Body Weight Change During and After€Hospitalization for Acute Heart€Failure:€Patient

13 Pages·2016·1.27 MB·English

JACC: HEART FAILURE VOL. 5, NO. 1, 2017
ª2017 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION ISSN 2213-1779/$36.00
PUBLISHED BY ELSEVIER http://dx.doi.org/10.1016/j.jchf.2016.09.012
FOCUS ISSUE: THINKING OUTSIDE THE BOX:
PATHOPHYSIOLOGY, PREDICTION, AND RISK
Body Weight Change During and
After Hospitalization for Acute
Heart Failure: Patient Characteristics,
Markers of Congestion, and Outcomes
Findings From the ASCEND-HF Trial
AndrewP.Ambrosy,MD,a,bLukaszP.Cerbin,MD,aPaulW.Armstrong,MD,cJavedButler,MD,MPH,MBA,d
AdrianColes,PHD,bAdamD.DeVore,MD,a,bMarkE.Dunlap,MD,eJustinA.Ezekowitz,MD,c
G.MichaelFelker,MD,a,bMaratFudim,MD,aStephenJ.Greene,MD,aAdrianF.Hernandez,MD,a,b
ChristopherM.O’Connor,MD,bPhilipSchulte,PHD,bRandallC.Starling,MD,fJohnR.Teerlink,MD,g
AdriaanA.Voors,MD,hRobertJ.Mentz,MDa,b
JACC:HEARTFAILURECME
Thisarticlehasbeenselectedasthemonth’sJACC:HeartFailureCME CMEObjectiveforThisArticle:Afterreadingthisarticle,thereadershould
activity,availableonlineathttp://www.acc.org/jacc-journals-cmeby beabletodiscuss:1)thecharacteristicsofpatientswithacuteheart
selectingtheCMEtabonthetopnavigationbar. failure(AHF);2)whatarethereasonswhypatientsmightnotexperience
adequateweightlossduringadmissionforAHF;and3)theclinical
AccreditationandDesignationStatement implicationsofweightchangesduringhospitalizationforAHF.
TheAmericanCollegeofCardiologyFoundation(ACCF)isaccreditedby CMEEditorDisclosures:Editor-in-Chief ChristopherO’Connor,MD,
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Mentz,MD,hasreceivedatravelscholarshipfromThoratec;
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issueofthejournal.
DeVore,MD,hasreceivedresearchsupportfromtheAmericanHeart
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followingtheinstructionsgivenattheconclusionoftheactivity. Johnson.Dr.ButlerhasreceivedresearchsupportfromtheNational
FromtheaDivisionofCardiology,DepartmentofMedicine,DukeUniversityMedicalCenter,Durham,NorthCarolina;bDivisionof
Cardiology, Duke Clinical Research Institute, Durham, North Carolina; cCanadian VIGOUR Centre, University of Alberta,
Edmonton,Alberta,Canada;dDivisionofCardiology,StonyBrookHeartInstitute,StonyBrook,NewYork;eDivisionofCardiology,
MetroHealthCampusofCaseWesternReserveUniversity,Cleveland,Ohio;fDivisionofCardiology,ClevelandClinic,Cleveland,
Ohio;gDivisionofCardiology,UniversityofSanFrancisco,SanFrancisco,California;andthehDivisionofCardiology,Universityof
Groningen,Groningen,theNetherlands.SciosandJohnson&JohnsonfundedtheASCEND-HFtrial.Dr.Armstronghasreceived
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2 Ambrosyetal. JACC: HEART FAILURE VOL. 5, NO. 1, 2017
BodyWeightChangeinAcuteHeartFailure JANUARY 2017:1–13
InstitutesofHealth(NIH),EuropeanUnion,andHealthResources Novartis,andThoratec;andhasreceivedbenefitsfromtheAmerican
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Novartis,OnoPharma,Takeda,Trevena,andZensun.Dr.DeVorehas Ingelheim,Cardio3Biosciences,Celladon,Merck,Novartis,Servier,
receivedresearchsupportfromAmgen,AmericanHeartAssociation, Torrent,andViforPharma.Dr.Teerlinkhasbeenaconsultantfor
andNovartis.Dr.EzekowitzhasreceivedconsultingfeesfromPfizer, Amgen,Bayer,Bristol-MyersSquibb,Cytokinetics,Gilead,Merck,
AbbottLaboratories,andServier;andresearchsupportfromAmgen Novartis,Relypsa,StealthBio-therapeutics,andZSPharma;andhas
andJohnson&Johnson.Dr.Felkerhasreceivedresearchfundingfrom receivedresearchfundingfromAmgen,Bayer,Bristol-MyersSquibb,
theNIH,Amgen,BGMedicine,Cytokinetics,Johnson&Johnson, Cardio3Biosciences,Medtronic,Novartis,St.Jude,andTrevena.Dr.
