What’s New in 2023 in the Management of Heart Failure?

Aug 26, 2023

What’s New in 2023 in the Management of Heart Failure?

The field of cardiology is well known for rapidly synthesizing the evidence from new and cleverly named clinical trials into diagnostic and therapeutic guidelines. The latest updates in guideline-directed medical therapy (GDMT) reflect the remarkable advances in management of one of the most common reasons for hospitalization: congestive heart failure (CHF). At our next Medicine Grand Rounds, Jonathan Davis, MD, director of the Heart Failure Program at ZSFG, will review the latest guidelines for treatment of heart failure, focusing on the 2022 ACC/AHA/HFSA Guidelines.

Speaker:
Jonathan Davis, MD, is associate professor and director of the Heart Failure Program in the Division of Cardiology at ZSFG. He is the recipient of the 2020 Henry F. (Chip) Chambers, MD Medicine Subspecialist Consultant of the Year Award. Jonathan was born and raised in San Francisco and attended medical school and internal medicine residency at UCSF. He continued on faculty as a Congestive Heart Failure service hospitalist and then completed fellowships in Cardiology, Advanced Heart Failure and Transplant Cardiology at Washington University in St. Louis. He then served as medical director for Mechanical Circulatory support at OHSU and was recruited back to ZSFG in 2018. He is a clinically renowned cardiologist and his research focuses on innovative care systems to reduce admissions for heart failure.

Note: Closed captions will be available within 48-72 hours after posting.

Program
Lekshmi Santhosh: Introduction
00:01:47-00:54:25 – Jonathan Davis, MD, associate professor and director of the Heart Failure Program in the Division of Cardiology at ZSFG
00:54:41-1:03:24 Q\u0026A

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Content

1.35 -> - Good afternoon everyone,

2.49 -> and welcome to UCSF Department of Medicine Grand Rounds.

6.03 -> I'm your host and Director of Grand Rounds,

7.253 -> Lekshmi Santhosh, filling in for our chair,

10.11 -> Dr. Bob Wachter while he's away.

12.03 -> It is my great pleasure

13.35 -> to introduce Dr. Jonathan Davis today

15.84 -> to talk to us about management of one of the most

18.6 -> important reasons for hospitalization,

20.73 -> one of the most common causes,

21.9 -> and that is heart failure.

23.58 -> The field of cardiology is really well known

25.53 -> for cleverly named trials

26.85 -> that they rapidly synthesize into evidence,

29.37 -> and Dr. Davis today is going to highlight

31.32 -> the latest evidence in GDMT,

33.6 -> Guideline Directed Medical Therapy,

35.25 -> and how we can apply the latest data to our patients.

38.64 -> This is gonna be a really high-yield,

40.38 -> practical and exciting talk.

42.36 -> A little bit more about Dr. Davis.

43.8 -> He's an Associate Professor

45.12 -> and Director of the Heart Failure Program

47.1 -> in the Division of Cardiology

48.45 -> at Zuckerberg San Francisco General.

50.34 -> He's a well-established clinician educator

52.56 -> who's an award-winning consultant and teacher.

55.35 -> He won the 2020 Dr. Chip Chambers

57.72 -> Medicine Subspecialist of the Year Award recently,

60.63 -> and he's a San Francisco native.

62.46 -> He was born and raised in San Francisco,

64.44 -> came to medical school and medicine residency at UCSF,

68.67 -> as well as a CHF hospitalist year here.

71.19 -> Then he went to fellowship in cardiology,

73.29 -> as well as advanced heart failure

75.15 -> and transplant cardiology

76.68 -> at Washington University in St. Louis,

78.96 -> took a brief detour as the Medical Director

81.48 -> for Mechanical Circulatory Support at OHSU,

85.53 -> and we were very lucky

86.64 -> to recruit him back to CSFG in 2018.

90.21 -> As a cardiologist, he is an esteemed clinician, educator,

93.54 -> and his research really focuses on

95.13 -> innovative care systems that reduce admissions for CHF.

98.82 -> It is my pleasure to welcome Dr. Jonathan Davis.

101.16 -> Thank you for speaking to us.

104.31 -> - Hi, an incredible introduction.

105.48 -> Thank you, thank you, thank you.

106.71 -> Thank you so very much

108.66 -> for the kind words of introduction,

109.92 -> and obviously for the invitation

112.05 -> to come speak today.

112.89 -> This is a real pleasure and privilege

114.33 -> to talk with y'all about something

116.4 -> that's obviously deeply important to me

118.89 -> and touches all of us.

120.12 -> And I think the goal of today

121.56 -> is to not just touch about, you know,

123.84 -> heart failure and its management,

125.13 -> but I really wanna try to make this applicable

127.86 -> to folks that don't see people

129.63 -> in a heart failure clinic,

131.19 -> maybe not even in cardiology clinic,

132.81 -> and kind of have some pearls and some takeaways.

136.14 -> So even if you're seeing someone

137.28 -> in a general medicine clinic

138.42 -> or in a different subspecialty clinic,

140.16 -> that some of this is hopefully relevant to you as well.

143.19 -> So with that, we will get going.

149.01 -> So we're gonna cover just a little bit

151.32 -> of the background on the epidemic of heart failure,

155.37 -> and just more and more

156.21 -> about how we're seeing an increasing volume

158.43 -> of heart failure patients.

159.39 -> And those numbers and resources needed to care for them,

162.54 -> and the cost of caring for them

163.53 -> is only going to continue to increase.

166.2 -> Probably about 60 to 70% of our talk

168.06 -> is gonna be an update on the most recent guideline statement

171.3 -> that came out just about a year ago

173.16 -> from the American College of Cardiology,

174.57 -> the American Heart Association,

175.403 -> and the Heart Failure Society of America.

178.08 -> It's a 150-page document.

179.43 -> I promise we're not going through all of it,

180.87 -> but I'm gonna pull out some of the key things

182.4 -> that I think will be really generally applicable,

184.98 -> hopefully to all of us.

186.51 -> And then I'll finish in the last 10 or 15 minutes or so

188.64 -> with some practical applications.

191.16 -> I can't help myself, but a few clinical pearls

193.62 -> and some tidbits about how we actually prescribe

196.02 -> and think about using some of the key medications.

199.38 -> What we're not gonna be talking about today

201.079 -> are some more advanced things,

202.467 -> VAD and transplant, for example,

204.12 -> but also some of the other devices,

206.82 -> invasive monitors like CardioMEMS,

209.64 -> that the medical therapy and the guidelines

212.31 -> and the data that support it are profound.

214.68 -> And as we'll talk about,

215.79 -> just being on some of these meds that we'll discuss

218.25 -> can have a profound, profound impact

220.2 -> on how our patients do, how they feel,

221.97 -> and how long they live.

223.2 -> And that's really gonna be the bulk of today's talk.

226.02 -> So with that, we'll just jump right in.

228.03 -> And heart failure is a public health emergency.

230.64 -> 64 million people worldwide are living with heart failure,

233.58 -> and an estimated six million Americans

235.44 -> over the age of 20 currently have heart failure,

238.02 -> with about a million new cases of heart failure annually.

241.56 -> And heart failure really is the endstage

244.29 -> of many medical conditions.

246.24 -> Endstage hypertension, endstage diabetes,

248.538 -> endstage valvular heart disease,

249.81 -> endstage coronary disease

251.43 -> all of these things can lead

252.69 -> to a diagnosis of heart failure,

254.1 -> obstructive sleep apnea, obesity,

256.14 -> thinking about heart failure

256.973 -> with preserved ejection fraction,

258.84 -> that really, as we'll talk about,

260.52 -> aggressive comorbidity management is crucial

264.03 -> as we think about the large volume of patients

266.01 -> dealing with heart failure disease.

268.38 -> 46% predicted increase in Americans from 2020 to 2030

273.54 -> as the population gets older

274.92 -> and these comorbidities have more time to mature.

277.41 -> And the prognosis, and I really wanna spend

279.66 -> a couple of slides putting this into context,

281.7 -> the prognosis and the comorbidity associated

284.4 -> with having the diagnosis of heart failure,

286.383 -> that if you get diagnosed with heart failure,

288.27 -> there's a 50% chance

289.53 -> that you will not be alive in five years.

292.02 -> Just think about that

292.853 -> how many diagnoses do we give folks where,

294.66 -> in five years from now,

295.53 -> there's a 50/50 chance that you will have died?

297.9 -> And some of the therapies we have available

299.82 -> can dramatically alter that natural history of the disease

303.39 -> which otherwise is universally fatal.

305.82 -> And the cost, this talk is not really focused on cost,

309.48 -> but just to point out,

310.68 -> it takes a lot of resources and costs a lot of money

313.14 -> to care for this patient population.

315.24 -> And those costs are only expected to increase

316.98 -> by 60%, over $20 billion, from 2020 to 2030.

322.05 -> So anything that we can do to get people on medical therapy

324.897 -> and keep them out of the emergency room,

326.22 -> out of the hospital and doing well and living longer,

328.92 -> and having better quality of life is absolutely critical.

332.76 -> And heart failure is a progressive disease.

335.7 -> And what I'm showing in this slide in the orange

338.94 -> is kind of the overall general clinical trajectory,

342.03 -> from doing well, compensated at the top,

344.64 -> and as you move down lower and lower,

347.73 -> getting worse and worse.

348.9 -> And the normal progression is you have an event,

351 -> you go into the hospital, for example,

352.77 -> your volume overload not doing well.

354.27 -> And we can diurese you, we adjust your medications,

356.79 -> but more often than not,

357.623 -> you're not quite as good as you were

359.85 -> when you were admitted to the hospital.

361.56 -> And then, over the course of time,

363.27 -> things get worse and worse.

364.32 -> The admissions start stacking up,

365.76 -> they get more frequent,

366.9 -> and they get more significant as people pass away.

370.2 -> And without medical therapy,

371.423 -> this is a universally progressive and fatal disease.

374.88 -> And the treatments we're gonna discuss in detail today

377.43 -> can really dramatically alter this,

380.28 -> if not, stop it, certainly slow it down

382.53 -> depending on when you're meeting the patient,

384.03 -> where along this path.

387.24 -> And to point out that once you have

389.58 -> the diagnosis of heart failure,

391.26 -> your prognosis is equally as poor.

394.02 -> There are many studies and many cohorts

395.88 -> that have shown this over the recent years.

398.964 -> I choose this one 'cause I just like

400.68 -> the visual representation of it.

402.84 -> The life expectant in the US overall,

405.15 -> starting on the left

405.99 -> in your average 65 to 69 year old,

407.97 -> and then moving into older, older age,

409.89 -> that your average life expectancy

411.27 -> is just under 20 years, 15 years,

413.13 -> 10-ish years as you get older.

415.98 -> But then looking down at the heart failure population,

418.47 -> light blue for heart failure

419.43 -> with reduced ejection fraction,

422.166 -> and the BEF is borderline

424.65 -> but mildly reduced ejection fraction in orange,

427.44 -> and gray is heart failure

428.37 -> with preserved ejection fraction,

429.99 -> and you can see the average expected survival is the same.

