:42] outcome trial. Many people have forgotten that this trial tested two doses and not only one, the 10 and the 25 milligram dose, and of course, with the success for improving kidney outcomes and heart failure hospitalization outcomes, we move forward into these two specialist areas, on the one hand, broadening it to the non-diabetic communities, but on the other end, narrowing it by focusing on the 10 milligram dose regardless of whether there is [inaudible 00:26:12]. And we basically now learn A, to use these drugs even earlier than we did in the big trials and we can now be sure to start their use in the hospital, and if you take the average change in quality of life results seen, you actually get a better result for the patient on quality of life when you start earlier than when you start late in the ambulatory studies where basically, in the chronic setting, maybe you have one and a half to two points difference. Here, you now have four and a half points in the study shown by Mikhail, and of course, it's also good to know that you can start this in any type of patient, regardless of their quality of life. The impact study from Christian, they basically moved it now even earlier, moving into the hospital space is possible based on EMPULSE. Moving it into the acute admission space is at least a consideration now based on what Christian here has shown. And he is actually addressing the one question I hear very often in my presentations about SGLT2 inhibitors, what about this 25 milligram dose? Is there a place for this in cardiology as well, and a possible place is shown here, not only that this is a safe thing to do, but also you get urinary output. Of course, we may in the future, want to see this compared, directly compared to the 10 milligram dose, but of course, the world is not created in one day, but needs more than one and so really, I think these two studies, on the one hand, address an important issue, when to start using them. On the other hand, show us a little bit of a glimpse to the future. Dr. Greg Hundley:           Very nice, Stefan, and listeners, we get to take advantage of having these authors, editors, and editorialists together and ask them what they see as the next study to be performed in this sort of sphere of research. So Mikhail, we'll start with you. In 30 seconds or less, what do you see as the next study to be performed in this arena of research? Dr. Mikhail Kosiborod:   I think, Greg, what we've learned recently, including from the EMPULSE trial, we have this population of patients in a hospital with heart failure's a huge issue as Justin mentioned, and until recently, we had very little [inaudible 00:28:31] for them beyond the usual kind of decongestion with loop diuretics and trying to make them feel better, but you look at outcome data. It really was a dearth of effective therapies that have meaningful impact on important outcomes. Now that's changing, SGLT2 inhibitors is one example. There are some other recent examples in this patient population, like a firm HF and iron deficient patients with heart failure. But the bottom line is it's no longer kind of a desert, if you will, of positive trials. We now have something we can do and I think what this proves is that we need to actually invest more, both in terms of resources and time to really do what we we're being able to do in other areas of heart failure and those patients with chronic, half and half where we can start developing pillars of therapy that can actually truly improve outcomes with this patient population and there is a lot going on that makes me optimistic that's going to be the case in the coming years. Dr. Greg Hundley:           Very nice. And Brendan? Dr. Brendan Everett:      Well, I think both trials mentioned today really pushed our understanding of this population forward. I think the biggest clinical question that I face when I'm caring for these patients is that we have four, at least, guideline directed therapies, right? We have beta blockers, we have ARBs, ACE inhibitors and ARNIs. We have mineral receptor antagonists and we have SGLT2 inhibitors. So which do we use in what order and how do we start them, and what kind of parameters do we use to guide us if we're limited either by renal function or by blood pressure or by some other factor. And we often, if not always, have one of those constraints that we're dealing with and so I would say the next step for me is trying to sort out which of these therapies and what order ought to be our highest priority for patients with acute decompensated heart failure as we move quickly from the acute decongestion stage towards discharge and a chronic therapy that will then be followed as an outpatient over the ensuing days and months. Dr. Greg Hundley:           Very nice. And Christian. Dr. Christian Schulze:     Thank you again, and Brandon pointed out very nicely. I mean, we have good evidence now for chronic heart failure treatment. We have the four columns of heart failure medical therapy. Questions that remain open is what do we do with all these patients that are now guideline medicated, come to the hospital with an acute decompensation? Should we carry on with the medication? Should we terminate and in particular, should be carry on with full dose, 50% dose of SGLT2 inhibitors, and the next question is, what dose should we use, in fact, for SGLT2 inhibitors? Is it in group effects or is sotagliflozin comparable to empagliflozin, and then is there a role for a step by scheme that we initially have in high dose therapy that we then downgrade to 10 milligrams on the chronic heart failure treatments, and then of course, quality of life is very important. We should ask this question also in this patient population that is early on treated, do we see benefits that carry on in the outpatient setting and do we see an effect of early treatment on long term benefits? Dr. Greg Hundley:           Justin? Dr. Justin Grodin:            Well, I would have to agree with all of my colleagues here on this call. I think all have raised really good points, but I think one very simple, and I'll echo some of Brendan's statements, but one very simple question is we know that when we decongest people and initiate a negative salt balance in the hospital for decompensated heart failure, we cause neurohormonal activation and there are a lot of downstream untoward effects from chronic decongestive therapies, and I think one of the more compelling things is we still yet have defined what is the best way to decongest individuals with swelling or volume overload in the hospital. Here, we have compelling studies with SGLT2 inhibitors for quality of life and really, the way patients feel. And this is really what's important to them, and then something very pragmatic to clinicians and let's make people pee more, but I think one of the compelling questions, and I don't know if it will be answered, is we have a lot of choices for supplemental therapies and different diuretic strategies when patients come in the hospital for decompensated heart failure, and I do think that these studies do move the needle with SGLT2 inhibitors. I think that's abundantly clear, but we still don't know what is the best way to dry out my patient or make my patient pee so that they feel better, but I do think that these studies do at least set the stage that there's some compelling advantages to SGLT2 inhibitors. Dr. Greg Hundley:           And then lastly, Stefan. Dr. Stefan Anker:            Thank you. Besides the detailed points mentioned by many, and Christian, totally support 25 versus 10 milligram, how long 25 milligram, if at all in the future. Besides this, I'm interested in the big picture question. So what about the post myocardial infarct congestion/heart failure situation, and there will be two trials in the next 18 to 24 months that report on this, and my pet kind of area is actually to treat heart failure where nobody thinks it is heart failure, and what I mean is for instance, advanced cancer patients, cardiac wasting cardiomyopathy. So the heart failure in sick cancer patients, and indeed, we are planning to do exactly that now in a study focusing on hospice care patients to really improve the quality of life, the very thing focus here on the EMPULSE trial. Dr. Greg Hundley:           Well, listeners, we want to thank our authors, Dr. Mikhail Kosiborod from Mid America Heart Institute in University of Missouri, and Christian Shults from the University Hospital in Jena, Germany. Also, our associate editors, Dr. Brendan Everett from Brigham and Women's Hospital in Boston, and Dr. Justin Grodin from University of Texas Southwestern in Dallas, Texas, and also, our editorialist, Dr. Stefan Anker from Charité in Berlin, Germany for bringing us these two manuscripts pertaining to two randomized clinical trials regarding the administration of the SGLT2 inhibitor, empagliflozin in acute heart failure, demonstrating first, marked improvement in heart failure symptoms and health related quality of life. And second, in those with estimated GFRs greater than 30 mls per minute, an augmentation of natriuresis in the setting of the co-administration of diuretics without deterioration in renal function. Well, on behalf of Carolyn and myself, we want to wish you a great week and we will catch you next week on the run. This program is copyright of the American Heart Association, 2022. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, please visit ahajournals.org.

