Definition and Efficacy

Cardiac markers are used in the diagnosis and risk

stratification of patients with chest pain and
suspected acute coronary syndrome (ACS). The
cardiac troponins, in particular, have become the
cardiac markers of choice for patients with ACS.
Indeed, cardiac troponin is central to the definition
of acute myocardial infarction (MI) in the
consensus guidelines from the American College of
Cardiology (ACC) and the European Society of
Cardiology (ESC).[1, 2, 3]

For example, patients with elevated troponin levels
but negative creatine kinase-MB (CK-MB) values
who were formerly diagnosed with unstable angina
or minor myocardial injury are now reclassified as
nonST-segment elevation MI (NSTEMI), even in
the absence of diagnostic electrocardiogram (ECG)
changes.

Similarly, only 1 elevated troponin level above the
established cutoff is required to establish the
diagnosis of acute MI, according to the ACC
guidelines for NSTEMI.[4]

These changes were instituted following the
introduction of increasingly sensitive and precise
troponin assays. Up to 80% of patients with acute
MI will have an elevated troponin level within 2-3
hours of emergency department (ED) arrival,
versus 6-9 hours or more with CK-MB and other
cardiac markers.

Accordingly, some have advocated relying solely
on troponin and discontinuing the use of CK-MB
and other markers.[5, 6, 7, 8, 9] Nevertheless, CK-
MB and other markers continue to be used in some
hospitals to rule out MI and to monitor for
additional cardiac muscle injury over time.

Note that cardiac markers are not necessary for the
diagnosis of patients who present with ischemic
chest pain and diagnostic ECGs with ST-segment
elevation. These patients may be candidates for
thrombolytic therapy or primary angioplasty.
Treatment should not be delayed to wait for cardiac
marker results, especially since the sensitivity is
low in the first 6 hours after symptom onset.
ACC/American Heart Association (AHA)
guidelines recommend immediate reperfusion
Definiie i eficacitate
Markeri cardiace sunt utilizate n diagnosticul i
stratificarea riscului de pacienti cu dureri in piept si
sindrom coronarian acut suspectat ( ACS ) . A
troponinei cardiace , n special , au devenit markerii
cardiace de alegere pentru pacientii cu ACS . ntr-
adevr , troponinei este esenial pentru definirea
infarctului miocardic acut ( MI) , n liniile
directoare consens de la Colegiul American de
Cardiologie ( ACC ) si a Societatii Europene de
Cardiologie ( ESC ) [ 1 , 2 , 3 ] .

De exemplu , pacientii cu niveluri crescute ale
troponinei dar creatinkinazei - MB ( CK - MB )
valori negative , care au fost anterior diagnosticat
cu angin instabil sau leziuni miocardice minore
sunt acum reclasificate ca - segmentului non -
supradenivelare MI ST ( NSTEMI ) , chiar i n
absena a electrocardiogramei (ECG ) schimbari de
diagnosticare .

Similar , numai 1 nivel troponinei mai suscutoff
stabilit este necesar pentru a stabili diagnosticul de
infarct miocardic acut , n conformitate cu liniile
directoare ACC pentru NSTEMI . [ 4 ]

Aceste modificri au fost instituite ca urmare a
introducerii de teste ce n ce mai sensibile i precise
troponinei . Pn la 80 % din pacientii cu infarct
miocardic acut va avea un nivel troponinei n
termen de 2-3 ore de la departamentul de urgenta (
ED ) sosire , comparativ cu 6-9 ore sau mai mult ,
cu CK - MB si a altor markeri cardiace .

n consecin , unii au susinut bazndu-se doar pe
troponina i ntrerupereautilizrii CK - MB i ali
markeri . [ 5 , 6 , 7 , 8 , 9 ] Cu toate acestea , CK -
MB i alte markeri continu s fie folosite n unele
spitale pentru a exclude MI i s monitorizeze
pentru un prejudiciu suplimentar miocardului
lungul timpului .

Reinei c markeri cardiace nu sunt necesare
pentru diagnosticul pacienilor care prezint cu
dureri in piept ischemic i EKG de diagnosticare cu
supradenivelare de segment ST . Acesti pacienti pot
fi candidati pentru terapia trombolitic sau prin
angioplastie primar . Tratamentul nu ar trebui s
fie amnat s atepte pentru rezultate marcator
cardiace , mai ales deoarece sensibilitatea este
sczut n primele 6 ore de la debutul simptomelor .
therapy for qualifying patients with ST-segment
elevation MI (STEMI), without waiting for cardiac
marker results.[10]

Go to Myocardial Infarction and Complications of
Myocardial Infarction for more complete
information on these topics.

Cardiac Troponins
The troponins are regulatory proteins found in
skeletal and cardiac muscle. Three subunits have
been identified: troponin I (TnI), troponin T (TnT),
and troponin C (TnC). The genes that encode for
the skeletal and cardiac isoforms of TnC are
identical; thus, no structural difference exists
between them. However, the skeletal and cardiac
subforms for TnI and troponin TnT are distinct, and
immunoassays have been designed to differentiate
between them.

Two different reference ranges are used in troponin
assays. The upper percentile reference limit gives
the upper limit of what can be expected in a
normal, healthy, adult population, while the
coefficient of variation (CV) is the percent
variation in assay results that can be expected when
the same sample is repeatedly analyzed.

According to the ACC/ESC guidelines, any
elevated measure of troponin above the 10% CV or
99th percentile upper reference limit in the
appropriate clinical setting is defined as an MI.

The sensitivity, specificity, and precision of the
different commercially available troponin assays
vary considerably. These differences are related to
a lack of standardization, the use of different
monoclonal antibodies, the presence of modified
TnI and TnT in the serum, and variations in
antibody cross-reactivity to the various detectable
forms of TnI that result from its degradation.

Only one manufacturer produces the TnT assay,
and its 99th percentile cutoffs and the 10% CV are
well established. However, up to 20-fold variation
has occurred in results obtained with the multitude
of commercial TnI assays currently available, each
with their own 99th percentile upper reference
limits and 10% CV levels.

In the GUSTO IV study, a relatively insensitive
ACC / American Heart Association ( AHA ) liniile
directoare recomanda terapia de reperfuzie
imediat pentru pacientii cu - segment ST ( IMA
ST ) de calificare , fr a mai atepta rezultatele
marcator cardiace . [ 10 ]

Du-te la infarct miocardic si a complicatiilor de
infarct miocardic pentru informaii mai complete cu
privire la aceste subiecte .

Troponinele cardiace
Cele troponinele sunt proteine de reglementare
gasite in muschii scheletici si cardiac . Au fost
identificate trei subuniti : troponina I ( TNI ) ,
troponina T ( TNT) , i troponina C ( CTN) .
Genele care codific pentru izoforme scheletice i
cardiace ale TnC sunt identice , astfel , nu exist
diferene structurale ntre ele . Cu toate acestea,
subformularele scheletice i cardiace pentru TNI si
troponina TNT sunt distincte , i imunotestele au
fost concepute pentru a diferenia ntre ele .

Dou intervale de referin diferite sunt utilizate n
teste troponin . Limita superioar de referin
procentual dlimita superioar a ceea ce poate fi
de ateptat ntr -o populaie normal , sntoas ,
pentru aduli , n timp cecoeficientul de variaie (
CV ) estevariaia n procente rezultatele testului ,
care poate fi de ateptat atunci cndaceeai prob
este analizat n mod repetat .

n conformitate cu liniile directoare ACC / ESC ,
orice msur ridicat a troponinei sus a CV-ului de
10 % sau limita a 99- percentila de referin
superioare n mediu clinic corespunztor, este
definit ca un MI .

Sensibilitatea , specificitatea , i precizia diferitelor
teste troponin disponibile comercial variaz
considerabil . Aceste diferene sunt legate de o
lips de standardizare ,utilizarea diferitelor
anticorpi monoclonali , prezena modificat TnI i
TnT nser , i variaiile anticorp reactivitate
ncruciat la diverse forme detectabile de TnI care
rezulta din degradarea acesteia .