RocheDiagnosticCorp.,andOtsuka;andconsultingfeesfromAmgen, MentzhasreceivedresearchsupportfromAmgen,AstraZeneca,Bris-
Cytokinetics,Roche,Otsuka,andNovartis.Dr.Hernandezhasreceived tol-MyersSquibb,GlaxoSmithKline,Gilead,Novartis,Otsuka,and
consultingfeesfromSanofi,Johnson&Johnson,AstraZeneca,and ResMed;andhasreceivedhonorariafromThoratec.Allotherauthors
Corthera;researchsupportfromAmylinandScios/Johnson&Johnson; havereportedthattheyhavenorelationshipsrelevanttothecontents
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receivedresearchsupportfromOtsuka,RocheDiagnostics,BGMedi-
cine,CriticalDiagnostics,Astellas,Gilead,GEHealthcare,andResMed. CMETermofApproval
Dr.StarlinghasreceivedconsultingfeesfromNovartis,BioControl,
andMedtronic;hasownership/partnership/principalinCardiomems; Issuedate:January2017
hasreceivedresearchsupportfromtheNIH,Medtronic,Biotronik, Expirationdate:December31,2017
EuropeanUnion,andHealthResourcesServiceAdministration;andisaconsultanttoAmgen,Bayer,BGMedicine,Cardiocell,
Celladon,Gambro,GEHealthcare,Medtronic,Novartis,OnoPharma,Takeda,Trevena,andZensun.Dr.DeVorehasreceived
researchsupportfromAmgen,AmericanHeartAssociation,andNovartis.Dr.EzekowitzhasreceivedconsultingfeesfromPfizer,
AbbottLaboratories,andServier;andresearchsupportfromAmgenandJohnson&Johnson.Dr.Felkerhasreceivedresearch
fundingfromtheNIH,Amgen,BGMedicine,Cytokinetics,Johnson&Johnson,RocheDiagnosticCorp.,andOtsuka;andconsulting
feesfromAmgen,Cytokinetics,Roche,Otsuka,andNovartis.Dr.HernandezhasreceivedconsultingfeesfromSanofi,Johnson&
Johnson,AstraZeneca,andCorthera;researchsupportfromAmylinandScios/Johnson&Johnson.Dr.O’Connorhasreceived
consultingfeesfromNovellaandAmgen;hasownership/partnership/principalinBiscardia,LLC;andhasreceivedresearchsupport
fromOtsuka,RocheDiagnostics,BGMedicine,CriticalDiagnostics,Astellas,Gilead,GEHealthcare,andResMed.Dr.Starlinghas
receivedconsultingfeesfromNovartis,BioControl,andMedtronic;hasownership/partnership/principalinCardiomems;has
receivedresearchsupportfromtheNIH,Medtronic,Biotronik,Novartis,andThoratec;andhasreceivedbenefitsfromtheAmerican
BoardofInternalMedicine.Dr.Voorshasreceivedconsultancyfeesand/orresearchgrantsfromAlere,Amgen,Anexon,Bayer,
BoehringerIngelheim,Cardio3Biosciences,Celladon,Merck,Novartis,Servier,Torrent,andViforPharma.Dr.Teerlinkhasbeena
consultantforAmgen,Bayer,Bristol-MyersSquibb,Cytokinetics,Gilead,Merck,Novartis,Relypsa,StealthBio-therapeutics,andZS
Pharma;andhasreceivedresearchfundingfromAmgen,Bayer,Bristol-MyersSquibb,Cardio3Biosciences,Medtronic,Novartis,St.
Jude,andTrevena.Dr.MentzhasreceivedresearchsupportfromAmgen,AstraZeneca,Bristol-MyersSquibb,GlaxoSmithKline,
Gilead,Novartis,Otsuka,andResMed;andhasreceivedhonorariafromThoratec.Allotherauthorshavereportedthattheyhaveno
relationshipsrelevanttothecontentsofthispapertodisclose.AnthonyDeMaria,MD,servedasGuestEditorforthispaper.
ManuscriptreceivedMay2,2016;revisedmanuscriptreceivedAugust15,2016,acceptedSeptember22,2016.
