Heart Failure TherapiesState of the Art 2017

Andrew J. Sauer, MDAssistant ProfessorDirector, Center for Heart FailureMedical Director, Heart TransplantationUNOS Primary Transplant Physicianasauer@kumc.edu

DisclosuresNovartis: Speaker HonorariumMedtronic: Speaker/Consultant Honorarium

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Learning Objectives• Understand the heart failure epidemiology trends• Review the 2017 Stage C HF Guidelines Update• Identify Stage D “Advanced” Heart Failure• Appreciate Contemporary LVAD Therapy• Recognize some temporary mechanical support

technologies in the critically ill patient

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Heart Failure Burden

1.JACCHF.2013;1:1-20.2. RoseEA,etal.Long-termmechanicalleftventricularassistanceforend-stageheartfailure.

NEngl JMed.Nov.2001;5;345(20):1435-43.4. Rogers,Butler,Lansman,etal.JAmColl Cardiol.2007;50:741-47.5. Hershberger,Nauman,Walker,etal.JCardFail.2003;22:616-24.6. Gorodeski,Chu,Reese,etal.Circ HeartFail.2009;2:320-24.7. Dataonfile.Pleasanton,Calif:Thoratec Corp.

Heart Failure Natural History

2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure

CitationThisslidesetwasadaptedfromthe2017ACC/AHA/HFSAFocusedUpdateofthe2013ACCF/AHAGuidelinefortheManagementofHeartFailure(JournaloftheAmericanCollegeofCardiology). PublishedonApril28,2017,availableat: Yancy,et.al.ACC/AHA/HFSA2017HeartFailureFocusedUpdate

Thefull-textguidelinesarealsoavailableonthefollowingWebsites:• AmericanCollegeofCardiology(www.acc.org)• AmericanHeartAssociation(professional.heart.org)• HeartFailureSocietyofAmerica(www.hfsa.org)

Stage C

Treatment of HF Stages A Through D

Treatment of HFrEF Stage C and D

†Hydral-Nitratesgreenbox:ThecombinationofISDN/HYDwithARNIhasnotbeenrobustlytested.BPresponseshouldbecarefullymonitored.‡See2013HFguideline.§ParticipationininvestigationalstudiesisalsoappropriateforstageC,NYHAclassIIandIIIHF.ACEIindicatesangiotensin-convertingenzymeinhibitor;ARB,angiotensinreceptor-blocker;ARNI,angiotensinreceptor-neprilysin inhibitor;BP,bloodpressure;bpm,beatsperminute;C/I,contraindication;COR,ClassofRecommendation;CrCl,creatinineclearance;CRT-D,cardiacresynchronizationtherapy–device;Dx,diagnosis;GDMT,guideline-directedmanagementandtherapy;HF,heartfailure;HFrEF,heartfailurewithreducedejectionfraction;ICD,implantablecardioverter-defibrillator;ISDN/HYD,isosorbidedinitratehydral-nitrates;K+,potassium;LBBB,leftbundle-branchblock;LVAD,leftventricularassistdevice;LVEF,leftventricularejectionfraction;MI,myocardialinfarction;NSR,normalsinusrhythm;andNYHA,NewYorkHeartAssociation.

Neprilysin Inhibition (ARNI: LCZ696)sacubatril-valsartan

Simplifiedschematicoftherenin–angiotensin–aldosteronesystem.

vonLueder TGetal.Circ HeartFail.2013;6:594-605

Simplifiedschematicofthenatriureticpeptidesystem(NPS).

vonLueder TGetal.Circ HeartFail.2013;6:594-605

PARADIGM HF

Kaplan–MeierCurvesforKeyStudyOutcomes,AccordingtoStudyGroup.

McMurray JJ et al. N Engl J Med 2014. DOI: 10.1056/NEJMoa1409077

PrimaryandSecondaryOutcomes.

