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EMERGENCY DIAGNOSIS AND TREATMENT OF ACUTE DECOMPENSATED HEART FAILURE (ADHF) - MARCH 2005
Produced by
2005 EMCREG-International
www.emcreg.org
EMERGENCY DIAGNOSIS
AND TREATMENT OF
ACUTE DECOMPENSATED
HEART FAILURE (ADHF)
IN THIS ISSUE
CME Monograph
from the ACEP 2005
Spring Congress Satellite
Symposium
Orlando, Florida
March 4, 2005
EMCREG-International
This educational monograph was supported in part by
an unrestricted educational grant from Scios.
Printed in t h e U S A
Produced by
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!S WE HAVE IMPROVED THE CARE OF PATIENTS WITH ACUTE CORONARY SYNDROMES !#3 PA
TIENTS WITH CARDIOVASCULAR DISEASE ARE LIVING LONGER THAN EVER %FFECTIVE INTERVENTIONS TO
DECREASE MORTALITY OF PATIENTS WITH !#3 HAVE INCREASED THE INCIDENCE OF HEART FAILURE
4HE COST OF HEART FAILURE NOW EXCEEDS BILLION A YEAR MOST OF WHICH IS DUE TO HOS
PITALIZATION 5NFORTUNATELY HEART FAILURE IS A CHRONIC CONDITION AND NEARLY HALF OF PA
TIENTS ADMITTED TO THE HOSPITAL ARE READMITTED WITHIN SIX MONTHS 4O DETERMINE OPTIMAL
THERAPY FOR PATIENTS WITH ACUTE DECOMPENSATED HEART FAILURE !$(& THE EMERGENCY
PHYSICIAN MUST BE ABLE TO CONlDENTLY DIAGNOSE PATIENTS WITH HEART FAILURE 4HIS REQUIRES
KNOWLEDGE OF THE DIAGNOSTIC METHODS USED TO IDENTIFY PATIENTS WITH HEART FAILURE AS WELL
AS KNOWLEDGE OF THE DIFFERENT ETIOLOGIES OF HEART FAILURE
3ORTING /UT THE %TIOLOGY OF (EART
&AILURE
4HE POTENTIAL ETIOLOGIES OF ACUTE HEART
FAILURE ARE MULTIFACTORIAL AND SHOULD
BE BROADLY DIVIDED INTO TWO CATEGORIES
THE UNDERLYING ETIOLOGY OF THE HEART
FAILURE AND THE ETIOLOGY OF THE ACUTE
PRECIPITANT THAT RESULTS IN WORSENING FROM
THE CHRONIC COMPENSATED STATE &OR SOME
PATIENTS PARTICULARLY THOSE PRESENTING FOR
THE lRST TIME THESE TWO COMPONENTS MAY
BE IDENTICAL 4HE MOST COMMON ETIOLO
GIES OF HEART FAILURE ARE CORONARY ARTERY
DISEASE AND LONG
STANDING HYPERTENSION
/THER POTENTIAL ETIOLOGIES INCLUDE DI
LATED HYPERTROPHIC AND RESTRICTIVE CAR
DIOMYOPATHIES MYOCARDITIS PERICARDIAL
TAMPONADE VALVULAR HEART DISEASE AND
SECONDARY EFFECTS OF PULMONARY DISEASES
OR METABOLIC DISORDERS
!LTHOUGH INVESTIGATION OF THE UNDERLYING
ETIOLOGY IS IMPORTANT TO HELP DETERMINE
WHETHER THERE IS A REVERSIBLE COMPONENT
OF THE DISEASE THIS IS USUALLY BEYOND THE
SCOPE OF THE EMERGENCY PHYSICIAN 4HERE
ARE HOWEVER SEVERAL ETIOLOGIES FOR HEART
FAILURE THAT THE EMERGENCY PHYSICIAN
SHOULD BE AWARE OF AS THEY MAY REQUIRE
MODIlCATION OF INITIAL THERAPY 4HESE ARE
SEVERE AORTIC STENOSIS IDIOPATHIC HYPER
TROPHIC SUBAORTIC STENOSIS OR HYPERTROPHIC
OBSTRUCTIVE CARDIOMYOPATHY AND PULMO
NARY HYPERTENSION )DENTIlCATION OF PA
TIENTS WITH THESE CONDITIONS IS IMPORTANT
BECAUSE AGGRESSIVE PRELOAD AND AFTERLOAD
REDUCTION CAN LEAD TO CARDIOVASCULAR COL
LAPSE SINCE THESE PATIENTS CANNOT INCREASE
THEIR FORWARD BLOOD mOW THROUGH THE
lXED MECHANICAL LESION SUCH AS A mOW
RESTRICTED AORTIC VALVE
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%MERGENCY $IAGNOSIS AND 4REATMENT OF
!CUTE $ECOMPENSATED (EART &AILURE !$(&
3EPARATE AND DISTINCT FROM THE INITIAL ETI
OLOGY IS THE CAUSE OF THE ACUTE PRECIPI
TANT #ONGESTIVE HEART FAILURE CAN BE EX
ACERBATED BY WORSENING OF THE UNDERLYING
CONDITION BY MEDICATION OR DIETARY NON
COMPLIANCE OR BY DEVELOPMENT OF NEW
OR COMPLICATING MEDICAL CONDITIONS EG
ISCHEMIA DYSRHYTHMIAS PULMONARY EM
BOLUS OR INFECTION !PPROXIMATELY
OF PATIENTS PRESENTING TO THE EMERGENCY
DEPARTMENT %$ WITH HEART FAILURE HAVE
A PRIOR DIAGNOSIS OF HEART FAILURE
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0ROGRESS IN THE $IAGNOSIS OF (EART &AILURE
4HE DIAGNOSIS OF HEART FAILURE HAS TRADI
TIONALLY BEEN CHALLENGING 2ELIANCE UPON
CLINICAL IMPRESSION ALONE LEADS TO DIAG
NOSTIC UNCERTAINTY BECAUSE THE SIGNS AND
SYMPTOMS OF HEART FAILURE ARE RELATIVELY
NONSPECIlC +EY SYMPTOMS SUCH AS SHORT
NESS OF BREATH ARE NONSPECIlC IN PATIENTS
WITH COMORBIDITIES SUCH AS REACTIVE AIR
WAY DISEASE ,IKEWISE ROUTINE LABORATORY
TESTS ELECTROCARDIOGRAMS AND RADIOGRAPHS
CANNOT BE RELIED UPON TO ALWAYS GUIDE AN
ACCURATE AND APPROPRIATE DIAGNOSIS
$ESPITE THESE CHALLENGES DIAGNOSTIC CA
PABILITIES IN HEART FAILURE HAVE IMPROVED
IN RECENT YEARS WITH RECOGNITION OF THE
ROLE THAT "
TYPE NATRIURETIC PEPTIDE ".0
PLAYS IN THE DISEASE )N ADDITION TO BEING
A PUMP THE HEART IS AN ENDOCRINE ORGAN
THAT FUNCTIONS TOGETHER WITH OTHER PHYSI
OLOGICAL SYSTEMS TO CONTROL mUID VOLUME
4HE MYOCARDIUM PRODUCES NATRIURETIC
PEPTIDES ONE OF WHICH IS ".0 A HORMONE
WITH DIURETIC NATRIURETIC AND VASCULAR
SMOOTH MUSCLE RELAXING ACTIONS ".0 IS
A NATURAL ANTAGONIST FOR THE SYMPATHETIC
NERVOUS SYSTEM AND THE RENIN
ANGIOTEN
SIN
ALDOSTERONE AXIS ".0 IS SECRETED IN
RESPONSE TO WALL STRETCH VENTRICULAR DI
LATION ANDOR INCREASED lLLING PRESSURES
-EASUREMENT OF ENDOGENOUS ".0 IS THUS
A CLINICALLY SENSIBLE WAY TO ASSESS WHETH
ER A PARTICULAR PATIENT HAS HEART FAILURE
4HE "REATHING .OT 0ROPERLY STUDY OF
PATIENTS WHO PRESENTED TO %$S WITH
SHORTNESS OF BREATH SHOWED THAT ".0 LEV
ELS ALONE WERE MORE ACCURATE PREDICTORS
OF THE PRESENCE OR ABSENCE OF HEART FAILURE
THAN ANY HISTORICAL FACTORS PHYSICAL lND
INGS OR LABORATORY VALUES ".0 LEVELS
WERE MUCH HIGHER IN PATIENTS WHO WERE
SUBSEQUENTLY DIAGNOSED WITH HEART FAIL
URE THAN IN THOSE DIAGNOSED WITH NONCAR
DIAC DYSPNEA PGD, VS PGD,
! ".0 CUTOFF VALUE OF PGM, HAD
A SENSITIVITY OF AND A SPECIlCITY OF
FOR DIFFERENTIATING HEART FAILURE FROM
OTHER CAUSES OF DYSPNEA AND A CUTOFF OF
PGM, HAD A NEGATIVE PREDICTIVE VAL
UE OF 7ITHOUT KNOWLEDGE OF ".0
LEVELS EMERGENCY PHYSICIANS HAD A
INDECISION RATE IN TRYING TO MAKE A DIAG
NOSIS ".0 LEVELS ADDED SIGNIlCANTLY TO
THE CLINICAL IMPRESSION AS IT WAS FOUND
THAT CLINICAL DECISION MAKING IN CONJUNC
TION WITH ".0 LEVELS COULD HAVE REDUCED
THE DIAGNOSTIC INDECISION RATE TO )N
MULTIVARIATE ANALYSES ".0 LEVELS ALWAYS
CONTRIBUTED TO THE DIAGNOSIS EVEN AFTER
TAKING INTO ACCOUNT lNDINGS FROM THE
HISTORY AND PHYSICAL EXAMINATION 4HUS
THE "REATHING .OT 0ROPERLY TRIAL DEMON
STRATED THAT ".0 LEVELS HAVE SIGNIlCANT
CLINICAL UTILITY FOR BOTH THE DIAGNOSIS
AND RISK STRATIlCATION OF HEART FAILURE
PATIENTS IN THE %$ "OTH DIASTOLIC AND
SYSTOLIC DYSFUNCTION ARE ASSOCIATED WITH
HIGH ".0 LEVELS OF MORE OR LESS THE SAME
DEGREE
"--"
1/
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-/
,/ 1,
/
".0 MUST BE USED WITH CAUTION IN CERTAIN
POPULATIONS !LTHOUGH ".0 CAN HELP DIF
FERENTIATE PULMONARY FROM CARDIAC ETIOLO
GIES OF DYSPNEA SOME TYPES OF LUNG DIS
EASE SUCH AS COR PULMONALE AND PULMO
NARY EMBOLISM HAVE ELEVATED ".0 LEVELS
HOWEVER ".0 IS NOT USUALLY ELEVATED AS TO
AS HIGH A LEVEL AS IT IS IN PATIENTS WITH HEART
FAILURE )N A SUBGROUP OF PATIENTS WITH A
HISTORY OF REACTIVE AIRWAY DISEASE IN THE
"REATHING .OT 0ROPERLY TRIAL OF SUB
JECTS WITH A HISTORY OF ASTHMA OR CHRONIC
OBSTRUCTIVE PULMONARY DISEASE WITHOUT A
HISTORY OF #(& WERE FOUND TO HAVE
NEWLY DISCOVERED #(& /NLY WERE
IDENTIlED IN THE %$ WHILE A ".0
PGM, IDENTIlED !DDITIONALLY ".0
LEVELS PGM, PROVIDED DIAGNOSTIC
INFORMATION BEYOND THAT OBTAINED FROM IN
DIVIDUAL CHEST RADIOGRAPHIC INDICATORS
4HERE IS A SIGNIlCANT INVERSE RELATIONSHIP
BETWEEN BODY WEIGHT BODY MASS INDEX
AND ".0 LEVELS 4HIN PATIENTS WITH HEART
FAILURE ARE MORE LIKELY TO HAVE ELEVATED ".0
VALUES IN THE ABSENCE OF HEART FAILURE #ON
VERSELY OBESE PATIENTS ARE MORE LIKELY TO
HAVE LOWER LEVELS OF ".0 FOR ANY GIVEN SE
VERITY OF HEART FAILURE !S A RESULT ".0 LEV
ELS SHOULD BE USED WITH CAUTION IN PATIENTS
WITH OBESITY UNLESS OF COURSE BASELINE ".0
VALUES ARE KNOWN 4HEN THE OBESE PATIENT
CAN BE FOLLOWED FOR DECOMPENSATION
4HE "REATHING .OT 0ROPERLY 4RIAL DEM
ONSTRATED THAT ".0 IS USEFUL FOR THE DIAG
NOSIS OF #(& IN THE %$ 4HE 2%$(/4
3TUDY SUGGESTS THAT ".0 MIGHT ALSO BE
USEFUL TO IMPROVE TRIAGE AND DISPOSITION OF
PATIENTS WHO PRESENT TO THE %$ WITH HEART
FAILURE 4HIS TRIAL DEMONSTRATED A hDISCON
NECTv BETWEEN THE PHYSICIAN PERCEPTION OF
THE SEVERITY OF HEART FAILURE AND THE ACTUAL
".0 VALUE )N THE lRST PHASE PATIENTS
VISITING %$S WITH COMPLAINTS OF BREATH
ING DIFlCULTY HAD ".0 MEASUREMENTS
TAKEN ON ARRIVAL 0HYSICIANS WERE BLINDED
TO ".0 RESULTS HOWEVER INCLUSION IN THE
TRIAL REQUIRED A ".0 PGML 0ATIENTS
DISCHARGED FROM THE %$ HAD HIGHER ".0
LEVELS THAN THOSE ADMITTED TO THE HOSPITAL
PGML VS PGML 7ITH RESPECT TO
THE ADMITTED PATIENTS HAD ".0 LEV
ELS PGML WHICH IS INDICATIVE OF LESS
SEVERE #(& -OST OF THESE PATIENTS WERE
PERCEIVED TO HAVE CLASS ))) OR )6 HEART FAIL
URE -ORTALITY FOR THESE PATIENTS WAS AT
DAYS AND ONLY AT DAYS SUGGESTING
THAT PATIENTS WITH HEART FAILURE AND LOW LEV
ELS OF ".0 MIGHT HAVE ACTUALLY BEEN SAFE
FOR DISCHARGE 7ITH RESPECT TO PATIENTS THAT
WERE ACTUALLY DISCHARGED HAD ".0
LEVELS PGM, !T DAYS MORTALITY
WAS 4HERE WAS NO MORTALITY OF THOSE
DISCHARGED WITH ".0 LEVELS PGM,
4HIS SUGGESTS THAT USE OF ".0 IN THE %$
MIGHT ALSO HELP DETERMINE WHICH WELL AP
PEARING PATIENTS ARE HIGH RISK FOR A BAD OUT
COME OVER THE SHORT TERM DAYS
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%LEVATED ".0 LEVELS ARE USEFUL FOR AS
SESSING RISK STRATIlCATION AND PROGNOSIS
IN PATIENTS WITH HEART FAILURE ".0 LEVELS
ARE RELATED TO CHANGES IN LIMITATIONS OF
PHYSICAL ACTIVITIES AND FUNCTIONAL STATUS
(ARRISON ET AL FOLLOWED PATIENTS FOR
MONTHS AFTER AN INDEX VISIT TO THE %$ FOR
DYSPNEA (IGHER ".0 LEVELS WERE ASSO
CIATED WITH A PROGRESSIVELY WORSE PROG
NOSIS 4HE RELATIVE RISK OF MONTH #(&
ADMISSION OR DEATH IN PATIENTS WITH ".0
LEVELS PGM, WAS TIMES THE RISK
OF PATIENTS WITH LEVELS LESS THAN 7HEN
COMBINED WITH TROPONIN ) BOTH TROPONIN )
AND ".0 ALONE AND IN COMBINATION PRE
DICT SURVIVAL IN #(& "OTH TOGETHER HAVE
ADDITIVE PROGNOSTIC RISK
%MERGENCY $IAGNOSIS AND 4REATMENT OF
!CUTE $ECOMPENSATED (EART &AILURE !$(&
4HE UTILITY OF ".0 TO DIAGNOSIS #(& IS WELL ESTAB
LISHED HOWEVER ITS ABILITY TO DRIVE TREATMENT IS STILL
UNDER STUDY 2%$(/4 )) IS A RANDOMIZED CONTROLLED
TRIAL COMPARING TREATMENT AND OUTCOMES OF PATIENTS
WHERE THERAPY IS GUIDED BY SERIAL ".0 MEASUREMENTS
IN THE EXPERIMENTAL GROUP 4HIS STUDY SHOULD SHED
SOME LIGHT ON THE UTILITY OF ".0 TO DRIVE TREATMENT
$UE TO THE VOLUMINOUS DATA ON THE CLINICAL UTILITY OF
".0 CONSENSUS PANEL GUIDELINES WERE RECENTLY PUB
LISHED 4HESE RECOMMENDATIONS STATE
% -ANY PATIENTS PRESENTING TO EMERGENCY SERVICES
WITH DYSPNEA A HISTORY PHYSICAL EXAMINATION
AND A CHEST X
RAY AND %#' SHOULD BE UNDERTAKEN
TOGETHER WITH LABORATORY MEASUREMENTS THAT
INCLUDE ".0
% !S ".0 LEVELS RISE WITH AGE AND ARE AFFECTED BY
GENDER COMORBIDITY AND DRUG THERAPY THE PLASMA
".0 MEASUREMENT SHOULD NOT BE USED IN ISOLATION
FROM THE CLINICAL CONTEXT
% )F THE ".0 IS PGM, THEN HEART FAILURE IS
HIGHLY UNLIKELY NEGATIVE PREDICTIVE VALUE
% )F THE ".0 LEVEL IS PGM, THEN #(& IS
HIGHLY LIKELY POSITIVE PREDICTIVE VALUE
% &OR ".0 LEVELS OF n ONE SHOULD CONSIDER
THE FOLLOWING CONDITIONS IN THE DIFFERENTIAL
DIAGNOSIS
A "ASELINE ".0 VALUE DUE TO STABLE UNDERLYING
DYSFUNCTION
B 2IGHT VENTRICULAR FAILURE FROM COR
PULMONALE
C !CUTE PULMONARY EMBOLISM
D 2ENAL FAILURE
s 0ATIENTS MAY PRESENT WITH #(& WITH NORMAL
".0 LEVELS OR WITH LEVELS BELOW WHAT
MIGHT ONE EXPECT CAN OCCUR IN THE FOLLOWING
SITUATIONS
A &LASH PULMONARY EDEMA n HOURS
B (EART FAILURE UP
STREAM FROM THE LEFT
VENTRICLE IE ACUTE MITRAL REGURGITATION
FROM PAPILLARY MUSCLE RUPTURE
C /BESE PATIENTS BODY MASS INDEX
KGM
,
,
-AISEL !3 +RISHNASWAMY 0 .OWAK 2- ET AL 2APID
MEASUREMENT OF " TYPE NATRIURETIC PEPTIDE IN THE EMERGENCY
DIAGNOSIS OF HEART FAILURE . %NGL * -ED
-C#ULLOUGH 0! .OWAK 2- -C#ORD * ET AL " TYPE NATRIURETIC
PEPTIDE AND CLINICAL JUDGMENT IN EMERGENCY DIAGNOSIS OF HEART
FAILURE ANALYSIS FROM "REATHING .OT 0ROPERLY ".0 -ULTINATIONAL
3TUDY #IRCULATION
-AISEL !3 -C#ORD * .OWAK 2- (OLLANDER *% 7U !("
$UC 0 /MLAND 4 3TORROW !" +RISHNASWAMY 0 !BRAHAM 74
#LOPTON 0 3TEG 0' !UMONT -# 7ESTHEIM ! +NUDSEN #7
0EREZ ! +AMIN 2 +AZANEGRA 2 (ERRMANN (# -C#ULLOUGH 0!
