https://doi.org/10.53453/ms.2025.6.7
The usefulness of sST2 and TNFα biomarkers in evaluating the
prognosis of patients with heart failure
Danielius Koncius
1
, Rosita Steponavičiūtė
1
, Jolanta Laukaitienė
1,2
1
Faculty of Medicine, Academy of Medicine, Lithuanian University of Health Sciences, Kaunas, Lithuania.
2
Department of Cardiology, Faculty of Medicine, Medical Academy, Hospital of Lithuanian University of Health
Sciences Kaunas Clinics, Kaunas, Lithuania
Abstract
Background and Aim. Heart failure (HF) remains a major global health burden, marked by high morbidity,
mortality, and healthcare costs. While biomarkers such as BNP and NT-proBNP are widely used in diagnosis and
management, their limitations have prompted investigation into additional markers. This review focuses on the
role of soluble ST2 (sST2) and tumor necrosis factor-alpha (TNFα) in HF, exploring their biological mechanisms,
association with inflammation, and potential clinical value.
Methods and Results. A non-systematic literature search was conducted using databases such as PubMed,
UpToDate, and ESC resources. Search terms included “heart failure diagnosis,” “biomarkers,” “NT-proBNP,”
and “precision medicine.” A total of 48 English and Lithuanian articles published between 2015 and 2025 were
reviewed, with emphasis on clinical guidelines and consensus statements from societies such as the ESC and
HFSA. NT-proBNP remains the most validated biomarker for HF diagnosis and management. sST2 has
demonstrated value in predicting mortality and rehospitalisation, particularly when used with natriuretic peptides.
TNFα, though less specific for diagnosis, offers insights into inflammatory activity and HF pathophysiology.
Together, these biomarkers support a multi-marker strategy for improved risk stratification.
Conclusion. NT-proBNP remains central to HF diagnosis, while emerging biomarkers like sST2 and TNFα
provide complementary prognostic information. Their integration into clinical practice may enhance precision in
heart failure care, though further research is needed to confirm their routine use.
Keywords: heart failure (HF), biomarkers, soluble suppressor of tumorigenicity-2 (sST2), tumour necrosis factor-
alpha (TNFα), NT-proBNP, natriuretic peptides, cardiovascular disease (CVD), high-sensitivity cardiac troponin
(hs-cTn).
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Medical Sciences 2025 Vol. 13 (4), p. 76-91, https://doi.org/10.53453/ms.2025.6.7
76
1. Introduction
Heart failure could be physiologically simplified and
described as the heart’s failure to meet the body's
demands, resulting in perfusion problems. Heart
failure is often a terminal complication of other
CVDs that are widely known as the leading cause of
morbidity and mortality in many nations worldwide
[1]. The evolution of IT and pharmacology has made
diagnosing, prognosis and treating HF easier,
making it a less fatal condition, thus prolonging
average lifespan, growth of comorbidities and risk
factors for HF, and more prolonged survival after
myocardial infarction [2] Though heart failure is still
hard to predict, biomarkers are one of the recently
widely-raised and recognised tools that help doctors
understand and diagnose it.
In the light of recent studies concerning biomarkers,
they are in the current day and age of personalised
medicine routinely used by physicians for
diagnostics, treatment plans and prognosis [3].
There are already established biomarkers, backed by
multiple studies and quality research, that have been
passed to be used in HF diagnostics and
management. For example, NT-proBNP and hs-cTn
have been integrated into the European (European
Society of Cardiology, ESC) and American
(American Heart Association, AHA) guidelines
since 2016. In the ESC guidelines, natriuretic
peptides are advocated for their value in the
diagnostics of HF, especially in the possibility of
excluding HF [4]. However, even if the data and
research point to the utility of biomarkers [5], their
limitations are usually easily pinpointed. Clinical
application of these biomarkers is limited by many
factors – including sometimes significant fluctuation
at various time points in decision making, whether
in the emergency room or the timeframe of inpatient
treatment through to discharge [6] or outpatient
primary care clinic [7]. Furthermore, other factors
have been proven to influence biomarker levels,
including age, sex, individual biological variation,
kidney function, etc. [8].
With these limitations in mind, it is no surprise that
not many biomarkers have yet made it past the
research stage and only a few are regarded as proven
and established enough to be used routinely. Given
that, this systematic review focuses on two
biomarkers that have been very noticeable and have
promising viewpoints from several recent studies –
sST2 and TNFα.
1.2. Biological Composition
ST2 is a member of the interleukin (IL)-1 receptor
family, whose gene is located on human
chromosome 2q12. Alternative promoter splicing
and 3
′
processing of the mRNA produce two
different forms: a soluble receptor, named sST2, or
a transmembrane receptor, named ST2L. ST2 was
first described in 1989. The literature mistakenly
called ST2 a “suppressor of tumorigenicity 2” when,
in fact, the original name it was given was “growth
stimulation expressed gene 2”, then renamed “serum
stimulation-2”, as it was first discovered to function
as a mediator of type 2 inflammatory responses [9].
Its role as a cardiac marker was suggested in 2002
by Weinberg et al., analysing the expression of 7.000
genes in cardiomyocytes undergoing mechanical
strain and noting that myocardial transcripts of ST2
increased significantly in response to this stimulus.
This is curious and important, as the primary source
of sST2 in the circulation in patients with HF does
not appear to be the heart. Indeed, it has been shown
that type 2 pneumocytes represent a relevant source
of sST2 in HF patients and concentrations of sST2
in pulmonary oedema from individuals with HF
strongly correlate to blood values. This link to
pulmonary pathophysiology may explain why sST2
correlates with the presence and severity of
pulmonary congestion in HF. This contrasts with
NPs, which are also upregulated in HF and correlate
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with pulmonary congestion but are only expressed
in cardiomyocytes and not the lungs. For this reason,
an additional role of sST2 relative to NPs for
evaluating the HF phenotype and prognosis seems
likely from a biological perspective [10].
The IL-33/ST2L axis is mainly a signalling
mechanism of the immune system but also has anti-
apoptotic, anti-fibrotic and anti-hypertrophic effects
in the heart. sST2 acts as a decoy receptor for IL-33,
thus blocking these positive effects. [11]. IL-33 is an
interleukin-1-like cytokine secreted by living cells in
response to cell damage. IL-33 functions as a danger
signal or an alarm by signalling the presence of
tissue damage to local immune cells after exposure
to pathogens, injury-induced stress, or death by
necrosis [3]. Once secreted, IL-33 binds the ST2L
receptor, and IL-33/ST2L signalling leads to
inflammatory gene transcription and ultimately to
the production of inflammatory cytoki-
nes/chemokines and an immune response [5,6].
sST2 avidly binds to IL-33 in competition with
ST2L, thus functioning as a decoy receptor for IL-
33. Therefore, the interaction of sST2 with IL-33
blocks the IL-33/ST2L system [12].
Tumour necrosis factor alpha (TNFα), on the other
hand, is an inflammatory cytokine from the TNF
ligand superfamily produced by macrophages,
monocytes or many other cells during acute
inflammation. Their primary role is intracellularly
signalling various events, causing necrosis or
apoptosis [13]. It was initially understood as an anti-
tumour and cytotoxic ligand, as its effect on the
necrotic regression of tumours was observed[14,15].