Doar un singur productor produce testul TNT, i
ei cutoffs percentila 99 i CV-ul de 10 %, sunt bine
stabilite . Cu toate acestea , pn la variaia de 20
de ori a avut loc n rezultatele obinute cu
multitudinea de teste comerciale TNI disponibile n
point-of-care TnI assay was used to screen patients
for study eligibility. In a subsequent study, the
blood samples were reanalyzed using the 99th
percentile cutoff of a far more sensitive central
laboratory TnT assay. The more sensitive 99th
percentile cutoff of this TnT assay identified an
additional 96 (28%) of 337 patients with a positive
TnT result but negative point-of-care TnI; these
patients had higher rates of death or MI at 30
days.[11]

In a similar reanalysis of the TACTICS-TIMI 18
trial, 3 different TnI cutoffs were compared on
1821 patients to evaluate the 30-day risk of death
or MI: the 99th percentile, 10% CV, and the World
Health Organization (WHO) acute MI cutoffs. (The
WHO cutoffs define acute MI using CK-MB and
report troponin levels as either a higher acute MI
level or a lower intermediate level that is
correlated with leak or minor myocardial
injury.)

Using the 10% CV cutoff identified, an additional
12% more cases were identified relative to the
WHO acute MI cutoff. The 99th percentile cutoff
identified an additional 10% of cases relative to the
10% CV cutoff, as well as a 22% increase in the
number of cases over the WHO acute MI cutoff.
Nevertheless, the odds ratios for the adverse
cardiac event rates of death or MI at 30 days were
similar for all 3 cutoffs, suggesting that the lower
cutoffs detected more patients with cardiovascular
risk without sacrificing specificity.[12, 13]

The National Academy of Clinical Biochemistry
(NACB) working with the ACC/ESC guidelines
has recommended adoption of the 99th percentile
upper reference limit as the recommended cutoff
for a positive troponin result. Ideally, the precision
of the assay at this cutoff level should be measured
by a CV that is less than 10%.

However, most TnI assays are imprecise at the 99th
percentile reference limit.[14] Some have therefore
recommended that the cutoff level be raised to the
slightly higher 10% CV level instead of the 99th
percentile reference limit to ensure adequate assay
precision.

In addition, studies have shown that populations
within the 99th percentile reference limit include
prezent , fiecare cu propriile lor limite 99-a
percentila de referin superioare i 10 % Nivelul
de CV .

In cadrul studiului GUSTO IV , un relativ
insensibil punct - de - ingrijire TNI testul a fost
folosit pentru a ecran pacientii pentru eligibilitate
de studiu . ntr -un studiu ulterior , probele de snge
au fost reanalizata utilizndcutoff percentila 99 a
unei mult mai sensibil central TnT test de
laborator . Mai sensibil cutoff percentila 99- a
acestui test TnT a identificat o sum suplimentar
de 96 ( 28 % ) din 337 de pacienti cu un rezultat
pozitiv, dar TNT negativ punct - de - ingrijire TNI ;
. Acesti pacienti au avut rate mai mari de deces sau
IM la 30 zile [ 11 ]

ntr- o reanalizarea similar a tacticile - TIMI 18
proces , 3 cutoffs TNI diferite au fost comparate pe
1821 de pacienti pentru a evalua riscul de 30 de zile
de decesul sau IM : percentila 99 , CV 10 % , iar
Organizaia Mondial a Sntii ( OMS ) acut
cutoffs MI . (OMS Cutoffs defini infarct miocardic
acut cu CK - MB i s raporteze nivelurile
troponinei fie ca un mare " nivel de IM acut " sau
un " nivel intermediar " inferior , care este corelat
cu " scurgere " sau " prejudiciu miocardic minore .
" )

Folosind10 % CV cutoff identificat , o
suplimentare de 12 % mai multe cazuri au fost
identificate n raportOMS acut MI tiere . 99 cutoff
procentual a identificat un supliment de 10 % din
cazurile raportate la10 % CV tiere , precum i o
cretere de 22 % a numrului de cazuri pesteOMS
acut MI tiere . Cu toate acestea , raporturile cote
pentru adverse rate de eveniment cardiace de deces
sau IM la 30 zile au fost similare pentru toate cele 3
cutoffs , sugerand ca cutoffs inferior detectat mai
multi pacienti cu risc cardiovascular , fr a
sacrifica specificitate [ 12 , 13 ] .

Academiei Nationale de Biochimie clinic ( NACB
) de lucru cu liniile directoare ACC / ESC a
recomandat adoptarea de limita de 99 percentila de
referin superioar ca cutoff recomandat pentru un
rezultat pozitiv troponinei . n mod ideal ,de
precizie a testului la acest nivel oprire trebuie
msurat printr-un CV care este mai mic de 10 % .

Cu toate acestea , majoritatea analizelor TNI sunt
patients with low troponin levels who nevertheless
have an elevated cardiac risk, and that the true 99th
percentile cutoff for a healthy patient population is
actually a factor of 10-50 lower. Accordingly, these
investigations suggest that higher sensitivity or
ultrasensitive troponin assays are necessary.[13]
The advantage of ultrasensitive troponins is based
on the premise that lower cutoff levels achieve
higher sensitivity that will allow earlier diagnosis,
often within 90 minutes of presentation.

To optimize the assays use in the ED, it is
important to be familiar with the particular troponin
assay available in the laboratory and to know
whether the cutoff is set at the 10% CV level or the
99th percentile upper reference limit.

Point-of-care assays
NACB recommendations specify that cardiac
markers be available on an immediate basis 24 h/d,
7 d/wk, with a turnaround time of 1 hour.[15]
Point-of-care (POC) devices that provide rapid
results should be considered in hospitals whose
laboratories cannot meet these guidelines.

POC assays for CK-MB, myoglobin, and the
cardiac troponins TnI and TnT are available. Only
qualitative TnT assays are available as POC tests,
but both quantitative and qualitative POC TnI
assays are currently marketed.

In a multicenter trial, the time to positivity was
significantly faster for the POC device than for the
local laboratory (2.5 h vs 3.4 h).[16]

In another multicenter study, which evaluated the i-
STAT POC TnI assay in comparison with the
central laboratory in 2000 patients with suspected
ACS, POC testing reduced the length of stay by
approximately 25 minutes for patients who were
discharged from the ED.[17, 18] The sensitivity of
current POC assays coupled with the benefit of
rapid turnaround time make the POC assays
attractive clinical tools in the ED.

Prognostic value of troponin
In addition to its use in the diagnosis of MI, an
elevated troponin level can identify patients at high
risk for adverse cardiac events.[19, 20]
Specifically, data from a meta-analysis indicated
that an elevated troponin level in patients without
imprecise la limita de referin percentila 99 . [ 14 ]
, prin urmare, Unii au recomandat canivelul cutoff
fi ridicat lanivelul uor mai mare CV 10 % n loc
delimita de 99 de referin procentual a asigura
precizie test adecvat .

n plus , studiile au artat c populaiile din limitele
de referin pentru percentila 99 include pacienti cu
niveluri scazute troponinei care au totui un risc
cardiac crescut , i c adevratul cutoff percentila
99 pentru o populaie sntoas pacientul este de
fapt un factor de 10-50 mai mic . n consecin ,
aceste anchete sugereaz c sensibilitatea mai mare
sau testele troponinei ultrasensitive sunt necesare [
13 ] Avantajul troponinelor ultrasensitive se
bazeaz pe premisa c nivelurile de limita minim
atinge o sensibilitate mai mare , care va permite
diagnosticul mai devreme , de multe ori n termen
de 90 de minute de prezentare . .

