“Diplomatura Superior Universitaria

de Insuficiencia Cardiaca Avanzada”

2022

Biomarcadores en
Insuficiencia Cardíaca
Dr Eduardo R Perna, FHFSA
Jefe División de Insuficiencia Cardíaca e Hipertensión Pulmonar
Unidad de Cuidados Intensivos Coronarios
Instituto de Cardiología “J. F. Cabral”, Corrientes, Argentina.
Comité de Insuficiencia Cardíaca e Hipertensión Pulmonar. FAC
Secretario. Consejo de Falla Cardíaca e Hipertensión Pulmonar de SIAC
pernaucic@hotmail.com

erp22

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Morrow DA, de Lemos JA. CirculaOon 2007;115:949 –52

Tang WH, et al. CirculaOon 2007;116:e99 –109
erp22 van Kimmenade RR, Januzzi, JL. Clin Chem 2012;58:127–138

7
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erp22

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erp22 van Kimmenade RRJ, Januzzi, JL. Clin Chem 2012;58:127–138

19
history 4 of cardiovascular 4 disease.
4 Details of the HDL other cholesterol
characteristics, concentration)
concentrationincluding HDL adjusted
were ethnicity,
cholesterol
1·61(95% forhistory
(1·45–1·78)conventional
concentration of
for risk 1·61
were factors (1·45–1·78) for
were 1·76 CI for 1·56–1·98) for the combination of

Coronary heart diea

Stroke risk

heartrisk
di
40 contributing studies are provided in the appendix the hypertension,
combinationuse were
of of1·76
coronary (95%
antihypertensive
heart
the CI
combination
disease 1·56–1·98)
andmedication,
of
stroke
coronary the heart
and combination
disease of stroke and
and

Stroke
coronary heartcoronary
disease heart
and disease
stroke; and stroke;
2·00 (1·77–2·26) 2·00 (1·77–2·26) for
(pp 12, 2 17–20).
12–16,23–26,28–51
2 systolic
1·47
NT-proBNP blood
(1·31–1·66) pressure,
concentration total
for the combination 1·47
(appendix and
the combination
HDL
(1·31–1·66)
of
p 24), andcholesterol
coronary for
focused
of theheart
coronary combination
concentration,
heart of for
disease, coronary heartfor coronary he
risk ratios
and stroke, and
28–34

Coronary
2
48 528 (51%) of participants were women and 61 451 on
(64%) 1 were from Europe, and mean
1
1
NT-proBNP y predicción de IC en sanos
age at baseline was 15
concentration,
disease,
(appendix
Risk
stroke,
909 participants pp 21,
ratios
andtheheart
and
fatal outcomes only (appendix
heart
for22,for
combination
estimated
29).
NT-proBNP
failure.
coronary1·81
disease,
failure;heart 1·67
Risk
heart
of stroke,
glomerular
pfailure;
coronary
35). In1·67
(1·45–1·93)
concentration
ratios and
disease
(1·58–2·07)
fi and
analyses
forfor
heart
ltration
for
heart
(1·45–1·93)
did
disease,
rate
coronary
NT-proBNP
stroke
failure.
of stroke, for
stroke,
heart
not concentration
stroke;
and heart
coronary
disease;
3·45concentration
(2·66–4·46)
heart disease;
were for did
failure observed
weaker notthan were tho
heart
61 years (SD The 10). Median NT-proBNP concentration was and During
materially 809 5251·81
change (1·58–2·07)
person-years
with further at for
risk
materially stroke;
(median
adjustment 3·45
follow-up (2·66–4·46) for heart concentration
Natriuretic Peptides Studies Collaboration: 12 202Metaanálisis
participants
failure; and
de
for 40heart estudios,
failure; andchange
failure
3·11coronary
(2·34–4·15)
fromfor
N=95.617
3·11 withbody-
seven
(2·34–4·15)
for
further
participantes
cardiovascular
with adjustment
for NT-proBNP sin ECV
cardiovascular
disease
fordisease
body- (appendix
7·8 years
mass
studies index [IQR
with 5·2–11·8]),
or estimated
available 5500
glomerular
mass
information index orheart
filtration
about disease,
estimated
rate,
BNP but glomerular
noted fi2;ltration
moderate rate, but
heterogeneity of risk ra
deaths due deaths
tofailure
additional due to additional
causes (figure causes (fi
2; appendix gure appendix
p 30). CRP con- p 30).
4002 reduced
they stroke, and 2212 heart
somewhat with they
adjustment outcomes
reduced for occurred.
somewhat
CRP con-with adjustment
16
16
16
16
Risk ratios were somewhat higher for fatal for than for non-
NT-proBNP(appendix
centration Risk pratios
concentration 23). waswere
Risk somewhat
non-linearly
centration
ratios for higher
(appendix
Cohorts/events associated
heart
(n/N) pfor
failure 23).fatalRiskthan for non-
ratios for heart
Risk ratio failure
(95%CI) for higher Risk ratio (95
fatal coronary heart disease (p<0·0001), but similar for
with the
were higher risk in of fatal
men coronary
each of
than these in heart
were diseases
women disease
higher (fi gure
(4·25 (p<0·0001),
1). 2·44;
in haemorrhagic
menvs than but
Risk similar for
in stroke
women NT-proBNP
(4·25 vsInconcentration*
2·44; HDL-C conce
risk ratio