#188 – Wenn Geld keine Rolle spielt, könnte man sich knapp zweihundert Dacia Jogger (voll ausgestattet) zulegen oder aber einen AMG ONE ordern. – Was würdest Du tun? Genau so entscheiden wie Stefan Anker? In der aktuellen Folge sprechen wir über die ersten Eindrücke mit dem Dacia-Kombi und teilen Erinnerungen an die Testfahrten mit dem vollelektrischen Cupra Born. Und natürlich plaudern wir über die technischen Daten des AMG-Renners – und die Folgen für manche Kunden. // Autotelefon – Der Podcast über Autos. // Jetzt abonnieren! Wir freuen uns über Bewertungen und Rezensionen! Kontakt zu uns bitte via http://instagram.com/autotelefonpodcast

CME credits: 0.25 Valid until: 22-02-2023 Claim your CME credit at https://reachmd.com/programs/cme/potassium-binders-as-enablers-of-raasi-therapy-diamond-topline-results/13260/ The DIAMOND trial recently released topline results, adding to the growing clinical evidence for the use of potassium binders in the management of hyperkalemia in patients with heart failure. So what do the data mean for our patients? Join Dr. Stefan Anker and Dr. Javed Butler as they discuss the value of these results and make sure you're staying up to date with the evolving data, guidelines, and practices.

CME credits: 0.25 Valid until: 22-02-2023 Claim your CME credit at https://reachmd.com/programs/cme/potassium-binders-as-enablers-of-raasi-therapy-diamond-topline-results/13260/ The DIAMOND trial recently released topline results, adding to the growing clinical evidence for the use of potassium binders in the management of hyperkalemia in patients with heart failure. So what do the data mean for our patients? Join Dr. Stefan Anker and Dr. Javed Butler as they discuss the value of these results and make sure you're staying up to date with the evolving data, guidelines, and practices.

