International Journal of Cardiology 363 (2022) 196–201

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International Journal of Cardiology

journal homepage: www.elsevier.com/locate/ijcard

Review

Biomarkers in heart failure: Relevance in the clinical practice

Abdulaziz Joury a, b, Hector Ventura a, c, d, Selim R. Krim a, c, d, *
a
John Ochsner Heart and Vascular Institute, Ochsner Medical Center, New Orleans, LA, United States of America
b
King Salman Heart Center, King Fahad Medical City, Riyadh, Saudi Arabia
c
Section of Cardiomyopathy & Heart Transplantation, John Ochsner Heart and Vascular Institute, Ochsner Clinic Foundation, New Orleans, LA, United States of
America
d
The University of Queensland School of Medicine, Ochsner Clinical School, New Orleans, LA, United States of America

A R T I C L E I N F O A B S T R A C T

Keywords: Early detection and risk stratification of patients with heart failure (HF) are crucial to improve outcomes. Given
Keywords:Heart failure the complexity of the pathophysiological processes of HF and the involvement of multi-organ systems in different
biomarkers stages of HF, clinical prognostication of HF can be challenging. In this regard, several biomarkers have been
Natriuretic peptides
investigated for diagnosis, screening, and risk stratification of HF patients. These biomarkers can be classified as
Diagnosis
Prognosis
biomarkers of myocardial stretch such as B-type natriuretic peptide, biomarkers of neurohormonal activation,
biomarkers of inflammation and oxidative stress and biomarkers of cardiac hypertrophy, fibrosis and remodel­
ing. In this paper, we summarize current evidence supporting the use of selected biomarkers in HF. We review
their diagnostic, prognostic and therapeutic role in the management of HF. We also discuss potential factors
limiting the use of these novel biomarkers in the clinical practice and highlight the challenges of adopting a
multi-biomarker strategy.

1. Introduction
Despite the improvement in diagnosis and treatment of heart failure
(HF), its prevalence continues to increase with a number exceeding 64
million affected individuals worldwide [1]. Given the high prevalence
and increasing incidence of HF, there has been great focus on the
development and improvement of diagnostic and prognostic tools. In
this regard, one major breakthrough in last 3 decades has been the
discovery and validation of biomarkers for the diagnosis and risk strat­
ification of patients with HF. These HF biomarkers can be classified into
several categories; biomarkers associated with myocardial and vascular
stretch; biomarkers that reflect an alteration in the neurohormonal
pathways and renin-angiotensin-aldosterone system (RAAS); bio­
markers seen in inflammation and the oxidative process; and finally,
biomarkers associated with myocardial and vascular fibrosis (Fig. 1)
[2–4]. Some of these biomarkers such as natriuretic peptides (NPs) have
been extensively investigated and strongly validated in the clinical
practice [2]. Other promising biomarkers have failed to enter the clin­
ical arena and remain under investigation [5,6]. In this review, we
provide data on cardiac biomarkers in HF and discuss their utility in the
diagnosis, risk stratification and as a guide to HF therapy. Our paper
does not aim to review all available HF biomarkers as this has already
been previously published [5–7], but rather discuss a select number of
biomarkers (Table 1) that, based on the literature evidence, might be the
most useful in the clinical practice. Additionally, we discuss potential
factors limiting their use while highlighting opportunities and chal­
lenges of adopting a multi-biomarker strategy.
2. Biomarkers of myocardial stretch
2.1. B-type natriuretic peptide (BNP)
In a large prospective study of 1586 patients who presented to the
emergency department with acute dyspnea, a BNP cutoff value of 100 pg
per milliliter had a sensitivity of 90%, a specificity of 76%, and an ac­
curacy of 83% for differentiating congestive HF from other etiologies of
dyspnea. The area under the receiver-operating-characteristic curve
when BNP was used to differentiate HF from other causes of dyspnea was
0.91 (95% CI, 0.90 to 0.93; p < 0.001). [8] Among hospitalized patients
with HF, persistent elevation of BNP level despite appropriate HF ther­
apy - referred to as BNP unresponsive - carried a significant risk of 180-
day mortality (26.4% vs. 13.2%, p < 0.001) [9]. A large systematic

* Corresponding author at: Section of Cardiomyopathy & Heart Transplantation, John Ochsner Heart and Vascular Institute, 1514 Jefferson Highway, New Orleans,
LA 70121, United States of America.
E-mail address: selim.krim@ochsner.org (S.R. Krim).

https://doi.org/10.1016/j.ijcard.2022.06.039
Received 25 January 2022; Received in revised form 2 June 2022; Accepted 10 June 2022
Available online 15 June 2022
0167-5273/© 2022 Elsevier B.V. All rights reserved.

