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everyone I would like to welcome you I'm.dr. Osama Gaber the director of the.Houston Methodist JC Walter jr..transplant center and this is our third.day of the George P noon conference.series and it is the doctor noon.symposium today celebrating his long.history of achievements and discussing.cardiothoracic organ failure management.and transplants it is also a compound.combined with the cardiovascular their.Grand Rounds so I want to welcome.everybody from our DeBakey Heart and.Vascular Center and ask them to please.look at the symposium today look at the.agenda there is a lot for you to do.actually here we have a amazing group of.speakers that have traveled to give us a.lot of their sort of experience and.expertise and it'd be great if you can.during the day walk in and out and and.listen to them because it promises to be.an amazing day I have just amazing.speakers today the one of the cme.requirements is of course that all.presentations would be free of.commercial bias and i want to inform you.that you will find at the end of the.program there is disclosure of all of.the speakers conflicts of interest we've.reviewed all the presentations and made.sure that there are no commercial.conflicts but if you feel that there is.this eme people are out there and you.can report that to them because we.strive to make sure that all of these.presentation are just what they need to.be academic and without commercial bias.the bathroom is right behind this room.so around that sign that says the.mattress transplant center you can find.the restrooms and we have quite a few.breaks and cookies and all things of.things that are going to happen during.the day as we do every year I thought I.would start by giving those.you who haven't been here the last.couple of days an overview of why we.have this and what's happening at the.Methodist transmen Center but also in my.very modest way shares some of dr. Nunes.accomplishments and why we have this in.his honor and we will continue to have.it as long as there is a Houston.Methodist Hospital because clearly what.he did here has been an amazing.basically transformed not just a.cardiovascular surgery or.transplantation but the whole hospital.so I think most of you have seen the.slide repeatedly but I think it's one of.the most important things that I keep.showing because the Methodist Hospital.about maybe around 2004 or so we've.lived this is the next year 2019 is the.centennial of Methodist but it's been up.for a hundred years now in a major part.of those hundred years has spent as the.teaching site and the hospital teaching.hospital for the better college of.medicine around 2004 that affiliation.ended and the Methodist Hospital made a.decision to become the major academic.medical center in the southern part of.the United States you can see these are.academic medical centers and probably.from where the dots are you can.recognize who they are and all of our.speakers are coming from these sort of.big academic medical centers and we have.decided the board did that we're going.to become the leading academic medical.center and that led to a lot of.recruitment reorganization structuring.and building of the research institute.in which we are sitting now.so about 640 thousand square foot of.research space with a state-of-the-art.training facility called mighty a.cyclotron very soon to have a seven.Tesla magnet animal facilities research.laboratories that really is starting the.transformation of the methodist is an.independent academic medical center the.Methodist is not just a hospital it's a.hospital system and it is a very highly.ranked hospital system in terms of.quality it has been the best Hospital in.Texas for as long as there has been that.sort of of nomenclature there's we have.been the best Hospital in Texas since.this started being given we have a I'm.sorry we have a magnet nursing is only.1% of all the hospitals in the United.States for magnetic nursing but we keep.that year after year because we.understand the value of superior nursing.we the top health care institution and.the fortune 100 best companies to work.for so that besides being academically.striving and have some of the excellent.results in terms of clinical operations.we are also a great place to work for.and we are only superseded by the.googles and the Microsoft's and all of.these companies that allow you to come.to work and you're short which we.couldn't do here of course the Houston.Methodist Transfer Center is ratite.priority for the hospital and the.hospital system and it doesn't operate.in a vacuum it's a collaboration between.I mean there's more cars to that circle.but these are the major contributors to.the transplant center it's that of.course the Methodist DeBakey Heart and.Vascular Center it's the home for all of.our cardiovascular surgeons it's the.home for all of our cardiac imaging all.of our facilities for cardiac.catheterizations operating rooms etc and.you probably now know where or of our.cardiovascular new hospital has come up.with all of these space state-of-the-art.sort of spaceship like facilities and on.campus we also have a excellent.collaboration as part of our transplant.center is the Department of Medicine and.the chronology metabolism pulmonary all.of these services really together form.what we would define as the Houston.Methodist JC Walter jr. transplant.center.and that Center is really the origin of.this conference that you're in today we.stand at the shoulders of giants and one.of those giants sits right here dr..George noon and this is a mr. first it's.by no means a comprehensive list but.we've done just about the first of.everything I think first twelve heart.transplants I'm gonna tell you a little.bit about this story dr. noon himself.did this first multi organ donor and.this was the first time that one donor.yielded multiple organs and in fact one.of the kidney recipients from that multi.organ donor ended up by marrying the.Methodist nurse that took care of him.and in the hospital we did of course the.nation's first implantation of the my.crew made the bacon noon VAD which is.another story that we're going to talk.about in a second but because the first.worldwide implantation was done in.Berlin by dr. noon dr. low B dr. DeBakey.and a German surgeon and we did the.first heart liver transplant in Texas.first multi organ transplant in patient.with ventricular assist device and up.till this past year we have the first.scalps called transplant the heart made.three recruitment study which I see that.the article is outside and that bad is.now being used clinically and we've got.an FDA approvals for a lot of our trials.in the last couple of years were really.going big-time into an institution.sponder sponsored clinical trials stem.cell and kidney transplantation CTL.therapies for viral infections we just.got the FDA approval about a month ago.so the we continue to be innovators and.the spirit of the people who really.started this program and got it to where.it is right now we've had a story of.growth and the transplant center and.yesterday I said that and I'm gonna say.it again.today this is not a company we don't.talk about growth in revenues and growth.we don't project we don't say we have to.grow this way what we're doing is we're.responding to patients demand 10 years.ago when we started this trip of growth.I remember when I first came to Houston.we looked I looked at the counties that.formed the metropolitan area and some of.them were growing at 25 27 percent a.year so you recognize that this sort of.human growth is going to generate the.growth and the need for medical services.and that of course happened and we're.able to respond to it this year between.left ventricular assist devices and.transplantations we're going to do about.600 procedures we're gonna cross the 500.for transplant procedures it makes us.the largest transplant center in the.whole region and of course this is not.just transplantation it's just a part of.what we do all of you of course it's.easier to describe that to the.cardiovascular people because they.understand advanced heart failure and we.actually get almost 3,000 referrals do.almost 2,000 evaluations and list our.lists have about maybe 1,700 people on.it so we're constantly managing heart.failure lung failure liver failure all.these sorts of things it's not just the.transplant procedures 500 doesn't.actually reflect what we do were busy.taking care of patients all day long and.making sure they are better as I said in.2017 we were the ninth in the nation and.now we joined the 500 club that's a very.elite club that we're gonna be part of.which is an amazing thing for our.institution and I think you guys I look.at the audience that there's so many.faces of the people who work day and.night to make sure that that happens so.I'm very grateful for all of you our.heart transplant program we're projected.to do maybe about 50 hearts this year I.know that the number on the slide that.changes every day because every time I.look at my phone you guys are doing.another heart and we actually take care.of a buck maybe three hundred and sixty.or so heart transplants.we're projected to do maybe up around 85.left ventricular assist devices and we.have close to 189.patience were following on a chronic.basis with that that's a and amazing.endeavor it's an amazing organization.that can do that and look at our results.on