 Good morning, everyone. I'm Joe Rogers, the president and CEO of the Texas Heart Institute and welcome to our global cardiovascular forum. I'm delighted this morning to be able to provide a talk to you on guideline directed heart failure management and the implications from some of the newest guidelines from the American College of Cardiology. So this is the document that I'm going to refer to throughout my talk. This was published last year in Jack. And I would just recommend that those of you who are attending pull this paper and spend some time with it. It's an excellent document, as we've learned to expect from the American College of Cardiology, that really reviews the guidelines to date and the data that underlies the recommendations. But I think the other part of this document that I found very interesting was it's very practical. And it provides all of us who take care of patients some really good advice about how to start and titrate medicines, when to switch drugs, how to think about coordinating care for our patients, and then focuses on some other issues like medication compliance and the cost of some of the medicines. The list of sort of how to's is over on the right side of this slide, but I would encourage you to pull this and spend an hour reading it. It's a very well done and thoughtful document. I'll spend the rest of my time talking through some of the issues that I think are most relevant and updates to the guidelines that we're all familiar with over the past decade or so. And I think it's an exciting time in heart failure because we finally have some new therapies that have been shown to reduce both the morbidity and the mortality of heart failure. I'll start with this just to remind you of the global prevalence of heart failure. This is a global forum and I wanted to make sure that those of you who are watching from other parts of the world have a sense about the prevalence of heart failure in your particular area. You can see that in North America we have sort of a moderate prevalence of heart failure in Central America. It's a little bit lower. There's some interesting hotspots in Southern Europe and in Eastern Europe, as you can see in this map. But no part of the world is excluded from the burden of heart failure on our patients. And there's some really sobering data that's being put out by the Heart Association suggesting that at least in the United States over a couple of decade period that the prevalence is expected to increase by almost 50%. And I suspect that that's a similar kind of theme across the globe. So I'm going to start with my comments and the document that I referred to earlier really talking about our strategy for heart failure with reduced ejection fraction. Those are people with ejection fractions of under 40%. And then I'll turn and spend a little bit of time talking about heart failure with preserved ejection fraction. But at least to start off with the guideline directed medical therapies and approaches for people with heft ref. And I want to just emphasize to you that one of the important parts of this document is an emphasis on the urgency of getting people started on therapy and getting their therapies titrated. In other words, this sort of somewhat laxadaisical approach to seeing someone in the office starting them on a heart failure medicine, seeing them back in six months is no longer considered to be standard of care. So what you see on the right side of this slide is a guideline about how you begin to approach that some studies to start off with when you are originally evaluating a patient with heart failure including some blood work to understand where they stand with regards to their natural peptide levels, some screening laboratories to make sure that their kidney function is okay and that there's not other causes for their symptoms, an electrocardiogram, a chest x-ray and echo. And in some of those patients they should have a cardiac MRI or a cardiac cath or a biopsy. And this document walks through the guidance around those issues. But the important box I think is right below that and it's that there's an emphasis on seeing people back in the short term to start those medicines, to titrate medicines, to add new medicines so that we get people on a very comprehensive guideline directed approach in the span of a couple of months. And then at the bottom of the slide you'll see that there are recommendations about how to follow those patients up and when to reassess and how to reassess. And maybe more importantly in this yellow box on the right side is what do you do if patients don't respond the way we expect the majority of patients to respond to a guideline directed medical therapy approach. And there's sort of a nifty mnemonic called I Need Help which you can see on the right side of the slide that outlines for all of us the patient population that's at high risk that you might consider referring for advanced heart failure therapies. So here's what we're seeing today about heffereff, symptomatic heffereff. And the foundational medical therapies really start with drugs that block the renal angiotensin and aldosterone system and you'll know that the drug Valsartan succubitril has been shown to be superior to ACE inhibitors and really is the preferred drug for blocking that system today. So the foundational therapy really is an arny. If they can't tolerate that an ACE inhibitor or an ARB coupled with a beta blocker. And you know there are three evidence-based beta blockers, carvetolol, the extended formulation of metoprolol and basoprolol. And then the third foundational therapy is a diuretic which we all know has not been shown to improve survival in heart failure but certainly is an important component of our therapies to minimize symptoms. So after you've established that baseline therapy then you can begin to tailor additional therapies based on the phenotype of the patient that you're seeing. On the far left side of