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A. Joury et al.
review assessed the utility of BNP in the prognosis of symptomatic and
asymptomatic HF patients and concluded that each increase of BNP by
100 pg/ml, was associated with a 35% increase in the relative risk of
death [10]. Despite the strong association between BNP levels and HF
severity, there has been an inconsistent correlation between the use of
BNP and the decision for early referral for evaluation for advanced heart
failure therapies (i.e. cardiac transplant, mechanical circulatory sup­
port) [11]. Thus, it is imperative to utilize BNP along with established
HF risk assessment tools (e.g., Seattle HF Model) [11]. Increasing age,
female sex, renal dysfunction and sacubitril/valsartan use are all known
factors associated with increased BNP levels even in the absence of HF
[5,6,12]. Obese patients on the other hand, tend to have lower BNP
levels. This finding can be related to a decrease in the production of BNP
and an increased clearance of BNP by natriuretic peptide receptors
present in adipocytes and complex interaction of natriuretic peptide
with steroid hormones [13]. Among HF patients with CKD stage III
which is defined as an estimated glomerular filtration rate (eGFR) is
<60 ml/min/1.73m2 -, BNP showed lower correlation with HF symp­
toms compared to patients with normal eGFR [14].
2.2. N-terminal proBNP (NT-proBNP)
Similar to BNP, the diagnostic value of NT-proBNP was evaluated in
the N-terminal Pro-BNP Investigation of Dyspnea in the Emergency
department (PRIDE) study, evaluating 600 patients admitted to the
emergency department for dyspnea. An NT-proBNP level < 300 pg/ml
was optimal for ruling out acute CHF, with a negative predictive value of
99%. Increased NT-proBNP was the strongest independent predictor of a
final diagnosis of acute CHF (odds ratio 44, 95% CI 21.0 to 91.0, p <
0.0001) [15]. Among patients with acute HF, a presenting NT-proBNP
concentration > 5180 pg/ml was strongly predictive of death by 76
days [odds ratio = 5.2, 95% confidence interval (CI) = 2.2–8.1, P <
0.001, 16]. In addition, NT-proBNP was found to be a strong prognostic
marker among patients with HF irrespective of ejection fraction (EF).
Specifically, for any 2.7-factor increase in NT-proBNP levels, the hazard
ratio for mortality was 1.96 in HF with reduced EF and 2.14 in HF with
preserved EF [17].
2.3. Troponins
Increased levels of troponins during admission for acute HF regard­
less of EF is common even in the absence of myocardial ischemia
[18,19]. In a study of 1469 patients with HF with reduced EF admitted
Fig. 1. HF Biomarkers and their respective pathways. HF: Heart failure; BNP: B-type natriuretic peptide NT-proBNP: N-terminal proBNP.
197
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International Journal of Cardiology 363 (2022) 196–201
for acute decompensation, 41.5% and 29.9% of patients had elevated
pre-discharge [median: 0.09 ng/ml; interquartile range (IQR):
0.06–0.19 ng/ml] and 1-month (median: 0.09 ng/ml; IQR: 0.06–0.15
ng/ml) troponin I levels, respectively [20]. After multivariate adjust­
ment, pre-discharge troponin I elevation was no longer associated with
12-month clinical outcomes. However, 1-month troponin I elevation
remained independently predictive of increased all-cause mortality [HR,
1.59, 95% CI 1.18–2.13] and cardiovascular mortality or HF hospitali­
zation (HR, 1.28, 95% CI 1.03–1.58) at 12 months. Interestingly, the
association between 1-month troponin I elevation and outcomes was
similar among patients with newly elevated (i.e. normal pre-discharge)
and those with persistently elevated levels (interaction p ≥ 0.16) [20].
Similarly, in a study of 34,233 admitted patients with HF with preserved
EF, 22.6% had elevated troponins I or T. After adjusted analysis, higher
serum creatinine level, black race, older age, and ischemic heart disease
were associated with troponin elevation [21]. In addition, high tropo­
nins I or T were a strong predictor of in-hospital mortality (odds ratio
[OR], 2.19; 95% CI, 1.88–2.56), greater length of stay (length of stay >4
days OR, 1.38; 95% CI, 1.29–1.47), and lower likelihood of discharge to
home (OR, 0.65; 95% CI, 0.61–0.71) [21]. Moreover, elevated troponins
I were strongly associated with increased risk of 30-day mortality
(hazard ratio [HR], 1.59; 95% CI, 1.42–1.80), 30-day all-cause read­
mission (HR, 1.12; 95% CI, 1.01–1.25), and 1-year mortality (HR,1.35;
95% CI, 1.26–1.45) [21]. In another large study of 808 patients admitted
with ADHF, 50% had elevated troponins I [22]. While higher troponin I
levels were predictive of in-hospital mortality (p = 0.01) and increased
length of stay (p = 0.01), no association with post-discharge outcomes at
30 or 180 days was noted [22]. In our opinion, troponins may be useful
in risk stratification of both acute and chronic HF patients in the absence
of acute coronary syndrome however we recommend exercising caution
as increased sensitivity of contemporary troponin assays may render
clinical interpretation difficult.
3. Biomarkers of neurohormonal activation
RAAS activation in HF population can be attributed to the dysregu­
lation of the sympathetic nervous system, central and peripheral che­
moreflexes, baroreflex and the state of renal hypoperfusion in HF
syndrome [3]. A small study by Nijst et al. compared plasma renin ac­
tivity (PRA) levels among different patient populations. PRA levels were
significantly higher in ambulatory chronic HF with reduced EF patients
[7.6 ng/ml/h (2.2; 18.1), p < 0.05] when compared to acute decom­
pensated HF with reduced EF patients [1.5 ng/ml/h (0.8; 5.7), p < 0.05]
A. Joury et al. International Journal of Cardiology 363 (2022) 196–201