heart transplantation exceeding.national exceeding expected what a great.team that I stand here to celebrate and.of course very befitting of doctor noon.lung transplantation that we're gonna.probably do maybe around 60 lung.transplants this year we take care of.close to 475 patients and our lung.transplant program has been you all know.some time about five or six years ago we.had a [ __ ] in the armor and a little.bit of low results but we've worked very.hard and look at where our results are.continuously improving and it's a great.testament to the leadership of the teams.that have been here doing lung.transplantation I want to just say a.couple of things about George noon.doctor noon and this is a picture of him.in the old days this handsome young man.doctor noon got his back Bachelor degree.from the University of Arizona in 1956.he took his medical degree from Baylor.College of Medicine did his surgical.residency at the Jefferson Davis.Hospital came back and joined Baylor for.these two years 50 65 and 66 he was.doing what they called advanced surgical.training he was in a faculty but.basically he had taken a lab somewhere.because that around this time Christian.Barnard did the first heart transplant.and dr. noon was really dr. deBakey's.way to start practicing training for.doing heart transplantation and that's.what he did and then in 1968 noon and.DeBakey performed the first heart same.year did the first lung and they were.the first ones in the United States in.fact that first lung transplant that dr..noon did was the first successful luck.transfer they've been attempts of lung.transplantation but that was the first.successful Hmong transplant this is.doctor Noonan his young years and you.can see there at that time he was in the.basement of some laboratory trying to do.heart and ventricular assist device.research on these animals because trying.to figure out how to do that.and clearly always had a bunch of people.that were around him that really.supported his work in his research.relationship between DeBakey and noon.was one of the really strongest things.that sort of catapult the Houston.Methodist upwards dr. DeBakey in 1963.went to Congress and was able to get ten.million dollars appropriated by NIH to.develop an artificial heart program.between Baylor and Rice and dr. noon was.right there as I said joining him around.that time and in fact with dr. DeBakey.anoon operated on some russian scientist.in 1970 who was involved in the Soviet.space program and so we had a joint.research program with the Soviets and.here is dr. noon I don't know if he can.recognize him in this picture and he's.having a heart-to-heart talk with the.head of the Soviet program for heart.transplantation the Soviets at that time.wanted to do also heart transplant and.they were interested in assist devices.and as dr. noon said it in an interview.they didn't end up by developing that in.Russia but what happened was they had a.lot of fun doing it and I'm certain it.relates to the amount of vodka that they.consumed during that time dr. DeBakey.anoon then went and really joined with.NASA and they started thinking of some.way that you can use NASA's expertise to.develop a left ventricular assist device.and that ended up by producing the.DeBakey new invent and I think the.greater story is they wanted to implant.it very quickly so they went first to.Germany I'm sorry to implant that VAD.and the surgeon in Germany was quite.resistant he didn't he thought that the.patient's gonna die that this pump was.an axial flow pump there it was the.first time ever that somebody is going.to have a pump and not have a pulse and.the German surgeons thought that this.guy is going to definitely die so.mightiest Lobby says the story that he.took him to the side and said to him.look if you don't do it here they have a.patient scheduled in Vienna in three.and they're gonna be the first one in.the world done in Vienna so he agreed to.do it and in fact the patient in Vienna.was the second patient that was done.with that that the baekje anoon shared.so many things together the relationship.extended many decades and made this.hospital what it is and in fact dr. noon.ended up by operating in dr. DeBakey in.his 90s when he had an aortic aneurysm.he wouldn't trust anybody else to.operate on him other than his long-term.compatriot dr. George noon.dr. noon managed to get some time.occasionally is a traveler a skier to.spend some time with his wife but I.think what he charged the most is the.grandkids which have always been one of.his passions and I want to really.recognize George P noon and George we do.stand on the shoulder of giants and your.[Applause].good morning my name is myung park i'm.the chief of a division of heart failure.and i welcome you all to our combined.cardiovascular Grand Rounds and our.opening session for George opinion.conference before I introduce our.speaker there are some housekeeping.items completion of the surveys is.important to maintain CMA accreditation.and continue to deliver appropriate.content we are videotaping live.streaming and we are on Facebook please.use the microphones to ask questions the.live streaming recordings are always.available for viewing on YouTube.immediately after the event we listen to.your feedback and now all for ABIM moc.credits if you haven't registered for.this we have information on the back.table for you and last but not least.don't forget don't forget about our.pumps and pipes conference December 3rd.pumps and pipes calm and as a reminder.this session will be followed with a.really lively discussion also on a state.of shock and and the care of the.patients in horizontal shock so we would.love to have you join us so please feel.free to attend now it is my honor to.introduce our speaker dr. Joseph Rogers.is a professor of medicine in the.division of cardiology at Duke.University and he is the chief medical.officer of Duke University Health.Systems he obtained his bachelor's.degree from the University of Kansas in.attending medical school at the.University of Nebraska he performed his.internal medicine residency in Nebraska.prior to research and clinical.cardiology training at Washington.University and st. Louis following his.fellowship he remained on faculty in.Washington University for 10 years prior.to moving to Duke dr. Rogers clinical.practice and research initiatives are.focused on advanced heart failure he.serves as a medical director of the.quartic transplant and medical service.support program at Washu and Duke his.research interests are focused on the.clinical application on mechanical.circulatory support devices her.transplantation and palliative care in.advanced her.he and his collaborators are also.developing new point-of-care testing.aimed at improving and management of.that patience he has authored nearly 200.articles in peer-reviewed journals.including Journal of American College of.Cardiology Journal of miracle jak heart.failure New England Journal Medicine.circulation and Journal of heart lung.transplantation dr. Rogers has served in.several institutional leadership roles.and is the immediate past treasurer for.the International Society of heart lung.transplantation he also was a chair of.Yunos thoracic committee during the most.recent modification to u.s. heart.allocation policy indeed he has his work.has shaped a lot of our current approach.and practice and treatment to our.patients with heart failure and with.that it is my privilege and honor to.introduce you to dr. Joe cerrados.[Applause].well I'll start with a couple of.thank-yous the first to dr. Park for.that gracious introduction that was very.kind thank you there's no time left on.my talk I'm so thanks very much for.having me the second is to dr. Gabriel.Ali's for the invitation to come and.speak this is really a wonderful.symposium and perhaps most importantly.to dr. noon it's always would be an.honor and a privilege to be able to come.and speak at a symposium that's named.after you and on behalf of all of us who.benefit from the things that you've done.in your career thank you so much for all.that you've contributed to the field of.heart disease and particularly in the.space of advanced heart failure thanks.dr. noon this is a kind of an.interesting opportunity here and I was.just as I was looking back behind into.the audience I was reflecting on the.fact that this is much different than it.is giving a talk in North Carolina where.there's almost no one in the front of.the auditorium and I sort of liken it to.going to the Baptist Church where all.the sinners sit in the back pews you.know it's it's nice it's nice at least.in Houston that people have moved down.toward the front of the auditorium.I'm gonna spend some time just trying to.update you on where I think we've seen.important advances in the field of.advanced heart failure I'll talk about.some older information they'll talk.about some newer things but I want to.just sort of give you a perspective from.from my view of where this is moving and.and I won't need to remind this very.savvy audience about the patient cohorts.that we're talking about but but this is.a helpful framework to consider my my.comments as you all know heart failure.is a a public nuisance it is an epidemic.and it's remarkably costly to the health.care system and we reframed the way we.think about heart failure several years.ago when the American College of.Cardiology and the American Heart.Association