 So, Stephanie, thank you for the kind invite, and it is good to, in many ways, come home. I remember walking the corridors and no shortage of excellence in work, and a lot of who I am today is because of my training. I think that holds true for most, and seeing familiar faces, friends, and colleagues is certainly a delight. So I very much appreciate the opportunity to dig in deep, if you will, to highlight heart failure in women. And my goals are to review the epidemiology, focus on evidence-based sex differences, keeping in mind both medications and how we're using devices to treat this population. But I think most important, despite improvements really over the last 20, 25 years, heart failure still remains common, costly, and lethal. We're 6 million patients with heart failure in the United States, up to as high as 10 million outpatient visits. And what it means in terms of morbidity for our patients, frequent hospitalizations. And I'm going to provide some updates from the heart disease and stroke statistics. But I do want to take a step back and highlight Senator Spector. I don't know if you all have heard of Senator Spector. This is 20 years ago, he unanimously was able to get passing of a Senate resolution to declare National Heart Failure Awareness Week. And he did so as highlighted by Dr. Willerson to highlight the relative inequities based on NIH funding. And for breast cancer, it's certainly an important disease. And lung cancer, 28 to 132 million for research, dismal when it comes to heart failure-related research support in terms of NIH funds, despite the prevalence of heart failure being, as mentioned, double these two diseases combined. So I don't know if you know or not, but it's tomorrow. It starts. Heart failure awareness week is tomorrow and all of next week. And I think it's important to highlight these gaps in knowledge. I think it's important to focus in on treatment awareness. And most importantly, each of us to do our part in knowing the implications of heart failure. Not only in women, but this unfortunate syndrome doesn't discriminate younger patients, males and females. It was highlighted the typical symptoms in women we know can present with atypical symptoms. But we're going to go over this very carefully. So Varani, who I believe is going to be given a talk, chaired this very nice update about heart disease and stroke statistics. And what you can appreciate is that over 3 million women in the United States with heart failure. And while the prevalence is a little lower than men, given that there's more women, there's actually more patients. And unfortunately, the mortality, when you look at newly diagnosed depressed EF and go out four to five years later, is still very, very alarming. And hospital discharges in this patient population is very concerning. And what it means for us in terms of our economics, this is a 30 billion estimated to be above a 50 billion cost to us over the next several years. So when you look at the National Health and Nutrition Examination Survey and focus in on females as highlighted in red compared to males, in the age group 40 to 50, the prevalence is actually higher. Now it is true as patients get older, the prevalence of heart failure is higher in terms of percent of the population for both men and women. I think it's very important to recognize, and this is excellent observations from the Eric community surveillance by sex and race in the United States, close to 10-year cohort. What you can appreciate is, while yes, women in green compared to males as it relates to rate acute to compensated first, acute to compensated heart failure episode for females is less than men, black females really across the board up to age of 74 have a higher event rate related to first decompensation than men. And I think that's not as recognized certainly as it should, and certainly an alarming rate compared to men even after the age of 75. So we're learning more about the epidemiology of heart failure mid-range EF, that's 40 to 50 percent in those with the clinical syndrome and preserved EF, EF greater than 50 percent with the clinical features of heart failure. And I think it's important to recognize if you look at the prevalence of those from the get with the guidelines, heart failure with preserved ejection fraction is actually more common in women. And that's an observation that stems from other data cohorts. And so when unfortunately this condition, whether it's depressed EF or preserved EF is associated with a number of comorbidities and I like to highlight those in females compared to males and those with reduced EF and preserved EF. And I think it's important to highlight underlying hypertension, certainly in those with preserved EF a bit more common. Less common is ischemic disease. Not that that's not a significant contributor to acquired cardiomyopathy. It's just less so in men. But this patient population needs to be screened for underlying coronary artery disease is a common reason for the heart failure. More valve disease in females. And in the setting of less tobacco use, less peripheral vascular disease compared to males. Now, one of the great things is not much great about heart failure with reduced ejection fraction. But one of the things is that we have guideline directed medical therapy. And I'm going to walk through guideline directed medical therapy and put in perspective highlights as it relates to analysis in females compared to males. Unfortunately, not to