Table 1 aldosterone (measured at the time of admission and at discharge) with

Role of biomarkers in the management of heart failure. outcomes among 211 patients admitted for acute HF. The authors
Biomarker Diagnosis Prognosis Therapy guidance stratified their patient population into 3 profiles; RAAS− /− (normal
PRA/normal aldosterone levels; n = 121 [57%]); RAAS+/− (elevated
BNP value of
>100 pg/ml has a Increase in BNP by PRA/normal aldosterone levels; n = 60 [28%]); and RAAS+/+ (high
90% sensitivity 100 pg/ml is PRA/high aldosterone levels; n = 30 [14%]). The RAAS+/+ profile had
BNP and 76% associated with a N/A the lowest blood pressure and serum sodium at admission, day-2 and
specificity for 35% increase in the discharge when compared to the other profiles. The RASS +/+ profile
diagnosis of HF RR of death [10]
[8]
was also associated with a longer duration of diuretic therapy as well as
NT-proBNP-guided at a higher dose of diuretics on discharge. One-year mortality in this
therapy was not more cohort increased throughout each profile with the highest rates seen
NT-proBNP
concentration >
effective than a usual among RASS +/+ profile [27]. Of note, a large number of patients with
care strategy in
5180 pg/ml is acute HF had normal PRA and plasma aldosterone levels. Both renin and
improving outcomes
NT-proBNP <300 strongly predictive of
(time-to-first HF aldosterone levels as assessed during admission but not at discharge
NT-pro pg/ml is optimal death by 76 days were independently associated with 1-year mortality and composite of
hospitalization or
BNP for ruling out [odds ratio = 5.2,
acute HF [15] 95% confidence
cardiovascular HF readmission/death [27]. These mixed results and the high assay and
mortality; adjusted biological variability of both PRA and plasma aldosterone remain the
interval (CI) =
hazard ratio [HR],
2.2–8.1, P < 0.001]
0.98; 95% CI,
main limiting factors for their use in clinical practice [28].
[16]
0.79–1.22; p = 0.88)
[51] 4. Biomarkers of cardiac hypertrophy, fibrosis and remodeling
High values at
discharge are
4.1. Soluble ST2 (sST2)
Troponins N/A associated with N/A
increased all-cause
mortality Suppression of tumorigenicity 2 (ST2) is an interleukin-1 receptor
[HR 1.59, 95% CI family member that is activated by mechanical strain in cardiac myo­
1.18–2.13] [20] cytes including myocardial hypertrophy, cardiac fibrosis, myocardial
High PRA are
Plasma modestly associated
injury and results in worsening in ventricular function [29]. Its soluble
renin N/A with adverse N/A form (sST2) is secreted and detectable in human serum and was found to
activity outcomes including be a strong predictor of mortality in both acute and chronic HF states
mortality [29–31]. In a study that included 593 patients who presented in the
[HR 1.11; 95%CI:
emergency department with dyspnea, sST2 levels were significantly
1.01–1.23, p = 0.04]
[26] higher among patients with acute HF compared to those without HF
sST2 ≥ 0.20 ng/ml is (sST2 was 0.50 vs. 0.15 ng/ml; p < 0.001). sST2 level ≥ 0.20 ng/ml was
sST2 N/A a strong predictor of N/A a strong predictor of death at 1 year in dyspneic patients as a whole (HR
death at 1 year = 5.6, 95% confidence interval [CI] 2.2 to 14.2; p < 0.001) as well as
[HR 5.6, 95%, CI:
those with acute HF (hazard ratio [HR] = 9.3, 95% CI 1.3 to 17.8; p =
2.2–14.2; p < 0.001]
[30] 0.03) [30]. In another study of 447 patients with acute HF, sST2 levels