Bacterial lipopolysaccharide has long been
considered one of the most important triggers for
TNFα production [16]. Yet now it is known that a
wide range of stimulation can cause TNFα
production in their respective cells – including viral,
parasitic, mycotic antigens, enterotoxins,
complement proteins, immune complexes,
interleukin (IL)-1, interferons and TNFα itself
(through autocrine stimulation)[17]. With a wide
array of activating mechanisms, it is helpful to note
that TNFα biosynthesis is suppressed by IL-4 and
other ligands that lower the concentration of cyclic
adenosine monophosphate [14]. Furthermore, it is
not stored intracellularly, and de novo synthesis can
be stimulated through various triggers. On the
contrary, TNFα as a cytokine can stimulate the
release of some anti-inflammatory factors, such as
IL-10, endogenous corticosteroids and prostanoids,
that negatively regulate its expression and bring
inflammation to a halt. All things considered, TNFα
is necessary for the communication between resident
cells in various systems and the cells of the immune
system – its primary role is controlling the immune
response and inhibiting its severity and
duration [15].
TNFα induces intracellular signalling events due to
its binding to one of two cell membrane-bound TNF-
receptors (TNFR) – TNFR1 and TNFR2. Both are
transmembrane glycoproteins, yet they are different
in their locations. TNFR1 is highly common and
expressed in every cell type in the human organism,
while TNFR2 is limited to immune and nervous
system cells and the endothelium [18]. The
interesting part is what happens further inwards, as
TNF binds to TNFR. TNFR1 has an associated death
domain (TRADD) – an adapter molecule that starts
the cascade for interactions with different kinases –
this pathway is exactly what commits the involved
cell to apoptosis [18]. In addition, other pathways
are stimulated, inducing the production of adhesion
molecules and chemokines, promoting the
attachment of inflammatory cells to the vascular
walls and their activation, as well as chemotaxis
[19].
Both sST2 and TNFα have a vital role in the
signalling pathways of the immune system. sST2,
belonging to the IL-1 family, has earned its
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reputation as an essential signalling cytokine, with
the IL-33/ST2L signalling axis also showing anti-
apoptotic, anti-fibrotic and anti-hypertrophic effects
on the cardiac myocytes. On the other hand, TNFα,
as one of many TNF ligands, works to signal,
mediate and stimulate or halt immune responses
with a pathway through its TRADD domain that
each cell type possesses in their TNFR1 receptor
responsible for inducing cell apoptosis. With their
biological and physiological standings analysed,
both cytokines have an essential role in the
pathogenesis of heart failure, and with it – practical
usability in determining the phenotype and
prognosis seems likely.
1.3. Inflammation And The Pathogenesis Of
Heart Failure
The article proving the correlation between
increased circulatory levels of TNFα and heart
failure with reduced ejection fraction (HFrEF) was
first published in 1990 [20]. It provided the earliest
evidence to the understanding cardiology still leans
on while explaining the pathophysiology of heart
failure – patients with chronic heart failure
experience constant, ongoing inflammation. This
has paved the way for multiple subsequent clinical
and experimental studies. One thing seemed
inevitable – in both acute and chronic heart failure,
activation of the innate and adaptive immune
systems plays an important role, so subsequently,
theories of utility in therapeutically targeting the
inflammatory response have also surfaced.
However, this new pathway for finding new
treatments faced disappointment in stage III of
clinical trials, and researchers started doubting that
the initial theory of inflammation has a crucial role
in the pathogenesis of heart failure [21–23]. Could
inflammation be the consequence and not the cause
of heart failure?
During myocarditis or other types of injury
(ischemia or volumetric hemodynamic overload),
innate and adaptive immune systems get activated.
Innate immunity works through a general,
nonspecific response, while the adaptive system is
specific through signalling and mediation provided
by B and T cells. After an injury to the myocardium,
the general inflammation provided by the innate
immune system ensures a cytoprotective response
that ensures a short-term adaptation to the stressor
[22]. If this response becomes unregulated and acute
inflammation becomes chronic, it leads to left
ventricular (LV) dysfunction and remodelling – the
basis of HFrEF.
This innate immune system response activation
starts with transmembranic and cytosolic pattern
recognition receptors (PRRs) that bind to pathogen-
associated molecular patterns (PAMPs) and
endogenous material from damaged and apoptotic or
necrotic cells (damage-associated molecular
patterns – DAMPs). These receptors are expressed
in various heart tissues, including cardiomyocytes,
tissue-resident immune cells, and endothelial cells.
Activating these PRRs results in biochemical
pathways that regulate gene expression, including
ones that encode pro-inflammatory cytokines and
chemokines [24].
Transcriptional profiling of human cardiac samples
showed that hearts with the expressed failure
phenotype and ones without it differ in the
expression profiles of genes related to this innate
immune response [25].
Currently, two evidence pathways prove that
inflammation in the myocardium is chronically
present in individuals with both ischemic and non-
ischemic heart failure. The first one is important to
this article – the presence of TNFα and IL-1β with
chemokines in patients with both ischemic and
dilated cardiomyopathy, but not in patients proven
not to have heart failure [26]. The second evidence
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line leads to naive and activated T lymphocytes,
macrophages and NK cells being observed in
histological specimens of patients with chronic heart
failure, both ischemic and non-ischemic. Yet, the
heart samples that were chosen for this study were
selected from patients with the absence of fresh
myocardial injury of any kind, viral or bacterial
infection and immunological abnormalities – which
proves that the presence of immune cells is
associated with heart failure itself and leads to the
idea that the degree of chronic inflammation in the
myocardium might be functionally significant [27].
So far, the non-cellular components of chronic
inflammation (such as TNFα, IL-1β, IL-6 and
others) have been shown to exert adverse inotropic
effects on isolated, contracting cardiomyocytes in
vitro, in intact animal hearts ex vivo and in vivo in
animal studies [28–31]. Studies that employed
prolonged pro-inflammatory signalling were
performed, and, for example, TNF was infused into
the peritoneal cavity of rats at concentrations like
those in patients with heart failure, resulting in
changes to LV dimensions and function that became
more pronounced over time [32]. Other studies also
showed that mice overexpression of the TNF gene
developed progressive LV dilatation. With that, it
was demonstrated that TNF activates specific
metalloproteinases that degrade extracellular
collagen matrix and, as a result – promote LV
dilatation [33].
Even with the role of inflammation in the
pathogenesis of heart failure, if not fully understood,
then at least explored enough to provide food for
thought of using it in prognosis or treatment, it is
crucial to learn from the previous failed stage III
clinical trials. Furthermore, the promising results of
the CANTOS trial show that inflammatory
biomarkers can be used to identify patients who
would benefit from an anti-inflammatory treatment
strategy [34]. Other inflammatory biomarkers (such
as sST2 and others) are perceived as applicable for
future further selection of patients for clinical anti-
inflammatory therapy trials. Another potential
strategy for a multi-biomarker approach could be
identifying patients with heart failure, in whom
chronic inflammation is associated with further
myocardial damage, as opposed to patients in whom
this immune response acts purely as a homeostatic
effort for dealing with hemodynamic triggers [27].
Chronic inflammation, in general, plays a vital role
in the pathogenesis of heart failure. Both innate and
adaptive immune systems have been proven to
participate in response to a wide array of myocardial
damage. Yet, their malfunction, which results in
chronic, uncontrolled inflammation, is something
research still does not seem to have a complete
biological picture of. Biomarkers, as avid
participants in the immune response, might provide
some light and utility not only in further research on
the role and pathways of chronic inflammation but,
predictably – in classifying patients according to the
physiology of their ailment and consequently - in
studies and trials on the prognosis and maybe even
anti-inflammatory treatment for patients with heart
failure.
