Heart Failure Therapies State of the Art 2017...Heart Failure (Journal of the American College of...

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