In this interview, Jeroen Bax, PhD, MD, FACC; Stefan Anker, MD, PhD; and Sherry-Ann Brown, MD, PhD, FACC, discuss the ESC Congress 2021 late breaker EMPEROR-Preserved, which evaluates the effect of empagliflozin for risk of cardiovascular death and hospitalisation for patients with heart failure and a preserved fraction with and without diabetes. Like what you hear? Get 20 episodes a month with CME/MOC credit at www.acc.org/ACCEL.

#152 – Welches Auto ist fast fünf Meter lang, ist ein nicht ganz zeitgemäßes SUV mit 150 Kilometer elektrischer Reichweite und kommt aus China? – Wer das Rätsel gelöst hat, darf gerne weiter hören und den Eindrücken von Stefan Anker lauschen. Wir besprechen das neuartige Konzept der IAA Mobility und schauen auf automobile Neuheiten wie den Mercedes-Benz EQE, das Smart Concept #1, den BMW i Vision Circular, den Cupra UrbanRebel, den VW ID. Life, den Microlino und den Dacia Jogger. // Autotelefon – Der Podcast über Autos. // Jetzt abonnieren! Wir freuen uns über Bewertungen und Rezensionen! Kontakt zu uns bitte via http://instagram.com/autotelefonpodcast

An interview with lead investigator on full results from EMPEROR-Preserved Trial, which affirm that empagliflozin lowers the risk of CVD for heart failure in patients with HFpEF.Welcome to this episode of Physician's Weekly Podcast. My name is Dr Rachel Giles, from Medicom Medical Publishers, in collaboration with Physician's Weekly.  This week I am recording this episode in the Italian alps, while attending the European Association of Urology Guidelines Panel meeting for Renal cell carcinoma, but we have 2 great in-depth  interviews for you this week.  Later in this episode, Physician's Weekly's Editorial Director Chris Cole interviews Dr. J. Stacey Klutts, a medical microbiologist at Rush University, about his op-ed in the Tampa Bay Times comparing the Delta variant of SARS-CoV-2 to Gorilla Glue, which went viral. And yes, the pun was intended. Dr Klutts also tells us about exactly how the vaccine was developed and how the Delta variant is detected in patients. Did you know there are currently 13 subtypes of the Delta variant? But first, we speak with the presenter at the European Society of Cardiology Annual Congress HOTLINE plenary talk, prof. Stefan Anker at the Charité Hospital in Berlin, Germany, about the full results of the EMPEROR-Preserved trial, which affirm that empagliflozin lowers the risk of cardiovascular death/hospitalization for heart failure in patients with heart failure and preserved ejection fraction (HFpEF), leading one expert to say this is “a big day for patients living with HFpEF, a big day for heart failure clinicians.”The primary endpoint—a composite of CV death and hospitalization for heart failure—was reduced by a relative 21% in patients treated with the sodium-glucose cotransporter 2 (SGLT2) inhibitor emagliflozin.Published simultaneously online in the New England Journal of Medicine, these results represent the first trial to show unequivocal benefit of any drug on major heart failure outcomes in patients with heart failure and a preserved ejection fraction. Anker SD, et al; EMPEROR-Preserved Trial Investigators. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. N Engl J Med. 2021 Aug 27.  Let us know what you thought of this week's episode on Twitter: @physicianswkly Want to share your medical expertise, research, or unique experience in medicine on the PW podcast? Email us at editorial@physweekly.com! Thanks for listening!

