3. AIM
1. To provide clinicians with guidance on the use of heart failure biomarkers
in clinical practice.
2. Objective, non-invasive, clinical assessment of patients with heart failure
4. Cardiac biomarkers
1. Reflect myocardial stretch, injury, and remodelling
2. To asses the diagnosis of patients presenting to the emergency
department and primary care settings with nonspecific symptoms
3. To establish disease prognosis and severity based on biomarker level
4. To screen patients with risk factors for HF to determine appropriate
interventions for prevention of disease development.
5. PATIENT ENCOUNTER NO1
A 68 year-old white, male retired construction worker presented to ED,
c/o dyspnea and fatigue for 1 week
Past H/O Hypertension and MI x 2 years ago
Medical h/o 50mg atenolol, 81mg aspirin and 20mg atorvas
Vitals:- BP- 146/86 mmhg HR:- 80bpm
Chest x-ray:- no congestion
BNP = 775 pg/mL
Hs-cTnT = 22 ng/L
6. BNP and NT-PRO BNP
BNP is a 32-amino acid protein that is released from the ventricles in
response to cardiac chamber wall stretch that results from volume
overload.
It mediates natriuresis, diuresis, vasodilation, and smooth-muscle
relaxation.
Compensatory mechanism to promote the restoration of fluid balance and
systemic hemodynamics.
7.
8. BNP vs NT-proBNP
The half life of BNP = 20mins
The half life of NT-pro-BNP = 120 mins ; THEREFORE the values of NT-pro-
BNP is 6times higher than BNP values.
Using these biomarkers can provide high diagnostic accuracy and can
assist with excluding other diagnoses, when levels of BNP and NT-proBNP
are low, they can be used to exclude HF.
9. In the Breathing Not Properly Multinational Study, a prospective study performed at 5 sites
in the United States and 2 sites in Europe, the impact of BNP testing on
the evaluation of acute dyspnea was evaluated by measuring the BNP
levels of 1586 patients presenting to the ED with dyspnea.
Patient diagnoses were made by physicians who were blinded to the results of the BNP
measurements. The patients were classified as having
dyspnea due to congestive HF (n = 744; 47%),
dyspnea due to noncardiac causes (with a history of left ventricular (LV) dysfunction [n =
72; 5%]), and
no congestive HF (n = 770; 49%).
10. Comparing the mean BNP levels in each group revealed that those in the congestive HF
group had significantly higher levels than those in the other 2 groups (P < 0.001).
The ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) study was a
prospective, single-site study that compared the value of NT-proBNP levels with clinical
assessment for the diagnosis of acute HF in 599 patients presenting to the ED with
dyspnea.
Clinical diagnoses were categorized as acute HF (n = 209; 35%) or not acute HF (n =
390; 65%). When the mean NT-proBNP levels in each of these groups were compared,
those with acute HF had significantly higher levels than those without acute HF (P <
0.001).
11.
12. cTnI or cTnT
Troponins are proteins involved in the contraction of striated muscle.
cTn exists as a complex of proteins that includes TnI, TnT, and troponin C
(TnC).
Elevated levels of cTnI and cTnT specifically reflect myocardial injury
because they are not expressed in skeletal muscle; consequently, these
biomarkers are highly sensitive
13. Elevations in cTn may result from various mechanisms—such as oxidative
stress, increased wall stress (such as in worsening HF), epicardial coronary
artery disease, neurohormonal activation, inflammatory cytokines,and
altered calcium handling—which may lead to reversible injury,myocyte
necrosis, troponin degradation, and myocyte apoptosis (ie,programmed
cell death)
14. Elevated cTn levels are associated with worse outcomes in HF. In the
ADHERE Registry, 4240 (6.2%) hospitalized HF patients positive for
troponins, as measured by elevated cTnI (≥1000ng/L) or cTnT (≥100ng/L),
required more cardiac procedures and had a longer duration of
hospitalization compared with the 63,684 patients who were troponin
negative (P < 0.001).