came up with a new way for.us to consider heart flare not just.based on functional status of a human.being but basically on cardiac structure.and function on risk for developing.heart failure and unprocess and I'm.gonna limit my comments principally to.the stage D patients this group of.patients who has refractory heart.failure and it's thought that this group.of people represents about five to ten.percent of all of the heart failure.population in the US which probably is.now approaching about five million.individuals I'm not gonna walk through.this for the sake of time and I think.that you have access to these slides but.I would refer you to this guidance.document about our current thinking.regarding the appropriate use of medical.therapies for heart failure and it.really is a very thoughtfully put.together schema that describes in a.stepwise fashion how you can tailor.medical therapy for patients who have.primarily systolic heart failure but you.can see that it encompasses our standard.sorts of therapies like ACE inhibitors.and beta blockers some of our newer.therapies including therapies like of.Aberdeen and the drug Valse are tends to.Cuba trill and and really again where.I'm going to focus my comments today are.what happens to patients when those um.guideline based therapies begin to fail.what are our approaches today to manage.that patient cohort so I'd like to start.with you by thinking a little bit about.how we figure out who those patients are.and I'll go through with you the way I.do it in the office and it's in no way.comprehensive because it would have.taken the entire hour but I hope when.you leave here using some of these.little tricks you'll be able to identify.the patient population that's beginning.to slide into a cohort that's going to.require some other kind of advanced.therapies or at least more thinking.about it and I would just point you at.the beginning to this work that was done.by Wayne levy several years ago where he.looked at patients with systolic heart.failure and he classified them based on.their New York Heart Association of.functional limitations he then went back.and he sub classified those patients.based on their Seattle heart failure.scores and I think what you can.appreciate in this figure is that New.York Heart Association functional.classes are insufficient to help us.predict risk I tend to think of this as.it gets you in the ball game but you.really need to do something else to try.to understand the patient's risk who's.sitting in front of you in the office or.in the hospital this is some newer data.that I think's important and we've shown.this several times over the last couple.of decades this is the most recent data.but I think the concept is an important.concept I when I first moved to Duke I.was struck by the number of patients.who'd have a hemodynamic measurement and.then left the catheterization laboratory.definitionally in cardiogenic shock and.I was seeing this patient five or six or.seven years later and I thought wow this.is really an interesting observation so.we had the chance to go back and look in.the escape registry to try to determine.the hemodynamic predictors of risk and.from that data set this paper was.published and it turns out that when we.stratified risk for death or heart.failure hospitalization and transplant.use of cardiac index was not very.predictive it.was really the presence of persistent.congestion and our collective inability.to lower the filling pressures that.discriminated between the people who.reach that end point and those who.didn't so point number one is if you're.unable to decongest a patient in the.office or in the hospital be concerned.that that patient is at high risk I.think that sometimes we become.complacent about the importance of.hospitalizations in a heart failure.patients life this is a sentinel event.in an individual who has heart failure.and it was shown beautifully in this.subgroup and are in this retrospective.analysis from the charms series of.trials and this is a little bit of a.complicated figure but let me just walk.you through it quickly time down here on.the x-axis risk of mortality on the.y-axis and what you can see is that.early on after a heart failure.hospitalization the mortality risk is.very very high and it comes down over.the ensuing two years but it never drops.all the way back down to the risk that.patients have who are never hospitalized.and maybe more importantly what is shown.on the right side of the slide and the.concept in this is the more frequently.patients are hospitalized and the longer.the time that they spend in the hospital.to achieve hemodynamic stability the.higher their risk in this very high risk.group patients or people who have been.hospitalized multiple times in the last.12 months with longer and longer.durations of hospitalization so the next.point in this risk stratification is pay.attention to hospitalizations watch of.these people are starting to come into.the hospital more frequently they're.spending more time in the hospital it's.a high-risk group we constantly think.about cardiac structure and function and.this again was some data from the charm.trial on the left just showing that the.lower the ejection fraction goes the.higher the risk for mortality no.surprise but we didn't dichotomize the.information in this analysis instead.looked at each action fraction is a.continuous variable and you can see that.there seems to be a bit of an inflection.point once the ejection fraction drops.in the 25 to 30 percent range and when.we think about car.structuring functions some very old data.from the save trial just demonstrating.patience with the largest ventricles.have the highest risk for mortality so.the next lesson in this is as you're.looking at echo reports or you're.reading echoes in the echo lab pay.attention the lower the ejection.fraction the larger the ventricles the.higher the risk of that patient most of.us rely heavily on this test is maybe.the best individual predictor of how.patients are likely to do in the next.couple of years this is an individual.undergoing a cardiopulmonary stress test.wired up for a stress test like you.would perform any stress test to look.for ischemia the difference of course.being that there's um some tubing up.here and basically this man has a scuba.mouthpiece in his mouth and we've.plugged his nose with a very expensive.clothes pin because what we're.interested in capturing or the air that.he's breathing in and out of his lungs.and it allows us to calculate his.maximal oxygen consumption and I've.shown you the formula for that here not.to bore you but to make the point that.in untrained individuals the AV o2.difference is usually fairly fixed so.for me I don't extract a lot more oxygen.when I go out and exercise now that's.not true about professional hockey.players and I used to use Lance.Armstrong as an example although I think.that that maybe not the best example.today but this tends to be a fairly.fixed number so what you're actually.being able to do with a non-invasive.test is measure the increase in cardiac.output with exercise it's a measure of.cardiac reserve and you can imagine if.you've lost cardiac reserve it's a bad.sign and this was shown elegantly by.Donna Mancini in the early 1990s.demonstrating that when the peak vo2 the.maximal oxygen consumption exceeded 14.the risk for those patients was very.very low it actually was about the same.as heart transplantation and we've used.the number 14 since this time as a risk.stratifying tool to figure out who.should go on to transplant and now who.should go on to mechanical circulatory.support so this is a very important test.if you see if you have someone you think.boy I'm really worried that this.individuals starting to slip I'm seeing.more hospitalizations I'm having more.trouble Deak ingesting the patient this.is a test that will help you further.risk stratify and for those of you who.might be thinking.about taking board examinations in the.future I highly recommend that you.remember the number 14 for me in the.office this is one of the most useful.tools and this was some work that Lynne.Stevenson had done when she was at the.Brigham and this is the observation that.patients who begin to develop.circulatory renal limitations to.standard heart clear therapy are in.trouble let me paint this picture for.you it's an individual who comes into.the office they oftentimes are.hypotensive cool and wet and you think.I'm worried I think what I need to do.probably is back off on some of the ACE.inhibitor or beta-blocker therapy they.need more diuretic I'm gonna check some.renal function but I'm worried and I'm.gonna see them back in a couple of weeks.you see them back a couple weeks later.they oftentimes look the same they're.there in able or unable to tolerate.standard heart failure therapies in that.patient cohort in Lynn's experience that.group of people who could no longer.tolerate a standard heart failure.therapies had about a 50% 6-month.mortality risk so watch that as another.marker another risk marker for mortality.people who've required inotropes and.especially chronic inotropes again high.risk for short-term mortality and should.be considered to move on to some of.their kinds of advanced heart player.therapies if available and I wanted to.just stop with you for a second and not.discount the expertise of smart.clinicians and I've already alluded to.the escape trial the escape trial