FOR THE ".0 -ULTINATIONAL 3TUDY )NVESTIGATORS "EDSIDE " TYPE
NATRIURETIC PEPTIDE IN THE EMERGENCY DIAGNOSIS OF HEART FAILURE WITH
REDUCED OR PRESERVED EJECTION FRACTION 2ESULTS FROM THE "REATHING
.OT 0ROPERLY ".0 -ULTINATIONAL 3TUDY * !M #OLL #ARDIOL
-C#ULLOUGH 0! (OLLANDER *% .OWAK 2- ET AL 5NCOVERING
HEART FAILURE IN PATIENTS WITH A HISTORY OF PULMONARY DISEASE
RATIONALE FOR THE EARLY USE OF " TYPE NATRIURETIC PEPTIDE IN THE
EMERGENCY DEPARTMENT !CAD %MERG -ED
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NATRIURETIC PEPTIDE LEVELS !RCH )NTERN -ED
-AISEL ! (OLLANDER *% 'USS $ ET AL 0RIMARY RESULTS OF THE RAPID
EMERGENCY DEPARTMENT HEART FAILURE OUTPATIENT TRIAL 2%$(/4 A
MULTICENTER STUDY OF B TYPE NATRIURETIC PEPTIDE LEVELS EMERGENCY
DEPARTMENT DECISION MAKING AND OUTCOMES IN PATIENTS PRESENTING
WITH SHORTNESS OF BREATH * !MER #OLL #ARDIOL
(ARRISON ! -ORRISON ,+ +RISHNASWAMY 0 ET AL " TYPE
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CARDIOVASCULAR DISEASES #ONG (EART &AILURE
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!CUTELY DECOMPENSATED HEART FAILURE !$(& IS A COMMON REASON FOR PATIENTS SEEKING
EMERGENCY DEPARTMENT %$ CARE AND THE LEADING -EDICARE DIAGNOSIS FOR HOSPITALIZED
PATIENTS OVER THE AGE OF (OSPITAL READMISSION FOR HEART FAILURE IS COMMON AP
PROXIMATELY OF PATIENTS ARE READMITTED WITHIN DAYS AND WITHIN MONTHS
2ECENT ADVANCES IN THE UNDERSTANDING OF THE COMPLEX PATHOPHYSIOLOGIC PROCESS THAT
EXACERBATE HEART FAILURE HAS LED TO IMPROVED DIAGNOSES AND EFFECTIVE %$ TREATMENT OF
THIS CLINICAL ENTITY
0ATHOPHYSIOLOGY AND (EMODYNAMIC
!SSESSMENT
)N THE PAST DECOMPENSATED HEART FAILURE
WAS FELT TO BE DUE TO VOLUME OVERLOAD
AND IMPAIRED FORWARD mOW 4REATMENT
WAS FOCUSED ON MAXIMIZING CARDIAC OUT
PUT )T HAS NOW BECOME APPARENT THAT IN
MOST !$(&PULMONARY EDEMA THERE IS
INCREASED SYSTEMIC VASCULAR RESISTANCE
SUPERIMPOSED ON REDUCED MYOCARDIAL RE
SERVE BOTH SYSTOLIC AND DIASTOLIC -ANY
VARIABLES PLAY A ROLE IN !$(& THAT EXAC
ERBATE LEFT VENTRICULAR ,6 DYSFUNCTION
AND LEAD TO DETERIORATION ,OW CARDIAC
OUTPUT RESULTS IN DECREASED RENAL mOW AND
STIMULATES NEUROHORMONAL ACTIVATION IN
CLUDING THE RELEASE OF ANGIOTENSIN )) $E
CREASED CARDIAC OUTPUT CAUSES PROGRESSIVE
BLOOD VOLUME EXPANSION FURTHER INCREAS
ING ,6 lLLING PRESSURES AND MYOCARDIAL
OXYGEN CONSUMPTION (YPOTENSION PRO
MOTES BARORECEPTOR ACTIVATION LEADING
TO INCREASED SYMPATHETIC TONE AND VASO
CONSTRICTION WHICH FURTHER INCREASES SYS
TEMIC VASCULAR RESISTANCE COMPROMISING
SYSTOLIC PERFORMANCE 4HERE IS MARKED
UP
REGULATION OF VASOCONSTRICTORS INCLUD
ING NOREPINEPHRINE ANGIOTENSIN )) AND
ENDOTHELIN ALDOSTERONE AND ARGININE VA
SOPRESSIN RISE CONTRIBUTING TO THE SALT AND
WATER RETENTION
4O COUNTER
BALANCE THE EFFECTS OF NEURO
HORMONES RELEASED BY THE SYMPATHETIC
NERVOUS SYSTEM AND THE RENIN
ANGIOTEN
SIN
ALDOSTERONE SYSTEM 2!!3 AND TO
MAINTAIN CIRCULATORY HOMEOSTASIS THE
BODY PRODUCES A FAMILY OF VASODILATOR
ANTIPROLIFERATIVE NATRIURETIC PEPTIDES THAT
PLAY AN IMPORTANT ROLE IN HEART FAILURE
!TRIAL AND "
TYPE NATRIURETIC PEPTIDES
ARE RELEASED FROM THE MYOCARDIUM IN RE
SPONSE TO INCREASED ATRIAL NATRIURETIC PEP
TIDE AND VENTRICULAR "
TYPE NATRIURETIC
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$IAGRAM INDICATING X TABLE OF HEMODYNAMIC PROlLES FOR PATIENTS
PRESENTING WITH HEART FAILURE -OST PATIENTS CAN BE CLASSIlED IN A
MINUTE BEDSIDE ASSESSMENT ACCORDING TO THE SIGNS AND SYMPTOMS
SHOWN ALTHOUGH IN PRACTICE SOME PATIENTS MAY BE ON THE BORDER BE
TWEEN THE WARM
AND
WET AND COLD
AND
WET PROlLES 4HIS CLASSIlCATION
HELPS GUIDE INITIAL THERAPY AND PROGNOSIS FOR PATIENTS PRESENTING WITH
ADVANCED HEART FAILURE !LTHOUGH MOST PATIENTS PRESENTING WITH HYPO
PERFUSION ALSO HAVE ELEVATED lLLING PRESSURES COLD AND WET PROlLE
MANY PATIENTS PRESENT WITH ELEVATED lLLING PRESSURES WITHOUT MAJOR
REDUCTION IN PERFUSION WARM AND WET PROlLE 0ATIENTS PRESENTING
WITH SYMPTOMS OF HEART FAILURE AT REST OR MINIMAL EXERTION WITHOUT
CLINICAL EVIDENCE OF ELEVATED lLLING PRESSURES OR HYPOPERFUSION WARM
AND DRY PROlLE SHOULD BE CAREFULLY EVALUATED TO DETERMINE WHETHER
THEIR SYMPTOMS RESULT FROM HEART FAILURE
1R
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PEPTIDE ".0 STRESS 4HEY INCREASE GLOMERULAR lL
TRATION RATE '&2 INHIBIT SODIUM REABSORPTION AND
REDUCE VASCULAR SMOOTH MUSCLE TONE CAUSING A DIURE
SIS NATRIURESIS AND BALANCED ARTERIAL AND VENOUS DILA
TION !LL THESE EFFECTS CONTRIBUTE TO REDUCED PLASMA
VOLUME BLOOD PRESSURE AND VENTRICULAR PRELOAD ".0
HAS LUSITROPIC RELAXING EFFECTS AND MAY BE ANTIlBROT
IC AND ANTIPROLIFERATIVE )N !$(& THE RELEASE AND
PRODUCTION OF STORED NATRIURETIC PEPTIDES ARE INSUFl
CIENT TO BALANCE THE mUID RETENTION OF THE 2!!3
2APID BEDSIDE ASSESSMENT OF !$(& CAN BE SIMPLI
lED BY PLACING THE PATIENT INTO ONE OF FOUR HEMODY
NAMIC PROlLES Q}i R 4WO KEY HEMODYNAMIC
PARAMETERS ARE THE PRESENCE OR ABSENCE OF ELEVATED
lLLING PRESSURES WET OR DRY AND ADEQUACY OF PERFU
SION WARM OR COLD #ONGESTION CORRESPONDS TO EL
EVATED PULMONARY CAPILLARY WEDGE PRESSURE 0#70
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AND IMPAIRED PERFUSION IS SUGGESTED BY A LOW CARDIAC
INDEX 'REATER THAN OF PATIENTS PRESENTING WITH
!$(& ARE CONGESTED WET 4HEY MAY HAVE ADEQUATE
OR REDUCED PERFUSION WITH THE MAJORITY EXPERIENCING
ELEVATED SYSTEMIC VASCULAR RESISTANCE #ONGESTION
ELEVATED lLLING PRESSURE IN !$(& IS REPRESENTED
BY DYSPNEA AND ORTHOPNEA AND ELEVATED JUGULAR VE
NOUS PRESSURE 2ALES WHILE A HELPFUL SIGN ARE ABSENT
IN OF PATIENTS WITH CHRONICALLY ELEVATED lLLING
PRESSURES DUE TO PULMONARY LYMPHATIC COMPENSATION
0ERIPHERAL EDEMA IS RELATIVELY INSENSITIVE TO ELEVATED
lLLING PRESSURES AND ASSOCIATED WITH MANY NONCARDI
AC CAUSES 4HE THIRD HEART SOUND 3 WHILE A SENSITIVE
MARKER IS RARELY APPRECIATED 4HE MOST READILY AVAIL
ABLE INDICATOR OF PERFUSION IS BLOOD PRESSURE AND PULSE
PRESSURE 4HIS RAPID ASSESSMENT SYSTEM ALLOWS FOR AP
PROPRIATE TARGETING OF THERAPY IN !$(& PATIENTS
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$ETERMINING THE %TIOLOGY OF !CUTE
$ECOMPENSATION AND 3ETTING
4REATMENT 'OALS
4HE ETIOLOGIES OF !$(& ARE MULTIFACTORI
AL BUT CAN BE DIVIDED INTO TWO CATEGORIES
THE UNDERLYING THE HEART FAILURE AND
THE ACUTE PRECIPITANT THAT RESULTS IN DE
TERIORATION FROM THE CHRONIC COMPENSATED
STATE )N PATIENTS PRESENTING FOR THE lRST
TIME THE TWO COMPONENTS ARE IDENTICAL
4HE MOST COMMON CAUSES OF HEART FAIL
URE ARE CORONARY ARTERY DISEASE AND LONG
STANDING HYPERTENSION /THER ETIOLOGIES
INCLUDE DILATED HYPERTROPHIC AND RESTRIC
TIVE CARDIOMYOPATHIES MYOCARDITIS PERI
CARDIAL TAMPONADE VALVULAR HEART DISEASE
AND SECONDARY EFFECTS OF PULMONARY AND
METABOLIC DISORDERS 5NDERSTANDING THE
UNDERLYING ETIOLOGY IS IMPORTANT IN HELP
ING TO DETERMINE IF THERE IS A REVERSIBLE
COMPONENT PRESENT 4HE EMERGENCY PHY
SICIAN MUST BE AWARE OF NUMBER OF SPE
CIAL CAUSES OF HEART FAILURE THAT REQUIRE
CONSIDERATION WHEN MAKING THERAPEUTIC
DECISIONS )N SEVERE AORTIC STENOSIS ID
IOPATHIC HYPERTROPHIC SUBAORTIC STENOSIS
OR HYPERTROPHIC OBSTRUCTIVE CARDIOMY
OPATHY AND PULMONARY HYPERTENSION AG
GRESSIVE AFTERLOAD REDUCTION CAN LEAD TO
CARDIOVASCULAR COLLAPSE AS THESE PATIENTS
CANNOT INCREASE THEIR FORWARD BLOOD mOW
IN THE FACE OF A lXED MECHANICAL LESION
'REATER THAN OF PATIENTS PRESENTING
TO THE %$ WITH !$(& HAVE A PRIOR DIAG
NOSIS OF HEART FAILURE !N ACUTE PRECIPI
TANT CAN OFTEN BE IDENTIlED %XACERBA
TION OR WORSENING OF THE UNDERLYING CON
DITION CAN BE DUE TO MEDICATION OR DIETARY
NON
COMPLIANCE OR THE DEVELOPMENT OF A
NEW OR COMPLICATING MEDICAL CONDITION
SUCH AS ISCHEMIA DYSRHYTHMIA PULMO
NARY EMBOLUS OR INFECTION 4REATMENT
DEPENDS ON THE SEVERITY OF THE SYMPTOMS
AND DECOMPENSATION TIME COURSE
4HERAPEUTIC GOALS IN !$(& PATIENTS CAN
BE DIVIDED IN THREE PHASES 4HE PRIMARY
GOAL IN THE %$ IS RESTORATION OF OXYGEN
ATION ORGAN PERFUSION AND TOTAL BODY
mUID BALANCE 4HIS IS ACCOMPLISHED BY
REVERSING ACUTE HEMODYNAMIC ABNORMAL
ITIES AND RELIEVING SYMPTOMS )NTERMEDI
ATE GOALS INCLUDE MINIMIZING END ORGAN
DAMAGE REDUCING HOSPITALIZATION DURA
TION AND INITIATION OF BENElCIAL MEDICAL
THERAPIES AND SHOULD COMMENCE IN THE
%$ ,ONG TERM GOALS FOCUS ON REDUCING
READMISSION AND IMPROVING LONG TERM
SURVIVAL WITH TREATMENT THAT DECREASES
DISEASE PROGRESSION 4HIS OCCUR AFTER THE
PATIENT LEAVES THE %$ 7HILE NATIONAL
GUIDELINES EXIST FOR MANY ACUTE CARDIO
VASCULAR CONDITIONS THERE ARE NO CONSEN
SUS GUIDELINES FOR THE MANAGEMENT OF
!$(& 'IVEN THE LACK OF RANDOMIZED
CONTROLLED TRIALS CONSENSUS THAT INCORPO
RATES EVIDENCE BASED LITERATURE AND EXPERT
OPINION SHOULD BE USED AS GUIDELINES
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/UR IMPROVED UNDERSTANDING OF THE ETIOL
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IDENTIlED THE 2!!3 AND NEUROHORMONAL
PATHWAYS AS TARGETS OF THERAPY AND MAY
EXPLAIN THE BENElTS OF NEUROHORMONAL
BLOCKERS SUCH AS ANGIO
CONVERTING EN
ZYME !#% INHIBITORS BETA
BLOCKERS AL
DOSTERONE BLOCKERS EG SPIRONOLACTONE
AND SUPRAPHYSIOLOGIC DOSES OF NATRIURETIC
PEPTIDES SUCH AS !.0 AND ".0 IN THE
TREATMENT OF HEART FAILURE
%MERGENCY $IAGNOSIS AND 4REATMENT OF
!CUTE $ECOMPENSATED (EART &AILURE !$(&
)NITIAL THERAPY SHOULD BE GUIDED BY THE PATIENTS
HEMODYNAMIC PROlLE Q}iR &OR PATIENTS
WITHOUT EVIDENCE OF ELEVATED lLLING PRESSURES OR
HYPOPERFUSION DRY AND WARM NO IMMEDIATE
INTERVENTION IS NEEDED #ARE SHOULD FOCUS ON
MAINTAINING STABLE VOLUME STATUS AND PREVENTING
DISEASE PROGRESSION 4HESE PATIENTS RARELY PRES
ENT TO THE %$ )N PATIENTS WITH ELEVATED lLLING
PRESSURES BUT ADEQUATE PERFUSION WET AND WARM
THERAPY AIMS TO DIURESE !SSUMING THEY ARE AL
READY RECEIVING !#% INHIBITORS THE GOAL IS TO EN
HANCE THEIR DIURETIC REGIMEN )N MORE ADVANCED
CASES THE USE OF INTRAVENOUS LOOP DIURETICS AND
VASODILATORS SUCH AS NITROGLYCERIN OR NESIRITIDE
CAN ACCELERATE SYMPTOM RESOLUTION 4HE MAIN
CHALLENGE IS AVOIDING HYPOTENSION )N THIS SITU
ATION INOTROPIC THERAPY IS CONTRAINDICATED &OR
CONGESTED ELEVATED lLLING PRESSURE PATIENTS WITH
CLINICAL HYPOPERFUSION WET AND COLD IT IS USUALLY
NECESSARY TO hWARM UP IN ORDER TO DRY OUTv &OR
THESE PATIENTS IN WHOM REmEX RESPONSES SUPPORT
THE FAILING CIRCULATION `
BLOCKERS AND !#% INHIB
ITORS MAY NEED TO BE WITHDRAWN UNTIL STABILIZATION
IS ACHIEVED ,OW CARDIAC OUTPUT IS OFTEN ASSOCI
ATED WITH HIGH SYSTEMIC VASCULAR RESISTANCE AND
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!*2 ABDOMINAL JUGULAR REmEX "I0!0 BILEVEL POSITIVE AIRWAY
PRESSURE ".0 B NATRIURETIC PEPTIDE #) CARDIAC INDEX
#0!0 CONTINUOUS POSITIVE AIRWAY PRESSURE $/% DYSPNEA ON
EXERTION (*2 HEPATOJUGULAR REmEX *6$ JUGULAR VENOUS DISTENTION
0#70 PULMONARY CAPILLARY WEDGE PRESSURE 0.$ PAROXYSMAL
NOCTURNAL DYSPNEA 3"0 SYSTOLIC BLOOD PRESSURE 3#R SERUM
CREATININE 3/" SHORTNESS OF BREATH 362 SYSTEMIC VASCULAR
RESISTANCE
MAY IMPROVE WITH VASODILATOR THERAPY ALONE 4HERE
REMAINS CONTROVERSY ABOUT THE ROLE OF INOTROPIC
VASO
DILATOR AGENTS SUCH AS DOBUTAMINE AND MILRINONE DUE
TO THE INCREASED RISK FOR ISCHEMIC EVENTS AND TACHYAR
RHYTHMIAS 0ATIENTS WITH LOW CARDIAC OUTPUT WITHOUT
EVIDENCE OF ELEVATED lLLING PRESSURE COLD AND DRY
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MAY BE SURPRISINGLY STABLE AND DO NOT PRESENT WITH
URGENT SYMPTOMS 5NLESS THEY HAVE SUBNORMAL lLLING
PRESSURES VOLUME DEPLETED OR EXCESSIVE VASODILATION
THEY OFTEN DO NOT IMPROVE ACUTELY )NOTROPIC INFUSION
WHILE HELPING THE SYMPTOMS MAY LEAD TO DEPENDENCY
AND TACHYPHYLAXIS
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0HARMACOLOGIC /PTIONS
!N IDEAL AGENT FOR !$(& WOULD BE ONE
THAT RAPIDLY REDUCES 0#7 RELIEVING SYMP
TOMS AND HYPOXIA INDUCES BALANCED ARTE
RIAL AND VENOUS DILATION LACKS POSITIVE
INOTROPIC EFFECTS PROMOTES NATRIURESIS
AND DOESNT CAUSE REmEX NEUROENDOCRINE
ACTIVATION
$IURETICS ARE TRADITIONALLY USED TO REDUCE
PRELOAD THEREBY IMPROVING SYMPTOMS IN
!$(& PATIENTS 4HEY DO NOT HAVE ANY
DIRECT MYOCARDIAL BENElT BUT ACTIVATE THE
NEUROHORMONAL SYSTEM LEADING TO ALDOSTE
RONE ELEVATION $IURETICS HAVE BEEN USED
FOR DECADES AND MOST PROVIDERS ARE VERY
COMFORTABLE WITH THEM DESPITE THE FACT
THAT THEY LACK OF EVIDENCE OF IMPROVED
MORTALITY )NTRAVENOUS FUROSEMIDE CAUSES
A DECREASE IN 0#70 AND RIGHT ATRIAL PRES
SURE AS A RESULT OF VENODILATION AND DIURE
SIS 4HERE IS A CONCOMITANT DECREASE IN
STROKE VOLUME INCREASE IN SYSTEMIC VAS
CULAR RESISTANCE AND PRONOUNCED SPIKE IN
NEUROHORMONAL ACTIVATION )NCREASES IN
THE 2!!3 AND SYMPATHETIC NERVOUS SYS
TEM ACTIVATION NOREPINEPHRINE LEVELS
CAN BE SEEN SHORTLY AFTER FUROSEMIDE IN
FUSION
)N ONE TRIAL OF HIGH
DOSE LOOP DIURETICS