Dr. Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. We're your co-hosts, I'm Dr. Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Dr. Greg Hundley: And I'm Dr. Greg Hundley, associate editor, director of the Pauley Heart Center at VCU health in Richmond, Virginia. Well, Carolyn, our feature discussion, actually our whole issue, is going to involve the flozins, empa, dapa, et cetera, but that feature discussion will get some results from the EMPEROR-Reduced trial. Well Carolyn, how about we grab a cup of coffee and this is your area, so we're going to let you run with it today. Dr. Carolyn Lam: Man, and I can't wait to talk about this. Yes, the sodium-glucose cotransporter 2 inhibitors or SGLT2 inhibitors, are indeed now the foundational therapies for patients with heart failure with reduced ejection fraction. Initially developed to improve glucose control in patients with type II diabetes, SGLT2 inhibitors have beneficial cardiovascular and renal effects in patients with diabetes, HFrEF, chronic kidney disease. Well, today's issue contains two pre-specified subgroup analyses from DAPA-HF and EMPEROR-Reduced, both trials evaluating SGLT2 inhibitor effects on renal outcomes, as well as cardiovascular outcomes, by baseline renal function in patients with HFrEF. The first paper comes from Dr. Jhund and colleagues from the University of Glasgow and it is revolving around the DAPA-HF trial. Dr. Greg Hundley: Ah Carolyn, tell us a little bit about DAPA-HF. Dr. Carolyn Lam: Gladly. In DAPA-HF, the SGLT2 inhibitor, dapagliflozin, reduced the incidence of the primary composite outcome of cardiovascular death or worsening heart failure in patients with HFrEF, with and without diabetes and an estimated GFR of greater or equal to 30. Of more than 4,700 patients with a baseline GFR, 41% had a GFR less than 60. The effect of dapagliflozin on the primary and secondary outcomes did not differ by GFR category or examining GFR as a continuous variable. The pre-specified composite renal outcomes, which in DAPA-HF was a more than 50% sustained decline in GFR, end stage renal disease or renal death. Now this composite renal outcome was not reduced by dapagliflozin, but the rate of decline of GFR between days 14 and 720 was less with dapagliflozin. Dr. Greg Hundley: Carolyn, what's the take home message here? Dr. Carolyn Lam: Dapagliflozin slowed the rate of decline in GFR in patients with HFrEF, both in patients with and without diabetes. There was no difference in the efficacy of dapagliflozin by baseline renal function in preventing the risk of cardiovascular death or worsening heart failure. Dr. Greg Hundley: Okay, well now how about the EMPEROR-Reduced trial? Dr. Carolyn Lam: All right. Well, let me remind you first that in EMPEROR-Reduced the SGLT2 inhibitor empagliflozin also reduced cardiovascular death or heart failure hospitalization and total heart failure hospitalization and slowed the progressive decline in kidney function in patients with heart failure with reduced ejection fraction with and without diabetes. Now, more than 3,700 patients were randomized, of whom 53% had chronic kidney disease, defined as a GFR less than 60 or a urinary albumin to creatinine ratio above 300 milligrams per gram. Empagliflozin reduced the primary outcome and total heart failure hospitalizations in patients with and without chronic kidney disease. Empagliflozin also slowed the slope of GFR decline and the risk of the pre-specified composite kidney outcome, now defined as a sustained, profound decline in GFR, chronic dialysis or transplant, was reduced similarly in patients with and without chronic kidney disease. Dr. Carolyn Lam: The effect of empagliflozin on the primary composite outcome of cardiovascular death and heart failure hospitalization, as well as the key secondary outcomes of total heart failure hospitalization and GFR slope, were consistent across the broad range of baseline kidney function measured by clinically relevant GFR subgroups or by albuminuria and including patients with a GFR as low as 20. Above all, empagliflozin was well tolerated in these patients with chronic kidney disease. All of this is discussed in a beautiful editorial by doctors Carnicelli and Robert Mintz. Dr. Carolyn Lam: Now, can I tell you about yet another paper with the SGLT2 inhibitors? This time a pre-specified comparison of the effect of empagliflozin in patients with and without diabetes. Dr. Greg Hundley: Ah, great Carolyn. What did this study find? Dr. Carolyn Lam: Well, this is from Dr. Stefan Anker from Berlin and colleagues, including myself and of the more than 3,700 patients enrolled in EMPEROR-Reduced, 50% had diabetes, 34% had pre-diabetes and 16% had normal glycemia. Empagliflozin reduced the risk of the primary outcome similarly in patients with and without diabetes. Patients with and without diabetes also did not differ with respect to the effect of empagliflozin on total heart failure hospitalizations, on the decline in EGFR over time or on the risk of serious adverse renal outcomes. Among these end points, the effects of the drug did not differ in patients with pre-diabetes or normal glycemia. When analyzed as a continuous variable, baseline HbA1c did not significantly modify the benefits of empagliflozin on the primary outcome. Empagliflozin also did not lower HbA1c in patients with pre-diabetes or normal glycemia and was not associated therefore with an increased risk of hypoglycemia. Dr. Greg Hundley: Carolyn what's the take home message here? Dr. Carolyn Lam: Well, empagliflozin significantly improved cardiovascular and renal outcomes in patients with HFrEF, independent of baseline diabetes status and across the continuum of HbA1c. Dr. Greg Hundley: Very nice Carolyn. Well, my paper comes from professor Wai Ho Tang and it's a basic science paper. Carolyn, aberrant expression of circular RNA or CircRNA, contributes to human diseases. CircRNAs regulate gene expression by sequestering specific microRNAs. In this study, the authors investigated whether CircMAP3K5 could act as a competing endogenous microRNA-22-3p sponge and regulate neointimal hyperplasia. Dr. Carolyn Lam: Wow, that's interesting. And what were the results? Dr. Greg Hundley: Carolyn, the authors identified that CircMAP3K5 is a master regulator of TET2-mediated, vascular smooth muscle differentiation. Targeting CircMAP3K5, microRNA-22-3p and the TET2 axis, may provide a potential therapeutic strategy for diseases associated with intimal hyperplasia, including restenosis as well as atherosclerosis. Dr. Carolyn Lam: Oh, nicely summarized. Thanks Greg. Well, we've got other papers in today's issue. There's