88 8 ischaemic and (p=0·44). the

8 ischaemic and
ratios
p<0·0001), (top inthird vs bottom
participants with ahaemorrhagic
third
p<0·0001), low of
body-mass stroke
NT-proBNP
in participants index(p=0·44).
with a risk lowInratios the
body-mass index
risk ratio

ratio
Composite outcomes same participants, corresponding with lower

ratio
concentration)
than a heart
highdisease same
adjusted
body-mass participants,
stroke index for thanconventional
(3·61 corresponding
a32/8323
high
vs 2·76; risk
body-mass
p=0·0004), risk
factors ratios
index withvslower
(3·61 2·76; p=0·0004),
Stroke risk ratio
diease

riskrisk
44 4 Coronary plus HDL cholesterol concentration were 1·61 1·76 (1·56–1·98)
(1·45–1·78) for 1·61 (1·45–1·7
4 were
and in1·76 (95%
studies HDL
CI
that had cholesterol
1·56–1·98)
stored and forconcentration
samples
in the
studies combination
for that
10 were
years
had 1·61
of
or
stored (1·45–1·78)
samples for
for 10 years or
failure

failure
Coronary heart disease plus stroke plus heartthe 22/6582
failurecombination of coronary heart disease and 2·00 (1·77–2·26)
stroke and 1·47 (1·31–1·6
Heartheart

Stroke coronary
fewer before heart the combination
disease
analysis andlonger
than fewerof
stroke; coronary
2·00
than
before heart
10(1·77–2·26)
analysis
years disease
for and stroke and
22 2 Individual outcomes 1·47 (1·31–1·66) for(6·20thethan vs longer
combination thanof10 years (6·20
coronary heartvs
Heart
the combination 1·47
of (1·31–1·66)
coronary heart for theOtherwise,
disease, combination
stroke, risk andof pcoronary31–32). heart
Coronary

2 2·68;
Coronaryp=0·0018;
heart disease appendix pdisease,
2·68;31–32). p=0·0018;
stroke,
34/4716 andappendix
heart failure. Otherwise,
1·67 (1·45–1·93)risk 1·87 (1·67–2·
heart
Fatal failure;
ratios did not 1·67disease,
(1·45–1·93) stroke,
vary substantially forand
ratios coronaryheart
did with failure.
heart
not disease;
Risk22/1052 ratios forlevels
vary
NT-proBNP substantially
of concentration with levels
2·30 (1·64–3·21)
did not of 1·39 (1·16–1·6
P
NT-proBN r mul1propósito
11 1
1 1·81 (1·58–2·07)
conventional
Non-fatal risk for Riskstroke;
factors ratios in for
3·45
or materially
conventional
other NT-proBNP
(2·66–4·46)
34/3643 risk for
clinically concentration
factors heartor in other
relevant didclinically
not relevant
1·55 (1·34–1·79) 2·03 (1·78–2·
change with further adjustment for body-
a y ACV.
failure;
Stroke 1 and1·53·11
subgroups materially
2(2·34–4·15)
(appendix change
for
2·5 pp subgroups 31–32). with We
cardiovascular further
(appendix adjustment
disease
observed pp for body-
31–32). We observed
do CV
30/3768 1·81 (1·58–2·07) 1·35 (1·14–1·6

• Marca ollo de IC isquémic

5 10 20 50 100 200 5001000 0·5 5 110 20 1·550 1002 200 5001000 2·5 0·5

primaria
mass index or estimated glomerular filtration rate, but
deaths
HDL-C due tosimilar massfindings
additional index
causes orin estimated
(fi gure glomerular
2; appendix pndings
30).filtration rate, but
el desarr
(pg/mL) qualitatively qualitatively
analyses similar
that defifi ned in analyses that defi ned
rdiopa9a
Ischaemic 20/2583 1·70 (1·39–2·09) 1·52 (1·23–1·8

evención
NT-proBNP concentration (pg/mL) HDL-C
NT-proBNP
concentration
concentration
(mmol/L) concentration (mmol/L)
they reduced somewhat with adjustment for CRP con-
e
• Predic la predicción de ca grar la IC en la pr
16 16
16 Risk
thirds ratios
separately
Haemorrhagic they
were somewhat
for men reduced higher
and somewhat
thirds
women, for fatal
separately
19/552 with
thanfor
excluded adjustment
for non-and for
people
men CRP con-
women, excluded people
1·61 (1·22–2·12) 1·12 (0·84–1·
centration 15/476p (appendix p 23). Risk ratios for2·08 heart failure
Figure 1: Associations of NT-proBNP andFigure HDL-C1:concentrations
Associations ofwith NT-proBNP and HDL-C fatal
with coronary
Unclassified
concentrations
high baseline centration
heart
with disease (appendix
(p<0·0001),
concentrations
with high of23).
but Risk
similar
baseline
NT-proBNP, ratios
con for heart failure
forcentrations of (1·52–2·84)
NT-proBNP, 1·28 (0·94–1·
ncia ra inte were 16/2021 higher in men than in women (4·25 vs 2·44;
• Pote iría pa
first-onset
8 coronary heart disease, stroke, first-onset
and8 heart coronary
failure heart disease, stroke,ischaemic
and
Heartheart
failurefailureand were
haemorrhagic higher in
strokemen than
(p=0·44). in women
In the (4·25 vs 2·44; 3·45 (2·66–4·46) 1·28 (1·08–1·
excluded the initial 5 yearsp<0·0001), excluded
of follow-up, the initial
and 5were yearswithofa low follow-up, and index
were
ición serv
8
in participants body-mass
Heart failure risk ratio

Risk ratios adjusted for age, smoking status, Risk

history
ratiosofadjusted
diabetes,forsystolic
age, smoking
blood status, history of diabetes, systolic blood