McMurray JJ et al. N Engl J Med 2014. DOI: 10.1056/NEJMoa1409077

Pharmacological Treatment for Stage C HF With Reduced EF

Renin-Angiotensin System Inhibition With ACE-Inhibitor or ARB or ARNI

I

ACE-I:ATheclinicalstrategyofinhibitionoftherenin-angiotensinsystemwithACEinhibitors(LevelofEvidence:A), ORARBs(LevelofEvidence:A), OR ARNI(LevelofEvidence:B-R)inconjunctionwithevidence-basedbetablockers,andaldosteroneantagonistsinselectedpatients,isrecommendedforpatientswithchronicHFrEF toreducemorbidityandmortality.

NEW: Newclinicaltrialdatapromptedclarificationandimportantupdates.ARB:A

ARNI:B-R

COR LOE Recommendations Comment/Rationale

Pharmacological Treatment for Stage C HF With Reduced EF

Renin-Angiotensin System Inhibition With ACE-Inhibitor or ARB or ARNI

COR LOE Recommendations Comment/Rationale

I ARNI:B-R

InpatientswithchronicsymptomaticHFrEF NYHAclassIIorIIIwhotolerateanACEinhibitororARB,replacementbyanARNIisrecommendedtofurtherreducemorbidityandmortality.

NEW:Newclinicaltrialdatanecessitatedthisrecommendation.

Pharmacological Treatment for Stage C HF With Reduced EF

Renin-Angiotensin System Inhibition With ACE-Inhibitor or ARB or ARNI

COR LOE Recommendations Comment/Rationale

III:Harm B-R

ARNIshouldnotbeadministeredconcomitantlywithACE inhibitorsorwithin36hoursofthelastdoseofanACEinhibitor.

NEW:AvailableevidencedemonstratesapotentialsignalofharmforaconcomitantuseofACEinhibitorsandARNI.

III:Harm C-EO

ARNIshouldnotbeadministeredtopatientswithahistoryofangioedema.

NEW:Newclinicaltrialdata.

Pharmacological Treatment for Stage C HF With Reduced EF

Ivabradine

COR LOE Recommendations Comment/Rationale

IIa B-R

IvabradinecanbebeneficialtoreduceHFhospitalizationforpatientswithsymptomatic(NYHAclassII-III)stablechronicHFrEF(LVEF≤35%)whoarereceivingGDEM*,includingabetablockeratmaximumtolerateddose,andwhoareinsinusrhythmwithaheartrateof70bpmorgreateratrest.

NEW:Newclinicaltrialdata.

*Inotherpartsofthedocument,theterm“GDMT”hasbeenusedtodenoteguideline-directedmanagementandtherapy.Inthisrecommendation,however,theterm“GDEM”hasbeenusedtodenotethissameconceptinordertoreflecttheoriginalwordingoftherecommendationthatinitiallyappearedinthe“2016ACC/AHA/HFSAFocusedUpdateonNewPharmacologicalTherapyforHeartFailure:AnUpdateofthe2013ACCF/AHAGuidelinefortheManagementofHeartFailure”.

HFpEF Trends in Heart Failure

NEngl JMed2006;355:251-9.

NEngl JMed2006;355:251-9.

Trends in HF

Barry A. Borlaug, and Margaret M. Redfield Circulation. 2011;123:2006-2014

Response to treatment HFrEF vs HFpEF

Shah,A.M.&Pfeffer,M.A.(2012) ThemanyfacesofheartfailurewithpreservedejectionfractionNat.Rev.Cardiol.doi:10.1038/nrcardio.2012.123

*ElectricalandMechanicalRepolarizationHeterogeneity

Pharmacological Treatment for Stage C HF With Preserved EF

I B

SystolicanddiastolicbloodpressureshouldbecontrolledinpatientswithHFpEF inaccordancewithpublishedclinicalpracticeguidelinestopreventmorbidity

2013recommendationremainscurrent.

I C

DiureticsshouldbeusedforreliefofsymptomsduetovolumeoverloadinpatientswithHFpEF.

2013recommendationremainscurrent.

COR LOE Recommendations Comment/Rationale

IIb B-R

InappropriatelyselectedpatientswithHFpEF(withEF≥45%,elevatedBNPlevelsorHFadmissionwithin1year,estimatedglomerularfiltrationrate>30mL/min, creatinine<2.5mg/dL,potassium<5.0mEq/L),aldosteronereceptorantagonistsmightbeconsideredtodecreasehospitalizations.