JACC: HEART FAILURE VOL. 5, NO. 1, 2017 Ambrosyetal. 3
JANUARY 2017:1–13 BodyWeightChangeinAcuteHeartFailure
Body Weight Change During and
After Hospitalization for Acute
Heart Failure: Patient Characteristics,
Markers of Congestion, and Outcomes
Findings From the ASCEND-HF Trial
AndrewP.Ambrosy,MD,a,bLukaszP.Cerbin,MD,aPaulW.Armstrong,MD,cJavedButler,MD,MPH,MBA,d
AdrianColes,PHD,bAdamD.DeVore,MD,a,bMarkE.Dunlap,MD,eJustinA.Ezekowitz,MD,c
G.MichaelFelker,MD,a,bMaratFudim,MD,aStephenJ.Greene,MD,aAdrianF.Hernandez,MD,a,b
ChristopherM.O’Connor,MD,bPhilipSchulte,PHD,bRandallC.Starling,MD,fJohnR.Teerlink,MD,g
AdriaanA.Voors,MD,hRobertJ.Mentz,MDa,b
ABSTRACT
OBJECTIVESThisstudysoughttoexaminetherelationshipsbetweenin-hospitalandpost-dischargebodyweight
changesandoutcomesamongpatientshospitalizedforacuteheartfailure(AHF).
BACKGROUND BodyweightchangesduringandafterhospitalizationforAHFandtherelationshipswith
outcomeshavenotbeenwellcharacterized.
METHODSAposthocanalysiswasperformedoftheASCEND-HF(AcuteStudyofClinicalEffectivenessofNesiritideand
DecompensatedHeartFailure)trial,whichenrolledpatientsadmittedforAHFregardlessofejectionfraction.In-hospitalbody
weightchangewasdefinedasthedifferencebetweenbaselineanddischarge/day10,whereaspost-dischargebodyweight
changewasdefinedasthedifferencebetweendischarge/day10andday30.Spearmanrankcorrelationsofweightchange,
urineoutput(UOP),anddyspneareliefasassessedbya7-pointLikertscalearedescribed.LogisticandCoxproportional
hazardsregressionwasusedtoevaluatetherelationshipbetweenweightchangeandoutcomes.
RESULTS Studyparticipantswithcompletebodyweightdata(n¼4,172)hadameanageof65(cid:2)14years,and66%weremale.
Ischemicheartdiseasewasreportedin60%ofpatientsandtheaverageejectionfractionwas30(cid:2)13%.Themedianchangein
bodyweightwas(cid:3)1.0kg(interquartilerange:(cid:3)2.1to0.0kg)at24hand(cid:3)2.3kg(interquartilerange:(cid:3)5.0to(cid:3)0.7kg)by
discharge/day10.Athour24,therewasaweakcorrelationbetweenchangeinbodyweightandUOP(r¼(cid:3)0.381),andminimal
correlationbetweenbodyweightchangeanddyspnearelief(r¼(cid:3)0.096).Afterriskadjustment,increasingbodyweightduring
hospitalizationwasassociatedwitha16%increaseperkginthelikelihoodof30-daymortalityorHFreadmissionforpatients
showingweightloss#1kgorweightgainduringhospitalization(oddsratioperkgincrease1.16,95%confidenceinterval[CI]:1.09
to1.27;p<0.001).Amongthesubsetofpatientsexperiencing>1-kgincreaseinbodyweightpost-discharge,increasingbody
weightwasassociatedwithhigherriskof180-daymortality(hazardratioperkgincrease1.16;95%CI:1.09to1.23;p<0.001).
CONCLUSIONS Asubstantialnumberofpatientsexperiencedminimalweightlossorfrankweightgaininthecontextofan
AHFtrial,andincreasingbodyweightinthissubsetofpatientswasindependentlyassociatedwithaworsepost-
dischargeprognosis. (JAmCollCardiolHF2017;5:1–13)©2017bytheAmericanCollegeofCardiologyFoundation.
T
here aremorethan1millionhospitalizations directed medical therapies, there have been few ad-
foracuteheartfailure(AHF)annuallyinthe vancesintheinpatientmanagementofAHF,andthe
UnitedStates,representing1%to2%ofallad- cornerstone of decongestion remains diuretics (5).
missions(1).Signsandsymptomsofcongestiondueto Despite the fundamental role congestion plays in
elevatedcardiacfillingpressuresarethemostcommon AHF, there is little consensus among clinicians with
precipitant for hospitalization and readmission (2,3). respect to assessing and grading congestion during
As a result, relieving congestion has traditionally hospitalization. Moreover, limited data exist
beenoneoftheprimarygoalsoftherapyduringhospi- regardingtheassociationbetweencongestion,symp-
talization(4).Althoughtheoutpatientmanagementof toms, changes in weight, and outcomes in patients
heartfailure(HF)hasbeentransformedbyguideline- followingahospitalizationforAHF.