an ECG challenge by Dr. Frész on acute coronary syndrome with tall R waves and inverted T waves in the precordial leads, an ignored entity. We have an exchange of letters between Drs. Vandecasteele and Zhao regarding the article, Cardiac Over Expression of PDE4B Blunts β-Adrenergic Response and Maladaptive Remodeling in Heart Failure. Dr. Greg Hundley: Thanks Carolyn. I have some Research Letters. The first Research Letter is entitled, “Cardiovascular Toxicities Associated with Loperamide: An Analysis of the World Health Organization Pharmacovigilance Database,” and the corresponding author is Dr. Pierre Ollitrault. The second Research Letter is entitled, “Incessant Pericarditis as a Risk Factor for Complicated Pericarditis and Hospital Admission,” and it comes from Professor Massimo Imazio. And then finally, there's a White Paper (Frontiers) for atrial fibrillation screening research priorities from the NHLBI workshop with the corresponding author being Dr. Emelia Benjamin from Boston University School of Medicine. Well Carolyn, how about we jump in to more SGLT2 and another feature discussion? Dr. Carolyn Lam: Yes, can't wait. Thanks Greg. Dr. Greg Hundley: Well listeners, we're now to our feature discussion and we have with us today, Dr. Milton Packer from Baylor University Heart Vascular Center in Dallas and also our own associate editor, Dr. Justin Ezekowitz from Edmonton. Milton, welcome and wanted to ask you first off, tell us a little bit about the background that got you to want to perform this study. And what hypothesis did you want to address? Dr. Milton Packer: Greg, first of all, I'm delighted to be here with you and Justin. And as everyone knows, SGLT2 inhibitors have had a remarkable track record in trials of type II diabetes, trials of chronic kidney disease and now trials of patients with heart failure and a reduced ejection fraction. And in these trials, SGLT2 inhibitors have had two important benefits. The first benefit has been a reduction in serious heart failure events, primarily a reduction in heart failure hospitalizations. And the second has been a reduction in serious adverse renal outcomes. And that has been now shown consistently in trial after trial in diverse populations. Dr. Milton Packer: Now we carried out a trial called EMPEROR-Reduced with was the trial in patients with heart failure and a reduced ejection fraction. It was a sister study, so to speak, with a very parallel trial called DAPA-HF, which was carried out with dapagliflozin. And both DAPA-HF and EMPEROR-Reduced were studies, were trials of SGLT2 inhibitors, dapagliflozin and empagliflozin in people with heart failure and a reduced ejection fraction. And they produced remarkably consistent results. And specifically a reduction in serious heart failure events and serious adverse renal events. Dr. Milton Packer: But the trial studied complimentary patient populations. We studied patients that were a bit sicker than patients in DAPA-HF. And Greg, what's really fun is that each trial designed its own case report forms so that we collected information that the investigators were really interested in and they were not necessarily the same types of information across the two trials. One of the things that was really interesting about EMPEROR-Reduced was we were really interested in these heart failure events. We wanted to understand them. We wanted to understand whether they occurred as outpatients, inpatients. If they occurred as inpatients, what kind of hospitalizations were these? Were these serious hospitalizations? Were these short term, very mild hospitalizations? This paper, the hypothesis in this paper was to take a look at what empagliflozin did in patients with heart failure and reduced ejection fraction, specifically with respect to outpatient and inpatient worsening heart failure events. Dr. Greg Hundley: Very nice. How many patients did you include? What were the characteristics of the study population? And what was the design? Dr. Milton Packer: We enrolled, randomized 3,730 patients. All patients had heart failure with a reduced ejection fraction. All were receiving all appropriate treatments for heart failure. Interestingly, 20% were receiving nephrolysin inhibitors, which is really a very high percentage, but they were also receiving inhibitors, renin-angiotensin system beta blockers, mineralocorticoid receptor antagonists and they were patients who had an average ejection fraction of about 27%, which is much lower than most heart failure trials recently. They also had meaningfully elevated levels of natriuretic peptides. These were sicker patients and they had a much higher placebo event rate. They were randomized double-blind, one to one ratio to either placebo or empagliflozin. Dose was 10 milligrams once daily. And this was added to all previously existing therapy and patients were followed for double-blind therapy for an average duration of 16 months and we recorded prospectively information on outpatient and inpatient heart failure events. Dr. Greg Hundley: Very nice. What did you find, Milton? Dr. Milton Packer: We originally reported that in this trial, there was a reduction with empagliflozin on heart failure hospitalizations and that reduction was about 30%. We wanted to know, well, what else was going on with respect to these heart failure events? And so we asked the question, well, did empagliflozin reduce urgent and emergency room visits for heart failure? Did empagliflozin change the types of hospitalizations? We recorded the use of positive inotrophic drugs, vasopressor drugs, vasodilator drugs, cardiac devices, intervention, surgical interventions. And we found out that across the entire spectrum of heart failure outcomes, there was a reduction in serious outcomes with empagliflozin and they all were around a 30% reduction in risk. They varied a little bit from about 28 to 33, but approximately all were in the same ballpark. And what was really interesting was we had a fair number of hospitalizations where patients required IV inotropic drugs, vasopressors, mechanical intervention, they were reduced by 30% with empagliflozin. Hospitalizations associated with intensive care reduced by 30% with empagliflozin. Dr. Milton Packer: And then we looked at outpatient events. Outpatient intensification of diuretics reduced by 30, 33% with empagliflozin. We looked at New York heart class. And what was really interesting was that patients treated with empagliflozin had a 20 to 40% greater likelihood of showing improvement in New York heart class and a 20 to 40% lower likelihood of showing worsening in New York heart class. And those benefits, we're