ignore mid-range or preserved EF. The reason I say that is, yes, when you look at large cohorts of patients, all cause mortality is worse in those that have the clinical syndrome with reduced EF as exemplified in the right curve compared to the blue and the preserved EF curve. But all cause re-hospitalizations are higher in those with preserved EF, likely due to comorbidities and heart failure re-hospitalizations common in certainly in both groups. And whether it's coronary artery disease or hypertension, I think this has been well defined, at least in global terms, the underlying pathophysiology with a compromise in stroke volume and output. There's increased neurohormonal response due to underlying sympathetic stimulation, elevation of the RAS system. This lends to systemic vasoconstriction, increases the volume status and the aphrodol, which is deleterious for the heart. It's unfortunately a vicious cycle. I'm not going to spend a lot of time trying to define to you the underlying physiology differences between males and females. Other than the highlight, we certainly know that estrogen compared to androgens and its effect on the heart, vasculature, skeletal muscle, and the kidney are different. And while some of these may seem to be beneficial as it relates to attenuation of hypertrophy or vasodilation, it truly hasn't been studied in terms of how to tease out the underlying physiology and tailor our therapy to get the most benefit. And so I mentioned the management of heart failure with reduced EF as well defined, and this stems from the update from quite yancy and colleagues as it relates to the guidelines. And I know it's a bit small and we won't go through the details, but we implement this medicine to curb morbidity and maximize survival because we've known that those patients with a depressed EF less than 40%, prior symptoms of breathlessness or current symptoms, their annual rate may be as high as 10 to 15%. And we tried to alter the projection because those that define or fall into this category more in keeping with end-stage heart failure, their annual risk will certainly be above 25%. And when we think there's more than a 50% chance of one of our patients dying over the ensuing 12 to 18 months, we're worried about end-stage heart failure. And so before I get into the details of the different trials, I will take a step back, if you will. This is a nice publication from my colleague Eileen Sheeth at the Cleveland Clinic, and she looked at the percent of women in these landmark heart failure trials. And I do appreciate it's a bit small, but when you look at the range from 0 to 40%, and focus in on those main or landmark beta-blocker trials, mineral retocorticoid antagonistic trials, the RELS trial, the Solve Treatment Trial, which is one of the first that put ACE inhibition on the map, 20%. So 20% representation, which is under representation. And so the Solve Treatment Trial, we certainly appreciate work that stems back closer to 30 years ago when you're on and out, real compared to placebo, all causing mortality reduction and a composite of death or heart failure hospitalization, overwhelmingly favorable. And even in the absence of symptoms, if there is an incidental detection, if you will, by workup of an EF less than 40%, and you're on an ACE inhibitor, which you should be put on versus placebo, while there's not an improvement in mortality, there's an improvement in the composite meaningful endpoint of reduction in death or heart failure development or heart failure hospitalization. And so what is the data as it relates to ACE inhibition use in females? And so this is a nice analysis of six trials, and you can appreciate when you look at the relative risk and the line of unity that it spans, and the confidence intervals are broad, and you focus in on the Solve Treatment, it should position us as a community to say, okay, is ACE really working as well as it does in males? Not to say we shouldn't be using it. So ARB is certainly important in blunting this abnormal pathway I've highlighted to optimize outcome, and we've learned from landmark trials and those that are intolerant to ACE, being on, for example, Valsartan or Candesartan is associated with significant improvements in survival or cardiovascular death or heart failure hospitalization. And when you look at an analysis of ARB in females with heart failure, compared to ACE, certainly more reassuring as it relates to the hazard ratios and the confidence intervals. So ARB certainly in this patient population seem to be very helpful, and this is a very nice analysis from Dr. Hudson in college. He's now dated probably about 13 years back, and he looked at cumulative survival in women when we're on a ARB yellow compared to ACE gray, and on your right-hand side of the screen, men, same comparison, and you can appreciate by Kaplan curve comparison that in multivariate risk adjustment, women had better survival on ARB than ACE. No difference when you compare to men. I don't know how much of that is recognized, to be honest with you, not only in the heart failure community, but the community at large. Now beta blockers have been cornerstone in addition to ACE and or ARB. That's because these landmark trials nicely highlighted significant risk reduction in all cause mortality. Remember the United States, we have Carvetal Law, Byspropal Law, or Metopal Law succinate that we should be using. And when you look at the effects of beta blocker on mortality in men and