Pentru a optimiza utilizarea testului n ED , este
important s fie familiarizai cu deosebit
troponinei disponibil n laborator i de a ti dac
cutoff este stabilit la nivelul CV 10 % sau limita de
99 percentila de referin superioar .

Teste punct - de - ingrijire
Recomandrile NACB precizeaz c markeri
cardiaci fi disponibile pe o baz imediat 24 de ore /
zi , 7 zile / sptmn , cu un timp de rspuns de 1
or . [ 15 ] la punctul de ingrijire ( POC )
dispozitive care ofer rezultate rapide ar trebui s
fie luate n considerare n spitale, laboratoare ale
caror nu pot rspunde acestor linii directoare .

Teste POC pentru CK - MB , mioglobinei , iar
cardiace troponinei TNI i TNT sunt disponibile .
Doar teste calitative TnT sunt disponibile ca teste
POC , dar att cantitative, ct i calitative POC
testele TNI sunt n prezent comercializate .

ntr -un studiu multicentric ,timp pentru pozitivitate
a fost semnificativ mai rapid pentruaparatul POC
dect pentrulaborator local ( 2,5 ore vs 3,4 h ) . [
16 ]

ntr-un alt studiu multicentric , care a evaluat POC
TNI testul i-STAT n comparaie cu laboratorul
central de la 2000 de pacienti cu SCA suspectate ,
testare POC a redus durata de edere de
aproximativ 25 de minute pentru pacientii care au
ST-segment elevation is associated with a nearly 4-
fold increase in the cardiac mortality rate.[21] In
patients without ST-segment elevation who were
being considered for thrombolytic therapy, initial
TnI levels on admission correlated with mortality at
6 weeks, but CK-MB levels were not predictive of
adverse cardiac events and had no prognostic
value.[19]

Other studies revealed that an elevated troponin
level at baseline was an independent predictor of
mortality, even in patients with chest pain and
acute MI with ST-segment elevation who were
eligible for reperfusion therapy.[22, 23]

Finally, the TIMI IIIB, GUSTO IIa, GUSTO IV
ACS, and FRISC trial all demonstrated a direct
correlation between the level of TnI or TnT and the
mortality rate and adverse cardiac event rate in
ACS.[19, 22, 24, 25, 26]

Creatine KinaseMB
Prior to the introduction of cardiac troponins, the
biochemical marker of choice for the diagnosis of
acute MI was the CK-MB isoenzyme. The criterion
most commonly used for the diagnosis of acute MI
was 2 serial elevations above the diagnostic cutoff
level or a single result more than twice the upper
limit of normal. Although CK-MB is more
concentrated in the myocardium, it also exists in
skeletal muscle and false-positive elevations occur
in a number of clinical settings, including trauma,
heavy exertion, and myopathy.

CK-MB first appears 4-6 hours after symptom
onset, peaks at 24 hours, and returns to normal in
48-72 hours. Its value in the early and late (>72 h)
diagnosis of acute MI is limited. However, its
release kinetics can assist in diagnosing reinfarction
if levels rise after initially declining following
acute MI.

In the CRUSADE registry, a review of almost
30,000 patients revealed that discordant troponin
and CK-MB results occurred in 28% of patients.
However, patients who were troponin negative but
CK-MB positive had in-hospital mortality rates that
were not significantly increased from patients who
were negative for both biomarkers.[27]

Similarly, in a report of more than 10,000 patients
fost evacuate din ED . [ 17 , 18 ] sensibilitatea
testelor de POC actuale cuplate cu beneficiul de
timp de rspuns rapid a face teste POC instrumente
clinice atractive n ED .

Valoarea de prognostic a troponinei
In plus fata de utilizarea sa n diagnosticul de MI ,
un nivel troponinei pot identifica pacientii cu risc
crescut de evenimente adverse cardiace . [ 19 , 20 ]
Mai exact , datele de la o meta- analiz a artat c
un nivel troponinei la pacieni fr ST -
supradenivelare de segment este asociat cu o
crestere de aproape 4 ori a ratei mortalitii
cardiace . [ 21 ] la pacieni fr supradenivelare de
segment ST care au fost luate n considerare pentru
tratament trombolitic , nivelurile iniiale TNI la
admitere, corelate cu mortalitatea la 6 sptmni ,
dar CK - nivelurile de MB nu au fost de predictie
de evenimente adverse cardiace i a avut nici o
valoare de prognostic . [ 19 ]

Alte studii au evideniat c un nivel troponinei la
momentul initial a fost un predictor independent de
mortalitate , chiar si la pacientii cu dureri in piept si
infarct miocardic acut cu supradenivelare de
segment ST care au fost eligibili pentru terapia de
reperfuzie . [ 22 , 23 ]

n cele din urm ,IIIB , GUSTO IIa , GUSTO IV
ACS , i FRISC studiu TIMI demonstrat tot o
corelaie direct ntre nivelul de TNI sau TNT i
rata mortalitii i rata evenimentelor adverse
cardiace n ACS . [ 19 , 22 , 24 , 25 , 26 ]

Creatinkinazei - MB
nainte de introducerea a troponinelor cardiace ,
marker biochimic de alegere pentru diagnosticul de
IM acut a fost izoenzimei CK - MB . Criteriul cel
mai frecvent utilizate pentru diagnosticul de IM
acut a fost de 2 cote de serie peste nivelul cutoff
diagnostic sau un singur rezultat mai mult dect de
dou ori limita superioar a normalului . Dei CK -
MB este mai concentrat n miocard , este , de
asemenea, exista in muschii scheletici si cresteri
fals - pozitive apar ntr-o serie de setari clinice ,
inclusiv traume , efort greu , i miopatie .

CK - MB apare pentru prima dat de 4-6 ore de la
debutul simptomelor , vrfuri La 24 ore , i revine
la normal n 48-72 de ore . Valoarea n diagnosticul
precoce i tardiv ( > 72 h ) de infarct miocardic
with ACS from the multicenter GRACE registry,
in-hospital mortality was highest when both
troponin and CK-MB were positive, intermediate in
troponin-positive/CK-MB-negative patients, and
lowest in patients in whom both markers were
negative and in those who were troponin-
negative/CK-MB-positive.[28] Thus, an isolated
CK-MB elevation has limited prognostic value in
patients with a non-ST elevation ACS.

CK-MB/CK relative index
The relative index calculated by the ratio of CK-
MB (mass) to total CK can assist in differentiating
false-positive elevations of CK-MB arising from
skeletal muscle. A ratio of less than 3 is consistent
with a skeletal muscle source, while ratios greater
than 5 are indicative of a cardiac source. Ratios
between 3 and 5 represent a gray zone. No
definitive diagnosis can be established without
serial determinations to detect a rise.

The CK-MB/CK relative index was introduced to
improve the specificity of CK-MB elevation for
myocardial infarction. However, sensitivity for
acute MI falls when concurrent cardiac injury and
skeletal muscle injury is present. In an ED-based
study to evaluate the CK-MB relative index
compared with the absolute CK-MB, specificity
was increased, but with a loss of sensitivity.[29]

The CK-MB/CK relative index is useful if patients
have only an MI or only skeletal muscle injury, but
not if they have both. Therefore, in the combined
setting of acute MI and skeletal muscle injury
(rhabdomyolysis, heavy exercise, polymyositis),
the fall in sensitivity is significant.

Note that the diagnosis of acute MI must not be
based on an elevated relative index alone, because
the relative index may be elevated in clinical
settings when either the total CK or the CK-MB is
within normal limits. The relative index is only
clinically useful when both the total CK and the
CK-MB levels are increased.