1.4. Comparison With Already Established
Biomarkers. Clinical Value
An ideal biomarker in HF should be (1) measured
non-invasively and at low cost, (2) highly sensitive
to allow for the early detection of the disease, (3)
unaffected or minimally affected by comorbid
conditions, and (4) responsive to treatment effects
[2]. Well used biomarkers are crucial in ensuring
precise treatment and risk management [35]. The
most established biomarkers in HF are B-type
natriuretic peptide (BNP) and its co-secreted amino-
terminal pro-peptide fragment (NT-proBNP), which
reflect cardiac transmural wall stress. BNPs are
strong predictors of HF presence and severity and
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provide prognostic information [36]; therefore, BNP
and NT-proBNP have a class 1 recommendation in
the current European Society of Cardiology (ESC)
and American College of Cardiology/American
Heart Association (ACC/AHA) HF guidelines for
these indications [3,4]. With that, BNP and NT-
proBNP continue to receive attention from the ESC
and other expert organisations in regards to their
diagnostic value and therefore will keep their
features in clinical recommendations [37].
Beyond their well-established diagnostic role in
acute and chronic settings, the role of BNP and NT-
proBNP in risk stratification is gaining more
momentum in clinical practice. Low values of NPs
at discharge reflect the achievement of greater
decongestion, which correlates with a lower risk of
re-hospitalization and death. In addition, the pre-
discharge value can be used to determine the
intensity of monitoring and the timing for follow-up
visits [5].
However, there are significant limitations to
natriuretic peptide (NP) testing in HF. Most
important is the impact caused by conditions
commonly associated with HF, such as atrial
fibrillation (AF), kidney dysfunction and obesity, as
well as a wide range of cardiac and non-cardiac
abnormalities associated with an increase in parietal
tension without necessarily being linked to fluid
retention. NP concentrations also vary substantially
with age and sex, which introduces difficulties in
using thresholds for decision-making. Beyond these
issues, the concentrations of BNP and NT-proBNP
only reflect one aspect of the considerably complex
pathophysiology of HF. Accordingly, a broader
palette of biomarkers would be expected to provide
an essential depth of understanding of individuals
affected by the diagnosis. One of those would be
soluble ST2 (sST2), which was first classified as an
indicator of ventricular myocyte stress but is mainly
produced in extracardiac tissues in response to
inflammatory and fibrotic stimuli, representing an
indicator of the myocardial fibrotic process and a
predictor of cardiac remodelling [9].
Regarding sST2, it is crucial to remember its
nonspecific nature, resulting in utility limitations
and rendering it unusable for heart failure
diagnostics. Yet, it has been proven helpful in risk
management. A meta-analysis performed with 4835
patients diagnosed with acute HF discovered that
both discharge and admission sST2 values were
accurate in predicting all-cause (HR 2.46 [1.80–
3.37] and 2.06 [1.37–3.11], respectively), and CVD
related mortality (HR 2.29 [1.41–3.73] and 2.20
[1.48–3.25], respectively)– furthermore, discharge
sST2 values predicted rehospitalisation for HF
patients (HR 1.54 [1.03–2.32]) [38]. A 150-patient
study has also helped predict 3-month mortality
during a hospital stay regardless of BNP or NT-
proBNP [39]. The Translational Initiative on Unique
and Novel Strategies for Management of Patients
with Heart Failure (TRIUMPH) conducted a cohort
study on 496 patients with acute HF and performed
seven separate measurements in 1 year. Similar
results were shown – baseline sST2 showed a
reliable prediction of all-cause or CVD-related death
or HF-related hospitalisation (HR for each standard
deviation increase of log
2
(ST2): 1.30 [1.08–1.56]).
Meanwhile, the regularly repeated tests proved even
more valuable – the changes across measurements
were more reliable for predictions (HR for each
standard deviation increase of the log value
2
(ST2):
1.85 [1.02–3.33]) independently from NT-proBNP
[40]. sST2 and its independency from high-
sensitivity troponin-T (hs-TnT) and NT-proBNP and
the prognostic value have been pointed out [41].
Furthermore, the fact that sST2 is less influenced by
age than the two biomarkers, as mentioned earlier, is
also prominent in studies [42].
With all the evidence in mind, it is worth mentioning
that sST2 has been prevalent in ACC/AHA
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guidelines for quite some time. They recommend its
measurement for evaluating the prognosis of
patients with chronic HF (recommendation class IIb,
B level of evidence) [43]. Meanwhile, ESC
guidelines are more cautious and mention a lack of
evidence as the explanation for not recommending
the usage of sST2 measurements in clinical
practice [4].
As for TNFα – the same issues as with sST2 arise,
non-specificity being one of the main ones.
Especially with its prominence in autoimmune and
rheumatic diseases, the utility of the TNFα titres
appears slim. Still - a study with 60 patients was
conducted, tracking various established and
experimental biomarkers and their relation to CVD-
related mortality. They found a significant
correlation between raised TNFα titres and lowered
left ventricle ejection fraction (LVEF) (mean LVEF
value was around 22%), as well as between TNFα
titres and NYHA classes (55% of patients with
abnormal values were in NYHA class IV) [44]. It is
worth mentioning that TNF, the possible
cardioprotective effects and TNFα receptors, by
their right, are mentioned in a fair number of articles
as a potential target for pharmacological treatment.
However, this is out of the scope of this study; for
further reading, please refer to [45]. Various studies
have been conducted and show a broad scope of
significant relation between the negative inotropic
phenotype of heart failure and TNFα [46]. Yet, with
progress reports, it seems like TNFα and its primary
utility will continue to treat and manage illness and
complications rather than diagnostics and risk
evaluation, making these aspects incomparable to
established and new cardiac biomarkers.
New studies have shown even more new
biomarkers, that are worth scientific attention – for
example, BMP10, which has shown potential in
acute dyspnea studies[47]. The evidence and,
consequently, agreements are straying towards
acknowledging both the triumphs and downfalls of
already established biomarkers such as BNP, NT-
proBNP or hs-TnT, yet also leaning towards multi-
biomarker approach as the safest middle ground for
the management of HF [48]. This tactic has already
started to appear vaguely in recommendations as
new biomarkers are taking their place next to the
tried and tested ones, even though the evidence is
still lacking for it to be entirely trustworthy and
make its way into day-to-day practice [43]. Yet, the
chances for a multi-biomarker approach to make it
in time are positively hopeful, already by the
biophysical properties of the markers and by the
studies that are already testing their value, showing
significant chances of lowering HF-related
morbidity and mortality if evaluated, prepared,
proven and placed among what we already know.
3. Results
Recent literature highlights NT-proBNP as a
cornerstone in the diagnosis and management of
heart failure, with strong support from international
guidelines. Emerging biomarkers such as soluble
ST2 (sST2) and tumor necrosis factor-alpha (TNF-
α) provide additional prognostic value, particularly
in identifying inflammatory activity and myocardial
stress. The integration of these biomarkers into
clinical algorithms improves diagnostic precision
and supports individualized treatment strategies.
