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  Pleasecitethisarticleinpressas:OkazakiH,etal.Newscoringsystem(APACHE-HF)forpredictingadverseoutcomesinpatientswithacuteheartfailure:EvaluationoftheAPACHEIIandModifiedAPACHEIIscoringsystems.JCardiol(2014),http://dx.doi.org/10.1016/j.jjcc.2014.03.002 ARTICLE IN PRESS G Model  JJCC-870;No.ofPages9 JournalofCardiologyxxx(2014)xxx–xxx ContentslistsavailableatScienceDirect  Journal   of    Cardiology  journalhomepage:www.elsevier.com/locate/jjcc Original   article New   scoring   system   (APACHE-HF)   for   predicting   adverse   outcomes   inpatients   with   acute   heart   failure:   Evaluation   of    the   APACHE   II   andModified   APACHE   II   scoring   systems Hirotake   Okazaki   (MD) a ,   Akihiro   Shirakabe   (MD,   PhD) a , ∗ ,   Noritake   Hata   (MD,   PhD) a ,Masanori   Yamamoto   (MD,   PhD) a ,   Nobuaki   Kobayashi   (MD,   PhD) a ,Takuro   Shinada   (MD,   PhD) a ,   Kazunori   Tomita   (MD) a ,   Masafumi   Tsurumi   (MD) a ,Masato   Matsushita   (MD) a ,   Yoshiya   Yamamoto   (MD) a ,   Shinya   Yokoyama   (MD,   PhD) a ,Kuniya   Asai   (MD,   PhD) b ,   Wataru   Shimizu   (MD,   PhD,   FJCC) b a DivisionofIntensiveCareUnit,ChibaHokusohHospital,NipponMedicalSchool,Chiba,Japan b DepartmentofCardiovascularMedicine,NipponMedicalSchool,Tokyo,Japan a   r   t   i   c   l   e   i   n   f   o  Articlehistory: Received2December2013Receivedinrevisedform4February2014Accepted19February2014Availableonlinexxx Keywords: AcuteheartfailuresyndromeMortalityPrognosisScoring a   b   s   t   r   a   c   t Background:   No   scoring   system   for   assessing   acute   heart   failure   (AHF)   hasbeen   reported. Methods   and   results:   Data   for   824   AHF   patients   were   analyzed.   The   subjects   were   divided   into   an   alive( n   =   750)   and   adead   group   ( n   =74).   We   constructed   apredictive   scoring   system   based   oneight   significantAPACHE   IIfactors   in   the   alive   group   [mean   arterial   pressure   (MAP),   pulse,   sodium,   potassium,   hematocrit,creatinine,   age,   and   Glasgow   Coma   Scale   (GCS);   giving   each   one   point],   defined   as   the   APACHE-HF   score.Thepatients   were   assigned   to   five   groups   bythe   APACHE-HF   score   [Group   1:   point   0( n   =   70),   Group   2:points   1   and   2   ( n   =   343),   Group   3:   points   3and4( n =   294),   Group   4:   points   5and   6( n   =106),   and   Group5:   points   7   and   8   ( n   =   11)].   A   higher   optimal   balance   was   observed   inthe   APACHE-HF   between   sensitivityand   specificity   [87.8%,   63.9%;   area   under   the   curve   (AUC)   =   0.779]   at2.5   points   than   in   the   APACHE   II(47.3%,   67.3%;   AUC   =   0.558)   at   17.5   points.   