hey Paul I seem to only get sick on weekdays why why do I feel like I've heard this one before okay tell I must have a weakend immune [Music] system H I was expecting a a cardiac pun but all right yeah well you know we're time is time is out the essence PA the curbsiders podcast is for entertainment education and information purposes only and the topics discussed should not be used Sol dagos treat cure or prevent any diseases or conditions furthermore The View and statements expressed on this podcast are Solly those of the hosts and should not be interpreted perect official policy or position of any entity aside from possibly cash more hos and affiliate Outreach programs if indeed there are any in fact there are none pretty much we are responsible if you screw up you should always do your own homework and let us know when we're welcome back to the curbsiders I'm Dr Matthew Frank wad here with my great friend and America's primary care physician maybe even the primary care physician Dr Paul Nelson Williams hey Paul that is certainly a primary care position hey Matt how are you I'm doing great because this is the first of two episodes that were doing with Dr kson Dr Michelle kson um this is on heart failure with reduced ejection fraction or as you like to call it Paul Hef ref love it love it more abbreviations all right Paul and before before we tell them about our wonderful guest what is it that we do on curbsiders sure Matt well as a reminder we are the intern medicine podcast we use expert interviews to bring you clinical pearls and practice changing knowledge uh and Matt I'd be happy to tell you about our guest in our episode if you like yeah please do so we are joined once again by the amazing Dr Kon Dr Michelle Kon of kson rules Fame on Twitter and of Cardiology Fame elsewhere Dr kson is a professor of medicine at Cedar siai and the Director of Education in heart failure and transplantation she graduated from Harford college and yel medical school she completed residency at Brigham and Women's Hospital and Cardiology fellowship at John's Hopkins where she also received a PhD in clinical investigation Dr kson is part of the ACC aha hypertrophic cardiopathy guidelines and the heart failure guidelines the board of directors to the heart failure Society of America former interm editor-in-chief of the Journal of Heart and Lung transplantation and the associate editor for the Journal of the American College of Cardiology so she's done some things Matt her essays and poems have appeared in the New England Journal medicine jamama and analon journal medicine perhaps you've heard of them her book mastering the art of patient care is available from Springer publishing in this episode we go through Hef ref specifically so she talks about sort of her initial work up determining the underlying ideology how she approaches guideline directed medical therapy and some of the ways that we be um helping the patients in the office as we tiate medications and counsel them about their what their prognosis looks like and some of the ancillary therapies we may consider once we stray outside of our pillars and a reminder to the audience that this and most episodes are available for CME for all health professionals through VCU Health at curbsiders vcuhealth.org and if you haven't done so already sign up for our patreon at patreon.com curbsiders where you can get twice monthly bonus episodes adree episodes access to our Discord the cash laac Vault all sorts of cool stuff patreon.com Michelle welcome back to the show thank you so much for joining us again this is I guess your third time and you're G about to do your fourth time right after this uh for the hepf episode but before we get into talking about Hef can you please remind the audience actually tell them what is a current hobby or interest that you have maybe it's skateboarding if they're watching the on YouTube they can see all the skateboards in the background yes no I have a terrible sense of spatial awareness so you won't get me anywhere near a skateboard cooking is the only other thing I'm good at besides Cardiology and I'll tell you a 30 second anecdote so at the end of my CV I tout my cooking prowess I talk about my famous peanut butter cookies and once a colleague was reviewing my CV and he challenged me he said I don't think your peanut butter cookies are that good he happened to live in Cleveland the heart failure Society of America meeting was going to be in Cleveland in a few months I said meet me in the lobby I'll have your cookies I made them I froze them I packed them in tupperw I put them in my suitcase TSA had no problem with it and I was Vindicated he said they were the best peanut butter cookies he'd ever had is the hard failure Society ever going to meet in Philadelphia because you know Paul and I would love some cookies we could certainly set something up as long as you promise to give me a fair and honest assessment of how delicious they are I do and peanut butter one of my favorite foods so yeah I I think I would have no problem doing that honestly you got I mean this is breaking news because we we had a brownie incident I think was it our very first episode if I'm not mistaken the peanut butter cookies is newest to me so I'm we'll talk afterwards about that so good well Paul we have a very ambitious schedule tonight so I think we should just get into a case from cash laac Memorial and we should mention that the great Dr Deb gor uh wrote this case so please accredit any jokes in there audience you know please attribute them to her and her her fantastic wit all right well with that Preamble let's learn about Mr Smith who is a 62-year Old Gentleman no real previous medical history that we know about before we had a recent hospitalization where he was diagnosed with heart failure so he's coming into our our Outpatient Clinic for his first outpatient visit after he was discharged from an area Hospital not affiliated with cash Memorial health upon a review of the discharge material we find that he presented with shortness of breath and L edema so a nice classic story and Echo done at that time revealed a left ventricular ejection fraction of 25% modit to fear mro regurgitation during this hospitalization he was treated with di diuretics started on the Cil and discharged on the Cil 5 milligrams in near homeopathic dose mopal tart rate 12.5 milligrams twice daily and 40 milligrams of oral feride in our office he says he's feeling better um since he was hospitalized which that's good um instead of sleeping in kryer he's now sleeping in his bed again but he's still using two pillows to help with his breathing he can walk up a fats without stopping um but he does get winded when he gets to the top which which is a a difference from his his Baseline prior to his hospitalization uh his legs still feel a little bit swollen but better than they did weeks ago on examination his blood pressure is 134 over 82 his heart rate is 82 in regular um respirations are un labored O2 sad is fine his jugular Venus pressure is elevated about 2 centimeters above the clavicle when he's sitting nearly upright and he does have pitting edema to his knees he's shaken by this hospitalization so he'd like to get back on track with his health and so we've got this patient who comes to us with his journey started let's say um and in terms of his new heart failure diagnosis so feeling better but clearly not optimized so Michelle where where would you start with this