Increased Galactin 3 correlated not only with HF severity and 1 year mortality, but also
Galactin 3 N/A is associated with N/A remained a strong predictor of mortality in both HF with preserved EF
adverse outcomes
(HR 1.41; 95% CI 1.14–1.76, p = 0.002) and HF with reduced EF (HR
[HR 1.95, 95% CI
1.2–3.1, p = 0.004] 1.20, 95% CI 1.10–1.32, p < 0.001) [31]. Although the measurement of
[35] serum sST2 for the diagnosis of HF is less useful, serum sST2 concen­
trations strongly predict death at 1 year in the acute setting indepen­
Abbreviations: BNP: B-type natriuretic peptide; HF: Heart failure; NT-proBNP:
dently of natriuretic peptides [30]. Using sST2 in combination with NPs
N-terminal proBNP; PRA: Plasma renin activity; pg: picogram; N/A: not appli­
cable; RR: relative risk; sST2: Soluble ST2. may enhance the prognostic ability of each marker [32]. Unlike NPs,
sST2 is less affected by age, renal function, and body mass index [32].
or healthy volunteers [1.4 ng/ml/h (0.6; 2.3), p < 0.05]. [23] Only in
4.2. Galactin 3
acute decompensated HF with reduced EF patients, were PRA levels
associated with increased cardiovascular mortality or HF readmissions
Galactin 3 is a beta-galactosidase-binding lectin that is released by
(p = 0.035). Interestingly, no significant difference in PRA levels were
activated macrophages in the cardiac myocytes and plays a key role in
noted between acute decompensated HF with reduced EF patients and
promoting ventricular remodeling [33]. This established marker of
healthy volunteers (p = 0.13) [23]. In another study by Park et al. using
fibrosis has been investigated in several clinical settings. Among 3353
a PRA cut-off value of 3.3 ng/ml/h, PRA was found to be a strong in­
individuals without HF who were enrolled in the Framingham Offspring
dependent predictor for mortality and HF hospitalization (HR = 1.205;
Cohort, a 1-standard deviation increase in Galactin 3 was a strong pre­
p = 0.007) [24]. Ueda et al. similarly studied the relationship between
dictor of incident HF (HR: 1.23; 95% CI: 1.04 to 1.47; p = 0.02 and all-
PRA (using a cut-off value of 3.4 ng/ml/h) with outcomes in acute HF
cause mortality (HR: 1.15; 95% CI: 1.04 to 1.28; p = 0.01) even after
and found a very strong correlation between higher levels of PRA and
adjustment [34]. Among 240 patients with stable chronic HF followed
cardiovascular mortality (HR 2.56; 95% CI: 1.6–4.1, p < 0.0001) [25].
for a mean of 3.4 years, plasma galectin-3 levels were strongly related to
Lowering the cut-off value of PRA to 2.44 ng/ml/h in a post-hoc analysis
outcome (HR 1.95, 95% CI 1.24–3.09, p = 0.004) [35]. In another study
of the Biased Ligand of the angiotensin II Type 1 Receptor in Patients
of 599 patients presenting with dyspnea, Galactin 3 levels were signif­
with Acute Heart Failure (BLAST-AHF) trial resulted in a modest but
icantly higher in subjects with HF compared with those with no HF,
statistically significant association between the values of PRA and out­
though Galactin 3 remained inferior to NTproBNP for the diagnosis of
comes including worsening HF or mortality (HR 1.11; 95% CI:
acute HF [36]. Interestingly, receiver operating characteristic analysis
1.01–1.23, p = 0.04) [26]. More recently, J. Biegus et al. [27] conducted
for mortality prediction at 60 days, showed that, for 60-day prognosis,
a single-center study that further explored the association of PRA and
galectin-3 had the greater area under the curve (AUC) at 0.74 (p =

