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

28 Pages·2017·3.12 MB·English

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY VOL. 70, NO. 6, 2017
ª2017 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION, ISSN 0735-1097/$36.00
THE AMERICANHEARTASSOCIATION,INC.,AND THEHEART FAILURESOCIETY OFAMERICA http://dx.doi.org/10.1016/j.jacc.2017.04.025
PUBLISHED BY ELSEVIER
CLINICAL PRACTICE GUIDELINE: FOCUSED UPDATE
2017 ACC/AHA/HFSA Focused Update of
the 2013 ACCF/AHA Guideline for
the Management of Heart Failure
AReportoftheAmericanCollegeofCardiology/AmericanHeartAssociation
TaskForceonClinicalPracticeGuidelinesandtheHeartFailureSocietyofAmerica
DevelopedinCollaborationwiththeAmericanAcademyofFamilyPhysicians,
AmericanCollegeofChestPhysicians,andInternationalSocietyforHeartandLungTransplantation
Writing ClydeW.Yancy,MD,MSC,MACC,FAHA,FHFSA,Chair FrederickA.Masoudi,MD,MSPH,FACC**
Group MariellJessup,MD,FACC,FAHA,ViceChair PatrickE.McBride,MD,MPH,FACCyy
Members* PamelaN.Peterson,MD,FACC,FAHAz
BiykemBozkurt,MD,PHD,FACC,FAHA*y LynneWarnerStevenson,MD,FACC*z
JavedButler,MD,MBA,MPH,FACC,FAHA*z CherylWestlake,PHD,RN,ACNS-BC,FAHA,FHFSA{
DonaldE.Casey,JR,MD,MPH,MBA,FACCx
MonicaM.Colvin,MD,FAHAk
MarkH.Drazner,MD,MSC,FACC,FAHA,FHFSAz *Writinggroupmembersarerequiredtorecusethemselvesfromvotingon
sectionstowhichtheirspecificrelationshipswithindustrymayapply;see
GerasimosS.Filippatos,MD*
Appendix1fordetailedinformation.yACC/AHATaskForceonClinical
GreggC.Fonarow,MD,FACC,FAHA,FHFSA*z PracticeGuidelinesLiaison.zACC/AHARepresentative.xACPRepresentative.
MichaelM.Givertz,MD,FACC,FHFSA*{ kISHLTRepresentative.{HFSARepresentative.#CHESTRepresentative.
StevenM.Hollenberg,MD,FACC# **ACC/AHATaskForceonPerformanceMeasuresRepresentative.
yyAAFPRepresentative.
JoAnnLindenfeld,MD,FACC,FAHA,FHFSA*{
ThisdocumentwasapprovedbytheAmericanCollegeofCardiologyClinicalPolicyApprovalCommittee,theAmericanHeartAssociationScience
AdvisoryandCoordinatingCommittee,theAmericanHeartAssociationExecutiveCommittee,andtheHeartFailureSocietyofAmericaExecutive
CommitteeinApril2017.
TheAmericanCollegeofCardiologyrequeststhatthisdocumentbecitedasfollows:YancyCW,JessupM,BozkurtB,ButlerJ,CaseyDEJr,ColvinMM,
DraznerMH,FilippatosGS,FonarowGC,GivertzMM,HollenbergSM,LindenfeldJ,MasoudiFA,McBridePE,PetersonPN,StevensonLW,WestlakeC.
2017ACC/AHA/HFSAfocusedupdateofthe2013ACCF/AHAguidelineforthemanagementofheartfailure:areportoftheAmericanCollegeof
Cardiology/American Heart AssociationTask Force on Clinical Practice Guidelinesand the HeartFailure Society of America.J AmColl Cardiol.
2017;70:776–803.
ThisarticlehasbeencopublishedinCirculationandtheJournalofCardiacFailure.
Copies:ThisdocumentisavailableontheWorldWideWebsitesoftheAmericanCollegeofCardiology(www.acc.org),theAmericanHeartAssociation
(professional.heart.org),andtheHeartFailureSocietyofAmerica(www.hfsa.org).Forcopiesofthisdocument,pleasecontacttheElsevierReprint
Departmentviafax(212-633-3820)ore-mail([email protected]).
Permissions:Multiplecopies,modification,alteration,enhancement,and/ordistributionofthisdocumentarenotpermittedwithouttheexpress
permissionoftheAmericanCollegeofCardiology.RequestsmaybecompletedonlineviatheElseviersite(https://www.elsevier.com/about/our-
business/policies/copyright/permissions).
JACC VOL. 70, NO. 6, 2017 Yancyetal. 777
AUGUST 8, 2017:776–803 2017ACC/AHA/HFSAHeartFailureFocusedUpdate
ACC/AHATask GlennN.Levine,MD,FACC,FAHA,Chair FedericoGentile,MD,FACC
ForceMembers PatrickT.O’Gara,MD,FACC,FAHA,Chair-Elect SamuelGidding,MD,FAHA
JonathanL.Halperin,MD,FACC,FAHA, MarkA.Hlatky,MD,FACC
ImmediatePastChairzz JohnIkonomidis,MD,PHD,FAHA
JoséJoglar,MD,FACC,FAHA
SanaM.Al-Khatib,MD,MHS,FACC,FAHA SusanJ.Pressler,PHD,RN,FAHA
KimK.Birtcher,PHARMD,MS,AACC DumindaN.Wijeysundera,MD,PHD
BiykemBozkurt,MD,PHD,FACC,FAHA
RalphG.Brindis,MD,MPH,MACCzz
JoaquinE.Cigarroa,MD,FACC zzFormerTaskForcemember;currentmemberduring
thewritingeffort.
