N-Terminal proB-type Natriuretic Peptide Improves the Management of Patients with Suspected Acute Heart FailurePrimary Results of the Canadian Multicenter IMPROVE-CHF Study
Gordon W. Moe, MD; Jonathan Howlett, MD; Hanna Zowall, PHD; for the Canadian Multicenter IMPROVE-CHF Study Investigators
Gordon W. Moe, MD; Jonathan Howlett, MD; Hanna Zowall, PHD; for the Canadian Multicenter IMPROVE-CHF Study Investigators (Figure 1 Flow diagram presenting the enrollment, intervention allocation, follow-up, and data analysis of the trial in compliance with the Consolidated Standards of Reporting Trials (CONSORT)) (Figure 2 Median NT-proBNP levels in the adjudicated diagnostic categories. Boxes, interquartile ranges; I bars, maximum and minimum values. HF, heart failure.) (Figure 3 Receiver-operating characteristic curves for clinical judgment, NT-proBNP, and clinical judgment plus NT-proBNP.)
From the University of Toronto, St. Michael"s Hospital, Toronto, Ontario, Canada (G.W.M.); McGill University, Montreal, Quebec, Canada (H.Z.); and Dalhousie University, Queen Elizabeth II Health Sciences Center, Halifax, Nova Scotia, Canada (J.H.) Correspondence to Gordon W. Moe, MD, St Michael’s Hospital, 30 Bond Street, Toronto, Ontario, Canada, M5B1W8. Email: moeg@smh.toronto.on.ca
Background Acute heart failure (HF) has emerged to be a public health problem worldwide. In the United States, hospitalizations for HF has increased from 377 000 in 1979 to 1 093 000 in 2003.1,2 In Canada, a country that adopts a system of universal health insurance,3 patients admitted with acute HF experience high in-hospital and one-year mortality4-7 and early readmission to hospital for HF is frequent.8,9 B-type natriuretic peptide (BNP) and the amino-terminal fragment of the precursor protein (NT-proBNP), have been shown to be useful in establishing the diagnosis of acute HF and providing short-term prognostic information in patients presenting to urgent care settings with dyspnea.10-14 However, previous landmark trials, particularly those of NT-proBNP, had either involved relatively small number of patients15,16 or were conducted in a single institution.17,18 Furthermore, the larger-scale studies of BNP and NT-proBNP were conducted in centers in the United States where per capita health care spending is about twice of that of Canada.19 These published data, while exceedingly important, are not necessarily applicable to countries like Canada which has a publicly funded universal coverage system(Table 1 Baseline Characteristics of Patients Presenting to Seven Canadian Emergency Departments with Dyspnea).
Methods and Results In a Canadian multicenter trial, we tested the hypothesis that NT-proBNP testing improves the management of patients presenting with dyspnea to emergency departments (EDs) in a universal health coverage model by prospectively evaluating the diagnostic of NT-proBNP and the clinical and economic impact of management guided by NT-proBNP results. A total of 501 patients presenting with dyspnea to seven Canadian EDs were studied. Physicians committed to a diagnosis later adjudicated by cardiologists blinded to assay results. Patients were randomized to usual care or NT-proBNP-guided management. Preliminary results are shown in the tables and figures. Median NT-proBNP level among the 231 subjects (46%) with diagnoses of HF was 3717 pg/ml versus 340 pg/ml in those without, P<0.00001. In establishing a diagnosis, adding NT-proBNP to clinical judgment enhanced accuracy, the area under the receiver-operating characteristic curve increased from 0.82 to 0.90, P<0.00001. Knowledge of NT-proBNP results reduced the duration of EDs visit (6.3 to 5.6 hours, P=0.038), number of patients re-hospitalized (51 to 33, P=0.044) and cost of all EDs visits and hospitalizations (US