198

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A. Joury et al.
0.0001) when compared to NT-proBNP AUC of 0.67 (p = 0.009).
Additionally, in a multivariate logistic regression analysis, an elevated
level of galectin-3 was the best independent predictor of 60-day mor­
tality (odds ratio 10.3, p < 0.01) [36]. Galectin-3 may be particularly
useful in conjunction with NPs to further help identify AHF patients who
may need closer post-hospital discharge follow-up [36].
5. Future clinical applications and areas of uncertainty
5.1. Single vs. serial measurements
Although single measurements (on admission or at discharge) of
several cardiac biomarkers have shown to be strong predictors of out­
comes in the acute and chronic HF setting, serial monitoring of these
biomarkers may be even more useful for risk stratification and identi­
fying patients who remain at particularly high risk. Indeed, many of
these biomarkers may vary between acutely decompensated (pre-and
post-decongestion) and chronically stable patients, therefore longitudi­
nal monitoring of these biomarkers may be even more useful for prog­
nostication during optimization of guideline directed medical therapy
[37–39]. In acute HF, both admission, predischarge and the relative
change in NP levels during hospital treatment were strong predictors of
death or hospital readmission at 6 months [37–39]. Similarly, serial
measurements of sST2 were stronger predictors for mortality than a
single baseline value [40,41]. Among stable chronic HF patients, serial
concentrations of sST2 also predicted worsening HF, rehospitalization,
heart transplantation, and death, better than BNP or NT-proBNP, and
independently predicted reverse myocardial remodeling (OR 1.22, 95%
CI 1.04–1.43, p < 0.01) [41]. On the other hand, a single measurement
of galectin-3 level (done on admission) predicted mortality up to 4 years,
independently of established echocardiographic markers of disease
severity [42].
It is important to highlight that the most recent ACC/AHA guidelines
favor the use of admission levels of NPs (IA recommendation) [43]. In
chronic HF, a strong recommendation (IA) is given for the use of NPs to
establish prognosis and disease severity, while no recommendation is
given for the use of markers of fibrosis such as troponins, sST2 and
Galactin 3 [43]. In our practice, with few exceptions (i.e., advanced HF)
we find the delta change of NP levels between admission and discharge
to be very useful to assess for response to therapy (i.e., adequate
decongestion). In chronic ambulatory HF patients, serial monitoring of
NPs in patients deemed at high risk for HF readmissions may be useful
however we do advise caution when such a strategy is adopted.
5.2. Multi-biomarker strategy
The multi-marker approach has successfully been adopted for risk
stratification and prognostication in clinical settings such as cancers,
acute coronary syndromes and cardiac amyloidosis [44–46]. As shown
in the previous sections, several promising biomarkers may be used now
in HF to enhance screening for specific pathways, prognostication and
potentially improve therapy. The ongoing conundrum remains the se­
lection and combination of individual biomarkers that would be the
most clinically useful in specific clinical scenarios [47–49]. A multi-
marker strategy can only reach the clinical arena if the selected bio­
markers can be measured using simple and readily available assays at a
low cost. Additionally, the combination of these biomarkers must pro­
vide significant incremental value that would improve clinical decision
making beyond the value of the biomarkers individually [47,48]. The
latter was highlighted in a large study of 628 patient recently admitted
with acute decompensated HF where several novel biomarkers (mid-
regional pro-adrenomedullin, mid-regional pro-atrial natriuretic pep­
tide, copeptin, high-sensitivity cardiac troponin T (hs-cTNT), sST2,
galectin-3, cystatin C, combined free light chains and high sensitivity C-
reactive protein) were measured [50]. The incremental prognostic value
of these selected biomarkers was then assessed within an extensive
199
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International Journal of Cardiology 363 (2022) 196–201
model containing established predictors of outcome including age,
gender, comorbidities, heart rate, systolic blood pressure and BNP [50].
Although high levels of all biomarkers were associated with increased
unadjusted risk of mortality, after multivariable analysis only mid
regional pro-adrenomedullin, hs-cTnT, combined free light chain, high-
sensitivity c-reactive protein, and sST2 remained independent pre­
dictors of mortality. After dichotomization of the novel biomarkers, the
presence of at least three elevated biomarkers identified patients at
greatest risk of death. Perhaps the most important take home message as