• Su med
Exploratory
same participants, outcome p<0·0001),
corresponding in participants
riskfatal ratios with
with arecording
low body-mass
lower index
Heart failure risk ratio

restricted to studies recording restricted

both to body-mass
studies
and non-fatal both vsfatal andp=0·0004),
non-fatal
Stroke risk ratio

pressure, and total cholesterol and HDL-C concentration

pressure, and total(HDL-Ccholesterol
concentration
and HDL-C concentration (HDL-C concentration than a high index (3·61 2·76;
Death due to other cardiovascular disease‡ 20/551 3·11 (2·34–4·15) 1·11 (0·86–1·
only for4 NT-proBNP concentration analysis)
4 only
andfor4
stratifi
NT-proBNP
ed by sex.
concentration HDL
Analyses analysis) outcomes cholesterol
and stratifi ed by(appendix than
sex. Analyses pa 33).
concentration highSimilar
body-mass
were 1·61
outcomes findings index
(1·45–1·78)
(appendix (3·61
were p also vs 2·76;
for
33). Similar p=0·0004),
findings were also
and in studies that had stored samples for 10 years or
involved 4716 coronary heart disease outcomes involved(from
471634coronary
cohorts),heart
3768disease
stroke outcomesthe(from
noted combination
34 cohorts),
in analyses and
of
3768 in studies
coronary
stroke
that heart
compared
noted that
disease
inhad
studies stored
and
analyses stroke
grouped samples
that andby
comparedfor 10 yearsstudies or grouped by
outcomes
NT-proBNP concentration fewer before 0·75analysis
1 1than
·5 2longer3 than 4 105 years (6·20 vs
2 (from 30 cohorts), and 2021 heart outcomes
failure
2 outcomes
(from 30 cohorts),
(from 16 andcohorts).
2021 heart1·47
failure(1·31–1·66)
NT-proBNP outcomes (from fewer 16
forcohorts).
concentration
HDL-C concentration thebefore analysis
combination
assay
NT-proBNP type than
of longer
coronary
or
concentration
generation than
heart 10assay
years type(6·20 vs generation
or
2
The size of the circles is proportional to theThe inverse
size of the variance
circles is proportional
of the to the inverse of the variance of the 2·68; p=0·0018; appendix Risk ratio (95% p CI)31–32). Otherwise, risk
disease,from
(appendix stroke,
p 32),and 2·68; heart
compared p=0·0018;
failure.
studies
(appendix appendix p 31–32). Otherwise, riskerent lengths
respective estimate. Error bars are 95% CIs,respective
estimatedestimate.
from floatedErrorvariances.
bars are 95% CIs, estimated floated variances. ratioswith didpdiff 32),
erent
not compared
lengths
vary studies
substantially with diff with levels of
ofRisk
follow-up ratios ratios
forNT-proBNP
(appendix p did
NT-proBNP34), not
used
of follow-up
pervary
concentration substantially
one(appendix
SD did
higher pnot
log
34), with levels of
or used per one SD higher log
1
HDL-C=HDL 1
cholesterol. NT-proBNP=N-terminal-pro-B-type
HDL-C=HDL cholesterol.
natriuretic
NT-proBNP=N-terminal-pro-B-type
peptide. Figure 2: Associations natriuretic
of peptide. and HDL-C concentrations with several incident
1 conventional risk factors infirst-onset
other cardiovascular
clinically outcomes
relevant
materially
Risk ratios adjusted change conventional
for age, with status,
smoking further riskadjustment
history offactors or in
diabetes, systolic other
forbloodbody- clinically
pressure, and totalrelevant
cholesterol and HDL-C concentration (HDL-C conce
5 10 20 50 100 200 5001000NT-proBNP 0·5 1 concentration
1·5 2analysis) subgroups
2·5and stratifi ed by sex. HDL-C=HDL(appendix
cholesterol. pp 31–32). We observed
NT-proBNP=N-terminal-pro-B-type natriuretic peptide. *Top versu
5 10 20 50 100 200 5001000 0·5 1 subgroups
mass 2index2·5or estimated glomerular filtration rate, but
1·5 (appendix pp 31–32). We observed
www.thelancet.com/diabetes-endocrinology VolNT-proBNP
4 Octoberconcentration
2016
www.thelancet.com/diabetes-endocrinology (pg/mL) of NT-proBNP
Vol
HDL-C4 Octoberconcentration.
2016(mmol/L)
concentration †Bottom versus qualitatively
top third of HDL-C similar
concentration.findings‡Subsumes indeaths
analyses that843
due to cardiac definedhypertensive disease,
arrhythmia,
16 NT-proBNP concentration (pg/mL) they (mmol/L)
HDL-C concentration
embolism, reduced
complications
qualitatively
somewhat
and ill defined with similar
adjustment
descriptions
findingsfor CRP in analyses
con- that defiand nedperipheral vascular disease.
erp22 thirds ofseparately
heart disease, sudden
for men death,and aorticwomen,
Lancet aneurysms, excluded
Diabetes Endocrinol people
2016; 4: 840–49
centration (appendix
Figure 1: Associations of NT-proBNP and HDL-C concentrations with
thirds p separately
23). Risk ratios for men for andheartwomen, failure excluded people
Figure 1: Associations of NT-proBNP and HDL-C concentrations with with high baseline concentrations of NT-proBNP,
8 first-onset coronary heart disease, stroke,were and heart failure in with
higher men than high in baseline
women con centrations
(4·25 vs 2·44; of NT-proBNP,