patient as he presents in your office just almost completely um tabular Rosa for you perfect so the first thing you have to do when someone presents with a newly diagnosed cardiomyopathy the first question you have to ask is why why does he have a cardiomyopathy because if you can identify an underlying ideology it may allow you to have disease directed therapy to improve his heart function symptoms prognosis and also gives him a sense of what what are the treatable causes so what do we think about when we think about newly diagnosed cardiomyopathy you want to think about coronary artery disease first and foremost especially if you have a 62y Old Gentleman older man coronary disease is going to be on your list whether you do a stress test or you do a coronary CT andram or you do an invasive andram it's truly dealer's Choice based on your pre-test probability and what's easily accessible and available at your institution the other things you're going to want to look at lwh hanging fruit you you want to think about could there be a thyroid disease could there be some kind of diabetes contributing could this patient have HIV could they have hemocromatosis so the lwh hanging fruit in addition to the classic history physical social history for elicit substances three generation family history for potential familial genetic contribution is going to be those sorts of test thyroid functions hemoglobin A1c HIV serum fertin transferin and then you might do more focused workup is if your history and physical leads you in a certain direction is there anything suggestive of a rheumatologic condition is there a signal from the three generation family history that you should do genetic testing are you concerned about amalo dois you guys have a great episode on that what about substance use cocaine methamphetamines prom L can lead to a cardiomyopathy is it something a zebra like acromegaly could they have some form of infiltrative disease for which you'll get a cardiac MRI so start with the common things and then use your history and physical to guide you for the less common things I think we could do that Paul as internists we're pretty good at thinking through a differential diagnosis and ordering tests I I think like an order set where I can just click off everything yeah you like you like the lime panel on every order well it's part of the fatigue panel which I'm a big fan of so yeah absolutely okay you guys are violating a lot of Kon rules right now and I'm going to try to just remember don't check a test that won't change your management before you check a test make sure you know what to do with a positive negative or indeterminate result or you shouldn't be ordering it so for this patient that we presented to you he has extra fluid and this always gets suggested to me how about we check the BNP compare it to their prior BNP if we if we diares them can we follow the BNP where are we at with that okay so let's talk about BNP B type ntic peptide released from The ventricle and response to increased LV wall stress so a marker of volume overload and congestion let's talk about what the guidelines tell us which is based on what the evidence tells us when is a BNP useful it's useful to support or excluded diagnosis of heart failure so it's a great test for a patient showing up to the ER with no prior history and shortness of breath and there's a concern of heart failure a BNP can help in that setting it's useful on a patient admitted to the hospital with decompensated heart failure to establish prognosis remarkably in one study if your B&P was over 5,000 88.5% in hospital mortality that is useful to get a sense of the trajectory of hospitalization however what is it not useful the evidence for treatment guidance based on serial BNP or anti-rnp is insufficient so you should not guide your diuresis based on serial assessment of BNP you should guide it based on your physical exam so in this patient an elevated jvp edema symptoms of orthopnea though improved and disp on exertion this is a slam dunk this patient is congested and they should be diarrheas titrated to their symptoms and their physical exam not to their BNP level it's so important to remember that the laboratory evaluation must be interpreted in the context of the clinical presentation so use your BNP but don't hang every management decision on it yeah and how much stock do you put in you know how it's affected by age and obesity totally there's you know obesity will lower your BNP age will increase your BNP kidney dysfunction will increase your BNP so you have we have a lot of factors here and then you do the thought experiment if I have a patient who has disp on exertion or thopia elevated jvp and edema and their BNP is low am I going to say oh you're not wet because they happen to be obese or they happen to have heart failure with preserved ejection fraction where it can be low I'm not going to not diares them let's take the other patient they feel great they walk 30 minutes a day they sleep flat their jvp is normal they have no edema their BMP is high am I going to empirically diares them no so you have to remember exactly as you know there are pitfalls to the B&P where can be falsely low or chronically high and it can't do the daytoday serial assessment of diuretics and volume status I I've seen that latter example all the time and especially for a patient with health anxiety who otherwise feels great a BMP is checked they're optimized it's elevated they're like now what is my heart bad I'm like I I'm not sure what to do with this information like I'm I'm sorry you look good U I guess we can check it again and see if it does something but even that is sort of deeply unsatisfying so that's that's very no I basically tell them the only thing we should do is go back in time and not have checked it and short of that we should never check it again yeah I mean you you get a lot of patients especially when you're working in the hospital setting and they're admitted and they say oh their BNP was is 10,000 this time last time it was 5,000 does that mean it's worse you know it's but like you told if it's above 5,000 it's a bad prognosis right that's just like the the fact that they've had a BNP that high that's right but you're not going to say oh it's falling which means I'm diuresing them appropriately or it's rising so I'm not diuresing them appropriately that serial assessment is completely unhelpful and we're trying to change hearts and Minds here no pun intended not checking serial assessment of BNP it is not beneficial okay Paul do you ever struggle with the order of medications here it's so funny you mention that Matt yeah we we were talking a little bit before we started Michelle I think one of the circumstances I will see is that a patient presents just like this they are started on their their treatment Journey as we talk about they they feel much better but not well yet and not sort of all the guideline directed therapies are on board and sometimes it's even hard to tell why that might be the case whether it's Insurance barriers or electrity abnormality or what have you so I I guess for you I think I've even asked you this before if you had sort of a rank order preference as to what we should be starting and when like how do you how do you think about that broadly and then maybe use that to transition into sort of the pillars of therapy perfect so well I guess I sort of have to start with the pillars of therapy right because the four