| Biomarker | miR-223 / miR-503-5p | Full name | MicroRNA-223 / MicroRNA-503-5p | Molecular Type | Nucleic acid (RNA) |
| Molecular Formula | Molecular Weight | ~22 nt (~6.6 kDa each) | Core Functional Dimensions | Subtype classification, inflammation assessment | |
| Disease(or Constitution) | Heart failure | Disease Subtypes | / | ||
| Organ | Myocardium, immune cells | Test Sample / Technology Platform | Plasma (RT-qPCR, Olink RNA panel) | ||
| Pathobiological Mechanisms | miR-223 inhibits myocardial fibrosis and is highly expressed in HFpEF. miR-503-5p distinguished HFrEF from HFpEF | ||||
| Clinical Availability Status | Research validation: - Wong, such studies have shown that 8-micrornas panel (including miR-503-5p) to distinguish HFrEF from HFpEF AUC = 0.88; -Mir-223 was positively correlated with hs-CRP in HFpEF (r=0.45) | ||||
| Notes and Dynamics | 8-micrornas panel (miR-503-5p, miR-193-a-5p) associated with the NT-proBNP subtype can correct the 27% to 93% HF miscalculation; MiR-223 in the expression level is 2.3 times that of HFrEF HFpEF and pulmonary vascular resistance (PVR) positive correlation (r = 0.50); It can be used as an indicator to monitor the efficacy of anti-inflammatory therapy (such as Ziltivekimab) for HFpEF | ||||
| Biomarker | miR-132 | Full name | MicroRNA-132 | Molecular Type | Nucleic acid (RNA) |
| Molecular Formula | Molecular Weight | ~22 nt (~6.6 kDa) | Core Functional Dimensions | Prognostic assessment and therapeutic targets | |
| Disease(or Constitution) | Heart failure | Disease Subtypes | / | ||
| Organ | Myocardium, neurons | Test Sample / Technology Platform | Plasma (RT-qPCR, small RNA sequencing) | ||
| Pathobiological Mechanisms | Myocardial cells are up-regulated during stress and promote myocardial hypertrophy and remodeling by inhibiting SIRT1. Digoxin could further up-regulate the expression of SIRT1 | ||||
| Clinical Availability Status | Cutting-edge research/clinical trials: - HF-REVERT test (Ⅱ) evaluation (DR132L) the curative effect of miR-132 drug resistance; -A >5-fold increase in miR-132 in acute HF suggested a HR of 2.9 for 1-year mortality | ||||
| Notes and Dynamics | DR132L, a miR-132 antagonist, improved LVEF by 5.2% in patients with HFrEF in phase Ib trial. MiR-132 and myocardial fibrosis markers (PIIINP) positive correlation (r = 0.62), and can be used as anti fibrosis treatment the curative effect of monitoring indicators; The ischemic miR-132 HF patients were significantly higher than that of ischemic HF, can assist the cause identification | ||||
| Biomarker | cfDNA | Full name | Cell-free DNA | Molecular Type | Nucleic acids (fragments of DNA) |
| Molecular Formula | Molecular Weight | ~150-200 bp (~99-132 kDa) | Core Functional Dimensions | Monitoring of myocardial damage and assessment of graft rejection | |
| Disease(or Constitution) | Heart failure | Disease Subtypes | / | ||
| Organ | Heart failure | Test Sample / Technology Platform | Plasma (real-time qPCR, Shotgun sequencing) | ||
| Pathobiological Mechanisms | Myocardial cells are released during apoptosis/necrosis to reflect the degree of myocardial injury. Donor-derived cfDNA (cfdDNA) can monitor rejection after heart transplantation | ||||
| Clinical Availability Status | Study validation/specific scenarios available: - GRAfT queue confirmed cfdDNA monitoring acute heart transplant rejection of AUC = 0.92; -cfDNA >10ng/ml in acute HF suggests a 2.3-fold increase in 30-day mortality | ||||
| Notes and Dynamics | Heart transplantation in cfdDNA > 0.25% can be diagnosed acute rejection (sensitivity 81%, specificity 85%), 81% less invasive biopsy; Acute HF cfDNA level and cardiac troponin I (cTnI) positive correlation (r = 0.51), and reflect the degree of myocardial injury; The black HF patients after transplantation cfdDNA rise 2 times that of white patients, need to pay close attention to racial differences | ||||