seeing within 28 days after randomization. This early effect is really interesting and it's generated a lot of discussion. And so we looked at our Kaplan Meier curves for the composite of cardiovascular death, heart failure hospitalizations, urgent care, emergent care visits, and we found that the two curves separated quite early and reached statistical significance only 12 days after randomization. This is a very early effect. I want to add that this early separation of curves has been reported previously with beta blockers, with mineralocorticoid receptor antagonists, with neprilysin inhibitors and now we can add this early separation with SGLT2 inhibitors. Dr. Greg Hundley: Very nice, Milton. Well, I'd like to turn now to our associate editor, Dr. Justin Ezekowitz. and Justin you've seen a lot manuscripts come pass through your hands. What attracted you to this manuscript? And then how do you put the findings that Milton has just described in the context with the other results that we have been witness to regarding SGLT2 inhibitors? Dr. Justin Ezekowitz: Thanks Greg. And also, thanks Milton for letting us look at this remarkable manuscript as I do think the clinical implications for a manuscript like this are quite profound. The first thing that really strikes me is we often get worried about looking at a number of different end points. Within a clinical trial, we often don't want to have too many looks at the data because of the risk of finding something that is spurious, is high, but in this case, the way the data was collected and the exploration is quite valuable. We can look at any one of the combinations of clinical end points that actually have direct clinical relevance for a clinician and the patient. And this paper really explored that in a lot of data, in a lot of depth and also helped us by putting the caveats around these findings that this is exploration, but it does anchor it in the SGLT2 world, but also the heart failure world. Dr. Justin Ezekowitz: And Milton, I think one of the striking findings that you showed and it's buried in many of the great figures and tables, is that one in two patients had something happen in the next year. In the next 12 months, that patient walking into an office for a routine followup, one in two had something and the reduction was pretty remarkable across the end point. Milton, I wanted to pick your brain on this one, just to understand when you look at the intensification of diuretics, that was anything from adding another 20 milligrams of furosemide, to doubling or tripling that. Do you think these findings are pretty ubiquitous across the patients enrolled? Or do you think they're a niche finding in only some patients at the highest risk? Dr. Milton Packer: Well, we actually looked at that. We actually looked at whether baseline variables influenced the effect on intensification of diuretics and it was across the board. Well, let me just say, across the board in the patients that we studied and obviously can't make reference to people we didn't study, but we didn't find any particular subgroup that responded particularly well with respect to either a hospitalizations or diuretic intensification or New York heart class changes. But Justin, there's one thing that you just said that is so important. And that is, our patient population was characterized by their physicians, 70% as having class II heart failure. And a lot of physicians think that class II heart failure represents a stable population, clinically stable population. And as you said, one in two patients in our study during followup had worsening heart failure, either represented as an inpatient or outpatient event. A class II patient with heart failure and reduced ejection fraction, even though they're getting optimal medical therapy, is not a clinically stable patient. Dr. Greg Hundley: Very, very interesting finding. Well, just to ask each of you, maybe Milton first and then Justin next, Milton, what do you think is the next study that we need to perform in this patient population using this class of drugs? Dr. Milton Packer: We're really excited about a new phase of heart failure research with SGLT2 inhibitors, which is to look at the impact of these drugs in patients with heart failure and a preserved ejection fraction. DAPA-HF and EMPEROR-Reduced were trials of inpatients with hard failure and a reduced ejection fraction. But we really, about half patients with heart failure, have an ejection fraction of greater than 40%. We really need to understand what SGLT2 inhibitors can do for these patients. And here's the good news. And there are two large scale trials that are both nearing completion. And the first of those trials will be reporting out in about nine months from now with the next trial following about six months later. We will in the next 12 to 18 months, have two major large scale trials of these drugs in a population which is highly different and yet complimentary to the patients who have been studied to date. Dr. Greg Hundley: Justin, how about you? Dr. Justin Ezekowitz: Well, to compliment what Milton is suggesting, I think that's one area. And I think the other area is in implementation science. Now that we have four big classes or groups of drugs, is to how to start these and how to optimize these efficiently in the first month to two months or even three months so the patients can get the benefit for all these medications. And I think what we need to really study is how do we do that? Because we have the drugs but the implementation is where we're not quite there yet. If we get the implementation and testing, randomized strategies and how to do it, I think we may be able to help more patients globally than with the addition of even any new drug that may come out onto the markets soon or in the future, as that remains one of our challenging topics. Dr. Greg Hundley: Well listeners, we want to thank Dr. Milton Packer for bringing this study to us at Circulation and also our own associate editor, Dr. Justin Ezekowitz and really highlighting how the initiation of this SGLT2 inhibitor, empagliflozin, at 10 milligrams per day, in a heart failure reduced ejection fraction population with an average left ventricular ejection fraction of 27%, resulted in a 12 day, at 12 days into therapy, a separation of the development of adverse heart failure related events that was then sustained over the next 16 months. Dr. Greg Hundley: Well, on behalf of Carolyn and myself, I want to wish everyone a great week and we will catch you next week on the run. Dr. Greg Hundley: This program is copyright of the American Heart Association, 2021.  