4. Discussion
Therapeutic translation is challenging, particularly
in complex conditions like heart failure. Research
indicates that using sST2 alongside NT-proBNP
enhances prediction accuracy for adverse outcomes,
but this approach is not comprehensive. It is
essential to grasp the mechanisms behind sST2
synthesis and the binding assay sites. Clinicians
require clarity on when to measure sST2 levels and
how this information can enhance patient care. In
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acute heart failure, checking sST2 levels upon
admission and discharge is advisable. Failure to see
a decrease in these levels may indicate heightened
risks for patients, such as extended hospital stays,
more rapid adjustments to heart failure medications
after stabilisation, and rigorous monitoring for
pulmonary congestion. In cases of chronic heart
failure, sST2 levels can indicate outcomes and the
potential for reverse remodelling when treatments
are followed consistently. Assessing sST2 is vital for
risk stratification and can be considered alongside
natriuretic peptides and troponins; however, more
research is needed to confirm its role in directing
treatment choices, like altering medications or
referrals for defibrillator placement. Although TNFα
is less specific to cardiac stress than sST2, it reflects
systemic inflammation in heart failure patients.
While combining TNFα with cardiac-specific
biomarkers could enhance risk prediction, its value
as an independent prognostic factor remains
uncertain. Combining these biomarkers may yield a
more comprehensive evaluation of heart failure
severity, considering cardiac-specific and systemic
inflammatory responses. This multimarker strategy
should aid in better risk categorisation and enable
more tailored treatment options.
5. Clinical Perspectives
Biomarkers play a crucial role in the modern clinical
management of heart failure. NT-proBNP remains
the most reliable and widely recommended marker
for diagnosing heart failure, particularly in patients
presenting with nonspecific symptoms such as
dyspnea. Emerging biomarkers, including soluble
ST2 (sST2) and tumor necrosis factor-alpha (TNF-
α), offer additional prognostic information by
reflecting myocardial stress and inflammatory
activity. While their routine use in clinical practice
is still evolving, they may prove valuable in
identifying high-risk patients and tailoring therapy.
The integration of biomarkers into clinical
algorithms enhances diagnostic accuracy, supports
early intervention, and enables a more
individualized approach to treatment. Ongoing
research and guideline updates will further clarify
the role of these emerging markers in everyday
practice.
6. Conclusions
Biomarkers such as NT-proBNP have a well-
established role in the diagnosis, risk stratification,
and management of heart failure, as confirmed by
recent guidelines and expert consensus. Emerging
markers like sST2 and TNF-α offer additional
insights into disease severity, inflammation, and
prognosis, although their routine clinical use is still
being defined. While biomarker-guided strategies
are shaping a more precise approach to heart failure
care, further studies are needed to fully integrate
novel biomarkers into standardized clinical practice.
Their careful application can enhance diagnostic
accuracy, support earlier intervention, and
contribute to more personalized treatment pathways.
References
1. Vasan RS. Biomarkers of cardiovascular
disease: Molecular basis and practical
considerations. Vol. 113, Circulation. 2006. p.
2335–62.
2. Castiglione V, Aimo A, Vergaro G, Saccaro
L, Passino C, Emdin M. Biomarkers for the
diagnosis and management of heart failure. Vol. 27,
Heart Failure Reviews. Springer; 2022. p. 625–43.
3. Meijers WC, Bayes-Genis A, Mebazaa A,
Bauersachs J, Cleland JGF, Coats AJS, et al.
Circulating heart failure biomarkers beyond
natriuretic peptides: review from the Biomarker
Study Group of the Heart Failure Association
(HFA), European Society of Cardiology (ESC). Eur
J Heart Fail [Internet]. 2021;23:1610–32. Available
Journal of Medical Sciences. 4 Jun, 2025 - Volume 13 | Issue 4. Electronic - ISSN: 2345-0592
83
from:
https://onlinelibrary.wiley.com/doi/10.1002/ejhf.23
46
4. Ponikowski P, Voors AA, Anker SD, Bueno
H, Cleland JGF, Coats AJS, et al. 2016 ESC
Guidelines for the diagnosis and treatment of acute
and chronic heart failure. Vol. 37, European Heart
Journal. Oxford University Press; 2016. p. 2129–
2200m.
5. Miller WL, Hartman KA, Burritt MF, Grill
DE, Rodeheffer RJ, Burnett JC, et al. Serial
biomarker measurements in ambulatory patients
with chronic heart failure: the importance of change
over time. Circulation [Internet]. 2007 Jul [cited
2024 Jul 19];116(3):249–57. Available from:
https://pubmed.ncbi.nlm.nih.gov/17592074/
6. Omar HR, Guglin M. Discharge BNP is a
stronger predictor of 6-month mortality in acute
heart failure compared with baseline BNP and
admission-to-discharge percentage BNP reduction.
Int J Cardiol [Internet]. 2016 Oct 15 [cited 2024 Jul
19];221:1116–22. Available from:
https://pubmed.ncbi.nlm.nih.gov/27467969/
7. Piek A, Meijers WC, Schroten NF,
Gansevoort RT, de Boer RA, Silljé HHW. HE4
Serum Levels Are Associated with Heart Failure
Severity in Patients With Chronic Heart Failure. J
Card Fail [Internet]. 2017 Jan 1 [cited 2024 Jul
19];23(1):12–9. Available from:
https://pubmed.ncbi.nlm.nih.gov/27224553/
8. Meijers WC, van der Velde AR, Muller
Kobold AC, Dijck-Brouwer J, Wu AH, Jaffe A, et
al. Variability of biomarkers in patients with
chronic heart failure and healthy controls. Eur J
Heart Fail [Internet]. 2017 Mar 1 [cited 2024 Jul
19];19(3):357–65. Available from:
https://pubmed.ncbi.nlm.nih.gov/27766733/
9. Riccardi M, Myhre PL, Zelniker TA, Metra
M, Januzzi JL, Inciardi RM. Soluble ST2 in Heart
Failure: A Clinical Role beyond B-Type Natriuretic
Peptide. J Cardiovasc Dev Dis [Internet]. 2023 Nov
1 [cited 2024 Aug 2];10(11). Available from:
https://pubmed.ncbi.nlm.nih.gov/37998526/
10. Castiglione V, Aimo A, Vergaro G, Saccaro
L, Passino C, Emdin M. Biomarkers for the
diagnosis and management of heart failure. Heart
Fail Rev [Internet]. 2022 Mar 1 [cited 2024 Aug
2];27(2):625–43. Available from:
https://pubmed.ncbi.nlm.nih.gov/33852110/
11. Castiglione V, Aimo A, Vergaro G, Saccaro
L, Passino C, Emdin M. Biomarkers for the
diagnosis and management of heart failure. Vol. 27,
Heart Failure Reviews. Springer; 2022. p. 625–43.
12. Pusceddu I, Dieplinger B, Mueller T. ST2
and the ST2/IL-33 signalling pathway–
biochemistry and pathophysiology in animal
models and humans. Clinica Chimica Acta. 2019
Aug 1;495:493–500.
13. Horiuchi T, Mitoma H, Harashima SI,
Tsukamoto H, Shimoda T. Transmembrane TNF-α:
Structure, function and interaction with anti-TNF
agents. Rheumatology. 2010 Mar 1;49(7):1215–28.
14. Pocino K, Carnazzo V, Stefanile A, Basile
V, Guerriero C, Marino M, et al. Tumor Necrosis
Factor-Alpha: Ally and Enemy in Protean
Cutaneous Sceneries. Int J Mol Sci [Internet]. 2024
Jul 16 [cited 2024 Aug 2];25(14):7762. Available
from: /pmc/articles/PMC11276697/
15. Aggarwal BB, Gupta SC, Kim JH.
Historical perspectives on tumor necrosis factor
and its superfamily: 25 years later, a golden
journey. Blood. 2012 Jan 19;119(3):651–65.