LesleyH.Curtis,PHD,FAHA
LeeA.Fleisher,MD,FACC,FAHA
TABLE OF CONTENTS
PREAMBLE..................................... 777 9.5.2.TreatingHypertensioninStageCHFrEF:
Recommendation..................... 791
1.INTRODUCTION .............................. 779 9.5.3.TreatingHypertensioninStageCHFpEF:
Recommendation..................... 791
1.1. MethodologyandEvidenceReview............ 779
9.6. Sleep-DisorderedBreathing:Recommendations..792
1.2. OrganizationoftheWritingGroup ............ 779
1.3. DocumentReviewandApproval .............. 779 REFERENCES .................................. 793
6.INITIALANDSERIALEVALUATIONOFTHE APPENDIX1
HFPATIENT .................................780
AuthorRelationshipsWithIndustryandOtherEntities
6.3. Biomarkers ...............................780 (Relevant) ....................................798
6.3.1.BiomarkersforPrevention:
Recommendation..................... 781 APPENDIX2
6.3.2.BiomarkersforDiagnosis: ReviewerRelationshipsWithIndustryand
Recommendation..................... 782 OtherEntities(Comprehensive) ................. 800
6.3.3.BiomarkersforPrognosisorAddedRisk
Stratification:Recommendations ........ 782 APPENDIX3
Abbreviations .................................803
7.TREATMENTOFSTAGESATOD ...............784
7.3. StageC...................................784 PREAMBLE
7.3.2.PharmacologicalTreatmentforStageCHF
WithReducedEjectionFraction: Since1980,theAmericanCollegeofCardiology(ACC)and
Recommendations .................... 784
AmericanHeartAssociation(AHA)havetranslatedscien-
7.3.2.10. Renin-AngiotensinSystemInhibition
tificevidenceintoclinicalpracticeguidelines(guidelines)
WithAngiotensin-ConvertingEnzyme
withrecommendationstoimprovecardiovascularhealth.
InhibitororAngiotensinReceptor
BlockerorARNI:Recommendations . 784 Theseguidelines,whicharebasedonsystematicmethods
7.3.2.11. Ivabradine:Recommendation ..... 786 to evaluate and classify evidence, provide a cornerstone
7.3.3.PharmacologicalTreatmentforStageC forqualitycardiovascularcare.TheACCandAHAsponsor
HFpEF:Recommendations ............. 789 the development and publication of guidelines without
commercial support, and members of each organization
9.IMPORTANTCOMORBIDITIESINHF ............790 volunteer their time to the writing and review efforts.
GuidelinesareofficialpolicyoftheACCandAHA.
9.2. Anemia:Recommendations..................790
9.5. Hypertension(NewSection) ................. 791 IntendedUse
9.5.1.TreatingHypertensiontoReducethe Practice guidelines provide recommendations applicable
IncidenceofHF:Recommendation ...... 791 to patients with or at risk of developing cardiovascular
778 Yancyetal. JACC VOL. 70, NO. 6, 2017
2017ACC/AHA/HFSAHeartFailureFocusedUpdate AUGUST 8, 2017:776–803
disease. The focus is on medical practice in the United SelectionofWritingCommitteeMembers
States, but guidelines developed in collaboration with The Task Force strives to avoidbias by selecting experts
other organizations may have a global impact. Although from a broad array of backgrounds. Writing committee
guidelinesmaybeusedtoinformregulatoryorpayerde- members represent different geographic regions, sexes,
cisions,theirintentistoimprovepatients’qualityofcare ethnicities, races, intellectual perspectives/biases, and
andalignwithpatients’interests.Guidelinesareintended scopesofclinicalpractice.TheTaskForcemayalsoinvite
todefinepracticesmeetingtheneedsofpatientsinmost, organizations and professional societies with related in-
butnot all,circumstancesandshouldnot replaceclinical terests and expertise to participate as partners, collabo-
judgment. rators,orendorsers.
ClinicalImplementation RelationshipsWithIndustryandOtherEntities
Guideline recommended management is effective only TheACCandAHAhaverigorouspoliciesandmethodsto
when followed by healthcare providers and patients. ensure that guidelines are developed without bias or
Adherence to recommendations can be enhanced by improper influence. The complete relationships with in-
shared decision making between healthcare providers dustry and other entities (RWI) policy can be found
and patients, with patient engagement in selecting in- online. Appendix 1 of the current document lists writing
terventionsbasedonindividualvalues,preferences,and committee members’ relevant RWI. For the purposes of
associatedconditionsandcomorbidities. full transparency, writing committee members’ compre-
hensive disclosure information is available online.
MethodologyandModernization
Comprehensive disclosure information for the Task
The ACC/AHA Task Force on Clinical Practice Guidelines
Forceisalsoavailableonline.