this slide, if a patient has reasonable kidney function and a preserved and a potassium that's in therapeutic range there's compelling evidence to start a mineralocorticoid receptor antagonist. On the second column there's a compelling and growing body of evidence to use SGLT2 inhibitors and I'll review that in just a little bit. A flexible diuretic regimen. And then for a patient population whose self identifies as African American who's already on good background therapy and has sufficient blood pressure you might consider adding the combination of hydrolzine and nitrates. And finally on the right side of the slide for individuals who have a persistent heart rate of over 70 and once you get them on all of those other therapies and they have class 2 and 3 symptoms you could consider the addition of evaporidine and in this document there's fairly clear guidance about how to use this combination of medicines most effectively in patients with heffereff. I wanted to focus in a little bit on the arnes just because this is the newer class of drugs as we talked about to block the renan angiotensin system and I just wanted to highlight for you the contraindications and cautions for the use of this class of drugs. Remember that it's still important for us to stop ACE inhibitors for at least 36 hours before we start an arne allow that washout period before you start the drug and remember that patients who have a history of angioedema for any cause should not be started on an arne therapy. It's contraindicated in pregnancy in women who are breastfeeding and individuals with severe liver disease those who are on Alaskarin who are diabetics and individuals who have a hypersensitivity to an ARB because remember Valsartan is a component of those drugs. It should be used in caution with people who have kidney insufficiency, who have mild to moderate liver disease, who have renal artery stenosis, who start off either hypotensive or who are volume depleted. So those are some pretty easy guidelines to use as we think about using that class of drugs and there's one drug in that class today for our patients with HEFREF. The other foundational therapies and we talked a little bit about the beta blockers, the flexible diuretic regimen, I wanted to highlight a couple of issues related to the MRAs which is in column E. Remember that the data that we have to support these comes from some of the early trials like the Rawls trial demonstrating a reduction in cardiovascular mortality and heart failure hospitalization with some very important caveats. One is patients should have preserved kidney function and a potassium level that's in a normal range before we start this class of drugs and it's very important that you do follow-up renal function testing on that patient population and the guidelines are pretty specific. They say if your patient's not terribly compliant or you're worried that you may not be able to get those follow-up laboratory studies done, you really have to be thoughtful about using this class of drugs because of the risk of worsening kidney function or hyperkalemia. And then on the right side of this slide, this new class of drugs, the SGT-2 inhibitors, and the story about this is really a fascinating story. A group of drugs that started off as a group of compounds used to treat diabetes, but we've subsequently found them to be effective both in HEF-REF and HEF-PEF and I'll show you that data. And some of the contraindications and cautions for the use of these drugs, that class of drugs is contraindicated in type 1 diabetes and those who have a hypersensitivity, women who are breastfeeding and those on dialysis. And some cautions to think about as you're starting the couple of different choices you have, a depagliflozin or impagliflozin based on baseline kidney function, whether there's a history of mycotic genital infections in people who have ketoacidosis and acute kidney injury. And remember there's always a risk for your sepsis and forniase, gangrene. But the data is very interesting and compelling. I still don't know that we have a clear idea of how this class of drugs works in a HEF-REF population. I've shown some putative mechanisms for this class of drugs on the left side of the slide. But on the top right of the slide, what you see is a meta-analysis showing this very consistent pattern and message that patients who have HEF-REF treated with an SGLT-2 inhibitor have reductions in cardiovascular death and hospitalizations for heart failure as a combined endpoint. They have reductions of both of those components of that combined primary endpoint. They have improvements in a composite renal outcome. And if you look at all-cause mortality, it favors the use of the drug. And down in the middle on the bottom of this slide is the data from the Emperor Reduce Trial, which took a cohort of patients and randomized them. This is a heart failure population with reduced ejection fractions. On good background therapy, randomized them either to impaglifluosin or placebo. And the epaglifluosin group had a reduction in cardiovascular death and heart failure hospitalization. So now the therapy is getting a little confusing. And I'm going to veer from the guideline document that I alluded to earlier just to provide you a little bit of perspective from two luminaries in the field. This is some work that John McMurray and Milton Packer published last year in the European Journal of Heart Failure where on the left side of the slide you can see how we all learned how to manage HEF-REF starting with an ACE inhibitor and ARB and then adding a beta blocker and then adding an MRA. And this is why it took so long to get patients on contemporary heart failure therapy. But these two heart failure experts have said, why don't you think about doing this in a different way and condensing this and starting with both a beta blocker and an SGLT-2 inhibitor and then rapidly adding on in the span of a couple of weeks an