The use of B-type natriuretic peptide in the emergency department for the diagnosis and management of acute decompensated heart failure for patients presenting with acute shortness of breath

Heart failure is a major cause of ED presentations with shortness of breath. Most patients presenting to the ED with HF are admitted to hospital(80%), leading to enormous cost and a major impact on the use of hospital beds. It is extremely difficult to diagnose and treat heart failure, particularly in the emergency care setting. In early 2000s, an assay for B-type natriuretic peptide (BNP) in blood became available to assist in the diagnosis of heart failure,and also BNP, as nesiritide, was formulated as an IV medication for treatment of heart failure. BNP and a precursor hormone (NT-proBNP) are released by the heart in response to increased ventricular tension or pressure caused by the heart being under strain. Some overseas studies on these assays and nesiritide have shown promising results in diagnosing and treating acute decompensated heart failure (ADHF). But there were no local data available in the Australian context. This thesis assessed the clinical role of the B-type natriuretic peptide in two randomised controlled trials and two meta-analyses. The BNP diagnostic study was designed to assess whether the use of a BNP test will alter clinical outcomes and improve accuracy in diagnosing ADHF patients. This study included 612 patients presenting to the ED at the Alfred Hospital and The Northern Hospital with acute shortness of breath. The results of this study showed no differences between the BNP test group and the control group in hospital admission rate (85.6% vs. 86.6% respectively); length of hospital stay (median, 4.4 days vs. 5.0 days respectively; P=0.94), or in the management of patients in the emergency department. At a cut-off of 101pg/mL, the accuracy, sensitivity, and specificity of the BNP test were 71%, 92%, and 51%, respectively. The optimum cut-off point for the BNP test in our study, derived from the receiver operating characteristic (ROC) curve of the BNP test against the final diagnosis of HF was 265pg/mL: accuracy, 82%; sensitivity, 83%; and specificity, 81%. The area under the curve (AUC) of the ROC curve for diagnosing heart failure using the BNP test result alone was 0.87 (95% CI, 0.83 to 0.91). There was no significant difference between this value and that obtained when the diagnosis of heart failure was made by ED physicians without the benefit of BNP results (AUC 0.88; 95% CI, 0.84 to 0.92 P=0.73). The systematic review and meta-analysis of BNP testing included 5 randomised controlled trials (RCTs) with a total of 2513 patients and showed that BNP testing decreased the length of hospital and critical care unit stay in the tested group compared with the control group, with a mean difference of 1.22 days (CI: 2.31 to 0.14 days) for hospital stay and 0.56 days (CI: 1.06 to 0.05 days) for critical care stay; BNP testing did not significantly affect hospital mortality rates. The systematic review and meta-analysis on nesiritide included 11 trials and a total number of 9242 patients. The results showed no significant differences between the nesiritide group and the control group on 30 day all-cause mortality and readmission: the odds ratio (OR) was 0.96 (95% CI: 0.77, 1.19) and 0.95 (95% CI: 0.66, 1.36), respectively. The risk of hypotension was significantly higher in the nesiritide group (OR: 2.54; 95% CI: 1.62, 4.00). We also found a small but significant rise in the risk of worsening renal function for the nesiritide group (OR: 1.30; 95% CI: 1.04, 1.62). The exploratory double blinded, randomised controlled study investigated the role of natriuretic peptides in the form of intravenous (IV) nesiritide infusion in the treatment of acutely decompensated heart failure patients with obstructive airways disease. This study included 6 patients with 2 in the nesiritide and 4 in the placebo control group. It compared the difference between baseline measurements of respiratory rate, FEV1, FVC, PEF and dyspnoea score with those at 4 hours post initiation of treatment for the two groups. Patients in the nesiritide group showed non-significant directional trend towards to improvement in all five outcomes. The mean differences for the nesiritide and the control group for respiratory rate (per minute) -3.5 and -1.75, respectively; for FEV1 (L) 0.23 and 0.06, respectively; for FVC(L)0.23 and -0.11, respectively; for PEF (L/s) 1.20 and 0.13, respectively; and for dyspnoea score -1.25 and -0.75, respectively. In conclusion, even though the BNP diagnostic study conducted in Australia did not show favourable results, a systematic review of the international studies showed that measuring BNP concentration can assist in the diagnosis of heart failure at the emergency department for patients presenting with shortness of breath and can improve clinical outcomes. However, B-type natriuretic peptide as an IV treatment for patients with acute decompensated heart failure patient did not improve clinical outcomes. Although IV BNP treatment did not increase mortality, there is still a concern that it may worsen renal function. Based on these findings, nesiritide is not recommended to be used as a routine treatment for acute decompensated heart failure. On the other hand, the bronchodilator effect of nesiritide could be further investigated for patients with chronic obstructive airways disease.