25
first-onset coronary heart disease, stroke, and heart failure excluded the C-index initial 5CI) years of follow-up, C-index change (95% andCI)were C-index change (95%
Risk ratios adjusted for age, smoking status, p<0·0001), excluded
insystolic
participants the
withinitiala low 5body-mass years (95% of indexfollow-up, and were
e risk ratio

history of diabetes, blood

Risk ratios adjusted for age, smoking status, history of diabetes, systolic blood
pressure, and total cholesterol and HDL-C concentration (HDL-Cbody-mass
concentration restricted to studies recording both fatal and non-fatal versus preceding mo
versus reference model
4 pressure, and total cholesterol and HDL-C concentration (HDL-C than a high
concentration restricted indexto studies
(3·61 vsrecording 2·76; p=0·0004), both fatal and non-fatal
only for NT-proBNP concentration analysis) and stratifiedoutcomes
Composite by sex. Analyses outcomes (appendix p 33). Similar findings were also
 TIMI Biomarker Score for Heart cantly reduce HHF risk in this low-risk
gliptin treatm
Failure in Diabetes and Clinical group over the time horizon of the trial
an increased r
Benefit of Dapagliflozin (hazard ratio [HR] for dapagliflozin vs. pla-
Predicción de hospitalización por IC
When applied to the full biomarker cebo 0.98 [95% CI 0.50–1.92]). By con-
for saxagliptin
0.25–3.95]). A
cohort from the DECLARE-TIMI 58 trial, trast, patients in the intermediate-, high-,
mediate-, high
the TIMI Biomarker Score for Heart Fail- and very-high-risk categories all derived
ries, there w
ure in Diabetes
TIMI Biomarker Score: N=6.106 (Derivación: identified
rama placebo significant
SAVOR- TIMI 53) ay 7.251
significant treatment
(Validación: ramabenefit
placebofrom patients treat
DECLARE-TIMI 58) cebo (HR 1.26
gradient of ab
Variable Puntos ing to risk ca
HIC previa 2 risk differenc
Fig. 7).
TnT-as (ng/l)
<6 0 CONCLUSIO
6 - 10 1 In this study,
a novel biom
10 - <14 2
predicting HH
≥14 3 cohorts of pa
NT-proBNP (ng/l) atheroscleroti
score leverage
< 50 0 of two wid
50 - <125 2 markers—hsT
single clinical
125 - <450 4
score perform
≥450 6 to patients
Total 0-11 (effectively l
erp22 0-3 4-6 7-8 9-11 performance
Berg DD, et al. Diabetes Care. 2021 Nov;44(11):2573-2581
Figure 1—Incidence rates of HHF by risk category in the derivation and validation cohorts. Risk demonstratin
was categorized as low risk (0–3 points), intermediate risk (4–6 points), high risk (7–8 points),

31 and very high risk (9–11 points). Incidence rates of HHF are shown for each risk category. The
incident HF e
biomarker-based risk score identified a gradient of HHF risk with comparable incidence rates in risk score i
 Segmenta
(≤54 Ohm
1198 Januzzi, Jr. et al. Whole bo

Dx de ICA en EME
NT-proBNP in the Emergency Department (≤441 Oh
BIVA (Z(X
BIVA, HI (

BIA = bio
Meta-análisis de 52 cohortes con 17.893 pacientes. standard

Prevalencia de IC 45,6% (IC95% = 44,9 to 46,4), rango 29-79%.

LR (+) = VP = S LR+
T A B L E 3 Comparison of ROC Curves for NT-proBNP–Based Diagnosis of Acute HF Across Patient SubgroupsLR-
FP 1–E Sintomas (ortopnea, DPN, disnea de reposo, sin tos productiva) 1,9-1,1 0,74-0,88
LR (-) = FN = 1 – S
Historia (IRC, ICC, arritmias, IM, FA; EAC,Sensitivity Specificity
DLP, HTA, sin EPOC) PPV
3,4-1,3 0,58-0,90 NPV
VN E Patients with eGFR <60.0 ml/min/1.73 m2 89.3 (84.0–94.6) 68.3 (61.6–75.0) 66.5 (61.4–71.2) 97.3 (90.1–99.3
Examen físico (Ing. Yugular, R3,2 reflujo HY, edema, soplos, rales, sibilancias, 4,0-0,6 0,4-1,19
LR LR U tilidad Patients with eGFR $60.0 ml/min/1.73 m 70.3 (62.7–77.9) 89.6 (87.6–91.7) 51.9 (46.3–57.4) 98.1 (96.8–98.8
sin fiebre)
positivo negativo Patients with body mass index <30.0 kg/m2 90.3 (84.8–95.7) 85.0 (81.9–88.0) 56.4 (51.1–61.5) 100.0 (—)
10 <0,1
ECG (isquemia, T invertida, FA, depresión
A ltam entePatients with body mass index $30.0 kg/m
2
72.1y(65.0–79.2)
elevación ST, ritmo
87.0 sinusal normal) 60.72,9-0,6
(84.2–89.8) 0,78-1,03
(54.9–66.1) 96.2 (94.1–97.6
relevante Male 80.5
Rx de torax (lineas B, edema intersticial, (74.5–86.4)edema
cefalización, 84.8 (81.9–87.8)
alveolar, derrame 61.06,5-2,3
(56.0–65.8) 97.5 (95.5–98.6
0,95-0,43
5–10 0,1–0,2 B uena Femalepleural, cardiomegalia) 77.8 (69.9–85.6) 88.5 (86.0–91.1) 54.5 (48.5–60.5) 98.5 (97.0–99.3
2–5 0,5–0,2 R egular Black 82.4 (73.8–91.1) 90.4 (87.7–93.2) 58.7 (51.2–65.8) 98.7 (97.0–99.4
BNP (100, 200, 500) 9,1-1,9 0,34-0,05
<2 > 0,5 M ala Nonblack 78.7 (73.0–84.4) 84.5 (81.9–87.2) 58.5 (53.9–62.9) 97.9 (96.2–98.8
NT-proBNP
Presence (300, 1000, 1500)
of atrial fibrillation 87.2 (80.5–94.0) 56.6 (47.8–65.4) 3,1-1,8
60.7 (55.5–65.8) 0,09-0,32 100.0 (—)