was a.pulmonary artery catheter trial where.patients were randomized to either be.managed with a PA catheter or bedside.guided therapy but we ran a concomitant.registry in escape and we the registry.was populated by patients in whom the.investigators didn't think there was.equipoise for randomization most of the.time because the clinicians thought this.person was too sick and it turns out.that when we compared the registry.patients to the trial patients the.registry patients spent twice as much.time in the index hospitalization and.their six-month mortality risk was 1/3.so we've got very interested in this.observation what what did clinicians see.that distinguished a registry patient.that was thought to need a PA catheter.to help guide their management from.those who could be randomized in the.trial and we looked at a variety of.different baseline characteristics we.looked at hemodynamics medicines.demographics and actually we couldn't.find anything that was really predictive.and so what I walked away from this.analysis thinking is pay attention to.that little voice in your head that says.I think something's wrong with this.patient because you're probably right.unless you're somebody who's chronically.wrong when you ask yourself that.question but if you if there's some.voice in your head that says I'm really.worried something seems wrong with this.patient we just remember this piece of.data and that patient may be much more.like a registry patient than a trial.patient and you should think about doing.some other testing to help risk stratify.and then I'll close this part of my talk.with this that the the European Society.for cardiology the heart failure section.of that just came out with this.pneumonic to help us remember who's at.risk for mortality who has advanced.heart flayer and I won't walk through.all of it because I've already talked.about many of these things but if you.can remember I need help that's the.mnemonic that many people are walking.around now with the this slide and their.slide deck saying just try to remember.this mnemonic and what goes along with.it to try to help risk stratify a.patient cohort that you're seeing in the.ether and the officer in the hospital so.so when you have identified this.high-risk patient what are the choices.that you have for therapies and the.reason I made this slide was because I.actually do this I'm in the office I.hold my hand out and I walk down my.fingers which I thought was kind of.elementary school ish but but it works.for me and and I think that I wanted to.just I'm not gonna spend a lot of time.talking about sting on contemporary.therapy but I would argue that this.patient cohort if you've gotten to this.point is already failing contemporary.therapy and we've already talked about.the fact that they have a high risk.we've talked a little bit about the use.of inotropes.and it's it's a short-term bridging.solution it's a palliative solution but.it's not a solution.that will provide extended quality and.length of life and it leaves me with.these last three options which I'm going.to spend the rest of my time speaking.about transplantation mechanical.circulatory support and I'll close by.making just a quick mention of an.increasingly important intervention.which is palliative care so I'll start.with transplantation since this is the.focus of much of the last several days.conversations just to remind you that in.the United States what we've seen over.the last couple of years has been a nice.uptick in the number of transplants.being performed and and there are a.number of reasons for this and some of.them I'll try to elucidate for you but I.in just a minute but I wanted to remind.you of the incredible data set that we.have to support transplantation as a.therapy but also to remind you the.outstanding outcomes so this is data.from the International Society for heart.and lung transplantation over the.entirety of the experience so from 1982.through the middle of 2015 and you can.see that at ten years the average.survival rates still about 50% that.condition if you live a year after a.heart transplant your average survivals.in the 12 to 13 year range and many of.our programs have survivors out in the.20-year range this probably is far.superior to anything else that we have.and I think many programs are still.trying to move patients toward.transplantation if they're a good.candidate and recognizing that we are.still donor limited so what are some of.the things that have happened in.transplantation that have caused that.increase in the number we've seen over.the last couple of years I can tell you.that one of those societal challenges.that we have right now is the opioid.epidemic and I'm not proud to tell you.that three of the top ten cities in the.United States for opioid mortality or.North Carolina but we have seen an.uptick especially in young donors who.are dying of drug overdoses and it's.tragic and as a society we need to.really begin grappling with this issue.more aggressively but there are a couple.of other items that have occurred that.have been really interesting and that is.the growing interest and use of.hepatitis C positive donors and it's.based on the observations.and clinical trials that have.demonstrated that this is now a curable.disease with some of the new anti.hepatitis C antivirals and this is just.a paper that was published earlier this.year from the Vanderbilt group looking.at the outcomes of patients who were.treated with hepatitis C positive donors.that cure rates are very very high in.fact in some small series the curates.are 100% and the and oftentimes these.are young otherwise healthy donors we.don't have any experience understanding.what the long term implications of that.are and I think it'll be important for.us to continue to follow this cohort of.patients over the longer term to try to.understand whether there are any adverse.effects from using these donors the.other thing that's I think a little bit.of a game changer or at least it has.been in our institution is the change in.the way we're procuring and.transplanting hearts and is most in the.audience know this is the way we've.always done it we've gone and procured.in Oregon we've packed it in a cooler.full of ice and we've transported it.across the country into our operating.rooms and into our recipient but there.is a new strategy that's being employed.in several places in the United States.which is a warm perfusion device to.which the heart can be attached we.profuse donor blood the heart continues.to beat and interestingly it can be.monitored during transport and while.we're waiting and the power of this.technology really became obvious to me.early in our experience when we actually.took a flight that was about an hour to.an hour and a half longer than we.normally would take to procure a donor.heart and on the way back we were.delayed by several hours because of a.thunderstorm the ischemic time for that.heart was between 8 & 9 hours and it.worked perfectly and so I think that.there's some really interesting.potential advantages to this kind of.approach particularly for patients who.are very very sick because it might.allow you to go farther to try to find a.suitable donor heart for your recipient.I also wanted to quickly walk through.some of the changes that are occurring.with heart allocation this actually went.into effect last month and so we're.still waiting to understand whether.there were any unintended consequences.but the way that we allocate.in the united states is shown on this.slide there's and think of it in two.ways there's a prioritization strategy.and an allocation strategy and the.prioritization czar shown over here on.the left side i won't read through all.these but the status 1a patients are.very high-risk for short-term mortality.these are oftentimes people who are.committed to an intensive care unit on.some kind of support there's a status 1b.patients who are patients who are very.ill bit more stable and then the status.to patients are sort of everybody else.and in the united states right now less.than 5% of the patients being.transplanted across the country in.aggregate are status to patients 95% are.status 1a and 1b and the way we allocate.hearts is shown over here on the right.and i've just out of convenience showing.you st. louis as the epicenter where a.donor might be found and the what you.can see is that when a donor would be.identified in st. louis it would be.offered locally for the status 1a and 1b.patients and if there was not a patient.that was suitable for that match it.would go out in a 500-mile circle for.the one a's and one b's and if there was.no one in that area it would go back.locally for the people who were at home.waiting on oral medical therapy that's.how the system works today i'm sorry it.did work a month ago.or it didn't work a month ago actually.so again I won't read all this but I.think many of us who were thinking about.allocation policy in the United States.realized that there were several real.challenges with the way we were.approaching this and and all maybe most.importantly allocation Oregon allocation.is dictated to us by the federal.government it's a in a rule called the.final rule which is a really altruistic.way to think about it there's some very.important principles like this is a.societal good and you should make the.best use of a societal resource there.are things like that that we should have.an efficient system