COMPARED TO LOW DOSE DIURETICS COM
BINED WITH INTRAVENOUS VASODILATORS
PATIENTS TREATED WITH HIGH
DOSE FUROSE
MIDE DID SIGNIlCANTLY WORSE IN ALL OUT
COME MEASURES ! RECENT ANALYSIS OF
EIGHT SMALL TRIALS FOUND THAT THERE WAS
GREATER DIURESIS AND A BETTER SAFETY PRO
lLE IF DIURETICS WERE GIVEN AS A CONTINU
OUS INSTEAD OF BOLUS INFUSION 7HILE
INTRAVENOUS DIURETICS PROMOTE NATRIURESIS
AND DIURESIS THEY DO SO AT THE EXPENSE OF
NEUROHORMONAL ACTIVATION AND SYSTEMIC
VASOCONSTRICTION THAT PREVENTS REDUCTION
OF VENTRICULAR lLLING PRESSURES $IURETIC
RESISTANCE IS A CLINICAL STATE IN WHICH
DIURETIC RESPONSE IS DIMINISHED OR LOST
4HIS MAY BE CAUSED BY PRERENAL AZOTE
MIA HYPONATREMIA SODIUM RETENTION OR
ALTERED DIURETIC PHARMACOKINETICS 4HERE
IS A CYCLE OF LOW CARDIAC OUTPUT LEADING TO
DIMINISHED RENAL PERFUSION WHICH IN TURN
PRODUCES VOLUME OVERLOAD AND WORSENS
HEART FAILURE 4HESE DELETERIOUS EFFECTS
ARE EVEN MORE PRONOUNCED IN PATIENTS
WITH UNDERLYING RENAL INSUFlCIENCY $I
URETIC REQUIREMENTS INCREASE AS THE HEART
FAILURE PROGRESSES
!RGININE VASOPRESSIN IS A NEUROHORMONE
PRODUCED BY THE CENTRAL NERVOUS SYSTEM IN
RESPONSE TO CHANGES IN SERUM OSMOLARITY
SEVERE HYPOVOLEMIA OR HYPOTENSION /NE
APPROACH TO ANTAGONIZING VASOPRESSINS
ACTION IS TO SELECTIVELY BLOCK ITS RECEPTOR
RESULTING IN AQUARESIS WITHOUT ELECTROLYTE
IMBALANCES OR NEUROHORMONAL STIMULA
TION 4HE NOVEL COMPOUND TOLVAPTAN IS
AN ANTAGONIST THAT CAUSES INCREASED URINE
OUTPUT AND DECREASES BODY WEIGHT AND
EDEMA /NE STUDY LOOKED AT WEIGHT RE
DUCTION FOLLOWING HOURS OF INFUSION IN
PATIENTS WITH IMPAIRED VENTRICULAR FUNC
TION %& 4HERE WAS NO DIFFERENCE
IN IN HOSPITAL MORTALITY OR WORSENING OF
HEART FAILURE 4HIS NOVEL AGENT SHOWS
PROMISE OF FACILITATING mUID LOSS WITHOUT
ADVERSE SEQUELAE IN PATIENTS WITH REDUCED
SYSTOLIC FUNCTION
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)NOTROPES HAVE BEEN A MAINSTAY OF THERA
PY FOR !$(& BECAUSE OF THEIR BENElCIAL
EFFECTS ON HEMODYNAMIC PARAMETERS
NAMELY INCREASING CARDIAC CONTRACTILITY
WHICH IMPROVES CARDIAC OUTPUT )NOTRO
PES ARE USED INFREQUENTLY IN THE %$ DUE
%MERGENCY $IAGNOSIS AND 4REATMENT OF
!CUTE $ECOMPENSATED (EART &AILURE !$(&
PRIMARILY TO LOGISTICAL CONCERNS 2ECENT LARGE STUDIES
DEMONSTRATED A LACK OF EFlCACY IN MANY !$(& PA
TIENTS AND EXPOSED SAFETY CONCERNS )NOTROPES INCREASE
HEART RATE AND MYOCARDIAL OXYGEN DEMAND AGGRAVATE
ISCHEMIA PRECIPITATE ARRHYTHMIAS AND CAN CAUSE HY
POTENSION ! TRIAL COMPARING DOBUTAMINE VERSUS NE
SIRITIDE DEMONSTRATED THAT DOBUTAMINE INCREASES VEN
TRICULAR ECTOPY AND VENTRICULAR TACHYCARDIA -ILRI
NONE FAILED TO DEMONSTRATE SIGNIlCANT IMPROVEMENTS
IN LENGTH OF HOSPITALIZATION SYMPTOM RELIEF OR MORTAL
ITY COMPARED TO PLACEBO )T WAS HOWEVER ASSOCIATED
WITH SUSTAINED HYPOTENSION AND TACHYARRHYTHMIAS IN
THE /04)-%
#(& TRIAL $OBUTAMINE IS PREFERRED
IN PATIENTS WHO ARE HYPOTENSIVE SYSTOLIC "0
MM (G SINCE IT EXERTS ITS EFFECTS BY STIMULATING `
ADRENERGIC RECEPTORS (IGHER DOSES ARE OFTEN REQUIRED
IN PATIENTS ON CHRONIC `
BLOCKER THERAPY -ILRINONE
IS A PHOSPHODIESTERASE INHIBITOR AND ITS ACTION IS NOT
IMPACTED BY CONCOMITANT `
BLOCKER USE -ILRINONE
DOESNT INCREASE MYOCARDIAL OXYGEN CONSUMPTION
OR EFFECT HEART RATE TO THE SAME DEGREE THAT DOBUTA
MINE DOES )N GENERAL GIVEN THEIR INABILITY TO AFFECT
OUTCOME AND INCREASED INCIDENCE OF ADVERSE EFFECTS
INOTROPIC SUPPORT SHOULD BE RESERVED FOR PATIENTS WITH
VERY LOW CARDIAC OUTPUT 4HEY SHOULD ONLY BE USED IN
THE %$ SETTING ON PATIENTS WITH SYMPTOMATIC HYPOTEN
SION UNTIL FURTHER THERAPY INTRA
AORTIC BALLOON PUMP
CAN BE INSTITUTED
#ALCIUM SENSITIZERS SUCH AS LEVOSIMENDAN PRODUCE
INCREASED INOTROPY IN A CYCLIC !-0
INDEPENDENT
FASHION BY INCREASING THE SENSITIVITY OF TROPONIN # TO
INTRACELLULAR IONIZED CALCIUM AS WELL AS PERIPHERAL
VASODILATION THROUGH THE VASCULAR +
!40ASE CHAN
NELS !N EFFECTIVE POSITIVE INOTROPE LEVOSIMENDAN
INCREASES IN STROKE VOLUME AND CARDIAC INDEX AND DE
CREASES 0#70 RIGHT ATRIAL PRESSURES PULMONARY AR
TERIAL PRESSURES AND MEAN ARTERIAL PRESSURES )N THIS
STUDY THE HEMODYNAMIC EFFECTS WERE MAINTAINED DUR
ING A HOUR INFUSION AND FOR AT LEAST HOURS AFTER
DISCONTINUATION 7HEN LEVOSIMENDAN WAS ADDED TO
DOBUTAMINE IN .EW 9ORK (EART !SSOCIATION CLASS )6
PATIENTS REFRACTORY TO DOBUTAMINE AND FUROSEMIDE
OF PATIENTS GETTING ALL THREE AGENTS COMPARED TO
NONE IN THE STANDARD GROUP EXPERIENCED A IN
CREASE IN CARDIAC INDEX 4HIS EXCITING AGENT IS IN THE
EARLY CLINICAL TRIALS
6ASODILATORS REDUCE PRELOAD AND AFTERLOAD ENHANCING
VENTRICULAR FUNCTION AND CARDIAC OUTPUT BY IMPROVING
RESTING HEMODYNAMICS 6ASODILATORS REDUCE VENTRIC
ULAR lLING PRESSURES 0#70 AND PRELOAD AND OVER
TIME MYOCARDIAL OXYGEN CONSUMPTION 6ASODILATORS
ALSO DECREASE SYSTEMIC VASCULAR RESISTANCE 362 OR
AFTERLOAD REDUCE VENTRICULAR WORKLOAD INCREASE
STROKE VOLUME AND IMPROVE CARDIAC OUTPUT
.ITRATES IN PARTICULAR NITROGLYCERIN HAVE BEEN THE
lRST LINE PREHOSPITAL AND %$ THERAPY FOR PATIENTS WITH
SEVERE SYMPTOMS .ITRATES NITROGLYCERIN AND NITRO
PRUSSIDE ACT BY INCREASING CYCLIC GUANOSINE MONO
PHOSPHATE IN THE VASCULAR SMOOTH MUSCLE LEADING TO
VASODILATION 4HEY IMPROVE SYMPTOMS AND DECREASE
0#70 RELATIVELY QUICKLY .ITROGLYCERIN USE IS LIMITED
BY FEAR OF HYPOTENSION AND NEED FOR TITRATION SECOND
ARY TACHYPHYLAXIS YET IT IS FREQUENTLY UNDERDOSED
.ITROGLYCERIN HAS DIRECT AFFECTS ON LARGE CORONARY AR
TERIES AND INCREASES COLLATERAL mOW MAKING IT A USEFUL
IN PATIENTS WITH MYOCARDIAL ISCHEMIA (OWEVER THERE
ARE NO TRIALS LOOKING AT ITS OUTCOME EFlCACY .ITRO
PRUSSIDE WHILE EFlCACIOUS IS USED INFREQUENTLY DUE
TO CONCERNS ABOUT THIOCYANATE TOXICITY ESPECIALLY IN
THE FACE OF HEPATIC OR RENAL HYPOPERFUSION DYSFUNC
TION )T CAN ALSO PRECIPITATE PROFOUND HYPOTENSION
EXACERBATE ISCHEMIA BY INDUCING CORONARY STEAL AND
REQUIRES INVASIVE MONITORING "OTH OF THESE AGENTS
CAUSE REmEX ACTIVATION OF THE 2!!3 AND SYMPATHETIC
NERVOUS SYSTEM WHICH LIMITS THEIR LONG TERM USE
!NGIOTENSIN CONVERTING ENZYME !#% INHIBITION
BLOCKS CONVERSION OF ANGIOTENSIN ) INTO ANGIOTENSIN ))
RESULTING IN DIMINISHED SYSTEMIC VASCULAR RESISTANCE
BLOOD PRESSURE PRELOAD AND AFTERLOAD !#% INHIBITORS
ALSO BLOCK THE DEGRADATION OF BRADYKININS A NATURAL
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LY OCCURRING VASODILATOR !#% INHIBITOR
THERAPY INCREASES RENAL PERFUSION AND DE
CREASE RENAL VASCULAR RESISTANCE IMPROV
ING GLOMERULAR lLTRATION RATE BY INDUCING
VASODILATION IN BOTH AFFERENT AND EFFERENT
ARTERIOLES 4HE MAJOR DRAWBACK TO THE USE
OF INTRAVENOUS !#% INHIBITORS SUCH AS
ENALAPRILAT IN THE ACUTE SETTING IS ITS PRO
PENSITY TO INDUCE HYPOTENSION )N THE STA
BLE PATIENT THE AGENTS MAJOR LIMITATIONS
ARE RENAL INSUFlCIENCY AND ANGIOEDEMA
%NALAPRILAT HAS BEEN USED IN THE SETTING
OF !$(& SECONDARY TO UNCONTROLLED HY
PERTENSION /RAL !#% INHIBITORS ARE REC
OMMENDED EARLY OUT FOR THOSE PATIENTS
NOT ALREADY RECEIVING THEM (OWEVER THE
PATIENT MUST BE HEMODYNAMICALLY STABLE
BEFORE THESE AGENTS ARE INITIATED AND THIS
LIMITS THEIR AGGRESSIVE UP FRONT USE IN THE
%$ !NGIOTENSIN RECEPTOR BLOCKER CAN BE
SUBSTITUTED IN PATIENTS WHO CANT TOLERATE
!#% INHIBITORS
2ECENT ATTENTION HAS BEEN FOCUSED ON THE
ACUTE BLOCKADE OF DELETERIOUS NEUROHOR
MONES %NDOTHELIN %4 IS A VASOCON
STRICTOR PEPTIDE RELEASED FROM VASCULAR
ENDOTHELIUM AND SMOOTH MUSCLE OF THE
RENAL AND PULMONARY SYSTEMS 4EZOSEN
TAN IS A HIGHLY SPECIlC AND POTENT %4
RECEPTOR ANTAGONIST 4HERE IS A DOSE DE
PENDENT INCREASE IN CARDIAC INDEX DUE TO
VASODILATION AND DECREASE IN 0#70 )N
THE 2)4: PROJECT TEZOSENTAN IMPROVED
HEMODYNAMIC BUT NOT CLINICAL OUTCOME OF
PATIENTS WITH ACUTE HEART FAILURE ! RECENT
TRIAL EVALUATING LOWER DOSES IN HOSPITAL
IZED !$(& PATIENTS WITH DYSPNEA DESPITE
INITIAL TREATMENT SHOWED INCREASED CAR
DIAC INDEX AND DECREASED 0#70 WITHIN
HOURS AT THE MGHOUR AND MGHOUR
TREATMENT GROUPS AND BY HOURS IN THE
MGHOUR COHORT 4HE EFFECT CONTINUED
BEYOND TREATMENT DISCONTINUATION IN THE
MGHOUR GROUP %NDOTHELIUM LEVELS
WERE INCREASED IN THE HIGHER DOSE GROUPS
SUGGESTING SYMPATHETIC NERVOUS SYSTEM
ACTIVATION BUT NOT IN THE MGHOUR SUB
SET 4EZOSENTANS EFFECT WHILE CLINICALLY
SIGNIlCANT IS NOT PRESENTLY APPROPRIATE
FOR THE %$ GIVEN ITS DELAYED ONSET
4HE NATRIURETIC PEPTIDE FAMILY CONSISTS OF
FOUR DISTINCT PEPTIDES !TRIAL NATRIURETIC
PEPTIDES !.0 AND "
TYPE NATRIURETIC PEP
TIDES ".0 ARE STRUCTURALLY SIMILAR #
TYPE
NATRIURETIC PEPTIDES #.0 AND $
TYPE NA
TRIURETIC PEPTIDES $.0 ARE LESS WELL CHAR
ACTERIZED !TRIAL AND "
TYPE NATRIURETIC PEP
TIDES HAVE IMPORTANT CENTRAL AND PERIPHERAL
SYMPATHOINHIBITORY EFFECTS $AMPENING OF
THE BARORECEPTORS SUPPRESSED RELEASE OF
CATECHOLAMINE FROM AUTONOMIC NERVE lND
INGS AND ESPECIALLY SUPPRESSION OF SYM
PATHETIC OUTmOW FROM THE CENTRAL NERVOUS
SYSTEM HAVE ALL BEEN REPORTED
4HE LONG
TERM CONTINUOUS INFUSION OF
!.0 HAS BEEN SHOWN TO BE CLINICALLY
USEFUL IN PATIENTS WITH SEVERE ACUTE HEART
FAILURE (EMODYNAMIC MEASUREMENTS
EVALUATED BY 3WAN
'ANZ CATHETER SIGNIl
CANTLY IMPROVED WITH !.0 )N A RECENT
STUDY HEMODYNAMIC INDICES CHARACTER
IZED BY DECREASES IN RIGHT ATRIAL PRES
SURE MEAN PULMONARY ARTERIAL PRESSURE
AND 0#70 AND AN INCREASE IN CARDIAC
INDEX WERE OBSERVED AFTER !.0 INFU
SION ,EFT VENTRICULAR PERFORMANCE WAS
ENHANCED WITHOUT THE DEVELOPMENT OF
TOLERANCE 4HE ACTIVATION OF THE 2!!3
PROMOTES STRUCTURAL REMODELING OF THE
HEART AND PROGRESSION OF HEART FAILURE
!.0 THEREBY IMPROVED LEFT VENTRICULAR
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FUNCTION POSSIBLY BY BLUNTING MYOCARDIAL
REMODELING 7HILE AVAILABLE IN !SIA
AND %UROPE !.0 IS NOT APPROVED FOR USE
IN THE 5NITED 3TATES
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PRODUCED IN THE VENTRICLES IN RESPONSE TO
INCREASED WALL STRESS THAT OCCURS FROM VOL
UME OVERLOAD IN !$(& PATIENTS .ESIRIT
IDE IS THE lRST NATRIURETIC PEPTIDE IDENTI
CAL TO ENDOGENOUS ".0 TO BE AVAILABLE
IN THE 5NITED 3TATES FOR THE TREATMENT OF
!$(& 7ITHIN MINUTES OF ADMINISTRA
TION NESIRITIDE PRODUCES SIGNIlCANT REDUC
TIONS IN 0#70 RIGHT ATRIAL PRESSURE AND
SYSTEMIC VASCULAR RESISTANCE AS WELL AS
CONCOMITANT INCREASES IN STROKE VOLUME
AND CARDIAC OUTPUT .ESIRITIDE HAS ADDI
TIONAL ADVANTAGES OVER OTHER VASODILATORS
SUCH AS NITROGLYCERIN INCLUDING DIURESIS
NATRIURESIS AND LUSITROPY 4HE BENElCIAL
CORONARY ARTERY EFFECTS OF NITROGLYCERIN
ARE ALSO PRESENT IN NESIRITIDE !DDITION
ALLY NESIRITIDE LACKS THE PROARRHYTHMIC
AND TACHYCARDIA SEEN WITH INOTROPES AND
MANY VASODILATORS
4HE 6ASODILATION IN THE -ANAGEMENT OF
!CUTE #ONGESTIVE (EAR &AILURE 6-!#
TRIAL COMPARED THE USE OF NESIRITIDE NI
TROGLYCERIN OR PLACEBO IN ADDITION TO STAN
DARD THERAPY IN PATIENTS WITH !$(&
4HIS SAFETY AND EFlCACY TRIAL FOUND THAT
NESIRITIDE REDUCED 0#70 MORE THAN EI
THER NITROGLYCERIN OR PLACEBO AT HOURS
AND HOURS )MPROVEMENTS IN DYSPNEA
AND GLOBAL CLINICAL STATUS IN THE NESIRIT
IDE TREATED PATIENTS WERE GREATER THAN
THOSE IN THE PLACEBO RECIPIENTS AND SIMI
LAR TO THOSE IN THE NITROGLYCERIN GROUP
.ESIRITIDES HEMODYNAMIC EFFECTERS WERE
LONG
LASTING WITHOUT THE NEED FOR UPWARD
TITRATION WHEREAS TITRATION WAS NECESSARY
IN ORDER TO MAINTAIN NITROGLYCERINS EF
FECT 4HIS WAS MOST STRIKING IN THE SUBSET
OF PATIENTS WITH RIGHT HEART CATHETERS ON
A CONSTANT DOSE OF NITROGLYCERIN WHERE
RAPID ATTENUATION OF THE DESIRED EFFECT AND
RISE IN 0#70 WAS SEEN AT HOURS
".0 DOESNT INCREASE HEART RATE OR PRO
VOKE ARRHYTHMIAS AND HAS NO INOTROPIC
EFFECTS 4HIS LACK OF ARRHYTHMOGENICITY
IS ESPECIALLY IMPORTANT IN HEART FAILURE
PATIENTS WITH ATRIAL lBRILLATION AND THOSE
PREDISPOSED TO VENTRICULAR TACHYCARDIA
4HE 02%#%$%.4 STUDY COMPARED THE
PROARRHYTHMIC EFFECTS OF DOBUTAMINE VER
SUS DOSES OF NESIRITIDE IN PATIENTS
$OBUTAMINE SIGNIlCANTLY INCREASED VEN
TRICULAR TACHYCARDIA EVENTS .ESIRITIDE
DID NOT INCREASE HEART RATE DESPITE GREATER
REDUCTION IN BLOOD PRESSURE "OTH AGENTS
WERE EQUALLY EFFECTIVE IN IMPROVING SIGNS
AND SYMPTOMS OF HEART FAILURE #OMPARED
TO DOBUTAMINE NESIRITIDE REDUCED
DAY
HOSPITAL READMISSIONS FOR HEART FAILURE AND
HAD LOWER
MONTH MORTALITY
)N THE 0ROSPECTIVE 2ANDOMIZED /UTCOMES
3TUDY OF !CUTELY $ECOMPENSATED #ON
GESTIVE (EART &AILURE 4REATED )NITIALLY
IN /UTPATIENTS WITH .ATRECOR 02/!#
4)/. STUDY PATIENTS WERE RANDOM
IZED TO STANDARD CARE OR AT LEAST HOURS
OF NESIRITIDE INFUSION IN AN %$ OBSERVA
TION SETTING )MPORTANTLY NONE OF THESE PA
TIENTS WAS SUBJECT TO INVASIVE OR )#5 LEVEL
MONITORING IN THE %$ YET DID WELL -OR
TALITY RATES AND COMPLICATIONS WERE SIMILAR
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BETWEEN THE TWO GROUPS .ESIRITIDE WAS
ASSOCIATED WITH A REDUCTION IN HOSPI
TAL READMISSION WITHIN DAYS COMPARED
