The incidence rate of heart failure is increasing with the aging of the population. It is very important for early diagnosis and optimal treatment. Biomarkers of heart failure can assist in the prediction, early diagnosis, prognosis evaluation and treatment of heart failure. They are very important for the prevention and treatment of heart failure. Natriuretic peptides (NP) is the earliest and most widely used marker of heart failure. It plays an important role in various clinical applications, but its disadvantage is that the specificity is not consistent in different clinical situations. In recent years, various new biomarkers have been coming out, which provide more help for the diagnosis and treatment of heart failure.
Introduction to heart failure
Note: 1eft ventricular ejection fraction, LVEF: left ventricular ejection fraction; Heart failure with reduced ejection fraction, hfref; Heart failure with mid range ejection fraction, hfmref
According to LVEF, it is divided into hfref, HFPEF and hfmref; According to the time and speed of heart failure, it can be divided into chronic heart failure and acute heart failure. Most patients with acute heart failure were partially relieved after hospitalization and turned into chronic heart failure; Patients with chronic heart failure often need hospitalization because of acute exacerbation of various incentives. At present, it is considered that heart failure is a chronic and spontaneous progressive disease. The activation of neuroendocrine system leading to myocardial remodeling is the key factor causing the occurrence and development of heart failure. Myocardial remodeling can initially produce partial compensation for cardiac function, but with the intensification of myocardial remodeling, cardiac function gradually changes from compensation to decompensation, with obvious symptoms and signs. Therefore, according to the occurrence and development process of heart failure, it is divided into four stages (Table 2), which aims to emphasize that prevention is the focus of heart failure. The New York Heart Association (NYHA) cardiac function classification is a commonly used clinical cardiac function evaluation method (Table 2), which is often used to evaluate the changes of patients' symptoms with the course of disease or treatment .
Note: stage a: pre heart failure stage; Stage B: preclinical heart failure stage; Stage C: clinical heart failure stage; Stage D: refractory end-stage heart failure
Heart failure diagnosis process
Comprehensive and accurate diagnosis is the premise and basis of effective treatment for patients with heart failure. The diagnosis and evaluation of heart failure depend on medical history, physical examination, laboratory examination, cardiac imaging and functional examination. The diagnosis process of chronic heart failure is shown in Figure 1.
Figure 1 diagnostic flow chart of chronic heart failure
Introduction to heart failure markers
At present, the range of biomarkers of heart failure is expanding, which can be divided into the following categories according to different pathophysiological mechanisms: ① cardiomyocyte traction: BNP / NT proBNP, atrial natriuretic peptide (ANP); ② Cardiomyocyte injury: troponin (CTN), especially high-sensitivity troponin; ③ Neuroendocrine system activation: catecholamines, renin, angiotensin II, aldosterone, etc; ④ Extracellular matrix remodeling and fibrosis: matrix metalloproteinases (MMPs), galectin-3, soluble ST2, etc; ⑤ Inflammation: high sensitivity C-reactive protein (hs CRP), tumor necrosis factor (TNF), etc.
Natriuretic peptide is the most classic marker to reflect myocardial volume load and the change of ventricular wall pressure. BNP and NT proBNP in the atrial natriuretic peptide family are the most widely used biomarkers in the diagnosis and treatment of heart failure. They are helpful to the diagnosis and differential diagnosis, risk stratification, efficacy monitoring and prognosis evaluation of acute and chronic heart failure. They are also helpful to find patients with early heart failure and screen high-risk groups of heart failure. Further study of these markers will help to clarify the pathogenesis of heart failure, better treat heart failure and improve the prognosis of heart failure.
When cardiomyocytes are stimulated by pressure / traction, i.e. ventricular volume dilation and pressure load increase, they first form a pre proBNP containing 134 amino acids, and then the signal peptide of 26 amino acids at the N-terminal is cut off by protease to become proBNP containing 108 amino acids, The latter was equimolar cleaved into an NT proBNP with 76 amino acids in the N-terminal and a BNP with 32 amino acids in the ring structure. They are mainly produced and secreted into the blood by ventricular muscle. Ventricular muscle has no function of storing BNP / NT proBNP, and atrial muscle can also produce a certain amount of BNP / NT proBNP.