that you should try.to take care of the sickest people some.really important concepts in the final.rule and as we looked at our current.policy we didn't think it aligned very.well.with the final rule here's an example of.this when we looked at a group of.patients who would be listed at high.priority for heart transplantation the.risk of death varied dramatically but in.a current system these patients would.all be listed at the same status so it.really didn't align very well with the.general theme or concepts underlying the.final rule there's some other challenges.with organ allocation and I showed you.st. Louis conveniently because it's in.the middle of the country but you know.if you live in Seattle your concentric.500-mile circles begin going out into.the ocean or up into Canada and how does.that advantage or disadvantage patients.waiting there and here's one of the more.interesting challenges this is the.Hudson River so New Jersey's over here.in New York's over here there are.different organ allocation areas so a.patient who is waiting on ECMO at.Columbia in Manhattan could be bypassed.over patient called in from home at.Newark Beth Israel 15 miles away because.it's separated by a river and some.artificial boundaries and while it might.make sense to everyone in this room that.we've divided the country up this way.try to explain this to a human being.who's got a family member who's dying.there is no way that we could ever.justify this kind of an allocation.policy so what we've done is.reshuffled the deck a little bit and.we've gone from a three-tiered system to.a six tiered system and again I'm not.going to read all of these to you but.this is the system that was implemented.last month and you can see what we've.tried to do is is group like conditions.and when I say like conditions they're.based on a patient's risk for dying on.the heart transplant waiting list and.then re and then reprioritized them and.the other thing that we've done is we've.changed the way we're going to allocate.hearts such that the sickest group of.patients the status one and the status.two patients will not only be offered.organs locally but they'll at first.offer will go out to 500 miles to that.group and we actually originally posed.proposed a thousand and got pushback.appropriately from the opie o--'s in the.community saying we think that a.thousand miles is probably too far so.the compromise was to drop it back to.five hundred miles but the idea is that.these sick sick patients should have.access to the most potential donors that.they possibly can have to try to get a.life-saving transplant and the modeling.data that we have I'll just show you.three slides one is I think that we got.it right if you look at the risk for.mortality and I'll just highlight few.that on the y-axis the numbers are.different the status one patients have a.significantly higher risk than the.status twos the twos higher than the.threes the the fours and the fives are.about the same the inactives go up a.little bit so it looks like as we.reshuffled the prioritization that we.got it right that we lumped groups of.patients together with similar risk what.we're going to project based on our.modeling is this sickest patients are.actually going to be transplanted much.faster than they're being transplanted.today and based on gun on the modeling.we think that their mortality risks at.two years following transplant are going.to be roughly the same the status ones.will be a little bit higher than the.others you can see that the status fives.are a little bit higher they're 24 month.mortality risk you might say well is.that a flaw in the system remember the.status fives are the multi organ.transplants and I can tell you is a.heart transplant we always will blame.the other.the other thing that we did was we.classified VAD complications these look.different than the complications that.you'll see if you look at them up in the.inner max registry what we tried to do.is define complications of such.significant severity that it threatened.a patient's life on a VAD and the.challenge that we saw as we looked at.the data was that there were no uniform.definitions being used and we were all.over the board across the United States.and including some people who may have.actually been doing some things.inappropriately to elevate their.patients status on the waiting list so.now all of the center's will be working.under a same set of guidelines if you.want to classify your patients having a.bad complication you'll need to utilize.this strategy to other innovations that.I think we built into this and I am.gonna give credit to John Kobashi gawe.for making us think harder about this.after we initially put this together.John said I think that you're missing.some really important concepts and so we.went back to the drawing board and came.back with a couple of other ideas one is.that we should have a uniform definition.for shock so for patients who are being.put on as a high priority on the heart.transplant waiting list they're going to.have to achieve some objective criteria.that define them and being shocked being.in shock and in fact as I'll show you I.think in a minute if on temporary.support you're gonna have to go back and.prove again that your patients in shock.a few weeks later in order to maintain.that higher priority and we did the same.thing around ventricular tachycardia we.wanted to make sure that people who were.being classified as being high priority.because of VT or VF were following the.same rules across the United States so.I'm gonna stop there with transplant and.I wanted to move on to some of the.things that are occurring with.mechanical circulatory support and I'll.just highlight for you these are the.three dominant devices that are being.used in the United States the heart mate.- which is you saw earlier from dr. some.of the slides that were shown.introducing dr. noon an axial flow pump.and then - centrifugal flow pumps the.heart mate 3 and the HVAC and I won't go.through the technical differences.between these but I wanted to highlight.for you some of the recent clinical.trials that show us the potential.value of this approach and to highlight.this I wanted to just mention to you a.couple of studies the first was the.endurance trial using the H VAT and in.this trial we compared two different.device strategies we compared the axial.flow pump to the centrifugal flow pump.in a large cohort of patients with the.primary endpoint at two years being.survival without a disabling stroke or.the need to operate on the patient to.repair or replace the device the trial.was designed as a non-inferiority trial.so we were trying to show equivalency.between these two pumps and in fact what.we did was we were able to demonstrate.that we were able to demonstrate that.the centrifugal flow pump had a very.similar primary outpoint statistically.the same as the older axial flow pump.and if you break this down a little bit.you can see the differences in the.potential endpoint so there's the.differences in mortality which were not.significant there was fewer device.malfunctions in the study group the.stroke rate was just a tiny bit higher.but we thought sound found something.that was really interesting and required.additional study from that endurance.trial and it's shown in the adverse.event table and I would just highlight.for you a couple of things first the GI.bleeding rate remains very high about a.third of the patients will experience GI.bleeding in the first two years but I.wanted to just show you this interesting.observation that the stroke rate over.two years with the H fed was almost 30%.compared to 12% with the older device.and the question is what's driving that.so we went back and we did some.retrospective studies looking in large.datasets and what we found was not only.was anticoagulation an important factor.but it looked to us based on what we.could see that that hypertension was an.important driver especially of.hemorrhagic stroke and so we did another.trial which I like to laugh and say we.cleverly called endurance to same pumps.same strategies around implantation same.kind of patient courts the big.difference was we focused ourselves on.trying to be sure that we lowered the.systemic blood pressure to under 90.millimeters of mercury as a mean.arterial pressure.and what we were able to demonstrate in.the endurance supplemental trial was.that the that we did not reach our.standpoint of reducing stroke but it was.largely because we statistically didn't.design this study the way we would have.in hindsight but what I wanted to show.you was this important reduction in.hemorrhagic strokes we actually think as.we as I look back on the data from this.trial I think what I can tell you today.is managing blood pressure particularly.with the H that is an important part of.the post implant management and we.should try with that pump for sure to.try to target the mean arterial.pressures under ninety millimeters of.mercury and then the trial that has made.an incredible splash for us in the last.several last couple of years has been.the momentum trial and and I think the.investigators in the momentum trial.deserve credit for a number of things.enrolling patients remarkably quickly.very good data collection but they also.broke down an important barrier for us.and all of our trials up to this point.have looked at patients who were being.bridged to transplantation or patients.who