female patients as was done in this very nice publication led by Lynn Warner Stevenson, you can appreciate very reassuring risk reduction observations and confidence intervals that don't span that line of unity, at least as much when compared to the ACE data I showed you. So beta blockers seem very, very favorable. And as patients progress, certainly with New York Heart Class III moderate breathlessness, despite the use of ACE or ARB or beta blocker, spurnal lactone would be indicated and that stems from the landmark Rails trial, which is now, again, a little bit more than 20 years old. And when you look at the Rails trial and the more contemporary trial that has demonstrated the efficacy of using an aldosterone antagonist and less symptomatic patients in New York Heart Class II from the Ephesus trial, but spurnal lactone use in females compared to male, very, very favorable. So very reassuring that this medicine is working as much as we would hope for. And often forgot about combination pill, hydrosine, and isodilin. For those patients that are persistently symptomatic, this stemmed from patients self-defined African-Americans, despite background use of ACE, beta blocker, or aldactone, a survival advantage in adding this medication. And I think this AHAV trial was very, very important, because when you look at the contemporary trial, the VA cooperative study, only men were studied. I think that would not be permissible today. But in the AHAV trial, increased survival in both females and males, and when you look at the specifics related to those females on hydrosine, that's the IH white compared to the placebo, improvement in survival, reduction in first hospitalization. So very, very reassuring. So I'm going to talk about more novel drugs or relatively new. This stems back from the fast tracking from the FDA in 2015. I'm not going to spend a lot of time on i-vabberting, but I do want to talk about intrestal. And when you have heart failure, your endogenous vasoactive peptides are compensatory. They are associated with reduction in vascular tone, reduction in cardiac fibrosis, and less sodium retention. So neprolysin inhibition will minimize the degradation of these very favorable endogenous vasoactive peptides with a thought that our own body's enhancement would prevent progression of this disease. Now, this needs to be saccubitrile, needs to be coupled with an ARB to blunt the concomitant increase in RAS. So this led to the paradigm heart failure trial, which was landmark largest heart failure trial ever, comparing intrestal 400 milligrams versus an aliparine. An aliparine was chosen, but it is the gold standard in terms of outcome endpoints compared to ARB. And dose matters in this regard, and so that's why 20 milligrams was used. And when you look at the results, primary endpoints, significant reduction in New England Journal tends not to publish P values. And in this case, they did, and I think Milton Packer was influential in that regard. But you can see significant improvement, not only the primary end point, but significant improvement in survival while being on intrestal instead of an ACE inhibitor. So very, very, very remarkable observations. And where the field's moving is using this medication in the hospital. So those patients that have a decompensated heart failure episode, that is a red flag. Patients, when you look at large cohorts, like from the Mass General Setaguchi and colleagues, they've been admitted to four times the hospital mortality may be as high as 40% over the ensuing 12 months. So every hospitalization should be a red flag, not only to understand what provoked that hospitalization, try to render someone new volumic, but to put them on a medicine that's gonna alter the trajectory. And so this wasn't powered to look at clinical outcomes, Velasquez and Collies, but they did look at changing N-terminal probe BMP and being on intrestal, used once your OSFASO active meds were on a stable dose of diuretic, was very favorable and very well tolerated. And so the question is, well, what are the observations related to the use of this medicine in females? And unfortunately, much like is the case when I showed you the under-representation in the landmark trials, only about 21, 22% of females in this international, very, very large study. This was a stage C heart failure with reduced DF patient population, median injection fraction around 29%. The vast majority were New York Heart Class two and three. So there's been a nice examination of looking at not only the paradigm heart failure trial, but Paragon, which was positioned and put to examine the role of intrestal and those with heart failure with prosertia. And Beacon Boskert, my colleague and friend who's now the president of the Heart Failure Society of America, put a very nice editorial with Justin Zequitz from Canada. And what they highlighted in this depiction is what we learned in that all subgroups within the paradigm heart failure, including women and men, equally benefited. And so Arnie and those with heart failure reduced DF is a sound observation. Now, before going into some of the more contemporary observations of the use and intrest on those with heart failure with preserve DF, I do wanna highlight that this has been very a disappointing journey as it relates to the use of beta blockers, ACE inhibitors, ARBs, mineral corticord receptor antagonists to move the needle on meaningful outcome in this patient population. I can state it fairly