pillars of guideline directed medical therapy for heart failure with reduced ejection fraction are the Angiotensin receptor neply inhibitor cital Valsartan which is superior to an Ace inhibitor which is in turn Superior to an ARB that's the first pillar the second pillar is the evidence-based beta blocker balol carvol or sustained release tool the third pillar is the mineralic corticoid antagonist the ainon or spironolactone and the fourth pillar is the sglt2 inhibitor igin or dagin so within those classes there's a class effect they're all fine but the Arne is better than the ace inhibitor is better than the ARB for the first pillar so what order do you do them there's a lot of schools of thought on this there are some people out there who say simultaneous initiation just go for and start all four at once to those people I say I don't know if you actually take care of patients because every time you give a medicine to a patient it's like you're entering into a contract of trust right take this mysterious pill and it will make you feel better and it will not make you feel worse and they trust you and if you give them four at once and they do feel worse and no one knows which one caused it that's a violation of trust so I'm all about rapid sequence initiation then you have to ask yourself what order when it comes to Rapid sequence initiation and I'll tell you there's one point to keep in mind remember which medicine actually help you feel better acutely and which medicines do not they all help you live longer they all help keep you out of the hospital but which ones help you feel better acutely and which don't well the one that does not help you feel better is the beta blocker in fact patients might feel a little worse after you started so you want to hold off on that until they're optimized on the others so I typically start with the Arie followed by the MRA followed by the sglt2 inhibitor and when I'm confident they are beautifully optimized decongested then I'll slip in the beta blocker now you might say to me well I prefer to start with the sglt2 inhibitor followed by the MRA followed by the arat say fine um you know that the order of those three hard to hard to parse out which is best but then if you said to me they only have a certain amount of blood pressure to spend what am I going to spend my blood pressure on I can't spend it on the Arie plus the MRA plus the sglt2 which one of those should have be well then I'd say to you you know the MRA and the sglt2 inhibitor really don't bottom out blood pressure that much so try to get that Arnon first since it's the foundational therapy really the therapy upon which all other studies were performed and then you slip in the other ones after that so that's my philosophy think of what will cause acute hemodynamic benefit through their effects on vasod dilation Arie natur resis diuresis m GT2 inhibitor and then think about the beta blocker which is good for long-term remodeling but really can be poorly tolerated in someone who's decompensated can I ask about the the order of the the Arie Ace ARB I which I I might be lightly surprised about I I think at least in terms of treating hypertension I always am much bigger ARB fan than I am an Ace inhibitor fan and I would just think in terms of transitioning to an Arie if you have the ARB on board that also might be a little bit easier potentially so I I guess can you talk to me about the evidence making Aces a little bit better in the circumstance because that's a little bit counterintuitive to me yes me too me too me too if I'm treating hypertension I will always give an ARB or an ace because I don't want someone to have some random angioedema five years from now totally unpredictably and show up an ER and then everyone's upset totally if it's hypertension give the ARB over the a inhibitor now if you look at the clinical trials the foundational Landmark trials in heart failure with reduced ejection fraction starting way back in 1987 with the consensus trial captopril save lives and that's really where the Journey of Ras inhibition began later on they did studies comparing arbs to Aces and you know what ACE inhibitors won so it's unequivocally true that ACE inhibitors are better than arbs for this one indication and one indication only heart failure with reduced ejection fraction then of course Paradigm HF 2014 knocked the ace inhibitor off its Throne the Arne once a cubital bartan compared to a nil in an active control head-to-head trial so now it's clearly established RNA is better than ACE inhibitors better than ARB ARB so if I had the opportunity to have a fresh patient in front of me who's newly diagnosed I just start the Army why not they're there sitting in front of me why would I start with something else when I've got the best therapy at my disposal now you would say well but in the Paradigm trial there was a runin and you know that was for trial purposes really pathophysiologically the shortest distance between two straight line two points is a straight line just start them straight on the Arie and I'll only go to an Ace inhibitor instead if it's a cost issue or if it's a tolerance is like they're just too hypotensive to tolerate the Dual V vasod dilation of the inital valaran plus it's twice daily dosing whereas I could just slip in 2.5 of linil at bedtime and maybe avoid some of the hypotension and I only reach for an ARB if they have angio edema to an ace because that would contraindicate the AR because Ares have high risk of angioedema because the suub tril leads to increased Brady in the same way an Ace inhibitor does so that's really the hierarchy but I see no reason not to just start with the AR if that fresh patient is sitting in front of you with the Arie I find that the biggest barrier is cost maybe the second biggest barrier is hypotension and that that was the runin right the the runin in the Paradigm HF trial was to to weed out the patients that just couldn't tolerate from a blood pressure standpoint yes so let me tell you my philosophy that first the cost issue let's all give thanks to the unsung heroes of medicine our pharmacists we are very lucky to have a pharmacist attached to our heart failure Clinic who helps us with the arduous process of blackbox of making things affordable second point is I always am very open with PTI I say I think this is the best medicine for you but I know everything about Cardiology and absolutely nothing about what the sticker price will be when you take this prescription to the pharmacy so if it is too high you should not mortgage your house to take this medication you should let me know there are other Alternatives which are maybe incrementally not as good but certainly not worth mortgaging your house to afford this one right like the hypotension issue so this this is I'm going to say something controversial isn't that great I tell my patients when I start them on gdmt in clinic I say I want you to go home and I don't want you to check your blood pressure I don't want to know what it is until we have our two-e follow-up appointment and maybe it's over the phone and that one time I want to see what your blood pressure is or when you come back to Clinic the only reason I want you to check your blood pressure when you leave my office is if you feel poorly in some way because if you feel great by definition your blood pressure is great so I don't care if it's 90 over 60 I don't care if it's 88 over 50 or it's 110 over 70 if you feel good and you