CK-MB isoforms
The CK-MB isoenzyme exists as 2 isoforms: CK-
MB1 and CK-MB2. Laboratory determination of
CK-MB actually represents the simple sum of the
isoforms CK-MB1 and CK-MB2. CK-MB2 is the
tissue form and initially is released from the
acut este limitat . Cu toate acestea , cinetica sale
de eliberare poate ajuta la diagnosticarea
reinfarctizarea dac nivelul crete dup ce a refuzat
iniial urmtoarele infarct miocardic acut .

n registru cruciada , o revizuire a aproape 30.000
de pacienti a aratat ca discordanta troponina i
rezultatele CK - MB a avut loc in 28 % dintre
pacienti . Cu toate acestea , pacientii care au fost
troponina negativa , dar CK - MB pozitiv au avut
rate de mortalitate in spital , care nu au crescut
semnificativ de la pacientii care au fost negative
pentru ambele biomarkeri . [ 27 ]

De asemenea, ntr-un raport de mai mult de 10.000
de pacienti cu SCA din registrul GRACE
multicentric , mortalitatea intraspitaliceasc a fost
mai mare atunci cnd att troponina i CK - MB au
fost pozitive , intermediar la pacientii troponin-
positive/CK-MB-negative , i cea mai mic n
pacientii la care ambele markeri au fost negative i
n cei care au fost troponin-negative/CK-MB-
positive . [ 28 ] Astfel , un izolat CK - MB elevaie
a limitat valoarea de prognostic la pacientii cu un
non - ST ACS altitudine .

Index relativ CK-MB/CK
Indicele relativ, calculat prin raportul dintre CK -
MB ( masa ) total a CK pot ajuta la diferenierea
cresteri fals - pozitive ale CK - MB decurg din
muschii scheletici . Un raport mai mic de 3 este n
concordan cu o surs de muchi scheletici , n
timp ce raporturi mai mari de 5 indic o surs
cardiace . Indicatori ntre 3 i 5 reprezint o zon
gri . Nici un diagnostic definitiv poate fi stabilit
fr determinri de serie pentru a detecta o cretere
.

Indicele relativ CK-MB/CK fost introdus pentru a
mbuntispecificitatea CK - MB elevaie pentru
infarct miocardic . Cu toate acestea , sensibilitatea
de infarct miocardic acut scade atunci cnd
prejudiciului cardiace concomitent i leziuni
musculare scheletice este prezent . ntr-un studiu de
ED pe baz pentru a evaluaindicele relativ CK -
MB comparativ cuabsolut CK - MB , specificitate
a fost crescut , dar cu o pierdere de sensibilitate . [
29 ]

Indicele relativ CK-MB/CK este util n cazul n
care pacienii au doar un MI sau leziuni musculare
myocardium after MI. It is converted peripherally
in serum to the CK-MB1 isoform rapidly after
symptom onset.

Normally, the tissue CK-MB1 isoform
predominates; thus, the CK-MB2/CK-MB1 ratio is
typically less than 1. A result is positive if the CK-
MB2 is elevated and the ratio is greater than 1.7.

CK-MB2 can be detected in serum within 2-4 hours
after onset and peaks at 6-9 hours, making it an
early marker for acute MI. Two large studies
evaluating its use revealed a sensitivity of 92% at 6
hours after symptom onset, compared with 66% for
CK-MB and 79% for myoglobin.[30, 31] The
major disadvantage of this assay is that it is
relatively labor intensive for the laboratory.

Myoglobin
Myoglobin is a heme protein found in skeletal and
cardiac muscle that has attracted considerable
interest as an early marker of MI. Its low molecular
weight accounts for its early release profile:
myoglobin typically rises 2-4 hours after onset of
infarction, peaks at 6-12 hours, and returns to
normal within 24-36 hours.

Rapid myoglobin assays are available, but overall,
they have a lack of cardiospecificity. Serial
sampling every 1-2 hours can increase the
sensitivity and specificity; a rise of 25-40% over 1-
2 hours is strongly suggestive of acute MI.
However, in most studies, myoglobin only
achieved 90% sensitivity for acute MI, so the
negative predictive value of myoglobin is not high
enough to exclude the diagnosis of acute MI.

The original studies that evaluated myoglobin used
the WHO definition of acute MI that was based on
a CK-MB standard. With the adoption of a troponin
standard for acute MI in the ACC/ESC definition,
the sensitivity of myoglobin for acute MI is
substantially reduced. This significantly diminishes
its utility, and a number of studies have indicated
that contemporary cardiac troponin assays render
the use of myoglobin measurements
unnecessary.[6, 8]

Testing Strategy
In patients with definite or possible ACS, serial
evaluation of cardiac markers is essential to
numai scheletici , dar nu n cazul n care ambele au
. Prin urmare , n stabilirea combinat de infarct
miocardic acut i leziuni musculare scheletice (
rabdomioliz , exerciiu greu , polimiozita ) ,
scderea sensibilitii este semnificativ .

Reinei c diagnosticul de infarct miocardic acut
nu trebuie s se bazeze pe un index relativ ridicat
singur , deoarece indicele relativ pot fi crescute in
setarile clinice, atunci cand, fie total CK sau CK -
MB este n limite normale . Indicele relativ este
util numai atunci cnd att clinicCK totale si
nivelurile CK - MB sunt crescute.

Izoforme CK - MB
CK - MB izoenzima exist ca 2 izoforme : CK -
MB1 i CK - MB2 . Determinarea n laborator a
CK - MB reprezinta , de fapt, simpla suma
izoforme CK - MB1 i CK - MB2 . CK - MB2 este
forma tesuturi si iniial este eliberat de la nivelul
miocardului dup MI . Acesta este convertit
periferic n ser la CK - MB1 izoenzimei rapid dup
debutul simptomelor .

In mod normal , predominesutul CK - MB1
izoform , astfel ,raportul CK-MB2/CK-MB1 este
de obicei mai puin de 1 . Un rezultat este pozitiv
dacCK - MB2 este nlat iraportul este mai mare
dect 1,7 .

CK - MB2 poate fi detectat n ser n decurs de 2-4
ore de la debut i vrfuri la 6-9 ore , ceea ce face un
marker precoce de infarct miocardic acut . Dou
studii clinice mari evaluare utilizarea sa relevat o
sensibilitate de 92 % dup 6 ore de la apariia
simptomelor , n comparaie cu 66 % pentru CK -
MB i 79 % pentru mioglobin . [ 30 , 31
]dezavantaj major al acestui test este faptul c este
relativ muncii intensiv pentrulaborator .

mioglobina
Mioglobina este o proteina heme gasit in muschii
scheletici si cardiace , care a atras un interes
considerabil ca un marker precoce de MI .
Conturilor sale cu greutate molecular mic pentru
profilul de eliberare timpurie : mioglobina se ridic
de obicei 2-4 ore de la debutul infarctului , vrfuri
la 6-12 ore , i revine la normal in urmatoarele 24-
36 de ore .

Testele mioglobina rapide sunt disponibile , dar n
diagnosing acute MI.

The American College of Emergency Physicians
(ACEP) recommends 3 different testing strategies
for ruling out NSTEMI in the ED[32] . One
strategy is to use a single negative CK-MB, TnI, or
TnT measured 8-12 hours after symptom onset.

Another strategy is to use negative myoglobin in
conjunction with a negative CK-MB mass or
negative TnI measured at baseline and at 90
minutes in patients presenting less than 8 hours
after symptom onset.

A third approach is to use a negative 2-hour delta
CK-MB in conjunction with a negative 2-hour delta
TnI in patients presenting less than 8 hours after
symptom onset.

Note that ACEP does not specify whether to use
the 99th percentile cutoff, the 10% CV cutoff, or
the WHO acute MI cutoffs for troponin.

The 90-minute rule-out with myoglobin
recommended by ACEP was based on a study that
used myoglobin in conjunction with either CK-MB
or TnI.[33] The CK-MB/myoglobin protocol
yielded a sensitivity of 92% at 90 minutes, and the
myoglobin/TnI combination yielded a sensitivity of
97% at 90 minutes.