NEW: CurrentrecommendationreflectsnewRCTdata.

Pharmacological Treatment for Stage C HF With Preserved EF

COR LOE Recommendations Comment/Rationale

IIb B

TheuseofARBsmightbeconsideredtodecreasehospitalizationsforpatientswithHFpEF.

2013recommendationremainscurrent.

Anemia

Important Comorbidities in HF

Anemia

COR LOE Recommendations Comment/Rationale

IIb B-R

InpatientswithNYHAclassIIandIIIHFandirondeficiency(ferritin<100ng/mLor100to300ng/mLiftransferrinsaturationis<20%),intravenousironreplacementmightbereasonabletoimprovefunctionalstatusandQoL.

NEW: Newevidenceconsistentwiththerapeuticbenefit.

III:NoBenefit B-R

InpatientswithHFandanemia,erythropoietin-stimulatingagentsshouldnotbeusedtoimprovemorbidityandmortality.

NEW: Currentrecommendationreflectsnewevidencedemonstratingabsenceoftherapeuticbenefit.

What About Heart Failure Complicated by Shock?

Who is a Stage D HF Patient?

Cardiogenic Shock

Intra-Aortic Balloon Pump: 2015

IABP post AMI: SHOCK-II Trial

Temporary Support Devices

We Can’t Transplant Everybody

1. Currentestimatesofadultpatientswithadvancedheartfailure(HF)intheUnitedStates,withprojectedleftventricularassistdevice(LVAD)candidates.U.S.populationestimateisderivedfromU.S.Censusdata.EstimateofHFprevalenceisderivedfromlatestAmericanHeartAssociation(AHA)statistics.

2. UNOSWebsite:http://optn.transplant.hrsa.gov3. O’Connell.AdvancedHeartFailureTherapiesForum,Atlanta.2013.

Ventricular Assist Device: State of the Art 2017

MCS vs Medical Therapy

MCS vs Medical Therapy

Evolution of Devices

10 Main Points on LVAD 20171. LVAD: The Big Picture2. LVAD: Hemodynamic Optimization3. LVAD Device Trends 2006-20164. LVAD Trial Data Summary & New Devices5. Adverse Event Rate Trends6. Quality of Life7. Cost of Device Implantation8. Cost Effectiveness9. LVAD and Electrophysiology10.The Future10/23/17 38

1. LVAD: THE BIG PICTURE

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2. LVAD: HEMODYNAMICOPTIMIZATION

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3. LVAD IMPLANTTRENDS: 2006-2016

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4. LANDMARK TRIALS& NEW TECHNOLOGY

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5. ADVERSE EVENT RATES

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6. QUALITY OF LIFE

Quality of Life Data: INTERMACS

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7. COST: WHAT DRIVES COST?

What Drives the VAD Implant Cost?

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Post Implant Length of Stay of Patients Discharged Alive

0

5

10

15

20

25

30

Days Intermacs

TUKH

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8. COST-EFFECTIVENESS

DT LVAD: Costs, QALYs, ICER

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Pulsatile to CF – LVAD Transition

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Beyond the Index Admission: Costs

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9. LVAD & Electrophysiology

LVAD: EP Topics• ICD Implantation Post-LVAD• Tachy-therapies settings• LV lead ON vs OFF• Atrial fibrillation treatments• VT Ablation

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10. THE FUTURE

Future Developments & Challenges• Driveline removal (totally internal LVAD)• Minimally invasive implantation• Continuous hemodynamic monitoring

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10 Main Points on LVAD 20171. Heart failure epidemic: large and growing2. Novel pharma and device therapies

-ARNI to replace ARB/ACE-I-HCN blockers-ambulatory PA pressure monitoring devices

3. Lacking data / guidelines on HFpEF4. System innovations are key5. Refer early for Stage D HF patients

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Andrew J. Sauer, MDAssistant ProfessorDirector, Center for Heart FailureMedical Director, Heart TransplantationUNOS Primary Transplant Physicianasauer@kumc.edu