(Task Force) continuously reviews, updates, and mod-
ifies guideline methodology on the basis of published EvidenceReviewandEvidenceReviewCommittees
standards from organizations including the Institute of When developing recommendations, the writing com-
Medicine (1,2) and on the basis of internal reevaluation. mitteeusesevidence-basedmethodologiesthatarebased
Similarly,thepresentationanddeliveryofguidelinesare on all available data (4–7). Literature searches focus on
reevaluated and modified on the basis of evolving randomizedcontrolledtrials(RCTs)butalsoincludereg-
technologies and other factors to facilitate optimal istries, nonrandomized comparative and descriptive
dissemination of information at the point of care to studies, case series, cohort studies, systematic reviews,
healthcare professionals. Given time constraints of busy andexpertopinion.Onlykeyreferencesarecited.
healthcare providers and the need to limit text, the An independent evidence review committee (ERC) is
current guideline format delineates that each recom- commissioned when there are 1 or more questions
mendation be supported by limited text (ideally, <250 deemed of utmost clinical importance that merit formal
words) and hyperlinks to supportive evidence summary systematic review. This systematic review will strive to
tables. Ongoing efforts to further limit text are under- determinewhichpatientsaremostlikelytobenefitfroma
way. Recognizing the importance of cost-value consid- drug, device, or treatment strategy and to what degree.
erations in certain guidelines, when appropriate and CriteriaforcommissioninganERCandformalsystematic
feasible, an analysis of the value of a drug, device, or review include: a) the absence of a current authoritative
intervention may be performed in accordance with the systematicreview,b)thefeasibilityofdefiningthebenefit
ACC/AHA methodology (3). and risk in a time frame consistent with the writing of a
To ensure that guideline recommendations remain guideline, c) the relevance to a substantial number of
current,newdataarereviewedonanongoingbasis,with patients, and d) the likelihood that the findings can be
full guideline revisions commissioned in approximately translated into actionable recommendations. ERC mem-
6-year cycles. Publication of new, potentially practice- bers may include methodologists, epidemiologists,
changingstudyresultsthatarerelevanttoanexistingor healthcareproviders,andbiostatisticians.Whenaformal
new drug, device, or management strategy will prompt systematic review has been commissioned, the recom-
evaluation by the Task Force, in consultation with the mendations developed by the writing committee on the
relevant guideline writing committee, to determine basisofthesystematicreviewaremarkedwith“SR”.
whether a focused update should be commissioned. For
additional information and policies regarding guideline Guideline-DirectedManagementandTherapy
development, we encourage readers to consult the ACC/ The term guideline-directed management and therapy
AHA guidelinemethodology manual (4) andother meth- (GDMT) encompasses clinical evaluation, diagnostic
odologyarticles(5–8). testing, and pharmacologicalandprocedural treatments.
JACC VOL. 70, NO. 6, 2017 Yancyetal. 779
AUGUST 8, 2017:776–803 2017ACC/AHA/HFSAHeartFailureFocusedUpdate
Fortheseandallrecommendeddrugtreatmentregimens, ACC,AHA,andEuropeanSocietyofCardiologyandother
the reader should confirm the dosage by reviewing scientific meetings and that were published in peer-
product insert material and evaluate the treatment reviewed format from April 2013 through November
regimen for contraindications and interactions. The rec- 2016.TheevidenceissummarizedintablesintheOnline
ommendations are limited to drugs, devices, and treat- Data Supplement. All recommendations (new, modified,
mentsapprovedforclinicaluseintheUnitedStates. and unchanged) for each clinical section are included to
provide a comprehensive assessment. The text explains
ClassofRecommendationandLevelofEvidence new and modified recommendations, whereas recom-
The Class of Recommendation (COR) indicates the mendations from the previous guideline that have been
strengthof the recommendation,encompassingthe esti- deleted or superseded no longer appear. Please consult
matedmagnitudeandcertaintyofbenefitinproportionto thefull-textversionofthe2013HFguideline(9)fortext
risk. The Level of Evidence (LOE) rates the quality of and evidence tables supporting the unchanged recom-
scientific evidence that supports the intervention on the mendations and for clinical areas not addressed in this
basisofthetype,quantity,andconsistencyofdatafrom focused update. Individual recommendations in this
clinicaltrialsandothersources(Table1)(4–6). focused update will be incorporated into the full-text
GlennN.Levine,MD,FACC,FAHA guideline in the future. Recommendations from the
Chair,ACC/AHATaskForceonClinical prior guideline that remain current have been included
PracticeGuidelines for completeness, but the LOE reflects the COR/LOE sys-
tem used when the recommendations were initially
1. INTRODUCTION developed. New and modified recommendations in this
focused update reflect the latest COR/LOE system, in
Thepurposeofthisfocusedupdateistoupdatethe“2013 which LOE B and C are subcategorized for greater speci-
ACCF/AHA Guideline for the Management of Heart Fail- ficity (4–6). The section numbers correspond to the full-
ure” (9) (2013 HF guideline) in areas in which new evi- textguidelinesections.
dencehas emergedsince itspublication.For thisupdate
andfutureheartfailure(HF)guidelines,theHeartFailure 1.2. OrganizationoftheWritingGroup
Society of America (HFSA) has partnered with the ACC
For this focused update, representative members of the
and AHA to provide coordinated guidance on the man-
2013 HF guideline writing committee were invited to
agementofHF.
participate. They were joined by additional invited
The scope of the focused update includes revision to
members to form a new writing group, which is
the sections on biomarkers; new therapies indicated for
referred to as the 2017 HF focused update writing
stage C HF with reduced ejection fraction (HFrEF); up-
group. Members were required to disclose all RWI
dates on HF with preserved ejection fraction (HFpEF);
relevant to the data under consideration. The group
new data on important comorbidities, including sleep
was composed of experts representing general cardiol-
apnea, anemia, and hypertension; and new insights into
ogists, HF and transplantation specialists, electrophys-
thepreventionofHF.
iologists, pharmacists, and general internists. The 2017
Thisfocusedupdaterepresentsthesecondpartofa2-
HF focused update writing group included representa-
stage publication; with the first part having been pub-
tives from the ACC, AHA, and HFSA, as well as the
lished as the “2016 ACC/AHA/HFSA Focused Update on
American Academy of Family Physicians, American
New Pharmacological Therapy for Heart Failure” (10),
College of Chest Physicians, American College of Phy-
whichintroducedguidanceonnewtherapies,specifically
sicians, and International Society for Heart and Lung
fortheuseofanangiotensinreceptor–neprilysininhibitor
Transplantation.