WITH STANDARD THERAPY AND A SUBSTANTIAL
DECREASE IN TOTAL LENGTH OF STAY OVER THE
ENSUING MONTHS AFTER THE INDEX VISIT
)N A POOLED ANALYSIS FROM THE 02/!#
4)/. 6-!# AND .3'%4 TRIALS
THE SHORT TERM RISK OF DEATH FROM NESIRIT
IDE WAS INVESTIGATED !S NONE OF THE
STUDIES INCLUDED IN THE POOLED ANALYSIS
WERE POWERED TO DETERMINE MORTALITY DIF
FERENCES THERE IS NO CONCLUSIVE EVIDENCE
OF HARM 4HE MANUSCRIPT CONCLUDED THAT
WHEN COMPARED TO NONIONOTROPIC BASED
THERAPY NESIRITIDE MAY BE ASSOCIATED WITH
AN INCREASED RISK OF DEATH &URTHER STUDY
WITH MORTALITY OUTCOMES OF NESIRITIDE
COMPARED TO CONVENTIONAL THERAPY HAVE
YET TO OCCUR !S WITH ANY NEW THERAPY
THE FAVORABLE ATTRIBUTES MUST BE WEIGHED
AGAINST THE POTENTIAL RISKS
%ARLY 'OAL $IRECTED 4HERAPY
%ARLY GOAL DIRECTED THERAPY %'$4 AP
PROACH EMPHASIZES AGGRESSIVE UPFRONT
TREATMENT BECAUSE PRELIMINARY EVALU
ATIONS HAVE SHOWN THAT PATIENTS TREATED
EARLY OUT TEND TO HAVE SHORTER HOSPITAL
STAYS AND BETTER OUTCOMES THAN THOSE
WHOSE INTERVENTION IS DELAYED )T AIMS
TO ACHIEVE HEMODYNAMIC AND RESPI
RATORY IMPROVEMENT PROMPT RELIEF OF
SYMPTOMS ENHANCED DECISION MAKING
IN THE %$ WITH AN EMPHASIS ON TIMELY
TRANSITION TO INPATIENT CARE IF INDICATED
EARLY INITIATION OF THERAPY ALSO FACILITATES
HOSPITAL DISCHARGE AND AVOIDANCE OF
HIGH RESOURCE UTILIZATION #ARE NEEDS
TO FOCUS ON RAPID INITIATION OF PROVEN
THERAPIES THAT IMPROVE PATIENT SYMPTOM
AND CARDIORESPIRATORY STATUS WITHOUT
PLACING THE PATIENT AT RISK FOR IMMEDIATE
ARRHYTHMIA HYPOTENSION ISCHEMIA AND
DELAYED WORSENING RENAL INSUFlCIENCY
TOXICITY ADVERSE EVENTS 4HERE IS GROW
ING EVIDENCE THAT %'$4 HAS BOTH CLINICAL
AND ECONOMIC ADVANTAGES OVER MORE CON
SERVATIVE TREATMENT APPROACHES
4HERE IS A SUBPOPULATION OF PATIENTS
MODERATELY SICK REQUIRING MORE THAN A
FEW HOURS OF CARE WHO DONT NECESSARILY
NEED HOSPITAL ADMISSION 4HE AVAILABILITY
OF AN %$ OBSERVATION UNIT MAKES GOOD
CLINICAL AND ECONOMIC SENSE %'$4 CAN
BE INITIATED AND PATIENTS MONITORED FOR
IMPROVEMENT 0ATIENT SELECTION IS CRITI
CALLY IMPORTANT IN DETERMINING WHO WILL
MOST BENElT FROM AN OBSERVATION UNIT
STAY MATCHING ACUITY WITH AVAILABLE SER
VICES 'ENERAL SELECTION CRITERIA INCLUDE
THE FOLLOWING
ADEQUATE SYSTEMIC PERFUSION NORMAL
MENTAL STATUS
EVIDENCE OF REASONABLE
HEMODYNAMIC STABILITY (2 AND
BEATSMIN SYSTOLIC "0
AND MM (G OXYGEN SATURATION
NO EVIDENCE OF ACUTE CARDIAC
ISCHEMIA BY %#' OR BIOMARKERS
CHEST X RAY lNDINGS COMPATIBLE WITH
THE DIAGNOSIS OF HEART FAILURE
DIAGNOSIS OF (& ".0 PG
M, WITHOUT OTHER CONFOUNDING
MORBIDITIES
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MONARY CONGESTION VOLUME OVERLOAD
AND AN ASSESSMENT OF PERFUSION CARDIAC
OUTPUT Q}i R 7HILE TREATMENT AL
GORITHMS FOCUS ON PARENTAL THERAPY DUR
ING THE EARLY PHASE CONTINUATION OF THE
PATIENTS CHRONIC HEART FAILURE MEDICA
TION INCLUDING BLOCKERS AND !#% IN
HIBITORS ARE IMPORTANT -ILD CONGESTION
IMPROVES WITH INTRAVENOUS DIURETICS
-ONITORING OF URINE OUTPUT IS CRITICAL &OR
THOSE WITH NORMAL RENAL FUNCTION A GOAL OF
MLHR IS ACCEPTABLE 0ATIENTS WITH IN
ADEQUATE RESPONSE TO FUROSEMIDE SHOULD
BE ASSESSED FOR THE PRESENCE OF MODERATE
TO SEVERE VOLUME OVERLOAD AND VASODILA
TOR THERAPY SHOULD BE CONSIDERED )NTRA
VENOUS NITROGLYCERIN OR NESIRITIDE SHOULD
BE STARTED IN PATIENTS WITH ADEQUATE BLOOD
PRESSURE TO SPEED RELIEF OF CONGESTION
)F NITROGLYCERIN IS USED IT WILL BE NECES
SARY TO UP TITRATE THE INFUSION FREQUENTLY
0ATIENTS WITH EVIDENCE OF POOR PERFUSION
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4REATMENT OPTIONS FOR PATIENTS WITH HEART FAILURE AFFECT
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THE PATHOPHYSIOLOGICAL MECHANISMS THAT ARE STIMULATED
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IN HEART FAILURE !NGIOTENSIN
CONVERTINGnENZYME !#%
INHIBITORS AND ANGIOTENSIN
RECEPTOR BLOCKERS DECREASE
AFTERLOAD BY INTERFERING WITH THE RENINnANGIOTENSINnALDOSTERONE SYSTEM RESULTING IN PERIPHERAL VASODILATATION 4HEY ALSO
AFFECT LEFT VENTRICULAR HYPERTROPHY REMODELING AND RENAL BLOOD mOW !LDOSTERONE PRODUCTION BY THE ADRENAL GLANDS IS
INCREASED IN HEART FAILURE )T STIMULATES RENAL SODIUM RETENTION AND POTASSIUM EXCRETION AND PROMOTES VENTRICULAR AND
VASCULAR HYPERTROPHY !LDOSTERONE ANTAGONISTS COUNTERACT THE MANY EFFECTS OF ALDOSTERONE $IURETICS DECREASE PRELOAD
BY STIMULATING NATRIURESIS IN THE KIDNEYS $IGOXIN AFFECTS THE .A + n!40ASE PUMP IN THE MYOCARDIAL CELL INCREASING
CONTRACTILITY )NOTROPES SUCH AS DOBUTAMINE AND MILRINONE INCREASE MYOCARDIAL CONTRACTILITY "ETA
BLOCKERS INHIBIT THE
SYMPATHETIC NERVOUS SYSTEM AND ADRENERGIC RECEPTORS 4HEY SLOW THE HEART RATE DECREASE BLOOD PRESSURE AND HAVE
A DIRECT BENElCIAL EFFECT ON THE MYOCARDIUM ENHANCING REVERSE REMODELING 3ELECTED AGENTS THAT ALSO BLOCK THE ALPHA
ADRENERGIC RECEPTORS CAN CAUSE VASODILATATION 6ASODILATOR THERAPY SUCH AS COMBINATION THERAPY WITH HYDRALAZINE AND
ISOSORBIDE DINITRATE DECREASES AFTERLOAD BY COUNTERACTING PERIPHERAL VASOCONSTRICTION #ARDIAC RESYNCHRONIZATION THERAPY
WITH BIVENTRICULAR PACING IMPROVES LEFT VENTRICULAR FUNCTION AND FAVORS REVERSE REMODELING .ESIRITIDE BRAIN NATRIURETIC
PEPTIDE DECREASES PRELOAD BY STIMULATING DIURESIS AND DECREASES AFTERLOAD BY VASODILATATION %XERCISE IMPROVES PERIPH
ERAL BLOOD mOW BY EVENTUALLY COUNTERACTING PERIPHERAL VASOCONSTRICTION )T ALSO IMPROVES SKELETAL
MUSCLE PHYSIOLOGY
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SHOULD BE CONSIDERED FOR INOTROPIC SUPPORT $OBUTA
MINE SHOULD BE STARTED IN PATIENTS WITH LOW CARDIAC
OUTPUT AND SYSTOLIC BLOOD PRESSURE MM (G 4HEY
MAY REQUIRE VASOPRESSOR SUPPORT IF HYPOTENSION DE
VELOPS 0ATIENTS WITH LOW CARDIAC OUTPUT BUT ADEQUATE
BLOOD PRESSURE MAY BENElT FROM MILRINONE ESPECIAL
LY IF THEY ARE ALREADY TAKING BETA
BLOCKERS 4HOSE RE
QUIRING INOTROPIC SUPPORT WILL REQUIRE ADMISSION TO AN
INTENSIVE CARE UNIT 4HOSE RECEIVING VASODILATORS CAN
OFTEN BE MANAGED IN A LESS ACUTE SETTING TELEMETRY OR
%$ OBSERVATION UNIT 0RELIMINARY ANALYSIS FROM THE
!$(%2% REGISTRY INDICATED THAT LENGTH OF STAY WAS
REDUCED BY UP TO A THIRD IN PATIENTS RECEIVING VASO
ACTIVE AGENTS VASODILATORS NESIRITIDE OR INOTROPES IN
THE %$ OR OBSERVATION UNIT COMPARED WITH PATIENTS
WHO HAD VASOACTIVE THERAPY INITIATED IN THE HOSPITAL
4HIS EARLY INITIATION OF EMERGENCY DEPARTMENT THERAPY
IS ASSOCIATED WITH LOWER HOSPITAL MORTALITY DECREASED
FREQUENCY OF INVASIVE PROCEDURES AND DECREASED )#5
LENGTH OF STAY 4HUS EARLY TARGETED VASOACTIVE THERAPY
IN THE !$(& PATIENT SEEMS TO BE VERY PROMISING
.EW PHARMACOLOGICAL AGENTS UNDER INVESTIGATION AT
TEMPT TO ENHANCE OUR UNDERSTANDING OF ABNORMAL
NEUROENDOCRINE FUNCTION IN HEART FAILURE "Y SPECIl
CALLY TARGETING KEY POINTS SUCH AS THE ACTIVATION AND
FEEDBACK PROCESS THEY MAY PREVENT DISEASE PROGRES
SION AND ACUTE DECOMPENSATION 7HILE WE AWAIT
NEW TREATMENT MODALITIES CURRENT %$ EFFORTS MUST
FOCUS ON THE EARLY IMPLEMENTATION OF EFFECTIVE STRATE
GIES TO IMPROVE SYMPTOMS AND CORRECT THE UNDERLYING
PHYSIOLOGY
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!$(& INITIAL THERAPY WITH OXYGEN AND DIURETICS WILL
NOT ADEQUATELY REDUCE lLLING PRESSURES OR IMPROVE
CARDIAC OUTPUT ENOUGH TO IMPROVE SYMPTOMS )NOTRO
PES IMPROVE SYMPTOMS IN THE SHORT
TERM BUT ARE DEL
ETERIOUS IN THE LONG
RUN 6ASODILATORS ARE FREQUENTLY
NECESSARY AS THEY ADDRESS THE PRIMARY UNDERLYING
PATHOPHYSIOLOGY OF HEART FAILURE .ITROGLYCERIN AND
NITROPRUSSIDE ARE EFFECTIVE BUT THEIR USE IS HAMPERED
BY ADVERSE EFFECTS AND LIMITATIONS .ATRIURETIC PEP
TIDES SUCH AS NESIRITIDE WITH THEIR NEUROHORMONAL
ANTAGONISM MAY OFFER SEVERAL BENElTS OVER CONVEN
TIONAL VASODILATORS AND INOTROPES FOR THE TREATMENT OF
!$(& )T HAS BEEN SHOWN THAT NESIRITIDE CAN BE USED
SAFELY IN THE %$ AND UPFRONT USE CAN REDUCE HOSPITAL
LENGTH OF STAY
%MERGENCY $IAGNOSIS AND 4REATMENT OF
!CUTE $ECOMPENSATED (EART &AILURE !$(&
,
,
-
+IVIKKO - ,EHTONEN , #OLUCCI 73 3USTAINED HEMODYNAMIC
EFFECTS OF INTRAVENOUS LEVOSIMENDAN #IRCULATION
!GHABABIAN 26 !CUTELY DECOMPENSATED HEART FAILURE
OPPORTUNITIES TO IMPROVE CARE AND OUTCOMES IN THE EMERGENCY
DEPARTMENT 2EV #ARDIOVASC -ED SUPPL 3
-AGNER ** 2OYSTON $ (EART &AILURE "R * !NESTH
.ANAS *. 0APAZOGLOU 00 4ERROVITIS *6 ET AL (EMODYNAMIC
EFFECTS F LEVOSIMENDAN ADDED TO DOBUTAMINE IN PATIENTS WITH
DECOMPENSATED ADVANCED HEART FAILURE REFRACTORY TO DOBUTAMINE
ALONE !M * #ARDIOL
&ONAROW '# 4HE TREATMENT TARGETS IN ACUTE DECOMPENSATED HEART
FAILURE 2EV #ARDIOVASC -ED 3
.OHRIA ! ,EWIS % 3TEVENSON ,7 -EDICAL MANAGEMENT OF
ADVANCED HEART FAILURE *!-!
6ANDERHEYDEN - "ARTUNEK * 'OETHALS - "RAIN AND OTHER
NATRIURETIC PEPTIDES MOLECULAR ASPECTS %UR * (EART &AIL
3TRAIN 7$ 4HE USE OF RECOMBINANT HUMAN "
TYPE NATRIURETIC
PEPTIDE IN THE MANAGEMENT OF ACUTE DECOMPENSATED HEART FAILURE
)NT * #LIN 0RACT
(OLLANDER * 0HARMACOLOGIC MANAGEMENT OPTIONS IN THE EMERGENCY
DEPARTMENT !DV IN (EART &AIL
6AN DER 7AL -( *AARSMA 4 VAN 6ELDHUISEN $* .ON COMPLIANCE
IN PATIENTS WITH HEART FAILURE HOW CAN WE MANAGE IT %UR * (EART
&AIL
7ELSCH *D (EISER 2- 3CHOOLER -0 ET AL #HARACTERISTICS
AND TREATMENT OF PATIENTS WITH HEART FAILURE IN THE EMERGENCY
DEPARTMENT * %MERG .URS
3HARMA - 4EERLINK *2 ! RATIONAL APPROACH FOR THE TREATMENT OF
ACUTE HEART FAILURE CURRENT STRATEGIES AND FUTURE OPTIONS #URR /PIN
#ARDIOL
-OAZEMI + #HANA * 7ILLARD !- +OCHERIL !' )NTRAVENOUS
VASODILATOR THERAPY IN CONGESTIVE HEART FAILURE $RUGS !GING
4ORRE !MIONE ' 9OUNG *" #OLUCCI 73 ET AL (EMODYNAMIC
AND CLINICAL EFFECTS OF TEZOSENTAN AN INTRAVENOUS DUAL ENDOTHELIN
RECEPTOR ANTAGONIST IN PATIENTS HOSPTIALIZED FOR ACUTE
DECOMPENSATED HEART FAILURE * !M #OLLL #ARDIOL
#OTTER' +ALUSKI % 3TANGL + ET AL 4HE HEMODYNAMIC AND
NEUROHORMONAL EFFECTS OF LOW DOSE TEZOSENTAN AN ENDOTHELIN !"
RECEPTOR ANTAGONIST IN PATIENTS WITH ACUTE HEART FAILURE %UR * (EART
&AIL
DE $ENUS 3 0(ARAND # 7ILLIAMSON $2 "RAIN .ATRIURETIC PEPTIDE
IN THE MANAGEMENT OF HEART FAILURE #HEST
+ASAMA 3 4OYAMA 4 +UMAKURA ( ET AL %FFECTS OF INTRAVENOUS
ATRIAL NATRIURETIC PEPTIDE ON CARDIAC SYMPATHETIC NERVE ACTIVITY IN
PATIENTS WITH DECOMPENSATED CONGESTIVE HEART FAILURE * .UCL -ED
#OHN *. &ERRARI 2 3HARPE . #ARDIAC REMODELING CONCEPTS AND
CLINICAL IMPLICATIONS n A CONSENSUS PAPER FROM AN INTERNATIONAL
FORUM ON CARDIAC REMODELING * !M #OLL #ARDIOL
$I$OMENICO 2* 0ARK (9 3OUTHWORTH -2 ET AL 'UIDELINES FOR
ACUTE DECOMPENSATED HEART FAILURE TREATMENT !NN 0HARMACOTHER
6-!# INVESTIGATORS )NTRAVENOUS NESIRITIDE VS NITROGLYCERIN FOR
TREATMENT OF DECOMPENSATED CONGESTIVE HEART FAILURE A RANDOMIZED
CONTROLLED TRIAL *!-!
#ODY 2 #LINICAL TRAILS OF DIURETIC THERAPY IN HEART FAILURE
RESEARCH DIRECTIONS AND CLINICAL CONSIDERATIONS * !M #OLL
#ARDIOL! !
3ILVER -! (ORTON $0 #HALI *+ %LKAYAM 5 %FFECT OF NESIRITIDE
VERSUS DOBUTAMINE ON SHORT TERM OUTCOMES IN THE TREATMENT OF
PATIENTS WITH ACTUELY DECOMPENSATED HEART FAILURE !M * #OLL
#ARDIOL
+UBO 3( #LARK - ,ARAGH *( ET AL )DENTIlCATION OF NORMAL
NEUROHORMONAL ACTIVITY IN MILD CONGESTIVE HEART FAILURE AND
STIMULATING EFFECT OF UPRIGHT POSTURE AND DIURETICS !M * #ARDIOL
#OTTER ' -ETZKOR % +ALUSKI % ET AL 2ANDOMIZED TRIAL OF
HIGH DOSE ISOSORBIDE DINITRATE PLUS LOW DOSE FUROSEMIDE VERSUS
HIGH DOSE FUROSEMIDE PLUS LOW DOSE ISOSORBIDE DINITRATE IN SEVERE
PULMONARY EDEMA ,ANCET
3ALVADOR $2+ 2EY .2 2AMOS '# 0UNZALAN &%2 #ONTINUOUS
INFUSION VERSUS BOLUS INJECTION OF LOOP DIURETICS IN CONGESTIVE HEART
FAILURE #OCHRANE $ATABASE 3YSTEMATIC 2EVIEWS #$
'HEORGHIADE - .IAZI ) /UYANG * ET AL 6ASOPRESSIN 6 RECEPTOR
BLOCKADE WITH TOLVAPTAN IN PATIENTS WITH CHRONIC HEART FAILURE
RESULTS FROM A DOUBLE BLIND RANDOMIZED TRIAL #IRCULATION
3TEVENSON ,7 #LINICAL USE OF INOTROPIC THERAPY FOR HEART FAILURE
LOOKING BACKWARD OR FORWARD #IRCULATION
"URGER !* (ORTON $0 ,E*EMETEL 4 ET AL %FFECT OF NESIRITIDE
AND DOBUTAMINE ON VENTRICULAR ARRHYTHMIAS IN THE TREATMENT OF
PATIENTS WITH ACUTELY DECOMPENSATED CONGESTIVE HEART FAILURE THE
02%#%$%.4 STUDY !M (EART *
#UFFE -3 #ALIFF 2- !DAMS +& ET AL 3HORT TERM INTRAVENOUS
MILRINONE FOR ACUTE EXACERBATION OF CHRONIC HEART FAILURE *!-!
0EACOCK 7& %MERMAN #, THE 02/!#4)/. STUDY GROUP 3AFETY
AND EFlCACY OF NESIRITIDE IN THE TREATMENT OF DECOMPENSATED HEART
FAILURE IN OBSERVATION PATIENTS * !M #OLL #ARDIOL !
#OLUCCI 73 %LKAYAM 5 (ORTON $ ET AL )NTRAVENOUS NESIRITIDE A
NATRIURETIC PEPTIDE IN THE TREATMENT OF DECOMPENSATED CONGESTIVE HEART
FAILURE .ESIRITIDE 3TUDY 'ROUP. %NGL * -ED
3ACKNER "ERNSTEIN *$ +OWALSKI - &OX - ET AL 3HORT TERM 2ISK
OF $EATH !FTER 4REATMENT 7ITH .ESIRITIDE FOR $ECOMPENSATED
(EART &AILURE ! 0OOLED !NALYSIS OF 2ANDOMIZED #ONTROLLED 4RIALS
*!-!
