Pro-BNP Peptide in the diagnosis and prognosis of heart failure

PICHON RIVIERE, A.; AUGUSTOVSKI, F.; GARCIA MARTI, S.; GLUJOVSKY, D.; ALCARAZ, A.; LOPEZ, A.; BARDACH, A.; CIAPONI, A

Documento de Evaluación de Tecnologías Sanitarias

IECS

Año: 2012 p. 1 - 30

1668-2793

Heart Failure (HF) is currently one of the main public health problems in the occidental countries for its high prevalence (0.5 to 2%) and high mortality rates. Natriuretic peptides are found in the neurohormonal mechanisms involved in the pathophysiology of HF. These are hormones found in various tissues but are synthesized and stored mainly in atrial and ventricular myocytes. Serum levels of natriuretic peptides, particularly brain natriuretic peptide (BNP) and aminoterminal proBNP portion, correlate with ventricular filling pressure and wall stress. The presence of a normal proBNP level would exclude the possibility of systolic dysfunction in a patient with dyspnea, their use accordingly postulated for the differential diagnosis of dyspnea in the emergency. Quantitative analysis of proBNP has also been proposed to assess the prognosis of patients with heart failure and monitor their response to treatment.TechnologyBrain natriuretic peptide (BNP) is secreted by cardiac myocytes in response to increased pressure and/or increased ventricular volume. It is stored in the form of pro-BNP which at the time of excretion is divided into the inactive N-terminal portion (NT-pro-BNP) andactive BNP. The determination of pro-BNP correlates with the degree of left ventricular dysfunction and is easily measured by radioimmunoassay and ultrafast techniques.ObjectiveEvaluate the available evidence on diagnostic utility and insuring the use of proBNP in patients with suspected heart failure. This is an update of the rapid response report ?Utility of pro-BNP peptide in the Diagnosis and Prognosis of Heart Failure? published in July 2005.MethodsA search was conducted in the major bibliographic databases DARE, NHS EED generic internet search engines, health technology assessment agencies and health funders. Priority was given to the inclusion of systematic reviews, randomized controlled trials (RCTs), health and economic technology assessments, clinical practice guidelines and insurance policies of other health systems.ResultsFor this report, the results from four systematic reviews were used along with 4 clinical practice guidelines and data from insurance policies offered by some health funders.In 2009, a systematic review was published on the impact of therapeutic strategies using pro-BNP (and other biomarkers) on the mortality of patients with chronic heart failure. Follow-up times ranged between 3 and 18 months. In the meta-analysis, to compare the mortality in the strategy that used the proBNP against the standard strategy, the hazard ratio (HR) was 0.69 (95% Cl 0.55 to 0.86), with a sensitivity analysis that offered a range of HR from 0.62 to 0.71. Two studies provided an analysis of subgroups in patients younger and older than 75 years, observing a greater benefit in the younger age group, with HR 0.38 and 0.92 respectively.In 2010 another systematic review of BNP and proBNP in patients with heart failure observed mortality rates similar to those of the previous one. Only one of the included studies evaluated a rate of hospitalization in the group using proBNP to decide what treatment should be implemented and, compared with the use of clinical patterns, there were no clinically significant differences (RR 0.69, Cl 95% 0.31 to 1.58).In 2009 a systematic review was conducted on the diagnosis of heart failure in primary care. When comparing proBNP with BNP there were no statistically significant differences in their diagnostic ability (OR 1.20, 95% Cl 0.30 to 4.80). There were no differences in the comparison with an electrodiogram (OR 0.43, 95% Cl 0.59 to 3.15). The reported sensitivity was 93% (similar to the BNP and slightly higher than the ECG which was 89%), and with a specificity of 65% (lower than the BNP which was 74% but higher than the ECG which was 56%).In 2010 a systematic review was published of pro-BNP in patients with pleural effusion due to heart failure, 1120 patients with pleural effusion were included (429 case and 691 controls of other origin, mainly cancer). The gold standard for considering the cardiac origin was clinical. The sensitivity was 94% (95% CI, 90%-97%) and specificity of 94% (95% CI, 89%-97%), and the diagnosis of OR 246 (95% Cl, 81-745).A guide published by the national health technology assessment agency in the UK (NICE) recommends the measurement of BNP or proBNP in patients with suspected heart failure without precious infarctions and to indicate urgently (within 2 weeks) a 2D Doppler echocardiography and specialist assessment for patients with suspected heart failure and those with pro-BNP levels of about 2000 pg/ml (236 pmol/liter), or within 6 weeks for those with values between 400 and 2000 pg/ml (47-236 pmol/liter). On the other hand, it suggests that the pro-BNP values below 400 pg/ml (47 pmol/liter) make the diagnosis of heart failure unlikely.In 2010, the Heart Failure Society of America (AFSA) released guidelines on clinical practice on heart failure which recommended against the routine request of proBNP and BNP in asymptomatic patients as part of the structural evaluation of the heart, but does recommend it as medication in patients with suspected heart failure with uncertain diagnosis, or in patients with suspected acute decompensated heart failure, evaluated for dyspnea, and for signs and symptoms of heart failure.In 2009, an update was published of the guidelines for 2005 from the U.S. cardiologists College (ACC) in conjunction with the American Heart Association (AHA), which recommend assessing proBNP (or BNP) in the patient?s initial assessment presented in urgency with suspected heart failure, which can help to improve the risk stratification.A guide for clinical management of heart failure published by the Scottish SIGN agency reported that the sensitivity for diagnosing heart failure is 91% (95% CI 88% to 93%), similar to the BNP, with a specificity of 76% (95% CI 75% to 77%), slightly higher than the BNP. It suggests considering that very low values can be discarded and very high values make the diagnosis of this condition very likely, rather than using specific cut points. It recommends the use of BNP, proBNP, or electrodiogram, before prescribing an echocardiodiogram in patients with suspected heart failure.Most of the health financing agents surveyed believe that pro-BNP measurement is medically necessary in patients with dyspnea to make the differential diagnosis between heart failure and pulmonary disease. However, not everyone agrees on insuring its use in monitoring the response to treatment in heart failure. Some propose the need to use this marker in conjunction with other clinical and diagnostic methods, while some mention BNP but not pro-BNP.ConclusionsPro-BNP is a marker that is often used in the diagnosis of heart failure, seen in most cases as equivalent to BNP. It has a high sensitivity but moderate specificity, similar to BNP. Its use is usually recommended in patients with dyspnea or pleural effusion for the differential diagnosis of decompensated heart failure and other non-cardiac diseases, in conjunction with other diagnostic studies. Its levels indicate the risk of heart failure, being higher when the level of proBNP is higher.Moreover, in relation to monitoring patients with heart failure, results from meta-analysis of randomized clinical trials showed that in patients whose therapeutic strategy was decided based on the levels of proBNP, the mortality rate was significantly reduced compared to the usual strategies. However, practice guidelines do not usually include the use of proBNP in monitoring patients with chronic heart failure.In conclusion, pro-BNP is a marker that would have diagnostic value in patients with heart failure but is not currently recommended in deciding therapeutic behaviors in such patients.