ACEP acknowledges the relative lack of specificity
for myoglobin and that many of the myoglobin
studies did not define MI per the ACC/ESC
guidelines. Nevertheless, it is difficult to
comprehend the ACEP clinical policy that accepts
a missed MI rate of 3-8%.

ACEPs recommendations on the use of delta CK-
MB and delta TnI are based on determining the
change in the level of TnI or CK-MB on samples
drawn 2 hours apart. However, the delta TnI
evaluation is partially based on the use of older TnI
assays and outdated WHO acute MI cutoffs in a
retrospective study. Therefore, ACEPs
recommendation to use a delta TnI in conjunction
with a delta CK-MB may not be generalizable to
other commercially available troponin assays.
Caution must be used when using ACEPs
recommendations in ED patients with chest pain
and suspected ACS.
general , au o lips de cardiospecificity . De
prelevare a probelor de serie la fiecare 1-2 ore
poate crete sensibilitatea i specificitatea , o
cretere de 25-40 % de 1-2 ore este puternic
sugestiv de infarct miocardic acut . Cu toate acestea
, n cele mai multe studii , mioglobina realizat doar
sensibilitate 90 % pentru IM acut , astfel nct
valoarea predictiv negativ a mioglobinei nu este
suficient de mare pentru a excludediagnosticul de
infarct miocardic acut .

Studiile originale pe care mioglobina evaluat folosit
definiia OMS IM acut , care a fost bazat pe un
standard de CK - MB . Odat cu adoptarea unui
standard troponinei pentru infarct miocardic acut n
definiia ACC / ESC , sensibilitatea de mioglobina
pentru IM acut este redus substanial . Acest lucru
reduce semnificativ utilitatea sa , i o serie de studii
au artat c testele contemporane troponinei
cardiace face utilizarea de msurtori mioglobina [
6 , 8 ] inutile .

testarea Strategia
La pacientii cu SCA definite sau posibil , evaluarea
serie de markeri cardiace este esenial pentru
diagnosticarea infarct miocardic acut .

Colegiul American al Medicilor de urgenta ( ACEP
) recomanda trei strategii diferite de testare pentru a
exclude NSTEMI n ED [ 32 ] . O strategie este de
a folosi un singur negativ CK - MB , TNI , sau
TNT msurat 8-12 ore de la debutul simptomelor .

O alt strategie este de a folosi mioglobina negativ
n combinaie cu un negativ CK - MB sau TNI
negativ, efectuate la nceputul i la 90 minute la
pacienii care prezint mai mult de 8 ore de la
debutul simptomelor .

O a treia abordare este de a utiliza un negativ de 2
ore delta CK - MB , n combinaie cu un negativ de
2 ore delta TNI la pacienii care prezint mai mult
de 8 ore de la debutul simptomelor .

Reinei c ACEP nu se specific dac s utilizeze
cutoff 99 percentila ,10 % CV oprire , sau cutoffs
OMS acute MI pentru troponina .

90 de minute de regula , cu mioglobina recomandat
de ACEP sa bazat pe un studiu care a folosit
mioglobina n combinaie fie cu CK - MB sau TNI

The following table outlines the recommended
sampling frequency after ED admission for the
different cardiac markers.

Table 1. Sampling Frequency of Cardiac Markers
(Open Table in a new window)

Baseline 3-4 h 6-9 h 12-24 h >24 h
CK-MB isoforms, myoglobin X X X

CK-MB, TnI, TnT X X X X



(only if very high risk)



Late presenters



(TnI, TnT)



X
The sample time at 3-4 hours is useful in the ED or
chest pain observation unit where rapid triage and
early diagnosis are essential. In other patients
admitted for ACS, biomarkers drawn at the 3- to 4-
hour interval are not as important as they are at the
6- to 9-hour mark. The ACC/AHA guidelines for
the treatment of patients with unstable angina and
NSTEMI recommend a baseline sample upon ED
arrival and a repeat sample 6-9 hours after
presentation.

Few studies on the "time to positivity" have been
performed, but serial samples that become positive
in the 12- to 24-hour window are considered
unlikely, unless the patient has ongoing symptoms
of ischemia after admission. Acute MI can
therefore be ruled out in patients with negative
serial marker results through the 6- to 9-hour period
after presentation.

Cardiac Markers in Therapeutic Management
Clinical trials have demonstrated the benefits of
using cardiac markers as an indicator for specific
. [ 33 ]CK-MB/myoglobin protocol a dat o
sensibilitate de 92 % , la 90 de minute,
icombinaia mioglobinei / TnI dat o sensibilitate
de 97 % , la 90 de minute.

ACEP recunoate lipsa relativ de specificitate
pentru mioglobina i c multe dintre studiile de
mioglobina nu a definit MI pe liniile directoare
ACC / ESC . Cu toate acestea , este dificil de
neles politica de clinica ACEP c accept o rat
MI ratat de 3-8 % .

Recomandrile ACEPs cu privire la utilizarea de
delta CK - MB i Delta TNI se bazeaz pe
determinarea schimbrii nivelului de TNI sau CK -
MB , pe eantioane prelevate dou or n afar . Cu
toate acestea , evaluarea delta TNI se bazeaz
parial pe utilizarea de teste n vrst TNI i
depite OMS cutoffs IM acut intr-un studiu
retrospectiv . De aceea , recomandarea ACEPs a
utiliza o delta TnI coroborat cu un delta CK - MB
nu pot fi generalizate la alte teste troponin
disponibile comercial . Precauie trebuie s fie
utilizate atunci cnd se utilizeaz recomandrile
ACEPs la pacienii ED cu dureri in piept si ACS
suspectate .

Tabelul de mai jos prezint frecvena recomandat
de prelevare a probelor dup admitere ED pentru
diferite markeri cardiaci .

Tabelul 1 . Frecvena de eantionare a markerilor
cardiace ( Deschidere mas ntr-o fereastr nou )

De baz 3-4 ore 6-9 ore 12-24 de ore > 24 ore
CK - MB izoforme , mioglobina X X X
CK - MB , TNI , TNT X X X X



( numai n cazul n risc foarte ridicat )



prezentatori trziu



( TNI , TNT)


therapeutic interventions in ACS. However, this
use remains investigational; currently, no validated
therapeutic algorithms are based on an isolated
positive marker result in the absence of other
clinical or ECG findings.

Subgroup analysis of trials with low molecular
weight heparin (LMWH) showed a decreased
cardiac event rate in patients with a positive result
for TnT and who were treated with an LMWH.[34,
35]

Similarly, in the PRISM trial, patients with an
elevated TnI who were treated with the
glycoprotein (GP) IIb/IIIa inhibitor tirofiban
(Aggrastat) demonstrated a significant decrease in
cardiac events compared with patients without an
elevated TnI level. No significant difference in
outcomes was seen in patients without TnI
elevations who were treated with tirofiban when
compared with placebo.[36]

In the PURSUIT trial, patients who were treated
with the GP IIb/IIIa inhibitor eptifibatide
(Integrilin) within 6 hours of symptom onset
obtained the greatest benefit, and subgroup analysis
showed that patients with an elevated troponin
level also had better responses to therapy than did
those whose troponin result was negative.[37]

Finally, in the TACTICS-TIMI 18 trial, patients
with elevations in TnI or TnT had a significant
reduction in death, MI, or rehospitalization for
ACS within 6 months after being treated with early
invasive therapy consisting of aspirin, heparin,
tirofiban, and catheterization/revascularization
within 4-48 hours.[38, 39] Subset analysis noted
that an elevation of CK-MB did not benefit the
early invasive group when compared with the
conservative management group. However, early
invasive therapy did benefit the subgroup of
patients with elevated troponin levels but normal
CK-MB levels.[40]

These studies suggest that a positive troponin result
alone is an independent predictor of high risk for
adverse cardiac events, and that therapy with
LMWHs and/or GP IIb/IIIa inhibitors appears to
confer the most benefit on patients with elevated
cardiac troponins levels.


