Figures
- FIGURE 1
Molecular pathways of synthesis and release of B-type natriuretic peptide (BNP) and N-terminal prohormone of BNP (NT-proBNP). aa: amino acid; cGMP: cyclic guanosine monophosphate; GC: guanylyl cyclase; MAPK: mitogen-activated protein kinase; NPR: natriuretic peptide receptor; PKC: protein kinase C. #: candidate enzymes which may produce 29aa or 32aa BNP depending on cleavage site [22, 23].
Tables
- TABLE 1
Comparison of European Society of Cardiology (ESC)/European Respiratory Society (ERS) and REVEAL 2.0 prognostic tools
Variable ESC/ERS guidelines REVEAL 2.0 risk score calculator# Low risk: <5% Intermediate risk: 5–10% High risk: >10% −1 unless indicated +1 +2 unless indicated WHO PH Group 1 subgroup APAH-CTD Heritable PoPH (+3) Demographics Male, age >60 years Clinical signs of right heart failure Absent Absent Present Comorbidities eGFR<60 mL·min−1/1.73 m2 or renal insufficiency Symptom progression No Slow Rapid Vital signs SBP <110 mmHg
HR >96 beats·min−1Syncope No Occasional syncope Repeated syncope All-cause hospitalisations ≤6 months ≥1 NYHA/WHO FC I, II III IV I III IV 6MWD >440 m 165–440 m <165 m ≥440 m (−2)
320–<440 m<165 m CPET Peak V′O2 >15 mL·min−1·kg−1
(>65% pred)
V′E/V′CO2 slope <36Peak V′O2 11–15 mL·min−1·kg−1
(35–65% pred)
V′E/V′CO2 slope 36–44.9Peak V′O2 <11 mL·min−1·kg−1
(<35% pred)
V′E/V′CO2 slope ≥44.9BNP/NT-proBNP plasma levels BNP <50 ng·L−1
NT-proBNP <300 ng·L−1BNP 50–300 ng·L−1
NT-proBNP 300–1400 ng·L−1BNP >500 ng·L−1
NT-proBNP >1400 ng·L−1BNP<50 ng·L−1
NT-proBNP <300 ng·L−1BNP 200–800 ng·L−1 BNP ≥800 ng·L−1
NT-proBNP ≥1100 ng·L−1Imaging/echocardiography RA area <18 cm2
No pericardial effusionRA area 18–26 cm2
No or minimal pericardial effusionRA area >26 cm2
Pericardial effusionPericardial effusion Haemodynamics/right heart catheterisation RAP <8 mmHg
CI ≥2.5 L/min/m2
SvO2 >65%RAP 8–14 mmHg
CI 2.0–2.4 L/min/m2
SvO2 60–65%RAP >14 mmHg
CI <2.0 L/min/m2
SvO22 <60%PVR <5 Wood units Mean RAP >20 mmHg within 1 year Pulmonary function test DLCO <40% pred ESC/ERS guidelines state that, while not all variables need to be assessed, WHO FC and at least one measurement of exercise capacity (6MWD or CPET) should be taken as a minimum, and assessment of right ventricular (RV) function (BNP/NT-proBNP or echocardiography) is recommended. REVEAL 2.0 includes 11 variables including modifiable and non-modifiable with each score corresponding to a risk for mortality at 1 year. To mirror the ESC/ERS approach the REVEAL score can also be split into three groups (low risk ≤6, intermediate risk 7–8, high risk ≥9) [1, 9]. REVEAL: Registry to Evaluate Early And Long-term PAH Disease Management; WHO: World Health Organization; PH: pulmonary hypertension; NYHA: New York Heart Association; FC: functional class; CPET: cardiopulmonary exercise test; 6MWD: 6-min walk distance; BNP: B-type natriuretic peptide; NT-proBNP: N-terminal pro-hormone of BNP; APAH-CTD: pulmonary arterial hypertension associated with connective tissue disease; PoPH: portopulmonary hypertension; eGFR: estimated glomerular filtration rate; SBP: systolic blood pressure; HR: heart rate; V′O2: oxygen consumption; V′E: minute ventilation; V′CO2: carbon dioxide production; RA: right atrium; RAP: right atrial pressure; CI: cardiac index; SvO2: mixed venous oxygen saturation; PVR: pulmonary vascular resistance; DLCO: diffusing capacity of the lungs for carbon monoxide. #: add/subtract for each variable to get overall score.