JACC VOL. 71, NO. 11, 2018

Ultrasonido
Absence pulmonar
of atrial fibrillation (lineas B, derrame pleural)
75.6 (69.3–81.8) 90.4 (88.6–92.1) 7,4-2,0
57.1 (52.1–62.0)
Januzzi, Jr. et al.
0,16-0,49
98.0 (96.8–98.7
1197
Patients with HFrEF 90.8 (85.1–96.5) 38.6 (24.2–53.0) 76.7 (72.1–80.8) 75.0 (38.7–93.5
MARCH 20, 2018:1191–200 NT-proBNP in the Emergency8,3-2,5
Eco a la cabecera (patrón restrictivo, FE baja, aumento DDVI) Department0,21-0,30
Patients with HFpEF 72.6 (61.5–83.7) 68.6 (58.8–78.4) 62.5 (54.1–70.2) 80.4 (68.2–88.7
LR+ ≥ 4, LR- bajo Bioimpedancia 10,6-2,0 0,13-0,34
Values are % (95% confidence interval). Performed with the Elecsys proBNP II Assay in all enrolled subjects. Sensitivity, specificity, and PPV refer to results
Figurefor 2.
age
to results for the age-independent rule-out cutoff of 300 pg/ml. Martindale JC, et al. Acad Emerg Med 2016;23:223–242 natriuretic
erp22
AUC ¼ area under the curve; eGFR ¼ estimated glomerular filtration rate; HFpEF ¼ heart failure with preserved ejection fraction; HFrEF ¼ heart failure with
T A B L E 2 NT-proBNP Cutpoints for the Diagnosis or Exclusion of Acute Decompensated HF

37
operating characteristic; other abbreviations as in Table 2.
Acute HF þ Acute HF # Total

Confirmatory (“rule-in”) cutpoints

 Table 4 shows that comorbidities and prognostic factors are

on 8 April 2019. Downloaded from http://heart.bmj.com/ on 9 April 2019 by guest. Protected by copyright.
evenly distributed among the higher NT-proBNP discharge
category in patients with HFpEF and HFrEF (61% and 60% of
patients, respectively) but are unevenly distributed within the
lower discharge NT-proBNP category in patients with HFpEF

PN y función ventricular Figure 1 Relationship between 6-month all-cause mortality and

the three types of heart failure adjusted for age ≥75 years, peripheral
compared with in patients with HFrEF (37% of patients versus
24% of patients, respectively, p=0.011). There were no differ-
ences in survival between patients with HFpEF and HFrEF as
edema at admission, systolic blood pressure (SBP) <115 mm Hg, compared in a low (≤3000 pg/mL) or in a high (>3000 pg/mL)
hyponatraemia (sodium levels <135 mmol/L) and serum urea levels ≥15 NT-proBNP discharge category in KM analysis (online supple-
NT-proBNP, pg/mL, ICFEp (≥50%) mmol/L. HFmrEF, heart failure(40%–49%)
ICFErm with mid range ejection fraction; HFpEF,
ICFEr (<40%)
mentary materials). P=
heart failure with preserved ejection fraction; HFrEF, heart failure with
median (IQR) (n=283) reduced ejection fraction.(n=169) (n=776)
DISCUSSION
It was previously reported that a doubling of natriuretic peptides
Admisión 4436 (2590–8669) 5254 (3037–10868) 7173 (4039–13264) <0.001
for the highest quartile of absolute NT-proBNP values at at discharge carries a HR of 1.4 for (18 months) mortality, simi-
7
discharge (HR 5.68, 95% CI 2.24 to 14.36 and HR 4.79, 95% CI larly for patients with HFpEF as for patients with HFrEF. In
Alta 2147 (1114–4161) 2743 (1351–6047) 3695 (1611–7738)
2.76 to 8.33, respectively). Table 2B shows that for HFpEF and
<0.001
our study, for every twofold increase in discharge NT-proBNP,
HFrEF, both reduction percentage levels of 30%–60% (HR the multivariably adjusted HR for 6-month mortality was 1.71
Reducción % 47 (25–68) 45 (17–70) 47
3.28, 95% CI 1.07 to 10.12 and HR 1.79, CI 0.99 to 3.26,
(19–70) 0.693
in patients with HFpEF and 1.60 in patients with HFrEF, which

Reducción de ICFEp (FE ≥ 50%) ICFEr (FE < 40%)

NT-proBNP
Mortalidad por todas las causas a 6 m
> 60% 1 1
30-60% 3.28 (1.07 - 10.12) 1.79 (0.99 - 3.26)
≤ 30% 4.60 (1.47 - 14.40) 3.36 (1.93 - 5.85)
Readmisión CV/mortalidad por todas las causas a 6 m
> 60% 1 1
30-60% 1.41 (0.83 - 2.38) 1.78 (1.32 - 2.42)
≤ 30% 1.69 (1.06 - 2.71) 2.21 (1.63 - 3.00)
Figure 2 Relationship between 6-month all-cause mortality and the four categories of admission and discharge NT-proBNP levels as well as for the
categories of percentage reduction during hospitalisation according to the types of HF. HF, heart failure; HFmrEF, heart failure with midrange ejection
Salah K, et al. Heart 2019 (epub) doi:10.1136/ heartjnl-2018-314173
erp22 fraction; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction NT-proBNP, N-terminal pro-B-type
natriuretic peptide.