The   multivariate   Cox   regression   model   identified   belongingto   Group   5[hazard   ratio   (HR):   7.764,   95%   confidence   interval   (CI)   1.586–38.009],   Group   4   (HR:   6.903,95%CI   1.940–24.568)   or   Group   3   (HR:   5.335,   95%CI   1.582–17.994)   to   be   anindependent   predictor   of 3-year   mortality.   The   Kaplan–Meier   curves   revealed   apoorer   prognosis,   including   all-cause   death   andHFevents   (death,   readmission-HF),   in   Group   5and   Group   4than   in   the   other   groups,   in   Group   3than   inGroup   2or   Group   1,   and   in   Group   2   than   in   Group   1. Conclusions:   The   new   scoring   system   including   MAP,   pulse,   sodium,   potassium,   hematocrit,   creatinine,age,   and   GCS   (APACHE-HF)   can   be   used   to   predict   adverse   outcomes   of    AHF.©2014   Published   byElsevier   Ltd   on   behalf    of     Japanese   College   of    Cardiology. Introduction TheAcutePhysiologyandChronicHealthEvaluation(APACHE)scoringsystemwasfirstestablishedin1981topredicttheprogno-sisinpatientsreceivingintensivecare(Fig.1A)[1].Subsequently, theAPACHEII,III,andIVsystemswerepublishedoverthepast20years[2–4]. ∗ Correspondingauthorat:DivisionofIntensiveCareUnit,ChibaHokusohHospi-tal,   NipponMedicalSchool,1715Kamagari,Inzai,Chiba270-1694,Japan.Tel.:+81476991111;fax:+81476991911. E-mailaddress: s6042@nms.ac.jp(A.Shirakabe). TheAPACHEIIsystemconsistsofthreeparts,includingtheacutephysiologyscore,chronichealthpoints,andagepoints.ThetotalnumberofpointsforthethreepartsiscalculatedastheAPACHEIIscore.Thisscorehasbeenreportedtobepredictiveofadverseoutcomesinpatientsrequiringintensivecare,suchasthosewithrespiratorydisease,severepancreatitis,orseveresepsis[5–9].However,thisscoringsysteminvolvesmanyfactors, asdescribedabove;therefore,itcannotbeappliedeasily,andclinicianshesitatetouseitineverypatient.Inpreviousobservationalstudies,variouspredictivefactorsfordetectingadverseoutcomesinacuteheartfailure(AHF)patientshavebeenidentified,includingage[10],anemia[11],renalinsuf- ficiency[12,13],poorliverfunction[14],highuricacid[15],high lactate[16],lowcholesterol[12,16],elevatedbloodglucose[17], http://dx.doi.org/10.1016/j.jjcc.2014.03.0020914-5087/©2014PublishedbyElsevierLtdonbehalfofJapaneseCollegeofCardiology.  Pleasecitethisarticleinpressas:OkazakiH,etal.Newscoringsystem(APACHE-HF)forpredictingadverseoutcomesinpatientswithacuteheartfailure:EvaluationoftheAPACHEIIandModifiedAPACHEIIscoringsystems.JCardiol(2014),http://dx.doi.org/10.1016/j.jjcc.2014.03.002 ARTICLE IN PRESS G Model  JJCC-870;No.ofPages92   H.Okazakietal./JournalofCardiologyxxx(2014)xxx–xxx Fig.1. Definitionofeachscoringsystem.(A)TheAPACHEIIscoringsystemwas   definedinthisstudy.