weren't transplant candidates and.what we saw was an awful lot of mixing.of those patient populations the bridge.patients were being kept on devices for.prolonged periods of time people who.started off as as non transplant.candidates became transplant candidates.so one of the other really important.innovations in this study was that we.started to think of this more in terms.of short term support regardless of why.it was put in and where we were going.and long term support and I'm going to.show you the two-year outcome so this is.the long-term cohort this is the most.recent data that was published in New.England Journal earlier this year.comparing the heart mate 3 to the heart.mate to the primary endpoint was.survival free from stroke or a need to.repair replace the device and you can.see that the patients who received the.centrifugal flow pump had a.statistically better outcome.dramatically so than the patients who.receive the axial flow pump and as one.of the Supplemental tables to that.manuscript the other thing I wanted to.highlight for you here's the here's the.actuarial survival rates.and you know it's getting really.interesting now that we have two year.survival rates on a VAD that are.approaching 85% they're coming close.very close to transplantation and it.raises some provocative questions about.whether or not there could be a trial.coming in the future that begins to look.at transplantation versus mechanical.support in certain patients just a.couple of other really quick comments.one is about putting bads in less sick.people and if you look at the inter max.profiles the ones twos and threes or.people who are inotrope dependent the.fours fives and sixes are not I know.Coke dependent but there's a gradation.from horribly ill to much less sick and.what we know about Bad's really is in.the classroom in term acts profiles one.two three we wanted to try to understand.what happens if you put devices and.people who still have a a definitional.indication for VAD but aren't to the.point that they need inot ropes so we.designed the roadmap trial it was a non.randomized trial people could pick I.want a VAD or I want to stay on my.medical therapy the primary endpoint at.12 months was survival with an.improvement in six-minute walk distance.by 75 meters and you can see that in the.group of patients who elected to have an.LVAD rather than stan medical therapy.they had about a two and a half fold.increase in the likelihood of achieving.that positive outcome and when we went.back and we looked at the two-year.outcomes we saw a similar kind of.advantage to the people who elected to.go on mechanical circulatory support if.you dissect this out a little bit more.and you have to be careful because the.numbers are small the real benefits seem.to be in the people who were bumping up.against inotropes the people who are.much less sick maybe didn't get the same.kinds of benefits and the trade-off for.these patients was a higher risk of.adverse events and I showed you some of.those in an earlier table the quality of.life date is very consistent with these.newer devices it doesn't matter whether.you're looking at functional endpoints.New York Heart Association functional.class.heartful your specific quality of life.tools or a more general quality of life.tool we see an early and sustained.improvement in quality of life measures.and functionality and people treated.with a VAD but the trade-off again is.the adverse events and this was a very.sobering report that came out of the.national database inter max.demonstrating that within two years.about 80 percent of people had.experienced one of these important major.adverse events including death stroke.device malfunction bleeding an infection.and I think what we'll see in VAD trials.over the next several years are really.going to focus us in on how can we take.a good therapy and mitigate some of.these adverse effects what do we have in.our control as clinicians to try to.manage this patient population better.and reduce their risk of having the.morbidity associated with VADs and I.think that one of the more exciting.parts of of this bad story is the.potential that we can use VADs to.stabilize terribly sick people and use.them as a platform to recover the heart.and this was some work that came out of.the NIH cardiac surgical Network trials.where we had injected mizenko --ml.precursor cells in the heart at the time.of that implantation this was a small.trial it was meant to make sure that.people didn't get a low sensitized they.did not but the there was some.interesting sub studies to suggest that.the people who got the cells might have.actually done a little bit better as we.tried to wean their pumps and this study.has been redone it's this the data is.undergoing analysis but watch for the.results of this trial because this may.be an important observation is an.adjunct therapy to VADs and I wanted to.close with with one other comment.because on my on my hand the on the very.right side of those fingers was the idea.that people aren't all going to be.candidates for advanced heart failure.therapies and we need to be thinking.about that the larger population how we.care for them as they begin to fail.therapy and it led us to a clinical.trial called the palais jeff trial which.was a single center trial that enrolled.a hundred and fifty patients over the.span of a couple of years and the.primary endpoint.Palli Jeff was improvement in quality of.life measured either by the Kansas City.cardiomyopathy score or a palliative.care specific quality of life to a call.the facet pal it was a co primary.endpoint and what we were able to.demonstrate in the group of patients.that had guideline directed medical.therapy with a palliative care overlay.was that over the span of six months.patients had an improvement in quality.of life they had improvements in their.anxiety and depression scores they had.improvements in their spirituality.concerns it did not improve survival in.this cohort but it wasn't waited to do.that but as a proof of concept that we.should be thinking about how we can.engage larger teams of patients and.surround this vulnerable patient.population with the kinds of health care.professionals that can help them through.these difficult challenges as they.approach them of their life pal HF I.think was a powerful message that that's.the it's an important adjunct for the.patients so I'll close this way and just.remind you that there have been few.advances in the medical therapies for.the most advanced heart failure patients.I would argue that we've not found a.therapy in the last probably decade.that's really targeted these stage D.patients that makes them better it's.important to risk stratify and I gave.you a variety of different tools at the.beginning of my talk to think about how.you might risk stratify patients and.hopefully they were practical enough.that when you walk out of the auditorium.and you start to see these patients.later today or next week you can use.some of those tricks.I think transplantation today still.remains the gold standard for the.management of these patients if they.qualify and hopefully the new allocation.system will improve our ability to get.hearts into the sickest patients in a.reasonable way and this will be.monitored over the next several years to.make sure that there are no unintended.consequences the new VAD trials have.been very encouraging I think that I'm.really struck by what we're seeing in.those actuarial survival curves for.momentum but I think that we're.developing finally a therapy that may.actually challenge transplantation as a.gold standard but I think the thing we.don't have is the long-term data with.the devices and finally I just would.remind you to begin thinking.about integrating palliative care into.your approaches so thank you very much.for the kind opportunity to visit dr..noon thank you so much for the honor to.speak in your symposium dr. Rogers thank.you so much for that really a terrific.discussion on our complicated topic of.heart failure love to open up for any.question answer from the audience and.we'll take a moment out for those.attendees who are just attending the the.Grand Rounds but please note that we.will be having really great lectures are.following this encore agenda shock and.for those who can attend will be love to.have you join us got to be much dr..Rogers as always elegant and very.engaging thank you for that great.overview you've covered I have a lot of.questions which and we always love to.kind of your comments are very.thoughtful but ma I I wanted to.understand the discussions and science.behind the allocation system in specific.to this weaning criteria which I think.is necessary to your point I think this.is a this is a first step in a change.which was needed but how do we reconcile.with how much we don't know about how to.wean a balloon pump and what is weaning.mean when someone's on a balloon pump.for one week or sis a month and how do.we factor that in yes so you've asked a.really pivotal question I think in the.space what is the science behind it.zero prayer pretty much I'll tell you.and again I I think John kibosh Agha was.really pivotal in making us think a.little bit harder and go back to the.drawing board around this issue there.there was a general concern expressed by.the community that there were programs.who weren't necessarily following the.spirit of.prioritization and that a lot of if you.look