| Biomarker | sCD146 | Full name | Soluble CD146 | Molecular Type | protein |
| Molecular Formula | Molecular Weight | ~85 kDa | Core Functional Dimensions | Diagnosis of congestion and assessment of endothelial function | |
| Disease(or Constitution) | Heart failure | Disease Subtypes | / | ||
| Organ | Vascular endothelial cells, smooth muscle cells | Test Sample / Technology Platform | Plasma (ELISA and western blot method) | ||
| Pathobiological Mechanisms | Connexin, which is released in response to endothelial injury caused by venous congestion, specifically reflects systemic venous congestion | ||||
| Clinical Availability Status | Gayat et al. showed that the AUC for diagnosis of acute HF was 0.87 (close to 0.92 for NT-proBNP); positively correlated with IVC diameter (reflecting right heart pressure) (r=0.48) | ||||
| Notes and Dynamics | The NT-proBNP in "grey zone" (300-900 pg/ml), sCD146 can improve diagnostic accuracy (NRI = 0.23); Chronic HF sCD146 > 5 ng/ml tip 6 months 1.7 times increased risk of worsening heart failure; It is not affected by renal function and is suitable for patients with CKD and HF | ||||
| Biomarker | MR-proADM / ADM | Full name | Mid-regional pro-adrenomedullin / Adrenomedullin | Molecular Type | Protein |
| Molecular Formula | Molecular Weight | ADM: ~5 kDa; MR-proADM: ~5 kDa | Core Functional Dimensions | Diagnosis, prognosis, and evaluation of congestion | |
| Disease(or Constitution) | Heart failure | Disease Subtypes | / | ||
| Organ | Vascular endothelial cells, myocardium, adrenal medulla | Test Sample / Technology Platform | Plasma (ELISA, Luminex) | ||
| Pathobiological Mechanisms | Vascular endothelial cells release, regulate the vascular barrier function, and blood vessel tension, volume overload, reflect the vascular congestion state | ||||
| Clinical Availability Status | Clinical validation/guidelines mentioned: - testified MR BACH-proADM predict acute HF AUC = 0.74 90-day mortality (superior to BNP); -ESC guidelines (2021) mention for HF risk stratification | ||||
| Notes and Dynamics | MR-proADM half-life (6 h) longer than ADM (20 min), plasma better stability and suitable for clinical testing; MR in acute HF-proADM > 1.2 nmol/L prompt 30-day mortality HR = 3.85, especially suitable for low BMI (< 25 kg/m²) patients; An anti-ADM antibody (Adrecizumab) has entered phase iia trials for the treatment of severe interstitial hyperemia | ||||
| Biomarker | CA125 | Full name | Carbohydrate antigen 125 | Molecular Type | Protein |
| Molecular Formula | Molecular Weight | ~200-500 kDa | Core Functional Dimensions | Congestion monitoring, treatment guidance | |
| Disease(or Constitution) | Heart failure | Disease Subtypes | / | ||
| Organ | Ovarian epithelium, pleural/peritoneal mesothelial cells, myocardium (congestion-induced) | Test Sample / Technology Platform | Plasma (immunoassay, chemiluminescence) | ||
| Pathobiological Mechanisms | Skin cells between interstitial pressure/inflammatory stimulate secretion, direct reflect vascular congestion (e.g., pleural effusion, peripheral edema) | ||||
| Clinical Availability Status | Early clinical research validation / : - CHANCE-HF experiments confirm its guiding value of diuretic therapy; -Prognostic value is superior to NT-proBNP in HF patients with severe tricuspid regurgitation (TR) | ||||
| Notes and Dynamics | Acute HF CA125 > 35 u/ml tip residual hyperemia, did not drop to normal discharge (< 35 u/ml) is 6 months and 2.1 times increased risk of hospitalization; In chronic HF, CA125 was highly correlated with right ventricular dysfunction (e.g., TAPSE<18mm) (r=0.53); With the NT-proBNP can promote HFpEF congestion detection accuracy (AUC from 0.82 to 0.89) | ||||