can go about your day without almost fainting every time you stand up then the number is not important to me and I think that it also lets patients know they're not so focused on this number and it allows more optimal and effective gdmt titration yeah you know Paul I don't know if you find this too I mean I I'm still seeing the majority of patients with heart failure um they seem to be Ace ARB ba uh beta blocker and MRA because those are just like affordable a lot of the Medicare patients like the their co-pay they do have a portion of cost sharing and it just seems like the the sglt2 Arie combo is just like can really be a lot of money for people yeah it's always yeah it's sort of a a tragically pleasant surprise when I see an Ary in the wild because I'm like oh good for them like but it's not yeah I agree with you that's not typically what I say and then you have to decide then say you say they only have a certain amount of money to spend are they going to spend on the Arne or are they going to spend on the sglt2 inhibitor right that's maybe they only have enough money for one of them honestly in that situation I truly believe in the power the synergistic power of the four pillars and in that situation put them on the generic linil and let them spend whatever funds they have on the sglt2 inhibitor that's great yeah that's very I think that's very practical way to go um yeah and and then you know sometimes you see you just see patients for what ever reason they're they're not on all four and it can be kind of hard to sort out but sometimes I think it's because maybe they didn't tolerate it or they had hyperemia hypotension that sort of thing so it sounds like you're just sort of getting as close as you can to the ideal situation based on cost and side effects and and everything am I anything else to say on that yeah you know for anyone who works in an electronic medical record system just searching for the drug is often really helpful like why aren't you on spoton this makes no sense to me oh oh now I can search and I see that note and it said you had a kf6 three times when someone tried so I think that's really helpful and then you can document so you have to ask yourself if a patient's not on the four pillars why not and if they are can I tight treat yeah okay maybe we should just mention the strong heart failure trial right so this was the one where they they they put patients they they were admitted with acute decompensated heart failure before they left the hospital they started them on the four pillars and then by six weeks they were trying to get them up to goal so maybe you can talk about what was goal what are the goal Doses and you already mentioned you know you you do the rapid sequence initiation but what do you think about that trial I think that trial is really really cool and now his because of when the enrollment started there was actually only three pillars in the trial sglt hadn't become standard of Care at the time of enrollment but Arnie Ace ARB beta blocker MRA you said by the time of Hospital discharge for admission for decompensated heart failure and then with two weeks the goal was to have them on a 100% of uh recommended doses and then they were followed for six months so what what does what are the drugs what are the max doses that we want it's 97103 for Securo Valsartan 200 for matool lainate and it's 25 for spironolactone and then for the SGL T2 inhibitor there only one dose 10 of adapin or empig loin and what was so remarkable to me about this trial is when they looked three months later much higher proportion of patients were on target doses if they were in this high intensity group as opposed to randomize to the usual Care Group I mean that's not necessarily so surprising you try to get someone on meds they get on meds what was really amazing was when they looked at six-month outcomes death heart failure hospitalization it was 15% in the high-intensity group it was 23% in the usual Care Group that's an absolute risk reduction of 8% in six months that's a huge effect size that to me is such really important evidence to work hard with your patients and Empower them to say listen if I get you on these pillars you're not going to see an effect in five years you're going to see a benefit within six months of being on these incredible therapies yeah I mean that's that is that is incredible I was it was exciting to hear that and you know I feel like I am I am seeing more patients now just anecdotally that are being discharged like more aggressively on more medications when they're initially sent out of the hospital from a heart failure exacerbation and uh that's that's also why close followup is necessary because sometimes the patients are they started me on like six things I don't know what any of this is and you kind of have to talk them through it yeah I mean the hospitalization is such it's a luxury right to check blood pressure and blood work every single day it's a it's a teachable moment it's a great opportunity but as you know you got to close the loop on followup to reinforce the importance of meds to check the heart blood pressure to check the Laboratories so that reinforcement is critical M so Michelle I've noticed a couple of times you said mopol su8 I will take take us back to our case for the patient was actually on mopol alar trait I have learned anecdotally a great way to make cardiologist mad is to use mopal alar trait for um he ref so could you talk me through how we might optimize why who cares um why do we care and then how would you optimize this patients regimen yeah first no you don't make cardiologists mad you just hurt our feelings right we're really sensitive and we just want what's best for the patients we're not we're what do a mom say I'm not angry with you I'm disappointed with you yes I'm I'm very disappointed okay so that there's the landmark clinical trials of beta blockers with heart failure with reduced ejection fraction used bisoprolol sustained release metoprolol metalol succinate and carvol there actually was a small trial somewhere in the 90s using the tartrate MOBA tartrate and patients didn't benefit now you could say maybe the trial was too small or maybe they just didn't give it right but for whatever reason we have to be guided by the evidence we have and there's only one class of medication for which there is a class effect and that is the beta blockers bopol carbol sustained release mopol mopol succinate so I would immediately switch this patient to the mopol succinate which of those three do I use for whatever reason in my hospital system bopol isn't commonly used it's usually a toss-up between carvol and sustained release mopol do I have a preference yes my preference is mopol succinate why because carvol is is twice daily and it has Alpha blocking properties so it's more likely to cause hypotension so if I want to slip on a beta blocker but I don't want to spend my money spend my blood pressure on a beta blocker I want to spend it on my Arie predominantly and then my MRA and sglt2 inhibitor then I'm going to want to give them the beta blocker that's least likely to lower their blood pressure and in addition a nice trick with a once a day medication is you can slip it in at that time so even if the Mone might cause fatigue if the peak effect is while they're sleeping who cares anyway so that's why I would immediately switch this guide to mopol succinate Quick Fix tell him to take it at bedtime and he's already