- TABLE 2
Comparison of B-type natriuretic peptide (BNP) versus N-terminal prohormone of BNP (NT-proBNP) in clinical practice
BNP NT-proBNP Active peptide, inducing compensatory mechanisms for cardiovascular injury/stress Active function not known, if any Half-life ∼22 min [14] Half-life ∼70 min [14] Correlates better with pulmonary haemodynamics in PAH [1, 67] Correlates better with prognosis in PAH [1, 67] Assays use different antibodies and standard materials (introduces challenges over consistency of results between products and protocols) Assays based on same antibodies and calibrators (gives relative consistency between products and protocols, but accuracy potentially reduced by glycosylation)# Must not be collected in non-siliconised glass tubes [19] Glass or plastic tubes can be used [19] Shorter stability in storage [19]
Assay dependent
Deterioration typically occurs within hours at all temperatures
Longer stability in storage [19]
7 days at room temperature
10 days at 4°C
≥2 months at −20°C
PAH: pulmonary arterial hypertension. #: extent of glycosylation may be influenced by pathology, e.g. increases seen in chronic renal failure, which would underestimate the true NT-proBNP level.
- TABLE 3
Comparison of 10 currently available BNP/NT-proBNP POCT devices
Device BNP/
NT-proBNPTime to result Subjects n Correlation with clinical laboratory (unless specified) [Refs] Quidel Triage BNP Test (formerly Alere Heart Check) BNP ∼15 min 2260 0.95 (versus Siemens ADVIA Centaur) [88] Maisel [87] (n=1586)
Ro [88] (n=250)
Lang [99] (n=150)
Monfort [84] (n=163)
De Vecchis [60] (n=111)Quidel Triage NT-proBNP Test (formerly Alere NT-proBNP) NT-proBNP ∼20 min 100 0.94 (versus Roche cobas 8000) Khezri [98] Roche cobas h 232 NT-proBNP ≤12 min 1887 0.97 (versus Roche cobas e602) [91] Bertsch [92] (n=1591)
Gils [90] (n=202)
Hex [91] (n=94)Philips Minicare BNP BNP ≤10 min 347 0.92 (versus Siemens ADVIA Centaur) Reenen [93] Abbott i-STAT BNP ∼9 min 400 0.98 (versus Siemens ADVIA Centaur) [88] Shah [94] (n=150)
Ro [88] (n=250)Mitsubishi PATHFAST NT-proBNP <17 min 326 0.99 (versus Roche Elecsys) [96] Peetz [96] (n=90)
Zaninotto [70] (n=236)Radiometer AQT90 FLEX NT-proBNP 11–21 min 77 >0.99 (versus Roche Elecsys 2010) Lepoutre [97] Response Biomedical RAMP NT-proBNP NT-proBNP ∼15 min 540 0.98 (versus Roche Elecsys 2010) Lee-Lewandrowski[89] Sekisui Medical Rapidpia BNP <15 min 57 0.93 (versus SHIONOSPOT)# Ishida [100] Shionogi SHIONOSPOT BNP ∼16 min 57 0.93 (versus Rapidpia)# Ishida [100] BNP: B-type natriuretic peptide; NT-proBNP: N-terminal prohormone of BNP; POCT: point-of-care testing. #: Sekisui Medical Rapidpia and Shionogi SHIONOSPOT are both POCT devices compared with each other in this study.
Jump To
- Article
- Abstract
- Abstract
- Introduction
- Physiology of natriuretic peptides and the role of BNP and NT-proBNP in cardiovascular disease and PAH
- BNP/NT-proBNP and comparison with pulmonary haemodynamics, echocardiographic and CMR metrics
- Risk stratification in PAH and the role of BNP/NT-proBNP
- Screening for PAH in systemic sclerosis
- BNP and NT-proBNP considerations for sampling
- Comparison of BNP and NT-proBNP as biomarkers in the clinical setting
- Point-of-care testing: what opportunities are there to improve patient outcomes in patients with PAH?
- What do we need to know before introducing POCT to PAH assessment?
- Conclusion
- Acknowledgements
- Footnotes
- References
- Figures & Data
- Info & Metrics