4 Ambrosyetal. JACC: HEART FAILURE VOL. 5, NO. 1, 2017
BodyWeightChangeinAcuteHeartFailure JANUARY 2017:1–13
ABBREVIATIONS Elementsofthehistoryandphysicalexam, reported. Briefly, the ASCEND-HF trial was a global,
AND ACRONYMS body weight change, and net fluid balance prospective, randomized, double-blind, placebo-
mustultimatelybeintegratedintoacompre- controlled trial designed to examine the short- and
AHF=acuteheartfailure hensiveevaluationofvolumestatusinorder long-term efficacy and safety of nesiritide, a recom-
BUN=bloodureanitrogen
to make vital treatment decisions regarding binant natriuretic peptide. A total of 7,141 patients
CI=confidenceinterval the duration and intensity of therapy and hospitalizedforHFasevidencedbydyspneaatrestor
HF=heartfailure patient disposition. However, the accuracy withminimalactivity,$1accompanyingsign,and$1
LOS=lengthofstay andreproducibilityofsurrogatemeasuresof objective measure were randomized to nesiritide or
NT-proBNP=N-terminal congestion and their associations with post- placebo,inadditiontostandardtherapy,within24h
pro–B-typenatriureticpeptide discharge outcomes remain unclear (6–8). of the first intravenous HF-related treatment. Rele-
NYHA=NewYorkHeart Thus,theobjectiveofthissecondaryanalysis vant exclusion criteria included a high likelihood to
Association of the global ASCEND-HF (Acute Study of be discharged from the hospital in #24 h or a co-
sCr=serumcreatinine
Clinical Effectiveness of Nesiritide and morbid condition with an associated life expectancy
UOP=urineoutput Decompensated Heart Failure) trial was to of<6months.TheASCEND-HFtrialwasconductedin
systematically characterize the relationship between accordance with the Declaration of Helsinki, the
body weight change during hospitalization and protocolwasindependentlyapprovedbytheinstitu-
following discharge and patient characteristics, tional review board or ethics committee at each
markersofcongestion,andoutcomes. participating center, and written informed consent
wasobtainedfromallparticipants.
METHODS
STUDY DEFINITIONS AND ENDPOINTS. Patient weight
OVERVIEW. Thestudydesign(9)andprimaryresults wasroutinelycollectedaccordingtolocalpracticeas
(10) of the ASCEND-HF trial have been previously part of study assessments. In-hospital body weight
TABLE1 PatientCharacteristicsbyBodyWeightChangeFromBaselinetoDischarge/Day10
WeightChangeClassification*
AllPatients SignificantLoss ModerateLoss NoLoss Gain
(N¼4,172) (n¼957) (n¼1,819) (n¼1,068) (n¼328) pValue
Demographics
Age,yrs 67(56to76) 65(54to75) 68(57to77) 66(56to75) 67(57to76) <0.001
Female 1,436(34.4) 266(27.8) 615(33.8) 421(39.4) 134(40.9) <0.001
Race <0.001
White 2,214(53.1) 576(60.3) 996(54.8) 459(43.0) 183(55.8)
BlackorAfricanAmerican 686(16.4) 184(19.2) 258(14.2) 162(15.2) 82(25.0)
Asian 1,027(24.6) 118(12.3) 451(24.8) 403(37.7) 55(16.8)
Other 244(5.8) 78(8.2) 114(6.3) 44(4.1) 8(2.4)
BaselineBMI,kg/m2 27(24to32) 30(26to35) 27(24to32) 26(22to30) 28(24to32) <0.001
Leftventricularejectionfraction,previous12months 28(20to35) 25(20to37) 29(20to35) 27(20to35) 27(20to40) 0.132
BaselineSBP 122(110to139) 124(112to140) 123(110to138) 120(110to138) 120(110to138) 0.017
BaselineDBP 74(67to83) 76(67to87) 74(67to82) 74(69to82) 72(63to81) <0.001
Baselineheartrate,beats/min 82(72to95) 82(71to96) 82(72to95) 82(72to95) 80(70to92) 0.112
Baselineweight,kg 78(64to95) 87(74to106) 76(63to92) 70(58to86) 79(64to97) <0.001
Clinicalprofile
Orthopnea 3,215(77.1) 785(82.1) 1,433(78.8) 744(69.7) 253(77.1) <0.001
Rales>1/3uplungfields 0.384
Nopulmonarycongestion 516(12.4) 129(13.5) 217(11.9) 128(12.0) 42(12.8)
<1/3uplungfields 1,361(32.6) 333(34.8) 592(32.5) 332(31.1) 104(31.7)