going to be on a better pillar yeah am am I hallucinating this or is molos Su andate the 25 milligram tab it it's one of the rare long acting tabs that can actually be split right you get 12.5 exactly exactly and what dose you start on is kind of f philosophical right I mean I tend to just start with 25 and even like spironolactone I just start with 25 I don't do the 12.5 I'm like whatever is a little less work for me because you know if you're gonna get hyperkalemia you're you're probably gonna it's you're gonna get it no matter what dose you give so that's just sort of a an efficiency thing on my standpoint but yes if I start the 25 and they don't tolerate it first of all it's a little concerning to me because intolerance of guideline directed medical therapy is a poor prognostic sign but then absolutely you can split it in half which is a nice trick and then we're checking metabolic panels probably every one to two weeks because hyperemia with Mo you know with the MRA the the Arie Ace ARB and uh and yeah I feel like the sglt2 was one of the easier ones to start generally Joel Joel to even told us he's he doesn't think you even need to really check anything because you know the egfr is going to temporarily go down a little bit but don't even worry about that so I'm not super aggressive if if they're just on that I'm not usually checking but for for these patients they seem be at Labs every at least every two weeks or so initially so during Jo dose adjustments usually about a week later check it and then once they're on stable doses really every three months is standard as for the Arie Ace ARB for the MRA and I agree with Dr Toff you know sglt2 you almost don't want to know about that little bump right just ignorance is bliss just if they're clinically doing well just follow them can I ask so for our patient here who's a little bit congested still but doing better would you fire off the hlt2 and leave the diuretic alone like I guess this is my larger question like how do you how do you think about the the diuretics are already on board when you're starting the sglt2 is or you just not worry about it yeah you know in the olden days when the olden days when we first started using the sglt2 Inhibitors we'd say oh no it's going to cause a big diuretic effect you better back off on your diuretic it turns out it doesn't really do that but that being said it's always such a joy to add these pillars these valaran the MRA and the sglt2 will all have a diuretic effect so they tend over time to need less Loop diuretic or need less augmentation and we know that Loop Diuretics in heart failure are a necessary evil right you got to take them so you're not congested and drowning in fluids but they don't actually offer any benefit whatsoever to your patient and maybe even potential detriment to your neuro hormonal system so if you can get these other agents on and allows you to minimize Lo diuretics it's a huge win so for this particular gentleman I would Pro you know he is still pretty symptomatic and his jvp is pretty high he's got a lot of Edema so what I would probably do is add the sglt2 also double as diuretic but see relatively quickly one to two weeks because at that point he may have been magically better and when I add the MRA maybe go down on the um Loop diuretic so with with the SGL t2s you know we talked about the egfr kind of you know going down slightly we know that's going to happen but uh for this cut off you know they they've studied it's I think imp pagla floen has been studied at lower egfrs and then deagen I haven't really put too much thought into that I'm kind of just using them almost regardless where are you at on that yeah I mean if you look at some of the heart failure guidance they'll tell you egfr 20 to 30 so to have heart failure with an egfr less than 20 I mean then the nephrologist is really in charge of everything right that's a hugely horrible kidney function so what the lesson is is exactly like you say you're pretty much not going to find anyone who's got who's not on dialysis who can't tolerate the sglt2 inhibitor and exactly like you said you don't want to obsess about that early bump in creatin if so don't look at the blood work look at the patient if the patient looks okay say we're just going to figure out if this is an outlier Trend let's recheck your blood work in two to three weeks MH okay so the the other stuff that's been around Paul remember in residency we're were using a lot of hydrazine and isosorbide uh dinitrate uh because you know we didn't have all these other medications yet and so I I'm curious as to where we're at with that now um Dr kson I I really I'm so glad you asked about um hydrazine isosorb dinitrate because to me this is a really good example Le of a term I think I coined indication creep okay so let's talk about Hydra IOD nitrate it's vasodilators right so back in the 80s all of the heart failure Giants of the day knew that afterload reduction was good for patients with heph right it stands to reason hemodynamically you got this poor weak failing heart you reduce their afterload and now this poor weak failing heart is less resistance it can pump better the stroke volume increases everyone's happy well there's a lot of different ways to decrease after load you could give an Ace inhibitor you could give hydran isosorbide you could give pricin and in fact the vft one trial which came out in 1986 tested hydraline isosorbide versus pricin versus placebo no surprise to anyone pressin didn't work and no one ever thought about it again unless they had BPH but the Raging debate of the mid 80s was which baso dilator is better is it isosorbide dinitrate hydrazine or is it the ace inhibitor and then the vft 2 trial came out and it was 1991 and they pitted the two against each other and is still isur by dinitrate hydroling lost so no one thought about it anymore it was the loser ACE inhibitors were the best until 2004 when the aaft trial came out which took patients self-described as black American with severely symptomatic Hef class 3 to four and gave them isal hydraline and there was a reduction in mortality so that's the sound bite if you're African-American and you have he Hef ref you should be on ISO isosorbide nitrate hydrazine that's the sound bite that's the indication creep you got to look at the fine print of that study what does the fine print of that study tell us it tells us that when that trial was published 2004 what was the best therapy around at the time ACE inhibitors and beta blockers well 90% of patients in that trial were on an Ace inhibitor 7 % were on a beta blocker and the Baseline blood pressure at the start of the trial was 120 millimeters Mercury can you think of a patient with severely symptomatic heft ref who actually has a blood pressure that high all of that to say that the AHF trial was focused on a very specific population of patients already on the best gdmt that existed at the time who still had blood pressure room and toir symptoms and showed a benefit all of that to say that isosorbide dinitrate hydrazine is not a substitute for the four pillars of gdmt it is an adjunctive therapy if your patient has happens to have blood pressure room despite the four pillars of gdmt and in observational studies of who actually meets those criteria it's about a 1% of patients in cohorts and in my clinical practice of I don't even know how many hundreds of patients I follow I have exactly one patient who has blood pressure room