(B)TheModifiedAPACHEIIscoringsystemwasconstructedbasedonthesignificantAPACHEIIfactorsinthealivegroup[meanbloodpressure(BP),sodium,potassium,creatinine,age,andGlasgowComaScale(GCS)]andwasgivenpointsbasedonthe   APACHEIIsystem.(C)TheAPACHE-HFscoringsystemwasconstructedbasedonthesignificantAPACHEIIfactorsinthealivegroup(meanBP,pulse,sodium,potassium,creatinine,hematocrit,age,andGCS)andwasgivenonepointforeachcut-offvalue.Thecut-offvalueforeachfactorwasdefinedbythereceiver-operatingcharacteristic(ROC)   curveasfollows:meanBP[91.5mmHg,areaundertheROCcurve(AUC)=0.678,  p <0.001),pulse(110.5beats/min,AUC=0.594,  p =0.008),sodium(137.5mmol/L,AUC   =0.613,  p =0.001),potassium(4.85mmol/L,AUC=0.601,  p =0.004),hematocrit(36.95mg/dL,AUC=0.617,  p =0.001),creatinine(1.475mg/dL,AUC=0.676,  p <0.001),age(71.5   years,AUC=0.572,  p =0.042)andGCS(13.5,AUC=0.567,  p =0.058)].  Pleasecitethisarticleinpressas:OkazakiH,etal.Newscoringsystem(APACHE-HF)forpredictingadverseoutcomesinpatientswithacuteheartfailure:EvaluationoftheAPACHEIIandModifiedAPACHEIIscoringsystems.JCardiol(2014),http://dx.doi.org/10.1016/j.jjcc.2014.03.002 ARTICLE IN PRESS G Model  JJCC-870;No.ofPages9 H.Okazakietal./JournalofCardiologyxxx(2014)xxx–xxx 3 hyperkalemia[12],hyponatremia[18],brain-typenatriureticpep- tide(BNP),andleftventricularejectionfraction.WithrespecttopatientswithAHF,nopredictivescoringsystemhasbeenestab-lished,andevaluationsoftheAPACHEIIsystemhaverarelybeenreported.We   thereforeevaluatedtheefficacyoftheAPACHEIIandournewlyestablishedscoringsystemforAHFpatients. Methods Subjects Clinicaldatawerecollectedfrom824patientswithAHFwhowereadmittedtotheintensivecareunitatChibaHokusohHospital,NipponMedicalSchoolbetweenJanuary2000andJuly2012.AHFwasdefinedaseithernew-onsetHFordecompensationofchronicHFwithsymptomssufficienttowarranthospitalization[19].HF wasdiagnosedaccordingtotheFraminghamcriteriaforaclinicaldiagnosisofHFbasedonthesatisfactionoftwomajorcriteriaoronemajorandtwominorcriteria[20].AllpatientshadaNewYork HeartAssociation(NYHA)functionalclassofeitherClassIIIorIV.AHFpatientswithoneofthefollowingcriteriawereadmittedtotheintensivecareunit(ICU)byphysician’sdecisioninthepresentstudy:(1)patientswhoneedhighprojectileoxygeninhalation(includingmechanicalsupport)totreatorthopnea,(2)patientswhoneedintropeormechanicalsupportwithlowbloodpressure,(3)patientswhoneedmanytypesofdiureticstoimprovethegeneralorlungedema.PatientswithHFcausedbyacutecoronarysyn-dromewereexcludedfromthestudy.Alldatawereretrospectivelyretrievedfromhospitalmedicalrecords. Procedure AHFpatientsweredividedintotwogroupsaccordingtoin-hospitalmortality:thealivegroup( n =750)andthedeadgroup( n =74).WeestablishedtwonewscoringsystemsforAHFcomparingthetwogroups.First,wecomparedtheAPACHEIIscorebetweenthetwogroupsusingaunivariateanalysis.Factorsassociatedwithsignificantlymorepointsinthealivegroupwereselectedtocon-structthenewscoringsystem.ThetotalscoreofthesignificantfactorsinthealivegroupwasdefinedastheModifiedAPACHEIIscore.Second,wecomparedthedataforAPACHEIIfactorsbetweenthetwogroupsusingaunivariateanalysis.We   