(ARNI)(valsartan/sacubitril)andasinoatrialnodemodu-
lator (ivabradine). That focused update was published
concurrently with the European Society of Cardiology’s 1.3. DocumentReviewandApproval
complete guideline, “2016 ESC Guidelines for the The focusedupdate was reviewed by 2 official reviewers
Diagnosis and Treatment of Acute and Chronic Heart each nominated by the ACC, AHA, and HFSA; 1 reviewer
Failure”(11). each from the American Academy of Family Physicians,
American College of Chest Physicians, and International
1.1. MethodologyandEvidenceReview SocietyforHeart andLungTransplantation;and19indi-
Toidentifykey datathatinfluenceguidelinerecommen- vidualcontent reviewers.Reviewers’ RWI information is
dations, the Task Force and members of the 2013 HF publishedinthisdocument(Appendix2).
guideline writing committee reviewed clinical trials that This document was approved for publication by the
were presented at the annual scientific meetings of the governingbodiesoftheACC,AHA,andHFSA.
780 Yancyetal. JACC VOL. 70, NO. 6, 2017
2017ACC/AHA/HFSAHeartFailureFocusedUpdate AUGUST 8, 2017:776–803
ApplyingClassofRecommendationandLevelofEvidencetoClinicalStrategies,Interventions,Treatments,or
TABLE 1
DiagnosticTestinginPatientCare*(UpdatedAugust2015)
6. INITIAL AND SERIAL EVALUATION duringinterpretationofnatriureticpeptidebiomarkerlevels
OF THE HF PATIENT inpatientsonARNI.In2studieswithARNI,NT-proBNPlevels
were reduced (12,14), with the reduction in 1 study being
6.3. Biomarkers associatedwithimprovedclinicaloutcomes(12).
Assays for BNP (B-type natriuretic peptide) and NT-proBNP Asubstantialevidencebaseexiststhatsupportstheuse
(N-terminal pro-B-type natriuretic peptide), which are both ofnatriureticpeptidebiomarkerstoassistinthediagnosis
natriureticpeptide biomarkers, have beenused increasingly orexclusionofHFasacauseofsymptoms(e.g.,dyspnea,
toestablishthepresenceandseverityofHF.Ingeneral,both weight gain) in the setting of chronic ambulatory HF
natriuretic peptide biomarker values track similarly, and (15–21)orinthesettingofacutecarewithdecompensated
either can be used in patient care settings as long as their HF (22–30), especially when the cause of dyspnea is un-
respectiveabsolutevaluesandcutpointsarenotusedinter- clear. The role of natriuretic peptide biomarkers in pop-
changeably.Notably,BNP,butnotNT-proBNP,isasubstrate ulation screening to detect incident HF is emerging
forneprilysin.Therefore,ARNIincreasesBNPlevels(12)but (31–37). Elevated plasma levels of natriuretic peptide
not NT-proBNP levels (13). Note that the type of natriuretic biomarkers are associated with a wide variety of cardiac
peptide assay that has been performed must be considered and noncardiac causes (Table 2) (38–42). Obesity may be
JACC VOL. 70, NO. 6, 2017 Yancyetal. 781
AUGUST 8, 2017:776–803 2017ACC/AHA/HFSAHeartFailureFocusedUpdate
associatedwithlowernatriureticpeptideconcentrations,
SelectedPotentialCausesofElevated
TABLE 2
and this may modestly reduce diagnostic sensitivity in NatriureticPeptideLevels(38–41)
morbidlyobesepatients(42).
Cardiac
Becauseoftheabsenceofclearandconsistentevidence
HF,includingRVsyndromes
for improvement in mortality and cardiovascular
Acutecoronarysyndromes
outcomes (43–62), there are insufficient data to inform
Heartmuscledisease,includingLVH
specificguidelinerecommendationsrelatedtonatriuretic
peptide–guidedtherapyorserialmeasurementsofBNPor Valvularheartdisease
Pericardialdisease
NT-proBNP levels for the purpose of reducing hospitali-
zationordeathsinthepresentdocument. Atrialfibrillation
Like natriuretic peptides, cardiac troponin levels may be Myocarditis
elevatedinthesettingofchronicoracutedecompensatedHF, Cardiacsurgery
suggestingmyocyteinjuryornecrosis(63).TroponinsIandT Cardioversion
respond similarly for acute coronary syndromes and acute Toxic-metabolicmyocardialinsults,includingcancerchemotherapy
decompensatedHF.ElevationsineithertroponinIorTlevels Noncardiac
inthesettingofacuteHFareofprognosticsignificanceand Advancingage
mustbeinterpretedintheclinicalcontext(64).