433.77 -> If you're 65 to 69, your prognosis,

436.8 -> your estimated time of survival

438.78 -> is about 3 1/2 years regardless of your EF type.

441.96 -> And that is true for the 70 to 74 year olds and older

445.53 -> that, once you have heart failure,

448.05 -> your prognosis is not good.

450.48 -> So it's very easy to think

451.71 -> that your ejection fraction is 20%,

453.57 -> you're in deep trouble,

454.44 -> but your EF is 65%, you know, in the normal range,

457.5 -> oh, you're in the clear.

458.52 -> That's actually not true.

459.63 -> Once you have heart failure, you're sick,

462.3 -> and your risk of something bad is very, very high.

466.2 -> And to further put this into context,

468.39 -> I have on the left the ASCVD risk,

471.81 -> which we calculate in primary care clinic all the time

474.03 -> thinking about the risk over the next number of years

477.45 -> of having a myocardial infarction or ischemic stroke.

480.36 -> And if someone is at a very high risk

482.25 -> of having this happen at 7%, oh my goodness,

484.47 -> we need to get them on a statin immediately,

486.63 -> they're such high risk.

488.28 -> And now you compare that to a heart failure patient

490.437 -> and that seven-ish and some-odd percent

492.72 -> doesn't even apply to your most stable

494.76 -> heart failure patient.

495.66 -> So on the left you'll see, you know,

499.23 -> your stable, "outpatient patient"

501.87 -> outpatient individual with heart failure

504.21 -> with reduced ejection fraction,

505.69 -> NYHA class II symptoms,

507.21 -> no recent hospitalizations.

509.22 -> That lowest "risk group" of heart failure patient

512.22 -> is still significantly higher risk

514.02 -> of coming to the hospital or dying in the next year

516.6 -> than your highest source ASCVD risk.

519.03 -> And we think about ASCVD all the time,

521.25 -> we think about cancer diagnoses all the time.

524.04 -> And you get the diagnosis of cancer

526.12 -> and you're like, oh my goodness,

526.953 -> I have cancer, you gotta to do this, this, this,

528.33 -> and that immediately because I have cancer.

530.73 -> There's not really that same visceral response

533.13 -> with most people when they find out

534.33 -> they have a diagnosis of heart failure,

536.13 -> but the risk is exceedingly, exceedingly high.

540 -> So I wanna move on in terms of

541.8 -> what we're gonna do about it.

543.15 -> It's a bad disease, there's a lot of it,

546.09 -> but what are we gonna do to treat these folks?

548.88 -> And there are many, many themes.

550.08 -> Again, this is a long guideline statement

552.39 -> that was put out last year,

553.98 -> but I wanna walk you through a couple of bigger items.

557.46 -> One is we'll touch on the revamped classification.

559.92 -> It is a little bit of alphabet soup,

561.24 -> so I want to kind of put a little bit of context to it

564.15 -> and make it a little bit better understood.

566.73 -> SGLT2 inhibitors, sodium-glucose cotransporter 2 inhibitors,

570.03 -> most commonly empagliflozin and dapagliflozin,

571.92 -> are here not only here to stay,

574.23 -> it seems like every clinical trial

575.55 -> that we find out something new

576.63 -> that it cures or treats, kidney disease,

579.6 -> diabetes, atrial fibrillation, MI, et cetera,

583.68 -> but really, across the ejection fraction spectrum now,

586.56 -> SGLT2 now have the best data regardless of EF,

590.43 -> and we'll talk about that.

592.17 -> I am gonna touch on, because this was a key inclusion,

595.68 -> was impact on disparities in vulnerable populations.

598.05 -> I'm gonna talk on that for just a few minutes

600.27 -> kind of about 2/3 of the way through the talk

602.64 -> because this was the first time that this area,

606.51 -> talking about social determinants of health,

607.83 -> talking about different populations,

609.6 -> different at-risk populations,

611.34 -> really made it in the guideline statement

612.75 -> and is being more of a focus now

613.923 -> with clinical trial enrollment

616.2 -> and how we think about patients with heart failure.

618.63 -> I'm going to very, very, very briefly

620.43 -> just touch on cardiac amyloidosis, just for one slide.

623.34 -> It is a change from the old guideline

625.14 -> in terms of how it was incorporated.

627 -> I'm just going to mention it

628.35 -> just so you know it's there,

629.37 -> but we're not gonna spend a great deal of time

630.87 -> talking about that.

632.67 -> But definitions, heart failure.

635.247 -> And we all think it's coming,

636.54 -> you know it when you see it, but as I mentioned,

638.85 -> once you have the syndrome of heart failure,

640.71 -> prognosis is equally as poor, and you don't need

643.14 -> an ejection fraction diagnosed heart failure.

645 -> It is a syndrome.

646.53 -> Symptoms are signs of heart failure

648.09 -> caused by structural functional abnormality in the heart

651.33 -> that are corroborated by a BNP

653.34 -> and objective evidence of congestion.

654.81 -> But you have to have dyspnea,

656.04 -> you have to have fluid retention,

657.72 -> and you have to have something wrong with your heart.

660.54 -> It is not an isolated BNP.

662.25 -> This comes up quite a bit.

663.63 -> Oh, their BNP is high.

664.68 -> Do they have heart failure?

665.513 -> Well, what is the syndrome that they're presenting with?

667.89 -> Or they have diastolic dysfunction on the echo.

669.99 -> Well, what is the syndrome they're presenting with?

672 -> Having a high BNP by itself

673.98 -> or diastolic dysfunction by itself on an echo read

676.95 -> do not give you the diagnosis of heart failure.

678.57 -> It is a clinical syndrome.

681.78 -> But there is kind of an alphabet soup, I admit,

683.85 -> of the nomenclature for heart failure.

687.75 -> And before we jump into the HFrEFs

689.452 -> and HFmrEFs and everything else,

691.47 -> that we've moved away from systolic

693.51 -> and diastolic heart failure.

694.74 -> Those were the terminologies for a long, long time.

697.14 -> And actually, billing,

699.057 -> if you happen to be doing billing

700.89 -> in your role as an attending or wherever you may be,

703.89 -> that, oftentimes, the billers still wanna

706.02 -> see the word systolic and diastolic

708.3 -> in your diagnosis for billing purposes.

710.91 -> But from a heart failure perspective,

713.34 -> we're not using those terms

714.51 -> because everyone with systolic dysfunction

716.43 -> necessarily has diastolic dysfunction,

718.62 -> and the opposite is also true.

720.81 -> But we talk about this in terms

721.98 -> of reduced ejection fraction, below 40%,

725.16 -> mildly reduced, 41 to 49%,

727.38 -> and preserved ejection fraction, greater than 50%.

730.47 -> As we'll talk about this mildly reduced

733.32 -> kind of gray area in between 41 to 49%

736.86 -> has been ignored for a long, long time.

738.54 -> Most clinical trials in the '80s, '90s, 2000s,

741.81 -> really focus on an EF less than 35 or 40%

745.11 -> or higher than 45 or 50% for the HFpEF.

747.537 -> And this middle range is only much more recently

749.82 -> in the last couple years,

751.8 -> first with a angiotensin receptor-neprilysin inhibitor,

754.924 -> ARNI, sacubitril/valsartan,

756.72 -> and then more recently with the SGLT2 inhibitors,

759.12 -> to really prioritize and incorporating

762.78 -> these folks into clinical trials.

765.12 -> But as we'll also see,

766.2 -> that the treatment really is almost a dichotomy.

769.02 -> If you have an ejection fraction

770.22 -> less than 50% or greater than 50%,

773.82 -> we're treating folks kind of really,

775.26 -> everyone, if it's below normal,

776.97 -> are gonna get the same meds.

777.9 -> And we'll go through the details for that.

779.94 -> But a key point I really wanna drive home on this slide

782.55 -> is the last line here,

783.84 -> is the heart failure with improved ejection fraction.

787.38 -> Previously, this was referred to as heart failure

789.51 -> with recovered ejection fraction.

792.03 -> And you'll say, "Well, recovered, improves,

793.777 -> "you know, tomato, tomato".

794.91 -> But actually, it makes a big difference

796.65 -> because we are not curing heart failure.

799.35 -> This is a chronic, incurable, lifelong disease.

802.02 -> We're trying to suppress it with medical therapy,

804.15 -> we're trying to put it into remission,

805.98 -> but we're not curing it.

807.45 -> And by saying heart failure

808.32 -> with recovered ejection fraction,

809.76 -> that leaves the room for a potential implication

811.47 -> like, "Oh, you've got a recovered EF.

812.857 -> "We can stop your medications".

814.227 -> And as we'll talk about, that's just not the case.

816.12 -> So by calling it improved ejection fraction,

818.37 -> it's going from below 40%,

820.033 -> a 10-point increase to above 40%.

822.54 -> Numbers aren't so important for this general audience,

824.79 -> but the point is that if the EF has come back up,

827.37 -> maybe back to normal,

828.78 -> we call it improved ejection fraction.

830.43 -> 'Cause as we'll talk,

831.27 -> we're gonna wanna stay on medical therapy.

833.28 -> We've not cured anything,

835.14 -> we've put it into remission.

837.18 -> And along those lines,

838.89 -> I just wanna highlight that there are four stages.

841.23 -> You probably are familiar with this.

842.88 -> Stage A, no one is gonna talk about stage A disease

845.55 -> because that's every single patient

846.75 -> you're ever gonna see with hypertension or diabetes.

849.42 -> Stage B, you have some kind of structural abnormality,

852.48 -> but you've never had symptoms.

854.28 -> 95% of the folks that we're gonna see in clinic

856.65 -> or in the hospital are stage C,

858.09 -> that they have heart failure,

858.923 -> they have the syndrome of heart failure,

860.49 -> they've had symptoms, and they may be at some stage

864.12 -> in terms of how well they're feeling,

865.29 -> how their ejection fracture is doing, for example.

867.57 -> But this is really 95% of folks.

869.58 -> And then there's the advanced heart failure folks

871.29 -> that are needing advanced therapies

873.9 -> with heart transplantation,

875.1 -> ventricular assists device,

876.33 -> they need to go see Dr. Klein and the team.

879.27 -> But the focus really is on this stage C,

881.94 -> and because stage C is 95%, 99%

884.76 -> of what we're gonna be seeing,

886.802 -> the guideline committee wanted

888.72 -> to flush this out just a little bit.

890.61 -> And so we're talking about these things

892.11 -> in terms of new onset or de novo heart failure

894.81 -> resolution of symptoms.

897.33 -> Again, it's not curing it,

898.953 -> that you have, maybe your EF is still low

900.99 -> but you're feeling great,

901.92 -> or your EF is improved up to normal

904.53 -> and you've put this into remission.

906.84 -> But this is where thinking about that

908.46 -> versus persistent heart failure,

909.9 -> that all these folks are technically stage C,

912.15 -> but just to apply a little bit more granularity

914.07 -> in terms of how we think about these folks.