easy. Nothing's worked to improve morbidity or mortality in those with heart failure with preserved ejection fraction. So what about intrestal? So this was a very important trial close to 5,000 patients, half of which received intrestal versus Valsartan. The primary endpoint was total hospitalizations for heart failure and cardiovascular death. This is a very tough group to treat. There's a heterogeneity in terms of underlying cause, but there was, importantly, in this trial, pre-specified group analysis. And there is a sound observation that women and those with heart failure of preserve DF may benefit. And so McMurray and colleagues more recently published their formal analysis and you can appreciate on your left the primary composite outcome and on your right the total hospitalizations for heart failure. Women on Valsartan and the dashed red compared to those on intrestal and a significant difference as it relates to improve outcome on this novel of combined medication. And when you look at tolerability, we've learned from the paradigm heart failure that on average you may see a seven to eight millimeter decrement in blood pressure. And so blood pressure was lower in those on intrestal, true for both women and men, but as it relates to elevated serum creatinine and elevated serum potassium, actually a little bit lower for both women and men and no other worrisome signals as it relates to intolerance specifically for females. So I think not only is there a benefit, there a safety. And so it begs the question is, this ejection fraction cut off and when we're in the echo lab we're trying to be as concrete and granular and there's an inter-observer, inter-observer variability that may span five, six percent at least try to quantitate as best we can and dead core labs to adjudicate this. But women have underlying differences as it relates to stroke volume and heart size and LV mass. And this is a nice observation from Solomon and colleagues that perhaps the treatment effect by EF and gender is different, blue compared to red where the rate ratio if lower more favorable as exemplified by being more favorable in females as it relates to the treatment effect of intresto in this patient population. So this was a nice, really new clinical perspective highlight that the clinical benefits of South Gibutral of Al-Sartan appeared to extend to a higher LV EF in women compared to men. So perhaps a potential target population in the future. And so become nicely compared in contrast to what we've learned from Arnie use in these very important trials and to summarize women benefited from Arnie as it relates to heart failure hospitalization reduction. There was no significant reduction in mortality but reassuring to see. And so at the end of the day, what is the summary as it relates to medicine use? And so certainly the guidelines tell us that either ACE or ARB or Arnie are class one recommendations to use this. But importantly, if you have someone's relatively stable but some degree of breathlessness with a EF under 40%, if they're female or male, keep in mind the data I mentioned related ACE inhibition, you would want to, if you were to want to ensure you're using the most available data, they should be on an Arnie, plus a beta blocker, plus their sperm along a Dostrona antagonist to best reduce morbidity and mortality. So let's switch gears and start talking about devices in heart failure. And ICDs certainly are indicated post-MI. Those are 40 days out to curb a sudden cardiac death. And in those with EF less than 35%, we have some symptoms to minimize dying from sudden cardiac death. There's been some discordance, if you will, in the literature as it relates to ICD survival, specifically among women. And here are the four really landmark trials. Scott Heft made it to definite and companion and you can appreciate when you look at the hazard ratio, whether there's clear benefit or not in women certainly be worth discussing. And when you look at appropriate shocks or inappropriate shocks, there are more inappropriate shocks in women, the red Kaplan-Meier curve and more appropriate shocks in men as it relates to ICD use. This doesn't mean we don't follow the guidelines and place ICDs, but it certainly begs the question on how much benefit are we getting given this gender difference. Now CRT has really changed our field and it permits us to try to normalize a heart for those that have overt remodeling. In current guidelines, we know when you have a left bundle branch block and a broad QRS over 150. And we look at the hazard ratio, specifically in those that are female compared to men, very consistent sound observations with tight confidence intervals. So that's certainly a no-brainer and consistent with guidelines. Very intriguing as we go into lower QRS, significant improvements in those females that underwent CRT compared to males, less so when the QRS is 120 to 129. We looked at 130 patients, my colleagues, a few years back at the Cleveland Clinic with a median follow-up of two years and defined response by an improvement in the F of about 10%. And you can appreciate this CRT and potential benefit even when the QRS is a little lower. So not to go against the guidelines in the context of a left bundle, but a broad QRS, but important observations highlighting these differences. And so there is incremental survival in both men and women who have heart failure with reduced DF. And you wanna ensure you're using this medication plus CRT and