Due to different biological half-life, different molecular size, different metabolites, different renal clearance status, different stability and intra individual and inter individual variation of BNP / NT proBNP, their changes are inconsistent. Their molar plasma ratio is not 1:1, and the two results cannot be compared directly .
Clinical application of NT proBNP and BNP
Clinical application of NT proBNP and BNP in diagnosis and differential diagnosis of heart failure
☑ Diagnosis and differential diagnosis of acute heart failure
The diagnosis and differential diagnosis of acute heart failure using BNP / NT proBNP is one of the main clinical applications of this index.
☑ Diagnosis and differential diagnosis of chronic heart failure
Different from acute heart failure, BNP / NT proBNP has higher diagnostic value in the clinical application of chronic heart failure. The cut-off values excluding the diagnosis of chronic heart failure were BNP < 35 ng / L, NT proBNP < 125 ng / L, and the negative predictive value was high. Within this range, the possibility of diagnosis of heart failure is very small. If it is higher than the above diagnostic limit, further examination is required, combined with clinical diagnosis, and non heart failure factors causing the increase of BNP / NT proBNP should be considered.
Guiding and monitoring role of NT proBNP and BNP in the treatment of heart failure
After treatment, the natriuretic peptide in patients with acute heart failure with reduced LVEF decreased significantly compared with the baseline value, suggesting that the treatment is effective. ☑ At present, it is considered that the therapeutic target value of natriuretic peptide in acute LVEF reducing heart failure:
① NT proBNP can be set as a decrease of ≥ 30% from the baseline value or an absolute value of < 4000 ng / L;
② BNP can be set as a decrease of > 50% from baseline or an absolute value of < 350-400 ng / L.
However, whether BNP / NT proBNP dynamic monitoring is needed for all hospitalized patients with acute heart failure to guide the treatment of heart failure is still controversial. It is suggested that on the basis of comprehensive judgment of clinical condition, BNP / NT proBNP levels should be monitored at least including baseline (attack / hospitalization) and stable condition (before discharge); If the patient's condition changes or is extremely critical and lacks hemodynamic monitoring, the level of natriuretic peptide can also be monitored.
☑ If the level of natriuretic peptide does not decrease after treatment during hospitalization, the following situations should be considered:
① The high natriuretic peptide level reflects the "dry" natriuretic peptide in patients with severe heart failure and poor prognosis;
② Patients may have other physiological conditions leading to the increase of natriuretic peptide level, coexisting diseases or combined medication;
③ The patient has no response to the current treatment measures and needs intensive treatment.
Guiding significance of NT proBNP and BNP in the prognosis of heart failure
The higher the BNP / NT proBNP level in patients with acute heart failure, the higher the risk of short-term and long-term adverse clinical events (including all-cause / cardiovascular death, all-cause / heart failure / cardiovascular hospitalization). The dynamic changes of natriuretic peptide during hospitalization and the detection level before discharge may be more valuable than the admission level in the evaluation of prognosis.
For patients with chronic heart failure, BNP / NT proBNP level is also an independent factor to predict adverse prognosis (including all-cause / cardiovascular disease death and all-cause / cardiovascular disease / heart failure hospitalization), but its boundary value for evaluating prognosis has not been fully defined. The value of regular and continuous monitoring of BNP / NT proBNP in patients with chronic heart failure is greater. The long-term stability of the detection value indicates that the risk of heart failure progression is low. The increase of the detection value indicates the deterioration of heart failure, which requires closer clinical monitoring and follow-up.
What factors should be considered to interpret the clinical results of BNP / NT proBNP?
KeYue Zhongkai myocardial marker antibody raw material recommendation:
 Chinese expert consensus on biomarkers of heart failure [J]. Chinese Journal of laboratory medicine, 2020,43 (2): 130-141
 Chinese guidelines for the diagnosis and treatment of heart failure 2018 [J]. Chinese Journal of cardiovascular disease, 2018, 46 (10): 760-789
 Application of B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide in clinical diagnosis and treatment of heart failure in grass-roots hospitals [J]. Chinese Journal of general practitioners, 2017, 16 (3): 169-173
Source: little orange lantern network