thenscoredthetotalnumberoffactorsspecifictosurvivaldischarge(givingonepointforeachfactor),definedastheAPACHE-HFscore.Thecut-off valueforeachfactortogiveonepointwasdefinedbythereceiver-operatingcharacteristic(ROC)curvesforthein-hospitalmortalityofeachfactor.We   determinedthescores(APACHEII,ModifiedAPACHEII,andAPACHE-HF)ineachpatientbasedondataobtainedatadmission,accordingtoapreviousreport[2],andevaluatedthesensitivity, specificity,andpositiveandnegativepredictivevaluefordifferen-tiatingthealiveanddeadgroups.ROCcurveswerecalculatedtopredicttheoptimalcut-offvalues.Furthermore,themid-termprognosiswasevaluatedintermsof all-causedeathandHFeventsdefinedasall-causedeathorread-missionduetoHF.Thepatientswereclinicallyfollowedupinaroutineoutpatientclinic.Forthepatientsfollowedupatotherinsti-tutes,thefinalprognosiswasdeterminedviatelephonecontact.Thepatientswereassignedtoanothertwogroupsaccordingtothecut-offvaluesoftheROCcurvesfortheAPACHEII,ModifiedAPACHEII,andAPACHE-HFscores.ThesurvivalrateswerethenanalyzedusingKaplan–MeiercurvesaccordingtotheAPACHEII,ModifiedAPACHEII,andAPACHE-HFscores.Theprognosticvalueof theAPACHE-HFscoreinthesegroupscomparedwiththatobservedinthegroupwithlowestpointasthereferentwasassessedusingaCoxregressionhazardmodel. Statisticalanalysis AlldatawerestatisticallyanalyzedusingtheSPSS20.0Jsoftwareprogram(SPSSJapanInstitute,Tokyo,Japan).Allnumericaldatawereexpressedasthemean ± standarddeviationormedian(rangeor25–75%interquartilerange)dependingonnormality.UnpairedStudent’s t  -testortheMann–Whitney U  -testwasusedtocomparethetwogroups.Normalitywas   assessedusingtheShapiro–Wilk W  -test.Comparisonsofallproportionsweremadeusingachi-squareanalysis.A  p -valueoflessthan0.05wasconsideredtobestatisti-callysignificant.ROCcurveswerecalculatedtopredictthecut-off values,andthesensitivity,specificityandarea,undertheROCcurve(AUC)weredetermined.Thesurvivalrateswereanalyzedbetweenthegroupsassignedbasedonthecut-offvaluesoftheROCcurvesforeachscoringsystemusingKaplan–Meiercurves,andsignificantdifferenceswerecalculatedusingthelog-ranktest.ACoxregres-sionanalysiswasperformedtoobtainthehazardratios(HRs)for90-daymortalityand90-dayHFevents.Subsequently,amultivari-ateanalysiswasperformedusingthevariableswitha  p -valueof <0.05intheunivariateanalysistoexaminetheirindependentasso-ciationswith90-daymortalityand90-dayHFevents.A  p -valueof lessthan0.05was   consideredtobestatisticallysignificant. Ethicalconcerns TheinstitutionalreviewboardatChibaHokusohHospital,Nip-ponMedicalSchoolapprovedthestudyprotocol. Results Patientcharacteristics Therelationshipbetweenthetreatment,includingrespiratorysupportandmedicationsprescribedduringthefirst5days,andin-hospitalmortalityareshowninTable1.Thepatientcohort