3ALTZBERG -4 "ENElCIAL EFFECTS OF EARLY INITIATION OF VASOACTIVE
AGENTS IN PATIENTS WITH ACUTE DECOMPENSATED HEART FAILURE 2EV
#ARDIOVASC -ED SUPPL
0EACOCK 7& (EART &AILURE -ANAGEMENT IN THE EMERGENCY
DEPARTMENT OBSERVATION UNIT 0ROG IN #ARDIOVAS $IS
%MERMAN #, 0EACOCK 7& THE !$(%2% INVESTIGATORS %VOLVING
PATETERS OF CARE FOR DECOMPENSATED HEART FAILURE IMPLICATIONS FROM
THE !$(%2% REGISTRY DATABASE !CAD %MERG -ED
9OUNG *" .EW THERAPEUTIC CHOICES IN THE MANAGEMENT OF ACUTE
CONGESTIVE HEART FAILURE 2EV #ARDIOVASC -ED 3
#OPYRIGHT %-#2%' )NTERNATIONAL
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$EPARTMENT OF %MERGENCY -EDICINE 4HE #LEVELAND #LINIC &OUNDATION
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$ISCUSS THE APPLICATION AND LIMITATIONS OF ".0 TESTING IN THE EMERGENCY SETTING
$ESCRIBE THE APPROPRIATE CANDIDATE FOR ".0 THERAPY
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! ".0 EXPERT CONSENSUS PANEL CONSISTING OF INDIVIDUALS WITH BASIC METHODOLOGIC AND
CLINICAL EXPERTISE WAS CONVENED IN TO CREATE A SUMMARY DOCUMENT TO HELP GUIDE
THE CLINICIAN ON THE RECENT EXPLOSION OF NATRIURETIC PEPTIDE .0 DATA 4HIS DOCUMENT
CONTAINS THE DATA FROM THEIR RECOMMENDATIONS MOST APPLICABLE TO THE EMERGENCY
PHYSICIAN
.ATRIURETIC 0EPTIDE 0HYSIOLOGY
-ORE THAN A PUMP THE HEART IS A CRITICAL
ENDOCRINE ORGAN FUNCTIONING WITH OTHER
PHYSIOLOGICAL SYSTEMS TO CONTROL mUID
VOLUME -YOCYTES MANUFACTURE A FAM
ILY OF PEPTIDE HORMONES TERMED THE .0S
REPRESENTED BY ATRIAL NATRIURETIC PEPTIDE
!.0 AND "
TYPE NATRIURETIC PEPTIDE
".0 2ELEASE OF THE .0S IS STIMULATED
BY VOLUME OVERLOAD AND PHYSIOLOGI
CALLY THEY HAVE POWERFUL DIURETIC NATRI
URETIC AND VASCULAR SMOOTH MUSCLE RELAX
ING ACTIONS )MPORTANTLY THEY ALSO SERVE
AS ANTAGONISTS TO THE SYMPATHETIC NERVOUS
SYSTEM AND THE RENIN
ANGIOTENSIN
ALDO
STERONE AXIS 2!!3 2ELEASE OF .0S
RESULTS FROM CARDIAC WALL STRETCH VENTRIC
ULAR DILATION OR INCREASED PRESSURES FROM
CIRCULATORY VOLUME OVERLOAD 4HE EFFECTS
OF .0S RESULT IN LOWERING BLOOD VOLUME
AND PRESSURE
".0 IS DERIVED FROM A PRECURSOR PRE
PRO".0 WHICH UNDERGOES SEVERAL CLEAV
AGES 4HE ASSAY RELEVANT PRODUCTS ARE
THE INERT . TERMINAL PRO ".0 FRAGMENT
AND PHYSIOLOGICALLY ACTIVE ".0 ".0S
ARE PREFERENTIALLY PRODUCED AND SECRETED
BY THE CARDIAC VENTRICLES ALTHOUGH mUID
OVERLOAD MAY CAUSE RAPID ".0 MANUFAC
TURE IN BOTH HEART CHAMBERS 4HE PRIMARY
FUNCTION OF .0S IS TO DEFEND AGAINST VOL
UME OVERLOAD !FTER RELEASE INTO CIRCULA
TION ".0 ACTIONS ARE MODULATED AT TARGET
SITES BY SPECIlC CELL MEMBRANE RECEP
TORS TERMED ! " AND # WHICH MEDIATE
PHYSIOLOGICAL ACTIONS BY CYCLIC '-0
#YCLIC '-0 HAS POTENT VASODILATORY AC
TIONS ".0 ALSO CAUSES AN INTRAVASCULAR
mUID SHIFT FROM THE CAPILLARY BED INTO THE
INTERSTITIUM WHICH CONTRACTS INTRAVASCU
LAR VOLUME AND DECREASES "0 )N ADDI
TION ".0 IS A 2!!3 ANTAGONIST WHERE IT
COUNTERACTS SODIUM CONSERVATION VASO
CONSTRICTION AND VOLUME RETENTION ".0
ALSO INHIBITS THE RELEASE OF RENIN FROM
KIDNEY CELLS AND ALDOSTERONE FROM ADRE
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%MERGENCY $IAGNOSIS AND 4REATMENT OF
!CUTE $ECOMPENSATED (EART &AILURE !$(&
NAL CELLS ".0 IS PRIMARILY METABOLIZED BY THE .02
#
RECEPTOR ALTHOUGH SOME ADDITIONAL DEGRADATION MAY
OCCUR BY NEUTRAL ENDOPEPTIDASE
.EUTRAL ENDOPEP
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"IOLOGIC $ETERMINANTS ON ".0 -EASUREMENTS
"LOOD LEVELS OF .0S ARE AFFECTED BY A VARIETY OF FACTORS
INCLUDING CIRCADIAN RHYTHM AGE EXERCISE AND BODY
POSTURE -ANY DRUGS INCLUDING DIURETICS ANGIOTENSIN
CONVERTING ENZYME INHIBITORS ADRENERGIC AGONISTS SEX
AND THYROID HORMONES GLUCOCORTICOIDS SODIUM INTAKE
AND OTHER CONDITIONS IMPACT LEVELS ".0 INCREASES WITH
AGE AND GENDER "ASELINE AND PATHOLOGIC LEVELS ARE
HIGHER IN WOMEN 4HE AGE INDUCED ".0 INCREASE
MAY BE DUE TO THE DECLINE IN MYOCARDIAL FUNCTION OR
TO DECREASED CLEARANCE
".0 !SSAY
)T SHOULD BE MADE CLEAR THAT THE ".0 ASSAY IS NOT A
STAND
ALONE TEST )TS GREATEST VALUE IS WHEN IT IS USED
WITH THE PHYSICIANS CLINICAL JUDGMENT AND WITH OTHER
APPROPRIATE TESTING 4HE 4RIAGE ".0 ASSAY SYSTEM IS
THE ONLY &$! APPROVED POINT
OF CARE ASSAY )T RE
QUIRES MINUTES TO PERFORM AND REPORTS ".0 LEVELS
FROM TO PGM, 4HIS ASSAY IS RATED AS MOD
ERATELY COMPLEX ASSAY PER #LINICAL ,ABORATORY )M
PROVEMENT !MENDMENTS #,)! REGULATIONS
".0 FOR $IAGNOSIS OF (EART
&AILURE
$ESPITE ADVANCES IN OUR UNDER
STANDING OF HEART FAILURE (&
PATHOPHYSIOLOGY DIAGNOSIS IS
STILL DIFlCULT 7HILE EMERGEN
CY DEPARTMENT %$ DIAGNOSIS
NEEDS TO BE RAPID AND ACCURATE
THE SIGNS AND SYMPTOMS OF (&
ARE NONSPECIlC 2ESPIRATORY
DISTRESS CAN PRECLUDE OBTAINING
THE HISTORY AND DYSPNEA IS NON
SPECIlC IN THE ELDERLY OR OBESE
2OUTINE LABS %#' AND X RAYS
ARE ALSO NOT ACCURATE ENOUGH TO
ALWAYS MAKE THE CORRECT DIAGNO
SIS
#/.3%.353 34!4%-%.43
'%.%2!, #/--%.43
4HE LABORATORY SHOULD PERFORM ".0 TESTING
ON A CONTINUOUS
HOUR BASIS WITH A
TURN
AROUND
TIME 4!4 OF MINUTES OR
LESS 4HE 4!4 IS DElNED AS THE TIME FROM
BLOOD COLLECTION TO NOTIlCATION OF RESULT
TO PHYSICIAN OR CAREGIVER %ITHER CENTRAL
LABORATORY INSTRUMENTATION OR POINT OF CARE
TESTING SYSTEMS ARE ACCEPTABLE
% )N CONSIDERING .0 MEASUREMENTS ONE
NEEDS TO CAREFULLY CONSIDER LABORATORY
AND BIOLOGIC VARIATION INCLUDING GENDER
SEX OBESITY AND RENAL FUNCTION
% 4HE RESULTS OF NATRIURETIC TESTING IS
DEPENDENT ON THE TYPE OF TEST YOU ARE
OBTAINING . TERMINAL PRO ".0 AND
BIOACTIVE ".0 ARE ./4 INTERCHANGEABLE
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4HE "REATHING .OT 0ROPERLY STUDY WAS A LARGE MUL
TINATIONAL PROSPECTIVE STUDY USING ".0 TO EVALUATE
DYSPNEA IN DYSPNEIC %$ PATIENTS ".0 LEVELS
WERE MEASURED ON ARRIVAL AND PHYSICIANS ASSESSED
THE PROBABILITY OF THE PATIENT HAVING (& 4WO CARDI
OLOGISTS BLINDED TO THE ".0 LEVEL REVIEWED ALL DATA
AFTER HOSPITALIZATION TO PRODUCE A hGOLD STANDARDv
CLINICAL DIAGNOSIS ".0 LEVELS ALONE MORE ACCURATELY
PREDICTED THE PRESENCE OR ABSENCE OF (& THAN ANY OTH
ER lNDING 4HE PGM, CUTPOINT HAD A SEN
SITIVITY AND SPECIlCITY FOR A (& DIAGNOSIS )N
MULTIVARIATE ANALYSIS ".0 LEVELS ALWAYS CONTRIBUTED
TO THE DIAGNOSIS EVEN AFTER CONSIDERING FEATURES OF THE
HISTORY AND PHYSICAL EXAMINATION
".0 LEVELS MAY ALSO HELP IN DISPOSITION DECISIONS
4HE 2APID %MERGENCY $EPARTMENT (EART &AILURE /UT
PATIENT 2%$(/4 4RIAL DEMONSTRATED A hSTRONG DIS
CONNECTv BETWEEN THE PERCEIVED SEVERITY OF (& AND
ILLNESS SEVERITY AS DETERMINED BY ".0 /N AVERAGE
PATIENTS DISCHARGED FROM THE %$ HAD A HIGHER ".0
THAN THOSE ADMITTED PGM, VERSUS PGM,
RESPECTIVELY ".0 ALSO PREDICTED OUTCOMES OF PATIENTS
DISCHARGED HAD A ".0 PGM, HOWEVER
THERE WAS NO MORTALITY AT DAYS IF THE ".0 WAS LESS
THAN PGM,
4HE 3WISS "!3%, 3TUDY EXAMINED COST
EFFECTIVE
NESS OF USING ".0 THROUGH THE DIAGNOSIS AND HOSPITAL
IZATION IN ACUTE DECOMPENSATED HEART FAILURE !$(&
)N PATIENTS %$ MEASUREMENT OF ".0 WAS ASSO
CIATED WITH A DECREASE IN HOSPITAL ADMISSIONS
A
DAY DECLINE IN LENGTH OF STAY AND AN SAV
INGS WITH NO EFFECTS ON MORTALITY OR RE
HOSPITALIZATION
RATES
".0 AND 2ENAL &AILURE
#HRONIC KIDNEY DISEASE #+$ INmUENCES THE CUT
POINT FOR ".0 )N GENERAL AS #+$ ADVANCES A HIGHER
".0 CUT
POINT IS IMPLIED ! CUT
POINT OF APPROXI
MATELY PGM, IS REASONABLE FOR THOSE WITH AN
#/.3%.353 34!4%-%.4 53).' ".0 4/
(%,0 42)!'% %$ 0!4)%.43 7)4( $930.%!
".0 IS OF DIAGNOSTIC UTILITY IN THE EVALUATION
OF PATIENTS WITH ACUTE DYSPNEA 4HUS IN
NEW PATIENTS PRESENTING WITH DYSPNEA TO
AN EMERGENCY SETTING A HISTORY PHYSICAL
EXAMINATION CHEST X
RAY AND %#' SHOULD
BE UNDERTAKEN TOGETHER WITH LABORATORY
MEASUREMENTS THAT INCLUDE ".0 #URRENT
DATA SUGGEST THE FOLLOWING GUIDELINES
% !S ".0 RISES WITH AGE AND IS AFFECTED
BY GENDER COMORBIDITY AND DRUG USE IT
SHOULD NOT BE USED IN ISOLATION FROM THE
CLINICAL CONTEXT
% )F THE ".0 IS PGM, THEN (& IS
HIGHLY UNLIKELY .06
% )F THE ".0 IS PGM, THEN (& IS
HIGHLY LIKELY 006
% )F THE ".0 IS n PGM, CONSIDER
A BASELINE ".0 ELEVATED DUE TO STABLE
UNDERLYING DYSFUNCTION RIGHT VENTRICULAR
FAILURE FROM COR PULMONALE ACUTE
PULMONARY EMBOLISM OR RENAL FAILURE
% 0ATIENTS MAY PRESENT WITH (& AND A
NORMAL ".0 OR WITH LEVELS BELOW WHAT
IS EXPECTED IN THE FOLLOWING SITUATIONS
mASH PULMONARY EDEMA n HOURS (&
UP
STREAM FROM THE LEFT VENTRICLE SUCH
AS WITH ACUTE MITRAL REGURGITATION FROM
PAPILLARY MUSCLE RUPTURE AND OBESE
PATIENTS BODY MASS INDEX ;"-)=
ESTIMATED GLOMERULAR lLTRATION RATE '&2 M,
MIN M 5SING THIS APPROACH ".0 MAINTAINS A
HIGH LEVEL OF DIAGNOSTIC UTILITY WITH AN AREA UNDER THE
2/# CURVE OF ACROSS ALL #+$ GROUPS
%MERGENCY $IAGNOSIS AND 4REATMENT OF
!CUTE $ECOMPENSATED (EART &AILURE !$(&
#/.3%.353 34!4%-%.43 #/-/2")$)4)%3
!.$ 30%#)!, )335%3 4(!4 ).&,5%.#% 4(%
).4%202%4!4)/. /& ".0 ,%6%,3
% ".0 IS ALTERED WITH CHRONIC RENAL
INSUFlCIENCY ESTIMATED '&2 M,
MIN WITH A RECALIBRATION OF THE CUT OFF
VALUE TO PGM,
% ".0 IS HELPFUL IN THE EVALUATION OF
DYSPNEA WHEN IT IS VERY LOW OR HIGH .4
PRO ".0 HAS GREATER CORRELATION WITH
E'&2 THAN ".0 HENCE LEVELS CAN BE
ELEVATED EVEN WITH THE NORMAL AGE RELATED
DECLINE OF RENAL FUNCTION IN THE E'&2
M,MIN RANGE
% 7HEN THE E'&2 IS BELOW M,MIN .
TERMINAL PRO".0 CAN BE CONSIDERABLY
ELEVATED AND IN THIS SETTING ITS UTILITY IN
THE EVALUATION OF (& IS UNKNOWN
% "ASELINE ".0 LEVELS MIGHT THEREFORE BE
IMPORTANT IN DIALYSIS PATIENTS AS CHANGES
MOST LIKELY REmECT VOLUME STATUS 4HUS
A PRE
DIALYSIS ".0 MAY HELP DETERMINE
THE AMOUNT OF VOLUME WHICH SHOULD BE
REMOVED
#ARDIOPULMONARY $ISEASE
3OME NON
(& CARDIOPULMONARY DISEASE MAY CAUSE
".0 ELEVATIONS 4HESE INCLUDE COR PULMONALE LUNG
CANCER PULMONARY EMBOLISM 0% AND PRIMARY PUL
MONARY HYPERTENSION )N THESE ".0 MAY BE ELEVATED
BUT NOT TO THE EXTENT FOUND IN !$(& )N 0% ".0 MAY
BE PROGNOSTIC SINCE PATIENTS WITH A ".0 IN THE UPPER
NORMAL RANGE OR PGM, HAVE A HIGHER MORTAL
ITY RATE !LTHOUGH ".0 IS NOT AN ADEQUATE SCREENING
TEST FOR 0% IN THE SETTING OF A SUSPECTED OR CONlRMED
EMBOLIC EVENT A ".0 ELEVATION IMPLIES 26 PRESSURE
OVERLOAD AND INCREASED MORTALITY RISK &INALLY IN PRI
MARY PULMONARY HYPERTENSION ".0 ELEVATIONS PAR
ALLEL THE EXTENT OF PULMONARY HEMODYNAMIC CHANGES
AND RIGHT (&
#/.3%.353 34!4%-%.4 ".0 ).
05,-/.!29 !.$ !33/#)!4%$ #!2$)!#
$)3%!3%
% )N APPROXIMATELY OF PATIENTS WITH
PULMONARY DISEASE ".0 IS ELEVATED
IMPLYING COMBINED (& AND LUNG DISEASE
COR PULMONALE OR A MISDIAGNOSIS WHEN
THE TRUE ETIOLOGY OF DYSPNEA IS (&
% )N THE SETTING OF 0% ".0 IS ELEVATED IN
OF CASES AND IS ASSOCIATED WITH 26
PRESSURE OVERLOAD AND A HIGHER MORTALITY
".0 IS NOT DIAGNOSTIC FOR ACUTE 0%
% 0ULMONARY DISEASE WHICH RESULTS
IN PULMONARY HYPERTENSION AND 26
PRESSURE OR VOLUME OVERLOAD CAN LEAD TO
ELEVATED ".0 LEVELS USUALLY IN THE RANGE
OF
PGM,
0RESERVED 3YSTOLIC &UNCTION 03& (EART &AILURE
$IASTOLIC MYOCARDIAL DYSFUNCTION ALSO KNOWN AS 03&
IS THE CAUSE OF (& IN AS MANY OF OF CASES AND
IS ALSO ASSOCIATED WITH HIGH ".0 ".0 HAS BEEN
FOUND TO BE APPROXIMATELY HALF AS HIGH IN 03& AS IN
CASES OF SYSTOLIC DYSFUNCTION
#/.3%.353 34!4%-%.4 ".0 ).
$)!34/,)# $93&5.#4)/.
% ".0 MIGHT BE USED TO DETECT PATIENTS
WITH DIASTOLIC DYSFUNCTION
% ".0 CONCENTRATIONS ABOVE AGE
ADJUSTED
CUT
POINTS MAY IDENTIFY ELDERLY PATIENTS
WITH DIASTOLIC DYSFUNCTION
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/BESITY
/BESITY IS AN IMPORTANT RISK FACTOR FOR CORONARY AR
TERY DISEASE AND (&
0HYSIOLOGICALLY ADIPOSE TIS
SUE IS RELATED TO THE NATRIURETIC CLEARANCE RECEPTOR
AND OBESITY CAN INTERFERE WITH THE USUAL DIAGNOSTIC
APPROACH TO (& -EHRA DOCUMENTED AN INVERSE RE
LATIONSHIP BETWEEN "ASAL -ETABOLIC )NDEX "-) AND
".0 ,OWER LEVELS OF ".0 IN THE OBESE "-) +G
- WERE NOTED DESPITE SIMILAR SEVERITY OF (& COM
PARED TO A LEAN COHORT AND NEARLY OF OBESE PA
TIENTS HAD ".0 PGM,
GROUPED INTO ".0 QUARTILES HOURS AFTER !#3 ONSET
AN INCREASING ".0 WAS ASSOCIATED WITH HIGHER
MONTH MORTALITY AND THIS RELATIONSHIP PERSISTED EVEN
WITHOUT EVIDENCE OF (& OR MYOCARDIAL NECROSIS
#/.3%.353 34!4%-%.4 ".0 ). 35$$%.
$%!4( !#3 !.$ #!$
7HEN USED TOGETHER ".0 AND CARDIAC
TROPONIN PROVIDE A MORE EFFECTIVE TOOL
FOR IDENTIFYING PATIENTS AT INCREASED RISK
FOR CLINICALLY IMPORTANT CARDIAC EVENTS RE
LATED TO (& AND !#3 -ULTIMARKER PANELS
WITH ".0 AND TROPONIN ARE NOW AVAILABLE
WHERE EACH OF THESE MARKERS PROVIDE
UNIQUE AND INDEPENDENT OUTCOME DATA
#/.3%.353 34!4%-%.4 ".0 ). /"%3)49
% 3INCE OBESE PATIENTS BODY MASS
INDEX ;"-)= KGM EXPRESS LOWER
LEVELS OF ".0 FOR ANY GIVEN SEVERITY
OF (& CAUTIONS SHOULD BE EXERCISED IN
INTERPRETING ".0 LEVELS IN SUCH PATIENTS
".0 AND !CUTE #ORONARY 3YNDROMES !#3
,ARGE STUDIES REPORT .0 ELEVATIONS IN UNSTABLE ANGINA
WITHOUT MYOCARDIAL NECROSIS !S ISCHEMIA MAY RE
SULT IN ONLY SMALL .0 ELEVATIONS THEIR SENSITIVITY AND
SPECIlCITY ARE INADEQUATE AS A hRULE OUTv TOOL (OW
EVER IF PRESENT AN ELEVATION OF .0 IN !#3 IS A POW
ERFUL PREDICTOR OF ADVERSE EVENTS )N PATIENTS
".0 AND 0ROGNOSIS
".0 ELEVATION IS A POWERFUL MARKER OF (& PROGNOSIS
)N PATIENTS FOLLOWED FOR MONTHS AFTER AN %$
VISIT FOR DYSPNEA THE RELATIVE RISK OF
MONTH (& AD
MISSION OR DEATH WAS TIMES HIGHER IF THE ".0 WAS
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!$(& THAN OTHER AGENTS 4HE USE OF NE
SIRITIDE IS ASSOCIATED WITH REDUCED lLLING
PRESSURES DECREASED PULMONARY VASCU
LAR RESISTANCE LOWERED CENTRAL VENOUS
PRESSURES AND REDUCTION IN SYSTEMIC "0
4HERE IS ALSO INCREASED CARDIAC OUTPUT DUE
TO THE UNLOADING EFFECT OF VASODILATATION
BUT WITHOUT REmEX TACHYCARDIA -OREOVER
REDUCING PRELOAD AND AFTERLOAD WITHOUT
INCREASING HEART RATE IS CONSISTENT WITH
DECREASED MYOCARDIAL OXYGEN CONSUMP
TION AND A DECREASE IN VENTRICULAR STRESS
A STIMULUS PRESUMED TO DRIVE THE NEU
ROHORMONAL ACTIVATION OF !$(& ,ASTLY
TOLERANCE TO THESE EFFECTS DOES NOT OCCUR
AND THESE CHANGES IN HEMODYNAMICS ARE
PRESENT AND PERSISTENT THROUGHOUT THE AD
MINISTRATION OF NESIRITIDE
4O DATE NESIRITIDE IS THE ONLY NATRIURETIC
PEPTIDE AVAILABLE IN THE 53 FOR )6 THERA
PY #OLUCCI ET AL IN THE %FlCACY 4RIAL
SHOWED THAT NESIRITIDE CAUSES A DOSE RE
LATED DECREASE IN 0#70 SYSTEMIC VAS
CULAR RESISTANCE MEAN RIGHT ARTERIAL PRES
SURE DYSPNEA FATIGUE A SIGNIlCANT IN
CREASE IN CARDIAC INDEX AND AN IMPROVE
MENT IN GLOBAL STATUS 4HE MOST COMMON
SIDE EFFECT WAS DOSE
RELATED HYPOTENSION
4HE #OMPARATIVE 4RIAL EVALUATED NE
SIRITIDE VERSUS MANY OTHER CARDIOVASCULAR
AGENTS INCLUDING DOBUTAMINE MILRINONE
NITROGLYCERIN DOPAMINE AND AMRINONE
'LOBAL CLINICAL STATUS FATIGUE AND DYS
PNEA IMPROVED IN ALL GROUPS WITH NO SIG
NIlCANT DIFFERENCES BETWEEN NESIRITIDE AND
STANDARD THERAPY 4HE MOST COMMON SIDE
EFFECTS WERE BRADYCARDIA AND DOSE
RELATED
HYPOTENSION
)N "URGER ET AL CONDUCTED THE
02%#%$%.4 STUDY )TS PRIMARY OBJEC
TIVE WAS TO COMPARE HEART RATE AND AR
RHYTHMIAS WITH TWO DOSES OF NESIRITIDE
OR GKGMIN TO DOBUTAMINE
4HEY CONCLUDED THAT ALTHOUGH INOTROPIC
(& THERAPIES INCLUDING DOBUTAMINE AND
MILRINONE ARE ASSOCIATED WITH FAVORABLE
HEMODYNAMIC AND SYMPTOMATIC EFFECTS
THEY CAUSE ARRHYTHMIAS AND TACHYCARDIA
WHICH MAY INCREASE MYOCARDIAL OXYGEN
DEMAND ISCHEMIA AND MORTALITY 4HEY
DEMONSTRATED FEWER ARRHYTHMIAS AND NO
HEART RATE INCREASE WITH NESIRITIDE &UR
THERMORE THE RATES OF
DAY READMIS
SION AND
MONTH MORTALITY WERE HIGHER
WITH DOBUTAMINE 4HE AUTHORS CONCLUDED
THAT NESIRITIDE IS SAFER THAN DOBUTAMINE
FOR SHORT
TERM !$(& MANAGEMENT
4HE 6-!# TRIAL WAS A SAFETY AND EF
lCACY STUDY OF INTRAVENOUS NESIRITIDE
VERSUS INTRAVENOUS NITROGLYCERIN OR PLA
CEBO IN !$(& PATIENTS WITH DYSPNEA
AT REST 3WAN 'ANZ CATHETERIZATION WAS
PERFORMED IN ROUGHLY HALF AT THE PHYSI
CIANS CHOICE 0ATIENTS WERE RANDOMIZED
INTO FOUR BLINDED GROUPS EACH RECEIVING
STANDARD THERAPY AND lXED DOSE NESIRIT
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SIMILAR IN BOTH GROUPS }i 4HEY CONCLUDED
THAT WHEN ADDED TO STANDARD CARE NESIRITIDE IMPROVES
HEMODYNAMIC FUNCTION MORE EFFECTIVELY THAN )6 NI
TROGLYCERIN OR PLACEBO
YIELD AN INTUITIVE RATIONALE AND A REASONABLE EVIDENCE
BASED APPROACH FOR !$(& ASSESSMENT AND MANAGE
MENT /NE OF THE MOST VALUABLE lNDINGS IS THAT BEGIN
NING VASOACTIVE THERAPY IN THE %$ IS ASSOCIATED WITH A
DAY REDUCTION IN HOSPITAL LENGTH OF STAY COMPARED
TO THERAPIES NOT INITIATED UNTIL AFTER ADMISSION 4HIS
SUGGESTS THAT THE CHOICE OF THERAPY IN THE %$ MAY CRITI
CALLY IMPACT THE COURSE OF THE PATIENT
)N ANOTHER EVALUATION A RISK ADJUSTED COMPARISON OF
OUTCOMES FROM THE !$(%2% REGISTRY OF MORE THAN
!$(& PATIENTS FOUND IMPROVED SURVIVAL WITH
VASODILATORS COMPARED TO INOTROPES 7HEN COMPARING
VASODILATORS THERE ARE SIMILAR OUTCOMES BETWEEN NE