for this combination after after I've optimized the four pillars so think of it only in rare situations when you've already optimized gdmt yes that's such a that's such a good way to frame it I I think once in a while you still see patients with just on hydrazine randomly and you know you don't know what their blood pressure Journey has been but I I'm still seeing more of it than I would like to Paul I I would say it's like the gab Aenon of blood pressure medications in in my opinion Paul what it's either a Hillary P or someone gets grandfathered in there's no in between like I don't see like anyone who's been started on it recently unless youve just run out of other options yes okay now maybe we should make Paul pronounce these but I'll I'll take it so I was gonna try okay Paul what what are the other two fancy ones that uh I've never prescribed probably never will um well let's SP because I was going to ask about the I brating pause to see if anyone makes a face that I mispronounced it because that was I remember when it came out I remember the study and there was like a lot of wild enthusiasm about it and I think I've rarely seen it out in the wild so I would love to know when you think about that and how you use that medication then Matt we can arm rle over who has to say the next one cool and I I I don't I've spent much of my life mispronouncing things is I say I Vine but potato potato I'm cool so it inhibits the funny current of the sinoatrial node which means uh it reduces heart rate without reducing contractility so technically because we know patients who live at a higher heart rate with he do worse if you can optimally lower their heart rate that should do better the shift trial showed it reduced heart failure hospitalizations and death in as a combined end point but again beware of indication creep in that study patients were already on Max tolerated beta blocker because beta blocker save lives and then and only then ivabradine was added so there's a lot of caveats if you're going to give a patient ivabradine they should be on Max tolerated beta blocker they should be in sinus rhythm because ivabradine can predispose to atrial fibrillation and they should have a heart rate above above 70 beats per minute because that was the inflection point in observational studies at which point uh uh prognosis worsened in patients with heph so I agree with you I don't use it that frequently either because I find if I can really max out my metalol sux andate to 200 milligrams qhs that heart rate isn't that high and really the effect size in the clinical trial was not that impressive so I would say I would relegate ivabradine really into the same drawer as Hydra isosorbide dinitrate maybe some benefit but avoid indication creep and then the third one is vericat I don't that's definitely wrong but this is an oral guano cycl stimulator yeah wait let me try and then we'll we'll take he the tiebreaker so I would have gone ver sigat oh you know what you're a little closer it's very seat yes that's that's that's what the experts say so no one says it very often because no one prescribes it very much so an oral Guan cycl stimulator it's supposed to do all kinds of wonderful things to the endothelium nitric oxide this and that so the Victoria trial was the landmark trial it was a very large trial like 5,000 patients and they had to be kind of sick they had to have symptoms or recent hospitalizations recent IB diuretic use randomized to VAR seat versus placebo pretty good Baseline gdmt in this population and the effect size was really small so at a follow up of around 30 months the point estimate of death and heart failure hospitalization was 29% in the placebo group 27% in the treatment arm high event rates let's let's say that I mean this is a sick population but very seat did not move the needle appreciably which is why the guidelines give it a relatively weak class 2B indication based on the minimal magnitude of benefits so here's how I think about very seat will I prescribe it in someone who I've attempted optimal gdmt who is still being hospitalized for heart failure yes I will use it in that population but I think about very seat as the start of the conversation not the end of the conversation meaning you're really sick every time you are hospitalized for heart failure you have a 30% chance of mortality within the next year so you're already in a sick subset I might be giving this to try to help but I already know from the clinical trial it's probably not going to help that much and let's have a larger conversation about what are your other options at this point given your poor prognosis so let's go back to our patient he has an EF under 25% so we're going to want that defibrillator right and then maybe you can comment on his mitro regurgitation as well yes I would love to so he may or may not need a defibrillator right because if he has a schic cardiopathy and we revascularize him and give him gdmt or if he has a non-ischemic cardiopathy and we optimize his gdmt and we check an echo cardiogram 3 to six months later he may have recovery of his ejection fraction in observational cohorts about 30% of patients can actually achieve this magical goal of heart failure with improved ejection fraction ejection fraction it goes from below 40% to above 50% I've seen it so many times with my own eyes it never gets old it is the best feeling in the world so you're not going to jump on that defibrillator for primary prevention you're going to first optimize your gdmt and maybe they won't need it at all ditto for cardiac resynchronization therapy this magical therapy that allows The ventricle to beat more synchronously that in that unlike defibrillators which just may save your life if you have an event CRT actually improves symptoms but again you would hold off unless they truly meet the criteria of that reduced ejection fraction along with the widen QRS after optim ization of gdmt and that same principle see what happens after you optimize gdmt applies to the mitro regurgitation I'm fascinated by secondary mitro regurgitation okay there's thing about mitro regurgitation primary means it's the valve's fault secondary means it's The ventricle fault because this poor failing ventricle is super dilated so those little leaflets can't COA anymore can't come together and therefore leakiness ensues back in the olden days they tried to do surgery but you know when you crack open the chest of someone with a low E F things do not go well surgery did not work and then all these amazing wizards of Interventional Cardiology I'm convinced they played a ton of video games as a kid they came up with these techniques where you could kind of basically play a video game inside the heart and clip the mitro valve together through a catheter-based approach and in doing so make the mitro regurgitation go away so the question is does it work or not and this is such a beautiful lesson in randomized trous because we think always in the hierarchy of evidence that randomized control trials are the truth they are the gold standard but when it comes to secondary mitro regurgitation in patients with heph we have one trial that said it was amazing and one trial that said it didn't work so what does that tell us what's the lesson there the lesson is yes randomized control trials tell you the truth but only the truth about the population they enrolled so mitro was the trial that showed no benefit it took patients that had severe Mr not a