916.5 -> And then obviously still stage C,

918.81 -> but it's getting worse,

919.68 -> they're kind of heading towards stage D,

920.85 -> they're heading towards end stage, they're on the verge,

923.46 -> but still technically stage C.

925.724 -> But this doesn't cover quite a lot of our patients.

928.98 -> But let's just jump into actually the medical management

931.89 -> and the guidelines behind these things.

933.42 -> So starting off, we're gonna talk about heart failure

935.67 -> with reduced ejection fraction.

937.05 -> We're gonna talk about

937.883 -> this mildly reduced ejection fraction,

939.18 -> preserved ejection fraction,

940.013 -> and preserved ejection fraction.

941.52 -> So the EF less than 40% first.

944.61 -> This is a lot, I'm gonna take you through this.

946.32 -> This is the main table, class I GDMT,

948.96 -> guideline-directed medical therapy.

950.73 -> You're gonna see that term a lot, GDMT,

952.65 -> guideline-directed medical therapy,

954.84 -> and it is quad therapy.

956.25 -> To summarize this chart, though,

957.81 -> the first three lines about our ACE/ARB or ARNI,

960.81 -> it is ARNI, ARNI is first line,

964.38 -> starting with the PARADISE-MI trial, excuse me,

967.41 -> PARADIGM and HFrEF trial, excuse me, in 2014.

971.07 -> And with many subsequent trials since then,

973.56 -> not only has ARNI,

974.427 -> the angiotensin receptor neprilysin inhibitor

977.005 -> sacubitril/valsartan X been shown

979.2 -> to be better than ACE or ARB,

980.55 -> it's shown that we don't need to start

982.14 -> with ACE or ARB first

983.25 -> and we should not be starting with ACE or ARB first.

986.34 -> And in fact, if someone is on an ACE or an ARB,

989.167 -> "doing well," they've been on their ACE inhibitor

991.08 -> for five years and they feel great,

993.15 -> those folks will still do better

994.65 -> if you switch them over to ARNI.

995.847 -> And it is worth changing things up

997.98 -> and you should change things up

999.45 -> 'cause folks actually do better

1001.58 -> the sooner you get them on to ARNI

1003.59 -> versus an ACE or an ARB.

1005.21 -> And this is a direct quote from the guidelines statement,

1007.857 -> "ACE/ARBs should only be considered

1009.59 -> in patients with contraindications, intolerance,

1012.05 -> and inaccessibility to ARNI."

1014.06 -> So if it's an insurance issue, if it's a BID medication,

1017.81 -> 'cause unfortunately ARNI is only available twice daily,

1020.9 -> but unless there's a reason why they can't get it,

1023.81 -> this is the default,

1025.4 -> that when you have someone with heart failure

1027.053 -> with reduced ejection fraction,

1029.33 -> There's no role for ACE or ARB

1030.8 -> unless they cannot get or cannot take the ARNI instead.

1035.21 -> And then the other three key medication,

1036.786 -> again, that is quad therapy,

1037.79 -> our beta blockers, our MRA, and our SGLT2.

1040.885 -> So our metoprolol and carvedilol are spironolactone

1043.965 -> and alprazolam

1044.927 -> And our SGLT2 empagliflozin and dapagliflozin.

1048.89 -> We'll go through some nuts and bolts of these things.

1050.6 -> But taken together the quad therapy is class I,

1054.71 -> saying, well gosh, four medications, that's a lot.

1057.47 -> Like do we really need all four?

1059.39 -> The answer is yes, we really need all four

1061.79 -> because it really, really works.

1063.89 -> And to get back when we're talking about risk

1065.99 -> and thinking about disease and treatments for it.

1070.37 -> I'd love to say,

1071.3 -> I don't love to say, but I say, you know,

1073.28 -> in conversation has come up, for example,

1075.17 -> if someone has cancer in the art shop, you don't do R,

1078.05 -> you don't do hop, you do R chop because that's what works,

1080.9 -> and these four medications work.

1082.317 -> I'm gonna show you some slides to hopefully convince you

1084.95 -> that the package deal can actually make people do better.

1088.76 -> So even compared to an active,

1091.07 -> compared to not compared to placebo,

1093.17 -> the background therapy of ACE or ARB and beta blocker.

1095.48 -> 'Cause unfortunately turns out in the United States

1096.86 -> that the MRA prescription rates are very, very, very low.

1100.88 -> Most people in the United States

1102.02 -> are getting historically ACE or ARB and a beta blocker.

1104.72 -> But if you do the quad therapy, ARNI, beta blocker,

1107.483 -> MRA, SGLT2 in comparison to ACE or ARB,

1112.13 -> you'll get a 62% reduction in cardiovascular death

1114.71 -> or hospitalization risk.

1115.88 -> You see a 50% reduction in cardiovascular death

1118.67 -> and a near 50% reduction in all cause mortality.

1122.54 -> Those are huge numbers,

1123.44 -> but to say visually a very visual person.

1125.39 -> And I think this figure is incredibly striking

1128.27 -> that if you put someone with heart failure

1131.15 -> with reduced ejection fraction on quadruple therapy

1134.42 -> with a contemporary four drug regimen

1136.85 -> in your average 55 year old versus just

1139.46 -> an ACE/ARB and a beta blocker,

1142.16 -> you want average can increase their life expectancy

1144.41 -> by almost six and a half years, six and a half years,

1148.067 -> 6.3 years of actual life.

1150.17 -> And if you look when these curves separate,

1152.72 -> that is really quickly.

1154.25 -> Again, this is not compared to placebo.

1155.78 -> This is an active compared to ACE/ARBs and beta blockers.

1157.91 -> They've been around for a long time

1160.1 -> that patients can do significantly, significantly better.

1163.19 -> And how, okay, well I met the person a little bit later.

1164.84 -> How about a 65 year old,

1166.517 -> and they competing risks of passing away as you get older.

1169.82 -> Almost four and a half years of extra life

1171.83 -> by starting your average 65 year old

1173.9 -> on quadruple therapy with this four drug regimen.

1176.72 -> These drugs really work.

1179.69 -> The next question comes up,

1181.04 -> I'm sorry, one last slide is,

1182.87 -> well how long you know, does it take a long time?

1185.39 -> No, it doesn't take a long time to start seeing benefits.

1188.39 -> That clinical benefits are apparent

1190.13 -> with these medications within a month, a month.

1193.37 -> So for example, if you're seeing someone in a hospital,

1195.59 -> and the average hospitalization

1197.18 -> for a heart failure patient is five to seven

1198.95 -> some odd days of diuresis and what have you,

1201.5 -> you're a quarter of the way there

1203.93 -> just by starting this medication in the hospital.

1206.42 -> And also to put this into context,

1208.61 -> if we think about a defibrillator,

1210.05 -> which is part of the mainstay of medical therapy

1211.97 -> for heart failure for many, many years now,

1214.55 -> you have to have a one year prognosis

1216.503 -> that if we don't think you're gonna live at least one year,

1219.53 -> we're not gonna put a defibrillator in you

1221.03 -> because you have to have a year for the curve to separate

1223.85 -> not so for 30 days beta blockers, 25 relative risk,

1227.66 -> percent relative risk reduction in dying,

1230.18 -> ARNI 42% relative risk reduction

1232.94 -> in cardiovascular hospitalization.

1234.5 -> Almost 40% is true for MRA and for SGLT2 death,

1239.24 -> heart failure, hospitalization or worsening heart failure,

1242.21 -> almost a 60% relative reduction

1244.46 -> in just 30 days after drug initiation.

1249.08 -> Nothing comes for free.

1250.37 -> AE adverse events,

1252.41 -> medical attributable adverse events

1254.18 -> and heart failure clinical trials.

1255.77 -> And I think this,

1257.24 -> I'm gonna walk you through this slide,

1258.71 -> this was actually just published a couple days ago

1260.78 -> looking at major heart failure clinical trials

1263.03 -> over the last 20 plus years,

1264.44 -> that's ACE/ARBs, neuralactin and neprilysin inhibitors,

1269.27 -> SGLT2 inhibitors and kind of looking at well

1272.816 -> what are the adverse event rates in the treatment group

1276.23 -> and what are the adverse event rates in the placebo group?

1278.84 -> And it turns out just we're gonna start on the upper left

1280.97 -> here and kind of work our way down the left column

1283.22 -> and down the right column.

1284.87 -> That adverse events are really common in patients

1287.18 -> with HFrEF regardless of whether or not

1288.976 -> you're getting a placebo or the intervention.

1291.35 -> In fact, a roughly 80% of all patients

1294.26 -> in GDMT guideline-directed medical therapy

1296.77 -> in GDMT trials had adverse events,

1299.3 -> 80% in the whole clinical trial.

1300.98 -> And that's a a lot of adverse events

1302.51 -> just by virtue of having heart failure.

1304.97 -> And the rates of adverse events are not that much higher

1309.05 -> with intervention versus placebo.

1311.12 -> For example, no significant difference

1312.8 -> for SGLT2 inhibitors, MRA or ARNI versus placebo

1316.19 -> and a little bit higher for ACE inhibitors.

1318.41 -> Patients randomized to intervention versus placebo

1320.39 -> have lower rates of severe adverse events.

1323.15 -> Think about that,

1323.983 -> putting you on treatment, less severe adverse events,

1325.88 -> which is good because we're treating your disease.

1328.52 -> Now moving to the right column.

1330.05 -> Some specifics for different medication classes,

1332.21 -> ACE inhibitors, no difference

1333.98 -> in the rates of drug discontinuation.

1335.93 -> A little bit higher dizziness.

1336.98 -> And obviously there's the cough that comes up

1339.38 -> not infrequently with ACE inhibitors

1341.06 -> that can be alleviated with switching

1343.55 -> to an angiotensin receptor blocker ARB or an ARNI,

1350.45 -> the angiotensin receptor neprilysin inhibitor.

1353.36 -> Beta blockers 1.1% less likely to stop the drug.

1356.36 -> No difference in most adverse events,

1358.28 -> but a little bit more dizziness.

1359.96 -> MRA the mineral corticoid receptor antagonist,

1362.66 -> no difference in drug discontinuation.

1364.4 -> There is a risk of gynecomastia

1367.01 -> that is alleviated by switching to eplerenone.

1369.68 -> I'll talk about that a little bit more

1370.85 -> when we talk about MRA specifically

1372.41 -> in terms of the nuts and bolts.

1374.36 -> And finally, SGLT2,

1375.5 -> no difference in drug discontinuation.

1377.33 -> In fact, if you look at

1378.2 -> some of the original diabetic safety trials,

1380.36 -> the rates of discontinuation were actually higher

1381.95 -> in the placebo group.

1383.27 -> Taken overall no difference in drug discontinuation,

1386.39 -> no difference in volume depletion or hypoglycemia.

1390.25 -> There is an increased rate in the genital infections

1392.51 -> and we'll come back to that.

1395.69 -> Mildly reduced ejection fraction.

1398.3 -> Again, not as much data here

1399.86 -> which is why we have lower levels of recommendation

1402.95 -> at 2a and at 2b for the major classes.