X
Timpul de prob la 3-4 ore este util n durere
unitatea de observare ED sau piept unde triaj rapida
si diagnostic precoce sunt esentiale . La ali
pacieni internai pentru ACS , biomarkeri trase la 3
- la interval de 4 ore nu sunt la fel de importante ca
sunt la 6 - de a marca 9 - or . Liniile directoare
ACC / AHA pentru tratamentul pacientilor cu
angina pectorala instabila si NSTEMI recomanda o
proba de referin la ED sosire i o prob, se repet
de 6-9 ore de la prezentare .

Au fost efectuate cteva studii pe " timp de
pozitivitate " , dar mostre de serie care devin
pozitive in 12 - la fereastra de 24 de ore sunt
considerate puin probabil , cu excepia cazului n
care pacientul are simptome in curs de desfasurare
de ischemie dup admitere . Prin urmare acut MI
poate fi exclus n cazul pacienilor cu rezultate
negative indicatoare de serie prin 6 - la perioada de
9 ore dup prezentarea .

Markeri cardiace n managementul terapeutic
Studiile clinice au demonstrat beneficiile de a
utiliza markeri cardiaci ca un indicator pentru
interventii terapeutice specifice n ACS . Cu toate
acestea , aceast utilizare rmne experimentale ; n
prezent , nu algoritmi terapeutice validate se
bazeaz pe un izolat rezultat pozitiv marker
nabsena altor constatri clinice sau ECG .

Analiza de subgrup de studii cu heparina cu
greutate moleculara mica ( HGMM ) au aratat o
rata a scazut eveniment cardiace la pacientii cu un
rezultat pozitiv pentru TNT i care au fost tratati cu
o HGMM . [ 34 , 35 ]

De asemenea, n procesul PRISM , pacientii cu un
TNI crescute , care au fost tratati cu glicoproteina (
GP ) IIb / IIIa tirofiban ( Aggrastat ) a demonstrat o
scdere semnificativ a evenimentelor cardiace
comparativ cu pacienii fr un nivel ridicat TNI .
Nici o diferenta semnificativa a rezultatelor a fost
observata la pacientii fara TNI creteri care au fost
tratati cu tirofiban comparativ cu placebo . [ 36 ]

n studiul PURSUIT , pacientii care au fost tratati
cu GP IIb / IIIa eptifibatid ( Integrilin ) n termen
de 6 ore de la debutul simptomelor a obinut cel
mai mare beneficiu , i analiza de subgrup a aratat
Troponins in CRF
Patients with chronic renal failure (CRF) who are
on hemodialysis are at increased risk of coronary
artery disease and acute ACS, and cardiovascular
disease accounts for about 50% of deaths in these
patients. Early studies revealed a high prevalence
of elevated cardiac troponin levels in patients with
CRF, and especially of TnT. However, the clinical
significance of an elevated TnT level is unclear.

Biochemical studies have demonstrated that the
troponin elevation originates from the myocardium
and is not related to the myopathy associated with
renal failure. Yet, patients with CRF frequently
have chronic congestive heart failure (CHF) and
hypertension, which may independently elevate the
troponin level. In addition, data suggest that
elevated troponin levels in asymptomatic patients
may reflect subclinical microinfarctions that are
clinically distinct from ACS.

Large prospective studies have confirmed the
association between TnT elevation and cardiac
mortality in patients with CRF. The GUSTO IV
ACS trial showed that patients with renal
insufficiency and an elevated TnT had the highest
overall risk of the composite endpoint of death or
acute MI,[41] and 2 other prospective studies
reported that an elevated TnTbut not TnI
increased the risk of long-term mortality.[42, 43]
Whether elevated TnT increases cardiac risk in the
short term (ie, 30 d) is unclear, but patients without
short-term risk may not require hospitalization and
potentially could be managed on an outpatient
basis.

It has been suggested that chronically elevated
troponin levels represent chronic structural
cardiovascular disease, such as prior MI, chronic
CHF, or hypertension in the setting of CRF. If true,
these patients are at higher cardiac risk compared
with the normal, healthy patient population and
troponin remains a useful marker in the setting of
CRF.[44, 45]

Note that dialysis does not affect TnT or TnI levels;
predialysis and postdialysis levels are essentially
unchanged. CK-MB, however, is dialyzable, and
levels are decreased postdialysis. Therefore, a
single elevated TnT level in patients with CRF and
possible ACS is nondiagnostic for acute MI in the
ca pacientii cu un nivel troponinei au avut , de
asemenea, rspunsuri mai bune la tratament a facut
decat cei al cror rezultat troponina a fost negativ [
37 ] .

n cele din urm , n tactica - TIMI 18 studiu ,
pacientii cu cresteri ale TNI sau TNT o reducere
semnificativ n moarte , IM , sau rehospitalization
pentru ACS termen de 6 luni dup ce a fost tratati
cu terapie invazive precoce format din aspirina ,
heparina , tirofiban , i cateterism / revascularizare
n termen de 4-48 ore [ 38 , 39 ] analiza de subgrup
observat . c o altitudine de CK - MB nu au
beneficiat grupul invazive precoce n comparaie cu
grupul de management conservator . Cu toate
acestea , terapia invaziv precoce a beneficia
subgrupul de pacieni cu valori troponinei dar
niveluri normale ale CK - MB . [ 40 ]

Aceste studii sugereaza ca un rezultat pozitiv
troponinei singur este un predictor independent de
risc crescut de evenimente adverse cardiace , i c
tratamentul cu HGMM i / sau GP IIb / IIIa pare s
conferemai multe beneficii la pacientii cu niveluri
crescute ale troponinelor cardiace .

Troponinelor n CRF
Pacienii cu insuficien renal cronic (IRC ), care
sunt n program de hemodializ sunt la risc crescut
de boli coronariene si ACS acute , i conturi de boli
cardiovasculare pentru aproximativ 50 % din
decesele la acesti pacienti . Primele studii a artat o
prevalen ridicat de niveluri crescute ale
troponinelor cardiace la pacientii cu CRF , i mai
ales de TNT . Cu toate acestea , semnificatia clinica
a unui nivel ridicat TNT este neclar .

Studiile biochimice au demonstrat ccota troponina
provine demiocard i nu este legat demiopatie
asociat cu insuficien renal . Cu toate acestea ,
pacientii cu CRF au frecvent insuficienta cronica
cardiaca congestiva ( ICC ) i hipertensiune
arterial , care poate crete n mod independent
nivelul troponinei . n plus , datele sugereaza ca
nivelurile troponinei crescute la pacientii
asimptomatici pot reflecta microinfarctions
subclinice , care sunt distincte clinic de la ACS .

Mari studii prospective au confirmat asocierea
dintre TnT altitudine si a mortalitatii cardiace la
pacientii cu IRC . GUSTO studiu ACSIV a artat
absence of other findings. Serial determinations are
usually required, with a focus on a rise in the
troponin level.

Ascertaining whether an elevated troponin in
patients with CRF represents true acute MI or a
false-positive result can be difficult. In patients
with cardiac risk factors who are deemed clinically
to be at moderate-high risk for ACS, the prudent
approach would be to observe and perform serial
cardiac markers over 6-9 hours. In low-risk
asymptomatic patients and in the absence of any
other findings indicative of ACS, the elevated
troponin result is more likely to be false positive
for acute MI.

Troponins in Nonischemic Heart Disease
A number of studies have demonstrated that TnT
can be used for risk stratification of patients with
CHF without ischemia. Specifically, elevated
cardiac troponins are associated with decreased left
ventricular ejection fraction and poor prognosis in
patients with CHF and are related to the severity of
heart failure.[46]

Isolated studies have shown evidence of MI and
elevated TnI levels in patients with subarachnoid
hemorrhage.[47] Vasoactive peptides released
during acute subarachnoid hemorrhage induce deep
T-wave inversions on ECG that indicate
myocardial injury. Similarly, TnT has been shown
to be an independent predictor of outcome in
patients with pulmonary embolism; right
ventricular strain or infarction from acute
pulmonary hypertension causes the elevated
troponin level.