16. Zou J, Guo P, Lv N, Huang D.
Lipopolysaccharide-induced tumor necrosis factor-
α factor enhances inflammation and is associated
with cancer (Review). Mol Med Rep. 2015 Sep
1;12(5):6399–404.
17. Zelová H, Hošek J. TNF-α signalling and
inflammation: Interactions between old
Journal of Medical Sciences. 4 Jun, 2025 - Volume 13 | Issue 4. Electronic - ISSN: 2345-0592
84
acquaintances. Inflammation Research. 2013
Jul;62(7):641–51.
18. Holbrook J, Lara-Reyna S, Jarosz-Griffiths
H, McDermott M. Tumour necrosis factor
signalling in health and disease. F1000Res. 2019;8.
19. Zelová H, Hošek J. TNF-α signalling and
inflammation: interactions between old
acquaintances. Inflamm Res [Internet]. 2013 Jul
[cited 2024 Aug 2];62(7):641–51. Available from:
https://pubmed.ncbi.nlm.nih.gov/23685857/
20. Levine B, Kalman J, Mayer L, Fillit HM,
Packer M. Elevated Circulating Levels of Tumor
Necrosis Factor in Severe Chronic Heart Failure.
New England Journal of Medicine [Internet]. 1990
Jul 26 [cited 2024 Aug 3];323(4):236–41. Available
from:
https://www.nejm.org/doi/full/10.1056/NEJM1990
07263230405
21. Mann DL. Innate immunity and the failing
heart: the cytokine hypothesis revisited. Circ Res
[Internet]. 2015 Mar 27 [cited 2024 Aug
3];116(7):1254–68. Available from:
https://pubmed.ncbi.nlm.nih.gov/25814686/
22. Frantz S, Falcao-Pires I, Balligand JL,
Bauersachs J, Brutsaert D, Ciccarelli M, et al. The
innate immune system in chronic cardiomyopathy:
a European Society of Cardiology (ESC) scientific
statement from the Working Group on Myocardial
Function of the ESC. Eur J Heart Fail [Internet].
2018 Mar 1 [cited 2024 Aug 3];20(3):445–59.
Available from:
https://pubmed.ncbi.nlm.nih.gov/29333691/
23. Dick SA, Epelman S. Chronic Heart
Failure and Inflammation: What Do We Really
Know? Circ Res [Internet]. 2016 Jun 24 [cited 2024
Aug 3];119(1):159–76. Available from:
https://pubmed.ncbi.nlm.nih.gov/27340274/
24. Mann DL. The emerging role of innate
immunity in the heart and vascular system: for
whom the cell tolls. Circ Res [Internet]. 2011 Apr
29 [cited 2024 Aug 3];108(9):1133–45. Available
from: https://pubmed.ncbi.nlm.nih.gov/21527743/
25. Toldo S, Abbate A. The NLRP3
inflammasome in acute myocardial infarction. Nat
Rev Cardiol [Internet]. 2018 Apr 1 [cited 2024 Aug
3];15(4):203–14. Available from:
https://pubmed.ncbi.nlm.nih.gov/29143812/
26. Bartekova M, Radosinska J, Jelemensky
M, Dhalla NS. Role of cytokines and inflammation
in heart function during health and disease. Heart
Fail Rev [Internet]. 2018 Sep 1 [cited 2024 Aug
3];23(5):733–58. Available from:
https://pubmed.ncbi.nlm.nih.gov/29862462/
27. Baumeier C, Harms D, Aleshcheva G,
Gross U, Escher F, Schultheiss HP. Advancing
Precision Medicine in Myocarditis: Current Status
and Future Perspectives in Endomyocardial
Biopsy-Based Diagnostics and Therapeutic
Approaches. J Clin Med [Internet]. 2023 Jul 31
[cited 2024 Aug 3];12(15). Available from:
http://www.ncbi.nlm.nih.gov/pubmed/37568452
28. Toldo S, Mezzaroma E, O’Brien L,
Marchetti C, Seropian IM, Voelkel NF, et al.
Interleukin-18 mediates interleukin-1-induced
cardiac dysfunction. Am J Physiol Heart Circ
Physiol [Internet]. 2014 Apr 1 [cited 2024 Aug
3];306(7). Available from:
https://pubmed.ncbi.nlm.nih.gov/24531812/
29. Gulick T, Chung MK, Pieper SJ, Lange LG,
Schreiner GF. Interleukin 1 and tumor necrosis
factor inhibit cardiac myocyte beta-adrenergic
responsiveness. Proc Natl Acad Sci U S A
[Internet]. 1989 [cited 2024 Aug 3];86(17):6753–7.
Available from:
https://pubmed.ncbi.nlm.nih.gov/2549546/
30. Yokoyama T, Vaca L, Rossen RD, Durante
W, Hazarika P, Mann DL. Cellular basis for the
negative inotropic effects of tumor necrosis factor-
alpha in the adult mammalian heart. J Clin Invest
[Internet]. 1993 [cited 2024 Aug 3];92(5):2303–12.
Journal of Medical Sciences. 4 Jun, 2025 - Volume 13 | Issue 4. Electronic - ISSN: 2345-0592
85
Available from:
https://pubmed.ncbi.nlm.nih.gov/8227345/
31. Yu XW, Kennedy RH, Liu SJ.
JAK2/STAT3, not ERK1/2, mediates interleukin-6-
induced activation of inducible nitric-oxide
synthase and decrease in contractility of adult
ventricular myocytes. J Biol Chem [Internet]. 2003
May 2 [cited 2024 Aug 3];278(18):16304–9.
Available from:
https://pubmed.ncbi.nlm.nih.gov/12595539/
32. Bozkurt B, Kribbs SB, Clubb FJ, Michael
LH, Didenko V V., Hornsby PJ, et al.
Pathophysiologically relevant concentrations of
tumor necrosis factor-alpha promote progressive
left ventricular dysfunction and remodeling in rats.
Circulation [Internet]. 1998 Apr 14 [cited 2024 Aug
3];97(14):1382–91. Available from:
https://pubmed.ncbi.nlm.nih.gov/9577950/
33. Zhang W, Chancey AL, Tzeng HP, Zhou Z,
Lavine KJ, Gao F, et al. The development of
myocardial fibrosis in transgenic mice with
targeted overexpression of tumor necrosis factor
requires mast cell-fibroblast interactions.
Circulation [Internet]. 2011 Nov 8 [cited 2024 Aug
3];124(19):2106–16. Available from:
https://pubmed.ncbi.nlm.nih.gov/22025605/
34. Svensson E, Madar A, Campbell C, He Y,
Circulation MS, 2018 undefined. TET2-driven
clonal hematopoiesis predicts enhanced response to
canakinumab in the CANTOS trial: an exploratory
analysis. Am Heart AssocEC Svensson, A Madar,
CD Campbell, Y He, M Sultan, ML Healey, K
D’Aco, A FernandezCirculation, 2018•Am Heart
Assoc [Internet]. [cited 2024 Aug 3]; Available
from:
https://www.ahajournals.org/doi/abs/10.1161/circ.