1406.13 -> But the big one is SGLT2,

1409.49 -> this again from its clinical trials

1411.506 -> for empagliflozin and dapagliflozin.

1413.883 -> You really span the full spectrum of ejection fraction

1416.51 -> more than any other really clinical trials

1418.19 -> have previous to this.

1419.81 -> And it was on the back of a trial

1421.43 -> that I'll show you shortly

1422.48 -> the emperor preserved clinical trial

1425.42 -> for empagliflozin and dapagliflozin

1428.69 -> has had a parallel trial but mildly reduced SGLT2

1433.94 -> decreasing hospital hospitalizations

1435.26 -> and cardiovascular mortality.

1436.52 -> And then at 2b, for ARNI, ACE/ARB and MRAs.

1440.33 -> And the reason that this is really lower

1442.667 -> and the highlight here is particularly among the patients

1444.323 -> with the lower EF is a lack of data.

1447.65 -> ARNI does have a clinical trial called paragon.

1449.93 -> We're not gonna go into that.

1451.13 -> That did show that the lower the eject,

1453.71 -> that was a HFpEF clinical trial.

1455.21 -> But the lower EF patients did much better

1457.1 -> than higher EF patients.

1459.35 -> And MRA, the famous top CATT trial,

1460.94 -> which we're not gonna get into had a lot of issues.

1464.27 -> So has an asterisk,

1465.68 -> but taken as a whole that the recommendations

1469.46 -> and the way we're really thinking about

1471.14 -> treating these folks is we're lumping everyone together.

1473.42 -> If your EF is below 50%, SGLT2, ARNI, beta blocker and MRA

1480.53 -> taken as a whole and we're doing that all together.

1483.92 -> So in terms of the thinking about other HFrEF,

1485.69 -> which kind of the three buckets,

1487.25 -> it's really two buckets below normal and above normal.

1491.81 -> The FDA made this a little bit easier for us to get ARNI

1495.08 -> just about two years ago, February of 2021,

1498.23 -> that the EF range was raised

1499.91 -> from less than 40% up to below normal.

1502.07 -> And I spoke with the Novartis folks

1503.45 -> as to why they did this to try to make it easier,

1507.65 -> easier "for providers to get".

1510.98 -> But I have had zero patients who have an EF below 50%

1514.88 -> that have not been able to get this medication

1516.74 -> for with a prior authorization

1518.06 -> or just prescribing an outright.

1520.16 -> But it is approved up to a

1521.577 -> "below normal ejection fraction".

1524.9 -> Moving in the HFpEF, this is still tough,

1527.24 -> this is still tough.

1528.08 -> So the class I recommended medication

1530.12 -> besides a loop diuretic the treatment of HFpEF,

1533.72 -> there're still unfortunately none.

1535.61 -> It is all about treating the comorbidities.

1538.28 -> If you're obese, helping them lose weight,

1539.9 -> if they have atrial fibrillation,

1541.13 -> get them in sinus for them.

1542.12 -> If they have sleep apnea,

1543.86 -> get them a sleep study, get them a CPAP mask,

1546.29 -> get them treated.

1547.123 -> But being as aggressive as they possibly can

1549.14 -> to treat the comorbidities

1550.73 -> is really the mainstay of the treatment of heart failure

1552.65 -> with preserved ejection fraction.

1554.72 -> The biggest news though in the guidelines

1556.73 -> that came out last year, excuse me,

1559.07 -> is the SGLT2 inhibitor which got a two-way recommendation.

1562.67 -> And that was based on this trial called Emperor-Preserved.

1567.62 -> The HFpEF trial is emperor reduces with emperor preserved

1570.53 -> that came out in October of 2021.

1573.92 -> The primary outcome was a composite cardiovascular death

1576.23 -> or hospitalization for heart failure.

1578.54 -> And in metas primary outcome it has a ratio 0.79.

1582.05 -> And you see the curves separate

1584.03 -> almost immediately after starting the medication.

1586.97 -> Now it was a composite endpoint of

1588.89 -> cardiovascular death and hospitalization

1590.63 -> for heart failure that was driven primarily

1592.73 -> by a reduction in risk of hospitalization.

1595.79 -> So we actually still don't have a medication

1597.68 -> that can really drive a reduction in mortality

1599.69 -> with heart failure with projection fraction.

1603.017 -> And we have so many clinical trials

1604.427 -> and so much data in heart failure reduced DF space

1606.89 -> that when this our first real positive clinical trial,

1610.64 -> ARNI got close with Paragon but didn't quite make it.

1613.55 -> Beta blockers ACE are PD5 inhibitors,

1618.26 -> nitrates all have been studied to HFpEF

1620.24 -> and this has been the most successful clinical trial.

1623.12 -> And as we'll talk about the effects are consistent

1625.16 -> in patients with or without diabetes.

1627.23 -> SGLT2 inhibitors are not diabetes medications anymore.

1630.83 -> Yes, they're developed as diabetes medications,

1633.29 -> but these are really cardiovascular medications.

1635.15 -> They are renal medications

1636.833 -> that also have some diabetic effects,

1639.44 -> but we should not be thinking about these

1640.79 -> as diabetes medications,

1642.2 -> have to be thinking about this family medicine

1644.06 -> as a heart medicine or also as a kidney medication as well.

1651.35 -> Also making this a little bit easier for us to get through

1654.02 -> prior authorizations and through insurance as last year,

1656.99 -> the FDA approved just over a year ago,

1660.02 -> empagliflozin for heart failure with any ejection fraction.

1663.5 -> So there should be no barriers, it's in the guideline,

1665.93 -> it's FDA approved.

1667.13 -> It's not off-label to use SGLT2 inhibitor

1669.32 -> across the EF spectrum.

1672.2 -> And just a summary of these recommendations,

1674.15 -> A two-way recommendation for SGLT2 inhibitor 2b for

1678.86 -> mineral corticoid receptor antagonist,

1680.57 -> especially on patients with lower ejection fraction.

1683.48 -> And same thing for ARNI

1684.47 -> particularly among patients on EF

1685.76 -> of the lower end of the spectrum.

1687.71 -> So as you get up into normal range EF

1689.87 -> and start into high normal and above normal EFs,

1692.99 -> the data are less strong

1694.07 -> to support the use of these medications.

1696.02 -> And plus with the ARNI

1697.13 -> if you get above normal injection fraction,

1699.02 -> the FDA has not approved it for that,

1700.37 -> so it's certainly gonna be more difficult to get.

1702.14 -> But this is the mainstay of medical treatment

1704.96 -> for heart failure with preserved ejection fraction.

1706.79 -> So my clinical practice

1708.65 -> is I get everyone on an SGLT2 inhibitor.

1710.81 -> I do my best to get everyone on an MRA,

1712.61 -> usually it's Spironolactone.

1714.59 -> And then if I can an angiotensin receptor blocker an ARB

1717.8 -> such as losartan.

1719.752 -> I have not had success getting ARNI for patients

1721.91 -> above a 50% ejection fraction based on an FDA decision.

1727.91 -> And finally improved ejection fraction.

1730.01 -> So improved EF again,

1731.42 -> those folks who start off with a low EF

1732.89 -> and now it's improved up into mild reduced

1735.95 -> if not normal range,

1738.56 -> don't stop the medications.

1741.59 -> And I have to say this again,

1743 -> don't stop the medications.

1745.61 -> We are not putting,

1746.81 -> we are not curing this disease,

1748.64 -> this is a chronic, we're trying to suppress it,

1750.98 -> we're trying to put it into remission.

1752.57 -> We are not curing the heart failure.

1755.36 -> So that ejection fraction, 65%,

1758.03 -> the person feels like a million bucks.

1759.8 -> They're doing awesome. Great.

1761.69 -> Stay on the medicines as a level one recommendation.

1766.58 -> We'll talk about some of the evidence on the next slide.

1768.77 -> This is based on a small clinical trial,

1770.96 -> but lots of cohort data over the years

1773.87 -> and the cohort data is really several thousand people.

1776.54 -> The one of the RCTs is pretty small,

1778.91 -> but I'm gonna show you it just cause it's so striking.

1781.34 -> Even if you're asymptomatic,

1782.66 -> don't stop the medication.

1784.79 -> This was just one small trial called TRED-HF

1788.3 -> that came out four years ago.

1791.72 -> This was small again, it was only 51 people.

1793.91 -> So yes, you have a whole class level one recommendation,

1796.79 -> but there are more data to support this.

1798.98 -> But just as one example,

1800.24 -> what can happen if you have someone

1801.74 -> who's "doing great" their EFs up to normal,

1805.01 -> they're feeling awesome, they have no symptoms,

1806.87 -> no edema, they're doing great.

1809.09 -> These folks were randomized

1810.32 -> to stay on their medical therapy or to stop.

1813.83 -> And the event rate was almost 50%

1816.5 -> in the control group where you're weaning off therapy

1820.19 -> between the treatment withdrawal group.

1821.63 -> So you can see the orange lines again,

1823.4 -> the numbers are in the smaller side,

1824.69 -> but the point is extended through other trials.

1827.39 -> But you see that the people

1829.04 -> that had their treatment withdrawn,

1830.21 -> their event rate just goes straight up and up and up and up.

1833.54 -> And by six months, almost half the patients

1836.3 -> who had stop their medications

1837.86 -> had the return of their heart failure symptoms,

1840.53 -> if not a reduction in their ejection fraction.

1842.78 -> So it doesn't take that long for the wheels to fall off.

1846.02 -> So just because things are looking good,

1848.3 -> you have to keep going with the medical therapy.

1850.22 -> And that's something that we have to know

1851.69 -> as the folks providing it.

1853.04 -> But also as incredibly important as we educate patients

1855.56 -> when they first get this diagnosis that look,

1857.6 -> it's a lot of medications,

1859.13 -> but they work and they're lifelong.

1861.35 -> That whenever I see someone that

1863.27 -> the echocardiogram comes back

1864.883 -> and the EF is back up to normal,

1866.57 -> the first thing I'd say is awesome.

1868.49 -> Second thing is we're not gonna stop.

1870.59 -> And just to, you have to have that mindset

1872.6 -> from the onset with patients as you're doing education,

1875.42 -> that even if things go great,

1876.68 -> which we hope they will, and hopefully they do,

1879.29 -> but we have to stick with medical therapy.

1883.19 -> I'm gonna spend just a few minutes talking about this

1885.2 -> because it has such an important implications.

1888.08 -> A, that it was included in the guidelines and is finally,

1890.33 -> finally getting more traction amongst the major societies

1893.45 -> in clinical trial designed.

1895.88 -> Thinking about these other populations.

1898.13 -> In fact, the word disparities

1899.6 -> in the last guideline statement

1901.79 -> that was initially in 2013

1902.99 -> had some small updates in 2016, 2017.

1905.66 -> The word disparities occurred twice

1908.03 -> in that entire documents.

1910.16 -> And now it has several whole sections

1912.17 -> with value statements to help draw much needed attention

1916.37 -> to other populations.

1918.35 -> And there's definitely a need for increased awareness.