Elevated troponin levels have also been
documented in other nonischemic cardiac disease
states, such as tachyarrhythmias, hypertension,
myocarditis, and myocardial contusion.

Emerging Markers
Investigations into emerging cardiac markers are
focusing on increasing diagnostic sensitivity and
specificity and on improving prognostic capability.

B-type natriuretic peptide
B-type natriuretic peptide (BNP) is secreted
primarily by the ventricular myocardium in
response to wall stress, including volume
c pacienii cu insuficien renal i un TnT
crescute au avut cel mai mare risc global de
obiectivul compozit de deces sau IM acut , [ 41 ] i
2 alte studii prospective au raportat ca un crescute
TNT , dar nu TNI- a crescut riscul de mortalitate pe
termen lung . [ 42 , 43 ] fie ridicat TnT creste riscul
cardiac pe termen scurt ( de exemplu , 30 d ) este
neclar , dar pacienii fr risc pe termen scurt nu
pot necesita spitalizare si potential ar putea fi
gestionate pe o ambulatoriu baz .

Acesta a fost sugerat c nivelurile cronic crescute
ale troponinelor reprezint bolile cardiovasculare
structurale cronice , cum ar fi MI nainte , cronice
CHF , sau hipertensiune arteriala in stabilirea de
CRF . Dac este adevrat , acesti pacienti sunt la
risc cardiac mai mare n comparaie cu , populatia
normala pacient sntos i troponina rmne un
marker util n stabilirea de CRF [ 44 , 45 ] .

Reinei c dializa nu afecteaz nivelurile de TNT
TNI , nivelurile de predializai i postdialysis sunt
n esen, neschimbate . CK - MB , cu toate acestea
, este dializabil , iar nivelurile sunt sczute
postdialysis . Prin urmare , un singur nivel ridicat
TnT la pacientii cu CRF i posibile ACS este
nondiagnostic pentru infarct miocardic acut n
absena altor constatri . Determinri de serie sunt
de obicei necesare , cu un accent pe o cretere a
nivelului troponinei .

Verifica dac un troponinei la pacieni cu IRC
reprezint adevrate IM acut sau un rezultat fals -
pozitiv poate fi dificil . La pacienii cu factori de
risc cardiac , care sunt considerate clinic pentru a fi
la risc moderat - mare pentru ACS , abordarea
prudent ar fi de a observa i de a efectua markeri
cardiaci seriale de peste 6-9 ore . La pacientii
asimptomatici cu risc sczut i n absena oricror
alte constatri indic ACS , rezultatul crescute ale
troponinelor este mult mai probabil s fie fals
pozitive pentru infarct miocardic acut .

Troponinele in bolile de inima nonischemic
Un numr de studii au demonstrat c TnT pot fi
folosite pentru stratificarea riscului la pacienii cu
ICC fr ischemie . Concret , troponinele cardiace
crescute sunt asociate cu scderea fraciei de ejecie
a ventriculului stng i prognostic saraci la
pacientii cu ICC i sunt legate de severitatea de
insuficienta cardiaca . [ 46 ]
expansion and pressure overload. Multiple studies
have demonstrated that BNP may also be a useful
prognostic indicator in ACS. The TIMI study group
performed several investigations showing that the
BNP level predicted cardiac mortality and other
adverse cardiac events across the entire spectrum of
ACS. The mortality rate nearly doubled when both
TnI and BNP levels were elevated.


In the TACTICS-TIMI 18 trial, an elevated BNP
level was associated with tighter culprit stenosis,
higher corrected TIMI frame count, and left
anterior descending artery involvement.[38] These
data suggest that increased BNP levels may
correlate with greater severity of myocardial
ischemia and could partially explain the association
between increased BNP levels and adverse
outcomes.

Data from OPUS-TIMI 16 and TACTICS-TIMI 18
demonstrated that baseline elevations of TnI, C-
reactive protein (CRP), and BNP levels in patients
with NSTEMI were independent predictors of the
composite endpoint of death, MI, or CHF.[48] The
PROMPT-TIMI 35 trial demonstrated that transient
myocardial ischemia during exercise testing was
associated with an immediate rise in BNP
levels.[49] In addition, the severity of ischemia was
directly proportional to the elevation in BNP.

The presence of acute CHF in patients with ACS is
a well-known predictor of adverse cardiac events
and higher risk. Therefore, it is not surprising that
an elevated BNP level, as a marker of CHF, is also
predictive of adverse cardiac events in patients with
ACS. Although BNP has been validated as a
diagnostic marker for CHF, insufficient data are
available to evaluate the use of BNP as a diagnostic
cardiac marker for ACS in the ED.

C-reactive protein
C-reactive protein (CRP), a nonspecific marker of
inflammation, is considered to be directly involved
in coronary plaque atherogenesis. Extensive studies
beginning in the early 1990s showed that an
elevated CRP level independently predicted
adverse cardiac events at the primary and
secondary prevention levels.

Data indicate that CRP is a useful prognostic

Studii izolate au artat dovezi de MI i niveluri
ridicate TNI la pacientii cu hemoragie
subarahnoidiana . [ 47 ] vasoactive peptide
eliberate n timpul hemoragie subarahnoidian acut
induce profunde rsturnri undei T pe ECG care
indic leziuni miocardice . Similar , TNT sa
dovedit a fi un predictor independent de rezultatul
la pacientii cu embolism pulmonar ; tulpina
ventriculului drept sau infarct de hipertensiune
pulmonara acuta cauzeaza nivelul troponinei .

Nivelurile de troponinei au fost , de asemenea,
documentate n alte state nonischemic boli cardiace
, cum ar fi tahiaritmii , hipertensiune , miocardita ,
i contuzie miocardic .

Markere n curs de dezvoltare
Investigaiile n markeri cardiaci n curs de
dezvoltare se concentreaz pe creterea
sensibilitii i specificitate de diagnostic i la
mbuntirea capacitii de prognostic .

B - peptidic natriuretic de tip
B - peptidic natriuretic de tip ( BNP ) este secretat
in principal de catre miocardul ventricular , ca
raspuns la stres perete , inclusiv expansiunea
volumului i supraincarcare de presiune . Multiple
studii au demonstrat c BNP poate fi , de
asemenea, un indicator de prognostic util n ACS .
TIMI Grupul de studiu efectuat mai multe
investigaii arat c nivelul BNP prezis mortalitii
cardiace i a altor evenimente adverse cardiace in
intregul spectru de ACS . Rata de mortalitate
aproape sa dublat de cnd au fost ridicate att la
nivel TNI i BNP .

n tactica - TIMI 18 proces , un nivel ridicat BNP a
fost asociata cu stenoza vinovat strict , mai mare
corectat TIMI numrul de cadru , i a plecat
implicarea anterioar artera descendent . [ 38 ]
Aceste date sugereaz c o cretere a nivelului BNP
pot fi corelate cu severitate mai mare de ischemie
miocardica i ar putea explica parial asocierea
dintre nivelele crescute de BNP si a rezultatelor
negative .

Datele de la OPUS - TIMI 16 i tactici de - TIMI
18 au demonstrat ca cresteri de baz ale TNI ,
proteinei C - reactive ( CRP ) , i nivelurile de BNP
la pacienii cu NSTEMI au fost predictori
indicator in patients with ACS, as elevated CRP
levels are independent predictors of cardiac death,
acute MI, and CHF. In combination with TnI and
BNP, CRP may be a useful adjunct, but its
nonspecific nature limits its use as a diagnostic
cardiac marker for ACS in the ED.