$1/3uplungfields 2,295(55.0) 495(51.7) 1,010(55.5) 608(56.9) 182(55.5)
JVD 2,440(58.5) 609(63.7) 1,128(62.0) 521(48.8) 182(55.5) <0.001
Peripheraledema 3,122(74.8) 870(90.9) 1,381(75.9) 644(60.3) 227(69.2) <0.001
NYHAfunctionalclassification 0.001
Notassessed 722(17.3) 199(20.8) 309(17.0) 158(14.8) 56(17.1)
I 175(4.2) 39(4.1) 81(4.5) 41(3.8) 14(4.3)
II 669(16.0) 153(16.0) 275(15.1) 185(17.3) 56(17.1)
III 1,772(42.5) 389(40.6) 823(45.2) 428(40.1) 132(40.2)
IV 834(20.0) 177(18.5) 331(18.2) 256(24.0) 70(21.3)
Continuedonthenextpage
JACC: HEART FAILURE VOL. 5, NO. 1, 2017 Ambrosyetal. 5
JANUARY 2017:1–13 BodyWeightChangeinAcuteHeartFailure
changewasdefinedastheabsolutedifferencebetween than the 99th percentile were excluded. In-hospital
baselineanddischargeorday10,whicheveroccurred body weight change was categorized as significant
first,whereaspost-dischargebodyweightchangewas loss(i.e.,change<(cid:3)5kg),moderateloss(i.e.,(cid:3)5kg#
definedastheabsolutedifferencebetweendischarge/ change<(cid:3)1kg),noloss(i.e.,(cid:3)1kg#change<1kg),and
day 10 and day 30. Study participants with a body gain(i.e.,change$1kg).Dyspneareliefwasmeasured
weight change less than the 1st percentile or greater 24 h after enrollment using a self-reported 7-point
TABLE1 Continued
WeightChangeClassification*
AllPatients SignificantLoss ModerateLoss NoLoss Gain
(N¼4,172) (n¼957) (n¼1,819) (n¼1,068) (n¼328) pValue
Medicalhistory
Myocardialinfarction 1,478(35.4) 307(32.1) 674(37.1) 378(35.4) 119(36.3) 0.075
Atrialfibrillation/flutter 1,490(35.7) 380(39.7) 666(36.6) 331(31.0) 113(34.5) <0.001
Hypertension 3,005(72.0) 715(74.7) 1,311(72.1) 728(68.2) 251(76.5) 0.002
Diabetesmellitus 1,758(42.1) 430(44.9) 765(42.1) 407(38.1) 156(47.6) 0.003
Hyperlipidemia 1,751(42.0) 406(42.5) 795(43.7) 378(35.4) 172(52.4) <0.001
Smokinghistory <0.001
Currentsmoking 551(13.2) 132(13.8) 220(12.1) 146(13.7) 53(16.2)
Priorhistoryofsmoking 1,507(36.1) 368(38.5) 704(38.7) 306(28.7) 129(39.3)
Nohistoryofsmoking 2,112(50.6) 455(47.6) 895(49.2) 616(57.7) 146(44.5)
HistoryofICD/CRT 399(9.6) 104(10.9) 170(9.3) 90(8.4) 35(10.7) 0.257
Historyofcerebrovasculardisease 509(12.2) 129(13.5) 219(12.0) 97(9.1) 64(19.5) <0.001
Historyofperipheralarterialvasculardisease 452(10.8) 105(11.0) 198(10.9) 89(8.3) 60(18.3) <0.001
Medicationatbaseline
ACEI/ARB 2,557(61.3) 597(62.4) 1,122(61.7) 633(59.3) 205(62.5) 0.441
Beta-blockers 2,448(58.7) 558(58.4) 1,115(61.3) 566(53.0) 209(63.7) <0.001
MRAs(aldosteroneantagonists) 1,109(26.6) 270(28.2) 498(27.4) 270(25.3) 71(21.6) 0.075
Calciumchannelblockers 527(12.6) 119(12.4) 248(13.6) 107(10.0) 53(16.2) 0.007
Nitrates 976(23.4) 225(23.5) 451(24.8) 223(20.9) 77(23.5) 0.124
Digoxin 1,085(26.0) 232(24.3) 475(26.1) 298(27.9) 80(24.4) 0.267
Loopdiureticuse(dosesinfurosemideequivalents)
Loopdiuretics,chronicallybeforeQE 2,643(63.4) 646(67.6) 1,139(62.6) 622(58.3) 236(72.0) <0.001
Totalloopdiureticdose,chronicallypre-qualifying 40(40to80) 60(40to80) 40(40to80) 40(40to80) 40(40to100) <0.001
episode,mg
Loopdiuretics,QEtorandomization 3,736(89.6) 853(89.1) 1,627(89.4) 961(90.1) 295(89.9) 0.907
Loopdiureticdose,QEtorandomization 80(40to120) 80(40to120) 80(40to120) 60(40to80) 80(40to120) <0.001
Loopdiuretics,QEto24hpost-randomization 3,868(92.7) 905(94.6) 1,691(93.0) 971(90.9) 301(91.8) 0.014
Loopdiureticdose,QEto24hpost-randomization 140(80to215) 160(102to269) 140(80to200) 120(80to180) 140(100to220) <0.001
Laboratoryvalues
Baselinecreatinine,mg/dl 1.2(1.0to1.6) 1.3(1.0to1.7) 1.2(1.0to1.6) 1.2(1.0to1.5) 1.3(1.0to1.6) <0.001
BaselineGFR,ml/min 58(44to75) 59(43to74) 58(44to75) 60(46to76) 57(41to73) 0.023