Anemia
Inadditiontonatriureticpeptidesandtroponins(65–67),
Renalfailure
multiple other biomarkers, including those of inflamma-
Pulmonary:obstructivesleepapnea,severepneumonia
tion,oxidativestress,vasculardysfunction,andmyocardial
Pulmonaryhypertension
andmatrixremodeling,havebeenimplicatedinHF(68–71).
Criticalillness
Biomarkersofmyocardialfibrosis,solubleST2receptor,and
Bacterialsepsis
galectin-3 are predictive of hospitalization and death and
Severeburns
mayprovideincrementalprognosticvalueovernatriuretic
peptide levels inpatients withHF (72–74).Strategiesthat ModifiedfromTable8ofthe2013HFguideline(9).
combinemultiplebiomarkersmayultimatelyprovebene- HF, indicates heart failure; LVH, left ventricular hypertrophy; and RV, right
ventricular.
ficialinguidingHFtherapyinthefuture,butmulticenter
studies with larger derivation and validation cohorts are This section categorizes the role of biomarkers into
needed(75,76).Severalemergingbiomarkersawaitvalida- prevention, diagnosis, prognosis, and added risk stratifi-
tion with well-defined outcome measures and prognostic cationtoclarifyevidence-basedobjectivesoftheirusein
accuracybeforetheycanreachtheclinicalarena(77–84). clinicalpractice.
6.3.1. BiomarkersforPrevention:Recommendation
Biomarkers:RecommendationforPreventionofHF
COR LOE RECOMMENDATION COMMENT/RATIONALE
ForpatientsatriskofdevelopingHF,natriuretic NEW:Newdatasuggestthatnatriureticpeptide
IIa B-R peptidebiomarker–basedscreeningfollowedbyteam- biomarkerscreeningandearlyinterventionmay
basedcare,includingacardiovascularspecialist preventHF.
SeeOnlineDataSupplements
optimizingGDMT,canbeusefultopreventthe
AandB.
developmentofleftventriculardysfunction(systolicor
diastolic)ornew-onsetHF(85,86).
Inalarge-scaleunblindedsingle-centerstudy(STOP-HF[TheStVincent’sScreeningtoPreventHeartFailure])(85),patientsatriskofHF(identified
bythepresenceofhypertension,diabetesmellitus,orknownvasculardisease[e.g.,stageAHF]),butwithoutestablishedleftventricularsystolic
dysfunction or symptomatic HFat baseline, were randomlyassigned to receive screening with BNP testing or usual primary care. Intervention-
groupparticipantswithBNPlevelsof$50pg/mLunderwentechocardiographyandwerereferredtoacardiovascularspecialistwhodecidedon
further investigation and management. All patients received further coaching by a specialist nurse who emphasized individual risk and the
importance of adherence to medication andhealthylifestyle behaviors. BNP-basedscreening reducedthecomposite endpointofasymptomatic
left ventricular dysfunction (systolic or diastolic) with or without newly diagnosed HF (85). Similarly, in another small, single-center RCT,
acceleratedup-titrationofrenin-angiotensin-aldosteronesystemantagonistsandbetablockersreducedcardiaceventsinpatientswithdiabetes
mellitusandelevatedNT-proBNPlevelsbutwithoutcardiacdiseaseatbaseline(86).Developingastandardizedstrategytoscreenandintervene
inpatientsatriskofHFcanbedifficultbecauseofdifferentdefinitionsofHFrisk,heterogeneityofprevalenceindifferentpopulations,variable
duration until clinical HF or left ventricular dysfunction develops, and variable interventions for risk factor modification or treatment. Further
studiesareneededtodeterminecost-effectivenessandriskofsuchscreening,aswellasitsimpactonqualityoflife(QoL)andmortalityrate.
782 Yancyetal. JACC VOL. 70, NO. 6, 2017
2017ACC/AHA/HFSAHeartFailureFocusedUpdate AUGUST 8, 2017:776–803
6.3.2. BiomarkersforDiagnosis:Recommendation
Biomarkers:RecommendationforDiagnosis
COR LOE RECOMMENDATION COMMENT/RATIONALE
Inpatientspresentingwithdyspnea,measurementof MODIFIED:2013acuteandchronicrecommendations
I A natriureticpeptidebiomarkersisusefultosupporta havebeencombinedintoadiagnosissection.
diagnosisorexclusionofHF(15–24,28–30).
SeeOnlineData
SupplementsAandB.
NatriureticpeptidebiomarkertestinginthesettingofchronicambulatoryHFprovidesincrementaldiagnosticvaluetoclinicaljudgment,especially
whentheetiologyofdyspneaisunclear(15–21).Inemergencysettings,natriureticpeptidebiomarkerlevelsusuallyhavehighersensitivitythan
specificity and may be more useful for ruling out than ruling in HF (20). Although lower values of natriuretic peptide biomarkers exclude the
presenceofHF,andhighervalueshavereasonablyhighpositivepredictivevaluetodiagnoseHF,cliniciansshouldbeawarethatelevatedplasma
levelsforbothnatriureticpeptideshavebeenassociatedwithawidevarietyofcardiacandnoncardiaccauses(Table2)(38–41).
6.3.3. BiomarkersforPrognosisorAddedRiskStratification:
Recommendations
Biomarkers:RecommendationsforPrognosis
COR LOE RECOMMENDATIONS COMMENT/RATIONALE
MeasurementofBNPorNT-proBNPisusefulforestablishing 2013recommendationremainscurrent.
I A prognosisordiseaseseverityinchronicHF(16,87–92).