1920.3 -> We have to have to have to be aware

1922.58 -> a biological factors,

1923.81 -> social determinants of health,

1925.37 -> and implicit biases that impact the burden of disease,

1928.31 -> decision making, patient experience,

1930.35 -> patient perception of their disease,

1932.24 -> patient where they are in terms of how they can engage

1936.29 -> and effective delivery

1937.16 -> of guideline-directed medical therapy.

1939.26 -> We are very good in the hospital and clinic of prescribing,

1941.96 -> you know, in the hospital we prescribe the right medication,

1944.33 -> they're leaving the hospital and this, this and that.

1946.43 -> But what happens when they get discharged

1948.44 -> and they get in the car and go home,

1949.85 -> and they get in the ambulance and go to rehab,

1952.07 -> wherever they may go, what happens next?

1954.62 -> The clinic visit ends,

1955.73 -> you have their after visit summary they leave,

1958.16 -> do the pills, get in their hand,

1959.63 -> do the pills, get in their mouth,

1960.95 -> do the other lifestyle things that you talk about.

1963.2 -> What actually happens after they leave that clinic visit?

1966.68 -> We have to be more explicit

1968.27 -> with how we think about these things.

1970.22 -> And for the first time,

1971.12 -> the guidelines statement really dives into that as well.

1974.18 -> And for example, the highest incident of heart failure

1975.89 -> is consistently observed in self-identified black patients.

1978.782 -> What are we doing in terms of systematically,

1981.53 -> in terms of our clinic,

1982.43 -> and in terms of our resources addressing this population,

1986.3 -> others that are higher risk of having something bad happen.

1990.08 -> And there are a lot of barriers to care engagement.

1992.78 -> And we're not gonna get through all of these,

1994.28 -> but as we think about our clinic structure,

1995.96 -> we think about our discharge planning,

1997.4 -> we think about what we have in our heart failure clinic

2000.28 -> or our primary care clinic,

2001.39 -> or whatever clinic we may be serving

2002.77 -> 'cause these are not limited to cardiology issues.

2004.6 -> This is for any specialty

2006.7 -> or anything that you're doing with patient care,

2009.25 -> their medical barriers, cognitive impairment,

2011.05 -> depression, substance use,

2012.4 -> their social barriers from financial food and insecurity,

2014.98 -> housing insecurity, how well can they read the instructions,

2018.91 -> what language you're giving them,

2019.9 -> the instructions in the health literacy level

2022.63 -> in terms of how you're doing it.

2024.1 -> So all these things that we really have to think about,

2027.13 -> for example, without going too long on this path,

2030.46 -> but you know, at San Francisco General,

2031.9 -> one thing that we started was a combined for patients

2034.78 -> with stimulant use disorder and heart failure.

2036.28 -> We started a joint co-management clinic

2038.23 -> with addiction medicine and hearty cardiology

2040.78 -> to try to tackle some of these multiple barriers

2042.73 -> in the same place at the same time,

2044.17 -> which has been very effective.

2045.73 -> So thinking about a multidisciplinary approach

2048.01 -> to addressing these barriers

2050.05 -> and reducing them as much as possible.

2053.23 -> And finally, the different populations

2055.57 -> do experience heart failure differently.

2057.22 -> And again, this is true

2058.053 -> for other non cardiovascular issues as well.

2060.4 -> Women, older adults, lower socioeconomic status populations,

2063.49 -> and then this black, Hispanic, et cetera.

2065.86 -> Populations have their

2067.51 -> different risk profiles

2069.79 -> and things that have to be considered.

2072.22 -> And I urge you, you know,

2073.383 -> this is an area of interest to go take a look

2075.7 -> at the guideline statement itself.

2078.34 -> And it really goes through nicely

2079.63 -> with each of these populations

2080.95 -> that showed what data are available,

2082.96 -> how they've been studied.

2084.31 -> Unfortunately, many clinical trials for heart failure

2086.92 -> and other things as well

2087.85 -> are primarily Caucasian white men, Caucasian men.

2092.35 -> So oftentimes these populations are not as well

2095.17 -> including in clinical trials.

2096.37 -> So what data do exist as far as risk

2099.55 -> and as far as target to interventions.

2103.48 -> As I mentioned before,

2104.313 -> I just didn't wanna throw this out there,

2106.15 -> just so you've heard of this,

2107.41 -> we're not gonna spend a lot of time talking about

2109.27 -> amyloid heart disease,

2110.53 -> but it did have some new recommendations

2112.11 -> in the guideline statement that would...

2115.27 -> Amanda Iris does have a, you know,

2116.813 -> a cardiac amyloid clinic and is actively engaged

2119.65 -> in clinical trials in contemporary management.

2122.543 -> I just do wanna mention very briefly

2124.57 -> that tafamidis, which is a transthyretin

2128.401 -> tetramer stabilization therapy, stabilizer therapy,

2131.35 -> did receive a class I recommendation for TTR cardiac amyloid

2137.35 -> and then also patients with cardiac amyloid,

2139.03 -> anti atrial fibrillation,

2139.96 -> that anticoagulation is reasonable

2141.37 -> regardless of your CHAD'S score.

2144.1 -> There are some updates in terms of screening patients

2146.38 -> for cardiac amyloid,

2148.3 -> thinking about what symptoms a patient with heart failure

2151.06 -> with preserved ejection fraction,

2152.38 -> increased wall thickness may have

2154.48 -> a little bit beyond the scope of the talk today,

2157.03 -> but there were some novel recommendations

2159.22 -> in terms of diagnosing

2161.2 -> and treating these folks that did not exist

2163.57 -> in the guidelines before.

2164.55 -> So I am gonna leave it at that with cardiac amyloid.

2166.93 -> I know it is very brief,

2168.7 -> but it was a key thing that did change in the statements.

2170.86 -> I just wanted to mention that.

2173.92 -> But I am gonna spend the last 10 or 15 minutes

2177.22 -> and leave time for questions.

2179.53 -> But I wanna talk about some practical considerations

2181.78 -> for prescribing GDMT,

2183.19 -> guideline-directed medical therapy

2185.32 -> that if you do not have to be,

2187.78 -> you should not have to be a heart failure cardiologist

2190.03 -> or a heart failure practitioner

2191.62 -> in a heart failure clinic to do some of these things.

2194.107 -> And as we'll talk about all of these medications,

2196.54 -> even if you're in a primary care clinic,

2197.95 -> you are familiar with all of them.

2199.54 -> Everyone is prescribed a beta blocker.

2201.07 -> Everyone is prescribed spironolactone,

2203.2 -> that these are familiar medications.

2204.613 -> It's just because we're wearing a heart failure hat

2206.8 -> when we prescribe them, shouldn't dissuade us

2209.44 -> unless say, well gosh,

2210.273 -> I'm in a different specialty clinic,

2211.51 -> I'm not primary care,

2212.47 -> I'm not cardiology, you can still,

2214.36 -> you see someone in your clinic and there's a GI thing,

2217.21 -> infectious disease thing, and you,

2218.89 -> oh, they have heart failure

2219.723 -> and they're on any medications.

2222.16 -> Say, "Hey FYI, primary care,

2223.637 -> "hey FYI, cardiologist,

2225.557 -> "I saw this patient with heart failure, they're not on,

2227.237 -> "I don't see a lot of these meds that I've heard about,

2229.217 -> "what do you think?"

2230.41 -> Even something like that can have a profound impact

2233.56 -> on bringing that recognition that's necessary

2235.87 -> to get folks on these medications.

2237.91 -> But for anyone that isn't a primary care clinic,

2240.52 -> isn't a cardiology clinic

2241.57 -> or isn't any other clinic in the hospital,

2242.833 -> what have you, that is gonna be thinking about

2245.11 -> prescribing these medicines,

2246.31 -> this is really for you to try to demystify things

2249.4 -> and give you just some key pearls

2251.29 -> to actually help you prescribe these.

2252.94 -> 'Cause I think the guidelines are important,

2255.01 -> but we have to actually do it as we've talked about,

2258.52 -> it's a bad disease and we don't actually

2260.86 -> put people on these medications.

2262.09 -> We're not gonna see any of the benefits

2263.92 -> that I've outlined already.

2266.23 -> So we're gonna talk about beta blockers,

2267.317 -> the ARNI, SGLT2, and spironolactone

2270.55 -> the four key classes.

2272.56 -> And beta blockers, Carvedilol, metoprolol succinate,

2276.64 -> not tartate, metoprolol succinate,

2278.47 -> the once a day long-acting version

2280.36 -> and bisoprolol have the key clinical data

2282.94 -> to support their use in heart failure

2284.32 -> with reduced ejection fraction.

2286.42 -> And if someone is on a different beta blocker,

2289.15 -> they're on metoprolol tartrate,

2290.5 -> atenolol, labetalol, switch them,

2292.99 -> it doesn't matter they've been on atenolol for 10 years

2294.76 -> and are doing great, doesn't matter.

2296.83 -> Switch them over and their chances of doing better

2299.29 -> for longer or higher on one of these medications,

2303.16 -> even metoprolol tartrate,

2304.96 -> please don't use that for patients

2306.31 -> with reduced ejection fraction.

2308.38 -> There was one clinical trial versus Carvedilol called comet,

2311.53 -> which one could argue was rigged

2313.24 -> against metoprolol tartrate,

2314.707 -> but that's a separate issue.

2316.265 -> Metoprolol tartrate really is meant to be

2317.74 -> in the hospital, used four times a day.

2320.137 -> But if you have someone with heart failure

2321.88 -> with reduced ejection fraction,

2323.17 -> you can put 'em on a betta blocker.

2325.24 -> One of these three metoprolol succinate,

2327.324 -> carvedilol or bisoprolol.

2329.23 -> And the dose is really important.

2331.218 -> This are old data from 1996,

2333.76 -> but it still holds true Carvedilol still carvedilol.

2336.594 -> And the higher the dose you got,

2338.89 -> the more benefit you tended to get.

2340.837 -> And the same is true for the other beta blockers as well.

2343.48 -> So some is better than none,

2344.77 -> more is better than less.

2346.78 -> So if you're saying,

2347.613 -> "oh, I got someone in clinic or in the hospital,

2349.367 -> "I'm only gonna increase one thing today".

2351.31 -> Make it the beta blocker.

2352.78 -> That we really wanna push the dose.

2354.82 -> That being said, you do have to sit on your hands

2356.98 -> just a little bit.

2358.48 -> You know, you're blocking the beta receptor,

2362.2 -> you know the adrenaline receptor in the heart

2364.72 -> that if you go up too much too fast,

2367.45 -> you could make people feel a little,

2368.68 -> eh, a little worn out.

2370.09 -> Like they're going up and down escalator.

2372.16 -> So in the outpatient setting,

2373.78 -> or really doing this every two weeks to get people a chance

2376.12 -> to get used to the dose and then go up.

2378.79 -> But we don't need to be waiting months.

2380.2 -> We should not be waiting months.

2381.37 -> But every two weeks you can make a dose change,

2384.19 -> and starting when they're at or near U bulimia.