BaselineBUN,mg/dl 25(18to38) 26(18to39) 26(18to40) 23(16to35) 27(19to41) <0.001
Baselinesodium,mmol/l 139(136to141) 139(136to141) 139(136to141) 139(136to141) 139(136to141) 0.294
Baselinehemoglobin,g/dl 13(11to14) 13(11to14) 13(11to14) 13(11to14) 13(11to14) 0.736
BaselineNT-proBNP,pg/ml 4,596 5,211 4,694 3,797 3,452 <0.001
(2,148to9,403) (2,744to10,581) (2,259to9,579) (1,772to7,902) (1,606to10,379)
BaselineBNP,pg/ml 976(524to1,850) 1,244(721to2,180) 988(523to1,775) 764(415to1,546) 914(527to1,891) <0.001
Clinicalcourse
ChangeinSBP(baselineto24h),mmHg (cid:3)10((cid:3)20to0) (cid:3)10((cid:3)20to0) (cid:3)9((cid:3)20to0) (cid:3)10((cid:3)20to0) (cid:3)9((cid:3)23to0) 0.470
ChangeinDBP(baselineto24h),mmHg (cid:3)6((cid:3)14to1) (cid:3)5((cid:3)14to2) (cid:3)6((cid:3)14to1) (cid:3)5((cid:3)13to0) (cid:3)6((cid:3)16to2) 0.820
Changeincreatinine(baselineto24h),mg/dl 0.0((cid:3)0.1to0.2) 0.0((cid:3)0.1to0.1) 0.0((cid:3)0.1to0.2) 0.0((cid:3)0.1to0.2) 0.0((cid:3)0.1to0.2) <0.001
Urinevolume(baselineto24h),ml 2,300 3,150 2,300 1,950 2,000 <0.001
(1,600to3,350) (2,100to4,500) (1,625to3,280) (1,400to2,638) (1,350to2,810)
LOS 5(3to8) 7(4to10) 5(3to7) 4(3to6) 4(3to7) <0.001
Valuesaremedian(interquartilerange)orn(%).*Significantloss:<(cid:3)5kg;moderateloss:(cid:3)5kgto(cid:3)1kg;noloss:(cid:3)1kgto1kg;gain:$1kg.
ACEI/ARB¼angiotensinconverting-enzymeinhibitor/angiotensinreceptorblocker;BMI¼bodymassindex;BNP¼B-typenatriureticpeptide;bpm¼beatsperminute;BUN¼bloodureanitrogen;
DBP¼diastolicbloodpressure;GFR¼glomerularfiltrationrate;ICD/CRT¼implantablecardioverterdefibrillator/cardiacresynchronizationtherapy;JVD¼jugularvenousdistension;LOS¼lengthofstay;
MRA¼mineralocorticoidreceptorantagonist;NT-proBNP¼N-terminalpro–B-typenatriureticpeptide;NYHA¼NewYorkHeartAssociation;QE¼qualifyingepisode;SBP¼systolicbloodpressure.
6 Ambrosyetal. JACC: HEART FAILURE VOL. 5, NO. 1, 2017
BodyWeightChangeinAcuteHeartFailure JANUARY 2017:1–13
categorical Likert scale (i.e., markedly worse ¼ (cid:3)3, (i.e., beta-blocker, angiotensin-converting enzyme
moderately worse ¼ (cid:3)2, minimally worse ¼ (cid:3)1, no inhibitor/angiotensin receptor blocker, mineralocor-
change¼0,minimallybetter¼1,moderatelybetter¼ ticoid receptor antagonist, digoxin, and inotropes),
2,andmarkedly better ¼3).Urine output (UOP)was loopdiuretics(i.e.,totalloopdiureticsinoralfurose-
measuredinmillilitersfrombaselinetohour24(11). mide equivalents from randomization to 24 h post-
The primary outcome of the ASCEND-HFtrialwas randomization), and treatment assignment (i.e.,
30-day all-cause mortality or HF hospitalization. nesiritidevs.placebo).Themethodofmultipleimpu-
Additional outcomes of interest for the present tationswasutilizedformissingdataforpre-specified
analysis were 30-day HF hospitalizations, all-cause covariates under the assumption that data were
mortality,andthecompositeofall-causemortalityor missing at random. Each adjustment variable had
all-cause hospitalization and 180-day all-cause mor- somedegreeofmissingness.Themajorityofthepre-
tality. An independent and blinded adjudication specifiedvariableshad<1%missingdata.Threevari-
committeedeterminedthecauseofallhospitalizations ableshadmorethan1%,but<10%,missingdata(Na;
anddeathsoccurringwithin30days.Hospitalization sCr;BUN).Inaddition,3variableshad>10%missing
forHFwasdefinedasadmissionforworseningsignsor data (ejection fraction 13.4%; NYHA functional class
symptomsofHFresultinginthenewadministrationof 17.3%; NT-proBNP 47.9%). Statistical analyses were
intravenous therapies, mechanical or surgical inter- performedusingSASsoftware,version9.4(SASInsti-
vention,orprovisionofultrafiltration,hemofiltration, tute,Cary,NorthCarolina).