| Biomarker | Galectin-3 (Gal-3) | Full name | Galectin-3 | Molecular Type | Protein |
| Molecular Formula | Molecular Weight | ~26 kDa | Core Functional Dimensions | Prognostic assessment and fibrosis monitoring | |
| Disease(or Constitution) | Heart failure | Disease Subtypes | / | ||
| Organ | Macrophages, hepatocytes, myocardium | Test Sample / Technology Platform | Plasma (ELISA) | ||
| Pathobiological Mechanisms | Secreted by macrophages, it promotes myocardial fibrosis by cross-linking extracellular matrix and participates in the activation of inflammation-fibrosis axis in the progression of HF | ||||
| Clinical Availability Status | Clinical validation/guideline mentions: -ESC guideline (2021) recommended for HF prognostic stratification (class Ⅱb recommendation); - BIOSTAT-CHF research confirms its prognostic value of HFpEF than HFrEF | ||||
| Notes and Dynamics | HFpEF Gal-3 increased in patients with more prominent (AUC = 0.74), and pulmonary capillary wedge pressure (PCWP) positive correlation (r = 0.42); In patients with chronic HF, Gal-3>17ng/ml suggested a 2-year mortality rate of HR=1.89, and the change trend could predict the treatment response. And SGLT2 inhibitor can decrease the Gal-3 levels, reflect the anti fibrosis drug | ||||
| Biomarker | sST2 | Full name | Soluble suppression of tumorigenicity 2 | Molecular Type | Protein |
| Molecular Formula | Molecular Weight | ~30 kDa | Core Functional Dimensions | Prognostic assessment and fibrosis monitoring | |
| Disease(or Constitution) | Heart failure | Disease Subtypes | / | ||
| Organ | Myocardium, immune cells, endothelial cells | Test Sample / Technology Platform | Plasma (ELISA, Olink Proximity Extension Assay) | ||
| Pathobiological Mechanisms | Belong to the IL-1 receptor family, as "decoy receptor" IL-33, inhibition of IL-33/ST2L pathway of myocardial protection, promote myocardial fibrosis and ventricular remodeling | ||||
| Clinical Availability Status | Clinical validation/guideline mentions: -ESC guideline (2021) mentions for HF prognostic stratification (class Ⅱb recommendation); -Multiple cohort studies (e.g., PRIDE, TRIUMPH) confirmed its independent prognostic value | ||||
| Notes and Dynamics | Low biological variability (CV<10%), not affected by age, renal function, BMI, suitable for long-term monitoring; Hospitalized in acute HF sST2 > 35 ng/ml mortality or hint 1 HR = 2.46, still rise when the discharge (>35 ng/ml) 54% increased risk of hospitalization; The combination of sST2 > 35ng/ml and Gal-3 can evaluate the "fibrosis burden" of HF patients and predict the efficacy of reversing remodeling | ||||
| Biomarker | hs-cTn / cTn | Full name | High-sensitivity cardiac troponin / Cardiac troponin | Molecular Type | Proteins |
| Molecular Formula | Molecular Weight | cTnI: ~24 kDa; cTnT: ~37 kDa | Core Functional Dimensions | Prognostic stratification and myocardial injury assessment | |
| Disease(or Constitution) | Heart failure | Disease Subtypes | / | ||
| Organ | Myocardium | Test Sample / Technology Platform | Plasma (high-sensitivity immunoassay, chemiluminescence) | ||
| Pathobiological Mechanisms | Myocardial stress/ischemia/necrosis in HF results in the release of intracellular cTn, which reflects the degree of myocardial microdamage and is independent of the pathological process of ventricular stress | ||||
| Clinical Availability Status | Clinical available/guidelines recommend: - ESC guidelines (2021) recommended for the prognosis of patients with HF assessment (Ⅱ class a recommendation); Elevated hs-cTn (>99th percentile) in acute HF suggests a 2-to 3-fold increase in 1-year mortality | ||||