138.suppl_1.15111
35. KENNEDY SG, GAGGIN HK.
Leveraging Biomarkers for Precision Medicine in
Heart Failure. J Card Fail [Internet]. 2023 Apr 1
[cited 2025 May 6];29(4):459–62. Available from:
https://onlinejcf.com/action/showFullText?pii=S10
71916423000659
36. Bayes-Genis A, Docherty KF, Petrie MC,
Januzzi JL, Mueller C, Anderson L, et al. Practical
algorithms for early diagnosis of heart failure and
heart stress using NT-proBNP: A clinical consensus
statement from the Heart Failure Association of the
ESC. Eur J Heart Fail [Internet]. 2023 Nov 1 [cited
2025 May 6];25(11):1891–8. Available from:
https://pubmed.ncbi.nlm.nih.gov/37712339/
37. Tsutsui H, Albert NM, Coats AJS, Anker
SD, Bayes-Genis A, Butler J, et al. Natriuretic
peptides: role in the diagnosis and management of
heart failure: a scientific statement from the Heart
Failure Association of the European Society of
Cardiology, Heart Failure Society of America and
Japanese Heart Failure Society. Eur J Heart Fail
[Internet]. 2023 May 1 [cited 2025 May
6];25(5):616–31. Available from:
https://pubmed.ncbi.nlm.nih.gov/37098791/
38. Aimo A, Vergaro G, Ripoli A, Bayes-Genis
A, Pascual Figal DA, de Boer RA, et al. Meta-
Analysis of Soluble Suppression
of Tumorigenicity-2 and Prognosis in Acute Heart
Failure. JACC Heart Fail. 2017 Apr 1;5(4):287–96.
39. Boisot S, Beede J, Isakson S, Chiu A,
Clopton P, Januzzi J, et al. Serial sampling of ST2
predicts 90-day mortality following destabilized
heart failure. J Card Fail [Internet]. 2008 Nov [cited
2024 Nov 11];14(9):732–8. Available from:
https://pubmed.ncbi.nlm.nih.gov/18995177/
40. van Vark LC, Lesman-Leegte I, Baart SJ,
Postmus D, Pinto YM, Orsel JG, et al. Prognostic
Value of Serial ST2 Measurements in Patients With
Acute Heart Failure. J Am Coll Cardiol. 2017 Nov
7;70(19):2378–88.
41. Emdin M, Aimo A, Vergaro G, Bayes-
Genis A, Lupón J, Latini R, et al. sST2 Predicts
Outcome in Chronic Heart Failure Beyond NT-
Journal of Medical Sciences. 4 Jun, 2025 - Volume 13 | Issue 4. Electronic - ISSN: 2345-0592
86
proBNP and High-Sensitivity Troponin T. J Am
Coll Cardiol [Internet]. 2018 Nov 6 [cited 2024
Nov 11];72(19):2309–20. Available from:
https://pubmed.ncbi.nlm.nih.gov/30384887/
42. Aimo A, Januzzi JL, Vergaro G, Richards
AM, Lam CSP, Latini R, et al. Circulating levels
and prognostic value of soluble ST2 in heart failure
are less influenced by age than N-terminal pro-B-
type natriuretic peptide and high-sensitivity
troponin T. Eur J Heart Fail [Internet]. 2020 Nov 1
[cited 2024 Nov 11];22(11):2078–88. Available
from: https://pubmed.ncbi.nlm.nih.gov/31919929/
43. Yancy CW, Jessup M, Bozkurt B, Butler J,
Casey DE, Colvin MM, et al. 2017
ACC/AHA/HFSA Focused Update of the 2013
ACCF/AHA Guideline for the Management of
Heart Failure: A Report of the American College of
Cardiology/American Heart Association Task
Force on Clinical Practice Guidelines and the Heart
Failure Society of America. Circulation [Internet].
2017 Aug 8 [cited 2024 Nov 11];136(6):e137–61.
Available from:
https://pubmed.ncbi.nlm.nih.gov/28455343/
44. Sudharshana Murthy KA, Ashoka HG,
Aparna AN. Evaluation and comparison of
biomarkers in heart failure. Indian Heart J. 2016
Apr 1;68:S22–8.
45. Rolski F, Błyszczuk P. Complexity of TNF-
α Signaling in Heart Disease. J Clin Med [Internet].
2020 Oct 1 [cited 2024 Nov 11];9(10):3267.
Available from:
https://pmc.ncbi.nlm.nih.gov/articles/PMC760131
6/
46. Schumacher SM, Naga Prasad S V. Tumor
Necrosis Factor-α in Heart Failure: an Updated
Review. Vol. 20, Current Cardiology Reports.
Current Medicine Group LLC 1; 2018.
47. Simonavicius J, Wussler D, Belkin M,
Luening K, Lopez-Ayala P, Strebel I, et al.
Diagnostic and prognostic utility of bone
morphogenetic protein 10 in acute dyspnea: a
cohort study. Clin Res Cardiol [Internet]. 2024
[cited 2025 May 6]; Available from:
https://pubmed.ncbi.nlm.nih.gov/39661145/
48. Topf A, Mirna M, Ohnewein B, Jirak P,
Kopp K, Fejzic D, et al. The Diagnostic and
Therapeutic Value of Multimarker Analysis in
Heart Failure. An Approach to Biomarker-Targeted
Therapy. Vol. 7, Frontiers in Cardiovascular
Medicine. Frontiers Media S.A.; 2020.
1. Vasan RS. Biomarkers of cardiovascular
disease: Molecular basis and practical
considerations. Vol. 113, Circulation. 2006. p.
2335–62.
2. Castiglione V, Aimo A, Vergaro G, Saccaro
L, Passino C, Emdin M. Biomarkers for the
diagnosis and management of heart failure. Vol. 27,
Heart Failure Reviews. Springer; 2022. p. 625–43.
3. Meijers WC, Bayes-Genis A, Mebazaa A,
Bauersachs J, Cleland JGF, Coats AJS, et al.
Circulating heart failure biomarkers beyond
natriuretic peptides: review from the Biomarker
Study Group of the Heart Failure Association
(HFA), European Society of Cardiology (ESC). Eur
J Heart Fail [Internet]. 2021;23:1610–32. Available
from:
https://onlinelibrary.wiley.com/doi/10.1002/ejhf.23
46
4. Ponikowski P, Voors AA, Anker SD, Bueno
H, Cleland JGF, Coats AJS, et al. 2016 ESC
Guidelines for the diagnosis and treatment of acute
and chronic heart failure. Vol. 37, European Heart
Journal. Oxford University Press; 2016. p. 2129–
2200m.
5. Miller WL, Hartman KA, Burritt MF, Grill
DE, Rodeheffer RJ, Burnett JC, et al. Serial
biomarker measurements in ambulatory patients
with chronic heart failure: the importance of change
over time. Circulation [Internet]. 2007 Jul [cited
Journal of Medical Sciences. 4 Jun, 2025 - Volume 13 | Issue 4. Electronic - ISSN: 2345-0592
87
2024 Jul 19];116(3):249–57. Available from:
https://pubmed.ncbi.nlm.nih.gov/17592074/
6. Omar HR, Guglin M. Discharge BNP is a
stronger predictor of 6-month mortality in acute
heart failure compared with baseline BNP and
admission-to-discharge percentage BNP reduction.