15. SOLUBLE ST2
Soluble ST2 is a protein biomarker of myocardial stress that correlates with
cardiac remodeling and myocardial fibrosis, such as in MI, acute coronary
syndrome, and HF.
The membrane-bound form of ST2 is a receptor for the inflammatory
cytokine, interleukin (IL)-33. In response to cardiac disease or injury, IL-33
binds to the ST2 receptor on the cell membrane and provides a
cardioprotective effect to preserve cardiac function. However, when
circulating levels of soluble ST2 are increased, it binds to IL-33 in the
circulation, which makes IL-33 unavailable to bind to ST2 on the cell
membrane. This blocks the beneficial antihypertrophic, antifibrotic, and
antiapoptotic effects of IL-33.
16. however, ST2 was calculated to be inferior to NT-proBNP as a diagnostic
marker.
A pooled analysis of data from 3 trials containing 447 patients with acute
HF showed that an elevated ST2 concentration is an independent predictor
of mortality in patients with HF with reduced ejection fraction (HFrEF) and
HF with preserved ejection fraction (HFpEF), with significantly increased
risk per ng/mL for HFrEF (P < 0.001) and for HFpEF (P = 0.002).
17. GALECTIN-3
Galectin-3 is a mediator of myocardial fibrosis, collagen production, and
cardiac remodeling that leads to altered cardiac function.
6 In HF, galectin-3 is secreted by activated macrophages, and increased
levels of galectin-3 are associated with poor prognosis.
18. In patients with chronic HF have shown that levels of plasma galectin-3 are
(1) also significantly higher than in patients without HF;
(2) increased proportionately with NYHA functional class;
(3) positively correlated with diastolic left atrial diameter and LV end-
diastolic diameter; and
(4) negatively correlated with LVEF.
Although not widely accessible, galectin-3 and other biomarkers of
myocardial fibrosis may be used in conjunction with NPs to provide
additive prognostic value.
19. In a prospective study of patients with chronic HF (n=150) and coronary
heart disease (n=261), increased galectin-3 levels in patients with HF were
an independent predictor of all-cause mortality and rehospitalization
within a 12-month follow-up period, with a cutoff level of 17.78ng/mL.
Similar findings were reported in a prospectively designed substudy of the
Coordinating Study of Evaluating Outcomes of Advising and Counseling in
Heart Failure (COACH; NCT02674438) trial of patients hospitalized for HF
and followed for 18 months.
20. A head-to-head comparison for long-term risk stratification in 876 ambulatory patients
with HF examined ST2 and galectin-3, which both reflect cardiac fibrosis and remodeling.
This study found that the assessment of galectin-3 was inferior to that of ST2.
However, when considered along with BNP assessment, elevated galectin-3 levels at
discharge after an episode of acute HF in 83 patients with chronic HF were strongly
predictive of outcomes at 18 months. Patients with BNP levels ≥500 pg/mL and galactin-3
levels ≥17.6 ng/ mL had a much higher likelihood of cardiovascular events (death by any
cause, cardiac transplantation, worsening HF requiring readmission to the hospital) during
18 months of follow-up compared with patients with BNP levels
21. CONCLUSION
Biomarkers have become increasingly useful in HF for various applications;
those recommended in the 2017 ACC/AHA/HFSA guideline update are
BNP, NT-proBNP, cTn, ST2, and galectin-3.
Clinicians must be aware that in patients with HF treated with ARNI
combination products, or neprilysin inhibitors, increases in BNP
concentrations will not necessarily be indicative of pathology or risk, and
NT-proBNP or another marker not affected by neprilysin inhibition should
be used, along with a physical examination and symptom assessment.
Biomarker assessments can be used to help confirm the diagnosis of HF
and to prevent the development of HF. Further research regarding the
biomarker-guided therapy will provide clinicians with evidence-based data
to improve patient care.