| Notes and Dynamics | Mild elevated hs-cTn was still associated with poor outcomes in patients with chronic HF, with AUC values of 0.72-0.78; Hs-cTn combined with NT-proBNP could improve the accuracy of risk stratification in HFpEF patients (NRI=0.18). The level of hs-cTn in patients with ischemic HF is significantly higher than that in patients with non-ischemic HF, which can help to identify the cause of HF | ||||
| Biomarker | APOE ε4 | Full name | Apolipoprotein Eε4 allele | Molecular Type | Nucleic acid (DNA) |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Susceptibility | ||
| Disease(or Constitution) | Liver Cirrhosis | Disease Subtypes | Compensated, Decompensated | ||
| Organ | Liver | Test Sample / Technology Platform | Whole blood (genotyping) | ||
| Pathobiological Mechanisms | Influence of lipid metabolism, especially related to cleared A beta efficiency is lower, carried A beta risk and time in advance. | ||||
| Clinical Availability Status | Clinical available (risk assessment) : conventional genetic tests available, but only for risk assessment, is not used for diagnosis. Important ethical issues are involved. | ||||
| Notes and Dynamics | It is the core variable of establishing risk stratification model; It is also an important stratification factor in treatment trials. | ||||
| Biomarker | GFAP | Full name | Glial fibrillary acidic protein | Molecular Type | Protein |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Susceptibility, early diagnosis | ||
| Disease(or Constitution) | Liver Cirrhosis | Disease Subtypes | Compensated, Decompensated | ||
| Organ | Liver | Test Sample / Technology Platform | Plasma (SIMOA) | ||
| Pathobiological Mechanisms | A sign of astrocyte activation. In AD, they may be activated early in the pathological response to Aβ. | ||||
| Clinical Availability Status | Frontier research: a large amount of evidence shows that it changes in the presymptomatic stage and is a potential risk warning marker. | ||||
| Notes and Dynamics | It is highly correlated with Aβ pathology and may reflect changes in the brain earlier than p-tau. | ||||
| Biomarker | Neurofilament light Chain (NfL) | Full name | Neurofilament light polypeptide | Molecular Type | Protein |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Monitoring, prognosis | ||
| Disease(or Constitution) | Liver Cirrhosis | Disease Subtypes | Compensated, Decompensated | ||
| Organ | Liver | Test Sample / Technology Platform | CSF/Plasma (SIMOA) | ||
| Pathobiological Mechanisms | Cytoskeletal proteins released after axonal injury are nonspecific markers of neuronal injury. | ||||
| Clinical Availability Status | Research/clinical monitoring tools: widely used in clinical trials for effectiveness monitoring indicators; It is used clinically to evaluate the overall progress of neurodegenerative diseases. | ||||
| Notes and Dynamics | It is elevated in a variety of diseases such as AD, MS, ALS, and is used to evaluate disease activity and treatment response. | ||||
| Biomarker | p-tau (181, 217) | Full name | Phosphorylated Tau (at threonine 181, 217) | Molecular Type | Protein |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Diagnosis, Prognosis | ||
| Disease(or Constitution) | Liver Cirrhosis | Disease Subtypes | Compensated, Decompensated | ||
| Organ | Liver | Test Sample / Technology Platform | CSF/plasma (SIMOA, IP-MS) | ||
| Pathobiological Mechanisms | Hyperphosphorylation of Tau leads to neurofibrillary tangles that disrupt the neuronal cytoskeleton. p-tau is a direct product of this process. | ||||