Int J Cardiol [Internet]. 2016 Oct 15 [cited 2024 Jul
19];221:1116–22. Available from:
https://pubmed.ncbi.nlm.nih.gov/27467969/
7. Piek A, Meijers WC, Schroten NF,
Gansevoort RT, de Boer RA, Silljé HHW. HE4
Serum Levels Are Associated with Heart Failure
Severity in Patients With Chronic Heart Failure. J
Card Fail [Internet]. 2017 Jan 1 [cited 2024 Jul
19];23(1):12–9. Available from:
https://pubmed.ncbi.nlm.nih.gov/27224553/
8. Meijers WC, van der Velde AR, Muller
Kobold AC, Dijck-Brouwer J, Wu AH, Jaffe A, et
al. Variability of biomarkers in patients with
chronic heart failure and healthy controls. Eur J
Heart Fail [Internet]. 2017 Mar 1 [cited 2024 Jul
19];19(3):357–65. Available from:
https://pubmed.ncbi.nlm.nih.gov/27766733/
9. Riccardi M, Myhre PL, Zelniker TA, Metra
M, Januzzi JL, Inciardi RM. Soluble ST2 in Heart
Failure: A Clinical Role beyond B-Type Natriuretic
Peptide. J Cardiovasc Dev Dis [Internet]. 2023 Nov
1 [cited 2024 Aug 2];10(11). Available from:
https://pubmed.ncbi.nlm.nih.gov/37998526/
10. Castiglione V, Aimo A, Vergaro G, Saccaro
L, Passino C, Emdin M. Biomarkers for the
diagnosis and management of heart failure. Heart
Fail Rev [Internet]. 2022 Mar 1 [cited 2024 Aug
2];27(2):625–43. Available from:
https://pubmed.ncbi.nlm.nih.gov/33852110/
11. Castiglione V, Aimo A, Vergaro G, Saccaro
L, Passino C, Emdin M. Biomarkers for the
diagnosis and management of heart failure. Vol. 27,
Heart Failure Reviews. Springer; 2022. p. 625–43.
12. Pusceddu I, Dieplinger B, Mueller T. ST2
and the ST2/IL-33 signalling pathway–
biochemistry and pathophysiology in animal
models and humans. Clinica Chimica Acta. 2019
Aug 1;495:493–500.
13. Horiuchi T, Mitoma H, Harashima SI,
Tsukamoto H, Shimoda T. Transmembrane TNF-α:
Structure, function and interaction with anti-TNF
agents. Rheumatology. 2010 Mar 1;49(7):1215–28.
14. Pocino K, Carnazzo V, Stefanile A, Basile
V, Guerriero C, Marino M, et al. Tumor Necrosis
Factor-Alpha: Ally and Enemy in Protean
Cutaneous Sceneries. Int J Mol Sci [Internet]. 2024
Jul 16 [cited 2024 Aug 2];25(14):7762. Available
from: /pmc/articles/PMC11276697/
15. Aggarwal BB, Gupta SC, Kim JH.
Historical perspectives on tumor necrosis factor
and its superfamily: 25 years later, a golden
journey. Blood. 2012 Jan 19;119(3):651–65.
16. Zou J, Guo P, Lv N, Huang D.
Lipopolysaccharide-induced tumor necrosis factor-
α factor enhances inflammation and is associated
with cancer (Review). Mol Med Rep. 2015 Sep
1;12(5):6399–404.
17. Zelová H, Hošek J. TNF-α signalling and
inflammation: Interactions between old
acquaintances. Inflammation Research. 2013
Jul;62(7):641–51.
18. Holbrook J, Lara-Reyna S, Jarosz-Griffiths
H, McDermott M. Tumour necrosis factor
signalling in health and disease. F1000Res. 2019;8.
19. Zelová H, Hošek J. TNF-α signalling and
inflammation: interactions between old
acquaintances. Inflamm Res [Internet]. 2013 Jul
[cited 2024 Aug 2];62(7):641–51. Available from:
https://pubmed.ncbi.nlm.nih.gov/23685857/
20. Levine B, Kalman J, Mayer L, Fillit HM,
Packer M. Elevated Circulating Levels of Tumor
Necrosis Factor in Severe Chronic Heart Failure.
New England Journal of Medicine [Internet]. 1990
Journal of Medical Sciences. 4 Jun, 2025 - Volume 13 | Issue 4. Electronic - ISSN: 2345-0592
88
Jul 26 [cited 2024 Aug 3];323(4):236–41. Available
from:
https://www.nejm.org/doi/full/10.1056/NEJM1990
07263230405
21. Mann DL. Innate immunity and the failing
heart: the cytokine hypothesis revisited. Circ Res
[Internet]. 2015 Mar 27 [cited 2024 Aug
3];116(7):1254–68. Available from:
https://pubmed.ncbi.nlm.nih.gov/25814686/
22. Frantz S, Falcao-Pires I, Balligand JL,
Bauersachs J, Brutsaert D, Ciccarelli M, et al. The
innate immune system in chronic cardiomyopathy:
a European Society of Cardiology (ESC) scientific
statement from the Working Group on Myocardial
Function of the ESC. Eur J Heart Fail [Internet].
2018 Mar 1 [cited 2024 Aug 3];20(3):445–59.
Available from:
https://pubmed.ncbi.nlm.nih.gov/29333691/
23. Dick SA, Epelman S. Chronic Heart
Failure and Inflammation: What Do We Really
Know? Circ Res [Internet]. 2016 Jun 24 [cited 2024
Aug 3];119(1):159–76. Available from:
https://pubmed.ncbi.nlm.nih.gov/27340274/
24. Mann DL. The emerging role of innate
immunity in the heart and vascular system: for
whom the cell tolls. Circ Res [Internet]. 2011 Apr
29 [cited 2024 Aug 3];108(9):1133–45. Available
from: https://pubmed.ncbi.nlm.nih.gov/21527743/
25. Toldo S, Abbate A. The NLRP3
inflammasome in acute myocardial infarction. Nat
Rev Cardiol [Internet]. 2018 Apr 1 [cited 2024 Aug
3];15(4):203–14. Available from:
https://pubmed.ncbi.nlm.nih.gov/29143812/
26. Bartekova M, Radosinska J, Jelemensky
M, Dhalla NS. Role of cytokines and inflammation
in heart function during health and disease. Heart
Fail Rev [Internet]. 2018 Sep 1 [cited 2024 Aug
3];23(5):733–58. Available from:
https://pubmed.ncbi.nlm.nih.gov/29862462/
27. Baumeier C, Harms D, Aleshcheva G,
Gross U, Escher F, Schultheiss HP. Advancing
Precision Medicine in Myocarditis: Current Status
and Future Perspectives in Endomyocardial
Biopsy-Based Diagnostics and Therapeutic
Approaches. J Clin Med [Internet]. 2023 Jul 31
[cited 2024 Aug 3];12(15). Available from:
http://www.ncbi.nlm.nih.gov/pubmed/37568452
28. Toldo S, Mezzaroma E, O’Brien L,
Marchetti C, Seropian IM, Voelkel NF, et al.
Interleukin-18 mediates interleukin-1-induced
cardiac dysfunction. Am J Physiol Heart Circ
Physiol [Internet]. 2014 Apr 1 [cited 2024 Aug
3];306(7). Available from:
https://pubmed.ncbi.nlm.nih.gov/24531812/
29. Gulick T, Chung MK, Pieper SJ, Lange LG,
Schreiner GF. Interleukin 1 and tumor necrosis
factor inhibit cardiac myocyte beta-adrenergic
responsiveness. Proc Natl Acad Sci U S A
[Internet]. 1989 [cited 2024 Aug 3];86(17):6753–7.
Available from:
https://pubmed.ncbi.nlm.nih.gov/2549546/
30. Yokoyama T, Vaca L, Rossen RD, Durante
W, Hazarika P, Mann DL. Cellular basis for the
negative inotropic effects of tumor necrosis factor-
alpha in the adult mammalian heart. J Clin Invest
[Internet]. 1993 [cited 2024 Aug 3];92(5):2303–12.