lot of effort into optimizing therapy or attention to the LV size Etc then you have co-opt which is quite a highly curated trial on Entry to be randomized to the mitro valve trans cathet or edgo Edge repair or standard therapy they had to have an EF between 20 and 50% and LV size less than 7 cm pal monary artery pressure less than 70 and they had to be optimized on guideline directed medical therapy as signed off by a heart failure specialist and I that is the sweet spot so what Co-op did that Mitra F didn't is they got the patients who were not too sick meaning the EF was too low the pulmonary pressures were too high the LV was too big me the horse was out of the barn and they also didn't enroll the patients that were too well because you know if you just optimized gdmt everything would get better and they wouldn't need this to begin with so coab took that sweet spot which is why the guidelines are very clear on the criteria of who should be referred for this mitro valve transcap edgo Edge repair AKA mitro valve tier which is they have to already be optimized and still have severe Mr and they LV can't be too big their EF can't be too low and their pulmonary pressures can't be too high and that's such an important lesson for our patients and also so one of my pet peeves in life because I have so many is checking a kneejerk echo cardiogram on a patient admitted with decompensated heart failure who has a known cardiomyopathy for two reasons number one if I already know their EF is 30% is a repeat Echo showing that it's 20 25 35 is that really going to change anything I do no second so sometimes I I do like to debate with my with my trainees and I say so why'd you get the Echo and they kind they know they know me by now they might say well we want to see if the patient is a candidate for the mitro valve tier and I say wait a second though this patient is decompensated do I really care about the degree of mitro regurgitation and the throws of an acute decompensation cancel that Echo that's order it prior to discharge when they are fully optimized so that's a reason I can't think of a good reason ever to check and Echo to document anything on a patient who's highly decompensated oh that's a really good that's a really good point because that's mostly when it gets checked like right when they come in before they're before you optimize them and if you already know the EF is low it it doesn't you don't need to speaking of the ejection fraction the Hef ref heart failure reduced ejection fraction when we talked to Dr yansy he taught us that heart failure uh with recovered ejection fraction was something that was being was noted at the time but a recent a resident told me I thought this was a cool thing a resident taught me that they changed it to heart failure with improved ejection fraction the term that you just used and that's because we wanted people to remind people that it has improved but it's not fully recovered we they still need to be on guideline directed therapy and that's the key point because sometimes if you look at an echo and it's their es 50% people forget that they need to be on these important medications you know I that's exactly right wordss matter and that's why we call it hardfield with appr prooved d f now and I remember back in the olden days when I would have a patient and I'd put them on their gdmt and their EF would recover and they'd say to me can I stop these meds now they're really annoying and I'd say I think so nobody really knows and I know you're really young and you don't be on medications forever let's stop one and check and Echo and stop another and who knows what'll happen and then the tread HF trial came out such an important beautiful trial listen it was only 50 patients but it got into the Lan because it had great study design and a really important clinical question so they took these patients who had heart failure with improved ejection fraction who were on gdmt and half of them they said stay on your gdmt and half of them they said you can stop your gdmt and then they said six months later how do you look they looked at LV size they looked at EF they looked at clinical heart bill it looked at BNP and what did they find no one had any relapse based on those four parameters if you continued gdmt but 44% had some form of relapse if you stop gdmt so really this is so important for us as clinicians because it's hard to tell a young person who feels great whose heart is normal to stay on four medications but now at least we have the backup of evidence to tell us you know what it's really in your best interest to do it so I still I do want to ask about some non-pharmacologic stuff uh but Paul you want to get back to the case and then we can ask any final questions for this yeah I was going it's almost I I don't want to ask I'm I I don't expect you know numbers Michelle but my sense of things is that re synchronization therapy is being offered less frequently because we've gotten so much better at managing with guideline directed medical therapy is that a real Trend or just sort of what I'm feeling in my heart because I feel like I just don't see it talked about as much because we're seeing the ejection fraction um yeah improves so much now now that we have these great medications that can be helpful for things I can't roll off a trial off the top of my head but I completely agree with you and what's so fascinating about the cardiac resynchronization therapy too is you know there are 30% non-responders so you really want to pick the right patient that QRS left bundle is so wide and the gdmt is totally perfect and there are patients who you've optimized their gdmt they feel amazing but their EF is still low and then you do the CRT and lo and behold the EF improved so it is still an important part of our armamentarium but you're exactly right push it off put the pills on first perfect thank you and along those lines so we'll go back to our patient sorry Matt um but he he's doing better we start him one um outpatient titration of his heart failure medications he is now on maximally tolerated doses of guideline directed medical therapy he can now carry his veries up a flight of stairs the single most important question we've ever asked in any physical exam ever um he's thinking about walking in an upcoming 5K Turkey Trot so we repeat his tte um now that we have him optimized and his ejection fraction is now 45% the mitro gation is now mild um and so less severe than it had been previously so we talked that we should not be stopping therapies but I guess what else does he need to see you I guess at this point would be another question I might ask so let's say we were we heroic primary care doctors and all this stuff on our own like when when should we actually have this patient see you and what else should be thinking about for this patient that's a great question and I do think fewer doctors are better and fewer doctor visits are better so if I tend to I I love doing gdmt titration I love doing the teleah Health visits every two weeks so if I get to the point where the EF is normalized like this gentleman did or near normalized 45% amazing I will check a second data point six months later just to confirm I don't that's not really in a guideline to me it stands to reason let's just get a second data point and then I tell them congratulations you're doing amazing see me once a year for an Echo do they need it is it fine if they're lost if they never see me again