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7HILE ".0 IS APPROVED BY THE &$! FOR (& DIAGNOSIS
ITS USEFULNESS TO MONITOR TREATMENT IS STILL UNDER STUDY
(OWEVER SOME SUGGESTIONS CAN BE MADE 7E BELIEVE
THAT ONE CAN STRATIFY PATIENTS TO THE HIGH
RISK CATEGORY IN
PART BY USING ".0 LEVELS &ONOROW RECENTLY ANALYZED
THE !$(%2% DATABASE AND FOUND THAT HIGH "5. LEVELS
PROVIDE A POOR PROGNOSIS FOR PATIENTS IN !$(& 4HUS
4HE CURRENT APPROVED USE OF NESIRITIDE IS FOR !$(&
!LTHOUGH GUIDELINE STATEMENTS ARE LACKING THE TOTALITY
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RISK PATIENTS }i{
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AND "5. LEVELS ARE LOWER RISK ONE CAN OFTEN
START TREATMENT WITH PARENTERAL DIURETICS 3UBSEQUENTLY
THEY CAN BE RECLASSIlED INTO LOW
OR HIGH
RISK GROUPS
BASED ON THEIR RESPONSE OVER THE NEXT n HOURS
4HOSE WITH AN ADEQUATE DIURESIS A FALL IN ".0 AND
NO DETERIORATION IN RENAL FUNCTION MAY BE CANDIDATES
FOR CONTINUED DIURETICSVASODILATORS UNTIL EUVOLEMIA
IS REACHED (OPEFULLY THIS WILL LEAD TO A ".0 LEVEL
PGM, IN THESE PATIENTS )N ONE STUDY PATIENTS
WHOSE DISCHARGE ".0 LEVELS WERE PGM, HAD A
REASONABLE LIKELIHOOD OF NOT BEING READMITTED WITHIN
THE FOLLOWING DAYS )F THE ".0 LEVEL WAS
PGM, THE VOLUME STATUS REQUIRED RE
EVALUATION )F
THE PATIENT IS NOT YET EUVOLEMIC NESIRITIDE MIGHT BE
CONSIDERED FOR HOURS
)F PATIENTS AFTER RECEIVING n HOURS OF INTRAVENOUS
DIURETICS HAVE AN INADEQUATE DIURESIS NO CHANGE OR AN
INCREASE IN ".0 AND WORSENING RENAL FUNCTION THEY
SHOULD BE CONSIDERED AT HIGH RISK )F THEIR SYSTOLIC "0
IS AT LEAST MM (G THEY CAN BE GIVEN n DAYS OF
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AND DIURETICS CAN BE USED UNTIL EUVOLEMIA IS ACHIEVED
0ATIENTS WITH SYSTOLIC "0S MM (G OFTEN NEED VA
SOPRESSORS ANDOR INOTROPES SOMETIMES UNDER 3WAN
'ANZ GUIDANCE )N OUR EXPERIENCE AT THE #LEVELAND
#LINIC IF THESE INDIVIDUALS SHOW IMPROVEMENT IN "0
AND SYMPTOMS WE WILL THEN TRANSITION THEIR THERAPY
TO NESIRITIDE )F THERE IS NO IMPROVEMENT ON INOTRO
PES OR PRESSORS FURTHER INVASIVE STRATEGIES SHOULD BE
CONSIDERED &INALLY IT IS CONCEIVABLE THAT IN PATIENTS
WHO ARE ADMITTED WITH VERY HIGH ".0 LEVELS OR HAVE
IMPAIRED RENAL FUNCTION NESIRITIDE MIGHT BE STARTED
IMMEDIATELY
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PROVIDED CONSENSUS APPROACHES FOR THE USE OF ".0
FOR THE DIAGNOSIS AND TREATMENT OF (& )DEALLY THE
USE OF THESE RECOMMENDATIONS WILL IMPROVE THE CARE
OF YOUR PATIENTS
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$ECOMPENSATED (EART &AILURE .ATIONAL 2EGISTRY !$(%2%
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!CUTE DECOMPENSATED HEART FAILURE !$(& REPRESENTS A MAJOR PUBLIC HEALTH PROBLEM
)N THE 5NITED 3TATES THERE ARE APPROXIMATELY MILLION HOSPITALIZATIONS ANNUALLY WITH
A PRIMARY DISCHARGE DIAGNOSIS OF !$(& .EARLY TWICE AS MANY HOSPITALIZATIONS ARE AS
SOCIATED WITH HEART FAILURE AS A SECONDARY DIAGNOSIS 4HESE NUMBERS ARE EXPECTED TO
INCREASE OVER THE NEXT TWO DECADES
(EART FAILURE TAKES A PARTICULARLY HIGH TOLL ON THE
ELDERLY 3INCE THE EARLY S !$(& HAS BEEN THE LEADING CAUSE OF HOSPITALIZATION IN
PERSONS OVER THE AGE OF YEARS 2EPORTED DEATH RATES APPEAR EXCESSIVE BOTH DURING
AND AFTER HOSPITALIZATION AND HIGH READMISSION RATES SUGGEST THAT INPATIENT CARE DOES NOT
RESULT IN EFFECTIVE LONG
TERM MANAGEMENT 4HE ENORMOUS DIRECT COSTS ASSOCIATED WITH
TREATING THE MILLION !MERICANS WITH CHRONIC HEART FAILURE ARE MOSTLY ATTRIBUTABLE TO
THE INPATIENT MANAGEMENT OF EPISODES OF DECOMPENSATION )T HAS BEEN PROPOSED THAT
THESE DISMAL STATISTICS EXIST IN PART DUE TO A POOR UNDERSTANDING OF THE CHARACTERISTICS
OF PATIENTS ADMITTED WITH !$(& AND HOW TO TREAT THEM )N THIS REGARD MOST INFORMA
TION ABOUT !$(& IS DERIVED FROM CLINICAL TRIALS THAT ARE SMALL HUNDREDS OF PATIENTS
AND POORLY REPRESENTATIVE OF PATIENTS HOSPITALIZED FOR !$(& DUE TO THE MANY INCLUSION
AND EXCLUSION OF SUCH TRIALS
! FEW REGISTRIES HAVE BEEN DEVELOPED TO EVALUATE CHRONIC HEART FAILURE IN THE OUTPA
TIENT COMMUNITY SETTING
4HE !CUTE $ECOMPENSATED (EART &AILURE .ATIONAL 2EGISTRY
!$(%2% WAS DEVELOPED TO PROVIDE A LARGE NATIONAL DATABASE DESCRIBING THE CLINICAL
CHARACTERISTICS PHYSICIAN PRACTICE AND TREATMENT PATTERNS AND OUTCOMES OF PATIENTS
HOSPITALIZED WITH !$(&
-ETHODOLOGY OF !$(%2%
!$(%2% IS A LARGE MULTICENTER REG
ISTRY DESIGNED TO AMASS A LARGE CLINICAL
DATABASE ON THE CLINICAL CHARACTERISTICS
MANAGEMENT AND OUTCOMES OF PATIENTS
HOSPITALIZED FOR !$(& ACROSS THE 5NITED
3TATES $ATA ARE COLLECTED ON THE EPISODE
OF HOSPITALIZATION BEGINNING WITH THE
POINT OF INITIAL CARE AND ENDING WITH THE
PATIENTS DISCHARGE TRANSFER OUT OF THE
HOSPITAL OR IN
HOSPITAL DEATH !$(%2%
IS SPONSORED BY 3CIOS )NC &REMONT
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!CUTE $ECOMPENSATED (EART &AILURE !$(&
#ALIFORNIA 4HE SPECIlC OBJECTIVES OF !$(%2% ARE
TO DESCRIBE THE DEMOGRAPHIC AND CLINICAL CHARAC
TERISTICS OF PATIENTS WHO ARE HOSPITALIZED WITH !$(&
INCLUDING SPECIlC SUBGROUPS OF INTEREST TO CHAR
ACTERIZE THE INITIAL EMERGENCY DEPARTMENT EVALUATION
AND SUBSEQUENT INPATIENT MANAGEMENT OF PATIENTS
HOSPITALIZED WITH !$(& TO IDENTIFY PATIENT CHAR
ACTERISTICS AND MEDICAL CARE PRACTICES ASSOCIATED WITH
IMPROVED HEALTH OUTCOMES IN PATIENTS HOSPITALIZED
WITH !$(& TO CHARACTERIZE TRENDS OVER TIME IN
THE MANAGEMENT OF !$(& AND TO ASSIST HOSPITALS
IN EVALUATING AND IMPROVING QUALITY OF CARE FOR PA
TIENTS HOSPITALIZED WITH HEART FAILURE !DDITIONAL GOALS
OF !$(%2% INCLUDE DEVELOPMENT OF PREDICTIVE MOD
ELS FOR MORTALITY COMPLICATIONS AND LENGTH OF HOS
PITAL STAY AND TO LINK WITH DE
IDENTIlED DATA ON LON
GITUDINAL TRENDS IN THE CLINICAL CARE AND OUTCOMES OF
REGISTRY PATIENTS !GGREGATE DATA FROM THE !$(%2%
DATABASE IS ALSO USED FOR THE OBSERVATIONAL STUDY OF
TREATMENT EFFECTS
3ITES WERE SELECTED TO REPRESENT THE hREAL WORLDv OF
!$(& 3ITES INCLUDED BOTH ACADEMIC HOSPITALS
AND NONACADEMIC HOSPITALS HOSPITALS AND WERE
GEOGRAPHICALLY DIVERSE INCLUDING HOSPITALS IN THE
.ORTHEASTERN 5NITED 3TATES HOSPITALS IN THE 3OUTH
HOSPITALS IN THE -IDWEST HOSPITALS IN THE 7EST
AND HOSPITALS IN THE -ID
!TLANTIC REGION 3OME OF
THE LARGEST ACUTE CARE HOSPITALS IN THE 5NITED 3TATES
ARE PARTICIPATING BUT SITES ARE DIVERSE IN SIZE RANGING
FROM TO BEDS 3ITES ARE REIMBURSED A NOMINAL
FEE FOR EACH COMPLETED CASE REPORT FORM
&OR THE PURPOSE OF THIS REGISTRY !$(& IS DElNED AS
EITHER NEW
ONSET HEART FAILURE OR DECOMPENSATION OF
CHRONIC ESTABLISHED HEART FAILURE WITH SYMPTOMS SUF
lCIENT TO WARRANT HOSPITALIZATION 0ATIENTS ARE IDEN
TIlED FOR INCLUSION IN THE REGISTRY FROM ADMISSIONS
GIVEN A DISCHARGE DIAGNOSIS OF HEART FAILURE BASED ON
)NTERNATIONAL #LASSIlCATION OF $ISEASES .INTH 2EVI
SION )#$
CODING %LIGIBILITY IS NOT CONTINGENT ON
THE USE OF ANY PARTICULAR THERAPEUTIC AGENT OR REGIMEN
0ATIENTS MAY BE MALE OR FEMALE AND MUST BE AT LEAST
YEARS OLD AT THE TIME OF HOSPITAL ADMISSION 4HE
REGISTRY IS ACCUMULATING DATA ON INDIVIDUAL HOSPITAL
IZATIONS NOT INDIVIDUAL PATIENTS AND IT IS POSSIBLE THAT
SOME PATIENTS MAY BE ENROLLED IN THE REGISTRY MORE
THAN ONCE 4HE GOAL OF THE REGISTRY IS TO ENROLL A REPRE
SENTATIVE PATIENT SAMPLE 3ITES ARE ENCOURAGED TO ENROLL
ADMISSIONS MEETING ENTRY CRITERIA AS CONSECUTIVELY AS
POSSIBLE (OSPITALS WITH MORE THAN ELIGIBLE PATIENTS
IN A MONTH ARE ALLOWED TO ENROLL A RANDOM SAMPLE OF
THESE CONSECUTIVE ADMISSIONS USING A *OINT #OMMIS
SION FOR !CCREDITATION OF (EALTHCARE /RGANIZATIONS
*#!(/ nAPPROVED SAMPLING METHOD 3PECIlCATIONS
-ANUAL FOR .ATIONAL )MPLEMENTATION OF (OSPITAL #ORE
-EASURES *#!(/ SECTION
$ATA ARE COLLECTED BY CHART REVIEW AND ENTERED USING
A WEB
BASED ELECTRONIC DATA CAPTURE %$# SYSTEM
DESIGNED BY 0HASE &ORWARD 7ALTHAM -ASS AND LI
CENSED BY THE STUDY CONTRACT RESEARCH ORGANIZATION
0HARMA,INK &() 2ESEARCH 4RIANGLE .# $ATA ARE
RECORDED CONCERNING DEMOGRAPHICS MEDICAL HIS
TORY NON
INTRAVENOUS AND INTRAVENOUS CARDIOVASCU
LAR MEDICATIONS INITIAL EVALUATION AT SITE HOSPITAL
CHRONIC INFUSION THERAPY HOSPITAL COURSE DISPOSITION
AND PROCEDURES )NFORMATION RELATED TO FOUR SPECIlC
ASPECTS OF THE *#!(/ QUALITY IMPROVEMENT INITIATIVE
FOR HEART FAILURE ARE ALSO CAPTURED PATIENT INSTRUC
TION ON DIET WEIGHT AND MEDICATION MANAGEMENT AT
DISCHARGE ASSESSMENT OF LEFT VENTRICULAR SYSTOLIC
FUNCTION DOCUMENTED OR SCHEDULED ANGIOTENSIN
CONVERTING ENZYME !#% INHIBITOR USE AT DISCHARGE
IN PATIENTS CONSIDERED CANDIDATES FOR THIS THERAPY
BASED ON ACCEPTED CLINICAL CRITERIA AND COUNSEL
ING ON SMOKING CESSATION IN CURRENT SMOKERS (UMAN
SUBJECTS CONSIDERATIONS PATIENT CONlDENTIALITY SITE
MONITORING AND OTHER SPECIlC METHODOLOGICAL ISSUES
HAVE BEEN PREVIOUSLY OUTLINED IN DETAIL ELSEWHERE
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)NSIGHTS FROM !$(%2%
&ROM /CTOBER THROUGH $ECEMBER
HEART FAILURE DISCHARGES WERE ENROLLED IN !$(%2%
4HE MEAN AGE OF PATIENTS WAS YEARS AND
WERE WOMEN -OST PATIENTS WERE WHITE OR BLACK
AND WERE COVERED BY -EDICARE OR -EDICAID
3EVENTY
SIX PERCENT OF PATIENTS ENROLLED HAD A
PRIOR HISTORY OF HEART FAILURE AND ONE
THIRD HAD A HISTO
RY OF ADMISSION FOR !$(& WITHIN THE PRIOR MONTHS
! HISTORY OF HYPERTENSION WAS COMMON AS WAS
CORONARY ARTERY DISEASE AND DIABETES
/THER IMPORTANT OR COMMON CO
MORBID CONDITIONS
INCLUDED HISTORY OF ATRIAL lBRILLATION CHRONIC
OBSTRUCTIVE PULMONARY DISEASE OR ASTHMA
AND CHRONIC RENAL INSUFlCIENCY -OST PATIENTS
PRESENTED WITH DYSPNEA 2ALES AND PERIPHERAL
EDEMA WERE PRESENT IN AND OF THE CASES
RESPECTIVELY /F PATIENTS WITH DOCUMENTED LEFT VEN
TRICULAR EJECTION FRACTION PRIOR TO ADMISSION HAD
PRESERVED OR ONLY MILDLY DEPRESSED SYSTOLIC FUNCTION
4HE CHARACTERISTICS OF PATIENTS ENROLLED IN !$(%2%
ARE VERY DIFFERENT FROM THOSE OF PATIENTS INCLUDED IN
CLINICAL TRIALS Q/>LiR
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WAS DAYS MEAN DAYS 4HE IN
HOSPITAL MORTAL
ITY RATE WAS FOR PATIENTS WHO RECEIVED
TREATMENT IN AN INTENSIVE CARE UNIT )#5 2EGISTRY
DATA ON THE *#!(/ QUALITY OF CARE INDICATORS SHOWED
THAT ONLY OF PATIENTS WERE GIVEN INSTRUCTION ON
DIET WEIGHT MONITORING ACTIVITY LEVEL WORSENING
SYMPTOMS FOLLOW
UP APPOINTMENTS AND MEDICATION
MANAGEMENT AT DISCHARGE !SSESSMENT OF LEFT VEN
TRICULAR SYSTOLIC FUNCTION WAS EITHER DOCUMENTED OR
SCHEDULED IN OF PATIENTS ! TOTAL OF OF THE
PATIENTS JUDGED ELIGIBLE TO RECEIVE AN !#% INHIBITOR
BY STANDARD CLINICAL CRITERIA WERE DISCHARGED ON THIS
MEDICATION #OUNSELING ON SMOKING CESSATION FOR CUR
RENT SMOKERS WAS GIVEN TO OF ELIGIBLE PATIENTS
!$(%2% -ORTALITY !NALYSES
4O DATE TWO PRIMARY ANALYSES OF MORTALITY HAVE BEEN
PERFORMED ON !$(%2% 4HESE INCLUDE A CLASSIlCATION
AND REGRESSION TREE #!24 ANALYSIS IN ALL PATIENTS TO
DElNE COVARIATE ADJUSTED ODDS RATIOS OF DEATH AND
A MULTIVARIABLE REGRESSION AND PROPENSITY ANALYSIS IN
PATIENTS RECEIVING )6 VASOACTIVE MEDICATIONS TO DE
lNE COVARIATE ADJUSTED PROBABILITY OF TREATMENT
4HE FORMER ANALYSIS ALLOWS THE DEVELOPMENT AND VALI
DATION OF A PREDICTIVE MODEL FOR IN
HOSPITAL MORTALITY
BASED ON PATIENT CHARACTERISTICS DISCERNED AT THE TIME
#HARACTERISTIC
#LINICAL 4RIALS
!$(%2%
!VERAGE !GE YEARS
'ENDER 7OMEN
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2ENAL )NSUFlCIENCY
5SUALLY EXCLUDED
0RESERVED ,6 3YSTOLIC &UNCTION
5SUALLY EXCLUDED
!TRIAL &IBRILLATION
$IABETES
%MERGENCY $IAGNOSIS AND 4REATMENT OF
!CUTE $ECOMPENSATED (EART &AILURE !$(&
OF PRESENTATION 4HAT IS THE #!24 ANALYSIS PROVIDES
n FOR THE lRST TIME n A WAY TO STRATIFY PATIENTS FOR RISK
OF IN
HOSPITAL MORTALITY 4HE LATTER ANALYSIS PERMITS
THE COMPARISON OF TREATMENT CHOICE ON OUTCOME 3PE
CIlCALLY THE COVARIATE AND PROPENSITY SCORE ADJUSTED
RISK OF IN
PATIENT MORTALITY WAS EVALUATED BY TREATMENT
STATUS COMPARING INTRAVENOUS DOBUTAMINE MILRINONE
NESIRITIDE AND NITROGLYCERINE
)N ORDER TO DEVELOP A PRACTICAL USER
FRIENDLY BEDSIDE
TOOL FOR RISK STRATIlCATION FOR PATIENTS HOSPITALIZED
WITH !$(& #!24 ANALYSIS OF THE !$(%2% DATA
BASE WAS PERFORMED USING THE lRST DISCHARGES
ENROLLED 4HE lRST HOSPITALIZATIONS FROM
/CTOBER THROUGH &EBRUARY SERVED AS THE
DERIVATION COHORT AND WERE ANALYZED TO DEVELOP THE
RISK PREDICTION MODEL 4HEN THE VALIDITY OF THE MODEL
WAS PROSPECTIVELY TESTED USING DATA FROM SUB
SEQUENT HOSPITALIZATIONS VALIDATION COHORT ENROLLED
IN !$(%2% FROM -ARCH THROUGH *ULY )N
HOSPITAL MORTALITY WAS SIMILAR IN THE DERIVATION
AND VALIDATION COHORTS 2ECURSIVE PARTITIONING
OF THE DERIVATION COHORT FOR VARIABLES INDICATED THAT
THE BEST SINGLE PREDICTOR FOR MORTALITY WAS HIGH AD
MISSION LEVELS OF BLOOD UREA NITROGEN * MGD,
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TO }i 4HE ODDS RATIO FOR MORTALITY
BETWEEN PATIENTS IDENTIlED AS HIGH AND LOW RISK WAS
CONlDENCE INTERVAL AND SIMI
LAR RESULTS WERE SEEN WHEN THIS RISK STRATIlCATION WAS
APPLIED PROSPECTIVELY TO THE VALIDATION COHORT 4HESE
RESULTS SUGGEST THAT !$(& PATIENTS AT LOW INTERME
DIATE AND HIGH RISK FOR IN HOSPITAL MORTALITY CAN BE
EASILY IDENTIlED USING VITAL SIGN AND LABORATORY DATA
OBTAINED ON HOSPITAL ADMISSION 4HE !$(%2% RISK
ASSESSMENT TOOL PROVIDES CLINICIANS WITH A VALIDATED
PRACTICAL BEDSIDE INSTRUMENT FOR MORTALITY RISK STRATI
lCATION 3IMILAR TO THE CONTEMPORARY APPROACH TO THE
TRIAGE AND MANAGEMENT OF CHEST PAIN PATIENTS BASED ON
RISK ASSESSMENT AT PRESENTATION THE !$(%2% #!24
ANALYSIS MAY ULTIMATELY HELP DIRECT THE PLACEMENT AND
THERAPY OF PATIENTS PRESENTING WITH !$(&
4O COMPARE IN HOSPITAL MORTALITY OF !$(& PATIENTS
RECEIVING PARENTERAL TREATMENT WITH ONE OF FOUR INTRA
VENOUS VASOACTIVE MEDICATIONS A RETROSPECTIVE ANAL
YSIS OF DATA FROM !$(%2% WAS PERFORMED $ATA
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CORRESPONDING VALUES FOR NESIRITIDE COMPARED WITH
MILRINONE AND DOBUTAMINE WERE n P
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GLYCERIN WAS n P 4HUS THERA
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ASSOCIATED WITH SIGNIlCANTLY LOWER IN HOSPITAL MOR
TALITY THAN POSITIVE INOTROPIC THERAPY IN HOSPITALIZED
!$(& PATIENTS IN !$(%2% 4HE RISK OF IN HOSPITAL
MORTALITY WAS SIMILAR FOR NESIRITIDE AND NITROGLYCERIN
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lNDINGS FROM RANDOMIZED CONTROLLED TRIALS AND SUP
PORT THE USE OF VASODILATORS NESIRITIDE OR NITROGLYC
ERIN AS lRST LINE INTRAVENOUS AGENTS FOR THE TREATMENT
OF !$(& 4HE SELECTION OF A SPECIlC INTRAVENOUS VA
SODILATOR MAY BE GUIDED BY THE RESULTS OF RANDOMIZED
CONTROLLED TRIALS /F COURSE INOTROPES MAY STILL PLAY
A ROLE FOR THOSE WHO PRESENT IN OR IN IMPENDING CAR
DIOGENIC SHOCK
FROM THE lRST PATIENT EPISODES FROM /CTOBER
THROUGH *ULY WERE INCLUDED IN THIS ANALY
SIS #ASES IN WHICH PATIENTS RECEIVED NITROGLYCERIN
NESIRITIDE MILRINONE OR DOBUTAMINE WERE IDENTIlED
AND REVIEWED N TO DETERMINE IF THE CHOICE
OF INTRAVENOUS VASOACTIVE THERAPY AFFECTED IN
HOSPITAL
MORTALITY 3INCE THE CHOICE OF THERAPY WAS NOT DIRECT
ED BY A PROTOCOL BUT BY CLINICIAN JUDGMENT OR PREFER
ENCE PROPER ADJUSTMENT BASED ON FACTORS INmUENCING
TREATMENT DECISION USING ADJUSTMENT FOR COVARIATES
AND PROPENSITY SCORING WERE MADE 2ISK FACTOR AND
PROPENSITY SCORE
ADJUSTED ODDS RATIOS /2S FOR IN
HOSPITAL MORTALITY WERE CALCULATED
0ATIENTS WHO RECEIVED INTRAVENOUS NITROGLYCERIN OR
NESIRITIDE HAD LOWER IN
HOSPITAL MORTALITY THAN THOSE
TREATED WITH DOBUTAMINE OR MILRINONE 4HE RISK FACTOR
AND PROPENSITY SCORE
ADJUSTED /2S FOR NITROGLYCERIN
WERE CONlDENCE INTERVAL ;#)= n
P ) AND n P ) COMPARED
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TRIALS (EART FAILURE PATIENTS ENROLLED IN CLINICAL TRIALS
ARE VERY DIFFERENT THAN HEART FAILURE PATIENTS IN THE
COMMUNITY AS DEMONSTRATED BY THE CHARACTERISTICS
OF MORE THAN DISCHARGES FOR !$(& IN !$
(%2% 4HE !$(%2% REGISTRY PROVIDES IMPORTANT
INSIGHTS INTO !$(& TREATMENT AND OUTCOMES THAT MAY
FAVORABLY IMPACT FUTURE CARE 3PECIlCALLY IT PROVIDES
US WITH A VALUABLE RISK ASSESSMENT TOOL AND WITH IN
SIGHTS INTO THE EFFECTS OF TREATMENT SELECTION ON OUT
COMES IN !$(& PATIENTS
"ONNEUX , "ARENDREGT ** -EETER + ET AL %STIMATING CLINICAL
MORBIDITY DUE TO ISCHEMIC HEART DISEASE AND CONGESTIVE HEART
FAILURE THE FUTURE RISE OF HEART FAILURE !M * 0UBLIC (EALTH
'HALI *+ #OOPER 2 &ORD % 4RENDS IN HOSPITALIZATION RATES
FOR HEART FAILURE IN THE 5NITED 3TATES EVIDENCE FOR
INCREASING POPULATION PREVALENCE !RCH )NTERN -ED
!MERICAN (EART !SSOCIATION HEART AND STROKE STATISTICAL
UPDATE $ALLAS 4EX !MERICAN (EART !SSOCIATION
#UFFE -3 #ALIFF 2- !DAMS +& ET AL 3HORT TERM INTRAVENOUS
MILRINONE FOR ACUTE EXACERBATION OF CHRONIC HEART FAILURE A
RANDOMIZED CONTROLLED TRIAL *!-!