Measurementofbaselinelevelsofnatriureticpeptide MODIFIED:Currentrecommendation
I A biomarkersand/orcardiactroponinonadmissiontothe emphasizesthatitisadmissionlevelsof
hospitalisusefultoestablishaprognosisinacutely natriureticpeptidebiomarkersthatareuseful.
SeeOnlineData decompensatedHF(27,93–100).
SupplementsAandB.
Higherlevelsofnatriureticpeptidebiomarkersonadmissionareusuallyassociatedwithgreaterriskforclinicaloutcomes,includingall-causeand
cardiovascularmortality,morbidity,andcompositeoutcomes,acrossdifferenttimeintervalsinpatientswithdecompensatedHF(20,27,29,93–101).
Similarly,abnormallevelsofcirculatingcardiactroponinarecommonlyfoundinpatientswithacutedecompensatedHF,oftenwithoutobviousmyocardial
ischemiaorunderlyingcoronaryarterydisease(CAD),andthisisassociatedwithworseclinicaloutcomesandhigherriskofdeath(95,99,102,103).
Studieshavedemonstratedincrementalprognosticvalueofthesebiomarkerstostandardapproachesofcardiovasculardiseaseriskassessment(29,95).
However,thereweredifferencesintheriskpredictionmodels,assaycutpoints,andlengthsoffollow-up(29).Furthermore,notallpatientsmayneed
biomarkermeasurementforprognostication,especiallyiftheyalreadyhaveadvancedHFwithestablishedpoorprognosisorpersistentlyelevated
levelsofbiomarkersinformersettings.Therefore,assaysofnatriureticpeptidebiomarkersforincrementalprognosticationshouldnotprecludegood
clinicaljudgment;anindividualizedapproachtoeachpatientisparamount.
DuringaHFhospitalization,apredischargenatriureticpeptide NEW:Currentrecommendationreflectsnew
IIa B-NR levelcanbeusefultoestablishapostdischargeprognosis observationalstudies.
(93,96,104–113).
SeeOnlineData
SupplementsAandB.
Predischargenatriureticpeptidebiomarkerlevelsandtherelativechangeinlevelsduringhospitaltreatmentarestrongpredictorsoftheriskofdeath
orhospitalreadmissionforHF(93,96,104–113).Severalstudieshavesuggestedthatpredischargenatriureticpeptidebiomarkerlevelshadhigher
reclassificationanddiscriminationvaluethanclinicalvariablesinpredictingoutcomes(96,106,108–111).Patientswithhigherpredischargelevels
and patients who do not have a decrease in natriuretic peptide biomarker levels during hospitalization have worse outcomes (96,106,108–111).
Althoughobservational orretrospective studieshavesuggested thatpatientswithnatriureticpeptide biomarkerreduction hadbetteroutcomes
than those without any changes or with a biomarker rise (93,107,112,113), targeting a certain threshold, value, or relative change in these
biomarkerlevelsduringhospitalizationmaynotbepracticalorsafeforeverypatientandhasnotbeentestedinaprospectivelarge-scaletrial.
ClinicalassessmentandadherencetoGDMTshouldbetheemphasis,andtheprognosticvalueofapredischargevalueorrelativechangesdoes
notimplythenecessityforserialandrepeatedbiomarkermeasurementsduringhospitalization.
JACC VOL. 70, NO. 6, 2017 Yancyetal. 783
AUGUST 8, 2017:776–803 2017ACC/AHA/HFSAHeartFailureFocusedUpdate
(continued)
InpatientswithchronicHF,measurementofotherclinically MODIFIED:2013recommendationshavebeen
IIb B-NR availabletests,suchasbiomarkersofmyocardialinjuryor combinedintoprognosissection,resultingin
fibrosis,maybeconsideredforadditiveriskstratification LOEchangefromAtoB-NR.
SeeOnlineData (27,95,98,99,103,114–119).
SupplementsAandB.
Biomarkersofmyocardialfibrosis(e.g.,solubleST2receptor,galectin-3,high-sensitivitycardiactroponin,andothers)arepredictiveofhospitalization
anddeathinpatientswithHFandalsoareadditivetonatriureticpeptidebiomarkerlevelsintheirprognosticvalue(117,119–126).Acombinationof
biomarkersmayultimatelyprovetobemoreinformativethansinglebiomarkers(127).
FIGURE1 BiomarkersIndicationsforUse
ColorscorrespondtoCORinTable1.
*OtherbiomarkersofinjuryorfibrosisincludesolubleST2receptor,galectin-3,andhigh-sensitivitytroponin.
ACCindicatesAmericanCollegeofCardiology;AHA,AmericanHeartAssociation;ADHF,acutedecompensatedheartfailure;BNP,B-typenatriureticpeptide;
COR,ClassofRecommendation;ED,emergencydepartment;HF,heartfailure;NT-proBNP,N-terminalpro-B-typenatriureticpeptide;NYHA,NewYorkHeart
Association;andpts,patients.
784 Yancyetal. JACC VOL. 70, NO. 6, 2017
2017ACC/AHA/HFSAHeartFailureFocusedUpdate AUGUST 8, 2017:776–803
7. TREATMENT OF STAGES A TO D 7.3.2.10. Renin-AngiotensinSystemInhibitionWith
Angiotensin-ConvertingEnzymeInhibitoror
7.3. StageC AngiotensinReceptorBlockerorARNI:
7.3.2. PharmacologicalTreatmentforStageCHFWithReduced Recommendations
EjectionFraction:Recommendations
(SeeFigure2andTable3).