2386.89 -> So if someone's in clinic or comes to the hospital,

2388.99 -> super volume overloaded,

2390.94 -> not the time to start it or increase the dose,

2392.83 -> but keep it going.

2393.94 -> Remember, unless the beta blocker

2395.5 -> is the reason the person's doing poorly,

2398.17 -> whether they're in cardiogenic shock

2399.52 -> or they're really bradycardic,

2401.583 -> if they've been on the same beta blocker dose

2403.99 -> for a long, long time, it's not the beta blocker's fault

2406.42 -> they're coming in volume overloaded.

2407.74 -> Look for other reasons.

2409.3 -> So when they come to the hospital,

2410.62 -> we're not decreasing the dose empirically.

2412.6 -> We're not switching the tartrate.

2414.22 -> If they've been on Carvedilol 25 for six months,

2416.62 -> stay on the Carvedilol 25,

2418.75 -> same thing if they've been on metoprolol

2420.07 -> a hundred milligrams for the last year

2422.17 -> and they're coming in normal tensive

2423.147 -> with a normal heart rate, it's not the metoprolol fault.

2425.98 -> Stay on the same dose

2428.59 -> and hopefully like up before they go home.

2430.75 -> But really we're trying to get the heart rate down

2432.28 -> into the '50s to '60s, that is the goal.

2434.38 -> We want the resting heart rate, nice and low.

2439.93 -> ARNI's, angiotensin receptor neprilysin inhibitors,

2442.63 -> the second newest class.

2444.19 -> Sacubitril valsartan is only one option currently for this.

2447.43 -> I wanna walk you through,

2448.57 -> especially where Sacubitril fits into this,

2450.94 -> and I'm gonna walk you through this diagram.

2452.44 -> It may look dizzy and I promise you've seen it all before.

2455.68 -> I'm gonna go through it step by step.

2457.6 -> But I think one of the biggest things

2459.34 -> in knowing how to take care of a person

2461.95 -> and start a person on this medication

2463.93 -> is knowing how it actually works

2466.12 -> and what it can do in terms of predicting what may happen,

2469.36 -> but also so we can navigate

2470.5 -> any kind of potential adverse events

2473.29 -> and keep people on these medications.

2474.88 -> So briefly, cardiac injury or overload.

2478.42 -> We get sympathetic nervous system, SNS and RAAS activation,

2482.11 -> the renin-angiotensin-aldosterone system.

2484.72 -> These two things rev up.

2486.19 -> So fight or flight, the brain says,

2488.29 -> where's all my blood, there must be a problem,

2490.21 -> let's fight or flight and let's activate this system.

2494.17 -> And we are very familiar with this.

2495.58 -> We have been modifying this with our beta blockers,

2497.86 -> our ACE/ARB, our MRAs for decades now,

2501.04 -> trying to get less vasoconstriction,

2503.5 -> less sodium retention,

2504.79 -> less fibrosis by blocking this pathway.

2507.94 -> But also you can see

2508.773 -> that we're not doing anything to the myocyte.

2510.57 -> So again, thinking about, you know,

2512.56 -> what are we doing and why,

2513.61 -> if the owners heart gets better,

2514.63 -> do we not stop medications.

2516.25 -> As I explained to patients

2517.27 -> who are putting a little cocoon around the heart

2519.49 -> to prevent it from getting more injured

2522.01 -> from this extra abnormal signaling

2523.75 -> that the brain is sending out

2524.92 -> because it thinks there's a problem,

2526.84 -> that there is a problem,

2527.673 -> but it's not a volume problem, it's a pump problem.

2531.13 -> And so by blocking the beta blockers or ACE/ARB,

2534.37 -> protecting the heart from this extra abnormal signaling.

2537.64 -> But okay, so we've been using ACE, we've been using ARBs,

2540.31 -> where does Sacubitril fit into this?

2542.29 -> So LCZ 696, that's what Sacubitril Valsartan

2545.62 -> was called back in...

2547.51 -> And then paradigm in 2014

2549.46 -> before it got its official name of Sacubitril Valsartan.

2553.03 -> So LCC 696 is an ARB, but it's also sacubitril.

2556.42 -> And sacubitril is an inhibitor of an inhibitor.

2558.97 -> And we're focusing on this pathway on the right,

2561.46 -> the neuro peptide system, ANP and BNP,

2565.66 -> Atrial natriuretic peptide

2566.56 -> and Brain natriuretic peptide,

2568.36 -> and neprilysin inhibits this pathway

2571.24 -> but we want more of it.

2572.35 -> So sacubitril controls a double negative

2574.69 -> inhibits an inhibitor, so we get more of this.

2577.93 -> So more ANP BNP means

2579.731 -> a more natriuretic and more (indistinct)

2586.136 -> vasodilation and less fibrosis.

2588.22 -> But sacubitril can be a diuretic,

2590.53 -> it can make people lose salt,

2591.94 -> it can make people diurese,

2594.61 -> can also beso dilate.

2595.93 -> It's incredibly effective

2597.28 -> for lowering blood pressure.

2598.93 -> But it can also make people pee.

2601.27 -> And we have to be mindful of that

2603.25 -> when we start this medication

2604.9 -> because there are so many, so many times

2607.36 -> when someone will start on this

2608.62 -> and they get a little lightheaded,

2609.49 -> a little dizzy or little prerenal,

2611.5 -> like, oh my goodness, they're not tolerating the ARNI.

2613.573 -> It's like, no, they're just a little prerenal,

2615.7 -> so let's take away the diuretic or give 'em some fluid back.

2618.34 -> And sure enough, that can make things better.

2620.53 -> But if we don't know how sacubitril works,

2622.99 -> we can't anticipate what could be an issue

2625.27 -> and we might wind up stopping this medication,

2627.457 -> and a person who might otherwise tolerate it

2629.26 -> and drive significant benefit from it.

2631.72 -> So just on one slide,

2632.74 -> a whole bunch of pearls just to throw out there.

2635.11 -> You have to have a washout from ACE inhibitors

2637.09 -> slipping off from ARB, so 36 hours.

2639.43 -> So if you're on lisinopril,

2640.84 -> 36 hours from your last dose

2642.34 -> to your first Sacubitril Valsartan dose.

2644.71 -> Easy in the hospital, not so easy in clinic,

2647.88 -> in the hospital, obviously every medication is timestamped.

2650.92 -> But in the clinic what I'll do is I'll say,

2652.63 -> all right, today is your last lisinopril dose,

2654.52 -> you're gonna skip tomorrow

2655.42 -> and you're gonna start entresto the next day.

2657.85 -> And maybe that's closer to 48 hours.

2659.62 -> But we ensure we get that 36 hour washout.

2662.68 -> There's multiple dosing.

2663.94 -> The milligrams are a little wonky,

2665.62 -> 24, 26, 49, 51, 97, 103.

2669.16 -> They actually add up to 50, 100, 200

2672.37 -> everywhere else except the United States.

2674.05 -> But outpatient, you're going up on the dose

2676.3 -> every two to four weeks in the hospital

2678.16 -> because of how the inpatient HFrEF trial was set up

2681.07 -> for called Pioneer.

2682.33 -> If you wanna read it,

2683.26 -> you get to make one dose increase at 48 hours.

2686.02 -> But again, the key in using this medication

2688.32 -> is the natural effects of sacubitril which are variable.

2691.06 -> Some people diurese a lot,

2692.53 -> some people not at all.

2694.06 -> But if you're developed some hypotension,

2695.86 -> some orthostatic hypotension,

2697.63 -> especially a new acute kidney injury, AKI,

2700.48 -> step one, decrease the loop diuretic.

2702.7 -> Step two, stop the loop diuretic.

2704.44 -> Step three, increase fluid intake.

2706.6 -> And step four is to do number three again.

2708.453 -> This is the only time I've ever actually brought

2710.8 -> a bottle of water to a patient in heart failure clinic was

2714.13 -> because they're having such a robust

2715.63 -> natriuretic effect to sacubitril.

2717.67 -> But if they're volume down,

2720.07 -> they come in with some diarrhea or they come in because

2722.77 -> they haven't been eating for a couple days,

2724.51 -> that could exacerbate this.

2726.85 -> So please keep that in mind

2728.26 -> as you're putting people on this medication.

2730.15 -> That if they're like euvolemic hypovolemic,

2733.18 -> get rid of the diuretic.

2734.35 -> If you're in the hospital

2735.34 -> and they're getting twice daily

2736.173 -> BMAX or Lasix for the diuresis,

2738.82 -> hold that evening dose

2739.9 -> if you're starting the entresto at night,

2741.73 -> because some folks can actually diurese quite a bit

2743.83 -> just with this medication.

2746.83 -> SGLT2 inhibitors, some nuts and bolts on this.

2749.62 -> Dapagliflozin or empa, either one,

2752.29 -> they're both 10 milligrams.

2753.55 -> We can talk about if you'd like offline

2755.44 -> about some of the subtle differences

2756.64 -> between their various clinical trials.

2758.8 -> But the take home is either one,

2760.26 -> it really comes down to which one

2761.83 -> you're gonna be able to get with the patient's insurance.

2764.86 -> And you don't need to switch from one to the other,

2766.78 -> whichever one you get that's gonna be cheaper, go with it.

2770.2 -> And it does not matter if you have diabetes or not.

2772.48 -> This is just as effective in patients

2774.1 -> without diabetes as with diabetes,

2775.84 -> so it is not a prerequisite,

2777.91 -> not a prerequisite to have diabetes.

2780.246 -> This is a medication that is developed

2782.53 -> as a diabetes medicine,

2783.43 -> but turned out to have a lot of other benefits

2785.47 -> even in and especially in non-diabetic patients.

2788.65 -> But there's type two diabetes.

2790.21 -> You cannot use this in type one diabetes

2792.04 -> given the risk of diabetic ketoacidosis.

2794.613 -> Your GFR can be really low,

2797.32 -> down to 20 in the clinical trials

2799.24 -> you can still start these medications.

2801.04 -> So very low renal function

2803.56 -> is still safe to start and should be started.

2806.26 -> And the most common adverse events, if you're gonna have it,

2808.69 -> are really the volume depletion

2809.83 -> but really in the hyperglycemic patient.

2812.429 -> We didn't really talk about the mechanism of SGLT2,

2814.72 -> but a sodium-glucose receptor

2818.38 -> and the kidney that makes you pee out more sugar,

2820.75 -> the higher your blood sugar level is.

2822.88 -> So if you're very hyperglycemic,

2824.65 -> you have more glucose urea.

2826.27 -> If you're euglycemic,

2827.35 -> you really shouldn't have any glucose urea.

2829.6 -> And this is why people thought

2830.44 -> it was gonna be a great diabetes medication

2832.18 -> because you shouldn't have much hypoglycemia and you don't.

2835.18 -> But if you're a non-diabetic individual,

2838 -> your volume diuresis effectiveness

2840.07 -> are very, very, very small.

2841.75 -> And it's really the diabetic folks with higher blood sugars

2844.66 -> that are gonna be more likely to get dehydrated

2847.87 -> and a diuretic effect from this.