included67.2%malesubjects,withamedianageof74years.Thesystolicbloodpressure(BP)valuesweresignificantlylower,thenumberofNYHAclassIVpatientswas   significantlyhigher,theserumhemoglobinlevelsweresignificantlylower,theserumurinaryacidlevelsweresignificantlyhigher,theserumBUNlev-elsweresignificantlyhigher,theserumC-reactiveprotein(CRP)levelsweresignificantlyhigher,andtheserumBNPlevelsweresignificantlyhigherinthedeadgroupthaninthealivegroup. DefinitionoftheModifiedAPACHEIIandAPACHE-HFscoring systems RegardingtheAPACHEIIscore,thefollowingsixfactorsweresignificantlydifferentbetweenthealivegroupandthedeadgroup:meanBP,sodium,potassium,creatinine,age,andGlasgowComaScale(GCS)(Table2).We   constructedapredictivescoringsystembasedonthesignificantAPACHEIIfactorsinthealivegroup(meanBP,sodium,potassium,creatinine,age,andGCS;givingpointsbasedontheAPACHEIIsystem),definedastheModifiedAPACHEIIscore(Fig.1B). Ontheotherhand,thefollowingeightfactorsweresig-nificantlydifferentbetweenthealivegroupanddeadgroup:meanBP,pulse,sodium,potassium,hematocrit,creatinine,age,andGCS(Table3).We   constructedapredictivescoringsys-tembasedonthesignificantAPACHEIIfactorsinthealivegroup(meanBP,pulse,sodium,potassium,creatinine,hemat-ocrit,age,andGCS;givingonepointbasedoneachcut-offvalue),definedastheAPACHE-HFscore(Fig.1C).Thecut-offvaluesfor  Pleasecitethisarticleinpressas:OkazakiH,etal.Newscoringsystem(APACHE-HF)forpredictingadverseoutcomesinpatientswithacuteheartfailure:EvaluationoftheAPACHEIIandModifiedAPACHEIIscoringsystems.JCardiol(2014),http://dx.doi.org/10.1016/j.jjcc.2014.03.002 ARTICLE IN PRESS G Model  JJCC-870;No.ofPages94   H.Okazakietal./JournalofCardiologyxxx(2014)xxx–xxx  Table   1 Relationshipsbetweenthepatientcharacteristicsandin-hospitalsurvival.CharacteristicTotal( n =824)Deadgroup( n =74)Alivegroup( n =750)  p -ValueAge(years)74(65–80)74(64–80)76(70–81)0.041Gender(male,%) 554(67.2%) 44(59.5%) 510(68.0%)0.153Type   (newonset,%)544(66.0%)43(58.1%)501(66.8%)0.157EtiologyIschemicheartdisease(yes,%)554(67.2%)44(59.5%)510(68.0%)1.000Cardiomyopathy(yes,%)141(17.1%)14(18.9%)127(16.9%)0.630Hypertensiveheartdisease(yes,%)143(17.4%)7(9.5%)136(18.1%)0.076Valvular(yes,%)117(21.5%)20(27.0%)157(20.9%)0.236Others(yes,%) 22(2.7%) 2(2.7%) 20(2.7%) 1.000PastmedicalhistoryHypertension(yes,%)612(74.3%)47(63.5%)565(75.3%)0.036Diabetesmellitus(yes,%)341(41.4%)32(43.2%)309(41.2%)0.805Dyslipidemia(yes,%)374(45.4%)25(33.8%)349(46.5%)0.038Vital   signsandstatusSBP(mmHg)160(132–186)131(107–168)162(138–188)<0.001SBP   >140mmHg   (yes,%)559(67.8%)31(41.9%)528(70.4%)<0.001SBP   100–140mmHg   (yes,%)232(28.2%)29(39.2%)203(27.1%)0.031SBP   <100mmHg(yes,%) 66(8.0%) 13(17.6%) 53(7.1%) 0.005Diastolicbloodpressure(mmHg)90(70–100)80(62–90)90(72–100)<0.001LVEF   (%)35.0(25–46)32(22–45)35(24–46)0.150LVEF   >40%(%)295(36.0%)23(31.9%)272(36.4%)<0.001NYHA(IV,%)667(80.9%)66(89.2%)601(80.1%)0.003LaboratorydataTotalbilirubin(mg/dL)0.6(0.4–0.8)0.7(0.4–1.0)0.6(0.4–0.8)0.166Urinaryacid(mg/dL) 6.8(5.5–8.1) 7.7(5.9–9.6) 6.7(5.3–8.0)0.001BUN   (mg/dL)23.2(17.9–33.1)36.4(21.5–48.7)22.7(17.5–31.8)<0.001Hemoglobin(g/dL)12.5(10.7–14.5)11.3(10.3–14.2)12.5(10.8–14.5)0.001CRP   (mg/dL)0.56(0.19–1.78)1.44(0.56–4.58)0.52(0.17–1.63)<0.001BNP   (pg/mL)805(415–1403)1363(927–1787)753(399–1312)<0.001RespiratorysupportEndotrachealintubation(yes,%)209(25.4%)36(48.6%)173(23.1%)<0.001NPPV   (yes,%) 310(37.6%)24(32.4%)286(38.1%)0.380Medication(cases)duringthefirst5daysFurosemide(yes,%)781(94.8%)66(89.2%)715(95.3%)0.047Nitroglycerin(yes,%)594(69.1%)37(50.0%)557(74.3%)<0.001Nicorandil(yes,%)95(11.5%)11(14.9%)84(11.2%)0.341Carperitide(yes,%) 449(54.5%)45(60.8%)404(53.9%)0.272Dopamine(yes,%)238(28.9.0%)41(55.4%)197(26.3%)<0.001Dobutamine(yes,%)117(21.5%)36(48.6%)141(18.8%)<0.001ACE-I/ARB(yes,%)333(40.4%)17(22.9%)316(42.1%)0.001  -Blocker(yes,%)196(23.8%)16(21.6%)180(24.0%)0.775Spironolactone(yes,%)296(35.9%)18(24.3%)278(37.1%)0.031OutcomeICU   hospitalization(days) 5(3–7) 7(4–17) 5(3–7)<0.001Total   hospitalization(days)29(18–49)30(13–82)29(18–47)0.489SBP,systolicbloodpressure;LVEF,leftventricularejectionfractionmeasuredonechocardiography;NYHA,NewYorkHeartAssociation;BUN,bloodureanitrogen;CRP,C-reactiveprotein;BNP,brainnatriureticpeptide;NPPV,non-invasivepositivepressureventilation;ACE-I,angiotensin-convertingenzymeinhibitorARB,angiotensinIIreceptor   blocker;ICU,intensivecareunit.  p -ValuebetweenthealivegroupanddeadgroupdeterminedaccordingtounpairedStudent’s t  -testandMann–Whitney U  -test.  Table2 RelationshipsbetweentheAPACHEIIscoreandin-hospitalmortality.All( n =825)Alivegroup( n =750)Deadgroup( n =75)  p -ValueTotalAPSBodytemperature( ◦ C)0.39 ± 0.570.38 ± 0.550.51 ± 0.670.162Mean   bloodpressure(mmHg)1.51 ± 1.361.54 ± 1.361.22 ± 1.330.036Pulse   (beats/min)1.53 ± 1.231.54 ± 1.221.39 ± 1.240.227Respiratoryrate(permin)1.36 ± 1.201.36 ± 1.191.38 ± 1.270.920A-aDO 2  (FiO 2  >0.5)orPaO 2  (FiO 2  <0.5)0.91 ± 1.460.90 ± 1.451.00 ± 1.520.778pH   1.59 ± 1.601.59 ± 1.601.58 ± 1.510.985Sodium(mmol/L)0.05 ± 0.350.04 ± 0.310.18 ± 0.600.001Potassium(mmol/L)0.22 ± 0.660.19 ± 0.610.46 ± 0.910.021Hematocrit(%)0.55 ± 0.900.54 ± 0.900.61 ± 0.880.511Creatinine(mg/dL)0.96 ± 1.350.90 ± 1.321.61 ± 1.51<0.001Whitebloodcell(/m 3 )0.16 ± 0.440.16 ± 0.440.14 ± 0.400.873Age   points5.05 ± 1.265.01 ± 1.295.39 ± 0.900.027Chronichealthpoints0.53 ± 1.540.51 ± 1.520.68 ± 1.630.386GlasgowComaScale0.94 ± 2.490.88 ± 2.401.59 ± 2.900.006APS,acutephysiologyscore.  p -ValuebetweenthealivegroupanddeadgroupdeterminedaccordingtoMann–Whitney U  -test.
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