43
4 Salah K, et al. Heart 2019;0:1–8. doi:10.1136/heartjnl-2018-314173
ompared to tively with serum
the stable hsTnT,
(-52.9 [-72.7 toplasma BNP
-30.4] %; and hemoglobin
p<0.001) and levels on admission (Table 2).
Increase in creatinine (yes) 0.001 2.06 (1.37–3.10) 0.001 2.08 (1.33–3.2
2] %; p<0.001). The use of inotropic agents and carperitide
Factor
T. The numbers associated
of patients with stable
groupor rising hsTnT levels at discharge
For abbreviations seeofTable
the normalized
1. (hsTnT
those of the
Wepersistently
and 373 (92%),
abnormal
used univariate
respectively.
associated
and group (hsTnTlogistic
multivariate
OR = odds ratio, CI = confidence interval.
0.00135
TnT-as en ICA
regression analyses to identify the parameters
with stable or rising hsTnT levels at discharge. Multivariate analysis identified prior
https://doi.org/10.1371/journal.pone.0173336.t003
ciated with changes in hsTnT levels
in hsTnT levels correlated positively with age, changes in
, and changes in creatinine (both net and percent), and nega-
BNP and hemoglobin levels on admission (Table 2).

ble or rising hsTnT levels at discharge

ate logistic regression analyses to identify the parameters
TnT levels at discharge. Multivariate analysis identified prior

Fig 1. Distribution of hsTnT level on admission to the hospital (A), at discharge (B), changes in hsTnT
levels (net) (C) and changes in hsTnT levels (percent) (D). The median (interquartile ranges) high
sensitive cardiac troponin T (hsTnT) levels on admission, at discharge, and changes in hsTnT levels (net)
were 0.038 (0.026 to 0.065), 0.032 (0.021 to 0.049), and -0.004 (-0.017 to 0.002) ng/ml, respectively. The
percent change of hsTnT was -12.0 (-39.8 to 7.4) %.
https://doi.org/10.1371/journal.pone.0173336.g001

ournal.pone.0173336 April 5, 2017 4 / 12

Fig 2. Comparison of (increase > +15%)estimates

Kaplan—Meier (betweenfor -15probability
and +15%)of (decrease > all
(A) free of -15%)cause death, (B
cardiovascular death, and (C) free of heart failure-related rehospitalization among the falling
parison
admission toof
erp22
theKaplan—Meier
hospital (A), at dischargeestimates
(B), changes in
T levels (percent) (D). The median (interquartile ranges) high
for
and probability
hsTnT
rising of (A)
groups. All cause free
death and of all Takashio
cause
cardiovascular death,
S, et
death were not(B)
al. PLoS ONE freeamong
2017;12(4):
different of the falling, s
e0173336.

ular death, atand

els on admission, (C) free
discharge, of heart
and changes in hsTnTfailure-related
(net) groups (Figrehospitalization
levelsrising amongwas
2A, B). HF-related rehospitalization the falling,
significantly stable,
lower in falling group (p = 0.0
groups.49
21 to 0.049), and -0.004 (-0.017 to 0.002) ng/ml, respectively. Thetest; Fig 2C).
rank
9.8 to 7.4) %.All cause death and cardiovascular death were not different among the falling, stable, and
 BM adicionados a la clínica
Mortalidad a 30 días Mortalidad a 1 año

Mallick A et al. Rev Esp Cardiol. 2015;68(6):514–525

erp22 Lassus J, et al. Int J Cardiol. 2013;168:2186–94.

55
 Bio-ADM

IL-6 ET-1

NT-proBNP
GDF-15

Valor del Ca 125 en IC CA125

CA125
BioADM
ET-1
IL-6
NT-proBNP
GDF-15
JACC: HEART FAILURE VOL. 8, NO. 5, 2020 Núñez et al. 395
MAY 2020:386–97 CA125 in Worsening Heart Failure

Wide availability Low cost

BIOSTAT-CHF CA125 840 Nú

CA

C E Derivación
N T R A L I LL U ST R A TN=2356, Validación
I O N CA125 as a Biomarker in Patients N=1630, pacientes
With Worsening Heart Failure hospitalizados por ICA o IC ambulatoria con empeoramiento

BIOMARKER CLUSTERING CONGESTION PROGNOSIS

Bio-ADM Composite Congestion Score (CCS) Overall Mortality, Hospitalization for HF

Hospitalization
IL-6 jugular venous peripheral Overall mortality
ET-1 orthopnea for HF
distension edema
NT-proBNP
GDF-15

CA125

CA125
BioADM
ET-1
IL-6
NT-proBNP
GDF-15
Wide availability Low cost
4.6
CA125

LogCA125, U/mL

Hazard ratio
2.0

Higher Risk Mortality/Readmission

4.4
1.5

Higher CA125
4.2
CONGESTION PROGNOSIS 1.0
Composite Congestion Score (CCS) Overall Mortality, Hospitalization for HF
4.0
Hospitalization
jugular venous peripheral Overall mortality
orthopnea for HF
distension edema 3.8 0.7

CA125 U/mL
3.6 0.5
CCS 0 CCS 1 CCS 2 CCS 3 0 100 200 300 400 500
Higher Congestion Higher CA125