RecommendationsforRenin-AngiotensinSystemInhibitionWithACEInhibitororARBorARNI
COR LOE RECOMMENDATIONS COMMENT/RATIONALE
Theclinicalstrategyofinhibitionoftherenin- NEW:Newclinicaltrialdatapromptedclarification
ACE-I:A
ARB:A angiotensinsystemwithACEinhibitors(Levelof andimportantupdates.
I Evidence:A)(128–133),ORARBs(LevelofEvidence:A)
ARNI:B-R (134–137),ORARNI(LevelofEvidence:B-R)(138)in
conjunctionwithevidence-basedbetablockers
(9,139,140),andaldosteroneantagonistsinselected
patients(141,142),isrecommendedforpatientswith
chronicHFrEFtoreducemorbidityandmortality.
SeeOnlineData Angiotensin-convertingenzyme(ACE)inhibitorsreducemorbidityandmortalityinheartfailurewithreduced
Supplements1,2,18-20. ejectionfraction(HFrEF).Randomizedcontrolledtrials(RCTs)clearlyestablishthebenefitsofACEinhibitionin
patientswithmild,moderate,orseveresymptomsofHFandinpatientswithorwithoutcoronaryarterydisease
(128–133).ACEinhibitorscanproduceangioedemaandshouldbegivenwithcautiontopatientswithlowsystemic
bloodpressures,renalinsufficiency,orelevatedserumpotassium.ACEinhibitorsalsoinhibitkininaseandincrease
levelsofbradykinin,whichcaninducecoughbutalsomaycontributetotheirbeneficialeffectthrough
vasodilation.
Angiotensinreceptorblockers(ARBs)weredevelopedwiththerationalethatangiotensinIIproduction
continuesinthepresenceofACEinhibition,driventhroughalternativeenzymepathways.ARBsdonotinhibit
kininaseandareassociatedwithamuchlowerincidenceofcoughandangioedemathanACEinhibitors;butlike
ACEinhibitors,ARBsshouldbegivenwithcautiontopatientswithlowsystemicbloodpressure,renalinsufficiency,
orelevatedserumpotassium.Long-termtherapywithARBsproduceshemodynamic,neurohormonal,andclinical
effectsconsistentwiththoseexpectedafterinterferencewiththerenin-angiotensinsystemandhavebeenshown
inRCTs(134–137)toreducemorbidityandmortality,especiallyinACEinhibitor–intolerantpatients.
InARNI,anARBiscombinedwithaninhibitorofneprilysin,anenzymethatdegradesnatriureticpeptides,
bradykinin,adrenomedullin,andothervasoactivepeptides.InanRCTthatcomparedthefirstapprovedARNI,
valsartan/sacubitril,withenalaprilinsymptomaticpatientswithHFrEFtoleratinganadequatedoseofeitherACE
inhibitororARB,theARNIreducedthecompositeendpointofcardiovasculardeathorHFhospitalization
significantly,by20%(138).ThebenefitwasseentoasimilarextentforbothdeathandHFhospitalizationandwas
consistentacrosssubgroups.TheuseofARNIisassociatedwiththeriskofhypotensionandrenalinsufficiencyand
mayleadtoangioedema,aswell.
TheuseofACEinhibitorsisbeneficialforpatientswith 2013recommendationrepeatedforclarityinthis
I ACE-I:A priororcurrentsymptomsofchronicHFrEFtoreduce section.
morbidityandmortality(128–133,143).
SeeOnlineData ACEinhibitorshavebeenshowninlargeRCTstoreducemorbidityandmortalityinpatientswithHFrEFwithmild,
Supplement18. moderate,orseveresymptomsofHF,withorwithoutcoronaryarterydisease(128–133).Datasuggestthatthere
arenodifferencesamongavailableACEinhibitorsintheireffectsonsymptomsorsurvival(143).ACEinhibitors
shouldbestartedatlowdosesandtitratedupwardtodosesshowntoreducetheriskofcardiovasculareventsin
clinicaltrials.ACEinhibitorscanproduceangioedemaandshouldbegivenwithcautiontopatientswithlow
systemicbloodpressures,renalinsufficiency,orelevatedserumpotassium(>5.0mEq/L).Angioedemaoccurs
in<1%ofpatientswhotakeanACEinhibitor,butitoccursmorefrequentlyinblacksandwomen(144).Patients
shouldnotbegivenACEinhibitorsiftheyarepregnantorplantobecomepregnant.ACEinhibitorsalsoinhibit
kininaseandincreaselevelsofbradykinin,whichcaninducecoughinupto20%ofpatientsbutalsomay
contributetobeneficialvasodilation.Ifmaximaldosesarenottolerated,intermediatedosesshouldbetried;
abruptwithdrawalofACEinhibitioncanleadtoclinicaldeteriorationandshouldbeavoided.
AlthoughtheuseofanARNIinlieuofanACEinhibitorforHFrEFhasbeenfoundtobesuperior,forthose
patientsforwhomARNIisnotappropriate,continueduseofanACEinhibitorforallclassesofHFrEFremainsstrongly
advised.