| Clinical Availability Status | Clinical validation/guideline recommendation: CSF p-tau is the core marker for the diagnosis of AD; Plasma p-tau217 showed excellent diagnostic performance. | ||||
| Notes and Dynamics | p-tau217 is more specific than p-tau181 and is a star molecule for the next generation of blood markers. | ||||
| Biomarker | Aβ42/40 ratio | Full name | Amyloid-β 42/40 ratio | Molecular Type | Protein |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Diagnosis, susceptibility | ||
| Disease(or Constitution) | Liver Cirrhosis | Disease Subtypes | Compensated, Decompensated | ||
| Organ | Liver | Test Sample / Technology Platform | CSF/Plasma (SIMOA, ELISA) | ||
| Pathobiological Mechanisms | Aβ42 aggregates into oligomers and plaques, leading to neurotoxicity; Aβ40 was relatively stable. Ratio reduction is A more reliable indicator of Aβ pathology than single indicator. | ||||
| Clinical Availability Status | Study validation/early clinical: CSF testing was included in the study criteria; Plasma testing is being validated on a large scale. | ||||
| Notes and Dynamics | Plasma Aβ42/40 is A hot spot for early screening and population screening, and it is expected to enter clinical practice. | ||||
| Biomarker | BNP/NT-proBNP | Full name | Brain natriuretic peptide / N-terminal pro-brain natriuretic peptide | Molecular Type | Protein |
| Molecular Formula | Molecular Weight | BNP: ~4 kDa; NT-proBNP: ~10 kDa | Core Functional Dimensions | Diagnosis, prognosis, and treatment monitoring | |
| Disease(or Constitution) | Heart failure | Disease Subtypes | / | ||
| Organ | Myocardium | Test Sample / Technology Platform | Plasma (ELISA and chemiluminescence method, POCT) | ||
| Pathobiological Mechanisms | Ventricular wall pressure/volume load increases trigger myocardial cells release, by activating NPR-A receptor to adjust water sodium excretion, vasodilation, antagonism RAAS system | ||||
| Clinical Availability Status | Clinical available/strong guidelines recommend: ESC/AHA guidelines (2021/2022) as HF diagnosis "Ⅰ class recommended", eliminate HF cutoff: BNP < 100 pg/ml, NT-proBNP < 300 pg/ml; NT-proBNP should be adjusted according to age in acute HF (<55 years >450pg/ml, 55-75 years >900pg/ml, >75 years >1800pg/ml) | ||||
| Notes and Dynamics | The half-life of NT-proBNP (90-120min) is longer than that of BNP (20min), and the plasma stability of NT-proBNP is better, which is more suitable for long-term monitoring of chronic HF. Obese patients (BMI>30kg/m²) need to reduce the cutoff to avoid false negative results. In conjunction with sacubitril/valsartan, degradation by pharmacological inhibition of the BNP, preferred the NT-proBNP curative effect evaluation | ||||
| Biomarker | TP53 mutation | Full name | Tumor Protein P53 gene mutation | Molecular Type | Nucleic acid (DNA) |
| Molecular Formula | / | Molecular Weight | / | Core Functional Dimensions | Diagnosis, prognosis |
| Disease(or Constitution) | Acute Myeloid Leukemia (AML) | Disease Subtypes | / | ||
| Organ | Blood, bone marrow | Test Sample / Technology Platform | Whole blood/bone marrow (genomic sequencing) | ||
| Pathobiological Mechanisms | The encoded cell cycle regulatory transcription factor exhibits abnormal DNA repair function after mutation, leading to uncontrolled cell proliferation. | ||||
| Clinical Availability Status | Clinical validation/Advanced therapies: ELN guidelines recommend early screening; targeted drugs under development. | ||||
| Notes and Dynamics | The results indicate a poor prognosis, with low complete response rate (CRR) and high recurrence rate. The combination of APR-246 and azacitidine demonstrated synergistic therapeutic effects and was granted orphan drug designation. | ||||