#098 - Die Videokonferenz zwischen Kanzleramt und magischem Auto-Dreieck (Baden-Württemberg, Bayern, Niedersachsen) hat kein nennenswertes Eregbnis gebracht: Ob eine Kaufprämie kommt, ist völlig unklar. Wir wundern uns und unterhalten uns derweil ein bisschen über das T-Roc Cabriolet von Volkswagen.  // Autotelefon - Der Podcast über Autos. // Jetzt abonnieren! Für Bewertungen und Rezensionen sind wir dankbar! Kontakt via http://instagram.com/autotelefonpodcast

#076 - Hat sich Stefan schon einen Tesla Cybertruck reserviert? Ist etwas gut nur weil es anders ist? Wie transportiert man ein echtes Cyber Girl? Was hat sich Mercedes-Benz beim Kühlergrill des Maybach GLS gedacht? Wie fährt sich der Polestar 1? Die Antworten geben Paul-Janosch Ersing und Stefan Anker. // Autotelefon - Der Podcast über Autos. // Jetzt abonnieren! Für Bewertungen und Rezensionen sind wir dankbar! Instagram: http://instagram.com/autotelefonpodcast

#039 - Nach zwei Generationen Auris feiert Toyota die Rückkehr des Corolla. Die Verantwortung dafür trägt ein Mann namens Yasushi Ueda - der Chefentwickler des neuen Corolla. Während Paul-Janosch Ersing über Hybridantriebe philosophiert, träumt Stefan Anker noch von seiner Testfahrt mit einem Lamborghini. // Autotelefon - Der Podcast über Autos. // Jetzt abonnieren! Danke für Rezensionen und Bewertungen.

#038 - Modelleisenbahn oder Auto-Rennbahn? Diese Frage beantworteten schaue Jungs früher gerne mit: "Beides!" – Heute lassen 24-Stunden-Rennen mit Slotcars nicht nur Kinderherzen höherschlagen. Stefan Anker hat sich auf eine solche, nahezu frauenlose Veranstaltung gewagt. // Autotelefon - Der Podcast über Autos. // Jetzt abonnieren! Danke für Rezensionen und Bewertungen.

#035 - Die "Welt" verzichtet seit Anfang des Jahres auf ein eigenes Auto-Ressort: sowohl in den gedruckten Ausgaben als auch online. Für Stefan Anker bedeutet das eine berufliche Neuorientierung - er ist jetzt genau so frei wie Paul-Janosch Ersing. Doch was ist eigentlich Freiheit? Ein Leben ohne Tempolimit?  // Autotelefon - Der Podcast über Autos. // Jetzt abonnieren! Danke für Rezensionen und Bewertungen.

#012 - Was hat Jennifer Rush damals gesungen? Daewoo, Daewoo und Du – das Auto, Dein Freund. In der aktuellen Episode von Autotelefon sind Stefan Anker und Paul-Janosch Ersing kurz davor, auch für neue Marken wie Cupra, DS oder Polestar komplett neue Werbesongs zu komponieren. Achso, und wie sieht nochmal gleich das neue Cupra-Logo aus? // Jetzt abonnieren! Folgt uns auf Instagram: http://instagram.com/autotelefonpodcast

Glückauf! Wir sind unterwegs zur Bildband-Präsentation von Stefan Anker und nutzen die Zeit dorthin zu einer neuen Podcast-Folge. Stefan hat die deutsche Rockband “Subway To Sally” über 1 Jahr lang bei allen Aktivitäten auf und neben der Bühne begleitet. Obendrein quatschen wir über das neue Sigma 14-24, Lightroom und tauschen uns (mal wieder) über amtliche […]