at our current criteria a lot of.the prioritization is based on a.physician's decision to do something.some of those things are dramatic like.putting a patient on ECMO and some of.them are less dramatic like putting.someone on an I know trope or putting.someone in an intensive care unit with a.pulmonary artery catheter when they.maybe could have been managed.differently so what we tried to do was.to go back and say we acknowledge the.fact that there is variability across.the country but we want everybody to.start playing by the same set of rules.and and so in order to maintain that.status you're going to have to be able.to demonstrate that your patients still.in shock and if they're not in shock you.don't have to remove the support you.don't have to do anything different your.patient except if they're no longer in.shock.you're going to have to downgrade them.to a patient cohort whose risk is.probably a similar - to an individual.who wasn't supported that way but but.that was the idea was really it was.really to address the concerns of the.larger community that that there was an.unevenness in the way we were utilizing.some of the therapies Joe thanks very.much for not only a great talk but for.your national leadership and helping us.help guiding us how to take care of.these patients I do have a question.about the new allocation system as you.very nicely pointed out having access to.organs for the sickest patients is very.important my question has to do with the.ECMO patients certainly there are among.the sickest patients who would.potentially benefit the most but we also.have data to show that those are the.patients who tend to benefit the least.from a heart transplant so could you.give us an insight as to what the.decision was behind that next time that.thank you very much it's a great.question I would respond in a in a.couple of ways one is we you have to.start that process somewhere and we made.the decision that we were going to focus.primarily on trying to mitigate waitlist.mortality and what you're I think.alluding to was that the post transplant.worked out.the ECMO is higher than some of the.other categories suspect even in the.status the new status one patients but.it was hard to ignore the ECMO patients.and they're very very high-risk for.short-term mortality in as we looked at.priority redoing the prioritization the.other thing that we had a lot of.conversation around was whether or not.we as a community really understand how.to use ECMO and use ECMO as an effective.bridge to transplantation and I might.argue that what we saw was people.lingering on ECMO for prolonged periods.of time and the committee thought that.that the risks might be you shaped that.right when you go on ECMO is someone's.very unstable with end-organ dysfunction.and in a shock state that their risk.would be high for transplant that may be.over some period of time the risk would.drop down and then as they stayed on.ECMO it probably is going to go back up.again so so we what we're hoping will.happen with this is that we'll begin to.understand whether you can identify that.patient cohort that hits the nadir of.that you shaped curve and maybe we can.actually understand how to transplant.from ECMO the other thing that we.discussed which is really important is.we believe that it will be.self-regulating so if programs across.the country decide we're gonna.transplant all kinds of patients off.ECMO for whatever reason if the outcomes.aren't good I think that those they'll.stop because we're so heavily.scrutinized with regards to our outcomes.most of the small programs can't absorb.that kind of mortality risk so I.appreciate the concern but I actually.think that we may learn something.interesting about using ECMO and I'm not.that worried that we're going to find.that this has a terrible national effect.on on post transplant outcomes for that.reason you can't go in front of her.thank you very much for your talk it was.very interesting I have a question about.how you're managing the waitlist and.what this has done to your staffing.model you know you have a long list of.clinical parameters to meet on the daily.basis every seven days you have the GI.bleeds for 42 days even the status sixes.or fives are going to need something.every 180 days and have you noticed that.there's been an increase in monitoring.and how do you manage to keep up with.this in the future yeah no thank you for.that question Mike are you somehow.involved in having to enter that data.I managed there's a long line of people.who are very angry with me right now.yeah you're right I would answer back in.a couple of ways one is that it's.important for us to ensure that the.veracity of the people who are listed.which is why the high priority patients.need to be reconfirmed you know more.frequently one of the other things that.we realized as we went through this.exercise was there's a lot of.information that we don't have and and I.think a number of people in the.community said what we really would like.the committee to do is come forward with.a hard allocation score but there are.giant gaps in our knowledge in that.database sensitisation is one of them.and I'm sure that you looked at the.sensitization screens and thought oh my.gosh why are they doing this to us.the other one is hemodynamics you know.the only time you have to I think submit.hemodynamics or when you put people on.the list if you've got them but there's.I don't think that there's a requirement.that you go back at least and re-entered.hemodynamics or it was very voluntary.yeah weird so so to answer your question.much more directly what we're trying to.do is we're trying to collect the data.elements that we thought would inform.the next iteration of the heart.allocation policy which probably will.include an H a s that's very similar to.an LS but we felt as we looked at this.information that we weren't quite where.we needed to be in terms of knowing the.data elements and the importance of them.in risk stratify.patience Joe great great target as.always one of the issues of allocation.is truly to get the sickest patients and.I get we got it in terms of by.ventricular heart failure being worse.and that's why ECMO is in status the new.status one the the fact that you do not.include endovascular support in status.one it's not a technology issue because.as we get better you know in overtime.rather than to have two central banks.put in for example to have to impel us.you know and but at the same time the.spirit is the same you you have sick.patients on both and maybe one program.doesn't have the technology to do the.more refined percutaneous support but.they're both sick and shouldn't they.both be status one yeah I mean it's a.great question.so we talked about this and and the.thought was in the reality amongst.friends is that we don't have a lot of.data in the you knows data set to help.us understand endovascular support.anyway so we knew the most about balloon.pumps but we knew very little in the.data set using devices like Impala and.tandem heart and all of the other.devices that are likely to come out so.we used balloon pump as the predicate.and we said these are the closest these.devices are closest to putting a balloon.pump in the other thing we thought was.that that there likely was to be a.difference today in the patient that is.coming out of an operating room with you.know rota flows or Sentra mags or.something probably different than.someone who goes into the cath lab and.has by ventricular percutaneous devices.put in it that assumption may or may not.be correct but that that's really how we.ended up stratifying them down into the.status to patient population thank you.very much no I I just had one very quick.question and comment first thank you so.much as with my.sniffing but is there a time for.something like an LA escort and the.heart where predicted survival versus.the severity of the disease and because.what Tom said really triggers this.question if you take somebody who was.like really really sick and you want to.crash find him but maybe he's over the.curve in terms of outcome yes would.there be a time to devise something like.that we yes is the answer I think that.we'll be able to be much more objective.about it with some of this new data.collection we did stop and think about.the post transplant outcomes again the.primary driver of that reprioritization.was pre transplant mortality but we.acknowledged the fact that there are.some disease conditions where the post.ran out post transplant outcomes weren't.as good as we'd hope we talked about it.I think you may have seen that I don't.remember off the top of my head how we.maybe move them just a little bit but.there wasn't a lot of movement based on.that parameter but I think it's an.important issue I think the next.go-around will be much more instructive.because we'll have a more robust data.set the other thing I've just highlight.for the young people in this room is.this is a tremendous opportunity to get.involved in you knows I didn't have a.lot of interest in policy when we.started but you can see that these kinds.of deliberations are great deliberations.they're very thoughtful their scientific.and they've changed the way we're going.to be thinking about practicing and I.think there's probably an opportunity.for almost everyone in this audience to.get involved in you know so I'd.encourage you to do so.[Applause].thanks to Rogers of the next.