ICD as appropriate with careful shared decision-making and discussing the benefits of risk with these patients. So let's transition into more advanced heart failure. And I highlighted that as patients are hospitalized, that's a red flag. And patients have that natural progression and we certainly worry about sudden cardiac death. I am from an abnormal rhythm, but we worry about progressive pump failure. And these are the types of patients that are having worsening shortness of breath, persistent fluid, despite your best efforts to use the medicines and devices I've highlighted. The sine qua non behind underlying progressive heart failure is elevated feeling pressure. And it creates secondary pulmonary hypertension. And the number one cause of right-sided heart failure, high CVP or abdominal swelling or leg swelling is left-sided heart failure. And so modes of monitoring have been investigated to understand if we can position ourselves to be more reactive before there's an onset of acute compensated event, both including patient triggered, healthcare provider triggered and more recently implantable devices. And the one I'm gonna just summarize is the PA sensor, the Cardiomem's device. And this is a very easy device that can be placed in the cath lab in the left pulmonary artery. It's wireless biocompatible, powered by radio frequency energy. And it can vary nicely as a patient lies down on a pillow, the prescriptions to do it every morning, can give us the pulmonary pressures. And these are calibrated in the cath lab. And so we now have more of a standard, if you will, not that we're minimizing the importance of acquired symptoms or minimizing the importance of surveillance clinic visits, but we're positioning ourself to react based on triggers of increased pulmonary pressures to alter the trajectory as it relates to congestion. So the landmark trial was a champion trial, which we participated in, this stage back now 2007, six, seven and 550 patients. All patients got the Cardiomem's, half we had access to the hemodynamics, the others we didn't. The primary endpoint was heart failure hospitalization and the specific target was trying to keep the pulmonary diastolic in the normal range under 18 to 20 millimeters of mercury. You did have the capability to follow mean pulmonary pressure and similarly trying to keep it under 25. And at your per your desire in terms of what kind of medicines you wanted to manage that. As it relates to the female representation, remember that common theme, whether it was the cornerstone medical therapy or the use of ARNI in the Cardiomem's, only about 28, 27% of females in this study. And this was, did also include one in five patients with an EF above 40%. So another opportunity to potentially understand the role of human dynamic remote monitoring and those with mid range or a true heart failure would preserve the F. And what the data nicely showed us, separation of the curve in around 60 days is that those with treatment meaning the device in place where we had access to the human dynamics, there was significantly less heart failure hospitalizations. And thankfully it was very, very safe as it related to device or system related complications and very meaningful secondary end points based upon days alive out of the hospital and how patients were feeling by quality of life questionnaires were more favorable on those on treatment meaning Cardiomem's in place with access to human dynamics compared to the controls. So this is the only intervention that we have to date that's gone through the rigors of a randomized control trial with all the caveats and limitations which we can talk about. Those with heart failure preserve the F, red Kaplan-Meier curve versus the blue where having the human dynamics is associated with less heart failure hospitalization. And there have been two data sets to understand these potential benefits indoor risks in a general use cohort, 2000 patients. And what we learned from that experience was that human dynamics were actually a little bit worse compared to the champion trial patient population but we were able to reduce the pressures that area under the curve is exemplified here was much less as it relates to reduction in pulmonary pressures. And very importantly, patients are this is a Medicare claims database patients are staying out of the hospital and we're comparing patients to themselves as you will pre-implant versus post-implant. And this is associated with cost reduction which certainly important in the context of the current more of cost struggles we have across the country with this patient population. So potentially very, very helpful the simple FDA indication class three at least class three symptoms, half for F or heart failure with preserve the F and one prior admit. We were pursuing a guide heart failure trial where we're trying to understand the utility of this system and management and those that are less sick in your current class two and not requiring a prior heart failure hospitalization but having an N terminal probe BMP above a certain level to understand the true benefits of using such a device. Now as patients progress despite what you're doing even if you're positioning yourself to understand human dynamics they progress with hospitalizations and let's say they're not needing to be in the hospital being on a trope dependent or have overt end stage heart failure with shock. You wanna position yourself to track these patients and understand