2850.042 -> And the key thing though is the genital mycotic infections

2853.12 -> are several percentage points higher in treatment

2855.46 -> than in placebo, especially in women in uncircumcised men.

2858.34 -> A lot of that does come down to hygiene

2860.56 -> but not bacterial infections.

2862.54 -> If you look at all of the diabetic safety trials,

2864.7 -> the cardiovascular focused trials,

2866.29 -> the heart failure trials,

2867.97 -> rates of your general bacterial UTIs are no different.

2871.99 -> It's the mycotic ones that are higher.

2874.03 -> So, someone had two e-Coli UTIs in the last year,

2877.42 -> don't do empa, that's actually not the case.

2880.24 -> And interestingly, and folks that get the mycotic infection,

2884.23 -> up to 80% of folks will never have one ever again,

2886.63 -> interestingly enough.

2888.19 -> But it is, if they do get it,

2889.718 -> fluconazol 150 milligrams by mouth times one,

2893.26 -> we'll take care of it.

2895.87 -> And again, we touched on this a little bit,

2897.85 -> but it does not take long to see benefit.

2900.67 -> Dapagliflozin submitted it's primary outcome in 28 days

2903.31 -> and empa in 34 days, so right around a month,

2905.47 -> we're seeing a statistically significant decrease

2907.9 -> in the primary outcome in their clinical trials.

2909.48 -> So it does not take while to start seeing benefit

2911.68 -> in these medications,

2913.54 -> and they not gonna affect blood pressure.

2915.16 -> I show a little bit extra for this

2917.8 -> and maybe folks are not using these as much

2919.69 -> in your own clinical practice,

2920.8 -> but on the left is from diabetic patients,

2923.14 -> on the right is in non-diabetic patients.

2924.97 -> This is from DAPA-HF,

2926.08 -> this is the 2019 Landmark HFrEF,

2928.72 -> heart failure reduced clinical trial.

2930.91 -> Though this trend has been reproduced

2932.41 -> in the heart failure with per DF population as well,

2934.69 -> that these medicines do not lower patient's blood pressure.

2938.08 -> If you look on the Y-axis,

2939.4 -> arterial mean change in systolic blood pressure,

2941.2 -> we're looking at a couple millimeters of mercury

2942.97 -> and it's not significant

2944.56 -> diabetic, non-diabetic,

2945.85 -> irrespective of ejection fraction.

2948.31 -> This medication's gonna be okay

2949.75 -> with people with lower blood pressure

2951.46 -> and should not lower your blood pressure,

2954.94 -> but it will impact the GFR transitively.

2957.19 -> As you're very familiar,

2958.24 -> if you start someone on ACE inhibitor or an ARB,

2960.25 -> you'll see a little bit of a bump in creatinine dip in GFR

2963.13 -> that gets better over time.

2964.69 -> And the same thing, this is from

2965.98 -> empagliflozin HF clinical trial.

2969.084 -> You can see that at about four weeks there is a dip,

2972.123 -> a nater in the GFR that comes back up.

2975.016 -> But if you look over the spanning time,

2977.02 -> the years of the clinical trial, the rate of reduction,

2980.05 -> the rate of renal function worsening

2982.42 -> gets blunted and it's renal protective

2985.06 -> in the long run to be on SGLT2 inhibitor in this population.

2990.1 -> And finally, don't forget Spironolactone.

2992.89 -> This is the least prescribed

2994.27 -> of the heart failure medication in the United States.

2996.67 -> Some reports up to two thirds of eligible patients

2999.22 -> are not getting this medication.

3001.53 -> But it has profound benefits.

3003.12 -> On the left this figures from RALES, R-A-L-E-S,

3006.6 -> the Landmark Clinical Trial from 1999

3008.61 -> that put this on the map.

3010.08 -> 11% absolute reduction risk in death, not relative risk.

3013.38 -> 11%, absolute risk of death,

3015.18 -> 30% relative risk, huge reduction in mortality.

3019.17 -> And you see the curve separate

3020.61 -> just within a couple of months.

3022.71 -> You do not need to be on other background medical therapy.

3025.02 -> So you do not need to wait until on maximum beta blocker

3027.48 -> or ARNI or what have you, you can just get them on it.

3030.42 -> This will not impact their blood pressure

3032.43 -> just like SGLT2.

3035.414 -> If you're actively working in primary care,

3036.75 -> think back to your primary care days,

3039.54 -> how often are you putting Spironolactone

3040.79 -> on folks with hypertension for their first line,

3042.81 -> second line, third line medication?

3044.31 -> These are not actively, this is not...

3047.937 -> I have a different slide that I'm happy to show you offline

3050.22 -> or after we're done.

3052.38 -> But spironolactone is not gonna lower your blood pressure

3054.72 -> in a heart failure patient.

3056.34 -> You can start a 12 and a half or 25 milligrams.

3058.62 -> You really only need to get the 25 milligrams

3060.78 -> to see the mortality benefit.

3062.64 -> The clinical trial is set up to go up to 50 milligrams

3065.16 -> where the average dose in the trial was 26,

3067.2 -> meaning pretty much everyone in the trial

3068.73 -> was on 25 milligrams.

3070.805 -> You do need to follow the potassium.

3072.99 -> You have to follow the potassium.

3076.02 -> In the clinical trial they check

3077.16 -> quite a few basic metabolic panels,

3078.81 -> BMPs three days a week,

3080.16 -> monthly to follow that potassium level.

3083.88 -> Now this is gonna be in clinic.

3085.59 -> We're not necessarily doing this as frequently,

3087.18 -> so I usually split the difference

3088.62 -> depending on their baseline renal function

3090.21 -> of where they're starting off at in terms of potassium.

3093.42 -> But at least at San Francisco General Hospital,

3095.28 -> a K of 5.1 is still normal.

3098.79 -> Without spending too much time on this,

3100.41 -> but it's very important that

3102.48 -> a low K 5.1, 5.2, 5.3 is okay.

3106.44 -> You have to be able to check it,

3108.06 -> you have to keep an eye on it,

3110.4 -> but at 5.1, 5.2, 5.3,

3112.74 -> the patient's gonna be okay

3113.76 -> and stay on a medication that has 11%

3116.46 -> absolute risk in making them die less.

3120.06 -> If someone, the most common thing I see

3121.86 -> is they've been on Spironolactone for weeks or for months.

3124.17 -> They've had many potassium levels checking.

3125.79 -> It's always been normal.

3126.69 -> Now all of a sudden it's high,

3129.36 -> low fives, high fives, what have you.

3132.45 -> Now if it's in the sixes,

3133.32 -> sure you obviously have to stop it

3134.64 -> and figure out what's going on,

3135.54 -> but in the low five, all of a sudden, why?

3137.97 -> Spironolactone if it's gonna make the potassium go up,

3140.04 -> shouldn't do it all of a sudden randomly,

3141.78 -> months or years into treatment,

3144.27 -> look for other offending agents

3146.28 -> before you just stop the Spironolactone.

3148.41 -> And lastly, the gynecomastia.

3150.872 -> 10 to 20% depending percent of men.

3154.32 -> The first sign that a man starts having

3155.82 -> any breast tenderness issue at all,

3157.41 -> I just switch it over.

3158.82 -> The longer they have gynecomastia,

3160.56 -> the longer it takes to go away

3162 -> after getting off Spironolactone and onto a CLA note.

3166.05 -> So with that, I'll leave us with about five,

3168.09 -> 10 minutes for questions.

3169.8 -> This is my last slide.

3173.58 -> We talk about contemporary, you know,

3175.32 -> advances in 2023 that the biggest thing

3178.56 -> are these medications,

3180.33 -> may not be the sexiest thing,

3181.56 -> not a device or some, you know,

3183.45 -> new cutting edge intervention,

3187.11 -> but it really, really, really works

3189.63 -> and can tremendously reduce patient stances of dying,

3192.18 -> coming back to the hospital,

3193.92 -> improve quality of life,

3195.24 -> reduce risk of sudden cardiac death,

3197.22 -> all sorts of benefits.

3198.81 -> And to remember a clinical stable heart

3200.82 -> failure person is not low risk.

3203.4 -> Remember the stablest heart failure patient

3204.9 -> still has over 10% chance of dying

3206.73 -> or coming to the hospital that year.

3208.56 -> That we have to be aggressive

3209.91 -> whether it's us providing the medications

3212.07 -> or saying, "Hey FYI, you know, provider so and so,

3215.887 -> "your patient has heart failure

3216.877 -> "they're not on these things".

3218.34 -> That we have to get people on these medications

3220.047 -> and we can't be afraid of clinical inertia.

3222.6 -> We have to know they're important.

3223.95 -> We have to educate patients at the time of diagnosis,

3226.62 -> hey, this is a lifelong disease.

3228.21 -> Let's talk about your understanding of the disease.

3230.43 -> Let's talk about the medications.

3231.72 -> We're gonna be adjusting doses,

3233.04 -> we're gonna be following these things,

3234.75 -> but we can make you feel better.

3235.89 -> We can make you live longer,

3236.85 -> but we're gonna have to do it together.

3238.71 -> And making sure you think about the barriers,

3240.63 -> the risks, the social determinant issues

3242.61 -> that may impact that,

3243.99 -> and how you can start making headway

3245.43 -> on those things early before it's too late.

3248.49 -> So yes, there are always risks of attempting to escalate,

3251.4 -> but I hopefully have told you that those risks are small,

3253.8 -> but the potential risks of not doing things,

3256.47 -> the risk is even greater.

3258.33 -> So with that, I will stop and thank you again so much

3262.41 -> for having me today,

3264.09 -> and I'm happy to take any questions.

3269.01 -> - Thank you so much.

3269.85 -> That was such an outstanding talk.

3272.01 -> You were just an esteemed educator

3273.69 -> and you really broke down and demystified

3276.21 -> how to start GDMT in a very practical way

3278.64 -> and reviewing the evidence.

3279.54 -> We have a bunch of questions

3280.56 -> from about 90 viewers logging in.

3283.47 -> So one of the questions is really about,

3285.18 -> with all these changes in therapy with GDMT,

3288.57 -> do you think that this might impact thresholds

3291.06 -> for actually needing ICD CRT

3293.61 -> with the improvement in medical therapy?

3295.71 -> And kind of the reverse of that question is,

3298.68 -> if we've gotten so much better at managing heart failure,

3302.16 -> why is that five year mortality still so sticky

3305.28 -> and why haven't we made progress

3307.11 -> in sort of treating underlying causes and curing it?

3310.5 -> - Two great questions.

3311.34 -> I actually wrote an editorial on this

3313.56 -> with a few colleagues about a year or so ago

3315.647 -> of the ICD question.

3317.7 -> That most of the ICD...

3319.29 -> I'll try to be brief with this.

3320.37 -> Most of those clinical trials

3321.63 -> were done before contemporary GDMT.

