Biomarkers in HF help in risk stratifying, prognosticating the patients on pharmacological management.

1. BIOMARKERS IN HEART
FAILURE
Dr. NAGULA PRAVEEN
MD,DM
Associate Professor of Cardiology,
Osmania Medical College/General Hospital, Hyderabad

2. Introduction
 HF is a complex clinical syndrome resulting from structural and functional impairment of
ventricular filling or ejection of blood.
 The global incidence and prevalence of HF have reached epidemic proportions, as
evidenced by the relentless increase in the number of HF hospitalizations, increased HF
deaths and the spiraling costs associated with the care of HF patients.
 Timely diagnosis, worsening and prognostication in HF patients is of utmost importance.
 Biomarkers provide a low cost, low risk, and quick turnaround method to confirm or exclude
a HF diagnosis, prognosticate HF, and more fundamentally, may provide substantial
information on the complex pathophysiology of HF.

3. Definition
 In 1998, the National Institutes of Health Biomarkers Definitions Working
Group defined a biomarker as a characteristic that is objectively measured
and evaluated as an indicator of normal biological processes, pathogenic
processes, or pharmacological responses to a therapeutic intervention.
 A more contemporary definition takes into account the effects of
treatments, interventions, and unintended environmental exposures as well.

4. First biomarker of HF
 Biomarker testing in HF dates
back several decades with the
first reported work done by
Braunwald et al where an early
CRP (C-reactive protein) assay
was used to analyze serum from
the affected patients.

5. Role in HF
 Should be easily measured with high analytical precision
 Should reflect important processes involved in HF presence and
progression
 Should not recapitulate clinical information already available at the bedside,
and
 Must provide clinically useful information for caregivers to more swiftly and
reliably establish/reject a diagnosis
 More accurately estimate prognosis
 Inform more successful therapeutic strategies.
 Only natriuretic peptides have met the requirements

6. Braunwald classification
 HF biomarkers be divided into six distinct categories with an additional one
reserved for biomarkers that have not yet been classified.

7. Biomarkers used in assessing patients with HF
Inflammation ( elucidating the pathogenesis of HF, prognosis,
risk stratification, at risk of heart failure )
C – Reactive protein
Tumor necrosis factor
Fas (APO-1)
Interleukins 1,6, and 18
Oxidative Stress (elucidating the pathogenesis of HF,
prognosis,risk stratification,targets of therapy)
Oxidized LDL
Myeloperoxidase
Urinary biopyrrins
Urinary and plasma isoprostanes
Plasma Malondialdehyde
Extracellular matrix remodeling ( elucidating the
pathogenesis of HF, potential targets of therapy)
Matrix metalloproteinases
Tissue inhibitors of metalloproteinases
Collagen propeptides
Propeptide procollagen type I
Plasma procollagen type III
Neurohormones (elucidating the pathogenesis of HF,
prognosis,risk stratification,targets of therapy)
Norepinephrine
Renin
Angotensin II
Aldosterone
Arginine vasopressin
Endothelin

8. Myocyte Stress (prognosis, risk stratification,
subjects at risk identification, targets of therapy,
diagnosis, monitoring therapy)
B type natriuretic peptide
N terminal pro-B type natriuretic peptide
Midregional proadrenomedullin
ST2
Myocyte injury ( elucidating the pathogenesis of HF,
prognosis,risk stratification,targets of therapy)
Cardiac specific troponins I and T
Myosin light chain kinase 1
Heart type fatty acid protein
Creatine kinase MB fraction
New Biomarkers (Prognostic information and risk
stratification)
Chromogrannin
Galectin 3
Osteoprotegerin
Adiponectin
Growth differentiation factor 15
Insulin like growth factor binding protein 7

11. Clinical Capabilities of HF Biomarkers
Iqbal et al. Cardiovasc Diagn Ther 2012

12. NATRIURETIC
PEPTIDES
The Game Changer

13. The ideal biomarker of HF
Natriuretic Peptide levels are
 Quantitative plasma biomarkers of heart failure (HF).
 Are accurate in the diagnosis of HF.
 Risk stratify emergency department (ED) patients with regard to the need for hospital admission
or direct ED discharge.
 Improve patient management and reduce total treatment costs in patients with acute dyspnoea.
 Admission values are powerful predictors of outcome in predicting death and re-hospitalisation
in HF patients.
 Levels at discharge aid in risk stratification of the HF patient.
 NP-guided therapy may improve morbidity and/or mortality in chronic HF.
 The combination of NP levels together with symptoms, signs and weight gain assists in the
assessment of clinical decompensation in HF.
 can accelerate accurate diagnosis of heart failure presenting in primary care.
 may be helpful to screen for asymptomatic left ventricular dysfunction in high-risk patients.

14. Four types
 1.ANP
 2.BNP
 3.CNP
 4.DNP
 Nesiritide ( used in management of HF)

19. ESC 2021 HF Guidelines
The diagnostic algorithm for heart failure
• Plasma concentrations of NPs are recommended as
initial diagnostic tests in patients with symptoms
suggestive of HF to rule out the diagnosis.
• Elevated concentrations support a diagnosis of HF, are
useful for prognostication and may guide further cardiac
investigation.
• However, it should be noted that there are many causes
of an elevated NP— both CV and non-CV—that might
reduce their diagnostic Accuracy.
• Conversely, NP concentrations may be
disproportionately low in obese patients
Recommended diagnostic tests in all patients
with suspected chronic heart failure
European Heart Journal (2021) 42, 3599- 3726

24. Effect of Sacubitril/valsartan on fibrotic markers in Heart Failure
European Journal of Heart Failure (2021) 23, 1610–1632

26. sST2

28. ST2 >35NG/ML

33. Multimarker strategies
A group of biomarkers(BNP , soluble fms-like
tyrosine kinase receptor , hsCRP , ST2 ,cTnI , uric
acid , and creatinine) , each reflecting a different
pathophysiologic pathway could be combined
into a multi marker score that would predict the
risk for an adverse outcome, defined as death,
cardiac transplantation, or placement of a
ventricular-assist device.
Each of these 7 biomarkers and their pathways
were reported to have been independently
associated with such an outcome.
The combined multi marker integer score
provided an excellent assessment of risk with the
hazard ratios of the intermediate- and higher-risk
tertiles (adjusted for clinical risk) significantly
elevated, to 3.5 and 6.8,respectively, compared
to that of the lowest-risk tertile
JACC: Heart Failure Vol. 1, No. 1, 2013 . Circ Heart Fail 2012;5:183–90.

34. Take home message
Several biomarkers have been developed and their diagnostic and prognostic
performances reported.
The gold standard markers are the natriuretic peptides and hs-cTn.
Rule in for HF 500 pg/ml for BNP, and rule out is 100 pg/ml
Beyond natriuretic peptides and cardiac troponins, soluble ST2 may be indicated to aid in the diagnosis
and risk stratification/prognosis in HF but additional research is warranted and is in progress.
In light of the existing evidence, a multimarker approach is suggested given the
complex pathophysiological processes underlying HF.

35. THANK YOU