trajectories as it relates to heart transplant LVAD or for select patients palliative care. And when you look at the really observation trials or registries Metamax roadmap in revival about 25 to 35% representation of women. And when you look at end organ interventions and I'll highlight some of the more contemporary observations in transplant 30% women and in VADs 20% women. This is a nice editorial from my colleague at the University of Colorado. So let's talk about transplant and it is still in my mind for select patients to gold standard as it relates to long term of rent free survival. And I illustrate here the median survival most contemporary ICTLT registry data 12.5 years after transplant. And when you look at females and males and you focus in on North America about 25% of heart transplants or to recipients of the female gender. Now one of the challenges is ensuring not only we get to transplant and we have good outcome which I'll show you it's making sure weightless mortality is as low as possible. So this is a nice analysis by my colleague Eileen Sheace and she looked at the old transplant model status one the sickest status one being status two and she did a Cox proportional hazards analysis and adjusted for risk factors we know will translate into more worrisome risk. And what she demonstrated is that being female is a concern as it relates to hazard rate above one for both those that were status one and status two. And when we look at the competing outcomes more males are receiving transplant but yet weightless mortality is greater in females. Certainly for those that I mentioned status one A and status two. And similarly as exemplified here this is the status two similar concept. So one would have to ask well why is that the case? What can we do differently? You know, one of the issues is perhaps this perception of women not appearing as sick more women for to be honest unclear reasons being inactivated and at least in the old transplant model a fewer women being without MCS at the time of receiving a transplant. And so this is gonna be very important moving forward with the new allocation system. Now how do patients do after transplant? I gave you the broad overview. So when you look at how females in green do compared to males long-term they actually have better survival. Meeting survival here 12.2 compared to 14, 11.4. And when you look at conditional survival if a female lives at least one year what is the survival long-term? 14.8 years compared to 13.6. And we spent a lot of time trying to match the right donor heart to the right recipient. And I put this just to illustrate the female to female combination is the best as it relates to comparison to certainly being cautious about gender mismatch in this select patient population. But why would females do better long-term? We have clear data to highlight that these patients develop less vasculopathy much like they have less ischemic disease on the front end less or greater freedom from coronary vasculopathy on the back end similarly to Achilles' Hill for transplant long-term not only vasculopathy but it's infection and cancer. The emails have greater freedom from oligency compared to males. So for the right patient whom we feel needs transplant we don't want them to die and they're gonna have a good outcome we wanna pursue aggressive means to get them there. So this is the new allocation system which changed October 2018 and it's now six status versus three status a clear definition to shock the purpose was to give hearts to those that needed it the most and we did a early investigation and what we're learning is that we are bridging with LVAD across the community less 42% in the old system, 23% in the new system. There's been a significant uptick in the use of temporary support across the board particularly a full four-fold increase in ECMO use in this patient population. New couple that with patients waiting for heart transplant worse hemodynamics a little bit prolonged ischemic time, wait time thankfully has gone down and there was no difference in weightless mortality but there's a lot of talk and discussion about whether the early observations of a decrement in post-transplant survival is gonna hold up and one's gonna wanna be very clear on where females fall in this context as it relates to the challenges we all know in terms of supporting these patients that are smaller and all the biases I've alluded to in terms of the old system and getting patients to transplant. Now while transplant is associated with overall good outcome, there is a epidemiologic mismatch as it relates to the number of patients that need an end organ intervention and this has now come up above 3,400 a year with the use of hep C donors and we're doing some decent donor novel interventions but even if we get up to 4,500 this still is not gonna meet the goal and so let's talk about MCS in the last remainder of my talk and so the first female patient to receive a VAD I saw Dr. Frazier here and I wanted to show him so we can talk about its truth but the baby places and a young lady from Monterey who had a post cardiotomy shock and after nine days she was actually improved and discharged home. Now this could be done then extra corporeal so one didn't have to worry about the bulkiness in terms of it being in the body. The technology has changed dramatically from these pulsatile pumps dependent upon bearing, wear and tear or influenced by it to these more smaller continuous flow pumps on