ARNI and if the patient is still doing well a couple of weeks later adding an MRA and then going on beyond that to titrate drug doses but at least as a way to get people on evidence-based guideline directed medical therapy this would be a way to sequence this in a more quick manner. So I want to turn from HEF-REF to HEF-PEF, the population of patients that have heart failure with preserved ejection fraction. This guideline has not been updated but I wanted to update you on some more recent clinical analyses that have been done. This was a paper that was published in Jack in 2017 and if you look at the guidelines on the left side of the slide this is very intuitive for most of us. It was controlling blood pressure, controlling AFib with RVR, revascularizing patients who were ischemic, controlling volume status with diuretics. That was sort of what we had in our toolbox for treating half the patients who have symptomatic heart failure who have preserved ejection fraction. But I wanted to review two trials in this series that I think are important and we should be thinking about. The first is Topcat and this actually ended up in the 2017 guideline as something you could consider adding spironolactone to this patient population and on the left side of the slide what you see are the results from the Topcat trial, a trial that randomized patients with HEF-PEF to either placebo or spironolactone and you'll remember that in that trial there was not a statistically significant difference in the primary endpoint of cardiovascular death, aborted cardiac arrest or heart failure hospitalization between the two groups. But I also want to emphasize to this audience that it mattered where you were enrolled in the trial. So they were having trouble enrolling in the study. They expanded the enrolling centers into Russia and Eastern Europe and the data for that analysis is shown on the right side of the slide. You can see that the patients who were enrolled in Russia and Eastern Europe had a much lower mortality rate than if you were in the Americas and there was no effect of the drug whereas if you were enrolled in the Americas spironolactone seemed to have a favorable effect. And so what I would argue is that if you're enrolling patients who look like a clinical trial patient it's likely that they're going to have an outcome that's much more similar to what we saw in the Americas in this analysis and spironolactone may actually provide an important advantage with regards to that combined primary endpoint that we talked about. So I would advocate for following the inclusion criteria for that trial and using spironolactone. And then I'll come back to the SGLT-2 inhibitors because the emperor preserved trial was presented and published last year a trial of empagliflozin in patients who have preserved ejection fractions but you didn't have to have diabetes to get into the trial. A 6,000 patient trial with a primary endpoint of cardiovascular death and heart failure hospitalization. And you can see a greater than 20% reduction in that primary endpoint in the patients who are randomized to empagliflozin versus placebo. I think the next time the HEPEF guidelines get updated you will see a strong recommendation for the use of empagliflozin in this patient population. I would be remiss to not remind you and the guidance document that I talked about at the beginning of this discussion emphasizes the management of comorbidities. Heart failure tends not to occur in isolation. It occurs with a variety of different medical conditions and frankly a variety of different psychosocial conditions. To get an optimal outcome in the patient population we have to be thinking about how to manage all of these other comorbidities to improve the outcomes for our patients. And finally there's a nice section in that document about when to consider referring a heart failure patient to someone who has advanced expertise in heart failure. So as you know there is a board examination for heart failure specialists and I would consider sending patients who have this high risk profile to a heart failure specialist. A new onset heart failure patient who may need additional evaluation. The chronic heart failure patients who need inotropes who are persistently have advanced symptoms who are hypotensive or can't tolerate medical therapies who have worsening kidney function, uncontrollable arrhythmias who are in and out of the hospital who have persistently low ejection fractions you need a second opinion or you can think about sending them for enrollment in a clinical trial. So I'll summarize and conclude this way by thinking a little bit about heifer F we know what the foundational medications are. Arnes, ACE inhibitors or ARBs with a preference to the arnes plus a beta block or in a loop diuretic I think there's compelling evidence for the addition of an SGLT-2 inhibitor and consideration of a mineralocorticoid receptor antagonor like spironolactone or a plarenone. And then hydrolzene nitrates in a Vabardine in a more select patient population for Heffpeth manage the comorbidities I think the Topcat data would suggest that if you're following the inclusion criteria that your patients will get a benefit from an MRA and this growing and interesting evidence about the use of SGLT-2 inhibitors in the Heffpeth population. But maybe most importantly is this idea that there is an urgency to get patients back in the office to get them on guideline directed therapy and to titrate them to the doses that we've been shown have been shown to be effective in clinical trials in reducing heart failure, morbidity, mortality and then don't forget that there are our colleagues who have advanced heart failure training who are very willing to see this patient population for those who are not responding to a guideline directed therapy approach. So thank you very much. I hope you enjoy the rest of the conference and I'll look forward to our panel discussion.