3323.79 -> And if you just send the RNA clinical trials

3326.13 -> and the rates of sudden cardiac death in those trials

3328.53 -> and you look in the SW2 heart failure trials

3330.96 -> and rates of sudden cardiac death,

3332.61 -> the rates are significantly reduced just by being on ARNI

3335.64 -> or just by being on SGLT2 independent of defibrillator,

3338.43 -> independent of everything else,

3340.74 -> that there has been a large call about, you know,

3344.16 -> revisiting that these indications

3346.32 -> that how much time should someone be on quad therapy

3349.56 -> before you reassess their ejection fraction?

3351.75 -> You know, how much do we say

3353.31 -> well, maybe a criteria should change.

3355.38 -> That's definitely not an area of much discussion.

3358.53 -> But GDMT, it works, you need to give it time to work.

3362.64 -> And depending on which meta-analysis or trial,

3365.64 -> you look at that some patients, you know,

3368.55 -> if you have an EF that's low enough to qualify

3370.62 -> for defibrillator, if you come back six or 12 months later,

3372.93 -> the vast majority of people don't need it anymore

3375.42 -> because their EF has come back up

3376.98 -> and they no longer qualify.

3378.84 -> But you have to be aggressive with medical therapy.

3380.427 -> And this gets us into this trying to answer

3382.17 -> the second question is why haven't this changed.

3387.27 -> And this is why this is so important in 2023

3389.34 -> to still talk about is the rates of actually prescribing

3391.68 -> these medications are appallingly low,

3396.42 -> that people just aren't being put on these meds.

3398.88 -> I took out the slide, it's in the talk it's hidden.

3403.14 -> There was a registry called CHAMP

3404.76 -> that looked at 150 primary care

3406.59 -> and cardiology clinics around the country,

3408.96 -> and just looked at prescription rates

3410.37 -> for patients that were eligible but not prescribed.

3412.44 -> And the rates of non utilization were high in beta blockers,

3417.99 -> high in just atrocious in MRA for example,

3421.53 -> that were just not prescribing these.

3424.53 -> I think we would see a major change if we can

3427.2 -> a be as aggressive as possible upfront with risk factor

3429.51 -> modification to get hypertension the most modifiable risk.

3432.63 -> But as soon as that person walks

3435.18 -> into your office to emergency room with heart failure,

3436.74 -> you get them on all the meds.

3439.5 -> We didn't talk about a trial that's called,

3441.03 -> if you wanna look up called Strong HF

3442.74 -> that just got published at AHA,

3444.18 -> American Heart Association a few months ago

3446.4 -> that randomized people the getting on meds

3448.11 -> like right now like in the hospital right after discharge

3450.72 -> versus just kind of taking your time.

3452.31 -> Standard care people did much better if we did it fast.

3456.06 -> So to answer your question,

3457.02 -> we just don't do it very well

3458.22 -> and that's why we're here today to talk about it.

3459.81 -> So you all can go and prescribe SGLT.

3462.39 -> - That's exactly right.

3463.41 -> A couple of questions about, you know, barriers to doing it.

3466.59 -> People are asking about what do you do in that patient

3469.08 -> with hypotension or marginal blood pressure,

3471.93 -> or what do you do in people who are really frail,

3474.57 -> have multi morbidities advanced age?

3477.57 -> How do you kind of sequentially approach that patient

3479.88 -> who has that marginal blood pressure

3481.77 -> and how aggressive do you go,

3483.06 -> especially in the inpatient setting.

3486.27 -> - There's a lot to unpack there.

3487.62 -> I'll try to hit on a couple things.

3491.1 -> So in terms of blood pressure,

3493.11 -> again, your MRA, your spironolactone,

3495.604 -> your SGLT2 should be able to get away

3497.34 -> without much of any impact on blood pressure.

3499.95 -> And there's plenty of data

3501.69 -> on clinical trials to support that.

3505.53 -> Really thinking about the volume status,

3507.51 -> especially if you have someone

3508.59 -> that you're switching over to ARNI

3510.24 -> and they start having more hypotension

3511.8 -> really being aggressive and not just peeling back

3514.05 -> the loop diuretic and stopping the diuretic

3516.51 -> but allowing them to drink more fluid.

3518.91 -> I'd say the vast, vast majority of my patients

3521.13 -> that I'm starting on, you know,

3522.21 -> blood pressures in the '90s are low 100s,

3524.52 -> starting on the ARNI.

3527.49 -> If I can modify the fluid enough,

3530.37 -> I can get the person on it.

3532.11 -> Yes, there're gonna people that are too sick,

3533.97 -> but the vast majority of people,

3535.38 -> if you really are aggressive at having hydrating them

3537.93 -> with the ARNI can get them on medical therapy.

3541.14 -> Beta blockers, metoprolol succinate, you know,

3544.5 -> especially low doses

3545.52 -> as pretty negligible blood pressure effects.

3548.67 -> You know swallowing a 12 and a half of metoprolol succinate,

3550.96 -> a half of a 25 milligram tab is actually lower

3553.47 -> than your equivalent lowest metoprolol tartrate dose

3555.51 -> that you can give in terms of safety.

3557.79 -> I dose it at night.

3559.47 -> If I have people that really marginal

3560.79 -> hyper blood pressure are really, you know,

3562.89 -> that I need to get on medical therapy

3564.047 -> 'cause their EF is super low,

3565.98 -> I'll even dose succinate twice daily

3567.69 -> just divide it in half.

3568.74 -> That can be more gentle.

3569.97 -> Again, that's in a more of a select patient population

3571.95 -> that's more sick to start off with.

3574.38 -> But I could certainly go on things.

3575.52 -> But the one thing about the elderly

3577.5 -> or maybe moving towards end of life

3579.39 -> that's a little bit different,

3580.38 -> but yes, elder individuals are not included

3583.05 -> as much in clinical trials.

3584.1 -> Most of these heart failure clinical trials

3585.21 -> are white men in their '60s.

3586.65 -> That's a separate issue that the guidelines,

3588.39 -> again with the disparity issue needs to be addressed.

3590.91 -> That being said, if you look at the time

3592.44 -> to benefit for quality, forget longevity

3596.01 -> if you have an elderly individual,

3597.72 -> just the quality of life aspects

3599.46 -> that these medications can improve

3601.02 -> take weeks to see benefit.

3602.61 -> Like SGLT2 in a couple weeks,

3604.32 -> the risk of coming to the hospital goes down.

3606.48 -> So even in folks that are older,

3608.22 -> you don't have to wait a year to see benefit

3610.41 -> like a defibrillator you can see benefit in weeks.

3612.87 -> So it is still certainly worth giving it a shot

3614.94 -> and trying these medications.

3616.56 -> But there's a lot in that question to unpack,

3618.51 -> but that's just some highlight things off my head.

3622.35 -> - Two last quick questions.

3623.58 -> You know, what is the future of the poly pill,

3626.01 -> the quad pill, putting these all together

3628.44 -> and can you speak a little bit about

3630.06 -> other innovations that your clinical practice has made?

3632.28 -> You touched on the meth use heart failure clinic

3635.43 -> and other programs like that.

3636.81 -> And also do you have a quick take

3638.58 -> on the use of other diuretics

3641.58 -> like acetazolamide that trial was featured

3644.52 -> at Society of Hospital Medicine National meeting this year

3646.98 -> and wondering what your take is as a cardiologist?

3650.01 -> - Oh my, yes. So lots of things.

3651.27 -> So the poly pill actually Colletta Young,

3653.49 -> one of the cardiology fellows is who's gonna be working on

3656.85 -> doing a project that's a few other folks around the country

3658.89 -> are doing this, but her project is really exciting.

3662.28 -> How to actually take all these pills

3663.51 -> and put it in one little capsule,

3664.8 -> a little bigger capsule.

3665.79 -> But you put meds in one capsule

3668.4 -> without having to worry about,

3669.57 -> you know, going to some manufacturer pharmacy,

3673.05 -> place somewhere and actually

3673.98 -> make these powders from scratch.

3675.36 -> But if the pills are small enough,

3676.92 -> can you physically put them in a capsule

3678.377 -> that's a little bit bigger, but take 'em all at once.

3681.06 -> And Collette's actually has a plug to her,

3684.48 -> whoever's listening for her grants submissions

3686.49 -> if you're on this, go approve it.

3689.13 -> But that could be a real game changer.

3690.72 -> I use a lot of bubble packs.

3692.82 -> Daniel's pharmacy, Script Site pharmacy,

3694.59 -> Alta Pharmacy in San Francisco do the service for free.

3697.65 -> They deliver to their door for free.

3700.53 -> So it's a no cost to the patient.

3701.79 -> I joke, I single handly keep these pharmacies in business

3704.46 -> because I do so many bubble packs

3705.81 -> 'cause it is a lot of polypharmacy.

3710.43 -> Cost thinking about patient access,

3712.23 -> thinking about working with your pharmacy colleagues,

3714.18 -> working with social work and case management partners

3717.27 -> in terms of the cost of these medications,

3719.357 -> 'cause some of 'em can be quite expensive

3721.11 -> depending on what your insurance is.

3722.52 -> But if you work with your clinical pharmacist

3724.8 -> or reach out to a clinical pharmacist,

3727.44 -> we had a great talk at our last inpatient, excuse me,

3730.29 -> cardiology, CME course in December

3732.36 -> where two of our pharmacists gave a talk

3733.65 -> about the myriad of resources that do exist

3735.9 -> to try to get these patients at a more...

3737.22 -> Get these medication a more effective cost.

3738.84 -> So work with your pharmacy colleagues on this.

3741.9 -> Acetazolamide has a lot to unpack.

3744.81 -> You can look at the length of stay

3745.86 -> for the hospitalization, seven versus nine days.

3747.96 -> I mean, folks were in the hospital a long time.

3749.46 -> Their doses of Lasix were not that aggressive.

3753.15 -> I don't think I'm gonna yet change my clinical practice.

3756.45 -> I think that trial would've won me over if the comparator

3759.48 -> had included a thiazide diuretic,

3762.12 -> you know, a metolazone, a chlorothiazide diarrheal

3765.78 -> and kind of seen those two things head-to-head

3767.55 -> 'cause we know they make you pee,

3770.13 -> they're highly effective.

3772.05 -> But to know in terms of a safety profile

3774.03 -> and the length of stay profile

3775.59 -> that we just don't have the head-to-head data.

3777.66 -> The only real head-to-head on even those medications

3780.15 -> is like a 60 person clinical trial

3782.31 -> that was really small from a couple years ago.

3785.76 -> I'm not...

3787.62 -> I'll stop there.

3788.453 -> 'Cause the advo trial is a lot to unpack,

3792.27 -> but I don't think it's necessarily a straight cut

3793.71 -> that we should be doing everything.

3794.64 -> Every patient should just get it off the top.

3797.34 -> - Well, thank you so much.

3798.33 -> This is a whirlwind tour.

3799.38 -> Really appreciate you.

3800.7 -> We'll see you back here next week

3802.08 -> for Medicine Grand Rounds.

3803.01 -> Thanks again.

Source: https://www.youtube.com/watch?v=3mMMDubQtQ4