but they continue all their meds will they be okay probably so I would say if you are the heroic internist and you have maximized your gdmt and you've achieved heart failure with improved ejection fraction and you've counseled your patient to stay on all their meds because it's really important and they continue to feel awesome continue to follow them yourself the red flags or alarms for which you would want to do something differently is if their clinical status changes if they start to have new exertional dmia symptoms or signs of decompensated heart failure that's a red flag to say uh oh let's dive deeper what are we missing is there something new going on how would you talk to this patient about salt and water intake we're not talking about hospitalized patients I I know there's been some studies there but what do you what how do you talk to them about salt and water you I think we've gone away from the Draconian two gam fluid two gram salt sodium restriction 2 lit fluid restriction because as there really isn't strong data to support it though it's hard to do the data right you can't dose humans with salt and fluids like you can dose a lab rat so again the studies might not be that Earth shattering because the studies are hard to do so here's my philosophy I tell because I have some patients who are on four pillars Max tolerated doses don't even need a DI IC and sometimes they call me In The Heat Of Summer and say I'm so dizzy I can't stand up I'm like no we're not going to reduce your meds yet because you've been tolerating them all winter we are going to give you some more salt so I really to me it's very individualized I tell patients there's no inherent danger to sodium sodium is not going to damage your heart but some people notice that when they eat more salt they feel worse they feel puffy they feel congested if you are one of those people avoid salt to improve your quality of life so that's for that outpatient who's rarely have ever admitted on great gdmt what about the super super tenuous patient who is in and out of the hospital being evaluated for heart transplant I say you are tenuous and you could probably look at a slice of pizza and end up in the hospital because you because you looked at sodium so we have to be very careful with you because we have already seen that your fluid balance is so difficult to manage based on your horrible heart your kidneys aren't great etc etc so I think it has to be a very individualized approach with the first and foremost recognition that salt is not inherently toxic it's just for some people that just can't handle it for their quality of life that kind of reminds me of like when sometimes people ask me can I eat this food or that food and I say well you have a glucose monitor and if you want to know what it does to your sugar you can run that experiment and I guess it's it's kind of the same thing with salt and water you know like your body will tell you if you're overdoing it I guess exactly yeah so you said like if everything's going well and you know we feel like we're doing okay they're on gdmt but who are patients that definitely need to see you so I survived Medical School through neonics and there is a great pneumonic for who's getting worse it's the I need help pneumonic published by Jay Bal wall in the Journal of heart lung transplant in 2017 just a little like Viewpoint article that is like taken over the world because it's so clinically important so what does the I need help ponic I they need IV otrs even either permanently or transiently to assist diuresis while hospitalized n they're nyha class 3 to four they have symptoms with with dressing showering minimal exertion e end organ dysfunction not doing well with the kidneys or the liver um other e ejection fraction so I don't love this one a lot but if your ejection fraction super low I mean it's not a great sign age hospitalization every heart failure hospitalization is a sentinal event e they're getting edema despite escalating doses of their diuretic that's a bad sign needing more diuretics to maintain L their blood pressure is low their heart rate is high and P Progressive intolerance of guideline directed medical therapy when you start having to peel back on gdmt because of real hypotension not oh my blood pressure is 88 and I feel great but I feel like I'm going to faint every time I stand up on my blood pressure is 78 that's a hugely concerning sign that they're having Progressive symptoms and I always talk about as Advanced heart failure specialist I think about this magical window where the heart is sick enough to need something like a transplant but the rest of the body is still well enough and that I need help pneumonic is so important to have a heightened awareness of all the horrible things that can happen to a patient whereby an early referral to an advanced heart failure specialist is important and I just remembered I forgot the D the D was def fibrillator shocks so add that to your list the I need help pneumonic H red flag alert sent to a specialist yeah probably if a patient's being shocked by their defibrillator I'm sending them I'm sending them your way I have wonderful news I don't need not need ponic if the patient is going through shots all right what are like two or three take- home points you want the audience to remember from this episode so gdmt the four pillars the Arie the evidence-based beta blocker the mineralic corticoid antagonist in the sglt2 inhibitor these help patients feel better stand out of the hospital live longer and potentially improve heart function so for every patient you see with heart failure with reduced ejection fraction ask yourself why are they not on these four pillars can I start them can I titrate yeah all right and anything you'd like to plug maybe a book that you've done well yes I've written a book it's called mastering the art of patient care it's published by Springer it's based on uh the wisdom of my mentors and all the mistakes I have made so you don't have to make them all yourself and this is really exciting just today hot off the press I got an awesome email from a trainee saying oh my gosh I read your book I was in an outside rotation at a really fancy institution and everyone was so impressed with my presentations because they were so clear and thoughtful and thank you so much for your book and I was so happy because that's why I wrote it fantastic All Right audience check that out order five or six copies you know do the right thing [Music] [Applause] this has been another episode of the curbsiders bringing you a little knowledge food for your brain hole yummy still hungry for more join our patreon and get all of our episodes add free plus twice monthly bonus episodes at [Music] patreon.com/scishow and to do that we want your feedback so email us at ask curbsiders gmail.com please also subscribe rate and review the show on Spotify Apple podcasts subscribe to us on YouTube uh a reminder that this and most episodes are available for CME through VCU Health at curbsiders VCU health.org special thanks to our writer and producer for this episode Dr Deb gor and to our whole curbsiders team our technical production is done by pod paste Elizabeth Proto runs our social media Jen W does our patreon Chris Manu moderates our Discord steart Bram composed our theme music and with all that until next time I've been Dr Matthew Frank Wad and as always I remain Dr Paul Nelson Williams thank you and goodbye [Music] [Applause]