4.6 Núñez, J. et al. J Am Coll Cardiol HF. 2020;8(5):386–97.

LogCA125, U/mL

Núñez, J. et al. J Am Coll Cardiol HF. 2020;8(5):386–97

Hazard ratio

2.0
erp22
Mortality/Readmission

4.4 Carbohydrate antigen 125 (CA125) correlates with parameters of congestion. CA125 is associated with higher risk of adverse events and is widely available
1.5
in daily clinical setting. ADM ¼ adrenomedullin; ET ¼ endothelin; GDF ¼ growth differentiation factor; IL ¼ interleukin; HF ¼ heart failure;

61
Higher CA125

4.2 NT-proBNP ¼ N-terminal pro-brain natriuretic peptide.

1.0
4.0
 AUGUST 2015:641–4 sNEP in Acute HF

Neprilysin en ICA
F I G U R E 1 Cox Regression Event-Free Survival Curves

0.67 ng/ml

Cox regression event-free survival curves show composite endpoints at 2 months (A) and at long-term follow-up (B). Age was included as a
erp22 covariate, and the median value for NEP was 0.67 ng/ml. CI ¼ confidence interval; HR ¼ hazard ratio; NEPBayes-Genis A, et¼al.soluble
¼ neprylysin; sNEP J Am Coll Cardiol HF 2015;3:641–4
neprylysin.

67
 Identificación del alta 1.0

adecuada con NT-proBNP 0.8

Sensitivity
0.6

0.4

0.2

0.0

0.0

Determinación BNP (pg/ml) NT-proBNP (pg/ml) Variables OR IC95% P 1.0

Ingreso 558±753 14055±14545 EPOC (S/N) 2.6 1.4-4.8 0.002
Alta 306±482 10233±13050 Infarto previo (S/N) 2.05 1.2-3.6 0.012 0.8
Reducción 12±292 28±58 CF 3-4 pre-admisión (S/N) 2.2 1.2-3.9 0.007

Sensitivity
Síntomas al alta (S/N) 2.0 1.1-3.6 0.022
P= <0.0001 <0.0001 0.6
NTproBNP > 9000 pg/ml (S/N) 3.1 1.8-5.3 <0.0001

Perna ER, et al. Eur J Heart Fail 2014 (Supp)

erp22 0.4

73 0.2
 Temario
Rol del laboratorio en el manejo de la IC
Una gota de sangre en IC es útil para…
…identificar riesgo de IC
…el diagnóstico
…estimar pronóstico
…identificar el alta apropiada post-HIC
…guiar la terapia
…cambiar paradigmas
…y además es útil en COVID-19
Conclusiones
erp22

79 Natriuretic Peptide–Guided Therapy for Heart Failure Ori

 Fig. 2 All-cause mortality. Unadjusted individual hazards ratios (HR) with 95% confidence intervals (CI) presented within IPD, aggregate dat
overall. Time-CHF reported results separately for patients with heart failure with reduced ejection fraction (HFrEF) [26] and patients with he
failure with preserved ejection fraction (HFpEF) [33]. HR for all-cause mortality was not available for the Protect study [30]. The HR and 95%
from Guide-It [11] was adjusted for age, sex, left ventricular ejection fraction, NT-proBNP, and the presence of diabetes mellitus. Note: weig

Pufulete et al. Systematic Reviews (2018) 7:112 TGPN from random effect analysis
Page 14 of 21

Meta-análisis
Mortalidad total Mortalidad CV

Fig. 3 Cardiovascular mortality. Odds ratio (OR) with 95% confidence intervals (CI) for five aggregate data studies. Note: weights are from r
Interacciones para mortalidad
effect analysis

• Edad < 75 años (HR 0.70, 95% CI 0.53–0.92) vs ≥

75 años (HR 1.07, 95% CI 0.84–1.37), p=0.034
• FEVI: ICFER (HR 0.84, 95% CI 0.71–0.99) vs ICFEp
(HR 1.33, 95% CI 0.83– 2.11) , p=0.026

Fig. 2 All-cause mortality. Unadjusted individual hazards ratios (HR) with 95% confidence intervals (CI) presented within IPD, aggregate data, and
overall. Time-CHF reported results separately for patients with heart failure with reduced ejection fraction (HFrEF) [26] and patients with heart
failure with preserved ejection fraction (HFpEF) [33]. HR for all-cause mortality was not available for the Protect study [30]. The HR and 95% CI
from Guide-It [11] was adjusted for age, sex, left ventricular ejection fraction, NT-proBNP, and the presence of diabetes mellitus. Note: weights are
Pufulete M, et al. Syst Rev. 2018;7(1):112.
erp22
from random effect analysis

85
 the patients who did not enter the study solely based on low NT-talization prior to death. For hospitalization data, see Table 3.
the proBNP (<125 pg/ml) there was a significant difference in 2
the primary endpoint between the control group and the groupKaplan-Meier analysis. The Kaplan-Meier analysis showed
ali-
er- TGPN – Prevención primaria
with low NT-proBNP concentrations. There was no differencedifferences between the 2 groups for the primary endpoint.
in survival between the intensified group and patients with lowThe difference was statistically significant (p ¼ 0.035)
ed. NT-proBNP concentrations (Online Fig. 1).
tor Cox regression models. Regarding the primary endpoint(Fig. 2). The same was true for the endpoints: all cause
er. PONTIAC
hospitalization or deathStudy: N=300
due to cardiac con DBT2,
disease, there wasNT-proBNP > 125 pg/ml, sin enfermedad CV. Asignación
ted randomizada a cuidado usual o manejo en unidad CV para tto con I-SRAA y BB
Table 3 Reasons for Hospitalizations
up
Hospitalization Due to All Control Intensified p Value
d 5
on Any reason 135 (45%) 77 (51%) 58 (39%) 0.02 Fig
ere Cardiovascular event 25 (8%) 18 (12%) 7 (5%) 0.02
at Cardiac event 19 (6%) 14 (9%) 5 (3%) 0.03
rol Red
Heart failure 8 (3%) 7 (5%) 1 (1%) 0.003
ach diffe
pi- Values are n (%).
e 3.
wed
nt.
35)
use