JACC VOL. 70, NO. 6, 2017 Yancyetal. 785
AUGUST 8, 2017:776–803 2017ACC/AHA/HFSAHeartFailureFocusedUpdate
(continued)
TheuseofARBstoreducemorbidityandmortality 2013recommendationrepeatedforclarityinthis
I ARB:A isrecommendedinpatientswithpriororcurrent section.
symptomsofchronicHFrEFwhoareintolerantto
ACEinhibitorsbecauseofcoughorangioedema
(134–137,145,146).
SeeOnlineData ARBshavebeenshowntoreducemortalityandHFhospitalizationsinpatientswithHFrEFinlargeRCTs(134–137).
Supplements2and19. Long-termtherapywithARBsinpatientswithHFrEFproduceshemodynamic,neurohormonal,andclinicaleffects
consistentwiththoseexpectedafterinterferencewiththerenin-angiotensinsystem(145,146).UnlikeACE
inhibitors,ARBsdonotinhibitkininaseandareassociatedwithamuchlowerincidenceofcoughandangioedema,
althoughkininaseinhibitionbyACEinhibitorsmayproducebeneficialvasodilatoryeffects.
PatientsintoleranttoACEinhibitorsbecauseofcoughorangioedemashouldbestartedonARBs;patients
alreadytoleratingARBsforotherindicationsmaybecontinuedonARBsiftheysubsequentlydevelopHF.ARBs
shouldbestartedatlowdosesandtitratedupward,withanattempttousedosesshowntoreducetheriskof
cardiovasculareventsinclinicaltrials.ARBsshouldbegivenwithcautiontopatientswithlowsystemicblood
pressure,renalinsufficiency,orelevatedserumpotassium(>5.0mEq/L).AlthoughARBsarealternativesfor
patientswithACEinhibitor–inducedangioedema,cautionisadvisedbecausesomepatientshavealsodeveloped
angioedemawithARBs.
Head-to-headcomparisonsofanARBversusARNIforHFdonotexist.ForthosepatientsforwhomanACE
inhibitororARNIisinappropriate,useofanARBremainsadvised.
InpatientswithchronicsymptomaticHFrEFNYHAclass NEW:Newclinicaltrialdatanecessitatedthis
I ARNI:B-R IIorIIIwhotolerateanACEinhibitororARB, recommendation.
replacementbyanARNIisrecommendedtofurther
reducemorbidityandmortality(138).
SeeOnlineData BenefitsofACEinhibitorswithregardtodecreasingHFprogression,hospitalizations,andmortalityratehavebeen
Supplements1and18. shownconsistentlyforpatientsacrosstheclinicalspectrum,fromasymptomatictoseverelysymptomaticHF.
SimilarbenefitshavebeenshownforARBsinpopulationswithmild-to-moderateHFwhoareunabletotolerate
ACEinhibitors.Inpatientswithmild-to-moderateHF(characterizedbyeither1)mildlyelevatednatriureticpeptide
levels,BNP[B-typenatriureticpeptide]>150pg/mLorNT-proBNP[N-terminalpro-B-typenatriuretic
peptide]$600pg/mL;or2)BNP$100pg/mLorNT-proBNP$400pg/mLwithapriorhospitalizationinthe
preceding12months)whowereabletotoleratebothatargetdoseofenalapril(10mgtwicedaily)andthen
subsequentlyanARNI(valsartan/sacubitril;200mgtwicedaily,withtheARBcomponentequivalenttovalsartan
160mg),hospitalizationsandmortalityweresignificantlydecreasedwiththevalsartan/sacubitrilcompound
comparedwithenalapril.ThetargetdoseoftheACEinhibitorwasconsistentwiththatknowntoimprove
outcomesinpreviouslandmarkclinicaltrials(129).ThisARNIhasbeenapprovedforpatientswithsymptomatic
HFrEFandisintendedtobesubstitutedforACEinhibitorsorARBs.HFeffectsandpotentialoff-targeteffectsmay
becomplexwithinhibitionoftheneprilysinenzyme,whichhasmultiplebiologicaltargets.UseofanARNIis
associatedwithhypotensionandalow-frequencyincidenceofangioedema.Tofacilitateinitiationandtitration,the
approvedARNIisavailablein3dosesthatincludeadosethatwasnottestedintheHFtrial;thetargetdoseusedin
thetrialwas97/103mgtwicedaily(147).Clinicalexperiencewillprovidefurtherinformationabouttheoptimal
titrationandtolerabilityofARNI,particularlywithregardtobloodpressure,adjustmentofconcomitantHF
medications,andtherarecomplicationofangioedema(14).
ARNIshouldnotbeadministeredconcomitantlywith NEW:Availableevidencedemonstratesapotential
III:Harm B-R ACEinhibitorsorwithin36hoursofthelastdoseofan signalofharmforaconcomitantuseofACEinhibitors
ACEinhibitor(148,149). andARNI.
SeeOnlineDataSupplement3. Oralneprilysininhibitors,usedincombinationwithACEinhibitorscanleadtoangioedemaandconcomitantuseis
contraindicatedandshouldbeavoided.AmedicationthatrepresentedbothaneprilysininhibitorandanACE
inhibitor,omapatrilat,wasstudiedinbothhypertensionandHF,butitsdevelopmentwasterminatedbecauseofan
unacceptableincidenceofangioedema(148,149)andassociatedsignificantmorbidity.Thisadverseeffectwas
thoughttooccurbecausebothACEandneprilysinbreakdownbradykinin,whichdirectlyorindirectlycancause
angioedema(149,150).AnARNIshouldnotbeadministeredwithin36hoursofswitchingfromortoanACE
inhibitor.