Myeloperoxidase
Myeloperoxidase (MPO) is a leukocyte enzyme
that generates reactant oxidant species and has been
linked to prothrombotic oxidized lipid production,
plaque instability, lipid-laden soft plaque creation,
and vasoconstriction from nitrous oxide depletion.
Early studies showed significantly increased MPO
levels in patients with angiographically
documented coronary artery disease[50] ; these
findings spurred further investigation into MPO as
a novel cardiac marker.

In 604 sequential patients presenting to the ED with
chest pain, elevated MPO levels independently
predicted increased risk for major adverse cardiac
events, including MI, reinfarction, need for
revascularization, or death at 30 days and at 6
months.[51] Among the patients who presented to
the ED with chest pain but who were ultimately
ruled out for MI, an elevated MPO level at
presentation predicted subsequent major adverse
cardiovascular outcomes. In a subgroup of patients
with negative baseline TnT, MPO levels were
significantly elevated at baseline, even within 2
hours after symptom onset.

MPO may be a useful early marker in the ED based
on its ability to detect plaque vulnerability that
precedes ACS. However, further validation studies
on MPO in the general ED chest pain population
are needed to determine its sensitivity and
specificity, as well as its negative and positive
predictive values.[52, 53]

Ischemia modified albumin
Ischemia modified albumin (IMA) is a novel
marker of ischemia that is produced when
circulating serum albumin contacts ischemic heart
tissues. IMA can be measured by the albumin
cobalt binding assay that is based on IMAs
inability to bind to cobalt.[54] A rapid assay with a
30-minute laboratory turnaround time has been
developed and marketed as the first commercially
available US Food and Drug Administration
independente de obiectivul compozit de deces , MI
, sau CHF . [ 48 ]PROMPT - TIMI 35 studiu a
demonstrat ca ischemie miocardica tranzitorie n
timpul testului de efort a fost asociata cu o crestere
imediata a nivelului de BNP [ 49 ] n plus ,
severitatea de ischemie a fost direct proporional
cu cota din BNP . .

Prezena CHF acuta la pacientii cu SCA este un
predictor cunoscut de evenimente adverse cardiace
si risc mai mare . De aceea , nu este surprinztor
faptul c un nivel ridicat BNP , ca un marker al
CHF , este , de asemenea, predictiv al
evenimentelor adverse cardiace la pacienii cu SCA
. Dei BNP a fost validat ca un marker de
diagnostic pentru CHF , sunt disponibile pentru a
evaluautilizarea BNP ca un marker cardiac de
diagnostic pentru ACS nED date insuficiente .

Proteina C - reactiva
Proteinei C - reactive ( CRP ) , un marker
nespecific al inflamatiei , este considerat a fi
implicat direct n aterogenez placa coronariene .
Studii extensive nceput la nceputul anilor 1990 au
aratat ca un nivel ridicat CRP independent a prezis
evenimente adverse cardiace la nivel prevenirea
primar i secundar .

Datele indic faptul c CRP este un indicator de
prognostic util la pacientii cu SCA , ca nivelurile
crescute de CRP sunt predictori independente de
deces cardiac , infarct miocardic acut , si CHF . n
combinaie cu TNI i BNP , CRP poate fi un
adjuvant util , dar natura sa nespecifice limiteaz
utilizarea sa ca un marker cardiac de diagnostic
pentru ACS in ED .

myeloperoxidase
Myeloperoxidase ( MPO ) este o enzim de
leucocite care genereaz specii oxidant reactantilor
si a fost legata de prothrombotic produciei de
lipide oxidate , instabilitatea placa , crearea placa
moale lipide - Laden , i vasoconstricia la epuizare
oxid de azot . Primele studii au aratat a crescut
semnificativ nivelurile de MPO la pacientii cu
boala arterelor coronare documentate angiografic [
50 ] ; aceste constatari stimulat investigatii
suplimentare in MPO ca un marker cardiac roman .

La 604 pacieni secveniale care prezinta la ED cu
dureri in piept , nivelurile de MPO crescute
(FDA)approved marker of myocardial ischemia.

Based on investigations of myocardial ischemia
induced by balloon inflation during percutaneous
coronary intervention, IMA levels rise within
minutes of transient ischemia, peak within 6 hours,
and can remain elevated for as long as 12 hours.

Studies on the use of IMA in patients with chest
pain in the ED found sensitivities that ranged from
71-98% and specificities of 45-65%, with a
negative predictive value of 90-97% for ACS.[55]

A multimarker approach in one study, using a
combination of ECG findings, TnT levels, and
IMA levels, achieved a sensitivity of 95% for
ACS,[56] while a second study calculated that the
combination of IMA, myoglobin, CK-MB, and TnI
increased the sensitivity to 97% for detecting
myocardial ischemia.[57]

However, IMA levels are also elevated in patients
with cirrhosis, certain infections, and advanced
cancer, which reduces the specificity of the assay.
Further validation and outcome studies are required
to evaluate IMAs use in the ED diagnosis of ACS
when the ECG and cardiac troponins levels are
nondiagnostic.
independent a prezis un risc crescut de evenimente
cardiace majore adverse , inclusiv MI , reinfarct ,
au nevoie de revascularizare , sau deces la 30 de
zile si la 6 luni. [ 51 ] Dintre pacientii care a
prezentat la ED cu dureri in piept , dar care au fost
n cele din urm exclus pentru MI , un nivel MPO
ridicat la prezentare a prezis reactiile adverse
cardiovasculare majore ulterioare . ntr-un subgrup
de pacienti cu negativ iniial TNT, nivelurile de
MPO au fost semnificativ crescute , chiar i n
termen de 2 ore de la debutul simptomelor .

MPO poate fi un marker precoce util nED bazat pe
capacitatea sa de a detecta vulnerabilitate placa
care precede ACS . Cu toate acestea , sunt necesare
studii suplimentare de validare pe MPO , ngeneral,
ED populaiei dureri in piept pentru a determina
sensibilitatea i specificitatea acestuia , precum i
valorile sale pozitive i negative predictive [ 52 , 53
] .

Ischemia modificat albumina
Ischemie modificat albumin ( IMA ) este un
marker roman de ischemie care este produs atunci
cnd circul albumin seric contacte esuturile
cardiace ischemice . IMA poate fi msurat
prinanaliza cu liant cobalt albumin , care se
bazeaz pe incapacitatea IMA de a lega de cobalt .
[ 54 ] Un test rapid cu un timp de 30 de minute cu
schimbare de direcie de laborator a fost dezvoltat
i comercializat caprimul disponibil comercial US
Food and Drug Administration ( FDA ) a aprobat -
marker de ischemie miocardica .

Pe baza investigaiilor de ischemie miocardic
indus de inflaie balon n timpul interventie
coronariana percutanata , nivelurile de IMA ridica
la cteva minute de ischemie tranzitorie , vrf de 6
ore , i pot rmne crescute pentru atta timp ct 12
ore.

Studii cu privire la utilizarea de IMA la pacientii cu
durere in piept in ED a constatat sensibilitile care
a variat de 71-98 % i specificul 45-65 % , cu o
valoare predictiv negativ de 90-97 % pentru ACS
. [ 55 ]

O abordare multimarker ntr-un studiu , folosind o
combinaie de constatri ECG , nivelurile de TNT,
i nivelurile de IMA , realizat o sensibilitate de 95
% pentru ACS , [ 56 ] n timp ce un al doilea studiu
a calculat c o combinaie de IMA , mioglobinei ,
CK - MB , i TnI crescutsensibilitatea la 97 %
pentru detectarea ischemiei miocardice . [ 57 ]

Cu toate acestea , nivelurile de IMA sunt , de
asemenea, crescut la pacienii cu ciroz , anumite
infectii , si cancer avansat , ceea ce reduce
specificitatea testului . Validarea in continuare si
rezultatele studiilor sunt necesare pentru a evalua
utilizarea IMA n diagnosticul ED a ACS atunci
cnd ECG i nivelul cardiace troponinelor sunt
nondiagnostic .