ordialysisspecificallyforthemanagementofpersis- FUNDING AND MANUSCRIPT PREPARATION. Scios
tentorworseningHF. Inc. (Mountain View, California) provided financial
STATISTICAL ANALYSIS. All continuous data were and material support for the ASCEND-HF trial. Data-
reported as median (25th to 75th percentiles) and as base management and statistical analysis were per-
frequencies and percentages for categorical data. formed by the Duke Clinical Research Institute. The
Baseline patient characteristics including de- authors take responsibility for the manuscript’s
mographics, medical history, laboratory values, and integrity,andhadcompletecontrolandauthorityover
medication use were compared by in-hospital body itspreparationandthedecisiontopublish.
weight change. Categorical variables were assessed
RESULTS
usingthechi-squaretestorFisherexacttest,whereas
continuousvariableswereevaluatedusinganalysisof
STUDY POPULATION. A total of 4,172 patients had
varianceorKruskal-Wallistesting,asappropriate.The
body weight measured at baseline and discharge/
relationshipbetweenin-hospitalbodyweightchange,
day10.Studyparticipantshadameanageof65(cid:2)14
dyspnea relief, and UOP was evaluated using the
years,65%weremale,and47%self-identifiedasnon-
Spearman rank correlation. The association between
white(Table1).Ischemicheartdiseasewasreportedin
in-hospitalbodyweightchangeand30-dayoutcomes
60%ofpatients,andtheaverageejectionfractionwas
was assessed using logistic regression. Cox propor-
30 (cid:2) 13%. The prevalence of cardiac and noncardiac
tional hazards regression was utilized to assess the
comorbiditieswashigh,andpatientswerewelltreated
association between in-hospital body weight change
withguideline-directedmedicaltherapies.
and 180-day mortality, similarly for post-discharge
CLINICAL COURSE OF BODY WEIGHT CHANGE. The
body weight change. To investigate the relationship
medianchangeinbodyweightwas(cid:3)1.0kg((cid:3)2.1to0.0)
betweenpost-dischargebodyweightchangeand180-
athour24and(cid:3)2.3kg((cid:3)5.0to(cid:3)0.7)atdischarge/day
daymortality,thereferencetimefor180-daymortal-
10 (Figure 1). Overall, 67% of patients (n ¼ 2,776)
itywasresettothedateofdischarge/day10.Piecewise
showedsignificant(i.e.,change<(cid:3)5kg)ormoderate
linearsplineswereusedtomodelthenonlinearrela-
weightloss(i.e.,(cid:3)5kg#change<(cid:3)1kg)duringhos-
tionship between body weight change and both 30-
pitalization,whereas26%(n¼1,068)showednoloss
and180-dayclinicaloutcomes.Modelswereadjusted
(i.e.,(cid:3)1kg#change<1kg)and8%(n¼328)experi-
for potential confounders including age, sex, body
enced weight gain (i.e., change $1 kg). Between
massindex,ejectionfraction),NewYorkHeartAsso-
discharge/day 10 and day 30, study participants re-
ciation (NYHA) functional class, heart rate, systolic
portedachangeofþ0.2kg((cid:3)1.3to2.0).At30days,26%
bloodpressure,Na,serumcreatinine(sCr),bloodurea
ofpatients(n¼945)showedsignificantormoderate
nitrogen (BUN), B-type natriuretic peptide (BNP)/
weightloss,whereas34%(n¼1,211)showednoloss,
N-terminalpro-BNP(NT-proBNP),comorbidities(cor-
onary artery disease, atrialfibrillation,diabetesmel- and40%(n¼1,438)experiencedweightgain.
litus type II, chronic kidney disease, chronic IN-HOSPITALBODYWEIGHTCHANGEANDPATIENT
obstructivepulmonarydisease),baselinemedications CHARACTERISTICS. Patientsexperiencingnoweight
JACC: HEART FAILURE VOL. 5, NO. 1, 2017 Ambrosyetal. 7
JANUARY 2017:1–13 BodyWeightChangeinAcuteHeartFailure
FIGURE1 In-HospitalBodyWeightChange
A
B
Thedistributionof(A)absoluteand(B)relativein-hospitalbodyweightchangeathour24,discharge/day10,andday30.
loss or weight gain during hospitalization tended lower natriuretic peptide levels at baseline, there
to self-identify as non-white and were more likely were no clinically significant between-group differ-
to be female. This subgroup of patients also had ences in the rate of prescription or dose of loop di-
a higher prevalence of cardiac and noncardiac uretics. With the exception of beta-blocker
medical comorbidities. Although patients ex- usage, there was no significant difference between
periencing no weight loss or weight gain had less groups in utilization of guideline-directed medical
severe signs and symptoms of volume overload and therapies.