ue Kaplan-Meier Curves of the Primary Endpoint

Figure 2 Hospitalization or Death Due to Cardiac Disease
Huelsmann M, et al. J Am Coll Cardiol 2013;62:1365–72 .
erp22 According to Treatment Strategy

Red line ¼ intensified group. Blue line ¼ control group. Log-rank test for overall

91
3
difference, p ¼ 0.035.
 JACC VOL. 68, NO. 22, 2016 Zile et al. 2433
DECEMBER 6, 2016:2425–36 NT-proBNP in HFrEF

Efecto del ARNI sobre los PN

C E N T R A L I LL U ST R A T I O N NT-proBNP in Patients With Heart Failure: Prognostic Implications of Changes
JACC VO

DECEMB

FIGU
Afte

Zile, M.R. et al. J Am Coll Cardiol. 2016;68(22):2425–36.

Zile, M.R. et al. J Am Coll Cardiol. 2016;68(22):2425–36.
erp22
Sacubitril/Valsartan is a first-in-class neprilysin, angiotensin receptor inhibitor that promotes vasodilation and reduces vasoconstriction (A). Effects of sacubitril/val-

97
sartan could be due to direct biochemical inhibition of neprilysin and the resultant biological effect on the determinants of natriuretic synthesis. By inhibiting neprilysin,
sacubitril/valsartan reduces degradation of B-type natriuretic peptide (BNP), resulting in an increase in BNP (C) and other vasoactive peptides. This might decrease both Risk
preload and afterload through diuretic and cell signaling effects. Increases in BNP and other vasoactive peptides could reduce the stimulus for natriuretic peptide pg/m
synthesis by acting on the determinants of its synthesis; this conclusion is supported by the observed decrease in NT-proBNP (B). Treatment with sacubitril/valsartan 1 mo
 Efectos de ARNI sobre NT-proBNP
en ICA
NT-proBNP (pg/mL) geometric mean by visit and treatment At discharge At Week 4 At Week 10
0
2200 Pre-discharge group (n=493) -5 -3.4

Percentage change from baseline

Post-discharge group (n=490)
Geometric mean plasma

3 días
2000 -10
NT-proBNP(pg/mL)

-15
1800
-20

1600 p=0.293 -25 -22*

-25*
-30 -28.2*
1400 p<0.001 p=0.388
-35 p<0.001 -33.7*
p<0.0001
1200
< 28%
p<0.001 p<0.001 -40 -38*
-45 p=0.257
1000 p<0.001
-50 Pre-discharge (n=493) Post-discharge (n=490)
800
Week 4 Week 10
Randomization Discharge Visit (week) • Rapid 28% reduction from baseline at discharge in
Pre-discharge, n 478 430 446 444 pre-discharge group
Post-discharge, n 473 310 450 439
• Once both groups were receiving
sacubitril/valsartan,
Time of optimized HF treatment without sacubitril/valsartan in post-discharge group the difference between the groups minimized
p-values indicate the change between randomization and every time point, in each arm
• Further reduction were observed at Weeks 4 and 10
compared with baseline1

Pascual-Figal D, et al. ESC Heart Fail 2018;5(2):327-368

erp22

103
 EVALUATE-HF Study
Puntos finales secundarios
Cambios en estructura cardíaca Cambios en función cardíaca

Sistólica Diastólica y acoplamiento

2 +0.6
1
Sacubitril/Valsartan Enalapril
3
Ventricular-Vascular
+1,9
Change from baseline to

0 2 +1,3
1
12 Weeks (mL/m 2)

-1 +0,3
1 +0,02 +0,03

Change from baseline to

-2 0 0

Change from baseline

12 Weeks (%)
-3 -2,2 -1 -0,3 -0,2 -1
-0,03 -0,003

to 12 Weeks
-4
-3,2 -3,3 -2
-5
-3 -2
-6 -1,4
-5,2 -4,9 -4
-7 -3
-5 p=0.24 p=0.58
-8 p=0.86 p=0.001 p=0.82
p=0.02 p=0.045 p=<0.001 -6 -4

LVEDVI LVESVI LAVI LVEF GLS -5

Mitral e’ Mitral E/e’ Ea/Ees
Velocity, cm/s

Desai AS, et al. JAMA. 2019;322(11):1077-1084.

erp22

109
 Temario
Rol del laboratorio en el manejo de la IC
Una gota de sangre en IC es útil para…
…identificar riesgo de IC
…el diagnóstico
…estimar pronóstico
…identificar el alta apropiada post-HIC
…guiar la terapia
…cambiar paradigmas
…y además es útil en COVID-19
Conclusiones
erp22

115
 Temario
Rol del laboratorio en el manejo de la IC
Una gota de sangre en IC es útil para…
…identificar riesgo de IC
…el diagnóstico
…estimar pronóstico
…identificar el alta apropiada post-HIC
…guiar la terapia
…cambiar paradigmas
…y además es útil en COVID-19
Conclusiones
erp22

121