heart mate two and the centrifugal pump, the HVAD and the newest one, the heart mate three. So Eileen, my colleague looked at LVADs in a more contemporary cohort as exemplified on your left and those that were supported by pulsatile devices the 24 month survival was pretty poor 42, 43% but no difference between the two and as it relates to male and females with the continuous flow LVADs 83% when you're survival. Concerning however, when we look at outcome first neurologic event after adjusting for risk factors that can influence outcome female gender was a risk factor and so that needs to be put in context with contemporary devices. Let me fast forward and give you a more contemporary snapshot this is from the nationwide inpatient sample certainly VADs are being used more commonly for women and men but if you look at the transient utilization by proportional percentage it's actually staying flat for women as highlighted in red. So when you look at the sex-based differences so in the older era before 2008, 2009 there was a gap between how women did versus men as it relates to inpatient mortality but in the contemporary era it actually looks much favorable. Now going back to those patients that aren't critically ill in the hospital but are in the clinic with high grade symptoms despite doing everything you can repeat hospitalizations to consider an LVAD or transplant listing there's merits a lot of discussion. As it relates to VAD candidacy one needs to go beyond survival because you're talking about quality of life and we learned that through the roadmap trial I had the privilege to oversee this my colleague looked at the two year data and without getting into the details we saw some very reassuring observations as it relates to being alive and being able to walk more than 75 meters and those supported by a VAD versus ongoing medical therapy improvements in New York Heart class and health related quality of life but we saw also more adverse events in those that received an LVAD in this Intermax 4 through 7 category not on a trope dependent. So it begs the question in current contemporary options of using these devices is there more complications or not in being focusing in on women and thankfully in the continuous flow era comparing men and women no significant increase in complications in fact perhaps some decrease acute kidney injury in females. So reassuring, this is our latest pump the Heartmate 3 based on true maglev it has the widest gaps it increases and decreases 30 times per minute to permit washout and this trial much like the other large LVAD trials you look at the percent men roughly around 80% so only 20% females. So it's reassuring that the data looks very promising Heartmate 3 compared to Heartmate 2 in terms of better survival at two years free of disabling stroke or needing to replace the pump or remove it from out functioning but we still don't have the data in a large cohort of women to truly understand its benefit. It is reassuring when looking at both males and females that with the Heartmate 3 not only is there less pump thrombosis because of the improvement in design and management less any stroke and less bleeding across the board and we haven't seen less GI bleeding ever in a randomized control trial in this cohort. So LVAD outcomes are improving and compared to where we were years ago the survival curves look good but it's above and beyond survival as it relates to making a decision for a select patient. So what do we need? We need sex specific research and I think this is challenging, easy to say but I think to understand true benefits and risks this is what would be needed. So I'm gonna conclude by highlighting some take home messages while there's a paucity of data one can say insufficient to determine optimal medical therapy for women with heart failure. I think the analysis I highlight is suggest certainly that beta blockers aldosterone, Tagus and Arnie and CRT are very, very beneficial. I would adhere to the guidelines as it relates to ICD. Use of the cardiomems in general can help curb heart failure hospitalizations as the best studied home remote monitoring. Women as it relates to end stage interventions have better survival than men after heart transplant and we're gonna need to be very clear about what happens in the new allocation era and in the current era these newer devices that are smaller with better selection, better management women are benefiting equally to that of men. And I think there's certainly a need for further investigation and awareness to understand this gender gap difference. So here's our staff, I was telling Stephanie Corinne Bob Silverman she oversees heart failure quality first thing I did when I got there was make sure Eileen Sheesh was a transplant director if you were paying attention I quoted her a number of times Maria Montes oversees our heart failure OPD Joni Albert just joined us Miriam Jacob oversees the fellowship and I'm gonna go back and went fast Karen James our lead for cardioluncology we want balance. So this will be at about 50% come July or August and so we're proud of that and when you step back and look at the real team we actually have a minority of men which is a good thing. I think that allows us to maintain our quality and our sanity. So with that I appreciate the opportunity to come back home, spend some time with you and do your part, know your heart I'm interested to see what you guys are doing for Heart Failure Awareness Week. Thank you.