+RUMHOLZ (- 0ARENT %- 4U . ET AL 2EADMISSION AFTER
HOSPITALIZATION FOR CONGESTIVE HEART FAILURE AMONG -EDICARE
BENElCIARIES !RCH )NTERN -ED
/#ONNELL *" 4HE ECONOMIC BURDEN OF HEART FAILURE #LIN #ARDIOL
3UPPL )))
4HE 3/,6$ )NVESTIGATORS 3TUDIES OF LEFT VENTRICULAR DYSFUNCTION
3/,6$ RATIONALE DESIGN AND METHODS TWO TRIALS THAT EVALUATE
THE EFFECT OF ENALAPRIL IN PATIENTS WITH REDUCED EJECTION FRACTION
!M * #ARDIOL
&RANCIOSA *! !BRAHAM 74 &OWLER - ET AL 2ATIONALE DESIGN AND
METHODS FOR A COREG CARVEDILOL HEART FAILURE REGISTRY #/(%2%
* #ARD &AIL
!DAMS +& /#ONNOR #- /REN 2- ET AL $EVELOPMENT OF A
MULTICENTER HEART FAILURE DATABASE INITIAL REPORT FROM THE UNITED
INVESTIGATORS TO EVALUATE HEART FAILURE * #ARD &AIL
!CKNOWLEDGMENTS
4HE !$(%2% 3CIENTIlC !DVISORY #OMMITTEE !$(%2%
)NVESTIGATORS AND #OORDINATORS AND 3CIOS )NC -EMBERS OF
THE !$(%2% 3CIENTIlC !DVISORY #OMMITTEE ARE 7ILLIAM
4 !BRAHAM -$ &!#0 &!## 4HE /HIO 3TATE 5NIVERSITY
(EART #ENTER #OLUMBUS /( +IRKWOOD & !DAMS *R -$
5NIVERSITY OF .ORTH #AROLINA #HAPEL (ILL .# 2OBERT ,
"ERKOWITZ -$ 0H$ (ACKENSACK 5NIVERSITY (OSPITAL
(ACKENSACK .* -ARIA 2OSA #OSTANZO -$ -IDWEST (EART
3PECIALISTS .APERVILLE ), 4ERESA $E -ARCO -$ 5NIVER
SITY OF #ALIFORNIA 3AN &RANCISCO #! #HARLES , %MERMAN
-$ #LEVELAND #LINIC #LEVELAND /( 'REGG # &ONAROW
-$ !HMANSON
5#,! #ARDIOMYOPATHY #ENTER ,OS !N
GELES #! -ARIE 'ALVAO -3. !.0
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4HIERRY ( ,E*EMTEL -$ !LBERT %INSTEIN (OSPITAL "RONX
.9 ,YNNE 7ARNER 3TEVENSON -$ "RIGHAM AND 7OMENS
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5NIVERSITY OF 4EXAS 3OUTHWESTERN -EDICAL #ENTER -EDICAL
#ENTER $ALLAS 48
!DAMS +& &ONAROW '# %MERMAN #, ET AL FOR THE !$(%2%
3CIENTIlC !DVISORY #OMMITTEE AND )NVESTIGATORS #HARACTERISTICS
AND OUTCOMES OF PATIENTS HOSPITALIZED FOR HEART FAILURE IN THE
5NITED 3TATES RATIONALE DESIGN AND PRELIMINARY OBSERVATIONS
FROM THE lRST CASES IN THE !CUTE $ECOMPENSATED (EART
&AILURE .ATIONAL 2EGISTRY !$(%2% !M (EART *
&ONAROW '# !DAMS +& !BRAHAM 74 9ANCY #7 FOR THE
!$(%2% 3CIENTIlC !DVISORY #OMMITTEE AND 3TUDY 'ROUP 2ISK
STRATIlCATION FOR IN HOSPITAL MORTALITY IN ACUTELY DECOMPENSATED
HEART FAILURE CLASSIlCATION AND REGRESSION TREE #!24 ANALYSIS OF
THE !$(%2% 2EGISTRY *!-!
!BRAHAM 74 !DAMS +& &ONAROW '# ET AL FOR THE !$(%2%
3CIENTIlC !DVISORY #OMMITTEE AND )NVESTIGATORS AND THE !$(%2%
3TUDY 'ROUP )N HOSPITAL MORTALITY IN PATIENTS WITH ACUTE
DECOMPENSATED HEART FAILURE TREATED WITH INTRAVENOUS VASOACTIVE
MEDICATIONS AN ANALYSIS FROM THE !$(%2% 2EGISTRY * !M #OLL
#ARDIOL IN PRESS
0UBLICATION #OMMITTEE FOR THE 6-!# )NVESTIGATORS )NTRAVENOUS
NESIRITIDE VS NITROGLYCERIN FOR TREATMENT OF DECOMPENSATED
CONGESTIVE HEART FAILURE A RANDOMIZED CONTROLLED TRIAL *!-!
#OPYRIGHT %-#2%' )NTERNATIONAL
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! MAJOR FACTOR LIMITING THE LONG
TERM EFlCACY OF CURRENT CONGESTIVE HEART FAILURE #(&
TREATMENT STRATEGIES IS A LACK OF COMPELLING DATA CONlRMING WHICH APPROACHES AND
THERAPIES WORK BEST IN MOST CLINICAL SITUATIONS 3TUDIES HAVE SHOWN THAT THE CARE GIVEN
TO #(& PATIENTS VARIES WIDELY BASED ON THE LOCATION WHERE PATIENTS RECEIVE TREATMENT
AND THE SPECIALTY OF THE PHYSICIAN WHO TREATS THEM )N THE ABSENCE OF ANY ESTABLISHED
STANDARDS OR BEST
PRACTICE GUIDELINES PHYSICIANS HAVE LITTLE EVIDENCE ON WHICH TO BASE
TREATMENT DECISIONS "ECAUSE OF THIS LACK OF CONSENSUS STANDARDS MANY #(& PATIENTS
RECEIVE LESS THAN OPTIMAL CARE 4HE .ATIONAL 2EGISTRY !$(%2% IS THE lRST NATIONAL
REGISTRY THAT PROSPECTIVELY COLLECTS OBSERVATIONAL DATA FROM ACROSS THE 5NITED 3TATES IN
ORDER TO TRACK AND STUDY THE MEDICAL MANAGEMENT OF PATIENTS HOSPITALIZED WITH ACUTE
DECOMPENSATED HEART FAILURE !$(& !$(%2% IS SPONSORED BY 3CIOS AND OVERSEEN
BY AN INDEPENDENT SCIENTIlC ADVISORY COMMITTEE OF NATIONALLY RECOGNIZED HEART FAILURE
EXPERTS 4O DATE MORE THAN HOSPITALS AND MORE THAN PATIENT CASES HAVE
BEEN ENTERED INTO THE !$(%2% REGISTRY MAKING IT THE LARGEST MOST EXTENSIVE REGISTRY
OF ITS KIND
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4HE ORIGINAL REGISTRY IS REFERRED TO AS THE
#ORE 2EGISTRY !S INTEREST IN THE LONG
TERM OUTCOMES OF THESE PATIENTS EMERGED
THE ,ONGITUDINAL -ODULE WAS DEVELOPED
TO FOLLOW THE COURSE OF THESE PATIENTS
BEYOND THE IMMEDIATE HOSPITALIZATION
AND INTO THE OUTPATIENT SETTING -ORE
RECENTLY THE !$(%2% $ISEASE -ANAGE
MENT 1UALITY )NITIATIVE FOR #ARE "EGIN
NING IN THE %MERGENCY $EPARTMENT -OD
ULE !$(%2% %$ $- WAS INITIATED TO
GIVE INSIGHT INTO THE TREATMENT PATTERNS
AND OVERALL QUALITY OF DISEASE MANAGE
MENT $- OF !$(& IN THE EMERGENCY
SETTING
$ISEASE -ANAGEMENT
4RADITIONAL APPROACHES TO THE TREATMENT
OF DISEASE HAVE BEEN A hCOMPONENT
BASED
MANAGEMENT MODELv WHEREBY SELECTED
PORTIONS OF THE DISEASE ARE MANAGED BY
CERTAIN SPECIALISTS THAT ADDRESS SPECIlC
ASPECTS OF THE PATIENTS ILLNESS )N THIS
SYSTEM THE INTERNIST OR CARDIOLOGIST FO
CUSES ON THE LONG
TERM MANAGEMENT OF
#(& WHEREAS THE EMERGENCY PHYSICIAN IS
CONCERNED WITH THE ACUTE STABILIZATION OF
A DECOMPENSATED STATE 4HE NEWER CON
CEPTS OF DISEASE MANAGEMENT INCORPORATE
THE ENTIRE SPECTRUM OF PATIENT CARE AND
INCLUDE THE FULL USE OF ANCILLARY HEALTH
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!CUTE $ECOMPENSATED (EART &AILURE !$(&
CARE AND SOCIAL SERVICES "ECAUSE !$(& PATIENTS HAVE
A COMBINATION OF BOTH AN ACUTE AND CHRONIC CONDITION IT
IS IMPORTANT TO BEGIN TO CONSIDER THE LONGITUDINAL COURSE
OF THEIR MANAGEMENT EVEN AS WE BEGIN THE STABILIZATION
PROCESS IN THE EMERGENCY DEPARTMENT %$ 4HIS CON
SIDERATION HAS BECOME MORE IMPORTANT IN RECENT YEARS
AS THE %$ HAS BECOME THE SAFETY
NET AND PRIMARY CARE
PROVIDER FOR MANY OF THESE PATIENTS )T IS NOT UNCOM
MON FOR !$(& PATIENTS TO BECOME FREQUENT PATIENTS
IN OUR EMERGENCY DEPARTMENTS "Y DEFAULT THE EMER
GENCY PHYSICIAN THEN BECOMES RESPONSIBLE FOR THEIR
OVERALL CARE AND MUST CONSIDER ISSUES SUCH AS ACCESS TO
OUTPATIENT MEDICATIONS THE RAMIlCATIONS OF THEIR INPA
TIENT MANAGEMENT AND THE LONGITUDINAL IMPACT OF EARLY
TREATMENT DECISIONS WITHIN THE EMERGENCY SETTING
4HERE IS CONSIDERABLE EVIDENCE TO SUGGEST THAT THE TREAT
MENT PLAN INITIATED BY THE EMERGENCY PHYSICIAN HAS A
SIGNIlCANT IMPACT ON THE LONG
TERM OUTCOMES OF OTHER
COMMON DISEASE PROCESSES SUCH AS PNEUMONIA AND
ACUTE CORONARY SYNDROMES )T IS REASONABLE TO EXPECT
THAT THE SAME WOULD BE TRUE IN THE TREATMENT OF !$(&
4HERE ARE TYPICALLY THREE COMMON ELEMENTS TO ANY
WELL
ORCHESTRATED DISEASE MANAGEMENT PROGRAM
)DENTIFY PATIENTS AT ELEVATED RISK OF ADVERSE
OUTCOMES
)NTERVENTION TO REDUCE THOSE RISKS
3YSTEMATIC EVALUATION TO ASSESS THE IMPACT OF THE
INTERVENTION
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PHYSICIAN TO THINK ABOUT THE PATIENTS PATHOLOGY FROM
BOTH THE SHORT
TERM AND LONG
TERM MANAGEMENT PER
SPECTIVES 4HIS IS PARTICULARLY IMPORTANT WHEN TREAT
ING CHRONIC DISEASES SUCH AS #(& DUE TO THE DIFFER
ENCES IN THE PATHOPHYSIOLOGIC MECHANISMS INVOLVED
IN THE ACUTE AND CHRONIC PRESENTATIONS #(& IN ITS
ACUTELY DECOMPENSATED FORM IS PRIMARILY A PROBLEM
OF PLUMBING 7ITHIN THE VASCULAR CONDUITS INVOLVED
IN !$(& THERE IS A MISMATCH IN THE PRESSURES RESIS
TANCES AND mUID VOLUMES REQUIRED TO MAINTAIN BLOOD
mOW OR CARDIAC OUTPUT WHICH FURTHER RESULTS IN A CON
GESTIVE STATE THAT LIMITS OXYGENATION BY THE LUNGS
4HIS CONDITION HAS THE POTENTIAL FOR POSITIVE FEEDBACK
AND CAN RAPIDLY SPIRAL TO AN UNSTABLE STATE 4RADITIONAL
THERAPIES SUCH AS NITROGLYCERIN MORPHINE AND DIURET
ICS CAN AMELIORATE THE CONGESTION BY MANIPULATION
OF THE ACUTE PLUMBING DERANGEMENT 4HE RESULT IS A
DRAMATIC CHANGE IN THE IMMEDIATE CLINICAL SITUATION
AND THE PATIENT OFTEN APPEARS ALMOST BACK TO NORMAL
IN TERMS OF SYMPTOMS (OWEVER DESPITE THIS ILLUSION
OF STABILITY THE CHRONIC PATHOPHYSIOLOGY OF #(& AND
THE UNDERLYING CAUSE OF THE DECOMPENSATION IS STILL
PRESENT 4HE CONGESTION AND mUID RETENTION OF THE
HEART FAILURE STATE IS A NATURAL PHYSIOLOGIC ADJUSTMENT
TO A DYSFUNCTIONAL 3TARLING
6ENOUS 2ETURN RELATION
SHIP AND IS NECESSARY TO BRING CARDIAC OUTPUT BACK TO
NORMAL }i 4HE COST OF THIS ADJUSTMENT IS
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HIGHER ATRIAL PRESSURES THAT CAN LEAD TO
PULMONARY EDEMA AND DYSPNEA WHICH
BRINGS THE PATIENT ACUTELY TO THE %$ )F
THIS MECHANISM IS NOT TAKEN INTO CONSID
ERATION IN THE DISPOSITION OF STABILIZED
!$(& PATIENT THEN THERE IS TREMENDOUS
POTENTIAL FOR OVERALL TREATMENT FAILURE
0ROPER DISEASE MANAGEMENT ALSO REQUIRES
A GLOBAL PERSPECTIVE OF ALL ASPECTS OF THE
PATIENTS PATHOPHYSIOLOGY TO BE SUCCESS
FUL
)N THE PAST FEW DECADES WE SAW AN EM
PHASIS ON AN EVIDENCE BASED APPROACH TO
$- WITH A FOCUS ON UTILIZING RESULTS FROM
CLINICAL TRIALS TO DICTATE THE BEST TREATMENT
OPTIONS FOR PATIENTS WITH SPECIlC DISEASE
STATES OR PRESENTATIONS -ORE RECENTLY
WE HAVE BEGUN TO REALIZE THE NECESSITY OF
BALANCING THIS POPULATION BASED PROBA
BILISTIC VIEW OF TREATMENT WITH A SCIEN
TIlC ORIENTED ANALYSIS OF THE PHYSIOLOGIC
NUANCES OF THE INDIVIDUAL PATIENT IN A
GOAL DIRECTED APPROACH TO MANAGEMENT
!$(& $- IS ESPECIALLY AMENABLE TO THIS
NOTION SINCE THERE IS LITTLE CURRENT TRIALS
BASED INFORMATION AND THE PATHOPHYSI
OLOGIC SPECTRUM OF DISEASE PRESENTATION
IS VARIED (OWEVER AS WE DEVELOP AN
EMERGENCY MEDICINE !$(& $- STRATEGY
IT IS IMPORTANT THAT WE LOOK AT THE PROCESS
AS A WHOLE AND THE IMPACT OF TREATMENT
PLANS ON OUTCOMES
&OR ALL THESE REASONS A REGISTRY THAT TRACKS
THE COURSE OF PATIENTS WITH !$(& FROM
THE EMERGENCY MEDICINE PERSPECTIVE CAN
BE INSTRUMENTAL IN DElNING THE BEST PRAC
TICES FOR FUTURE $-
!$(%2% %MERGENCY -EDICINE
-ODULE
4HE !$(%2% %MERGENCY -EDICINE
-ODULE IS EXPECTED TO BE THE VEHICLE
THROUGH WHICH A COMPREHENSIVE DISEASE
MANAGEMENT PROCESS IS DEVELOPED FROM
THE UNIQUE PERSPECTIVE OF EMERGENCY
MEDICINE AS A SPECIALTY "UILDING ON PRIOR
!$(%2% PROGRAMS THIS MODULE WAS DE
SIGNED BY EMERGENCY PHYSICIANS WITH THE
INTENTION OF ANSWERING SPECIlC QUESTIONS
OF INTEREST TO THOSE MANAGING !$(& PA
TIENTS THAT PRESENT TO THE %$ AND FOLLOWS
THEIR HOSPITAL COURSE AND OUTCOMES
0ROGRAM /BJECTIVES
4HE MAIN OBJECTIVES OF !(%2% %$ $-
ARE
$EVELOP A LARGE CLINICAL !$(&
DATABASE FROM ACUTE CARE HOSPITALS
ACROSS THE 5NITED 3TATES
%XAMINE THE CURRENT NATIONAL STATE
OF MEDICAL MANAGEMENT OF PATIENTS
PRESENTING TO THE %$ FOR !$(&
#OMPARE PREPOST OUTCOMES OF
IMPLEMENTATION OF A $ISEASE
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PRESENTATIONS OF !$(&
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IMPROVING QUALITY OF CARE BY
A TRACKING QUALITY INDICATORS
B PROVIDING MONTHLY AND QUARTERLY
SITE SPECIlC AND 5NITED 3TATES
BENCHMARK DATA
#HARACTERIZE TRENDS OVER TIME IN THE
MANAGEMENT OF !$(&
%MERGENCY $IAGNOSIS AND 4REATMENT OF
!CUTE $ECOMPENSATED (EART &AILURE !$(&
&OR THE !$(& PATIENT IN AN %$
SETTING
A $ESCRIBE DEMOGRAPHIC AND CLINI
CAL CHARACTERISTICS OF !$(&
B #HARACTERIZE THE INITIAL %$
EVALUATION SUBSEQUENT MAN
AGEMENT
C )DENTIFY CHARACTERISTICS AND
MEDICAL CARE ASSOCIATED WITH
IMPROVED OUTCOMES
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0ROGRAM $ESIGN
/VERVIEW 4HE STUDY DESIGN IS THAT OF A
MULTI
CENTER CONTINUOUS OBSERVATIONAL
QUALITY IMPROVEMENT INITIATIVE FOCUSING
ON THE MANAGEMENT OF PATIENTS TREATED
IN THE HOSPITAL FOR !$(& IN THE 5NITED
3TATES WITH AN EMPHASIS ON EMERGENCY
MEDICAL CARE )T IS EXPECTED THAT THERE
WILL APPROXIMATELY HOSPITALS PARTICI
PATING CONTINUOUSLY ENROLLING PATIENTS
FOR ABOUT MONTHS OR UP TO PA
TIENT EPISODES 3ITES ARE ELIGIBLE TO PAR
TICIPATE IF THEY ARE A CURRENT !$(%2%
SITE OR IF THEY ARE IN THE TOP LARGEST
5NITED 3TATES ACUTE CARE HOSPITALS WITH A
MEDIAN NUMBER OF ANNUAL (& DISCHARGES
OF ^ PATIENTS 3ELECTED ACADEMIC AND
COMMUNITY HOSPITALS WILL BE EQUALLY DIS
TRIBUTED ALONG THE SPECTRUM OF (& PATIENT
VOLUME AND GEOGRAPHY #OMPONENTS OF
THE %$ $- PROGRAM INCLUDE
4REATMENT ALGORITHMS
/RDER 3ETS
0HYSICIAN2. EDUCATION
0ATIENT %DUCATION
$ISCHARGE )NSTRUCTIONS
&EEDBACK LOOP DATA MONITORING
TOOLS
0ATIENT POPULATION 0ATIENT ELIGIBILITY IS
NOT LINKED TO A SPECIlC THERAPEUTIC AGENT
OR REGIMEN 0ATIENTS ELIGIBLE FOR ENTRY
INTO THE !$(%2% 2EGISTRY INCLUDE THOSE
OVER THE AGE OF ADMITTED TO AN ACUTE
CARE HOSPITAL AND TREATED ACTIVELY FOR
!$(& EITHER AS A NEW ONSET WITH DECOM
PENSATION OR AS CHRONIC HEART FAILURE WITH
DECOMPENSATION 4HIS WOULD INCLUDE THOSE
PATIENTS WHO RECEIVE A PRINCIPAL %$ OR
HOSPITAL DISCHARGE DIAGNOSIS OF !$(& OR
IS DIAGNOSED CLINICALLY AND IS DOCUMENTED
IN THE $2' CODES 0ATIENTS ARE EXCLUDED
IF !$(& IS A COnMORBID CONDITION BUT IS
NOT A PRINCIPAL FOCUS OF DIAGNOSIS OR TREAT