the authors of the study suggested was that dichotomization into low-
risk (0–2 elevated biomarkers) or high-risk (at least 3 elevated bio­
markers) would provide the greatest incremental prognostic value and
be most clinically useful for providers [50].
5.3. Use of HF biomarkers to guide therapy
The concept of biomarker-guided therapy is not new and has been
used with success in other areas such as oncology [44]. In HF, most of
the research has been done solely on NPs [9,10,51]. Indeed, lower levels
of NPs in HF have been associated with better outcomes. For instance,
among patients enrolled in the Valsartan Heart Failure Trial, those who
had greater reductions in BNP levels after randomization had the best
outcomes. Hence the heightened interest in use serial NPs monitoring to
guide HF therapy [9,10]. Unfortunately, after 2 decades of research,
most studies have yielded mixed results. Studies supporting the use of
NPs for therapy guidance in HF were small with favorable results mainly
driven by an increased number of clinic visits and more frequent therapy
adjustments in the NP’s guided arm [52,53]. Larger randomized trials
showed either non-inferiority or no benefit of a NP guided strategy when
compared to usual care. Notably, the Guiding Evidence Based Therapy
Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT)
[51], the largest randomized multicenter clinical trial of its kind,
compared a NT-proBNP guided therapy to usual care in high-risk pa­
tients with HF with reduced EF and was terminated prematurely for
futility [51]. Despite these mixed results, some important lessons can be
learned from these studies. First, most of the small positive studies on
biomarker-guided therapy showed a higher number of patients on
optimal guideline directed medical therapy (GDMT) (number of drugs
and dosage) in the NP guided group when compared to the usual care
group [52,53]. Interestingly, only a third of patients in the NP guided
therapy group achieved target NP levels suggesting that optimal dosage
of GDMT regardless of cardiac biomarker levels is associated with
improved survival in patients with HF with reduced EF [52,53]. This is
in line with current guidelines stating that adjustment of therapies in HF
with reduced EF should be based on achievement of maximally tolerated
target doses rather than targeting an individual’s response to therapy
using biomarkers. Second, as highlighted in the Guide-IT study [51],
despite more adjustments to therapy in the biomarker-guided group,
only half of the patients achieved target dosing. In addition, the pro­
portion of patients who achieved target NT-proBNP value of <1000 was
not significantly different between the NP-guided and the usual care
group. More importantly, clinical outcomes were not significantly
different between the 2 groups [51]. Third, a NP guided therapy
approach may not be applicable in all HF patients particularly those
with more advanced stage HF in whom NPs remain chronically elevated
and other factors such as hypotension may limit uptitration of GDMT.
Apart from NPs, data on the impact of GDMT on other cardiac bio­
markers has been limited and has yielded mixed results. A sub-analysis
data from the RELAX HF trial suggested that serelaxin may reduce hsTnT
concentrations in ADHF [54]. Similarly, neprilysin inhibition may
decrease hsTnT in chronic HF [55]. Angiotensin receptor blockers, beta-
blockers and MRAs have also shown to reduce sST2 levels [56,58].
However, in a large retrospective post hoc analysis of HFrEF patients,
spironolactone had a neutral effect on patients with elevated galactin 3
levels [59]. In summary, current data [52–58] does not support the use
of HF biomarkers to guide therapy. We also do not believe that NP
A. Joury et al. International Journal of Cardiology 363 (2022) 196–201

guided therapy should be used to optimize GDMT but may have a role in
HF with reduced EF patients once optimal or maximal GDMT has been
achieved to further identify those groups who may benefit from addi­
tional therapies.
6. Conclusion
As summarized in this paper, several cardiac biomarkers have shown
to be strong predictors of outcome in both acute and chronic HF. While
NPs remain the only biomarkers endorsed by recent ACC/AHA guide­
lines for diagnosis and risk stratification of HF, other biomarkers such as
hsTnT and sST2 may provide additional prognostic value. Finally, more
research is needed to identify a cost-effective multi-marker strategy that
will not only enhance risk stratification and prognostication but also
provide incremental clinical benefit including selection and assessment
of response to specific HF therapies.
Financial disclosure
This research did not receive any specific grant from funding
agencies in the public, commercial, or not-for-profit sectors.
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