8 Ambrosyetal. JACC: HEART FAILURE VOL. 5, NO. 1, 2017
BodyWeightChangeinAcuteHeartFailure JANUARY 2017:1–13
hospitalization, increasing body weight during hos-
TABLE2 CorrelationBetweenBodyWeightChangeand
pitalization was associated with a 16% increase (per
SurrogatesofCongestionat24H
kg) in the likelihood of 30-day mortality or HF read-
Variable1 Variable2 r* pValue
mission after risk adjustment (odds ratio per kg in-
Changeinbodyweight,kg Dyspnearelief (cid:3)0.09600 <0.0001 crease1.16,95%CI:1.09to1.27;p<0.001)(Table3).
Changeinbodyweight,kg Urineoutput (cid:3)0.38100 <0.0001
The association between in-hospital body weight
Dyspnearelief Urineoutput 0.11100 <0.0001
change and 180-day mortality did not reach the
*Spearmanrankcorrelationcoefficient. threshold for statistical significance (p ¼ 0.086) in
thissubsetofpatientsafterriskadjustment(Table4).
CORRELATIONBETWEENSURROGATEMARKERSOF By contrast, there was no statistically significant as-
CONGESTION. Athour24,therewasaweakcorrela- sociation between in-hospital body weight change
and 30-day and 180-day outcomes among patients
tion between change in body weight and UOP
(r ¼ (cid:3)0.381) and minimal correlation between body reportingweightloss>1kg.
weightchangeanddyspnearelief(r¼(cid:3)0.096)(Table2, Among the subset of patients experiencing >1-kg
increase in body weight post-discharge, increasing
Figures2to4).Inaddition,therewasminimalcorre-
lationbetweendyspneareliefandUOP(r¼0.111).The body weight was associated with a 16% increase
overlapping 95% confidence intervals (CIs) for the (per kg) in the risk of 180-day mortality after risk
adjustment(hazardratioperkgincrease1.16,95%CI:
meantrajectoryofsCrandBUNduringhospitalization
1.09to1.23;p<0.001)(Table5).Bycontrast,forpa-
andpost-dischargesuggestthatthesemarkersdidnot
tients reporting <1-kg weight gain or weight loss,
differ over time by in-hospital body weight change
decreasing body weight was associated with greater
(Figures5and6).
ASSOCIATION BETWEEN BODY WEIGHT CHANGE riskofdeathatday180(hazardratioperkgincrease
AND OUTCOMES. The relationship between body 0.93;95%CI:0.89to0.97).
weight change and 30-day and 180-day events was
nonlinear—demonstrating a general decrease in risk DISCUSSION
for patients who lost weight and an increase in risk
for patients who gained weight. Among patients This study found that more than 30% of patients
with weight loss #1 kg or weight gain during admitted for a primary diagnosis of AHF
FIGURE2 BodyWeightChangeandDyspnea
Thecorrelationbetweenin-hospitalbodyweightchangeanddyspneareliefat24h.
JACC: HEART FAILURE VOL. 5, NO. 1, 2017 Ambrosyetal. 9
JANUARY 2017:1–13 BodyWeightChangeinAcuteHeartFailure
FIGURE3 BodyWeightChangeandUOP
Thecorrelationbetweenin-hospitalbodyweightchangeandurineoutput(UOP)at24h.
experienceminimalweightlossorevenfrankweight and dosing of loop diuretics was comparable to
gain during hospitalization. Despite reporting fewer patients experiencing more marked in-hospital
signs and symptoms of congestion and lower weight loss. Although there was a weak correlation
natriureticpeptidelevelsatbaseline,theprescription between in-hospital body weight change and UOP,
FIGURE4 UOPandDyspnea
Thecorrelationbetweenurineoutput(UOP)anddyspneareliefat24h.
10 Ambrosyetal. JACC: HEART FAILURE VOL. 5, NO. 1, 2017
BodyWeightChangeinAcuteHeartFailure JANUARY 2017:1–13
FIGURE5 sCrandChangeinBodyWeight
Serumcreatinine(sCr)overtimebyin-hospitalbodyweightchange.CI¼confidenceinterval.
FIGURE6 BUNandChangeinBodyWeight
Bloodureanitrogen(BUN)overtimebyin-hospitalbodyweightchange.CI¼confidenceinterval.