How to generate an electronic signature for the Maryland Uniform Referral Form online

An all comprising solution for signing Maryland Uniform Referral Form is something any business can benefit from. CocoSign has found a way to develop a simple, acceptable-cost, and unassailable online system that you can use.

As long as you have your device and an efficient internet connection, you will have no problem esigning documents online. These are the simple points you need to follow to sign the Maryland Uniform Referral Form :

  1. Hit on the document you need to sign on your device and click 'Upload'.
  2. Tick 'My signature'.
  3. There are three ways to produce your signature: you can draw it, type it, or upload it. Take the one that you find most fitting.
  4. Once you have produced the signature, click 'Ok'.
  5. Finish by picking 'Done'.

Then you just need to finish the document signing and have it ready to be sent. The next step is up to you. You can forward the form to the receiver.CocoSign makes all the aspects of signing an electronic document easy and functional.

You get further features like 'Add fields,' 'Merge documents,' 'Invite to sign,' and a few others, all meant to make it user-friendly and comprehensive.

The best thing about CocoSign is that it functions on all the implements you deploying, so you can hang on it and can sign electronic documents despite of the device you are deploying.

How to create an electronic signature for the Maryland Uniform Referral Form in Chrome

Chrome is probably the most liked browser lately, and it's no wonder. It has all the features, integrations and extensions you can call for. It's extremely useful to have all the tools you use available, due to the browser extensions.

Therefore, CocoSign has go alone with Chrome, so you can just go to the Web Store to get the extension. Then, you can sign your form directly in the browser. These are a few simple points to lead you through the signing process:

  1. Hit on the link to the document that needs to be signed, and tick 'Open in CocoSign'.
  2. Use your registered account to log in.
  3. Hit on the link to the document that needs to be signed, and tick 'Open in CocoSign'.
  4. Get to 'My signature' and produce your unique signature.
  5. Find the right position on the page, write down the signature, and tick 'Done'.

After following the guide, you can either foward the document or share it to as many recipients as you need.

You will Hit on that CocoSign has made efforts to make your Chrome signing experience as satisying and glad as possible, by adding a wide range of handy features, like merging PDF files, adding multiple signers, and so on.

How to create an electronic signature for the Maryland Uniform Referral Form in Gmail?

Email is the important way to hand over documents lately, and going paperless has a lot of edges, speed being the main one. You can sign a document and have your partner receive it quickly.

Your email recipient is one click away. This simple process can be applied to any agreements that needs a signature: contracts, tax forms, and all kinds of agreements or declarations.

The great thing about CocoSign is that it helps you place your signature online the Maryland Uniform Referral Form in your Gmail, without having any other implements involved. You can do that using the CocoSign Chrome extension. There are only five simple points you need to follow to sign your form right in your Gmail account:

  1. Find the CocoSign extension in the Chrome Web Store, and add on it to your browser.
  2. Log into your Gmail account.
  3. Get to the Inbox and find the email containing the contract you need to sign.
  4. On the sidebar, you will find the button 'Sign'; click it and produce your own e-signature.
  5. Once you tick 'Done,' the signature will be completed, and the signed document will be automatically saved in a draft email generated by the CocoSign system.

Easy was the primary concern behind the efforts made by CocoSign to develop a legal and valid system that can allow you to quit physical signature.

Once you try the system, you will quickly become one of the plenty of satisfied clients who are enjoying the edges of e-signing their documents right from their Gmail account.

How to create an e-signature for the Maryland Uniform Referral Form straight from your smartphone?

Smartphones and tablets are so evolved lately, that you can deploying them for anything what you can do on your laptop and PC. That's why more and more people are operate business from these mobile devices, saving even more time.

It's also a huge benefit work at any where. As long as your internet connection is stable, you can conduct your business in whatever place.

When you need to sign a Maryland Uniform Referral Form , and you're working from home, the CocoSign web application is the answer. Signing and sending a legally binding document will take seconds. Here is what you need to do to sign a document on your cell phone:

  1. Use your browser to go to CocoSign and log in. If you don't already have an account, you need to register.
  2. Hit on the document that needs to be signed on the device and access to it.
  3. Open the document and go to the page to put down your signature.
  4. Tick on 'My Signature'.
  5. Personalize your unique signature, then add on it on the page.
  6. Once you have done, read the written part again, tick 'Done'.

All these points won't take long time duration, and once the document is signed, you decide the next step. You can either download it to the device or share it in an email or using a link.

A significant edge of CocoSign is that it's fitting with any mobile device, regardless of the operating system. It's the ideal alternative, and it flexibles workflow, it's legal.

How to create an e-signature for the Maryland Uniform Referral Form on iOS?

Creating an electronic signature on a device with iOS system is not at all tough. You can sign the Maryland Uniform Referral Form on your iPhone or iPad, using a PDF file. You will Hit on the application CocoSign has created especially for iOS users. Just go to use CocoSign.

These are the elements you need to sign the form right from your iPhone or iPad:

  1. Include the CocoSign app on your iOS device.
  2. Try your email to produce an account, or sign in with Google or Facebook.
  3. Hit on the PDF that needs to be signed on the phone or pull it from the cloud.
  4. Hit on the sector where you want to write down the signature; tick 'Insert initials' and 'Insert signature'.
  5. Insert your initials or signature, place them correctly, and save changes to the document.

After completing, the document is ready for the next step. You can download it to your iPhone and forward it. As long as you have a qualified internet connection, you can sign and send documents quickly.

How to create an electronic signature for the Maryland Uniform Referral Form on Android?

iOS has countless of users, there's no doubt of that, but most cell users have an Android operating system. To satisfy the needs, CocoSign has developed the system, especially for Android users.

You can obtain the app on Play Market, install it, and you should start signing documents. These are the points to sign a form on your Android device:

  1. If you already have a CocoSign account, sign in. If you don't have one yet, you can sign in using Google or Facebook.
  2. Tick on '+' to access to the document you want to sign, from cloud storage or using your camera.
  3. Hit on the sector where the signature must be placed and then use the popup window to insert your signature.
  4. Draw it on the page, confirm, and save the changes.
  5. The final step is to foward the signed document.

To send the signed form, just attach it to an email, and it will reach your others quickly. CocoSign is the best way to sign countless docs every day, all at a low cost. It's time to forget all about signing documents physically and keep it all electronic.

Maryland Uniform Referral Form FAQs

Here are the answers to some common inquiries regarding Maryland Uniform Referral Form . Let us know if you have any other confusion.

Need help? Contact support

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