MENT DURING THE %$ OR HOSPITAL EPISODE
3TAFF AND )NSTITUTIONAL REQUIREMENTS
3ITES MUST COMMIT TO UTILIZING A
$- STRATEGY AND WILL BE REQUIRED
TO IMPLEMENT AT LEAST THREE OF lVE
COMPONENTS LISTED BELOW
%ACH SITE MUST HAVE
s /NE %$ 0HYSICIAN AS THE 0RINCIPAL
OR #O
PRINCIPAL INVESTIGATOR
s /NE DEDICATED 2EGISTRY
#OORDINATOR
A 2EQUIRES ACCESS TO ALL %$ AND
HOSPITAL CHART DATA
B #AN PERFORM ELECTRONIC DATA
CAPTURE %$# ENTRY
s )NPATIENT PHYSICIANS SUCH AS
CARDIOLOGISTS
A %NCOURAGED TO PARTICIPATE AS
A #O
PRINCIPAL INVESTIGATOR
TO FACILITATE A FULLY INTEGRATED
$- 1UALITY )MPROVEMENT
PROGRAM
s %$ (& ALGORITHM
s (& ADMISSION ORDERS
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s 0HYSICIAN (& EDUCATION
s 0ATIENT (& EDUCATION
$ATA #OLLECTION 4HE !$(%2% 2EGISTRY IS A LARGE
DATABASE OF PRIMARY CLINICAL INFORMATION COLLECT
ED FROM HOSPITAL RECORDS OF PATIENTS AT SELECT IN
STITUTIONS NATIONWIDE .O PRIOR REGISTRY HAS CON
DUCTED RESEARCH AT THIS LEVEL ON THE CLINICAL CARE
OF PATIENTS WITH !$(& 5SING MEDICAL RECORDS
DATA ARE COLLECTED FROM THE POINT OF INITIAL CARE
THROUGH PATIENT DISCHARGE FROM THE HOSPITAL 4HE
REGISTRY IS COMPLETELY CONlDENTIAL AND ALL PA
TIENT DATA ARE KEPT ANONYMOUS THROUGH ENCRYPTED
TREATMENT $ATA INCLUDE
%
%
%
%
%
%
%
%
$EMOGRAPHICS
%-3 DATA
-EDICAL HISTORY
)NITIAL MEDICAL EVALUATION
(OSPITAL COURSE
-EDICATIONS
0ROCEDURES
% %$# SYSTEM ACCESS IS CONTROLLED BY THE DATA
COORDINATION CENTER AND SYSTEM ENTRY IS LIMITED
BY USERNAMEPASSWORDnPROTECTED LOGON
PROCEDURES
% (OSPITALS WILL BE PREVENTED FROM ACCESSING
ELECTRONIC CASE REPORT FORMS OR AGGREGATE DATA
FROM ANY HOSPITAL OTHER THAN THEIR OWN
4O FOLLOW THE PATIENT ACROSS RECURRING VISITS THE ,ON
GITUDINAL 5NIQUE )DENTIlER ,5)$ SYSTEM WILL BE
UTILIZED FOR CONlDENTIALITY
s
s
s
$ISPOSITION
4HE PROGRAM IS DESIGNED TO COLLECT DATA SURROUNDING
THE EPISODE OF HOSPITAL CARE THAT BEGINS IN THE %$ AS
THE POINT OF INITIAL CARE AND ENDS WITH %$ OR HOSPITAL
DISCHARGE TRANSFER OR DEATH )F THE INSTITUTION IS ALSO
A PART OF THE !$(%2% CORE THE PATIENT MAY TRACKED
UP TO DAYS AFTER ADMISSION $ATA ARE COLLECTED
THROUGH AN )NTERNET
BASED %$# SYSTEM 0ARTICIPATING
INSTITUTIONS ENTER DATA USING A STANDARD WEB BROWSER
CONNECTED TO AN %$# SYSTEM CUSTOMIZED FOR THE !$
(%2% REGISTRY 4HE SYSTEM HAS BEEN FULLY TESTED AND
IS COMPLIANT WITH FEDERAL REGULATIONS
% #&2 'UIDANCE ON #OMPUTERIZED 3YSTEMS
USED IN #LINICAL 4RIALS AND )#( '#0 GUIDELINES
% !LL SITE STAFF WILL BE TRAINED ON THESE REGULATIONS
s
#OMPUTER GENERATED UNIQUE IDENTIlER
A ,5)$ ENCRYPTION USES THE 53 &EDERAL
3TANDARD 3(!
B 4HE ,5)$ ALGORITHM WILL BE INDEPENDENTLY
VALIDATED BY "OOZ !LLEN (OMELAND 3ECURITY
)NFORMATION !SSURANCE #IVIL "USINESS
3EGMENT
7ITH A GIVEN SET OF VARIABLES A ,5)$ IS
GENERATED THAT CANNOT BE RELATED BACK TO AN
INDIVIDUAL
0ATIENT LEVEL VARIABLES USED TO CONSTRUCT THE
,5)$ ARE NOT STORED IN THE SYSTEM AND THIS
INFORMATION CANNOT BE DE
ENCRYPTED FROM THE
,5)$ STORED IN THE DATABASE
4HE ,5)$ IS STORED IN THE DATABASE ALONG WITH
PATIENT DATA AND ALLOWS FOR LONGITUDINAL TRACKING
OF HOSPITAL READMISSIONS AND PATIENT OUTCOMES
%NDPOINTS )N ORDER TO MEET THE OVERALL OBJECTIVES
OF THE 0ROGRAM A NUMBER OF SPECIlC ENDPOINTS ARE
TARGETED FROM WITHIN THE DATA COLLECTION PROCESS 4HE
MOST IMPORTANT OF THESE AREAS OF FOCUS INCLUDE
)MPACT OF $ISEASE -ANAGEMENT 4OOLS ON /UTCOMES
s ,ENGTH OF STAY SYMPTOMATOLOGY
s 2ECIDIVISM TIME TO TREATMENT
$ISPOSITION OF 0ATIENT
s BASED ON PRESENTATION PARAMETERS IE
#R
%MERGENCY $IAGNOSIS AND 4REATMENT OF
!CUTE $ECOMPENSATED (EART &AILURE !$(&
)MPACT OF DIURETICS RELATIVE TO OUTCOMES
s $OSE AND TIMING
s $ElNING WHICH PATIENTS ARE RESPONDERS
"I0!0 #0!0
s )MPACT ON DRUG THERAPY
s )MPACT ON SYMPTOMS OUTCOMES
s /XYGEN 3ATURATIONS
2ESOURCE UTILIZATION
s "ENElT OF OBSERVATION UNITS
4REATING 0HYSICIANS
s 0RIMARY #ARE 3PECIALISTS AND #ONSULTANTS
1UALITY )NITIATIVE 4HE !$(%2% 2EGISTRY ISSUES A
"ENCHMARK 2EPORT EACH QUARTER TO PARTICIPATING CLIN
ICS AND HOSPITALS 4HESE REPORTS SUMMARIZE REGISTRY
DATA COLLECTED ON ACUTE HEART FAILURE TREATMENT DURING
THE PREVIOUS YEAR 4HE REPORTS ALSO MAKE AVAILABLE
INSTITUTION
SPECIlC REGIONAL AND NATIONAL STATISTICS
SUCH AS QUALITY INDICATORS TO PARTICIPATING HOSPITALS
IN ORDER TO HELP THEM EVALUATE AND IMPROVE THE CARE
THEY PROVIDE TO PATIENTS 4HE GOAL IS FOR THE INDIVIDUAL
HOSPITAL TO UTILIZE THIS INFORMATION TO EFFECT CHANGE IN
ORDER TO OPTIMIZE OVERALL DISEASE MANAGEMENT
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&ONAROW '# !$(%2% 3CIENTIlC !DVISORY #OMMITTEE 4HE !CUTE
$ECOMPENSATED (EART &AILURE .ATIONAL 2EGISTRY !$(%2%
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DECOMPENSATED HEART FAILURE 2EV #ARDIOVASC -ED
3UPPL 3
0EACOCK 7& 2APID OPTIMIZATION STRATEGIES FOR OPTIMAL CARE OF
DECOMPENSATED CONGESTIVE HEART
FAILURE PATIENTS IN THE EMERGENCY
DEPARTMENT 2EV #ARDIOVASC -ED 3UPPL 3
%MERMAN #, #OSTANZO -2 "ERKOWITZ 2, #HENG - !$(%2%
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0EACOCK 7& (EART FAILURE MANAGEMENT IN THE EMERGENCY
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SYSTEMS 0RELIMINARY EVIDENCE FROM THE !$(%2%
#ORE 2EGISTRY AND A NUMBER OF OTHER CLINICAL TRIALS
INDICATE THAT THE EMERGENCY DEPARTMENT SHOULD BE THE
FOCAL POINT FOR THE DISEASE MANAGEMENT PROCESS OF
!$(& 4HE !$(%2% %$ $- PROGRAM PRESENTS A
REAL OPPORTUNITY FOR THE EMERGENCY MEDICINE COMMU
NITY TO BETTER UNDERSTAND THE ISSUES SURROUNDING THIS
DISEASE STATE AND TO OBJECTIVELY OUTLINE THE BEST COURSE
FOR OVERALL DISEASE MANAGEMENT
#OPYRIGHT %-#2%' )NTERNATIONAL
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4HE RISING PREVALENCE AND COST OF CARE FOR HEART FAILURE IS STAGGERING !LMOST MILLION
!MERICANS HAVE HEART FAILURE WITH NEW CASES DIAGNOSED EACH YEAR AT A TOTAL
COST OF BILLION 4HE INCIDENCE IS EXPECTED TO CONTINUE TO INCREASE DRAMATICALLY
DUE TO OUR AGING POPULATION PREVALENCE OF HEART FAILURE IN INDIVIDUALS OVER AGE
IMPROVED SURVIVAL FROM ACUTE CORONARY SYNDROMES !#3 AND MANAGEMENT AD
VANCES IN CARDIOVASCULAR DISEASES
(OSPITALIZATION ACCOUNTS FOR OVER OF HEART
FAILURE COSTS /VER HALF OF PATIENTS OLDER THAN YEARS WITH CONGESTIVE HEART FAILURE
#(& ARE READMITTED WITHIN MONTHS OF HOSPITAL DISCHARGE
7HILE MEDICAL RISK FACTORS ARE WELL KNOW TO BE ASSOCIATED WITH HOSPITAL READMISSION AGE
INCREASED LENGTH
OF
STAY AND NUMBER OF COMORBIDITIES OFTEN OVERLOOKED SOCIAL FACTORS
SUCH AS SINGLE MARITAL STATUS READINESS FOR DISCHARGE MEDICATION AND DIETARY NONCOM
PLIANCE ALSO INmUENCE THE CHANCE OF #(& READMISSION
(EART FAILURE DISEASE MAN
AGEMENT $- PROGRAMS ARE DESIGNED TO TARGET SOCIAL RISK FACTORS RESULTING IN DECREASED
RECIDIVISM
(EART &AILURE $ISEASE -ANAGEMENT
(EART FAILURE $- PROGRAMS HAVE PROVEN
TO BE EFFECTIVE AT REDUCING SUBSEQUENT
READMISSIONS IN THOSE DISCHARGED AFTER A
#(& ADMISSION )T HAS BEEN SUGGEST
ED THAT $- PROGRAMS ARE NEARLY AS EFFEC
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%$ HAVE A HIGH RATE OF RECIDIVISM AND
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OF THIS EMERGENCY PHYSICIANS HAVE THE
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OLD MALE TOBACCO SMOKER WITH A HISTORY
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SOME WHEEZING WHEN HE IS BREATHING 0HYSICAL
EXAMINATION REVEALS SCANT CRACKLES AT THE BASES
BILATERALLY WITH CM OF JUGULAR VENOUS DISTENTION
AN 3 HEART SOUND AND NO MURMUR 7HICH OF THE
FOLLOWING BEST SUPPORTS A DIAGNOSIS OF CONGESTIVE
HEART FAILURE
A #ARDIOMEGALY ON CHEST RADIOGRAPHY
B ! ".0 LEVEL OF PGD,
C .ORMAL CHEST RADIOGRAPHY
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7HICH OF THE FOLLOWING DISEASES CAN RESULT IN LOW
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A 2IGHT VENTRICULAR FAILURE FROM COR PULMONALE
B !CUTE PULMONARY EMBOLISM
C #(& IN AN OBESE PATIENT
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E !LL OF THE ABOVE
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ASSESSING THEN FOR WHICH OF THE FOLLOWING
A $EGREE OF CARDIAC PERFUSION AND PRESENCE OF
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C "LOOD PRESSURE AND PRESENCE OF CONGESTION
D 2ENAL FUNCTION AND VOLUME STATUS
E 2ENAL FUNCTION AND PERIPHERAL EDEMA
7HICH OF THE FOLLOWING IS NOT TRUE ABOUT THE ROLE OF
VASODILATORS IN ACUTELY DECOMPENSATED HEART
A 4HEY REDUCE PRELOAD AND AFTERLOAD
B -YOCARDIAL OXYGEN CONSUMPTION IS OFTEN
INCREASED
C 4HEY INCREASE STROKE VOLUME AND IMPROVE
CARDIAC OUTPUT
D 4HEY MAY CAUSE HYPOTENSION
E 4HE BEST HEMODYNAMIC INDICATOR OF VASODILATOR
THERAPY RESPONSE IS A DROP IN THE PULMONARY
CAPILLARY WEDGE PRESSURE
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FOLLOWING
A DECREASED MORTALITY
B LOWER )#5 ADMISSION RATE
C SHORTER HOSPITALIZATIONS
D FEWER INVASIVE PROCEDURES
E ALL OF THE ABOVE
!N ELEVATED TROPONIN IN THE SETTING OF ACUTE
DECOMPENSATED HEART FAILURE IS ASSOCIATED WITH
A LONGER )#5 HOSPITALIZATION
B INCREASED MORTALITY
C LONGER HOSPITALIZATION
D A HIGHER RATE OF INTUBATION AND BALLOON PUMP
USAGE
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A 0ATIENTS IN !$(%2% TEND TO BE OLDER
B !BOUT HALF THE PATIENTS IN !$(%2% ARE WOMEN
C 2ENAL INSUFlCIENCY PATIENTS ARE EXCLUDED FROM
!$(%2%
D 4HE !$(%2% POPULATION INCLUDES ACADEMIC AND
COMMUNITY CENTER
E !LL OF THE ABOVE ARE TRUE
)N THE !$(%2% INTRAVENOUS VASOACTIVE MORTALITY
ANALYSIS WHICH OF THE FOLLOWING STATEMENTS ARE TRUE
A 0ATIENTS WHO RECEIVED IN
HOSPITAL NITROGLYCERIN
HAD LOWER IN
HOSPITAL MORTALITY
B 0ATIENTS WHO RECEIVED INTRAVENOUS NESIRITIDE HAD
LOWER IN HOSPITAL MORALITY
C 0ATIENTS TREATED WITH DOBUTAMINE OR MILRINONE
HAD HIGHER IN
HOSPITAL MORTALITY
D ! AND # ARE CORRECT
E ! " AND # ARE CORRECT
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A 1UALITY CONTROL
B %DUCATION OF PHYSICIANS
C ,ABORATORY ACCREDITATION AND REGULATION
D $ElNED AND REGULATED TESTING PROCEDURES
E !LL OF THE ABOVE
&ACTORS THAT SHOULD BE CONSIDERED IN THE COST ANALYSIS
OF A POINT
OF
CARE TESTING PROGRAM INCLUDE ALL OF THE
FOLLOWING %8#%04
A ,ABORATORY RESULT TURN
AROUND
TIME 4!4
B 4IME TO DISPOSITION
C 0ATIENT AND PHYSICIAN CONSUMER DEMAND
D #OST OF TESTING PLATFORM AND REAGENTS
E !LL OF THE ABOVE ARE CORRECT
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4HE COMPONENTS OF DISEASE MANAGEMENT INCLUDE ALL
OF THE FOLLOWING EXCEPT
A 4REATMENT ALGORITHM
B !DMISSION ORDERS
C 0ATIENT DISCHARGE CHECKLIST
D 0ATIENT EDUCATION
E !LL OF THE ABOVE
0ATIENT EDUCATION AND A DISCHARGE CHECKLIST ARE TWO
DISEASE MANAGEMENT TOOLS THAT ARE USED TO IMPROVE
MEDICATION AND DIETARY COMPLIANCE IN AN EFFORT TO
DECREASE DAY HOSPITAL READMISSION 4HE CURRENT
DAY READMISSION RATE FOR HEART FAILURE PATIENTS
DISCHARGED FROM THE HOSPITAL IS APPROXIMATELY
A
B
C
D
%MERGENCY $IAGNOSIS AND 4REATMENT OF
!CUTE $ECOMPENSATED (EART &AILURE !$(&
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-AIL THE ANSWER SHEET TO
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/N A SCALE OF TO WITH BEING HIGHLY SATISlED AND
BEING HIGHLY DISSATISlED PLEASE RATE THIS PROGRAM WITH
RESPECT TO
(IGHLY SATISlED (IGHLY DISSATISlED
/FlCE OF #ONTINUING -EDICAL %DUCATION
5NIVERSITY OF #INCINNATI #OLLEGE OF -EDICINE
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#INCINNATI /(
/VERALL QUALITY OF MATERIAL
#ONTENT OF MONOGRAPH
/THER SIMILAR #-% PROGRAMS
(OW WELL COURSE OBJECTIVES WERE MET
#-% EXPIRATION DATE *UNE
7HAT TOPICS WOULD BE OF INTEREST TO YOU FOR FUTURE #-%
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7AS THERE COMMERCIAL OR PROMOTIONAL BIAS IN THE
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)N ACCORDANCE WITH #-% 3TANDARDS FOR #OMMERCIAL 3UPPORT OF #-% THE AUTHORS HAVE DISCLOSED THE FOLLOWING
RELEVANT RELATIONSHIPS WITH PHARMACEUTICAL OR DEVICE MANUFACTURERS
*UDD % (OLLANDER -$
2ESEARCH'RANTS#ONSULTANT "IOSITE #ONSULTANT 3CIOS
$OUGLAS - #HAR -$ #ONSULTANT 3CIOS
7 &RANK 0EACOCK -$ 'RANT2ESEARCH#ONSULTANT 3CIOS
7ILLIAM !BRAHAM -$
2ICHARD , 3UMMERS -$ #ONSULTANT AND SPEAKERS BUREAU 3CIOS
3EAN 0 #OLLINS -$
3PEAKER HONORARIA RESEARCH GRANTS AND CONSULTING FEES FOR 3CIOS
.ONE
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&ACULTY MEMBERS ARE REQUIRED TO INFORM THE AUDIENCE WHEN THEY ARE DISCUSSING OFF
LABEL UNAPPROVED USES
OF DEVICES AND DRUGS 0HYSICIANS SHOULD CONSULT FULL PRESCRIBING INFORMATION BEFORE USING ANY PRODUCT
MENTIONED IN THIS MONOGRAPH
4HIS EDUCATIONAL MONOGRAPH WAS SUPPORTED IN PART BY AN UNRESTRICTED EDUCATIONAL GRANT FROM 3CIOS
#OPYRIGHT %-#2%' )NTERNATIONAL
)NTERNATIONAL
W W W E M C R E G O R G
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