Available from:
https://pubmed.ncbi.nlm.nih.gov/8227345/
31. Yu XW, Kennedy RH, Liu SJ.
JAK2/STAT3, not ERK1/2, mediates interleukin-6-
induced activation of inducible nitric-oxide
synthase and decrease in contractility of adult
ventricular myocytes. J Biol Chem [Internet]. 2003
May 2 [cited 2024 Aug 3];278(18):16304–9.
Available from:
https://pubmed.ncbi.nlm.nih.gov/12595539/
32. Bozkurt B, Kribbs SB, Clubb FJ, Michael
LH, Didenko V V., Hornsby PJ, et al.
Pathophysiologically relevant concentrations of
Journal of Medical Sciences. 4 Jun, 2025 - Volume 13 | Issue 4. Electronic - ISSN: 2345-0592
89
tumor necrosis factor-alpha promote progressive
left ventricular dysfunction and remodeling in rats.
Circulation [Internet]. 1998 Apr 14 [cited 2024 Aug
3];97(14):1382–91. Available from:
https://pubmed.ncbi.nlm.nih.gov/9577950/
33. Zhang W, Chancey AL, Tzeng HP, Zhou Z,
Lavine KJ, Gao F, et al. The development of
myocardial fibrosis in transgenic mice with
targeted overexpression of tumor necrosis factor
requires mast cell-fibroblast interactions.
Circulation [Internet]. 2011 Nov 8 [cited 2024 Aug
3];124(19):2106–16. Available from:
https://pubmed.ncbi.nlm.nih.gov/22025605/
34. Svensson E, Madar A, Campbell C, He Y,
Circulation MS, 2018 undefined. TET2-driven
clonal hematopoiesis predicts enhanced response to
canakinumab in the CANTOS trial: an exploratory
analysis. Am Heart AssocEC Svensson, A Madar,
CD Campbell, Y He, M Sultan, ML Healey, K
D’Aco, A FernandezCirculation, 2018•Am Heart
Assoc [Internet]. [cited 2024 Aug 3]; Available
from:
https://www.ahajournals.org/doi/abs/10.1161/circ.
138.suppl_1.15111
35. KENNEDY SG, GAGGIN HK.
Leveraging Biomarkers for Precision Medicine in
Heart Failure. J Card Fail [Internet]. 2023 Apr 1
[cited 2025 May 6];29(4):459–62. Available from:
https://onlinejcf.com/action/showFullText?pii=S10
71916423000659
36. Bayes-Genis A, Docherty KF, Petrie MC,
Januzzi JL, Mueller C, Anderson L, et al. Practical
algorithms for early diagnosis of heart failure and
heart stress using NT-proBNP: A clinical consensus
statement from the Heart Failure Association of the
ESC. Eur J Heart Fail [Internet]. 2023 Nov 1 [cited
2025 May 6];25(11):1891–8. Available from:
https://pubmed.ncbi.nlm.nih.gov/37712339/
37. Tsutsui H, Albert NM, Coats AJS, Anker
SD, Bayes-Genis A, Butler J, et al. Natriuretic
peptides: role in the diagnosis and management of
heart failure: a scientific statement from the Heart
Failure Association of the European Society of
Cardiology, Heart Failure Society of America and
Japanese Heart Failure Society. Eur J Heart Fail
[Internet]. 2023 May 1 [cited 2025 May
6];25(5):616–31. Available from:
https://pubmed.ncbi.nlm.nih.gov/37098791/
38. Aimo A, Vergaro G, Ripoli A, Bayes-Genis
A, Pascual Figal DA, de Boer RA, et al. Meta-
Analysis of Soluble Suppression
of Tumorigenicity-2 and Prognosis in Acute Heart
Failure. JACC Heart Fail. 2017 Apr 1;5(4):287–96.
39. Boisot S, Beede J, Isakson S, Chiu A,
Clopton P, Januzzi J, et al. Serial sampling of ST2
predicts 90-day mortality following destabilized
heart failure. J Card Fail [Internet]. 2008 Nov [cited
2024 Nov 11];14(9):732–8. Available from:
https://pubmed.ncbi.nlm.nih.gov/18995177/
40. van Vark LC, Lesman-Leegte I, Baart SJ,
Postmus D, Pinto YM, Orsel JG, et al. Prognostic
Value of Serial ST2 Measurements in Patients With
Acute Heart Failure. J Am Coll Cardiol. 2017 Nov
7;70(19):2378–88.
41. Emdin M, Aimo A, Vergaro G, Bayes-
Genis A, Lupón J, Latini R, et al. sST2 Predicts
Outcome in Chronic Heart Failure Beyond NT-
proBNP and High-Sensitivity Troponin T. J Am
Coll Cardiol [Internet]. 2018 Nov 6 [cited 2024
Nov 11];72(19):2309–20. Available from:
https://pubmed.ncbi.nlm.nih.gov/30384887/
42. Aimo A, Januzzi JL, Vergaro G, Richards
AM, Lam CSP, Latini R, et al. Circulating levels
and prognostic value of soluble ST2 in heart failure
are less influenced by age than N-terminal pro-B-
type natriuretic peptide and high-sensitivity
troponin T. Eur J Heart Fail [Internet]. 2020 Nov 1
[cited 2024 Nov 11];22(11):2078–88. Available
from: https://pubmed.ncbi.nlm.nih.gov/31919929/
Journal of Medical Sciences. 4 Jun, 2025 - Volume 13 | Issue 4. Electronic - ISSN: 2345-0592
90
43. Yancy CW, Jessup M, Bozkurt B, Butler J,
Casey DE, Colvin MM, et al. 2017
ACC/AHA/HFSA Focused Update of the 2013
ACCF/AHA Guideline for the Management of
Heart Failure: A Report of the American College of
Cardiology/American Heart Association Task
Force on Clinical Practice Guidelines and the Heart
Failure Society of America. Circulation [Internet].
2017 Aug 8 [cited 2024 Nov 11];136(6):e137–61.
Available from:
https://pubmed.ncbi.nlm.nih.gov/28455343/
44. Sudharshana Murthy KA, Ashoka HG,
Aparna AN. Evaluation and comparison of
biomarkers in heart failure. Indian Heart J. 2016
Apr 1;68:S22–8.
45. Rolski F, Błyszczuk P. Complexity of TNF-
α Signaling in Heart Disease. J Clin Med [Internet].
2020 Oct 1 [cited 2024 Nov 11];9(10):3267.
Available from:
https://pmc.ncbi.nlm.nih.gov/articles/PMC760131
6/
46. Schumacher SM, Naga Prasad S V. Tumor
Necrosis Factor-α in Heart Failure: an Updated
Review. Vol. 20, Current Cardiology Reports.
Current Medicine Group LLC 1; 2018.
47. Simonavicius J, Wussler D, Belkin M,
Luening K, Lopez-Ayala P, Strebel I, et al.
Diagnostic and prognostic utility of bone
morphogenetic protein 10 in acute dyspnea: a
cohort study. Clin Res Cardiol [Internet]. 2024
[cited 2025 May 6]; Available from:
https://pubmed.ncbi.nlm.nih.gov/39661145/
48. Topf A, Mirna M, Ohnewein B, Jirak P,
Kopp K, Fejzic D, et al. The Diagnostic and
Therapeutic Value of Multimarker Analysis in
Heart Failure. An Approach to Biomarker-Targeted
Therapy. Vol. 7, Frontiers in Cardiovascular
Medicine. Frontiers Media S.A.; 2020.
Journal of Medical Sciences. 4 Jun, 2025 - Volume 13 | Issue 4. Electronic - ISSN: 2345-0592
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