#010 - Auf der Autobahn unterwegs sind Stefan Anker und Paul-Janosch Ersing in der Jubiläumsfolge. Dabei tauschen die beiden den einen oder anderen Gastro-Tipp aus und wundern sich über Leute, die an italienischen Mautstellen mit Münzen zahlen. Wie funktioniert die Rettungsgasse, wie wichtig ist guter Handyempfang und wer sammelt eigentlich sonst noch so diese Wertbons von Autobahn-WCs? // Jetzt abonnieren! Wir freuen uns über Feedback auf http://facebook.com/autotelefon

#009 - Was genau ist eigentlich Cabriowetter? Stoffverdeck oder Klappdach aus Stahl? Mütze oder Strohhut? Wie sieht's mit Rolldach-Autos und dem Targa aus? Diesen und anderen Fragen gehen Stefan Anker und Paul-Janosch Ersing in der neunten Folge ihres Podcasts nach. Und ganz nebenbei fallen auch Wörter wie Warmluftsee, Nackenföhn und Kopfhaut-Sonnencreme. // Autotelefon - Der Podcast über Autos. // Jetzt abonnieren! Wir freuen uns über Feedback auf http://facebook.com/autotelefon

Boxenluder wurden abgeschafft, die Qualität des Kraftstoffs ist überall auf der Welt 1A, echte Überraschungen gibt es bei Autorennen heutzutage nur noch in jedem siebten Ei. Kein Wunder, dass Stefan Anker und Paul-Janosch Ersing auch über die Anfänge des Motosports plaudern – als noch tollkühne Hallodris hinterm Lenkrad schwitzten. Was hat Motorsport mit Beach-Volleyball zu tun? Sollten Langstreckenrennen olympisch werden? Die Antworten gibt's nur hier zu hören! // Autotelefon - Der Podcast über Autos. // Jetzt abonnieren! Wir freuen uns über Feedback auf http://facebook.com/autotelefon

Wie beschreibt man einen Nissan Pulsar? Welche Highlights lassen sich an einer Honda Civic Limousine entdecken? Was fasziniert die Leute an einem VW Touran? Schwierig, schwierig. Autojournalisten sollten keine Fanboys sein. Darauf können sich Stefan Anker und Paul-Janosch Ersing einigen. Ansonsten haben die beiden in dieser Episode etwas unterschiedliche Ansichten - und untermauern diese mit messerscharfen Argumentationsketten. // Autotelefon - Der Podcast über Autos. // Jetzt abonnieren! Wir freuen uns über Feedback auf http://facebook.com/autotelefon

Anlässlich der "Auto China 2018" treffen sich Stefan Anker und Paul-Janosch Ersing mehr oder weniger zufällig in der chinesischen Millionenstadt Peking. In einem fensterlosen Besprechungsraum erörten die beiden Autojournalisten u.a. folgende Fragen: Sterben Automessen langsam aus? Für wen lohnt sich der enorme Aufwand noch? Was bringt einem ein Messebesuch? In einer Nebenrolle: die wahrscheinlich längste temporäre Rolltreppe der Welt. // Autotelefon - Der Podcast über Autos. // Jetzt abonnieren! Wir freuen uns über Feedback auf http://facebook.com/autotelefon

"Hey Mercedes, erzähl mir einen Witz!" – Was die neue Sprachbedienung in der neuen Mercedes-Benz A-Klasse auf diesen Wunsch antwortet, verraten Stefan Anker und Paul-Janosch Ersing in der dritten "Autotelefon"-Folge. Zum ersten Mal telefonieren die beiden nicht miteinander, da sie gemeinsam in einem Auto sitzen. // Autotelefon - Der Podcast über Autos. // Jetzt abonnieren! Wir freuen uns über Feedback auf http://facebook.com/autotelefon

Stefan Anker und Paul-Janosch Ersing sind sich einig: SUVs zählen nicht zu ihren Lieblingsautos. In der zweiten "Autotelefon"-Episode werden die Vor- und Nachteile der angesagten Pseudo-Geländewagen diskutiert. Mit dabei: ein Citroen E-Mehari und ein Auto, über das noch nicht gesprochen werden darf. // Autotelefon - Der Podcast über Autos. // Jetzt abonnieren! Wir freuen uns über Feedback auf http://facebook.com/autotelefon

Stefan Anker und Paul-Janosch Ersing besprechen in ihrer ersten Folge, was einen guten Autofahrer eigentlich ausmacht. Dabei wird im Detail geklärt, worauf es hinterm Lenkrad wirklich ankommt und was das Thema mit dem Bundestrainer zu hat. // Autotelefon - Der Podcast über Autos. // Jetzt abonnieren! Wir freuen uns über Feedback auf http://facebook.com/autotelefon